bluuebunny/crossref_metadata_2025 huggingface dataset:
Aquatic Plant and Dissolved Oxygen Changes in a Reference‐Condition Prairie Stream Subjected to Experimental Nutrient Enrichments
Authors: Suplee Michael W. , Sada Rosie , Feldman David L.
Published: March 2019

Effects of controlled nutrient additions on a prairie stream were studied using a before‐after‐control‐impact paired design. The site is in a reference condition with low soluble nitrate (NO3) and phosphate (soluble reactive phosphorus [SRP]) in summer (3 μg NO3‐N/L, 4 μg SRP/L). Nutrients were added to two reaches over the growing season at two levels (Low Dose — 39 μg NO3‐N/L and 4.4 SRP/L; High Dose — 119 μg NO3‐N/L and 15.6 μg SRP/L). Continuously measured dissolved oxygen (DO) and changes in aquatic flora were compared to an upstream Control. Enrichment led microalgae and filamentous algae to increase in density, areal coverage, and thickness, and the magnitude of the changes were largely concordant with dosing (more in the High Dose); algal growth also suppressed macrophytes in the High Dose. Enrichment caused significant increases in diel DO swings whose magnitudes were consistent with dosing level. In the High Dose, benthic algae flourished in the growing season and then senesced en masse in fall. The decomposing algae led DO to crash (ca. 0 mg/L on the bottom), but DO impacts were out‐of‐sync with peak algal growth and photosynthesis, which occurred weeks earlier. This finding provides a plausible explanation as to why high DO delta in streams impacts aquatic life even when concurrently measured DO is not low. When DO crashed, DO was longitudinally patchy, some areas having low DO near the bottom, others near saturation. Geomorphology and exposure to wind may have caused this pattern.
Safety of CT‐guided cervical nerve root corticosteroid injections
Authors: Lukies Matthew W , Teoh Wesley WH , Clements Warren
Published: March 2019

Introduction

Computed tomography‐guided cervical nerve root corticosteroid injections are a commonly performed procedure for cervical radiculopathy. There have been major complications such as spinal cord infarction and posterior circulation stroke reported mostly with X‐ray fluoroscopic‐guided methods, however, there is relatively little data on the safety of newer CT‐guided methods. The purpose of this study was to identify any major complications and evaluate the rate of minor complications from CT‐guided cervical nerve root corticosteroid injections performed in a tertiary public hospital.

Methods

Four hundred and three CT‐guided cervical nerve root injection procedures were identified over a period from July 2015 to January 2018 using the radiology information system (RIS) and data collected about the technique and any immediate complications. Patient follow‐up and delayed complications were then reviewed, either via outpatient clinic records or telephone consultation.

Results

Two hundred and eighty‐six procedures were performed by radiology registrars or fellows, and 117 by radiologists, most commonly via an anterolateral approach and injecting 4 mg (in 1 mL) of dexamethasone. Follow‐up data were obtained for all 403 procedures and identified 16 minor complications, but no major neurovascular complications.

Conclusion

The overall recorded rate of minor complications with CT‐guided nerve root injection was 4.0% with no major neurovascular complications, suggesting that CT‐guided transforaminal cervical corticosteroid injection is a safe procedure.
Are orthopaedic surgeons reading radiology reports? A Trans‐Tasman Survey
Authors: Kruger Paul , Lynskey Samuel , Sutherland Alasdair
Published: March 2019

Introduction

The attitudes of orthopaedic surgeons regarding radiology reporting is not well‐described in the literature. We surveyed Orthopaedic Surgeons in Australia and New Zealand to assess if they routinely review formal radiology reports.

Methods

An anonymized, 14 question online survey was distributed to consultant surgeons of the Australian and New Zealand Orthopaedic Associations (AOA, NZOA).

Results

Two hundred respondents completed the survey (Total number of Fellows: 283 NZOA, 1185 AOA). 18.5% of respondents always reviewed the formal Radiology report, 44.5% most of the time, 35% sometimes and 2% never. By imaging modality, MRI reports were the most frequently reviewed (92%), followed by ultrasound (74%) and nuclear medicine (63%). Only 10% of surgeons consulted formal reports for plain radiography. 55% of surgeons were still likely to disagree with the MRI report, followed by 46% for plain radiography. In cases of disagreement, only 21% of surgeons would always contact the reporting radiologist. The majority of Surgeons (85.5%) think there should be more collaboration between the disciplines, although only 50.5% had regular attendance of a Radiologist at their departmental audit.

Conclusions

This survey reveals that the majority of orthopaedic surgeons are not routinely reading radiology reports. This points towards a need for further interdisciplinary collaboration. To our knowledge, this is the first survey directly assessing attitudes of orthopaedic surgeons towards radiology reports.
A Volumetric Model for Evaluating Tight Sandstone Gas Reserves in the Permian Sulige Gas Field, Ordos Basin, Central China
Authors: CUI Mingming , FAN Aiping , WANG Zongxiu , GAO Wanli , LI Jinbu , LI Yijun
Published: March 2019

To accurately measure and evaluate reserves is critical for ensuring successful production of unconventional oil and gas. This work proposes a volumetric model to evaluate the tight sandstone gas reserves of the Permian Sulige gas field in the Ordos Basin. The reserves can be determined by four major parameters of reservoir cutoffs, net pay, gas‐bearing area and compression factor Z, which are controlled by reservoir characteristics and sedimentation. Well logging, seismic analysis, core analysis and gas testing, as well as thin section identification and SEM analysis were used to analyze the pore evolution and pore‐throat structure. The porosity and permeability cutoffs are determined by distribution function curve, empirical statistics and intersection plot. Net pay and gas‐bearing area are determined based on the cutoffs, gas testing and sand body distribution, and the compression factor Z is obtained by gas component. The results demonstrate that the reservoir in the Sulige gas field is characterized by ultralow porosity and permeability, and the cutoffs of porosity and permeability are 5% and 0.15×10–3 μm2, respectively. The net pay and gas‐bearing area are mainly affected by the sedimentary facies, sand body types and distribution. The gas component is dominated by methane which accounts for more than 90%, and the compression factor Z of H8 (P2h8) and S1 (P1s1) are 0.98 and 0.985, respectively. The distributary channels stacked and overlapped, forming a wide and thick sand body with good developed intergranular pores and intercrystalline pores. The upper part of channel sand with good porosity and permeability can be sweet spot for gas exploration. The complete set of calculation systems proposed for tight gas reserve calculation has proved to be effective based on application and feedback. This model provides a new concept and consideration for reserve prediction and calculation in other areas.
Early Paleozoic Granite in the Talate Mining District, Chinese Altay, and its Geological Significance for the Altay Orogenic Belt
Authors: LIU Feng , CHAI Fengmei , HAN Dan
Published: March 2019

Zircon dating, geochemical and Nd‐Sr isotopic analyses have been determined for samples from two granitic intrusions in the Talate mining district, Chinese Altay. Our data suggest that these intrusions were emplaced from 462.5 Ma to 457.8 Ma. These rocks have strong affinity to peralumious S‐type granite and are characterized by prominent negative Eu anomalies (δEu=0.20–0.35), strong depletion in Ba, Sr, P, Ti, Nb, Ta and positive anomalies in Rb, Th, U, K, La, Nd, Zr, Hf. Nd‐Sr isotopic compositions of the whole rock show negative ∊Nd(t) values (−1.21 to −0.08) and Mesoproterozoic Nd model ages (T2DM=1.20–1.30 Ga). Their precursor magmas were likely derived from the partial dehydration melting of Mesoproterozoic mica‐rich pelitic sources and mixed with minor mantle‐derived components, under relatively low P (≤1 kbar) and high T (746–796°C) conditions. A ridge subduction model may account for the early Paleozoic geodynamic process with mantle‐derived magmas caused by Ordovician ridge subduction and the opening of a slab window underplated and/or intraplated in the middle–upper crust, which triggered extensive partial melting of the shallow crust to generate diverse igneous rocks, and provided the heat for the crustal melting and juvenile materials for crustal growth.
Characters ofNummulites multiplicutiospiralisn. sp. from the Qarara Formation, Maghagha, Nile Valley, Egypt
Authors: AL MENOUFY Safia
Published: March 2019

Nummulites multiplicutiospiralisn. sp. is described and illustrated for both generations from a claystone of Lutetian age in the Middle Eocene Qarara Formation, Maghagha, Nile valley, Egypt. Previously considered to beNummulites gizehensis, we describe this form as a new species based on diameter of the test and protoconch sizes, septal shape and granulations. The primary feature of this species is spiral multiplication, seen in spiral section. The species is also characterized morphologically by lenticular to flat tests with rounded periphery, wrinkled to broadly meandering septal filaments and few granules on the periphery in microspheric forms. The granules are spirally arranged on the septal filaments in megalospheric forms. Chambers are longer than high and the spire is irregular. The new taxon belongs to theNummulites partschiGroup, SubgroupN. gizehensis. Reflexive coiling in the spiral may develop through ontogeny as inN. rollandi, the species which was considered to be an index species in the southern Tethys (Boukhary et al., 1982 and Boukhary et al. 2010). The characters of the new species, as well as its retrogenesis and reflexive coiling, should be further studied in general inNummulitesspp., to understand the importance of such characters phylogenetically.
Efficacy and safety of add‐on tacrolimus versus leflunomide in rheumatoid arthritis patients with inadequate response to methotrexate
Authors: Shin Kichul , Baek Han Joo , Kang Young Mo , Cha Hoon‐Suk , Kang Seong Wook , Park Sung‐Hwan , Jun Jae‐Bum , Lee Yun Jong , Choi In Ah , Song Yeong Wook
Published: March 2019

Aim

To investigate the efficacy and safety of tacrolimus (TAC) versus leflunomide (LEF) when combined with methotrexate (MTX) in rheumatoid arthritis (RA) patients.

Method

This was a 24‐week multi‐center, double‐blind, randomized, non‐inferiority study targeting RA patients with moderate to severe Disease Activity Score of 28 joints (DAS28 > 3.2) who showed inadequate response to MTX. Patients were randomized into TAC or LEF (add‐on to MTX) groups. Initial daily doses of TAC and LEF were 1.5 and 10 mg, respectively, for 4 weeks and then doubled until the end of the study. The primary endpoint was DAS28 comparison at 24 weeks.

Results

Eighty‐seven patients were screened in 10 centers and 75 patients were randomized into two groups. Baseline demographics were comparable between TAC + MTX and LEF + MTX groups. The TAC + MTX group was non‐inferior to the LEF + MTX group in terms of DAS28 at 24 weeks (mean difference of DAS28: −0.1812, 95% confidence interval: −0.8073, 0.4450). There was a greater number of adverse events in the LEF + MTX group (66 in LEF + MTX and 49 in TAC + MTX). Six patients presented with transaminitis in the LEF + MTX group compared with two patients in the TAC + MTX group.

Conclusion

The efficacy of TAC combined with MTX was non‐inferior to LEF + MTX. It had a reasonable safety profile in RA patients with moderate to severe disease activity (http://cris.nih.go.kr; KCT0000781).
Voluntary Ethanol Intake Produces Subregion‐Specific Neuroadaptations in Striatal and Cortical Areas of Wistar Rats
Authors: Lagström Oona , Danielsson Klara , Söderpalm Bo , Ericson Mia , Adermark Louise
Published: March 2019

Background

Addiction has been conceptualized as a shift from controlled recreational use toward compulsive and habitual drug‐taking behavior. Although the brain reward system is vital for alcohol reward and reinforcement, other neuronal circuits may be involved in controlling long‐term alcohol‐seeking and drug‐taking behaviors. The aim of this study was to outline alcohol‐induced neuroplasticity in defined cortical and striatal subregions, previously implicated in alcohol use disorder.

Methods

Male Wistar rats were allowed to voluntarily consume ethanol (EtOH) in an intermittent manner for 2 months, after which ex vivo electrophysiological recordings were performed and data compared with isolated water controls housed in parallel.

Results

Field potential recordings revealed an increase in field excitatory postsynaptic potentials (fEPSPs) in the dorsomedial striatum (DMS) of rats consuming EtOH, while a depression of evoked potentials was detected in the dorsolateral striatum (DLS). Mean activity in cortical (medial prefrontal cortex, lateral orbitofrontal cortex [OFC]), and accumbal regions (nucleus accumbens [nAc] core/shell) was not significantly altered as compared to water‐drinking controls, but a correlation between the amount of alcohol consumed and evoked potentials could be found in both dorsal striatal subregions, OFC, and nAc core. Removal of EtOH for 1 to 2 days was sufficient to restore neurotransmission in the DLS, while the increase in fEPSP amplitude sustained in the DMS.

Conclusions

These preclinical findings are in line with clinical observations indicating that alcohol produces neurophysiological transformations in dorsal striatal circuits, which in turn may lead to disruptions in decision‐making processes that could further promote alcohol misuse.
Severity of Substance Use Disorder: Utility as an Outcome in Clinical Settings
Authors: Dacosta‐Sánchez Daniel , Fernández‐Calderón Fermín , González‐Ponce Bella , Díaz‐Batanero Carmen , Lozano Óscar M.
Published: March 2019

Background

Some authors have pointed out the usefulness of the levels of substance use disorder (SUD) as a treatment outcome. However, in order to use this variable as an outcome measure, its impact needs to be addressed within a clinical context. The aim of this study was to analyze the sensitivity of SUD levels as a measure for detecting reliable changes and to make a comparison between the changes in SUD levels detected when using the number of criteria fulfilled and when using the reliable change index (RCI).

Methods

The sample consisted of 206 (106 in follow‐up) patients diagnosed with abuse/dependence on alcohol and cocaine, according to DSM‐IV criteria. The Substance Dependence Severity Scale for DSM‐5 was used to determine current alcohol use disorder (AUD) and cocaine use disorder (CUD). Number of DSM‐5 criteria fulfilled and RCI were used to determine the change in SUD levels.

Results

No association was found between adherence to/abandonment of treatment and AUD severity levels (χ2 = 7.029, p = 0.071) or CUD severity levels (χ2 = 2.044, p = 0.413). Statistical significant differences for levels of AUD (z = −3.870, p = 0.000) and CUD (z = −5.382, p = 0.000) were found between baseline assessment and follow‐up. According to the number of DSM‐5 criteria and RCI, the Kappa coefficient for the change in patient status (improved, worsened, or no change) was k = 0.61 for alcohol patients and k = 0.64 for cocaine patients. The “mild” category showed the greatest inconsistency between both procedures.

Conclusions

Levels of SUD are sensitive to the impact of treatment as measured by the difference between the baseline assessment and 3‐month follow‐up. However, conclusions differ according to whether the DSM‐5 criteria or the RCI is applied.
Predictors and Costs of 30‐Day Readmissions After Index Hospitalizations for Alcohol‐Related Disorders in U.S. Adults
Authors: Wani Rajvi J. , Tak Hyo Jung , Watanabe‐Galloway Shinobu , Klepser Donald G. , Wehbi Nizar K. , Chen Li‐Wu , Wilson Fernando A.
Published: March 2019

Background

In 2015, the Hospital Readmissions Reduction Program mandated financial penalties to hospitals with greater rates of readmissions for certain conditions. Alcohol‐related disorders (ARD) are the fourth leading cause of 30‐day readmissions. Yet, there is a dearth of national‐level research to identify high‐risk patient populations and predictors of 30‐day readmission. This study examined patient‐ and hospital‐level predictors for index hospitalizations with principal diagnosis of ARD and predicted the cost of 30‐day readmissions.

Methods

The 2014 Nationwide Readmissions Database was used to identify ARD‐related index hospitalizations. Multivariable logistic regression was used to estimate patient‐ and hospital‐level predictors for readmissions, and a 2‐part model was used to predict the incremental cost conditional upon readmission.

Results

In 2014, 285,767 index hospitalizations for ARD were recorded, and 18.9% of ARD‐associated hospitalizations resulted in at least one 30‐day readmission. Patients who were males, aged 45 to 64 years, Medicaid enrollees, living in urban and low‐income areas, or with 1 to 2 comorbidities had high risk of readmission. Index hospitalization costs were higher among readmitted patients ($8,840 vs. $8,036, p < 0.01). Predicted mean costs for readmissions on index stay with ARD were greater among those aged 45 to 64 years ($1,908, p < 0.001), Medicare enrollees ($2,133, p < 0.001), rural residents ($1,841, p < 0.01), living in high‐income areas ($1,876, p < 0.001), with 4 or more comorbidities ($2,415, p < 0.001), or admitted in large metropolitan hospitals ($2,032, p < 0.001), with large number of beds ($1,964, p < 0.001), with government ownership ($2,109, p < 0.001), or with low volume of ARD cases ($2,155, p < 0.001).

Conclusions

One in 5 ARD‐related index hospitalizations resulted in a 30‐day readmission. Overall, costs of index hospitalizations for ARD were $2.3 billion, of which $512 million were spent on hospitalizations that resulted in at least 1 readmission. There is a need to develop patient‐centric health programs to reduce readmission rates and costs among ARD patients.
Epigenetic therapy in hematological cancers
Authors: Dimopoulos Konstantinos , Grønbæk Kirsten
Published: March 2019

The increasing depth of knowledge about cancer biology throughout the last decades, has underlined the importance of not only genetic aberrations, but also epigenetic abnormalities in cancer cells. The extensive exploration of the cancer epigenome has provided insights into key pathways involved in tumorigenesis, as well as has allowed the development of novel epigenetic therapies. In this review, we will present the important role of epigenetic alterations in hematological diseases, with special focus on epigenetically‐based targeting of hematological malignancies.
Flood‐resilient urban parks: Toward a framework
Authors: Le To Quyen , Devisch Oswald , Trinh Tu Anh
Published: March 2019

Coastal cities are increasingly suffering from flooding events. At the same time, these cities are experiencing a process of rapid urbanisation. This paper introduces “flood‐resilient urban parks” as a strategy to address both challenges. It presents a working definition and proposes a conceptual framework to start developing such parks.
Concentration‐dependent cytokine responses of silica nanoparticles and role of ROS in human lung epithelial cells
Authors: Refsnes Magne , Skuland Tonje , Lilleaas Edel , Øvrevik Johan , Låg Marit
Published: March 2019

Reactive oxygen species (ROS) is regarded as a critical denominator in nanoparticle toxicology and inflammation. Previously, we have shown that silica nanoparticles sized 50 nm (Si50) induce release of CXCL8 and IL‐6 from BEAS‐2B cells, via mechanisms involving NFκB, p38 MAP kinase and TGF‐α‐activated EGF receptor. In the present study, the role of ROS‐mediated mechanisms in the concentration‐dependent Si50 induction of CXCL8 and IL‐6 responses was examined. Si50 (200 µg/mL) induced a time‐dependent ROS formation and a postponed increase in expression of haem oxygenase (HO‐1) mRNA and protein. Pre‐treatment with the ROS inhibitors N‐acetyl cysteine (NAC) and diphenyleneiodonium (DPI) partially attenuated CXCL8 and IL‐6 responses to 200 µg/mL, but not to 100 µg/mL Si50. The release of TGF‐α induced by Si50 (200 µg/mL) was significantly reduced by NAC, but not by DPI nor siRNA against NADPH oxidase DUOX‐1 (siDUOX‐1). Furthermore, siDUOX‐1 reduced Si50‐induced CXCL8, but not IL‐6. Both p38 and p65 phosphorylations were inhibited by siDUOX‐1, but for NAC only p65 phosphorylation reached a significant reduction. Neither NAC nor DPI reduced Si50‐induced CXCL8 and IL‐6 gene expressions. In conclusion, Si50‐induced CXCL8 and IL‐6 involved both ROS‐dependent and ROS‐independent mechanisms. Notably, the role of ROS seemed restricted to effects of higher concentrations of Si50 and not mediated via the gene expression.
Identification of compounds that inhibit the binding of Keap1a/Keap1b Kelch DGR domain with Nrf2 ETGE/DLG motifs in zebrafish
Authors: Raghunath Azhwar , Nagarajan Raju , Sundarraj Kiruthika , Palanisamy Kavipriya , Perumal Ekambaram
Published: March 2019

The Keap1‐Nrf2‐ARE system serves as a premier defence mechanism to curb oxidative stress, which remains as one of the major causes of ageing and pathogenesis in various diseases. Nrf2 is the principal master regulator of the cellular defence system, and its activation remains the prospective therapeutic approach against chronic diseases. One of the recent strategies is to disrupt Keap1‐Nrf2 protein‐protein interaction (PPI) that alters the docking of Keap1 with Nrf2 by compounds occupying a position in the Keap1 blocking the interface with Nrf2. In this study, we made an attempt to identify the compounds with anticancer, antioxidant and anti‐inflammatory properties to disrupt Keap1a/b‐Nrf2 PPI through in silico molecular docking in zebrafish. The phylogenetic analysis of Keap1 proteins revealed the existence of orthologous Keap1‐Nrf2‐ARE system in lower vertebrates that includes zebrafish. The DGR domains of zebrafish Keap1a and Keap1b were modelled with Modeller 9.19 using Keap1 of Mus musculus (PDB ID:5CGJ) as template. Based on the docking calculations, top hit compounds were identified to disrupt both Keap1a and Keap1b interaction with Nrf2 which include quercetin 3,4′‐diglucoside, flavin adenine dinucleotide disodium salt hydrate, salvianolic acid A, tunicamycin and esculin. The LC50 of esculin in 3 dpf zebrafish larvae is 5 mmol/L, and the qRT‐PCR results showed that esculin significantly increased the transcription of Nrf2 target genes—Gstpi, Nqo1, Hmox1a and Prdx1 in 3 dpf zebrafish larvae. These potential hits could serve as safer Nrf2 activators due to their non‐covalent disruption of Keap1‐Nrf2 PPI and be developed into efficacious preventive/therapeutic agents for various diseases.
Immunological and pathological effects of electronic cigarettes
Authors: Chen I‐Ling , Todd Ian , Fairclough Lucy C.
Published: March 2019

Electronic cigarettes (E‐cigarettes) are considered a preferable alternative to conventional cigarettes due to the lack of combustion and the absence of tobacco‐specific toxicants. E‐cigarettes have rapidly gained in popularity in recent years amongst both existing smokers and previous non‐smokers. However, a growing literature demonstrates that E‐cigarettes are not as safe as generally believed. Here, we discuss the immunological, and other, deleterious effects of E‐cigarettes on a variety of cell types and host defence mechanisms in humans and in murine models. We review not only the effects of complete E‐cigarette liquids, but also each of the main components—nicotine, humectants and flavourings. This MiniReview thus highlights the possible role of E‐cigarettes in the pathogenesis of disease and raises awareness of the potential harm that E‐cigarettes may cause.
Accounting for Phenology in the Analysis of Animal Movement
Authors: Scharf Henry R. , Hooten Mevin B. , Wilson Ryan R. , Durner George M. , Atwood Todd C.
Published: March 2019

The analysis of animal tracking data provides important scientific understanding and discovery in ecology. Observations of animal trajectories using telemetry devices provide researchers with information about the way animals interact with their environment and each other. For many species, specific geographical features in the landscape can have a strong effect on behavior. Such features may correspond to a single point (eg, dens or kill sites), or to higher dimensional subspaces (eg, rivers or lakes). Features may be relatively static in time (eg, coastlines or home-range centers), or may be dynamic (eg, sea ice extent or areas of high-quality forage for herbivores). We introduce a novel model for animal movement that incorporates active selection for dynamic features in a landscape. Our approach is motivated by the study of polar bear (Ursus maritimus) movement. During the sea ice melt season, polar bears spend much of their time on sea ice above shallow, biologically productive water where they hunt seals. The changing distribution and characteristics of sea ice throughout the year mean that the location of valuable habitat is constantly shifting. We develop a model for the movement of polar bears that accounts for the effect of this important landscape feature. We introduce a two-stage procedure for approximate Bayesian inference that allows us to analyze over 300 000 observed locations of 186 polar bears from 2012 to 2016. We use our model to estimate a spatial boundary of interest to wildlife managers that separates two subpopulations of polar bears from the Beaufort and Chukchi seas.
“Just a little help”: A qualitative inquiry into the persistent use of uterine fundal pressure in the second stage of labor in Spain
Authors: Rubashkin Nicholas , Torres Cinthia , Escuriet Ramon , Dolores Ruiz‐Berdún Maria
Published: March 2019

Introduction

Uterine fundal pressure, or the Kristeller maneuver (KM), is a non–evidence‐based procedure used in the second stage of labor to physically force the fetus to delivery. Even though officially banned, the KM is practiced in 25% of vaginal deliveries in Spain.

Methods

Using semi‐structured interviews (N = 10 women, N = 15 midwives, N = 3 obstetricians), we sought to understand how providers justify using the KM, and to describe the current circumstances in which the KM is practiced. Women described their preexisting knowledge of and experiences with the KM; providers described how they learned and practiced the KM. We used framework analysis to analyze the transcripts, and we consensus‐coded across three independent investigators.

Results

Providers reported practicing a new, gentler Kristeller to which official policy did not apply. Providers knew the KM posed risks, but they assumed the risks resulted from poor technical training. Providers did not learn the KM through standard means, and they practiced it in secret. Women knew about the KM before delivery, and many had planned to refuse the procedure. Providers made women's refusal more difficult by offering the KM in coded terms as “just a little help.” Women did not experience the KM as gentle, and the force of the procedure made their refusal nearly impossible.

Conclusions

The normal birth policy has failed to achieve its objectives due to maternity care providers’ unique logic surrounding a new KM technique. Women’s ability to refuse the Kristeller is limited.
Targeting of the unfolded protein response (UPR) as therapy for Parkinson's disease
Authors: Martinez Alexis , Lopez Nelida , Gonzalez Constanza , Hetz Claudio
Published: March 2019

Parkinson's disease is the second most common neurodegenerative disorder, leading to the progressive decline of motor control due to the loss of dopaminergic neurons in the substantia nigra pars compacta. At the molecular level, Parkinson's disease share common molecular signatures with most neurodegenerative diseases including the accumulation of misfolded proteins in the brain. Alteration in the buffering capacity of the proteostasis network during aging is proposed as one of the triggering steps leading to abnormal protein aggregation in this disease, highlighting disturbances in the function of the endoplasmic reticulum (ER). The ER is the main subcellular compartment involved in protein folding and quality control. ER stress triggers a signalling reaction known as the unfolded protein response (UPR), which aims restoring proteostasis through the induction of adaptive programs or the activation of cell death pathways when damage is chronic and cannot be repaired. Here, we overview most evidence linking ER stress to Parkinson's disease. Strategies to alleviate ER stress by targeting specific components of the UPR using small molecules and gene therapy are highlighted.
Glucose transporter 1 regulates the proliferation and cisplatin sensitivity of esophageal cancer
Authors: Sawayama Hiroshi , Ogata Yoko , Ishimoto Takatsugu , Mima Kosuke , Hiyoshi Yukiharu , Iwatsuki Masaaki , Baba Yoshifumi , Miyamoto Yuji , Yoshida Naoya , Baba Hideo
Published: March 2019

Glucose transporter 1 (GLUT1) expression is a prognostic marker for esophageal squamous cell carcinoma (ESCC). Recent work on GLUT1 and development of specific inhibitors supports the feasibility of GLUT1 inhibition as a treatment for various cancers. The anti–proliferative effects of GLUT1‐specific small interfering RNA (siRNA) and a GLUT1 inhibitor were evaluated in ESCC cell lines. Expression of pro–proliferative and anti–proliferative signaling and effector molecules was examined by western blotting and quantitative RT‐PCR. GLUT1 expression in pretreatment clinical biopsy samples was measured by immunohistochemistry and correlated with various clinicopathological parameters and response to chemotherapy. The reduction in standardized uptake value (SUV) of 18F‐fluoro‐deoxyglucose was calculated using the formula: ([pretreatment SUVmax – posttreatment SUVmax]/pretreatment SUVmax) × 100. GLUT1‐specific siRNA expression in ESCC cells inhibited their proliferation, increased expression of p27kip, and decreased expression of cyclin‐dependent kinase 6, pyruvate kinase muscle isozyme M2, lactate dehydrogenase A and phospho‐ERK1/2. Suppression of GLUT1 by siRNA increased low‐dose cisplatin‐induced inhibition of proliferation of TE‐11 ESCC cells, which express high GLUT1 levels. Similarly, BAY‐876, a GLUT1 inhibitor, enhanced cisplatin‐mediated inhibition of ESCC cell proliferation. GLUT1 expression in pretreatment biopsy samples was associated with the response to chemotherapy as well as the pathological tumor stage and histological response grade after esophagectomy. Finally, GLUT1‐negative tumors showed a significantly larger reduction in SUVmax (61.2% ± 4.5%) compared with GLUT1‐positive tumors (46.2% ± 4.4%). GLUT1 expression may be a surrogate marker of response to chemotherapy, and inhibition of GLUT1 may be a potential novel therapy for ESCC patients.
Sharper eyes see shyer lizards: Collaboration with indigenous peoples can alter the outcomes of conservation research
Authors: Ward‐Fear Georgia , Rangers Balanggarra , Pearson David , Bruton Melissa , Shine Rick
Published: March 2019

Our ecological studies on large varanid lizards in a remote region of tropical Australia reveal a direct benefit to collaboration with local indigenous people. Although they worked together, in pairs, western scientists and indigenous rangers found lizards with different behavioral phenotypes (“personalities”). The resultant broader sampling of the lizard population enabled us to detect positive effects of a conservation management intervention. Those effects would not have been evident from the subset of animals collected by western scientists, and hence, involvement by researchers from both cultures critically affected our conclusions and paved the way for large‐scale deployment of a novel conservation initiative in Northern Australia.
A single‐center analysis of early readmission after renal transplantation
Authors: Kim Steffan H. , Baird Grayson L. , Bayliss George , Merhi Basma , Osband Adena , Gohh Reginald , Morrissey Paul E.
Published: March 2019

Background

Thirty‐day readmission rates (early hospital readmission, EHR) are an important benchmark for quality improvement. Nationally, patients undergoing renal transplantation incur a 31% EHR rate. While national databases provide useful data, the impact of EHR on individual centers has received little attention. We proposed that an institutional review of EHR after renal transplantation may provide a benchmark for individual transplant programs and identify modifiable program‐specific issues to reduce EHR.

Methods

We reviewed 269 consecutive kidney transplant recipients over a five‐year period (2012‐2016). Early hospital readmission was modeled using generalized linear modeling assuming a binary distribution.

Results

About 21% of patients were readmitted within 30 days. Deceased kidney donation (DD), delayed graft functioning (DGF), anti‐thymocyte globulin (ATG) induction, diabetes, public insurance, weekend discharge, and low glomerular filtration rate (eGFR) at discharge were all identified as risk factors for readmission. Early hospital readmission was not correlated with risk of death (5.4% at 44 months: HR 2.2 (95% CI [0.7, 6.6]; P = 0.1473) or graft loss.

Conclusions

EHR after renal transplantation is common. Certain factors may predict an increased risk for EHR. A multi‐disciplinary approach to discharge planning may limit some EHR, but most complications and adverse events are unpredictable and require hospital‐level of care.
Characteristics, risks, and outcomes of post‐transplant lymphoproliferative disease >3 years after pediatric heart transplant: A multicenter analysis
Authors: West Shawn C. , Friedland‐Little Josh M. , Schowengerdt Kenneth O. , Naftel David C. , Pruitt Freeze Elizabeth , Smith Kelli S. , Urschel Simon , Michaels Marian G. , Kirklin James K. , Feingold Brian
Published: March 2019

Post‐transplant lymphoproliferative disorder (PTLD) is a significant complication after pediatric heart transplantation (HT), occurring in 5%‐15% of patients within 3 years. Data >3 years from HT are limited. We sought to describe the prevalence, risk factors, and outcomes of PTLD occurring late (>3 years) after pediatric HT in the Pediatric Heart Transplant Study from 1993 to 2010. Among 3844 primary HT patients, 110 (3%) developed late, nonrecurrent PTLD. The hazard rate for late PTLD was constant at 0.01 events/year out to 20 years after HT. Risk factors for late PTLD were younger age at HT (HR 1.06, P = 0.003) and Epstein‐Barr virus (EBV) naivety (HR 1.65, P = 0.02). Survival after late PTLD was 86% and 68% at 1 and 5 years, with nonwhite race (HR 2.27, P = 0.03) and earlier year of HT (HR 1.03, P = 0.04) independently associated with mortality. Acute rejection and infection were both common after late PTLD, occurring in 26% and 34% of patients. The constant late hazard and contribution of EBV to late PTLD suggest that vigilance for development of PTLD, including for EBV conversion, should persist indefinitely after pediatric HT. The reasons for elevated risk of death for nonwhites after late PTLD are unclear and warrant further investigation.
Emerging fungal infections in solid organ transplant recipients: Guidelines of the American Society of Transplantation Infectious Diseases Community of Practice
Authors: Shoham Shmuel , Dominguez Edward A. ,   the AST Infectious Diseases Community of Practice
Published: March 2019

These updated AST‐IDCOP guidelines review the epidemiology, diagnosis, and management of emerging fungi after organ transplantation. Infections due to numerous generally innocuous fungi are increasingly recognized in solid organ transplant (SOT) recipients, comprising about 7%‐10% of fungal infections in this setting. Such infections are collectively referred to as emerging fungal infections and include Mucormycetes, Fusarium, Scedosporium, and dematiaceous fungi among others. The causative organisms are diverse in their pathophysiology, uncommon in the clinical setting, have evolving nomenclature, and are often resistant to multiple commonly used antifungal agents. In recent years significant advances have been made in understanding of the epidemiology of these emerging fungal infections, with improved diagnosis and expanded treatment options. Still, treatment guidelines are generally informed by and limited to experience from cohorts of patients with hematological malignancies and/or solid and stem cell transplants. While multicenter randomized controlled trials are not feasible for these uncommon infections in SOT recipients, collaborative prospective studies can be valuable in providing information on the epidemiology, clinical manifestations, treatment strategies, and outcomes associated with the more commonly encountered infections.
Changes in spirits purchasing behaviours after privatisation of government‐controlled sales in Washington, USA
Authors: Kerr William C. , Ye Yu , Greenfield Thomas K.
Published: March 2019

Introduction and Aims

The privatisation of the Washington Liquor Monopoly in 2012 offered a unique opportunity to study spirits purchasing behaviour changes from a government to licensed system.

Design and Methods

Four representative cross‐sectional surveys of adults aged 18 and older in Washington state were recruited between January 2014 and October 2015 (Wave 1, N = 1202; W2, N = 804; W3, N = 823; W4, N = 662). Analyses compared spirits purchasing behaviours before privatisation from retrospective reports to current reports in the areas of travel distance, spirits quality, purchase frequency and size of bottle. Respondents also directly reported on changes in convenience, selection and prices.

Results

No significant changes were found in these aspects of purchasing. However, subgroup analyses found that younger drinkers 18–29 reduced travel distance and increased purchase frequency while drinkers aged 50 and older travelled further. Reduced travel distances were associated with grocery and drug stores while increased travel distances were associated with liquor superstores, wholesale stores and government stores in bordering states. Respondents reported that liquor purchasing was more convenient after privatisation but that the selection of spirits was better and prices were lower in the government‐controlled stores.

Discussion and Conclusions

The government monopoly stores were viewed as offering a wider selection of products and as having lower prices than those in the privatised system. The variety of store types in the licensed system allowed drinkers to select stores based on convenience, selection or prices, so that travel times increased for some buyers, presumably those seeking lower prices or a wider selection.
Endemic infection can shape exposure to novel pathogens: Pathogen co‐occurrence networks in the Serengeti lions
Authors: Fountain‐Jones Nicholas M. , Packer Craig , Jacquot Maude , Blanchet F. Guillaume , Terio Karen , Craft Meggan E.
Published: March 2019

Pathogens are embedded in a complex network of microparasites that can collectively or individually alter disease dynamics and outcomes. Endemic pathogens that infect an individual in the first years of life, for example, can either facilitate or compete with subsequent pathogens thereby exacerbating or ameliorating morbidity and mortality. Pathogen associations are ubiquitous but poorly understood, particularly in wild populations. We report here on 10 years of serological and molecular data in African lions, leveraging comprehensive demographic and behavioural data to test if endemic pathogens shape subsequent infection by epidemic pathogens. We combine network and community ecology approaches to assess broad network structure and characterise associations between pathogens across spatial and temporal scales. We found significant non‐random structure in the lion‐pathogen co‐occurrence network and identified both positive and negative associations between endemic and epidemic pathogens. Our results provide novel insights on the complex associations underlying pathogen co‐occurrence networks.
Local adaptation stops where ecological gradients steepen or are interrupted
Authors: Bridle Jon R. , Kawata Masakado , Butlin Roger K.
Published: March 2019

Population genetic models of evolution along linear environmental gradients cannot explain why adaptation stops at ecological margins. This is because, unless models impose reductions in carrying capacity at species’ edges, the dominant effect of gene flow is to increase genetic variance and adaptive potential rather than swamping local adaptation. This allows the population to match even very steep changes in trait optima. We extend our previous simulations to explore two nonlinear models of ecological gradients: (a) a sigmoid (steepening) gradient and (b) a linear gradient with a flat centre of variable width. We compare the parameter conditions that allow local adaptation and range expansion from the centre, with those that permit the persistence of a perfectly adapted population distributed across the entire range. Along nonlinear gradients, colonization is easier, and extinction rarer, than along a linear gradient. This is because the shallow environmental gradient near the range centre does not cause gene flow to increase genetic variation, and so does not result in reduced population density. However, as gradient steepness increases, gene flow inflates genetic variance and reduces local population density sufficiently that genetic drift overcomes local selection, creating a finite range margin. When a flat centre is superimposed on a linear gradient, gene flow increases genetic variation dramatically at its edges, leading to an abrupt reduction in density that prevents niche expansion. Remarkably local interruptions in a linear ecological gradient (of a width much less than the mean dispersal distance) can prevent local adaptation beyond this flat centre. In contrast to other situations, this effect is stronger and more consistent where carrying capacity is high. Practically speaking, this means that habitat improvement at patch margins will make evolutionary rescue more likely. By contrast, even small improvements in habitat at patch centres may confine populations to limited areas of ecological space.
Immunogenicity of Potomac horse fever vaccine when simultaneously co‐administered with rabies vaccine in a multivalent vaccine or as two monovalent vaccines at separate sites
Authors: McKenzie H. C. , Funk R. A. , Trager L. , Werre S. R. , Crisman M.
Published: March 2019

Background

Potomac horse fever (PHF) is a potentially fatal enterocolitis of horses caused byNeorickettsia risticii. The disease was originally recognised almost 40 years ago in the state of Maryland in theUS. It is now known to occur in many areas of North America, as well as having been described in South America and Europe. MonocomponentPHFvaccines are available, but clinical protection with vaccination has been reported to be inconsistent.

Objectives

This study was designed to assess the immunogenicity of a commercially available Potomac Horse Fever (PHF) vaccine when administered as either a monovalentPHFvaccine simultaneously co‐administered with a separate monovalent Rabies vaccine or as a multivalentPHF/Rabies vaccine in horses.

Study design

Randomised parallel group trial.

Methods

Ninety‐one client or University owned horses participated in this open‐label randomised study, with 45 horses receiving the monovalent vaccines at separate sites and 46 receiving the multivalent vaccine at a single site. SerumPHF IFAtitres were determined twice prior to vaccination and at 1, 2 and 3 months after vaccination.

Results

Both vaccination protocols exhibited poor immunogenicity, with only one‐third of all the animals demonstrating seroconversion, defined as an increase in titre of greater than 400 over baseline, at any time point after vaccination. The monovalentPHFvaccine exhibited significantly greater immunogenicity in terms of the number of horses exhibiting seroconversion, as compared to the multivalent vaccine, at one (20 vs. 11, P = 0.03) and two (18 vs. 9, p = 0.02) months post vaccination. The monovalentPHFvaccine also exhibited significantly greater immunogenicity in terms of the median (interquartile range)IFAtitres, as compared to the multivalent vaccine, at one (800 [200–1600] vs. 400 [200–800], P = 0.009) and 2 months (400 [200–1600] vs. 400 [100–800], P = 0.02) post vaccination. There was no significant difference between groups at 3 months in either seroconversion rate or medianIFAtiters.

Main limitations

This study did not assess the actual protective effects ofPHFvaccination but rather used the serologic response to vaccination as a surrogate biomarker of immunity.

Conclusions

The multivalentPHF/Rabies vaccine exhibited lower immunogenicity as compared to the monovalentPHFvaccine co‐administered with a separate Rabies vaccine.
Frailty, oral health and nutrition in geriatrics inpatients: A cross‐sectional study
Authors: Shwe Phu Sabei , Ward Stephanie A. , Thein Paul M. , Junckerstorff Ralph
Published: March 2019

Background

Poor nutritional status is a risk factor for the development of frailty. Likewise, oral health is independently associated with nutrition. The potential association between oral health and frailty in hospitalised elderly adults has, however, not previously been investigated.

Objective

To investigate the relationship between oral health and frailty in hospitalised elderly adults and to identify the predictors of frailty.

Method

A cross‐sectional study of 168 geriatric inpatients >65 years old was performed from August to December 2016. Patients of non‐English speaking background, with impaired cognition (MMSE <24), severe hearing or visual impairment or active delirium were excluded. Oral health, nutrition and frailty were assessed using previously validated tools, namely the Geriatric Oral Health Assessment Index (GOHAI), Mini Nutrition Assessment (MNA) and Reported Edmonton Frailty Scale (REFS). Other data collected included demographics, co‐morbidities, level of education and smoking/alcohol history.

Results

On univariate analysis, the REFS score decreased with better nutritional status/higher MNA (P < 0.001) and better self‐reported oral health/higher GOHAI (P = 0.023). Nutritional status accounted for 17% of variability in frailty assessment. On multivariate analysis, co‐morbidities (P < 0.001), MNA (P < 0.001) and living in residential care (P < 0.001) were independent predictors of frailty. After adjusting for nutrition and co‐morbidities, self‐reported oral health was found to have an independent negative association with frailty (P = 0.019).

Conclusion

Poor self‐reported oral health was found to be independently associated with frailty. Further research should be directed at whether interventions to maintain good oral health can prevent or slow the progression of frailty.