bluuebunny/crossref_metadata_2025 huggingface dataset:
The long road to protecting critical habitat for species at risk: The case of southern mountain woodland caribou
Authors: Palm Eric C. , Fluker Shaun , Nesbitt Holly K. , Jacob Aerin L. , Hebblewhite Mark
Published: May 2020

Identifying habitat that is essential to the recovery of species at risk, known as critical habitat, is a major focus of species at risk legislation, yet there has been little research on the degree to which these areas are protected. Here, we first review the provisions for protecting critical habitat on non‐federal lands within Canada's Species at Risk Act (SARA). Next, we use the declining southern mountain population of woodland caribou (Rangifer tarandus caribou) in British Columbia, Canada as a case study to show that identification of critical habitat does not guarantee its protection on non‐federal lands. Our analyses show that 909 km2 of critical habitat identified on provincial lands were logged in 5 years after it was legally identified under SARA. Existing provincial legislation and policies have provided incomplete protection of caribou critical habitat, and Canada's federal government has yet to exercise authority under SARA that could protect these areas. In the absence of nondiscretionary protection under provincial legislation, a combination of alternative mechanisms, involving all levels of government, Indigenous people, and industry, will be essential to protect critical habitat and help recover species at risk.
Interobserver agreement between pathologist, pulmonologist and molecular pathologist to estimate the tumour burden in rapid on‐site evaluation smears from endosonography and guided bronchoscopy
Authors: Natali Filippo , Cancellieri Alessandra , Giunchi Francesca , De Silvestri Annalisa , Livi Vanina , Ferrari Marco , Paioli Daniela , Betti Sara , Fiorentino Michelangelo , Trisolini Rocco
Published: May 2020

Objective

A growing number of studies have suggested that non‐pathologists can reliably assess the adequacy and malignancy in rapid on‐site evaluation (ROSE) smears prepared during endoscopic sampling procedures. However, no study has verified whether they can also consistently estimate the tumour burden, which is critical for the molecular profiling of lung cancer. We aimed to assess the interobserver agreement (IOA) between a pathologist, a pulmonologist (previously trained in lung and lymph node cytopathology) and a molecular pathologist for the tumour burden in ROSE smears.

Methods

The ROSE smears of consecutive patients with suspected lung cancer undergoing endosonography or guided bronchoscopy were assessed independently by a pathologist, a pulmonologist and a molecular pathologist (gold standard). The IOA for the tumour burden, assessed through k‐statistics, was the primary outcome.

Results

A total of 322 ROSE smears obtained from 162 patients were evaluated. The IOA between the molecular pathologist and pulmonologist was very good (moderate to substantial), although slightly inferior to the IOA between the molecular pathologist and pathologist in the whole slide set (k: 0.707, 95% confidence interval [CI]: 0.677‐0.739 vs 0.793, 95% CI: 0.762‐0.815), as well as in smears prepared from lymphadenopathy (k: 0.783, 95% CI: 0.760‐0.855 vs 0.827, 95% CI: 0.728‐0.892) or from pulmonary nodules/masses (k: 0.558, 95% CI: 0.416‐0.686 vs 0.715, 95% CI: 0.621‐0.767).

Conclusions

A professionally trained pulmonologist can reliably estimate the tumour burden in bronchoscopically derived ROSE smears, especially in the setting of lymphadenopathy. This can be particularly useful in institutions where a cytopathologist is not available regularly.
Linked color imaging followed by magnifying blue laser imaging identifies early gastric cancer in map‐like redness after successful Helicobacter pylori eradication
Authors: Dohi Osamu , Ishida Tsugitaka , Yoshida Naohisa
Published: May 2020

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Resilient selves: A theology of resonance and secularity
Authors: Gregersen Niels Henrik
Published: May 2020

This essay contrasts two visions of selfhood: the buffered, autonomous self, and the flexible, resonant self. The autonomous self, while robustly assertive and active, seeks to insulate itself from threats, thereby robbing it of vital connections to other selves and to nature. The resonant self, in contrast, risks more by standing in fluid relationships of resonance and dissonance with its social and natural environments. While the two stand in tension, a baptismal theology entails both elements of a sheltered self and a resonant self that remains flexible and responsive to the ups and downs of human experience. Conversely, even a secular‐minded person will have access to important zones of resonance.
Exposure to dipeptidyl‐peptidase‐4 inhibitors and COVID‐19 among people with type 2 diabetes: A case‐control study
Authors: Fadini Gian Paolo , Morieri Mario Luca , Longato Enrico , Bonora Benedetta Maria , Pinelli Silvia , Selmin Elisa , Voltan Giacomo , Falaguasta Daniele , Tresso Silvia , Costantini Giorgia , Sparacino Giovanni , Di Camillo Barbara , Tramontan Lara , Cattelan Anna Maria , Vianello Andrea , Fioretto Paola , Vettor Roberto , Avogaro Angelo
Published: May 2020

Because other coronaviruses enter the cells by binding to dipeptidyl‐peptidase‐4 (DPP‐4), it has been speculated that DPP‐4 inhibitors (DPP‐4is) may exert an activity against severe acute respiratory syndrome coronavirus 2. In the absence of clinical trial results, we analysed epidemiological data to support or discard such a hypothesis. We retrieved information on exposure to DPP‐4is among patients with type 2 diabetes (T2D) hospitalized for COVID‐19 at an outbreak hospital in Italy. As a reference, we retrieved information on exposure to DPP‐4is among matched patients with T2D in the same region. Of 403 hospitalized COVID‐19 patients, 85 had T2D. The rate of exposure to DPP‐4is was similar between T2D patients with COVID‐19 (10.6%) and 14 857 matched patients in the region (8.8%), or 793 matched patients in the local outpatient clinic (15.4%), 8284 matched patients hospitalized for other reasons (8.5%), and when comparing 71 patients hospitalized for COVID‐19 pneumonia (11.3%) with 351 matched patients with pneumonia of another aetiology (10.3%). T2D patients with COVID‐19 who were on DPP‐4is had a similar disease outcome as those who were not. In summary, we found no evidence that DPP‐4is might affect hospitalization for COVID‐19.
Prevalence and control of hypertension among patients on haemodialysis
Authors: Tsikliras Nikolaos , Georgianos Panagiotis I. , Vaios Vasilios , Minasidis Elias , Anagnostara Aggelina , Chatzidimitriou Christos , Syrganis Christos , Liakopoulos Vassilios , Zebekakis Pantelis E. , Balaskas Elias V.
Published: May 2020

Background

Earlier studies provided considerably variable estimates on the prevalence and control rates of hypertension in haemodialysis because of their heterogeneity in definitions and blood pressure (BP) measurement techniques applied to detect hypertension.

Materials and Methods

In this cross‐sectional study, 116 clinically stable haemodialysis patients from 3 dialysis centres of Northern Greece underwent home BP monitoring for 1 week with the validated automatic device HEM‐705 (Omron, Healthcare). Routine BP recordings taken before and after dialysis over 6 consecutive sessions were also prospectively collected and averaged. Hypertension was defined as: (a) 1‐week averaged home BP ≥ 135/85 mm Hg; (b) 2‐week averaged predialysis BP ≥ 140/90 mm Hg; and (c) 2‐week averaged postdialysis BP ≥ 130/80 mm Hg. Participants on treatment with ≥1 antihypertensives were also classified as hypertensives.

Results

The prevalence of hypertension was 88.8% by home, 86.2% by predialysis and 91.4% by postdialysis BP recordings. In all, 96 participants (82.7%) were being treated with an average of 2.0 ± 1.1 antihypertensive medications. Among drug‐treated participants, 32.6% were controlled by home, 50.5% by predialysis and 45.3% by postdialysis BP recordings. In multivariate logistic regression analysis, greater use of antihypertensive medications and postdialysis overhydration, assessed with bioimpedance spectroscopy, were both independently associated with higher odds of inadequate home BP control.

Conclusions

This study shows that the prevalence, but mainly the control rates of hypertension in patients on haemodialysis, differs between peridialytic and interdialytic BP recordings. Therefore, the wider use of home BP monitoring may improve the determination of BP control status in this high‐risk population.
The C‐terminal domains of the NMDA receptor: How intrinsically disordered tails affect signalling, plasticity and disease
Authors: Warnet Xavier L. , Bakke Krog Helle , Sevillano‐Quispe Oscar G. , Poulsen Hanne , Kjaergaard Magnus
Published: May 2020

NMDA receptors are part of the ionotropic glutamate receptor family, and are crucial for neurotransmission and memory. At the cellular level, the effects of activating these receptors include long‐term potentiation (LTP) or depression (LTD). The NMDA receptor is a stringently gated cation channel permeable to Ca2+, and it shares the molecular architecture of a tetrameric ligand‐gated ion channel with the other family members. Its subunits, however, have uniquely long cytoplasmic C‐terminal domains (CTDs). While the molecular gymnastics of the extracellular domains have been described in exquisite detail, much less is known about the structure and function of these CTDs. The CTDs vary dramatically in length and sequence between receptor subunits, but they all have a composition characteristic of intrinsically disordered proteins. The CTDs affect channel properties, trafficking and downstream signalling output from the receptor, and these functions are regulated by alternative splicing, protein–protein interactions, and post‐translational modifications such as phosphorylation and palmitoylation. Here, we review the roles of the CTDs in synaptic plasticity with a focus on biochemical mechanisms. In total, the CTDs play a multifaceted role as a modifier of channel function, a regulator of cellular location and abundance, and signalling scaffold control the downstream signalling output.
Soil organic carbon and clay content as deciding factors for net nitrogen mineralization and cereal yields in boreal mineral soils
Authors: Soinne Helena , Keskinen Riikka , Räty Mari , Kanerva Sanna , Turtola Eila , Kaseva Janne , Nuutinen Visa , Simojoki Asko , Salo Tapio
Published: May 2020

To achieve appropriate yield levels, inherent nitrogen (N) supply and biological N fixation are often complemented by fertilization. To avoid economic losses and negative environmental impacts due to over‐application of N fertilizer, estimation of the inherent N supply is critical. We aimed to identify the roles of soil texture and organic matter in N mineralization and yield levels attained in cereal cultivation with or without N fertilization in boreal mineral soils. First, the net N mineralization and soil respiration were measured by laboratory incubation with soil samples varying in clay and organic carbon (C) contents. Secondly, to estimate the inherent soil N supply under field conditions, both unfertilized and fertilized cereal yields were measured in fields on clay soils (clay 30–78%) and coarse‐textured soils (clay 0–28%). In clay soils (C 2.5–9.0%), both the net N mineralization and the cereal yields (without and with fertilization) decreased with increasing clay/C ratio. Moreover, in soils with high clay/C ratio, the agronomic N use efficiency (additional yield per kg of fertilizer N) varied considerably, indicating the presence of growth limitations other than N. In coarse‐textured soils, the yield increase attained by fertilization increased with increasing organic C. Our results indicate that for clay soils in a cool and humid climate, the higher the clay content, the more organic C is needed to produce reasonable yields and to ensure efficient use of added nutrients without high N losses to the environment. For coarse soils having a rather high mean organic C of 2.3%, the organic C appeared to improve agronomic N use efficiency. For farmers, simple indicators such as the clay/C ratio or the use of non‐N‐fertilized control plots may be useful for site‐specific adjustment of the rates of N fertilization.

Highlights

We aimed to identify simple indicators of inherent soil N supply applicable at the farm level.

In clay soils, the net N mineralization was found to correlate negatively with the clay/C ratio.

In coarse‐textured soils, agronomic N use efficiency improved with increasing soil organic C.

Clay soils with high clay/C ratio are at risk of low yield levels.
A proposed guideline for vagus nerve stimulator handling in palliative care and after death
Authors: Alhajaj Ghadd , Atkinson Jeffrey , Keezer Mark R. , Nikolic Ana , Myers Kenneth A.
Published: May 2020

Vagus nerve stimulation (VNS) is often used for patients with drug‐resistant epilepsy. Although this intervention may improve seizure control and mood, a number of factors must be considered when patients with VNS near end of life. We reviewed relevant literature to create a proposed guideline for management of patients with VNS in palliative care and after death. VNS has multiple possible side effects, including cough and swallowing difficulties. For patients with neurologic disease in palliative care, such adverse effects can severely affect quality of life and increase the risk for complications such as aspiration pneumonia. Patients with VNS should be screened regularly for such side effects, and VNS parameters should be adjusted if they are identified. If a patient requires urgent cardiac resuscitation involving external defibrillation, the VNS should be interrogated immediately afterwards to evaluate its function. During defibrillation, paddles should be placed perpendicular to the VNS, and as far as possible away from it. The VNS can be acutely turned off by taping the magnet to the patient's chest, thereby preventing any possible interference with restoration of a normal heart rhythm. After death, any staff involved with handling the body should be notified that a VNS is in place. The device must be removed prior to cremation, as it can explode with high heat. If the cause of death is unclear, a full postmortem examination should be undertaken, per sudden unexpected death in epilepsy guidelines. If there is concern about device malfunction, the device should be returned to the manufacturer for evaluation.
Genetics of equine bleeding disorders
Authors: Dahlgren Anna R. , Tablin Fern , Finno Carrie J.
Published: May 2020

Genetic bleeding disorders can have a profound impact on a horse's health and athletic career. As such, it is important to understand the mechanisms of these diseases and how they are diagnosed. These diseases include haemophilia A, von Willebrand disease, prekallikrein deficiency, Glanzmann's Thrombasthenia and Atypical Equine Thrombasthenia. Exercise‐induced pulmonary haemorrhage also has a proposed genetic component. Genetic mutations have been identified for haemophilia A and Glanzmann's Thrombasthenia in the horse. Mutations are known for von Willebrand disease and prekallikrein deficiency in other species. In the absence of genetic tests, bleeding disorders are typically diagnosed by measuring platelet function, von Willebrand factor, and other coagulation protein levels and activities. For autosomal recessive diseases, genetic testing can prevent the breeding of two carriers.
Parent–Child Relationships Among African Immigrant Families in Canada
Authors: Salami Bukola , Alaazi Dominic A. , Yohani Sophie , Vallianatos Helen , Okeke‐Ihejirika Philomina , Ayalew Tesfaye , Nsaliwa Christina
Published: May 2020

Objective

To examine the factors that influence parent–child relationships in African immigrant families in Alberta, Canada.

Background

African immigrants are increasingly migrating to high‐income countries, including Canada, in search of a better life. These immigrants often face several challenges, including parenting their children in new sociocultural contexts. We present findings from a critical ethnographic study of parent–child relationships among African immigrants in Alberta, Canada.

Method

Informed by transnational feminist theory, we conducted interviews with 14 African immigrant community leaders, 31 African immigrant parents, and 12 service providers and policymakers.

Results

We found that conflicting cultural practices and value systems, shifting power relations, low socioeconomic status, and gender relations exert both beneficial and strenuous influences on parent–child relations.

Conclusion

The determinants of parenting practices and parent–child relationships include the intersecting influences of gender, social class, culture, and changing power relations across transnational spaces.

Implications

Our findings suggest several policy and practice implications. In particular, we suggest a need to attend to diverse determinants of child well‐being, including income, gender relations, culturally sensitive service delivery, and changing power relations across transnational spaces.
The more the merrier: effects of macromolecular crowding on the structure and dynamics of biological membranes
Authors: Löwe Maryna , Kalacheva Milara , Boersma Arnold J. , Kedrov Alexej
Published: May 2020

Proteins are essential and abundant components of cellular membranes. Being densely packed within the limited surface area, proteins fulfil essential tasks for life, which include transport, signalling and maintenance of cellular homeostasis. The high protein density promotes nonspecific interactions, which affect the dynamics of the membrane‐associated processes, but also contribute to higher levels of membrane organization. Here, we provide a comprehensive summary of the most recent findings of diverse effects resulting from high protein densities in both living membranes and reconstituted systems and display why the crowding phenomenon should be considered and assessed when studying cellular pathways. Biochemical, biophysical and computational studies reveal effects of crowding on the translational mobility of proteins and lipids, oligomerization and clustering of integral membrane proteins, and also folding and aggregation of proteins at the lipid membrane interface. The effects of crowding pervade to larger length scales, where interfacial and transmembrane crowding shapes the lipid membrane. Finally, we discuss the design and development of fluorescence‐based sensors for macromolecular crowding and the perspectives to use those in application to cellular membranes and suggest some emerging topics in studying crowding at biological interfaces.
Abrupt changes in Great Britain vegetation carbon projected under climate change
Authors: Boulton Chris A. , Ritchie Paul D. L. , Lenton Timothy M.
Published: May 2020

Past abrupt ‘regime shifts’ have been observed in a range of ecosystems due to various forcing factors. Large‐scale abrupt shifts are projected for some terrestrial ecosystems under climate change, particularly in tropical and high‐latitude regions. However, there is very little high‐resolution modelling of smaller‐scale future projected abrupt shifts in ecosystems, and relatively less focus on the potential for abrupt shifts in temperate terrestrial ecosystems. Here, we show that numerous climate‐driven abrupt shifts in vegetation carbon are projected in a high‐resolution model of Great Britain's land surface driven by two different climate change scenarios. In each scenario, the effects of climate and CO2 combined are isolated from the effects of climate change alone. We use a new algorithm to detect and classify abrupt shifts in model time series, assessing the sign and strength of the non‐linear responses. The abrupt ecosystem changes projected are non‐linear responses to climate change, not simply driven by abrupt shifts in climate. Depending on the scenario, 374–1,144 grid cells of 1.5 km × 1.5 km each, comprising 0.5%–1.5% of Great Britain's land area show abrupt shifts in vegetation carbon. We find that abrupt ecosystem shifts associated with increases (rather than decreases) in vegetation carbon, show the greatest potential for early warning signals (rising autocorrelation and variance beforehand). In one scenario, 89% of abrupt increases in vegetation carbon show increasing autocorrelation and variance beforehand. Across the scenarios, 81% of abrupt increases in vegetation carbon have increasing autocorrelation and 74% increasing variance beforehand, whereas for decreases in vegetation carbon these figures are 56% and 47% respectively. Our results should not be taken as specific spatial or temporal predictions of abrupt ecosystem change. However, they serve to illustrate that numerous abrupt shifts in temperate terrestrial ecosystems could occur in a changing climate, with some early warning signals detectable beforehand.
Professional Perspectives of Youth Justice Policy Implementation: Contextual and Coalface Challenges
Authors: CASE STEPHEN , DREW JOHN , HAMPSON KATHY , JONES GARETH , KENNEDY DUSTY
Published: May 2020

This article offers a multilayered analysis of the subjective perspectives and experiences of key youth justice stakeholders; exploring the inherent dynamism, contradiction, non‐linearity, and contentiousness of youth justice policy implementation. We interrogate how professionals make sense and meaning of policy in the real world and how professional perspectives drive and shape their contributions to policy implementation nationally and locally. Contemporaneously, these analyses enable us to critically examine the caricatures, stereotypes, and assumptions that can (mis)inform common constructions, representations, and understandings of youth justice policy trajectories, including those relating to contextual stability, conceptual clarity, robust evidence bases, and purported foundations in stakeholder consensus.
IDPs in the Kurdistan Region of Iraq (KRI): Intractable Return and Absence of Social Integration Policy
Authors: Khedir Hewa Haji
Published: May 2020

This paper examines the protracted nature of displacement in the Iraqi context and places emphasis on the need for a social integration policy to bridge the deep cleavages of Iraqi society. Methodologically, the paper utilizes qualitative data by conducting focus‐group discussions with IDPs and semi‐structured individual interviews in KRI. In terms of return possibilities, while return in many ways is perceived to be not practical and to involve future risks, research findings show that a community‐based distinction needs to be made between IDPs from minority backgrounds and IDPs who belong to demographic majorities in the homeland locations. A second distinction is a geographic and political one as findings indicate that IDPs who take refuge in KRI, though remain largely dissatisfied with displacement conditions, are willing to stay in KRI longer in the hope of further security and reconstruction process in the violence‐affected areas. With respect to social integration policy, the paper outlines institutional, political and cultural explanations for a virtually absolute absence of social integration policy on national and regional levels. The paper suggests that the proposed social integration policy can capitalize practical implications of Social Contact Theory (SCT) in enhancing the integration of IDPs in the host communities.
Play in Mexican‐American mothers and toddlers is frequent, multimodal, and rich in symbolic content
Authors: Fletcher Katelyn K. , Cates Carolyn Brockmeyer , Mendelsohn Alan L. , Tamis‐LeMonda Catherine S.
Published: May 2020

Play offers rich opportunities for toddlers to develop motor, social, cognitive, and language skills, particularly during interactions with adult caregivers who may scaffold toddlers to higher levels of play than toddlers achieve on their own. However, research on play has narrowly focused on children from White, middle‐income backgrounds, leaving a dearth of knowledge about dyadic play in diverse cultural communities. We videorecorded 222 Mexican‐American mothers playing with their 2‐year‐old toddlers with a standard set of toys. Play behaviors were coded as nonsymbolic or symbolic (play type) and as expressed through manual, verbal, or multiple channels (play modality). Play between toddlers and mothers was frequent, high in symbolic content, and toddler play closely corresponded with mother play in type and modality: Toddlers’ nonsymbolic play related to mothers’ nonsymbolic play; toddlers’ symbolic play related to mothers’ symbolic play; toddlers’ manual play related to mothers’ manual play; and toddlers’ multimodal play related to mothers’ multimodal play. Play in Mexican‐American mothers and toddlers is frequent, multimodal, and symbolically rich, offering new directions for future research and practice.
Partitioning of Ce, as a simulant for Pu, in a multiphase ceramic nuclear waste form
Authors: Zhang Zhaoming , Spiers Kathryn M. , Vance Eric R. , Davis Joel
Published: May 2020

A pyrochlore‐rich multiphase ceramic waste form was prepared by the alkoxide‐route and consolidated by sintering in air. Cerium (Ce) was used as a surrogate for plutonium (Pu), which was found in both the major pyrochlore and minor perovskite phases, but not the minor rutile phase. A synchrotron‐based fluorescence X‐ray absorption near‐edge spectroscopy (XANES) imaging technique was employed to determine the Ce oxidation state in each of the two Ce‐containing phases. It was shown that the major pyrochlore phase contains only tetravalent Ce, whereas the minor perovskite phase incorporates exclusively trivalent Ce. The effect of sintering atmosphere was also investigated, which revealed a very different phase assemblage when sintered in argon (Ar). A major perovskite phase was produced under Ar with a minor zirconolite‐4M phase, both containing trivalent Ce. The composition of the minor rutile phase remained the same whether it was sintered in air or Ar. The results demonstrate the importance of controlling the oxidation state of multivalent waste ions in the design of ceramic waste forms.
Correlations of serum biochemistry profile with ultrasonic histogram of liver, gallbladder, and kidneys and morphometry of rescued long‐tailed macaques (Macaca fascicularis)
Authors: Cardenio Paul A. , Acorda Jezie A. , Lastica‐Ternura Emilia A.
Published: May 2020

Background

Serum biochemistry and ultrasonography can be useful diagnostic tools in evaluating the general health condition of long‐tailed macaques in rescue and rehabilitation centers.

Methods

This study was conducted to determine and correlate the serum biochemistry profile of 24 apparently healthy male and female rescued long‐tailed macaques (LTM) with the body weight, crown‐rump length, and ultrasonic histogram of liver parenchyma, gallbladder lumen, and renal cortices.

Results

There were no sex‐related differences in serum biochemistry values of aspartate aminotransferase, alanine aminotransferase, gamma‐glutamyl transferase, blood urea nitrogen, total cholesterol, and total protein. Creatinine was positively correlated with body weights and crown‐rump length. Multiple weak positive and negative correlations of organ‐specific serum parameters and mean ultrasonic histogram of liver, gallbladder, and kidneys were observed.

Conclusion

This study established the correlations of serum biochemistry profile with ultrasonic histogram of liver, gallbladder, and kidneys and morphometry of rescued LTM.
Maternal obesity reduces placental autophagy marker expression in uncomplicated pregnancies
Authors: Cohen Matthew , Guo Emily , Pucchio Aidan , de Vrijer Barbra , Shepherd Trevor G. , Eastabrook Genevieve
Published: May 2020

Aim

Obesity has been associated with changes in autophagy and its increasing prevalence among pregnant women is implicated in higher rates of placental‐mediated complications of pregnancy such as pre‐eclampsia and intrauterine growth restriction. Autophagy is involved in normal placentation, thus changes in autophagy may lead to impaired placental function and development. The aim of this study was to investigate the connection between obesity and autophagy in the placenta in otherwise uncomplicated pregnancies.

Methods

Immunohistochemistry and western blot analysis were done on placental and omental samples from obese (body mass index [BMI] ≥30 kg/m2) and normal weight (BMI <25 kg/m2) pregnant women with singleton pregnancies undergoing planned Caesarean delivery without labor at term. Samples were analyzed for autophagic markers LC3B and p62 in the peripheral, middle and central regions of the placenta and in omental adipocytes, milky spots and vasculature.

Results

As pre‐pregnancy BMI increased, there was an increase in both placental and fetal weight as well as decreased levels of LC3B in the central region of the placenta (P = 0.0046). Within the obese patient group, LC3B levels were significantly decreased in the placentas of male fetuses compared to females (P < 0.0001). Adipocytes, compared to milky spots and vasculature, had lower levels of p62 (P = 0.0127) and LC3B (P = 0.003) in obese omenta and lower levels of LC3B in control omenta (P = 0.0071).

Conclusion

Obesity leads to reduced placental autophagy in uncomplicated pregnancies; thus, changes in autophagy may be involved in the underlying mechanisms of obesity‐related placental diseases of pregnancy.
Primary aldosteronism: Higher volume load, cardiac output and arterial stiffness than in essential hypertension
Authors: Choudhary M. K. , Värri E. , Matikainen N. , Koskela J. , Tikkakoski A. J. , Kähönen M. , Niemelä O. , Mustonen J. , Nevalainen P. I. , Pörsti I.
Published: May 2020

Background

The diagnostics of primary aldosteronism (PA) are usually carried out in patients taking antihypertensive medications. We compared haemodynamics between medicated PA, medicated essential hypertension (EH), never‐medicated EH and normotensive controls (n = 130 in all groups).

Methods

The hypertensive groups were matched for age (53 years), sex (84 male/46 female) and body mass index (BMI) (30 kg m−2); normotensive controls had similar sex distribution (age 48 years, BMI 27 kg m−2). Haemodynamics were recorded using whole‐body impedance cardiography and radial pulse wave analysis, and the results were adjusted as appropriate. Radial blood pressure recordings were calibrated by brachial blood pressure measurements from the contralateral arm.

Results

Radial and aortic systolic and diastolic blood pressure was similar in PA and never‐medicated EH, and higher than in medicated EH and normotensive controls (P ≤ 0.001 for all comparisons). Extracellular water balance was ~ 4% higher in PA than in all other groups (P < 0.05 for all), whilst cardiac output was ~ 8% higher in PA than in medicated EH (P = 0.012). Systemic vascular resistance and augmentation index were similarly increased in PA and both EH groups when compared with controls. Pulse wave velocity was higher in PA and never‐medicated EH than in medicated EH and normotensive controls (P ≤ 0.033 for all comparisons).

Conclusions

Medicated PA patients presented with corresponding systemic vascular resistance and wave reflection, but higher extracellular water volume, cardiac output and arterial stiffness than medicated EH patients. Whether the systematic evaluation of these features would benefit the clinical diagnostics of PA remains to be studied in future.
Parental feeding concerns of infants and young children with oesophageal atresia
Authors: Menzies Jessica , Hughes Jennifer
Published: May 2020

Aim

Feeding problems have been described in young children with oesophageal atresia (OA). The primary aim of this study was to determine the specific concerns of parents and carers of infants and young children with OA regarding introducing solids and moving up to family foods.

Methods

A questionnaire was developed for parents and carers of infants and children with OA, aged 12 months to 6 years. Questionnaires were completed by 20 parents attending a multidisciplinary OA clinic between June 2016 and June 2017. Demographics and parental concern regarding feeding milestones were collected. The Montreal Children's Hospital Feeding Scale was completed.

Results

The majority of children (95%) had type C OA. Eleven (55%) parents agreed/strongly agreed that they were concerned about their child's feeding prior to the introduction of solids and about moving to more textured solids. The most common concern was choking and food impaction for both time points. Twelve (60%) parents agreed/strongly agreed that the majority of mealtimes in their child's first 1–2 years of life were stressful. Thirteen (65%) parents reported avoiding particular foods due to their child's OA. The majority of children (n = 17) had no feeding difficulty according to an objective scale, and the rest had minor difficulty.

Conclusions

Parental concern around feeding still exists in infants and children without a severe feeding difficulty. Multidisciplinary involvement, including a dietitian and speech pathologist, from an early age is important for infants and children with OA.
Long‐term postoperative pain evaluation in dogs with thoracolumbar intervertebral disk herniation after hemilaminectomy
Authors: Zidan Natalia , Medland Julia , Olby Natasha
Published: May 2020

Background

Chronic neuropathic pain is a common complication in people with spinal cord injury (SCI) but has not been investigated in dogs.

Objective

To determine the reliability of measuring spinal mechanical sensory thresholds (MSTs) in dogs and to compare MSTs of healthy dogs and dogs with SCI caused by acute thoracolumbar intervertebral disk extrusion after hemilaminectomy over a 1‐year period.

Study Design

Prospective study.

Animals

Thirty‐two healthy and 40 SCI dogs.

Methods

Dogs were divided into group 1 (healthy Dachshunds), group 2 (healthy dogs including several breeds), and SCI group. The MSTs were measured using algometry at an incision (thoracolumbar) and control site. Dogs in group 1 were tested once; those in group 2 were tested for 5 consecutive days; and SCI dogs were tested on days 7, 14, 28, 42, 180, and 365 postoperatively. The MSTs were compared among days in healthy and SCI dogs and between SCI and healthy dogs using mixed effect models. P < .05 was considered significant.

Results

At the incision site of SCI dogs, MST was significantly lower than in healthy dogs for 42 days postoperatively, but not subsequently. However, 4/27 dogs had control site MST below the reference range 1 year after surgery.

Conclusions and Clinical Importance

Mechanical sensory thresholds normalize by 6 months after surgery in most dogs with SCI. Approximately 15% of SCI dogs may develop chronic neuropathic pain. Improving long‐term pain assessment of SCI dogs is important for offering treatment options and advising owners.
Evaluation of a 3‐dimensional ultrasound device for noninvasive measurement of urinary bladder volume in dogs
Authors: DiFazio Matthew R. , Thomason Justin D. , Cernicchiaro Natalia , Biller David , Thomason Sasha , Harness Paxton
Published: May 2020

Background

The BladderScan Prime Plus (BPP; Verathon, Bothell, Washington) is an application‐specific, three‐dimensional ultrasound device used for human, point‐of‐care volumetry of the urinary bladder.

Objective

To estimate the BPP's accuracy, repeatability, and optimized settings for assessing urinary bladder volumes in dogs, a variable utilized in assessing micturition disorders.

Animals

Twenty‐four, client‐owned, healthy, male dogs presenting for routine examination.

Methods

Prospective examinations were conducted by an experienced ultrasonographer and a novice, selecting the BPP's “man” or “child” setting, and were compared to urine volume obtained by catheterization.

Results

Mean urine volume significantly varied by operator (P = .05), device setting (P < .001), and weight (P = .01); the “man” setting produced mean volumes nearer to catheterized volumes. The mean difference between BPP's “man” setting and catheterized volume was 0.88 mL, with maximal positive and negative disagreement of +23.2 mL to −55.3 mL (SD 19.0). Percent disagreement between BPP and catheterized volumes demonstrated a mean of −4.5%, with maximal positive and negative disagreement of +58.1% to −74.1% (SD 34.9). The experienced operator recorded volumes significantly (P = .05) higher than the novice, with difference in means of 3.2 mL. In dogs weighing >5.5 kg (n = 18/24), mean difference between BPP's “man” setting and catheterized measurements, regardless of operator, was not significant.

Conclusions

Although small magnitude interuser variability is present in BPP examinations, the device provides accurate, though imprecise quantification of bladder volume in canids weighing >5.5 kg.
Hepatocyte KLF6 expression affects FXR signalling and the clinical course of primary sclerosing cholangitis
Authors: Sydor Svenja , Manka Paul , van Buren Lea , Theurer Sarah , Schwertheim Suzan , Best Jan , Heegsma Janette , Saeed Ali , Vetter Diana , Schlattjan Martin , Dittrich Anna , Fiel Maria I. , Baba Hideo A. , Dechêne Alexander , Cubero Francisco J. , Gerken Guido , Canbay Ali , Moshage Han , Friedman Scott L. , Faber Klaas Nico , Bechmann Lars P.
Published: May 2020

Background & Aims

Primary sclerosing cholangitis (PSC) is characterized by chronic cholestasis and inflammation, which promotes cirrhosis and an increased risk of cholangiocellular carcinoma (CCA). The transcription factor Krueppel‐like‐factor‐6 (KLF6) is a mediator of liver regeneration, steatosis, and hepatocellular carcinoma (HCC), but no data are yet available on its potential role in cholestasis. Here, we aimed to identify the impact of hepatic KLF6 expression on cholestatic liver injury and PSC and identify potential effects on farnesoid‐X‐receptor (FXR) signalling.

Methods

Hepatocellular KLF6 expression was quantified by immunohistochemistry (IHC) in liver biopsies of PSC patients and correlated with serum parameters and clinical outcome. Liver injury was analysed in hepatocyte‐specific Klf6‐knockout mice following bile duct ligation (BDL). Chromatin‐immunoprecipitation‐assays (ChIP) and KLF6‐overexpressing HepG2 cells were used to analyse the interaction of KLF6 and FXR target genes such as NR0B2.

Results

Based on IHC, PSC patients could be subdivided into two groups showing either low (<80%) or high (>80%) hepatocellular KLF6 expression. In patients with high KLF6 expression, we observed a superior survival in Kaplan‐Meier analysis. Klf6‐knockout mice showed reduced hepatic necrosis following BDL when compared to controls. KLF6 suppressed NR0B2 expression in HepG2 cells mediated through binding of KLF6 to the NR0B2 promoter region.

Conclusion

Here, we show an association between KLF6 expression and the clinical course and overall survival in PSC patients. Mechanistically, we identified a direct interaction of KLF6 with the FXR target gene NR0B2.
Mutually constructive roles of Ail and LPS in Yersinia pestis serum survival
Authors: Singh Chandan , Lee Hwayoung , Tian Ye , Schesser Bartra Sara , Hower Suzanne , Fujimoto Lynn M. , Yao Yong , Ivanov Sergey A. , Shaikhutdinova Rima Z. , Anisimov Andrey P. , Plano Gregory V. , Im Wonpil , Marassi Francesca M.
Published: May 2020

The outer membrane is a key virulence determinant of gram‐negative bacteria. In Yersinia pestis, the deadly agent that causes plague, the protein Ail and lipopolysaccharide (LPS)6 enhance lethality by promoting resistance to human innate immunity and antibiotics, enabling bacteria to proliferate in the human host. Their functions are highly coordinated. Here we describe how they cooperate to promote pathogenesis. Using a multidisciplinary approach, we identify mutually constructive interactions between Ail and LPS that produce an extended conformation of Ail at the membrane surface, cause thickening and rigidification of the LPS membrane, and collectively promote Y. pestis survival in human serum, antibiotic resistance, and cell envelope integrity. The results highlight the importance of the Ail–LPS assembly as an organized whole, rather than its individual components, and provide a handle for targeting Y. pestis pathogenesis.
Outcomes of immunoglobulin‐associated mesangiocapillary glomerulonephritis: A South African experience
Authors: Chothia Mogamat‐Yazied , Panday Amaan Shabeer , Coetzee Liezel , Bates William
Published: May 2020

Aim

Immunoglobulin‐associated mesangiocapillary glomerulonephritis is currently the most common biopsy‐confirmed glomerulonephritis in Cape Town, South Africa. We aimed to determine the outcome of patients with a biopsy‐confirmed diagnosis of immunoglobulin‐associated mesangiocapillary glomerulonephritis at our centre.

Methods

A retrospective cohort study of adult patients was conducted from January 1, 2000 to December 31, 2016. The endpoint was a composite of doubling of creatinine and/or end‐stage renal disease and/or death. Cox univariable and multivariable proportional hazards models were used to examine the association between the composite endpoint and predictor variables. Survival curves were made with the use of Kaplan‐Meier estimates.

Results

A total of 70 patients were included in the study and their median duration of follow‐up was 30.4 months. Forty‐eight (68.6%) patients reached the composite endpoint. The proportion reaching this endpoint at 1, 3 and 5 years were 37.5%, 64.6% and 81.3%, respectively. Cox multivariable proportional hazards model identified a serum creatinine concentration > 200 μmol/L at the time of biopsy, moderate to severe interstitial fibrosis, ≥50% crescents and cyclophosphamide therapy as predictors of the composite endpoint.

Conclusion

Immunoglobulin‐associated mesangiocapillary glomerulonephritis remains a common glomerular pathological diagnosis in our setting and has poor outcomes. This may partially be explained by late presentation. Future research needs to focus on identifying the possible cause(s) of this common glomerular disease so that more targeted therapeutic approaches can be offered.
Isotopic composition and concentration of total nitrogen and nitrate in xylem sap under near steady‐state hydroponics
Authors: Hu Yi , Guy Robert D.
Published: May 2020

After root uptake, nitrate is effluxed back to the medium, assimilated locally, or translocated to shoots. Rooted black cottonwood (Populus trichocarpa) scions were supplied with a NO3−‐based (0.5 mM) nutrient medium of known isotopic composition (δ15N), and xylem sap was collected by pressure bombing. To establish a sampling protocol, sap was collected from lower and upper stem sections at 0.1–0.2 MPa above the balancing pressure, and after increasing the pressure by a further 0.5 MPa. Xylem sap from upper stem sections was partially diluted at higher pressure. Further analysis was restricted to sap obtained from intact shoots at low pressure. Total‐, NO3−‐N and, by difference, organic‐N concentrations ranged from 6.1–11.0, 1.2–2.4, and 4.6–9.4 mM, while discrimination relative to the nutrient medium was −6.3 to 0.5‰, −23.3 to −11.5‰ and − 1.3 to 4.9‰, respectively. There was diurnal variation in δ15N of total‐ and organic‐N, but not NO3−. The difference in δ15N between xylem NO3− and organic‐N suggests that discrimination by nitrate reductase is near 25.1 ± 1.6‰. When this value was used in an isotope mass balance model, the predicted xylem sap NO3−‐N to total‐N ratio closely matched direct measurement.
Efficacy and safety of three times daily dosing of tacrolimus in pediatric kidney transplantation patients: A single‐center comparative study
Authors: Alabdulkarim Zinah , Al‐jedai Ahmed , Alkortas Delal , Alhasan Khalid , Devol Edward
Published: May 2020

Background/Aim

Several PK studies have shown that most pediatric patients may require higher doses on a mg/kg basis compared to adults to attain similar therapeutic trough concentrations. The aim of this study was to compare the efficacy and safety of three times daily to twice a day dosing of tacrolimus in pediatric kidney transplant recipients at a major tertiary care transplant center.

Methods and Materials

Retrospective, single‐center, and comparative cohort study. All pediatric kidney transplant recipients received either tacrolimus BID (group 1) or tacrolimus TID (group 2).

Results

A total of 87 patients were included in this study; 48 patients received BID tacrolimus (group 1), and 39 patients received TID tacrolimus (group 2). The percentage of patients who achieved therapeutic trough concentrations in group 2 did not significantly differ from those in group 1 at day 7 (84.62% TID vs 83.33% BID; P = .42). The median time to reach therapeutic trough concentrations was three days in group 1 compared to four days in group 2.

Conclusion

No significant difference was observed between tacrolimus BID and TID dosing in the time to reach therapeutic trough concentration or in the proportion of patients achieving therapeutic trough concentrations at day 7.
Common Retailer Channel Revisited: The Role of Supply Network Size
Authors: Zheng Quan , Pan Xiajun Amy , Vakharia Asoo J.
Published: May 2020

This study is motivated by the ubiquitous practical existence of common retailer distribution channels (e.g., a grocery store offering multiple brands of the same product). Demand interdependence (product substitutability) among various brands is critical and thus we investigate its impact on firms’ profits. Using an economic framework with manufacturers operating as Stackelberg leaders, our analysis reveals unique and substantive insights dependent on the underlying market demand structure, and in some cases, the extent of supply coverage. For the Spence–Dixit–Vives demand structure, we find that competing manufacturers prefer to offer brands with low levels of substitutability while retailer’s preferences are moderated by the interaction effect between the number of competing brands and level of product substitutability (essentially the retailer prefers high levels of substitutability when the number of brands is “small," and vice versa). For the Shubik–Levitan demand structure, manufacturers may prefer high or low levels of product substitutability depending on the extent of supply coverage while the retailer always prefers high levels of product substitutability. These findings offer useful prescriptions for category management and persuasive advertising.
Unprecedented Challenges, Familiar Paradoxes: COVID‐19 and Governance in a New Normal State of Risks
Authors: Yang Kaifeng
Published: May 2020

This Viewpoint essay understands China's COVID‐19 responses through the lens of six paradoxes, focusing on normal and non‐normal governance, competing values, expertise and politics, centralization and decentralization, public and private, and technology and institutions. Preliminary lessons are drawn regarding pandemic governance: embedding resilience into all aspects of governance; developing a public value framework for pandemic governance and improving individuals' ethical capacity; institutionalizing policy capacity on pandemic governance and requiring expertise in relevant positions; balancing centralized coordination and decentralized responses with a stable and ready‐to‐work commanding center; enabling businesses and nonprofits for pandemic governance but regulating them appropriately; and enacting technologies to revolutionize pandemic governance with proper institutional safeguards.
Failure time studies with intermittent observation and losses to follow‐up
Authors: Cook Richard J. , Lawless Jerald F.
Published: May 2020

In health research interest often lies in modeling a failure time process but in many cohort studies failure status is only determined at scheduled assessment times. While the assessment times may be fixed upon study entry, individuals may become lost to follow‐up and miss visits subsequent to the time of loss to follow‐up. We consider a three‐state model to characterize a joint failure and loss to follow‐up process, and use it to investigate the impact of dependent loss to follow‐up on standard parametric, nonparametric, and semiparametric analysis. The effect of dependent loss to follow‐up is mitigated by fitting the joint model. The performance of standard methods is studied using the asymptotic theory of misspecified models, and the finite sample performance is examined for the standard and joint analyses through simulation studies. An application to data from a youth smoking prevention study is presented for illustration.