bluuebunny/crossref_metadata_2025 huggingface dataset:
Utility of hybrid SPECT/CT in primary melanoma lymphoscintigraphy: A retrospective case series
Authors: Tew Khimling , Farlow David
Published: November 2016

Introduction

Sentinel lymph node (SLN) biopsy is widely accepted as an important part of staging cutaneous malignant melanoma. Hybrid single photon emission computed tomography and computed tomography (SPECT/CT) may identify additional SLN and provide important information to the surgeon performing SLN biopsy. We report our experience at a major referral centre for melanoma surgery.

Methods

Retrospective case series of pre‐operative sentinel node lymphoscintigraphy for primary melanoma over a consecutive 12‐month period. All patients had planar imaging and hybrid SPECT/CT.

Results

At least 1 SLN was successfully identified in 82 of 86 eligible patients (95.3%). These 82 patients had 144 SLNs (mean 1.8). There were no patients where the SLN was seen only with SPECT/CT. Additional information was provided by SPECT/CT in 32 patients (39.0%). Histology reports were available for 52 patients, 9 (17.3%) had at least 1 SLN positive for metastatic disease.

Conclusions

We achieved a high rate of SLN identification. SPECT/CT was most frequently helpful when the primary melanoma was located in the head, neck and trunk. Routine use of SPECT/CT during lymphoscintigraphy provides important anatomical information and may reduce the false‐negative rate.
SNPs selected by information content outperform randomly selected microsatellite loci for delineating genetic identification and introgression in the endangered dark European honeybee (Apis mellifera mellifera)
Authors: Muñoz Irene , Henriques Dora , Jara Laura , Johnston J. Spencer , Chávez‐Galarza Julio , De La Rúa Pilar , Pinto M. Alice
Published: November 2016

The honeybee (Apis mellifera) has been threatened by multiple factors including pests and pathogens, pesticides and loss of locally adapted gene complexes due to replacement and introgression. In western Europe, the genetic integrity of the native A. m. mellifera (M‐lineage) is endangered due to trading and intensive queen breeding with commercial subspecies of eastern European ancestry (C‐lineage). Effective conservation actions require reliable molecular tools to identify pure‐bred A. m. mellifera colonies. Microsatellites have been preferred for identification of A. m. mellifera stocks across conservation centres. However, owing to high throughput, easy transferability between laboratories and low genotyping error, SNPs promise to become popular. Here, we compared the resolving power of a widely utilized microsatellite set to detect structure and introgression with that of different sets that combine a variable number of SNPs selected for their information content and genomic proximity to the microsatellite loci. Contrary to every SNP data set, microsatellites did not discriminate between the two lineages in the PCA space. Mean introgression proportions were identical across the two marker types, although at the individual level, microsatellites' performance was relatively poor at the upper range of Q‐values, a result reflected by their lower precision. Our results suggest that SNPs are more accurate and powerful than microsatellites for identification of A. m. mellifera colonies, especially when they are selected by information content.
DNAbarcoding of crickets, katydids and grasshoppers (Orthoptera) from Central Europe with focus on Austria, Germany and Switzerland
Authors: Hawlitschek O. , Morinière J. , Lehmann G. U. C. , Lehmann A. W. , Kropf M. , Dunz A. , Glaw F. , Detcharoen M. , Schmidt S. , Hausmann A. , Szucsich N. U. , Caetano‐Wyler S. A. , Haszprunar G.
Published: November 2016

We present aDNAbarcoding study on the insect order Orthoptera that was generated in collaboration between four barcoding projects in three countries, viz. Barcoding Fauna Bavarica (Germany), German Barcode of Life, Austrian Barcode of Life and Swiss Barcode of Life. Our data set includes 748COIsequences from 127 of the 162 taxa (78.4%) recorded in the three countries involved. Ninety‐three of these 122 species (76.2%, including all Ensifera) can be reliably identified usingDNAbarcodes. The remaining 26 caeliferan species (families Acrididae and Tetrigidae) form ten clusters that share barcodes among up to five species, in three cases even across different genera, and in six cases even sharing individual barcodes. We discuss incomplete lineage sorting and hybridization as most likely causes of this phenomenon, as the species concerned are phylogenetically young and hybridization has been previously observed. We also highlight the problem of nuclear mitochondrial pseudogenes (numts), a known problem in the barcoding of orthopteran species, and the possibility ofWolbachiainfections. Finally, we discuss the possible taxonomic implications of our barcoding results and point out future research directions.
Efficacy and safety of two dosages of canrenone as add‐on therapy in hypertensive patients taking ace‐inhibitors or angiotensin II receptor blockers and hydrochlorothiazide at maximum dosage in a randomized clinical trial: The ESCAPE‐IT trial
Authors: Derosa Giuseppe , Maffioli Pamela , D'Avino Maria , Sala Carla , Mugellini Amedeo , Vulpis Vito , Felis Salvatore , Guasti Luigina , Sarzani Riccardo , Bestetti Alessandro , Vanasia Massimo , Gaudio Giovanni ,   the ESCAPE‐IT Trial Investigators group
Published: November 2016

Aim

To evaluate the effects of canrenone as add‐on therapy in patients already treated with angiotensin‐converting enzyme inhibitors (ACE‐I) or angiotensin II receptor blockers (ARBs) and hydrochlorothiazide at the maximum dosage (25 mg/d).

Method

In this randomized, open‐label, controlled trial, we enrolled 175 Caucasian patients with essential hypertension not well controlled by concomitant ACE‐I or ARBs and hydrochlorothiazide. At baseline, 87 patients (57 males and 30 females) were randomized to add canrenone 50 mg, and 88 (56 males and 32 females) patients to canrenone 100 mg, once a day, for 3 months. At baseline and after 3 months, we evaluated blood pressure (BP), pulse pressure (PP), heart rate (HR), fasting plasma glucose (FPG), homeostasis model assessment insulin (HOMA Index), lipid profile, electrolytes, uric acid, estimated glomerular filtration rate (eGFR), plasma urea, aldosterone, B‐type natriuretic peptide (BNP), and galectin‐3.

Results

Blood pressure decreased with both dosages of canrenone, with a better effect with canrenone 100 mg (−20.26 vs −23.68 mm Hg for SBP, and −10.58 vs −12.38 mm Hg for DBP), without a clinically relevant increase in potassium levels. We did not observe any differences regarding FPG or HOMA Index, nor of lipid profile, with the exception of triglycerides, which increased compared to baseline with canrenone 50 mg (+0.25 vs +0.34 mEq/L). Creatinine slightly increased with canrenone 100 mg (+0.02 vs +0.05 mg/dL), although no variations of eGFR were observed in neither groups. There was an increase in aldosterone levels with canrenone 50 mg. No changes in BNP or galectin‐3 were recorded.

Conclusion

Both canrenone dosages gave a decrease in blood pressure, with a better effect with the higher dose, with only a slight increase in potassium and creatinine levels, which were not clinically relevant. Clinical Trials Registration Eudract number: 2010‐023606‐13; ClinicalTrials.gov NCT02687178.
Passive vertical integration and strategic delegation
Authors: Hunold Matthias , Stahl Konrad
Published: November 2016

With backward acquisitions in their efficient supplier, downstream firms profitably internalize the effects of their actions on their rivals' sales, while upstream competition is also relaxed. Downstream prices increase with passive, yet decrease with controlling acquisition. Passive acquisition is profitable when controlling acquisition is not. Downstream acquirers strategically abstain from vertical control, thus delegating commitment to the supplier, and with it high input prices, allowing them to charge high downstream prices. The effects of passive backward acquisition are reinforced with the acquisition by several downstream firms in the efficient supplier. The results are sustained when suppliers charge two‐part tariffs.
Information acquisition, referral, and organization
Authors: Grassi Simona , Ma Ching‐to Albert
Published: November 2016

Each of two experts may provide a service to a client. Experts' cost comparative advantage depends on an unknown state, but an expert may exert effort to get a private signal about it. In a market, an expert may refer the client to the other for a fee. In equilibrium, only one expert exerts effort and refers, and the equilibrium allocation is inefficient. Referral efficiency can be restored when experts form an organization, in which a referring expert must bear the referred expert's cost. However, the referred expert shirks from work effort because of the lack of cost responsibility.
Understanding in‐house transactions in the real estate brokerage industry
Authors: Han Lu , Hong Seung‐Hyun
Published: November 2016

About 20% of residential real estate transactions in North America are in‐house transactions, for which buyers and sellers are represented by the same brokerage. We examine to what extent in‐house transactions are explained by agents' strategic incentives as opposed to matching efficiency. Using home transaction data, we find that agents are more likely to promote internal listings when they are financially rewarded and such effect becomes weaker when consumers are more aware of agents' incentives. We further develop a structural model and find that about one third of in‐house transactions are explained by agents' strategic promotion, causing significant utility loss for home buyers.
Post‐IFRS Revaluation Adjustments and Executive Compensation
Authors: Chen Kevin C. W. , Tang Feng
Published: November 2016

International Financial Reporting Standards (IFRS) allow firms to record adjustments (gains or losses) from the revaluation of investment properties in their income statements. After Hong Kong adopted IFRS in 2005, property companies were required to move their revaluation gains and losses (RGL) from equity to income. We find RGL to be a significant determinant of executive compensation in these firms after 2005, but not before. We further find evidence that the RGL‐compensation association is driven by firms with relative weak corporate governance structure, such as firms in which the controlling shareholders own a relatively small percentage of shares, firms in which the controlling shareholders have control rights that exceed ownership rights, and firms that are no longer run by their founders.
A new family of standardized and symmetric indices for measuring the intensity and importance of plant neighbour effects
Authors: Díaz‐Sierra Rubén , Verwijmeren Mart , Rietkerk Max , de Dios Víctor Resco , Baudena Mara
Published: November 2016

Measurements of competition and facilitation between plants often rely upon intensity and importance indices that quantify the net effect of neighbours on the performance of a target plant. A systematic analysis of the mathematical behaviour of the indices is lacking and leads to structural pitfalls, e.g. statistical problems detected in importance indices.

We summarize and analyse the mathematical properties that the indices should display. We review the properties of the commonly used indices focusing on standardization and symmetry, which are necessary to avoid compromising data interpretation. We introduce a new family of indices ‘Neighbour‐effect Indices’ that meet all the proposed properties.

Considering the commonly used indices, none of the importance indices are standardized, and only RII (Relative Interaction Index) displays all the required mathematical properties. The existing indices show two types of symmetries, namely, additive or commutative, which are currently confounded, potentially resulting in misleading interpretations. Our Neighbour‐effect Indices encompass two intensity and two importance indices that are standardized and have different and defined symmetries.

Our new additive intensity index, NIntA, is the first of its kind, and it is generally more suitable for assessing competition and facilitation intensity than the widely used RII, which may underestimate facilitation. Our new standardized importance indices solve the main statistical problems that are known to affect Cimp and Iimp. Intensity and importance with the same symmetry should be used within the same study. The Neighbour‐effect Indices, sharing the same formulation, will allow for unbiased comparisons between intensity and importance, and between types of symmetry.
Measuring and interpreting sexual selection metrics: evaluation and guidelines
Authors: Anthes Nils , Häderer Ines K. , Michiels Nico K. , Janicke Tim
Published: November 2016

Routine assessments of overall sexual selection, including comparisons of its direction and intensity between sexes or species, rely on summary metrics that capture the essence of sexual selection. Nearly all currently employed metrics require population‐wide estimates of individual mating success and reproductive success. The resulting sexual selection metrics, however, can heavily and systematically vary with the chosen approaches in terms of sampling, measurement, and analysis.

Our review illustrates this variation, using the Bateman gradient, a particularly prominent sexual selection metric. It represents the selection gradient on mating success and – given the latter's pivotal role in defining sexual selection – reflects a trait‐independent integrative proxy for the maximum strength of sexual selection. Drawing from a recent meta‐analysis, we evaluate potential biases arising from study design, data collection and parameter estimation, and provide suggestions to mitigate such biases in future studies.

With respect to study design, we argue that currently almost inexistent manipulative studies must complement the dominating correlative studies to inform us about causality in sexual selection. With respect to data collection, we outline how different measures of mating and reproductive success affect the components of sexual (and natural) selection that are reflected in standard summary metrics. With respect to parameter estimation, we show the potential impact of decisions about data inclusion and the chosen quantitative approach on inferences of sexual selection and its sex difference.

We expect this meta‐analytical review to aid future studies in providing less biased and more informative estimates of sexual selection.
History, Physical Examination, Laboratory Testing, and Emergency Department Ultrasonography for the Diagnosis of Acute Cholecystitis
Authors: Jain Ashika , Mehta Ninfa , Secko Michael , Schechter Joshua , Papanagnou Dimitri , Pandya Shreya , Sinert Richard
Published: November 2016

Background

Acute cholecystitis (AC) is a common differential for patients presenting to the emergency department (ED) with abdominal pain. The diagnostic accuracy of history, physical examination, and bedside laboratory tests for AC have not been quantitatively described.

Objectives

We performed a systematic review to determine the utility of history and physical examination (H&P), laboratory studies, and ultrasonography (US) in diagnosing AC in the ED.

Methods

We searched medical literature from January 1965 to March 2016 in PubMed, Embase, and SCOPUS using a strategy derived from the following formulation of our clinical question: patients—ED patients suspected of AC; interventions—H&P, laboratory studies, and US findings commonly used to diagnose AC; comparator—surgical pathology or definitive diagnostic radiologic study confirming AC; and outcome—the operating characteristics of the investigations in diagnosing AC were calculated. Sensitivity, specificity, and likelihood ratios (LRs) were calculated using Meta‐DiSc with a random‐effects model (95% CI). Study quality and risks for bias were assessed using the Quality Assessment Tool for Diagnostic Accuracy Studies.

Results

Separate PubMed, Embase, and SCOPUS searches retrieved studies for H&P (n = 734), laboratory findings (n = 74), and US (n = 492). Three H&P studies met inclusion/exclusion criteria with AC prevalence of 7%–64%. Fever had sensitivity ranging from 31% to 62% and specificity from 37% to 74%; positive LR [LR+] was 0.71–1.24, and negative LR [LR–] was 0.76–1.49. Jaundice sensitivity ranged from 11% to 14%, and specificity from 86% to 99%; LR+ was 0.80–13.81, and LR– was 0.87–1.03. Murphy's sign sensitivity was 62% (range = 53%–71%), and specificity was 96% (range = 95%‐97%); LR+ was 15.64 (range = 11.48–21.31), and LR– was 0.40 (range = 0.32–0.50). Right upper quadrant pain had sensitivity ranging from 56% to 93% and specificity of 0% to 96%; LR+ ranged from 0.92 to 14.02, and LR– from 0.46 to 7.86. One laboratory study met criteria with a 26% prevalence of AC. Elevated bilirubin had a sensitivity of 40% (range = 12%–74%) and specificity of 93% (range = 77%–99%); LR+ was 5.80 (range = 1.25–26.99), and LR– was 0.64 (range = 0.39–1.08). Five US studies with a prevalence of AC of between 10% and 46%. US sensitivity was 86% (range = 78%–94%) and specificity was 71% (range = 66%–76%); LR+ was 3.23 (range = 1.74–6.00), and LR– was 0.18 (range = 0.10–0.33).

Conclusion

Variable disease prevalence, coupled with limited sample sizes, increases the risk of selection bias. Individually, none of these investigations reliably rule out AC. Development of a clinical decision rule to include evaluation of H&P, laboratory data, and US are more likely to achieve a correct diagnosis of AC.
Tigecycline Reduces Ethanol Intake in Dependent and Nondependent Male and Female C57BL/6J Mice
Authors: Bergeson Susan E. , Nipper Michelle A. , Jensen Jeremiah , Helms Melinda L. , Finn Deborah A.
Published: November 2016

Background

The chronic intermittent ethanol (CIE) paradigm is valuable for screening compounds for efficacy to reduce drinking traits related to alcohol use disorder (AUD), as it measures alcohol consumption and preference under physical dependence conditions. Air control‐treated animals allow simultaneous testing of similarly treated, nondependent animals. As a consequence, we used CIE to test the hypothesis that tigecycline, a semisynthetic tetracycline similar to minocycline and doxycycline, would reduce alcohol consumption regardless of dependence status.

Methods

Adult C57BL/6J female and male mice were tested for tigecycline efficacy to reduce ethanol (EtOH) consumption using a standard CIE paradigm. The ability of tigecycline to decrease 2‐bottle choice of 15% EtOH (15E) versus water intake in dependent (CIE vapor) and nondependent (air‐treated) male and female mice was tested after 4 cycles of CIE vapor or air exposure using a within‐subjects design and a dose–response. Drug doses of 0, 40, 60, 80, and 100 mg/kg in saline were administered intraperitoneally (0.01 ml/g body weight) and in random order, with a 1‐hour pretreatment time. Baseline 15E intake was re‐established prior to administration of subsequent injections, with a maximum of 2 drug injections tested per week.

Results

Tigecycline was found to effectively reduce high alcohol consumption in both dependent and nondependent female and male mice.

Conclusions

Our data suggest that tigecycline may be a promising drug with novel pharmacotherapeutic characteristics for the treatment of mild‐to‐severe AUD in both sexes.
Effective Reduction in High Ethanol Drinking by Semisynthetic Tetracycline Derivatives
Authors: Syapin Peter J. , Martinez Joseph M. , Curtis David C. , Marquardt Patrick C. , Allison Clayton L. , Groot Jessica A. , Baby Carol , Al‐Hasan Yazan M. , Segura‐Ulate Ismael , Scheible Matthew J. , Nicholson Katy T. , Redondo Jose Luis , Trotter David R. M. , Edwards David S. , Bergeson Susan E.
Published: November 2016

Background

New pharmacotherapies to treat alcohol use disorders (AUD) are needed. Given the complex nature of AUD, there likely exist multiple novel drug targets. We, and others, have shown that the tetracycline drugs, minocycline and doxycycline, reduced ethanol (EtOH) drinking in mice. To test the hypothesis that suppression of high EtOH consumption is a general property of tetracyclines, we screened several derivatives for antidrinking activity using the Drinking‐In‐the‐Dark (DID) paradigm. Active drugs were studied further using the dose–response relationship.

Methods

Adult female and male C57BL/6J mice were singly housed and the DID paradigm was performed using 20% EtOH over a 4‐day period. Mice were administered a tetracycline or its vehicle 20 hours prior to drinking. Water and EtOH consumption was measured daily. Body weight was measured at the start of drug injections and after the final day of the experiment. Blood was collected for EtOH content measurement immediately following the final bout of drinking.

Results

Seven tetracyclines were tested at a 50 mg/kg dose. Only minocycline and tigecycline significantly reduced EtOH drinking, and doxycycline showed a strong effect size trend toward reduced drinking. Subsequent studies with these 3 drugs revealed a dose‐dependent decrease in EtOH consumption for both female and male mice, with sex differences in efficacy. Minocycline and doxycycline reduced water intake at higher doses, although to a lesser degree than their effects on EtOH drinking. Tigecycline did not negatively affect water intake. The rank order of potency for reduction in EtOH consumption was minocycline > doxycycline > tigecycline, indicating efficacy was not strictly related to their partition coefficients or distribution constants.

Conclusions

Due to its effectiveness in reducing high EtOH consumption coupled without an effect on water intake, tigecycline was found to be the most promising lead tetracycline compound for further study toward the development of a new pharmacotherapy for the treatment of AUD.
Changes in interleukin‐6 levels during electroconvulsive therapy may reflect the therapeutic response in major depression
Authors: Järventausta K. , Sorri A. , Kampman O. , Björkqvist M. , Tuohimaa K. , Hämäläinen M. , Moilanen E. , Leinonen E. , Peltola J. , Lehtimäki K.
Published: November 2016

Objective

Interleukin‐6 (IL‐6) has been reported to be elevated in major depressive disorder (MDD) but decreased by antidepressive medication. IL‐6 levels are markedly elevated both after epileptic seizures and single electroconvulsive therapy (ECT) session, but long‐term changes in IL‐6 levels after ECT have not been studied. The correlation between immediate and long‐term changes in proinflammatory cytokines and outcome after ECT was investigated.

Method

Thirty patients suffering from MDD participated in the study. IL‐6, interleukin‐1β (IL‐1β) and interleukin‐1 receptor antagonist (IL‐1RA) levels were examined at baseline and at 2 and 4 h after the first, fifth and the last ECT sessions. The response to ECT was measured with Montgomery‐Åsberg Depression Rating Scale (MADRS).

Results

ECT repeatedly caused an increase in IL‐6 levels at the 4‐h time point. However, the baseline IL‐6 levels decreased among remitters, but not among non‐remitters, towards the end of ECT. IL‐1β levels were mostly below detectable level, and IL‐1Ra levels did not change during and after ECT.

Conclusion

ECT has distinct acute and long‐term effects on IL‐6 levels. Interestingly, the long‐term effect of ECT on IL‐6 seems to correlate with outcome, providing further evidence of the mechanism of action of ECT and supporting the inflammation theory in MDD.
Increase of poorly proliferated p63+/Ki67+ basal cells forming multiple layers in the aberrant remodeled epithelium in nasal polyps
Authors: Zhao L. , Li Y. Y. , Li C. W. , Chao S. S. , Liu J. , Nam H. N. , Dung N. T. N. , Shi L. , Wang D. Y.
Published: November 2016

Background

Aberrant epithelial remodeling with the ectopic expression of p63 (basal cell markers) is an important pathologic phenomenon seen in chronically inflamed airway epithelium such as in nasal polyps (NPs).

Methods

Biopsies were obtained from 55 NP patients and 18 healthy controls (inferior turbinate). Among NP patients, 15 were treated with oral and nasal steroids, so that two sets of NP biopsies were taken before and after the treatments. p63, Ki67, type IV β‐tubulin, and cell cycle markers were investigated in these specimens.

Results

The number of p63+ cells is significantly higher in both hyperplastic (1.53‐fold, P < 0.0001) and squamous metaplastic (2.02‐fold, P < 0.0001) epithelium from NPs than from healthy controls. There are three types of proliferative basal cells (p63+/Ki67+) which are in different phases of the cell cycle, such as G1 phase (type I cells), S to G2 phase (type II cells), and mitosis (type III cells). Of importance, some type I cells may arrest after proliferation although they may still be p63+/Ki67+. In healthy epithelium, the ratio of the type I and II cells is almost 50:50. However, less type II cells are found in hyperplastic epithelium (34.85%, P = 0.012) and in squamous metaplastic epithelium (30.77%, P = 0.02) together with the presence of type III cells (3.45%, P = 0.01). These findings were not changed after steroid treatments.

Conclusions

An increase of poorly proliferated basal cells forming multiple layers, which may stain for basal cell markers but does not form a proper epidermal barrier, is an important histopathologic phenomenon in aberrant remodeled epithelium of NPs.
Ageing acute surgical population: the Auckland experience
Authors: Linkhorn Hannah , Hsee Li
Published: November 2016

Background

This study provides data supporting the supposition that more elderly patients are requiring surgical care and illustrates the risks associated with acute surgical illness in elderly patients.

Methods

The clinical records database was accessed to identify all patients discharged from general surgery and acute surgical unit (ASU) during 2013 and 2014. These groups were stratified by age (over 80 years). Data were collected on number of patients discharged per year, length of stay, number of intensive care unit admissions and number of procedures and mortality rates.

Results

There is an increasing number of patients aged over 80 years who were discharged from ASU; 7.02% (n = 296) in 2013 and 8.20% (n = 344) in 2014. Patients aged over 80 years were spending 1.88 days (P‐value < 0.001) longer in hospital than those under 80 years in 2014. Mortality rates in 2013 were 3.716 deaths per 100 admissions and 5.814 per 100 admissions in 2014. In 2013, the risk ratio of death in hospital for patients over 80 years was 36.4 (P‐value < 0.001) times higher than patients under 80 years.

Conclusion

The mean length of stay and mortality rates are higher for patients over 80 years. Mortality rates are higher in acute admissions compared with elective admissions. This identifies a need for increased care for elderly patients admitted for acute surgical care. We suggest a trial of attaching a specialist geriatrician to the ASU who will provide a service for at risk patients.
Practice variation of vaginal birth after cesarean and the influence of risk factors at patient level: a retrospective cohort study
Authors: Vankan Emy , Schoorel Ellen N. , van Kuijk Sander M. , Mol Ben‐Willem J. , Nijhuis Jan G. , Aardenburg Robert , Alink Marleen , de Boer Karin , Delemarre Friso M.C. , Dirksen Carmen D. , van Dooren Ivo M. , Franssen Maureen T.M. , Kaplan Mesrure , Kleiverda Gunilla , Kuppens Simone M.I. , Kwee Anneke , Langenveld Josje , Lim Frans T. , Melman Sonja , Sikkema Marko J. , Smits Luc J. , Visser Harry , woiski Mallory , Scheepers Hubertina C. , Hermens Rosella P.
Published: November 2016

Introduction

Large practice variation exists in mode of delivery after cesarean section, suggesting variation in implementation of contemporary guidelines. We aim to evaluate this practice variation and to what extent this can be explained by risk factors at patient level.

Material and methods

This retrospective cohort study was performed among 17 Dutch hospitals in 2010. Women with one prior cesarean section without a contraindication for a trial of labor were included. We used multivariate logistic regression analysis to develop models for risk factor adjustments. One model was derived to adjust the elective repeat cesarean section rates; a second model to adjust vaginal birth after cesarean rates. Standardized rates of elective repeat cesarean section and vaginal birth after cesarean per hospital were compared. Pseudo‐R2 measures were calculated to estimate the percentage of practice variation explained by the models. Secondary outcomes were differences in practice variation between hospital types and the correlation between standardized elective repeat cesarean section and vaginal birth after cesarean rates.

Results

In all, 1068 women had a history of cesarean section, of whom 71% were eligible for inclusion. A total of 515 women (67%) had a trial of labor, of whom 72% delivered vaginally. The elective repeat cesarean section rate at hospital level ranged from 6 to 54% (mean 29.8, standard deviation 11.8%). Vaginal birth after cesarean rates ranged from 50 to 90% (mean 71.8%, standard deviation 11.1%). More than 85% of this practice variation could not be explained by risk factors at patient level.

Conclusion

A large practice variation exists in elective repeat cesarean section and vaginal birth after cesarean rates that can only partially be explained by risk factors at patient level.
Addition of an immunomodulator can reverse antibody formation and loss of response in patients treated with adalimumab
Authors: Ungar B. , Kopylov U. , Engel T. , Yavzori M. , Fudim E. , Picard O. , Lang A. , Williet N. , Paul S. , Chowers Y. , Bar‐Gil Shitrit A. , Eliakim R. , Ben‐Horin S. , Roblin X.
Published: November 2016

Background

Anti‐adalimumab antibodies (AAA) are associated with loss of clinical response (LOR). Addition of an immunomodulator has been shown to reverse immunogenicity and regain response with infliximab monotherapy. Similar data on adalimumab are lacking.

Aim

To study the impact of immunomodulator addition on the emergence of AAA and LOR among adalimumab therapy patients.

Methods

The databases of three tertiary medical centres were reviewed to identify patients who developed AAA during adalimumab monotherapy with resultant LOR, and received an immunomodulator as a salvage combination therapy. All sera were prospectively analysed using previously described ELISA assays. Clinical response was determined using appropriate clinical scores. Elimination of AAA, designated as ‘sero‐reversal’, elevation of drug levels and regained clinical response were the sought outcomes.

Results

Twenty‐three patients (21 Crohn's disease, and 2 ulcerative colitis) developed AAA with subsequent LOR and were thereafter prescribed an immunomodulator as salvage therapy (thiopurine n = 14, methotrexate n = 9). Eleven patients (48%) underwent sero‐reversal with gradual elimination of AAA, increase in drug trough levels and restoration of clinical response (median time to sero‐reversal 5 months). In 12 patients (52%), immunogenicity and loss of response could not be reversed. There was no difference between responders and nonresponders in the type of immunomodulators used or baseline clinical characteristics.

Conclusions

In almost half of inflammatory bowel disease patients developing anti‐adalimumab antibodies and loss of response, established immunogenicity of adalimumab can be gradually reversed by the addition of immunomodulator therapy with restoration of a clinico‐biological response. However, these observations need to be confirmed with larger studies.
New data on morphology and ultrastructure of skin photophores in the deep‐sea squid Histioteuthis bonnellii (Férussac, 1834), Cephalopoda: Histioteuthidae
Authors: Cavallaro Mauro , Battaglia Pietro , Guerrera Maria Cristina , Abbate Francesco , Levanti Maria Beatrice , Andaloro Franco , Germanà Antonino , Laurà Rosaria
Published: November 2016

Morphology and ultrastructure of skin photogenic organs in the deep‐sea squid Histioteuthis bonnellii from the Strait of Messina (Mediterranean Sea) was investigated. The photophore is formed by a glandular complex, made up of photogenic cells involved in the light production process, and a set of annexes (filter, reflector, pigmented layer and gelatinous body), with suggested dioptric function. The photocytes have an elongated shape, often arranged in an approximately radial series within the chamber, and show eccentric rounded euchromatic nucleus. The filter shows a membranous tissue made up of rows of cells, rich in smooth endoplasmic reticulum. The analysis on reflector's cells highlighted the presence of several iridosomal platelets in the cytoplasm, having irregular and sinuous shape. The pigmented layer and the gelatinous body provide protection to the organ and may have dioptric functions too. The photogenic organs were found to be innervated by nerves, and it was possible to confirm the strictly glandular nature of the photophores of this species. The detailed anatomical descriptions of the photophores of H. bonnellii extend our current knowledge and provide a scientific basis for future studies aimed to relate the evolution of photogenic system to the ecology of this squid.
Genetic variation in the miR‐708 gene and its binding targets in bipolar disorder
Authors: Fiorentino Alessia , O'Brien Niamh Louise , Sharp Sally Isabel , Curtis David , Bass Nicholas James , McQuillin Andrew
Published: November 2016

Objective

rs12576775 was found to be associated with bipolar disorder (BD) in a genome‐wide association study (GWAS). The GWAS signal implicates genes for the microRNAs miR‐708 and miR‐5579 and the first exon of the Odd Oz/ten‐m homolog 4 gene (ODZ4). In the present study, miR‐708, its surrounding region, and its targets were analyzed for potential BD‐associated functional variants.

Methods

The miR‐708 gene and surrounding regions were screened for variation using high‐resolution melting (HRM) analysis in 1099 cases of BD, followed by genotyping of rare variants in an enlarged sample of 2078 subjects with BD, 1303 subjects with schizophrenia, and 1355 healthy controls. Whole‐genome sequencing data from 99 subjects with BD were analyzed for variation in potential miR‐708 binding sites. The minor allele frequencies (MAFs) of these variants were compared with those reported in reference individuals.

Results

Three variants detected by HRM were selected to be genotyped. rs754333774 was detected in three cases of BD, two cases of schizophrenia, and no controls. This variant is located 260 base pairs upstream from miR‐708 and may play a role in controlling the expression of the miR. Four variants were identified in miR‐708 targets binding sites. The MAFs of each of these variants were similar in BD and reference samples.

Conclusions

We report a single recurrent variant located near the miR‐708 gene that may have a role in BD and schizophrenia susceptibility. These findings await replication in independent cohorts, as do functional analyses of the potential consequences of this variant.
Childbirth Education Class and Birth Plans Are Associated with a Vaginal Delivery
Authors: Afshar Yalda , Wang Erica T. , Mei Jenny , Esakoff Tania F. , Pisarska Margareta D. , Gregory Kimberly D.
Published: November 2016

Background

To determine whether the mode of delivery was different between women who attended childbirth education (CBE) class, had a birth plan, or both compared with those who did not attend CBE class or have a birth plan.

Methods

This is a retrospective cross‐sectional study of women who delivered singleton gestations > 24 weeks at our institution between August 2011 and June 2014. Based on a self‐report at the time of admission for labor, women were stratified into four categories: those who attended a CBE class, those with a birth plan, both, and those with neither CBE or birth plan. The primary outcome was the mode of delivery. Multivariate logistic regression analyses adjusting for clinical covariates were performed.

Results

In this study, 14,630 deliveries met the inclusion criteria: 31.9 percent of the women attended CBE class, 12.0 percent had a birth plan, and 8.8 percent had both. Women who attended CBE or had a birth plan were older (p < 0.001), more likely to be nulliparous (p < 0.001), had a lower body mass index (p < 0.001), and were less likely to be African‐American (p < 0.001). After adjusting for significant covariates, women who participated in either option or both had higher odds of a vaginal delivery (CBE: OR 1.26 [95% CI 1.15–1.39]; birth plan: OR 1.98 [95% CI 1.56–2.51]; and both: OR 1.69 [95% CI 1.46–1.95]) compared with controls.

Conclusion

Attending CBE class and/or having a birth plan were associated with a vaginal delivery. These findings suggest that patient education and birth preparation may influence the mode of delivery. CBE and birth plans could be used as quality improvement tools to potentially decrease cesarean rates.
Mode of Delivery and Long‐Term Health‐Related Quality‐of‐Life Outcomes: A Prospective Population‐Based Study
Authors: Petrou Stavros , Kim Sung Wook , McParland Penny , Boyle Elaine M.
Published: November 2016

Background

Relatively little is known about the effects of mode of delivery on long‐term health‐related quality‐of‐life outcomes. Furthermore, no previous study has expressed these outcomes in preference‐based (utility) metrics.

Methods

The study population comprised 2,161 mothers recruited from a prospective population‐based study in the East Midlands of England encompassing live births and stillbirths between 32+0 and 36+6 weeks’ gestation and a sample of term‐born controls. Perinatal data were extracted from the mothers’ maternity records. Health‐related quality‐of‐life outcomes were assessed at 12 months postpartum, using the EuroQol Five Dimensions (EQ‐5D) measure with responses to the EQ‐5D descriptive system converted into health utility scores. Descriptive statistics and multivariable analyses were used to estimate the relationship between the mode of delivery and health‐related quality‐of‐life outcomes.

Results

The overall health‐related quality‐of‐life profile of the women in the study cohort mirrored that of the English adult population as revealed by national health surveys. A significantly higher proportion of women delivering by cesarean delivery reported some, moderate, severe, or extreme pain or discomfort at 12 months postpartum than women undergoing spontaneous vaginal delivery. Multivariable analyses, using the Ordinary Least Squares estimator revealed that, after controlling for maternal sociodemographic characteristics, cesarean delivery without maternal or fetal compromise was associated with a significant EQ‐5D utility decrement in comparison to spontaneous vaginal delivery among all women (−0.026; p = 0.038) and among mothers of term‐born infants (−0.062; p < 0.001). Among mothers of term‐born infants, this result was replicated in models that controlled for all maternal and infant characteristics (utility decrement of −0.061; p < 0.001). The results were confirmed by sensitivity analyses that varied the categorization of the main exposure variable (mode of delivery) and the econometric strategy.

Conclusions

Among mothers of term‐born infants, cesarean delivery without maternal or fetal compromise is associated with poorer long‐term health‐related quality of life in comparison to spontaneous vaginal delivery. Further longitudinal studies are needed to understand the magnitude, trajectory, and underpinning mechanisms of health‐related quality‐of‐life outcomes following different modes of delivery.
Renal disease related to Waldenström macroglobulinaemia: incidence, pathology and clinical outcomes
Authors: Vos Josephine M. , Gustine Joshua , Rennke Helmut G. , Hunter Zachary , Manning Robert J. , Dubeau Toni E. , Meid Kirsten , Minnema Monique C. , Kersten Marie‐Jose , Treon Steven P. , Castillo Jorge J.
Published: November 2016

The incidence and prognostic impact of nephropathy related to Waldenström macroglobulinaemia (WM) is currently unknown. We performed a retrospective study to assess biopsy‐confirmed WM‐related nephropathy in a cohort of 1391 WM patients seen at a single academic institution. A total of 44 cases were identified, the estimated cumulative incidence was 5·1% at 15 years. There was a wide variation in kidney pathology, some directly related to the WM: amyloidosis (n = 11, 25%), monoclonal‐IgM deposition disease/cryoglobulinaemia (n = 10, 23%), lymphoplasmacytic lymphoma infiltration (n = 8, 18%), light‐chain deposition disease (n = 4, 9%) and light‐chain cast nephropathy (n = 4, 9%), and some probably related to the WM: thrombotic microangiopathy (TMA) (n = 3, 7%), minimal change disease (n = 2, 5%), membranous nephropathy (n = 1, 2%) and crystal‐storing tubulopathy (n = 1, 2%). The median overall survival in patients with biopsy‐confirmed WM‐related nephropathy was 11·5 years, shorter than for the rest of the cohort (16 years, P = 0·03). Survival was better in patients with stable or improved renal function after treatment (P = 0·05). Based on these findings, monitoring for renal disease in WM patients should be considered and a kidney biopsy pursued in those presenting with otherwise unexplained renal failure and/or nephrotic syndrome.
Sole rearrangement but not amplification of MYC is associated with a poor prognosis in patients with diffuse large B cell lymphoma and B cell lymphoma unclassifiable
Authors: Landsburg Daniel J. , Falkiewicz Marissa K. , Petrich Adam M. , Chu Benjamin A. , Behdad Amir , Li Shaoying , Medeiros L. Jeffrey , Cassaday Ryan D. , Reddy Nishitha M. , Bast Martin A. , Vose Julie M. , Kruczek Kimberly R. , Smith Scott E. , Patel Priyank , Hernandez‐Ilizaliturri Francisco , Karmali Reem , Rajguru Saurabh , Yang David T. , Maly Joseph J. , Blum Kristie A. , Zhao Weiqiang , Vanslambrouck Charles , Nabhan Chadi
Published: November 2016

Rearrangement of MYC is associated with a poor prognosis in patients with diffuse large B cell lymphoma (DLBCL) and B cell lymphoma unclassifiable (BCLU), particularly in the setting of double hit lymphoma (DHL). However, little is known about outcomes of patients who demonstrate MYC rearrangement without evidence of BCL2 or BCL6 rearrangement (single hit) or amplification (>4 copies) of MYC. We identified 87 patients with single hit lymphoma (SHL), 22 patients with MYC‐amplified lymphoma (MYC amp) as well as 127 DLBCL patients without MYC rearrangement or amplification (MYC normal) and 45 patients with DHL, all treated with either R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or intensive induction therapy. For SHL and MYC amp patients, the 2‐year progression‐free survival rate (PFS) was 49% and 48% and 2‐year overall survival rate (OS) was 59% and 71%, respectively. SHL patients receiving intensive induction experienced higher 2‐year PFS (59% vs. 23%, P = 0·006) but similar 2‐year OS as compared with SHL patients receiving R‐CHOP. SHL DLBCL patients treated with R‐CHOP, but not intensive induction, experienced significantly lower 2‐year PFS and OS (P < 0·001 for both) when compared with MYC normal patients. SHL patients appear to have a poor prognosis, which may be improved with receipt of intensive induction.
Impact of alcohol‐promoting and alcohol‐warning advertisements on alcohol consumption, affect, and implicit cognition in heavy‐drinking young adults: A laboratory‐based randomized controlled trial
Authors: Stautz Kaidy , Frings Daniel , Albery Ian P. , Moss Antony C. , Marteau Theresa M.
Published: November 2016

Objectives

There is sparse evidence regarding the effect of alcohol‐advertising exposure on alcohol consumption among heavy drinkers. This study aimed to assess the immediate effects of alcohol‐promoting and alcohol‐warning video advertising on objective alcohol consumption in heavy‐drinking young adults, and to examine underlying processes.

Design

Between‐participants randomized controlled trial with three conditions.

Methods

Two hundred and four young adults (aged 18–25) who self‐reported as heavy drinkers were randomized to view one of three sets of 10 video advertisements that included either (1) alcohol‐promoting, (2) alcohol‐warning, or (3) non‐alcohol advertisements. The primary outcome was the proportion of alcoholic beverages consumed in a sham taste test. Affective responses to advertisements, implicit alcohol approach bias, and alcohol attentional bias were assessed as secondary outcomes and possible mediators. Typical alcohol consumption, Internet use, and television use were measured as covariates.

Results

There was no main effect of condition on alcohol consumption. Participants exposed to alcohol‐promoting advertisements showed increased positive affect and an increased approach/reduced avoidance bias towards alcohol relative to those exposed to non‐alcohol advertisements. There was an indirect effect of exposure to alcohol‐warning advertisements on reduced alcohol consumption via negative affect experienced in response to these advertisements.

Conclusions

Restricting alcohol‐promoting advertising could remove a potential influence on positive alcohol‐related emotions and cognitions among heavy‐drinking young adults. Producing alcohol‐warning advertising that generates negative emotion may be an effective strategy to reduce alcohol consumption.

Statement of contribution

What is already known on this subject?

Exposure to alcohol advertising has immediate and distal effects on alcohol consumption.

There is some evidence that effects may be larger in heavy drinkers.

Alcohol‐warning advertising has been found to have mixed effects on alcohol‐related cognitions.

What does this study add?

Among heavy‐drinking young adults:

Alcohol advertising does not appear to have an immediate impact on alcohol consumption.

Alcohol advertising generates positive affect and increases alcohol approach bias.

Alcohol‐warning advertising that generates displeasure reduces alcohol consumption.
Perceived legitimacy follows in‐group interests: Evidence from intermediate‐status groups
Authors: Caricati Luca , Sollami Alfonso
Published: November 2016

In two experiments, the effect of (in)stability of status differences on the perception of perspective legitimacy and in‐group threat among intermediate‐status group members (i.e., nurses students or nurses) was analysed. Both studies indicated that in downwardly unstable condition, legitimacy was lower and in‐group threat was higher than in stable condition. In upwardly unstable condition, perceived legitimacy was higher and in‐group threat was lower than in stable condition. The indirect effects of (in)stability via in‐group threat on perceived legitimacy were significant.