bluuebunny/crossref_metadata_2025 huggingface dataset:
Increases in endogenous progesterone attenuate smoking in a cohort of nontreatment seeking women: An exploratory prospective study
Authors: Baker Nathaniel L. , Gray Kevin M. , Ramakrishnan Viswanathan , Tomko Rachel L. , McClure Erin A. , Carpenter Matthew J. , Saladin Michael E.
Published: June 2020

Despite advances in prevention and treatment, cigarette smoking remains a leading cause of preventable death in the United States. Although men and women are equally likely to attempt to quit smoking cigarettes, women are far less likely to achieve abstinence both during and following cessation treatment. Recent evidence suggests that ovarian hormone levels may play a role in successful abstinence attempts in women smokers. The primary goal of this exploratory prospective observational study was to estimate the association between within‐participant levels of progesterone and estradiol with associated cigarettes smoked per day in adult women smokers (n = 104). The primary study outcome was self‐reported cigarettes smoked per day (CPD) during a 2‐week observational period collected using a daily smoking diary. Additionally, participants collected saliva daily, from which hormone levels (progesterone and estradiol) were derived. Higher within‐participant progesterone levels were associated with a significant decrease in CPD (p = .008) whereas within‐participant estradiol levels were unrelated to CPD (p = .25). Regression models indicated a single change in the trajectory of smoking behavior for both within‐participant progesterone and estradiol. When progesterone values were below the change point, there was a significant inverse relationship between within‐participant progesterone levels and smoking behavior (p = .025) whereas the relationship was attenuated for higher within‐participant progesterone levels (p = .59). The effect of estradiol on smoking behavior was not significant when it was either below (p = .92) or above (p = .16) the change point. Higher within‐participant levels of progesterone but not estradiol are associated with reduced CPD in nontreatment seeking women smokers.
Scrotal Dowling–Degos disease caused by a novel frameshift variant in gamma‐secretase subunit presenile enhancer gene
Authors: Ren Jun , Zeng Li‐yue
Published: June 2020

We reported a Chinese pedigree with scrotal Dowling–Degos disease and evaluated the phenotypic and genotypic characteristics. In affected cases, pigmented macules were identified on the scrotum. The rashes increased, and the colour deepened progressively. No pain or pruritus were noticed, and no other skin folds were involved. Skin histopathology showed characteristic features of Dowling–Degos disease. A heterozygous PSENEN frameshift variant c.292delC（p.L98Wfs*47） was identified in affected cases. The variant was not found in dbSNP, 1000 Genomes project database and the ExAC Browser. The p.L98 and adjacent amino acids are highly conserved among species. Our cases expand the phenotypic and genotypic spectrum of PSENEN‐related Dowling–Degos disease.
Handheld, accelerometer‐based navigation versus conventional instrumentation in total knee arthroplasty: a meta‐analysis
Authors: Shihab Zaid , Clayworth Catriona , Nara Naveen
Published: June 2020

Background

Precise and accurate alignments in total knee arthroplasty are important predictors for survivorship and functional outcomes. We aim to compare accelerometer‐based navigation (ABN) to conventional instrumentation (CONV), patient‐specific instrumentation (PSI) and computer‐assisted surgery (CAS) in published literature.

Methods

A systematic search of publications from databases (MEDLINE, EMBASE and Cochrane) was obtained from inception to 15 August 2018. A random‐effects meta‐analysis was used to pool odd ratios for outliers greater than 3° for the hip‐knee‐ankle, coronal and sagittal femoral and tibial angles (CFA, CTA, SFA, STA). Secondary outcomes included procedural characteristics and functional outcomes.

Results

Thirteen studies, involving 1566 patients, met inclusion that compared ABN (50.2%) to CONV (49.8%) and five comparing ABN to CAS/PSI. The pooled odds ratios for percent outliers of greater than 3° from the mechanical axis for the hip‐knee‐ankle (relative risk 0.58, P = <0.05) and CFA (relative risk 0.42, P = 0.02) was significantly lower for ABN compared to CONV. The pooled odds ratios for CTA, SFA and STA were not significantly different. No differences were identified in comparison to PSI/CAS. There was no statistically significant difference in procedural characteristics and functional outcomes.

Conclusions

The use ABN in total knee arthroplasty is a successful method of increased precision and accuracy for the restoration of the mechanical axis. In addition, there is no significant compromise in procedural or functional outcomes.
Intraluminal nutrients acutely strengthen rat intestinal MRP2 barrier function by a glucagon‐like peptide‐2‐mediated mechanism
Authors: Tocchetti Guillermo N. , Domínguez Camila J. , Zecchinati Felipe , Arana Maite R. , Rigalli Juan P. , Ruiz María L. , Villanueva Silvina S. M. , Mottino Aldo D.
Published: June 2020

Aim

MRP2 is an intestinal ABC transporter that prevents the absorption of dietary xenobiotics. The aims of this work were: (1) to evaluate whether a short‐term regulation of intestinal MRP2 barrier function takes place in vivo after luminal incorporation of nutrients and (2) to explore the underlying mechanism.

Methods

MRP2 activity and localization were assessed in an in vivo rat model with preserved irrigation and innervation. Nutrients were administered into distal jejunum. After 30‐minutes treatments, MRP2 activity was assessed in proximal jejunum by quantifying the transport of the model substrate 2,4‐dinitrophenyl‐S‐glutathione. MRP2 localization was determined by quantitative confocal microscopy. Participation of extracellular mediators was evaluated using selective inhibitors and by immunoneutralization. Intracellular pathways were explored in differentiated Caco‐2 cells.

Results

Oleic acid, administered intraluminally at dietary levels, acutely stimulated MRP2 insertion into brush border membrane. This was associated with increased efflux activity and, consequently, enhanced barrier function. Immunoneutralization of the gut hormone glucagon‐like peptide‐2 (GLP‐2) prevented oleic acid effect on MRP2, demonstrating the participation of this trophic factor as a main mediator. Further experiments using selective inhibitors demonstrated that extracellular adenosine synthesis and its subsequent binding to enterocytic A2B adenosine receptor (A2BAR) take place downstream GLP‐2. Finally, studies in intestinal Caco‐2 cells revealed the participation of A2BAR/cAMP/PKA intracellular pathway, ultimately leading to increased MRP2 localization in apical domains.

Conclusion

These findings reveal an on‐demand, acute regulation of MRP2‐associated barrier function, constituting a novel physiological mechanism of protection against the absorption of dietary xenobiotics in response to food intake.
Grazing by wild red deer maintains characteristic vegetation of semi‐natural open habitats: Evidence from a three‐year exclusion experiment
Authors: Riesch Friederike , Tonn Bettina , Stroh Hans Georg , Meißner Marcus , Balkenhol Niko , Isselstein Johannes
Published: June 2020

Questions

Conservation management of semi‐natural open habitats today has to compensate for the decline of traditional practices of agricultural land use. Can wild and free‐ranging ungulates, such as red deer, contribute to the preservation of characteristic open habitat plant communities?

Location

Grafenwöhr military training area, Germany.

Methods

We set up a grazing exclusion experiment in grasslands (lowland hay meadows) and heathlands (European dry heaths) and monitored structural vegetation characteristics (sward height, bare soil, biomass contribution of Calluna vulgaris, litter height, woody species individuals) in open and fenced plots within a three‐year study period. We compared plant species richness, diversity and community composition before and after the experimental period.

Results

In grasslands, plant species diversity was significantly reduced in fenced compared to open plots and in both habitat types, plant community composition responded to the exclusion of red deer. When fences prevented red deer grazing, increasing height of sward and litter in both habitat types as well as reduced cover of bare soil and increasing number of woody plant individuals in heathlands indicated beginning succession. In annually mown grasslands, where the regrowth provides attractive forage for red deer, the differences between open and fenced plots were most pronounced.

Conclusions

Overall, our results indicate that the conservation value of the studied open habitat types started to decrease after red deer exclusion. Grazing by wild red deer can hence provide benefits to vegetation structure and diversity and could therefore enrich the set of tools available for the conservation management of semi‐natural open vegetation types.
Pharmacogenetics of trough serum anti‐TNF levels in paediatric inflammatory bowel disease
Authors: Salvador‐Martín Sara , Pujol‐Muncunill Gemma , Bossacoma Ferran , Navas‐López Víctor Manuel , Gallego‐Fernández Carmen , Segarra Oscar , Clemente Susana , Muñoz‐Codoceo Rosana , Viada Javier , Magallares Lorena , Martínez‐Ojinaga Eva , Moreno‐Álvarez Ana , Solar‐Boga Alfonso , Loverdos Inés , Merino‐Bohórquez Vicente , Balboa‐Vega María Jesús , Rodriguez‐Martinez Alejandro , Alvarez‐Vayo Concepción , Sanchez Cesar , Tolin Mar , Blanca‐García José Antonio , García‐Romero Ruth , Eizaguirre Francisco Javier , Sánchez‐Hernandez José Germán , de Caldas Rafael Gonzalez , Millán‐Jimenez Antonio , Aznal Elena , Abarca‐Zabalía Judith , Sanjurjo‐Sáez María , López‐Fernández Luis Andrés
Published: June 2020

Aims

Identifying DNA variants associated with trough serum anti‐tumour necrosis factor (TNF) levels could predict response to treatment in inflammatory bowel disease (IBD). To date, no specific studies have been performed in children. The aim of this study was to identify genetic variants associated with trough serum anti‐TNF levels and whether these variants are differential markers for infliximab and adalimumab.

Methods

We included 154 children (age < 18 years) from 17 hospitals who had been diagnosed with IBD and actively treated with infliximab or adalimumab. Twenty‐one polymorphisms were genotyped using real‐time PCR. Trough serum anti‐TNF levels were measured using enzyme‐linked immunosorbent assay (ELISA). The association between DNA polymorphisms and the therapeutic range or the absolute values of anti‐TNF drugs was analysed by Fisher exact test, student's t‐test and logistic regression.

Results

The variants rs5030728 (TLR4) and rs11465996 (LY96) were associated with subtherapeutic infliximab levels. rs1816702 (TLR2) was associated with supratherapeutic levels and rs3397 (TNFRSF1B) with subtherapeutic levels of adalimumab (P < .05). In addition, rs1816702 (TLR2) and rs2569190 (CD14) were associated with absolute values of trough serum adalimumab, and rs2569190 (CD14) was associated with absolute values of trough serum adalimumab and infliximab (P < .05).

Conclusion

Genotyping of these DNA variants before starting treatment may help to select the best anti‐TNF drug in paediatric patients. The SNP rs1816702 is the most promising marker for tailoring the anti‐TNF regimen in children with IBD. For the first time, DNA variants are associated with trough serum anti‐TNF levels.
Environmental conditions at the Last Interglacial (Eemian) site Neumark‐Nord 2, Germany inferred from stable isotope analysis of freshwater mollusc opercula
Authors: Milano Stefania , Pop Eduard , Kuijper Wim , Roebroeks Wil , Gaudzinski‐Windheuser Sabine , Penkman Kirsty , Kindler Lutz , Britton Kate
Published: June 2020

Mollusc biogenic carbonates are valuable records of past environmental conditions. In particular, carbonate oxygen (δ18O) and carbon (δ13C) stable isotopes can be used to reconstruct different physical and chemical parameters, according to the different genera used (marine, freshwater or terrestrial). The Last Interglacial (early Eemian) palaeolake of Neumark‐Nord 2 (NN2), Germany provides an excellent example of a Neanderthal archaeological site with abundant freshwater carbonate remains. As in other European contexts, one of the most abundant species is Bithynia tentaculata. In order to provide a robust regional baseline for the interpretation of the archaeological data, this study includes a calibration phase on modern B. tentaculata opercula. The results indicate that these calcitic structures are likely to be subjected to a growth slowdown/cessation during summer, which influences their geochemistry, reflecting mainly the water properties of the rest of the year. This modern calibration, together with the existing palaeoenvironmental reconstructions developed for NN2 (e.g. pollen data), represents a valuable opportunity to establish B. tentaculata opercula as reliable environmental proxies applicable to several other freshwater contexts. The isotope data of the NN2 opercula, in agreement with the pollen record, indicate that the major archaeological horizon was formed during a rather wet period and potentially in a semi‐forested environment. However, human occupation occurred also during drier phases at the site and within a wide temperature range, indicating the absence of restricted environmental preferences by the local Neanderthal groups.
Morphometry of lower cheek teeth of cave bears (Carnivora, Ursidae) and general remarks on the dentition variability
Authors: Baryshnikov Gennady F. , Puzachenko Andrey Y.
Published: June 2020

The variability of lower 6776 cheek teeth of spelaeoid (Ursus spelaeus,U. kanivetz,U. deningeri,U. kudarensis,U. saviniandU. rossicus) and arctoid lineages (extant and extinctU. arctos) recovered from 176 palaeontological localities was analysed by methods of univariate and multivariate statistics. For comparison, teeth ofU. minimusandU. etruscusspecies, which are ancestral taxa for cave bears and brown bear, were studied. The performed analyses indicate great variability of tooth crown in lower cheek teeth; no distinct general trend was identified in the changes, except for an increase in p4 roundness and in m3 size fromU. minimusto big cave bears. Centroids ofU. minimusandU. etruscusare at a great distance from those of cave bears;U. arctosoccupies an intermediate position between the two groups. Molar characteristics in general are close inU. saviniandU. rossicus. The bear species are differentiated in the morphospaces by morphometric variations in the lower cheek teeth but less markedly than in the morphospaces of the upper cheek teeth. A test of the inhibitory developmental cascade model showed that a linear relationship between lower molar dimensions became clear only after premolar p4 was included in the model. Evolutionary trends were found in the tooth changes with time (differently expressed in individual species and in different teeth) depending on environments, in particular on the elevation of the locality above the sea level. The allometric pattern differentiation does not always coincide with phylogenetic relationships between taxa, being most often revealed at the subspecies level. There is a dominant covariance between the upper and lower rows of teeth in accordance with the occlusion scheme. It may vary in manifestation depending on the particular species.
Utilization of speech‐language, occupational and physical therapy by diagnosis of autism spectrum disorder
Authors: Yingling Marissa E. , Bell Bethany A.
Published: June 2020

Background

Although Medicaid coverage of treatment for children with autism spectrum disorder (ASD) is expanding, we know little about when children receive speech‐language, occupational and/or physical therapy. The objective of this study was to examine the relationships between predisposing, enabling and need characteristics and utilization of speech‐language, occupational and physical therapy by diagnosis of ASD.

Methods

We integrated administrative, Medicaid and Census data using a large sample of children with ASD who enrolled in a 1915(c) Home and Community Based Medicaid waiver in a south‐eastern state (N= 1,968) to explore (1) the percent of treatment utilization by ASD diagnosis, (2) the type of therapy utilized and (3) the predisposing, enabling and need characteristics associated with utilization.

Results

The percent of utilization was 71%; 65.8% utilized SLT, 33.4% utilized OT and 18.4% utilized PT. Enabling (i.e., urbanicity, age of diagnosis and early intervention programme enrolment) and need (i.e., intellectual disability) characteristics were associated with utilization whereas predisposing social characteristics (i.e., sex and child race‐ethnicity and neighbourhood racial composition, poverty and affluence) were not associated with utilization.

Conclusions

Findings highlight the value in monitoring when children begin treatment. As governments in the United States and globally work to maximize children's potential, additional research that can inform efforts to facilitate earlier utilization will be key to promoting optimal outcomes.
Land rental markets and labor productivity: Evidence from rural China
Authors: Zhang Jian , Mishra Ashok K. , Zhu Peixin
Published: June 2020

This study investigates the impact of the land rental market on labor productivity in rural China. Particular attention is given to farm and nonfarm labor productivity. Using 2012 household‐level data and a multinomial endogenous switching treatment regression technique, we find that rural households renting in farmland increased labor productivity in the farm sector by about 55%, whereas labor productivity in the nonfarm sector decreased by about 6%. We also find that rural households renting out farmland had lower labor productivity in both the farm and nonfarm sectors by 13% and 9%, respectively. More family labor transferred from the farm to the nonfarm sector after renting out land.
IT Outsourcing and Vendor Cost Improvement Strategies under Asymmetric Information
Authors: Jain Tarun , Hazra Jishnu , Cheng T.C. Edwin
Published: June 2020

In this article, we study the scenario under which two information technology (IT) vendor firms compete for the outsourcing requirements of a client firm. The vendors' cost structures are private information. In addition, the vendors can improve their unit costs through learning‐by‐doing and by making investments in process improvement, that is, induced learning. We study the impacts of vendor‐based learning and process improvement in the asymmetric cost setting on the client firm's outsourcing strategy and the vendor firms' process improvement investments. Our analysis reveals that the client firm may adopt the single‐sourcing strategy or a combination of dual and single‐sourcing strategies depending on the learning efficiency of the vendor base. We also find that high heterogeneity in the vendor cost structure increases the first‐period outsourcing requirements of the client firm. Our findings provide interesting managerial implications for the IT outsourcing industry.
Role of Analytics for Operational Risk Management in the Era of Big Data
Authors: Araz Ozgur M , Choi Tsan‐Ming , Olson David L , Salman F. Sibel
Published: June 2020

Operational risk management (ORM) is critical for any organization, and in the big data era, analytical tools for operational risk management are evolving faster than ever. This paper examines recent developments in academic ORM literature from the data analytics perspective. We focus on identifying present trends in ORM related to various types of natural and man‐made disasters that have been challenging all aspects of life. Although we examine the broader operations management (OM) literature, we keep the focus on the articles published in the well‐regarded OM journals, including both empirical and analytical outlets. We highlight how the use of data analytics tools and methods have facilitated ORM. We discuss the need for data monitoring and the integration of various analytical tools into decision making processes by classifying the literature on application fields, analytics techniques, and the strategies used for implementation. We summarize our findings and propose a process to implement data‐driven ORM with future research directions.
Glucagon‐like peptide‐1 receptor agonists and sodium‐glucose co‐transporter‐2 inhibitors as combination therapy for type 2 diabetes: A systematic review and meta‐analysis
Authors: Mantsiou Chrysanthi , Karagiannis Thomas , Kakotrichi Panagiota , Malandris Konstantinos , Avgerinos Ioannis , Liakos Aris , Tsapas Apostolos , Bekiari Eleni
Published: June 2020

Aim

To assess the efficacy and safety of combination therapy with a glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) and a sodium‐glucose co‐transporter‐2 inhibitor (SGLT2i) in patients with type 2 diabetes.

Methods

We searched Medline, Embase, the Cochrane Library and grey literature sources up to 2 December 2019 for randomized controlled trials in adults with type 2 diabetes assessing the combination of GLP‐1RA and SGLT2i, either as co‐initiation therapy or as add‐on to each other, against placebo or an active comparator. The primary outcome was change in HbA1c. Secondary outcomes included change in body weight, blood pressure and estimated glomerular filtration rate, and incidence of severe hypoglycaemia, all‐cause mortality, cardiovascular mortality, myocardial infarction, stroke and hospitalization for heart failure. We pooled data using random effects meta‐analyses.

Results

Seven trials (1913 patients) were eligible. Compared with GLP‐1RA, GLP‐1RA/SGLT2i combination therapy was associated with a greater reduction in HbA1c (weighted mean difference −0.61%, 95% CI −1.09% to −0.14%, four studies), body weight (−2.59 kg, −3.68 to −1.51 kg, three studies) and systolic blood pressure (−4.13 mmHg, −7.28 to −0.99 mmHg, four studies). Compared with SGLT2i, GLP‐1RA/SGLT2i combination therapy reduced HbA1c (−0.85%, −1.19% to −0.52%, six studies) and systolic blood pressure (−2.66 mmHg, −5.26 to −0.06 mmHg, six studies), but not body weight (−1.46 kg, −2.94 to 0.03 kg, five studies). After excluding data for one trial that had a considerably longer duration than the remaining studies, body weight was also reduced versus SGLT2i (−1.79 kg, −2.99 to −0.59 kg, five studies). Combination therapy did not increase the incidence of severe hypoglycaemia. Data for mortality and cardiovascular outcomes were scarce.

Conclusions

GLP‐1RA/SGLT2i combination therapy seems to reduce HbA1c, body weight and systolic blood pressure without increasing the risk of severe hypoglycaemia compared with either GLP‐1RA or SGLT2i. No conclusions can be made regarding long‐term effectiveness or the effect on cardiovascular outcomes.
The impact of tocilizumab on anxiety and depression in patients with rheumatoid arthritis
Authors: Tiosano Shmuel , Yavne Yarden , Watad Abdulla , Langevitz Pnina , Lidar Merav , Feld Joy , Tishler Moshe , Aamar Suhail , Elkayam Ori , Balbir‐Gurman Alexandra , Molad Yair , Ehrlich Sharon , Abu‐Shakra Mahmoud , Amital Daniela , Amital Howard
Published: June 2020

Background

Mood disorders, such as anxiety and depression, are extremely prevalent among patients with rheumatoid arthritis (RA). In this study, we assessed the impact of treatment with tocilizumab (TCZ), an IL‐6 antagonist, upon anxiety and depressive symptoms in a cohort of RA patients.

Materials and Methods

Study participants were adults diagnosed with RA who received a weekly subcutaneous injection of tocilizumab for 24 weeks. We used the Hamilton Depression (HDRS) and Anxiety (HAMA) scores in order to assess the severity of depression and anxiety, respectively. RA disease activity indices and depression and anxiety levels were assessed at baseline, 4 weeks and study completion.

Results

Ultimately, 91 patients were included in the study. The mean age was 54 years, and the majority were female (79%). The mean score in all disease activity indices as well as depression and anxiety levels decreased dramatically from baseline to study completion. Sixty patients (66%) demonstrated a significant decrease in anxiety and/or depression levels. When logistic regression was performed, an HDRS score indicative of depression at study baseline demonstrated an independent association with a significant psychiatric response whilst older age and increased baseline weight were negatively associated. HAMA and HDRA scores correlated with the following RA disease activity parameters, respectively; HAQ‐DI (r = .4, .42), DAS28 (r = .29, .32) and CDAI (0.28 and 0.33), all of them were statistically significant (P < .01).

Conclusions

This study has demonstrated a favourable impact of TCZ therapy on parameters reflecting depression and anxiety severity in patients with RA.
How community adaptation affects biodiversity–ecosystem functioning relationships
Authors: Aubree Flora , David Patrice , Jarne Philippe , Loreau Michel , Mouquet Nicolas , Calcagno Vincent
Published: June 2020

Evidence is growing that evolutionary dynamics can impact biodiversity–ecosystem functioning (BEF) relationships. However the nature of such impacts remains poorly understood. Here we use a modelling approach to compare random communities, with no trait evolutionary fine‐tuning, and co‐adapted communities, where traits have co‐evolved, in terms of emerging biodiversity–productivity, biodiversity–stability and biodiversity–invasion relationships. Community adaptation impacted most BEF relationships, sometimes inverting the slope of the relationship compared to random communities. Biodiversity–productivity relationships were generally less positive among co‐adapted communities, with reduced contribution of sampling effects. The effect of community‐adaptation, though modest regarding invasion resistance, was striking regarding invasion tolerance: co‐adapted communities could remain very tolerant to invasions even at high diversity. BEF relationships are thus contingent on the history of ecosystems and their degree of community adaptation. Short‐term experiments and observations following recent changes may not be safely extrapolated into the future, once eco‐evolutionary feedbacks have taken place.
Psychoacoustics and neurophysiological auditory processing in patients with Charcot‐Marie‐Tooth disease types 1A and 2A
Authors: Choi J. E. , Seol H. Y. , Seok J. M. , Hong S. H. , Choi B.‐O. , Moon I. J.
Published: June 2020

Background and purpose

Hidden hearing loss has been reported in patients with Charcot‐Marie‐Tooth (CMT) disease; however, the auditory‐processing deficits have not been widely explored. We investigated the psychoacoustic and neurophysiological aspects of auditory processing in patients with CMT disease type 1A (CMT1A) and type 2A (CMT2A).

Methods

A total of 43 patients with CMT1A and 15 patients with CMT2A were prospectively enrolled. All patients with CMT disease had normal sound‐detection ability by using pure‐tone audiometry. Spectral‐ripple discrimination, temporal modulation detection and auditory frequency‐following response were compared between CMT1A, CMT2A and control groups.

Results

Although all participants had normal audiograms, patients with CMT disease had difficulty understanding speech in noise. The psychoacoustic auditory processing was somewhat different depending on the underlying pathophysiology of CMT disease. Patients with CMT1A had degraded auditory temporal and spectral processing. Patients with CMT2A had no reduced spectral resolution, but they showed further reduced temporal resolution than the patients with CMT1A. The amplitudes of the frequency‐following response were reduced in patients with CMT1A and CMT2A, but the neural timing remained relatively intact.

Conclusions

When we first assessed the neural representation to speech at the brainstem level, the grand average brainstem responses were reduced in both patients with CMT1A and CMT2A compared with healthy controls. As the psychoacoustic aspects of auditory dysfunctions in CMT1A and CMT2A were somewhat different, it is necessary to consider future auditory rehabilitation methods based on their pathophysiology.
Discovery of lipophilic two‐pore channel agonists
Authors: Gerndt Susanne , Krogsaeter Einar , Patel Sandip , Bracher Franz , Grimm Christian
Published: June 2020

Two‐pore channels (TPCs) have been a hot topic in recent literature. Their involvement in various diseases such as viral infections and cancer is of great interest for drug research. Due to their localization in the endolysosomal system and the lack of cell‐permeable activators, complex techniques were required for studying channel functions. Here, we review the first published lipophilic small‐molecule activators of TPCs. In independent high‐throughput screens, several new agonists were discovered, which now allow simple and fast investigation of TPCs in more detail in intact cells and in vivo. Zhang et al. identified tricyclic and phenothiazine antidepressants as TPC1 and TPC2 activators by screening a library of approved drugs. In contrast, Gerndt et al. screened an extensive compound library with mostly new chemotypes and drug structures. The latter resulted in two structurally distinct high‐affinity agonists, which are able to selectively activate TPC2 in either an NAADP‐ or PI(3,5)P2‐like manner. Here, we discuss the advantages and drawbacks of the identified molecules and their structural features. The versatility by which TPCs can be activated indicates many opportunities for future studies.
A reply to the ‘critical evaluation of the Oscillayers methods and dataset’
Authors: Gamisch Alexander
Published: June 2020

Brown, Hill & Haywood (2020) offered a critical evaluation of the theory and methods of the Oscillayers approach and attempted to test its utility by reproducing global circulation model (GCM)‐based palaeoclimatic reconstructions of two variables (Bio1 and Bio12) for four different time points (130 ka, 787 ka, 3.2 Ma and 3.3 Ma). They concluded that Oscillayers show poor agreement with independent GCMs and thus do not provide a robust approximation of palaeoclimate throughout the Plio‐Pleistocene. Here, I demonstrate that the authors underestimated the ability of Oscillayers to reproduce independent GCMs by not taking into account inter‐framework differences between the models used to generate the Oscillayers and PaleoClim datasets. However, upon correcting this systematic error, differences in Bio1 and Bio12 between Oscillayers and PaleoClim GCMs are less than ± 1°C or ± 50 mm, on average, in 35.9% (range: 11.8–59.0%) or 46.7% (20.8–66.0%) of values, respectively. Thus, the agreement between Oscillayers and PaleoClim is, on average, c. 1.5–2 times higher than estimated by Brown et al. (2020) and mostly well above the inter‐model agreement between two commonly used GCMs (CCSM and MIROC) for the Last Glacial Maximum. Consequently, I conclude that the Oscillayers approach does provide reasonably robust approximations of palaeoclimate throughout the Plio‐Pleistocene. Some clarifications are given.
Proximity and distance: Think tanks handling the independence paradox
Authors: Jezierska Katarzyna , Sörbom Adrienne
Published: June 2020

The credibility of think tanks is grounded in their image as independent experts. In order to gain authority to act, think tanks must be seen as independent, but in order to exert influence and gain funding, think tanks are forced to compromise this independent image. We focus on how think tanks handle this independence paradox. How do think tanks use different resources to construct an independent image? The aim of the article is conceptual, as we develop a theoretical model of the independence paradox. This conceptual work is based on empirical analysis of attempts by think tanks in Poland and Sweden to create independence while maintaining influence. The two desirables central for think tanks, independence and influence, force them to make strategic choices about their relations with various actors. We conclude that the processes of keeping distance and arranging proximity are at the core of the independence paradox.
How global performance assessments shape attitudes toward government decision‐making: Survey experimental evidence
Authors: Davies Emmerich , Gift Thomas , Lastra‐Anadón Carlos X.
Published: June 2020

Global Performance Assessments (GPAs), which rank countries on a range of policy areas, can encourage domestic demands for policy reform. Yet can they also affect at what level of government—local or national—citizens want reform to take place? We theorize that, by emphasizing how countries fare relative to others, GPAs prompt citizens to view domestic policy underperformance as a “national problem requiring national solutions.” This increases calls for vesting policymaking authority in the hands of central governments. We argue that this effect should be most salient when underperformance is presented as a threat to a country's security because it induces citizens to “rally ‘round the flag.” To test our theory, we field an original survey experiment in the United States using fictitious news articles manipulating both the source of performance monitoring information and how it is presented. In line with our prediction, respondents are most likely to demand policy centralization when underperformance is framed using GPAs and citizens are primed to think of low scores as a threat to their country's security. These results indicate that GPAs could eventually increase calls for expanding the purview of national‐level politicians over policymaking.
Management of comorbidities in haemophilia
Authors: Kempton Christine L. , Makris Michael , Holme Pål Andre
Published: June 2020

With the introduction of clotting factor concentrates in the early 1970s, significant improvements in quality of life and life expectancy of persons with haemophilia (PWH) were realized. Unfortunately, as a result of transmission of HIV and hepatitis C virus (HCV) by contaminated concentrates in the 1980s, many of these gains were lost. Now with four decades of PWH unexposed to contaminated factor products and current treatments capable of suppressing and eliminating HIV and HCV, respectively, the survival rate is once again increasing. In addition to the usual comorbidities associated with advanced age in the general population, several specific issues occur in patients with bleeding disorders. This manuscript explores the incidence and management of the comorbidities of the ageing PWH with a focus on cardiovascular disease and osteoporosis.
Preventing iatrogenic facial pressure ulcers during spinal surgery: Prospective trial using a novel method and review of literature
Authors: Haleem Shahnawaz , Mihai Ruxandra , Rothenfluh Dominique Andre , Reynolds Jeremy
Published: June 2020

To assess the outcome of a novel method of preventing facial pressure ulcers in spinal surgery and a review of literature. A prospective trial using a novel method of facial protection using paraffin tulle gras dressing to cover bony prominences during spinal surgical procedures was performed. Patients were reviewed at 24 hours and 6 weeks. A telephone survey was also conducted post discharge. Over an 8‐month period, 12 patients (7F:5M, age 9‐72 years) underwent spine surgery for tumour stabilisation (n = 7), deformity correction (n = 4), and degenerative presentation (n = 1) with mean operative time of 472 minutes (range 150‐785 minutes) in prone position. All patients were managed by the same team using an agreed protocol. No pressure ulcers were noted in our study. One patient sustained minimal erythema, which resolved after 24 hours. All patients were satisfied with the care received. Facial pressure ulcers though much reduced are still common in spinal surgery. The common factors are the long duration of surgery, shear, friction, moisture, and intrinsic factors. Our strategy of an appropriate facial support and constant vigilance helped eliminate the incidence of iatrogenic facial ulcers in spinal surgery.
Last months of life of people with intellectual disabilities: A UK population‐based study of death and dying in intellectual disability community services
Authors: Todd Stuart , Bernal Jane , Shearn Julia , Worth Rhian , Jones Edwin , Lowe Kathy , Madden Phil , Barr Owen , Forrester Jones Rachel , Jarvis Paul , Kroll Thilo , McCarron Mary , Read Sue , Hunt Katherine
Published: June 2020

Background

Population‐based data are presented on the nature of dying in intellectual disability services.

Methods

A retrospective survey was conducted over 18 months with a sample of UK‐based intellectual disability service providers that supported over 12,000. Core data were obtained for 222 deaths within this population. For 158 (71%) deaths, respondents returned a supplemented and modified version of VOICES‐SF.

Results

The observed death was 12.2 deaths per 1,000 people supported per year, but just over a third deaths had been deaths anticipated by care staff. Mortality patterns, place of usual care and availability of external support exerted considerable influence over outcomes at the end of life.

Conclusion

Death is not a common event in intellectual disability services. A major disadvantage experienced by people with intellectual disabilities was that their deaths were relatively unanticipated. People with intellectual disabilities living in supported living settings, even when their dying was anticipated, experienced poorer outcomes.
Consequences of Piscine orthoreovirus genotype 1 (PRV‐1) infections in Chinook salmon (Oncorhynchus tshawytscha), coho salmon (O. kisutch) and rainbow trout (O. mykiss)
Authors: Purcell Maureen K. , Powers Rachel L. , Taksdal Torunn , McKenney Doug , Conway Carla M. , Elliott Diane G. , Polinski Mark , Garver Kyle , Winton James
Published: June 2020

Piscine orthoreovirus genotype 1 (PRV‐1) is the causative agent of heart and skeletal muscle inflammation (HSMI) in farmed Atlantic salmon (Salmo salar L.). The virus has also been found in Pacific salmonids in western North America, raising concerns about the risk to native salmon and trout. Here, we report the results of laboratory challenges using juvenile Chinook salmon, coho salmon and rainbow trout injected with tissue homogenates from Atlantic salmon testing positive for PRV‐1 or with control material. Fish were sampled at intervals to assess viral RNA transcript levels, haematocrit, erythrocytic inclusions and histopathology. While PRV‐1 replicated in all species, there was negligible mortality in any group. We observed a few erythrocytic inclusion bodies in fish from the PRV‐1‐infected groups. At a few time points, haematocrits were significantly lower in the PRV‐1‐infected groups relative to controls, but in no case was anaemia noted. The most common histopathological finding was mild, focal myocarditis in both the non‐infected controls and PRV‐1‐infected fish. All cardiac lesions were judged mild, and none were consistent with those of HSMI. Together, these results suggest all three species are susceptible to PRV‐1 infection, but in no case did infection cause notable disease in these experiments.
Market Structure and Transaction Costs of Index CDSs
Authors: COLLIN‐DUFRESNE PIERRE , JUNGE BENJAMIN , TROLLE ANDERS B.
Published: June 2020

Despite regulatory efforts to promote all‐to‐all trading, the post–Dodd‐Frank index credit default swap market remains two‐tiered. Transaction costs are higher for dealer‐to‐client than interdealer trades, but the difference is explained by the higher, largely permanent, price impact of client trades. Most interdealer trades are liquidity motivated and executed via low‐cost, low‐immediacy trading protocols. Dealer‐to‐client trades are nonanonymous; they almost always improve upon contemporaneous executable interdealer quotes, and dealers appear to price discriminate based on the perceived price impact of trades. Our results suggest that the market structure is a consequence of the characteristics of client trades: relatively infrequent, large, and differentially informed.
Bad Credit, No Problem? Credit and Labor Market Consequences of Bad Credit Reports
Authors: DOBBIE WILL , GOLDSMITH‐PINKHAM PAUL , MAHONEY NEALE , SONG JAE
Published: June 2020

We study the financial and labor market impacts of bad credit reports. Using difference‐in‐differences variation from the staggered removal of bankruptcy flags, we show that bankruptcy flag removal leads to economically large increases in credit limits and borrowing. Using administrative tax records linked to personal bankruptcy records, we estimate economically small effects of flag removal on employment and earnings outcomes. We rationalize these contrasting results by showing that, conditional on basic observables, “hidden” bankruptcy flags are strongly correlated with adverse credit market outcomes but have no predictive power for measures of job performance.
The prevalence and findings of fibre‐optic endoscopic evaluation of swallowing in hospitalised patients with dysphagia
Authors: Benjapornlert Paitoon , Kagaya Hitoshi , Shibata Seiko , Matsuo Koichiro , Inamoto Yoko , Kittipanya‐ngam Pajeemas , Saitoh Eiichi
Published: June 2020

Swallowing disorder or dysphagia is quite common in hospitalised patients. Using fibre‐optic endoscopic evaluation of swallowing (FEES) is one of the clinical standards for evaluating swallowing disorder to prevent serious consequences such as aspiration pneumonia. This study aimed to determine the prevalence and the associated risk of dysphagia in hospitalised patients by using FEES finding. We retrospectively analysed the FEES records from the patients who were screened and suspected of swallowing problems by a certified nurse of dysphagia nursing (CNDN). The FEES findings were compared between dysphagia and without dysphagia to evaluate the associated risk of dysphagia. Six‐hundred and nine FEES records were analysed. We found dysphagia 76% in patients who suspected swallowing problems by CNDN. FEES was assessed after the subjects had been admitted for 22 days on average. There was no difference in age between dysphagia and without dysphagia participants. However, the advanced age (age > 85 years old) increased the odd of dysphagia 1.18, P = .03. The primary disease of the subjects was mainly cerebrovascular disease (24%) and pneumonia (22%). Abnormal FEES findings including soft palate elevation, velopharyngeal contraction, whiteout, volitional cough, glottis closure during breath holding, cough reflex and presence of secretion in pharynx were found in hospitalised patients with dysphagia. The prevalence of dysphagia was high in hospitalised patients. Hence, screening the swallowing problem by nurse and FEES evaluation is essential to detect and prevent the complication in the patient who has dysphagia.
How to choose your study design
Authors: Mellis Craig M
Published: June 2020

Research designs are broadly divided into observational studies (i.e. cross‐sectional; case–control and cohort studies) and experimental studies (randomised control trials, RCTs). Each design has a specific role, and each has both advantages and disadvantages. Moreover, while the typical RCT is a parallel group design, there are now many variants to consider. It is important that both researchers and paediatricians are aware of the role of each study design, their respective pros and cons, and the inherent risk of bias with each design. While there are numerous quantitative study designs available to researchers, the final choice is dictated by two key factors. First, by the specific research question. That is, if the question is one of ‘prevalence’ (disease burden) then the ideal is a cross‐sectional study; if it is a question of ‘harm’ – a case–control study; prognosis – a cohort and therapy – a RCT. Second, by what resources are available to you. This includes budget, time, feasibility re‐patient numbers and research expertise. All these factors will severely limit the choice. While paediatricians would like to see more RCTs, these require a huge amount of resources, and in many situations will be unethical (e.g. potentially harmful intervention) or impractical (e.g. rare diseases). This paper gives a brief overview of the common study types, and for those embarking on such studies you will need far more comprehensive, detailed sources of information.
Semi‐automatic intraosseous device (EZ‐IO) in a paediatric emergency department
Authors: Mori Takaaki , Takei Hirokazu , Sasaoka Yuta , Nomura Osamu , Ihara Takateru
Published: June 2020

Aim

Intraosseous access is an alternative to conventional intravenous access. A number of studies have demonstrated the utility and safety of EZ‐IO, a recently introduced semi‐automatic intraosseous device. However, few studies have investigated the use of EZ‐IO in the paediatric emergency setting. The aim of this study was to describe the epidemiological characteristics EZ‐IO use including complications among paediatric patients in a paediatric emergency department.

Methods

We conducted a retrospective descriptive study enrolling children younger than 16 years who visited our emergency department between January 2013 and August 2018. Data on age, gender, diagnosis, insertion success rate and complications were collected and analysed.

Results

Seventy‐two patients were enrolled; of these 38 (52.8%) were male. The median age was 9 months (interquartile range: 3–34.5 months). Of the total, 22 (30.6%) received more than one IO insertion. Ninety‐seven consecutive IO insertions were identified. The rate of successful insertions was achieved at 92.7% (90 insertions). There were 21 complications (21.6%), including 17 extravasations (17.5%) of fluid and four dermal abrasions (4.1%). We found no cases of complications that may have compromised patient safety.

Conclusions

The success rate of the EZ‐IO insertion was high in paediatric patients. However, we found a higher incidence of dermal abrasions, which might be a complication specific to children.
The association between metabolically healthy obesity and risk of cancer: A systematic review and meta‐analysis of prospective cohort studies
Authors: Lin Chien‐Ju , Chang Yu‐Chen , Cheng Ting‐Yao , Lo Kai , Liu Shu‐Jung , Yeh Tzu Lin
Published: June 2020

The risk of cancer among adults with metabolically healthy obesity (MHO) has not yet been established. We systematically searched from inception to 15 March 2020. We included prospective cohort studies that compared participants with MHO and participants with metabolically healthy non‐obesity (MHNO) for incidence of any type of cancer. Benign tumors, cancer mortality or cancer prognosis were not in the scope of our analysis. The Newcastle–Ottawa Scale was used for quality assessment. Ultimately, eight studies with a total of 12 542 390 participants were included. The pooled meta‐analysis using random effect model showed participants with MHO demonstrated a significantly increased risk of developing cancer (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.05 to 1.23; and I2 = 39%) than those with MHNO. The subgroup analysis revealed a higher pooled estimate (OR, 1.17; 95% CI, 1.01–1.35; and I2 = 56%) in comparison with metabolically healthy normal weight. No evidence of effect modification by age, sex, ethnicity, smoking, sample size or length of follow‐up was found. In conclusion, the present study reports a positive association between MHO and cancer incidence. All individuals with obesity, even in the absence of metabolic dysfunction, should be encouraged to lose weight.