bluuebunny/crossref_metadata_2025 huggingface dataset:
Concordance of PD‐L1 expression in matched urothelial bladder cancer specimens
Authors: de Jong Joep J , Stoop Hans , Nieboer Daan , Boormans Joost L , van Leenders Geert J L H
Published: July 2018

Aims

Programmed death ligand 1 (PD‐L1) expression has predictive value for response to immune‐checkpoint inhibitor treatment in urothelial cancer patients. The consistency of PD‐L1 expression among different specimen types, however, is unknown. The aim of this study is to compare PD‐L1 expression in matched transurethral resections of the bladder (TURB), cystectomy specimens and lymph node metastases of urothelial cancer patients.

Methods and results

We performed PD‐L1 (SP142) immunohistochemistry on whole tissue slides of 115 urothelial carcinoma patients who had undergone TURB, followed by radical cystectomy and/or pelvic lymph node dissection. The PD‐L1 assay was positive if PD‐L1 expression in immune cells occupied ≥5% of the tumour area. PD‐L1 was positive in 15 of 97 (15.5%) TURB, 17 of 98 (17.3%) cystectomies and nine of 49 (18.4%) lymph node metastases. Agreement of PD‐L1 assay outcome between cystectomy and TURB (kappa = 0.34; P = 0.002) and cystectomy and lymph node metastasis (kappa = 0.35; P = 0.034) was fair; there was no agreement between TURB and lymph node metastasis (kappa = 0.045; P = 0.82). Discordance of PD‐L1 outcome in matched TURB and cystectomy specimens occurred more frequently after neoadjuvant therapy (53.3% versus 25.4%; P = 0.03), and was not associated with other clinicopathological parameters.

Conclusions

Urothelial bladder cancer patients showed fair agreement of PD‐L1 assay outcome in cystectomies and matched TURB or lymph node specimens. PD‐L1 expression was discordant more often after neoadjuvant therapy. Therefore, immune‐checkpoint inhibitor studies should take into account specimen type and neoadjuvant therapy in assessing the predictive value of PD‐L1 expression.
Comparison of 48‐week efficacies of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide and nucleoside/nucleotide reverse transcriptase inhibitor‐sparing regimens: a systematic review and network meta‐analysis
Authors: Gallien S , Massetti M , Flandre P , Leleu H , Descamps D , Lazaro E
Published: July 2018

Objectives

To compare nucleoside/nucleotide reverse transcriptase inhibitor (NRTI)‐sparing regimens with tenofovir alafenamide (TAF)‐based combinations in HIV‐1‐infected adults, we performed a network meta‐analysis (NMA) to provide estimates of relative efficacy for these two regimens.

Methods

A systematic literature review (SLR) was performed to identify phase 3/4 randomized controlled clinical trials evaluating the efficacy of commonly used combination antiretroviral therapy (cART) including an NRTI backbone or that of commonly used NRTI‐sparing regimens. A Bayesian random‐effect model was used to compare virological suppression rates at 48 weeks for NRTI‐sparing regimens and elvitegravir/cobicistat/emtricitabine/TAF (E/C/F/TAF).

Results

Twenty‐three studies in treatment‐naïve patients identified by the SLR were included in the NMA, including four studies assessing NRTI‐sparing regimens. In treatment‐naïve patients, the probability of achieving virological suppression at 48 weeks was between 40% and 60% higher with E/C/F/TAF than with NRTI‐sparing strategies. The credible interval vs. darunavir/ritonavir (DVR/r) + raltegravir (RAL) and LPV/r monotherapy did not include 1. In the subgroup of naïve patients with viral load < 100 000 HIV‐1 RNA copies/mL, a credible difference was found between NRTI‐sparing treatments and E/C/F/TAF. Studies in treatment‐experienced patients were too heterogeneous to allow for an NMA.

Conclusions

The NMA results suggest that E/C/F/TAF represents a more effective option than NRTI‐sparing regimens in terms of 48‐week efficacy in treatment‐naïve patients. Furthermore, TAF pharmacological properties, as well as tolerability results in clinical studies, suggest a safety profile similar to that of NRTI‐sparing regimens. Thus, the E/C/F/TAF combination might represent a more appropriate option than NRTI‐sparing regimens for initiation of antiretroviral therapy in treatment‐naïve HIV‐infected patients.
Innovation in ceramic foam filters manufacturing process
Authors: Salvini Vânia R. , Luchini Bruno , Aneziris Christos G. , Pandolfelli Victor C.
Published: July 2018

Ceramic filters have singular properties such as high permeability and specific surface area associated to low density. Some examples of their use can be found in liquid metal deep filtration, water treatment, air purification, and others. These particular properties are dependent on the filters' manufacturing process. One of the most used techniques to produce filters is the replication method, which provides a tridimensional network of struts and interconnected pores. However, a common issue of all ceramic filters produced by this technique is their low mechanical strength due to the hollow struts and microcracking generated during the thermal decomposition of the sponge. Intending to address this limitation and produce filters with higher mechanical strength, this paper analyzed a modified process route for manufacturing filters. Samples of preheated Al2O3 filters were vacuum infiltrated with ceramic suspensions (Al2O3 and SiO2) of different solids concentrations (15‐40 wt%), particle size distribution (nano to micrometric size) at distinct processing times (1‐5 minutes). The data analysis indicated that the best balance among mechanical strength, mass, and strut thickness was achieved by infiltration with SiO2 colloidal suspension (40 wt%) per 1 minute. SEM analysis confirmed that the struts were filled and microcracks were sealed with colloidal particles.
Electrodiffusion of alkali ions in alkali niobophosphate glasses and glass‐forming melts
Authors: Markov Viktor A. , Sokolov Ivan A. , Kurushkin Mikhail V. , Povolotskiy Alexey V.
Published: July 2018

Electrical conductivity of Li(Na,K)2O‐Nb2O5‐P2O5 glasses and glass‐forming melts has been measured in a wide temperature range (298‐1173 K). Logarithm of the preexponential factor and activation energy of migration have been determined. Mixed alkali effect has been observed in niobophosphate glass‐forming melts. Diffusion coefficients for Li+, Na+, and K+ ions have been calculated. The influence of the type of alkali ion and Nb2O5 content on the diffusion coefficients has been determined.
Wealth Effects of Seasoned Equity Offerings: A Meta‐Analysis
Authors: Veld Chris , Verwijmeren Patrick , Zabolotnyuk Yuriy
Published: July 2018

We use meta‐analysis to review studies on announcement effects associated with seasoned equity offerings. Our sample includes 199 studies from 38 leading finance journals and Social Sciences Research Network working papers. The studies cover different countries, but the US is particularly well‐represented with 131 studies. We find a statistically significant mean cumulative abnormal return of −0.98%. Abnormal returns are more negative for equity issues by US companies and for non‐US rights issues and are less negative for private placements. In addition, wealth effects are more negative when the proceeds are used for debt reduction, when the SEO is issued shortly after IPO, and for issues by nondividend‐paying companies and industrial companies. We identify important avenues for future research.
Crystallization behavior of iron‐ and boron‐containing nepheline (Na2O·Al2O3·2SiO2) based model high‐level nuclear waste glasses
Authors: Deshkar Ambar , Ahmadzadeh Mostafa , Scrimshire Alex , Han Edmund , Bingham Paul A. , Guillen Donna , McCloy John , Goel Ashutosh
Published: July 2018

This study focuses on understanding the relationship between iron redox, composition, and heat‐treatment atmosphere in nepheline‐based model high‐level nuclear waste glasses. Glasses in the Na2O–Al2O3–B2O3–Fe2O3–SiO2 system with varying Al2O3/Fe2O3 and Na2O/Fe2O3 ratios have been synthesized by melt‐quench technique and studied for their crystallization behavior in different heating atmospheres—air, inert (N2), and reducing (96%N2–4%H2). The compositional dependence of iron redox chemistry in glasses and the impact of heating environment and crystallization on iron coordination in glass‐ceramics have been investigated by Mössbauer spectroscopy and vibrating sample magnetometry. While iron coordination in glasses and glass‐ceramics changed as a function of glass chemistry, the heating atmosphere during crystallization exhibited minimal effect on iron redox. The change in heating atmosphere did not affect the phase assemblage but did affect the microstructural evolution. While glass‐ceramics produced as a result of heat treatment in air and N2 atmospheres developed a golden/brown colored iron‐rich layer on their surface, those produced in a reducing atmosphere did not exhibit any such phenomenon. Furthermore, while this iron‐rich layer was observed in glass‐ceramics with varying Al2O3/Fe2O3 ratio, it was absent from glass‐ceramics with varying Na2O/Fe2O3 ratio. An explanation of these results has been provided on the basis of kinetics of diffusion of oxygen and network modifiers in the glasses under different thermodynamic conditions. The plausible implications of the formation of iron‐rich layer on the surface of glass‐ceramics on the chemical durability of high‐level nuclear waste glasses have been discussed.
Dense freeze‐cast Li7La3Zr2O12 solid electrolytes with oriented open porosity and contiguous ceramic scaffold
Authors: Buannic Lucienne , Naviroj Maninpat , Miller Sarah M. , Zagorski Jakub , Faber Katherine T. , Llordés Anna
Published: July 2018

Freeze casting is used for the first time to prepare solid electrolyte scaffolds with oriented porosity and dense ceramic walls made of Li7La3Zr2O12 (LLZO), one of the most promising candidates for solid‐state battery electrolytes. Processing parameters—such as solvent solidification rate, solvent type, and ceramic particle size—are investigated, focusing on their influence on porosity and ceramic wall density. Dendrite‐like porosity is obtained when using cyclohexane and dioxane as solvents. Lamellar porosity is observed in aqueous slurries resulting in a structure with the highest apparent porosity and densest ceramic scaffold but weakest mechanical properties due to the lack of interlamellar support. The use of smaller LLZO particle size in the slurries resulted in lower porosity and denser ceramic walls. The intrinsic ionic conductivity of the oriented LLZ ceramic scaffold is unaffected by the freeze casting technique, providing a promising ceramic scaffold for polymer infill in view of designing new types of ceramic‐polymer composites.
Hydration mechanisms of hybrid cements as a function of the way of addition of chemicals
Authors: Fernández‐Jiménez Ana , Garcia‐Lodeiro Inés , Maltseva Olga , Palomo Angel
Published: July 2018

In this study fly ash contents of up to 50% were used to produce binders with mechanical strength greater than or equal to type CEM I 42.5R cement (reference). The specific aim pursued in this research was to determine whether the procedure used to add the chemical activator (in solid or liquid form) can affect strength development in the cement or the nature of the reaction products formed. Two experimental procedures were deployed: (a) the chemical activator was dissolved in the mixing water; (b) the chemical activator was ground, as a solid, into the fly ash. The solid‐state method induced slightly higher mechanical strength than when the activator was dissolved in hydration water. The way the chemical activator was added affected not only early age reaction kinetics, but also the nature and composition of the reaction products, the liquid state favoring the formation of phases AFt and AFm.
Improvement of reliability and dielectric breakdown strength of Nb‐doped lead zirconate titanate films via microstructure control of seed
Authors: Ko Song Won , Zhu Wanlin , Fragkiadakis Charalampos , Borman Trent , Wang Ke , Mardilovich Peter , Trolier‐McKinstry Susan
Published: July 2018

A Pb(Zr,Ti)O3 (PZT) seed layer without Pb‐deficient defective areas was developed to improve the dielectric breakdown strength and lifetime of thin film piezoelectric actuators. The proportion of defective area in the seed layers was reduced by adjusting the amount of Pb excess in the solution, combined with implementation of a dense, large‐grained (>200 nm) Pt bottom electrode. The optimal Pb excess amount in the solution was about 20 at%; seeding was improved when a slightly Ti‐rich composition (relative to the morphotropic phase boundary) was utilized. It was found that the dielectric breakdown strength and lifetime of PZT films improved as the proportion of visible defective area on the PZT seed layer decreased. Dielectric breakdown strength increased from approximately 300 kV/cm to about 1 MV/cm. The lifetime, characterized by highly accelerated lifetime testing, was increased 60 times by reducing the fraction of defective area. The activation energy (Ea) and voltage acceleration factor (N) for failure of devices (eg, patterned PZT films) were 1.12 ± 0.03 eV and 4.24 ± 0.07 respectively.
Home blood pressure monitoring in the 21st century
Authors: Stergiou George S. , Kario Kazuomi , Kollias Anastasios , McManus Richard J. , Ohkubo Takayoshi , Parati Gianfranco , Imai Yutaka
Published: July 2018

Home blood pressure monitoring provides multiple measurements in the usual environment of each individual, allows the detection of intermediate hypertension phenotypes (white‐coat and masked hypertension), and appears to have superior prognostic value compared to the conventional office blood pressure measurements. Accumulating evidence suggests that home blood pressure monitoring improves long‐term hypertension control rates. Moreover, it is widely available, relatively inexpensive, and well accepted by patients. Thus, current guidelines recommend home blood pressure monitoring as an essential method for the evaluation of almost all untreated and treated patients with suspected or treated hypertension. Validated automated upper‐arm cuff devices with automated storage and averaging of readings should be used. The home blood pressure monitoring schedule for 4 to 7 days with exclusion of the first day (12–24 readings) should be averaged to provide values for decision making.
Validation protocols for blood pressure measuring devices in the 21st century
Authors: Stergiou George S. , Alpert Bruce S. , Mieke Stephan , Wang Jiguang , O'Brien Eoin
Published: July 2018

Blood pressure (BP) is a vital sign and the essential measurement for the diagnosis of hypertension. Therefore, its accurate measurement is a key element for the evaluation of many medical conditions and for the reliable diagnosis and efficient treatment of hypertension. In the last 3 decades prestigious organizations, such as the US Association for the Advancement of Medical Instrumentation (AAMI), the British Hypertension Society, the European Society of Hypertension (ESH) Working Group on BP Monitoring, and the International Organization for Standardization (ISO), have developed protocols for clinical validation of BP measuring devices. All these initiatives aim to standardize validation procedures and establish minimum accuracy standards for BP monitors. Unfortunately, only a few of the BP measuring devices available on the market have been subjected to independent validation using one of these protocols. Recently, the AAMI, ESH, and ISO experts agreed to develop a single universally acceptable standard (AAMI/ESH/ISO), which will replace all previous protocols. This major international initiative has been undertaken to best serve the needs of patients with hypertension, a public interested in cardiovascular health, practicing physicians, scientific researchers, regulatory bodies, and manufacturers. There is an urgent need to influence regulatory authorities throughout the world to make it mandatory for all BP measuring devices to have undergone independent validation before approval for marketing. Efforts need to be intensified to improve the accuracy of BP measuring devices, further optimize the validation procedure, and ensure that objective and unbiased validation data become available.
Blood pressure measurement in special populations and circumstances
Authors: Stergiou George S. , Dolan Eamon , Kollias Anastasios , Poulter Neil R. , Shennan Andrew , Staessen Jan A. , Zhang Zhen‐Yu , Weber Michael A.
Published: July 2018

According to the established validation protocols, a typical validation study of a blood pressure (BP) monitor includes general population adults with normal or elevated BP. It is recognized, however, that the automated (oscillometric) BP monitors may have different accuracy or uses in some special populations compared with adults in the general population. Thus, an automated BP monitor with proven accuracy in a general population of adults may not be accurate in a special population, and therefore separate validation is needed. Recognized special populations deserving separate validation are those for which there is theoretical, and also clinical evidence, that the accuracy of BP monitors in these groups differs from that in the general population. Young children, pregnant women (including those with preeclampsia), individuals with arm circumference >42 cm, and patients with atrial fibrillation are regarded as special populations. Adolescents, individuals older than 80 years, and patients with end‐stage renal disease or diabetes mellitus have also been considered as possible special groups, but there is still inadequate evidence of altered accuracy of BP monitors in these subjects. Validation studies should be performed in special populations and evaluated separately after the BP‐measuring device has successfully undergone a validation study in a general population (unless the test device is intended only for a special population). This article discusses issues relating to the measurement of BP and the diagnosis of hypertension in selected special populations, as well as in low‐resource settings, where a simplified yet efficient evaluation strategy is necessary.
Home blood pressure telemonitoring in the 21st century
Authors: Parati Gianfranco , Dolan Eamon , McManus Richard J. , Omboni Stefano
Published: July 2018

Blood pressure telemonitoring (BPT) is a telehealth strategy that allows remote data transmission of blood pressure and additional information on patients’ health status from their dwellings or from a community setting to the doctor's office or the hospital. There is sufficiently strong evidence from several randomized controlled trials that the regular and prolonged use of BPT combined with telecounseling and case management under the supervision of a team of healthcare professionals is associated with a significant blood pressure reduction compared with usual care, particularly in cases of patients at high risk. However, most current evidence is based on studies of relatively short duration (<12 months), and in the few studies that have investigated longer‐term outcomes, no evidence of better or sustained effect could be provided. In addition, no definition of the optimal BPT‐based healthcare delivery model could be derived from the studies performed so far, because of the heterogeneity of interventions, technologies, and study designs. BPT can also be provided in the context of “mobile health” (m‐health) wireless solutions, together with educational support, medication reminders, and teleconsultation. When BPT is integrated in an m‐health solution, it has the potential to promote patient's self‐management, as a complement to the doctor's intervention, and encourage greater participation in medical decision‐making. In conclusion, BPT has a potential key role in the management of patients with hypertension, since it seems to improve the quality of delivered care and allow for more effective prevention of the cardiovascular consequences of hypertension.
The clinical effects of l_arginine and asymmetric dimethylarginine: implications for treatment in secondary Raynaud's phenomenon
Authors: Curtiss P. , Schwager Z. , Lo Sicco K. , Franks A.G.
Published: July 2018

Secondary Raynaud's phenomenon (RP) is often the sentinel clinical finding in systemic sclerosis and may precede systemic disease by several years. Altered nitric oxide metabolism plays a critical role in both fibrosis and severe secondary RP phenotypes in these patients. Increased flux through inducible nitric oxide synthase (iNOS) drives cutaneous fibrosis. Failure of flux through endothelial nitric oxide synthase (eNOS) contributes to increased vasoconstriction and decreased vasorelaxation. The underproduction of nitric oxide by eNOS is in part due to increased levels of asymmetric dimethylarginine (ADMA), an endogenous competitive inhibitor of nitric oxide synthase. The inhibitory effects of increased ADMA levels may be counteracted increasing serum l_arginine, which is often an effective treatment strategy in these patients. As such, l_arginine_based therapies should be considered in managing secondary RP, particularly given their favourable safety and tolerability profile. While there is no established dosing regimen, studies of oral l_arginine in secondary RP suggest that divided dosing may begin at 1_2 g/day and may be titrated up to 10 g/day. Conversely, primary RP is not associated with increased ADMA production which likely accounts for the failure of l_arginine trials to show benefit in primary RP.
Suffering without a medical diagnosis. A critical view on the biomedical attitudes towards persons suffering from burnout and the implications for medical care
Authors: Engebretsen Karin Mohn
Published: July 2018

The search for causal explanations in medically unexplained syndromes such as burnout has not been resolved by evidence‐based medicine. A biomedical model encourages a reductionist diagnostic practice and a dualist split between physical and psychological symptoms. Therefore, diagnosing and treating these syndromes remains a challenge. Depression is a common aspect in burnout and, as a result, clinicians often diagnose burnout patients as depressed. The Norwegian government expects medical efficiency to reduce sick leaves. Medically treating depression has a documented effect. This practice may pose threats to the increasing number of individuals experiencing burnout. The clinical guidelines in evidence‐based medicine mirror what counts as knowledge in medical inquiry, which in turn shapes attitudes towards individual patients. The aim of this article is 2‐fold: firstly, to assess how the values that accompany the biomedical paradigm affect clinical care, and secondly, to replace the biomedical model with a genuine person‐centred approach.

In the study described, an existential phenomenological method was applied. Eight individuals, who experienced burnout, were included. They had been on long‐term sick leave (>1 year) due to symptoms of fatigue and pain and fulfilled the criteria for Exhaustion Disorder (ICD‐10, F43.8A). Their symptoms were not medically explained, and almost all the participants were labelled as depressed. Four themes emerged that described how they experienced living with burnout: “unhomelike being in the world,” “the limit of diagnosis,” “naked in the eyes of the public,” and “a path to hopelessness.”

I identify 2 main problems; firstly, the mismatch between the patient's experience of his or her illness and the doctor's interpretation of the condition can lead to ineffective treatment. Secondly, the interviewees struggled to be recognized as ill. Thus, the inherent values in the biomedical paradigm might have serious implications for the medical care of patients with burnout.
Using randomization tests to assess treatment effects in multiple‐group interrupted time series analysis
Authors: Linden Ariel
Published: July 2018

Rationale, aims, and objectives

Interrupted time series analysis (ITSA) is a popular evaluation methodology in which a single treatment unit's outcome is studied over time and the intervention is expected to “interrupt” the level and/or trend of the outcome, subsequent to its introduction. The internal validity of this analysis is strengthened considerably if the treated unit is contrasted with a comparable control group. However, multiple‐group ITSA typically has small sample sizes, and parametric methods for multiple‐group ITSA require strong assumptions that are unlikely to be met, possibly resulting in misleading P values. In this paper, randomization tests are introduced as a non‐parametric, distribution‐free option for computing exact P values.

Method

The effect of California's Proposition 99 (passed in 1988) for reducing cigarette sales is evaluated by comparing California (CA) to Montana (MT) and Idaho (ID)—the two best matched control states not exposed to any smoking reduction initiatives. Results from randomization tests are contrasted to those of interrupted time series analysis regression (ITSAREG)—a commonly used parametric approach for evaluating treatment effects in ITSA studies.

Results

Both approaches found ID and MT to be comparable to CA on their preintervention time series, and both approaches equally found CA to have statistically lower cigarette sales in the postintervention period (P < 0.01).

Conclusions

In these data, randomization tests computed P values comparable with ITSAREG, bolstering confidence in the intervention effect. Routinely including randomization tests as a complement, or alternative, to parametric methods is therefore beneficial because randomization tests are free of assumptions regarding sample size and distribution and are extremely flexible in the choice of test statistic.
Assessing the population transmission dynamics of tilapia lake virus in farmed tilapia
Authors: Yang Ying‐Fei , Lu Tien‐Hsuan , Lin Hsing‐Chieh , Chen Chi‐Yun , Liao Chung‐Min
Published: July 2018

A novel virus, tilapia lake virus (TiLV), has been identified as a key pathogen responsible for disease outbreak and mass mortality of farmed tilapia. We used a deterministic susceptible‐infectious‐mortality (SIM) model to derive key disease information appraised with published TiLV‐induced cumulative mortality data. The relationship between tilapia mortality and TiLVexposure dosages was described by the Hill model. Furthermore, a disease control model was proposed to determine the status of controlled TiLVinfection using a parsimonious control reproduction number (RC)‐control line criterion. Results showed that the key disease determinants of transmission rate and basic reproduction number (R0) could be derived. The medianR0estimate was 2.59 in a cohabitation setting with 2.6 × 105 TCID50 fish−1TiLV. The presentRC‐control model can be employed to determine whether TiLVcontainment is feasible in an outbreak farm by quantifying the current level of transmission. TheSIMmodel can then be applied to predict what additional control is required to manageRC < 1. We offer valuable tools for aquaculture engineers and public health scientists the mechanistic‐based assessment that allows a more rigorous evaluation of different control strategies to reduce waterborne diseases in aquaculture farming systems.
Low levels of progesterone and derivatives in cerebrospinal fluid of patients affected by status epilepticus
Authors: Meletti Stefano , Lucchi Chiara , Monti Giulia , Giovannini Giada , Bedin Roberta , Trenti Tommaso , Rustichelli Cecilia , Biagini Giuseppe
Published: July 2018

Neurosteroids such as allopregnanolone may play a role in epilepsy as positive modulators of inhibitory currents mediated by γ‐aminobutyric acid type A (GABAA) receptor. Indeed, these molecules have been consistently shown to be anticonvulsants in animal models, but their role is still unclear in patients. For this reason, we investigated neurosteroids in the cerebrospinal fluid (CSF) of patients with status epilepticus (SE) by liquid chromatography tandem‐mass spectrometry. Patients were retrospectively identified within subjects who received a lumbar puncture in the 2007–2017 period. Seventy‐three patients (median age 65, ranging from 13 to 94 years; 67% women) with SE were evaluated. Controls (n = 52, median age 53, ranging from 16 to 93 years; 65% women) were patients presenting with symptoms for which a lumbar puncture was required by clinical guidelines, and who were negative at the end of the diagnostic work‐up. Progesterone was 64% lower in patients with SE (p < 0.001). With respect to progesterone, upstream pregnenolone sulfate and pregnenolone did not change. Instead, downstream 5α‐dihydroprogesterone, pregnanolone and allopregnanolone were, respectively, 49% (p < 0.001), 21% (p < 0.01) and 37% (p < 0.001) lower than in controls. Duration or type of SE, age and sex did not consistently affect CSF neurosteroid levels in the SE cohort. Instead, pregnenolone sulfate (Spearman's ρ = 0.4335, p < 0.01), allopregnanolone (ρ = 0.4121, p < 0.05) and pregnanolone (ρ = 0.592, p < 0.001) levels significantly increased by aging in controls. We conclude that neurosteroidogenesis is defective in patients with SE.

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Factors associated with successful pregnancy in women of late reproductive age with uterine fibroids who undergo embryo cryopreservation before surgery
Authors: Takahashi Nozomi , Harada Miyuki , Tanabe Ryosuke , Takayanagi Akane , Izumi Gentaro , Oi Nagisa , Hirata Tetsuya , Wada‐Hiraike Osamu , Fujii Tomoyuki , Osuga Yutaka
Published: July 2018

Aim

The objective of this study is to determine the factors associated with successful pregnancy in women of late reproductive age with uterine fibroids who undergo embryo cryopreservation before surgery (ECBS).

Methods

Patients who underwent in vitro fertilization treatment with controlled ovarian stimulation from November 2010 to January 2017 in our university hospital were included. Twenty‐two patients older than 35 years of age at the first visit with cavity‐distorting uterine fibroids underwent ECBS, a three‐step therapeutic approach consisting of oocyte pick‐up, myomectomy and embryo transfer (ET), which are performed in this order. We retrospectively calculated the pregnancy rate and determined the factors associated with successful pregnancy.

Results

The mean age at ET of the patients who underwent ECBS was 40.9 years, with a pregnancy rate per ET of 36.8% (21/57). Of 22 patients, 10 (45.5%) successfully continued pregnancy beyond 12 weeks of gestation (ongoing pregnancy). An ongoing pregnancy was observed only among the patients with more than three frozen embryos. The ongoing pregnancy rates of patients with ≤five fibroids and ≤5 cm in the maximal diameter were significantly higher compared to the respective remaining group (90.0% vs 14.3% and 87.5% vs 33.3%).

Conclusion

ECBS is an effective strategy for infertile women of late reproductive age with cavity‐distorting uterine fibroids, especially when it is applied to the patients who can freeze at least three embryos before myomectomy, with five or less fibroids smaller than 5 cm in the maximal diameter.
Antimicrobial discovery from natural and unusual sources
Authors: Ali Salwa Mansur , Siddiqui Ruqaiyyah , Khan Naveed Ahmed
Published: July 2018

Objectives

Whether vertebrates/invertebrates living in polluted environments are an additional source of antimicrobials.

Key findings

Majority of antimicrobials have been discovered from prokaryotes and those which are of eukaryotic origin are derived mainly from fungal and plant sources. With this in mind, it is important to note that pests, such as cockroaches come across pathogenic bacteria routinely, yet thrive in polluted environments. Other animals, such as snakes thrive from feeding on germ-infested rodents. Logically, such species must have developed an approach to protect themselves from these pathogens, yet they have largely been ignored as a potential source of antimicrobials despite their remarkable capability to fight disease-causing organisms.

Animals living in polluted environments are an underutilized source for potential antimicrobials, hence it is believed that several novel bioactive molecule(s) will be identified from these sources to counter increasingly resistant bacterial infections. Further research will be necessary in the development of novel antimicrobial(s) from these unusual sources which will have huge clinical impact worldwide.
Clinical efficiency and safety of Hsp90 inhibitor Novobiocin in avian tibial dyschondroplasia
Authors: Nabi Fazul , Iqbal Muhammad K. , Zhang Hui , Rehman Mujeeb Ur , Shahzad Muhammad , Huang Shucheng , Han Zhaoqing , Mehmood Khalid , Ahmed Nisar , Chachar Bahram , Arain Muhammad A. , Li Jiakui
Published: July 2018

Tibial dyschondroplasia (TD) is a bone defect of broilers and other poultry birds that disturbs growth plate and it causes lameness. Previously we evaluated differential expression of multiple genes involved in growth plate angiogenesis and reported the safety and efficacious of medicinal plant root extracted for controlling TD. In this study, clinical and protective effect of an antibiotic Novobiocin (Hsp90 inhibitor) and expression of Hsp90 and proteoglycan aggrecan was examined. The chicks were divided into three groups; Control, thiram‐induced TD, and Novobiocin injected TD. After the induction of TD, the Novobiocin was administered through intraperitoneal route to TD‐affected birds until the end of the experiment. The expressions and localization of Hsp90 were evaluated by qRT‐PCR, immunohistochemistry (IHC) and western blot, respectively. Morphological, histological examinations, and serum biomarker levels were evaluated to assess specificity and protective effects of Novobiocin. The results showed that TD causing retarded growth, enlarged growth plate, distended chondrocytes, irregular columns of cells, decreased antioxidant capacity, reduced protein levels of proteoglycan aggrecan, and upregulated in Hsp90 expression (p < 0.05) in dyschondroplastic birds as compared with control. Novobiocin treatment restored growth plate morphology, reducing width, stimulated chondrocyte differentiation, sprouting blood vessels, corrected oxidative imbalance, decreased Hsp90 expressions and increased aggrecan level. Novobiocin treatment controlled lameness and improved growth in broiler chicken induced by thiram. In conclusion, the accumulation of the cartilage and up‐regulated Hsp90 are associated with TD pathogenesis and irregular chondrocyte morphology in TD is along with reduced aggrecan levels in the growth plate. Our results indicate that Novobiocin treatment has potential to reduce TD by controlling the expression of Hsp90 in addition to improve growth and hepatic toxicity in broiler chicken.
Asymmetric assortative mating and queen polyandry are linked to a supergene controlling ant social organization
Authors: Avril Amaury , Purcell Jessica , Brelsford Alan , Chapuisat Michel
Published: July 2018

Nonrecombining genomic variants underlie spectacular social polymorphisms, from bird mating systems to ant social organization. Because these “social supergenes” affect multiple phenotypic traits linked to survival and reproduction, explaining their persistence remains a substantial challenge. Here, we investigate how large nonrecombining genomic variants relate to colony social organization, mating system and dispersal in the Alpine silver ant,Formica selysi. The species has colonies headed by a single queen (monogynous) and colonies headed by multiple queens (polygynous). We confirmed that a supergene with alternate haplotypes—Sm and Sp—underlies this polymorphism in social structure: Females from mature monogynous colonies had the Sm/Sm genotype, while those from polygynous colonies were Sm/Sp and Sp/Sp. Queens heading monogynous colonies were exclusively mated with Sm males. In contrast, queens heading polygynous colonies were mated with Sp males and Sm males. Sm males, which are only produced by monogynous colonies, accounted for 22.9% of the matings with queens from mature polygynous colonies. This asymmetry between social forms in the degree of assortative mating generates unidirectional male‐mediated gene flow from the monogynous to the polygynous social form. Biased gene flow was confirmed by a significantly higher number of private alleles in the polygynous social form. Moreover, heterozygous queens were three times as likely as homozygous queens to be multiply mated. This study reveals that the supergene variants jointly affect social organization and multiple components of the mating system that alter the transmission of the variants and thus influence the dynamics of the system.
Review: Revisiting the human cholinergic nucleus of the diagonal band of Broca
Authors: Liu A. K. L. , Lim E. J. , Ahmed I. , Chang R. C.‐C. , Pearce R. K. B. , Gentleman S. M.
Published: July 2018

Although the nucleus of the vertical limb of the diagonal band of Broca (nvlDBB) is the second largest cholinergic nucleus in the basal forebrain, after the nucleus basalis of Meynert, it has not generally been a focus for studies of neurodegenerative disorders. However, the nvlDBB has an important projection to the hippocampus and discrete lesions of the rostral basal forebrain have been shown to disrupt retrieval memory function, a major deficit seen in patients with Lewy body disorders. One reason for its neglect is that the anatomical boundaries of the nvlDBB are ill defined and this area of the brain is not part of routine diagnostic sampling protocols. We have reviewed the history and anatomy of the nvlDBB and now propose guidelines for distinguishing nvlDBB from other neighbouring cholinergic cell groups for standardizing future clinicopathological work. Thorough review of the literature regarding neurodegenerative conditions reveals inconsistent results in terms of cholinergic neuronal loss within the nvlDBB. This is likely to be due to the use of variable neuronal inclusion criteria and omission of cholinergic immunohistochemical markers. Extrapolating from those studies showing a significant nvlDBB neuronal loss in Lewy body dementia, we propose an anatomical and functional connection between the cholinergic component of the nvlDBB (Ch2) and the CA2 subfield in the hippocampus which may be especially vulnerable in Lewy body disorders.
The role of the microbiome in nonhealing diabetic wounds
Authors: Kalan Lindsay R. , Brennan Meghan B.
Published: July 2018

Wound healing is a highly coordinated and complex process, and there can be devastating consequences if it is interrupted. It is believed that, in combination with host factors, microorganisms in a wound bed can not only impair wound healing but can lead to stalled, chronic wounds. It is hypothesized that the wound microbiota persists in chronic wounds as a biofilm, recalcitrant to antibiotic and mechanical intervention. Cultivation‐based methods are the gold standard for identification of pathogens residing in wounds. However, these methods are biased against fastidious organisms, and do not capture the full extent of microbial diversity in chronic wounds. Thus, the link between specific microbes and impaired healing remains tenuous. This is partially because local infection and, more specifically, the formation of a biofilm, is difficult to diagnose. This has led to research efforts aimed at understanding if biofilm formation delays healing and leads to persistent and chronic infection. Circumventing challenges associated with culture‐based estimations, advances in high‐throughput sequencing analysis has revealed that chronic wounds are host to complex, diverse microbiomes comprising multiple species of bacteria and fungi. Here, we discuss how the use of genomic methodologies to study wound microbiomes has advanced the current understanding of infection and biofilm formation in chronic wounds.
Effects of remifentanil maintenance during recovery on emergence delirium in children with sevoflurane anesthesia
Authors: Choi Eun Kyung , Lee Shiback , Kim Won Jae , Park Sang‐Jin
Published: July 2018

Background

Emergence delirium is a common complication of sevoflurane anesthesia in children.

Aims

We examined the effects of maintaining remifentanil infusion during the recovery period on the incidence of emergence delirium in preschool‐age children undergoing strabismus surgery under sevoflurane anesthesia.

Methods

Eighty children (aged 3‐7 years) were randomly assigned to either the control group (group C; intraoperative remifentanil infusion) or the intervention group (group R; intraoperative remifentanil infusion followed by remifentanil maintenance during the recovery phase). Intraoperative remifentanil infusion (0.2 μg/kg/min) was discontinued upon surgery completion in the group C, and was maintained until the discharge criteria were met at a dose of 0.05 μg/kg/min in the group R. The incidence of emergence delirium was assessed using a five‐point agitation scale and the Pediatric Anesthesia Emergence Delirium scale after arrival in the postanesthesia care unit. Postoperative pain was assessed using the Children's Hospital of Eastern Ontario Pain Scale.

Results

The incidence of emergence delirium according to the five‐point agitation scale (scores ≥ 4) was lower in the group R (33.3%) compared to the group C (68.3%) (odds ratio 0.206; 95% CI 0.080 to 0.531; P = 0.002). Similar results were obtained using the Pediatric Anesthesia Emergence Delirium scale (scores > 12), with an incidence of 5.1% in the group R and 34.0% in the control group (odds ratio 0.104; 95% CI 0.022 to 0.497; P = 0.001). The Children's Hospital of Eastern Ontario Pain Scale scores and occurrence of postoperative adverse events including laryngospasm, desaturation, nausea, and vomiting were similar between the two groups.

Conclusion

Maintaining a low dose of remifentanil (0.05 μg/kg/min) throughout the recovery phase attenuated the incidence of emergence delirium in children undergoing strabismus surgery under sevoflurane anesthesia.
Delivery of sevoflurane using a neonatal ventilator
Authors: Burstal Richard J , Threlfo Steven J
Published: July 2018

Background

Most anesthetic ventilators are designed to cope with a wide range of patient sizes and may lack precision at the lowest end of the minute volume scale. Neonatal intensive care ventilators on the other hand are designed specifically for this patient group, but are not able to deliver volatile anesthesia.

Aims

We aimed to adapt the neonatal ventilator currently in use in our institution to deliver sevoflurane by incorporating a vaporizer and a scavenging system.

Methods

We used a Diamedica draw‐over vaporizer incorporated into the ventilator circuit and a custom designed open interface scavenging system. A number of safety measures are described to ensure that this equipment is correctly inserted into the circuit.

Results

Bench testing revealed that the vaporizer output is linear and stable within the circuit flow range 4‐8 L/min in all modes except high frequency oscillation where concentrations are not predictable. The scavenging system was found to be effective and did not affect volumes, pressures or waveforms when ventilating a test lung over a wide range of flows and pressures. This remained the case over the full range of scavenger flow adjustment.

Conclusion

The addition of a Diamedica vaporizer to a Fabian neonatal ventilator was shown in bench testing to provide stable, linear vapor concentrations without compromise of ventilator function. The system should not be used in high frequency oscillation mode because concentrations will exceed those expected and will not maintain a linear relationship with the vaporizer setting.
Mood instability contributes to impulsivity, non‐suicidal self‐injury, and binge eating/purging in people with anxiety disorders
Authors: Peters Evyn M. , Bowen Rudy , Balbuena Lloyd
Published: July 2018

Objectives

The purpose of this study was to determine whether mood instability in people with anxiety disorders contributes to trait impulsivity, non‐suicidal self‐injury, and binge eating/purging.

Methods

Data were analysed from a general population sample of 7,221 adults (Mage = 51.0 years; 56.9% female). Logistic regression analyses with effect decompositions were used to establish the associations of five anxiety disorders (generalized anxiety disorder, social phobia, panic disorder, agoraphobia, and obsessive–compulsive disorder) with impulsivity, non‐suicidal self‐injury, and binge eating/purging, and then to determine the extent that adding mood instability to each model reduced these relationships.

Results

Participants with an anxiety disorder were more likely to report impulsivity compared to participants without an anxiety disorder (ORs = 2.40–3.92, all p < .001), but these relationships reduced by 59–78% and became non‐significant when mood instability was added to the models. Participants with an anxiety disorder were also more likely to report non‐suicidal self‐injury (ORs = 3.86–18.9, all p < .001) and binge eating/purging (ORs = 4.05–14.9, all p < .01); adding mood instability to the models reduced these relationships by at least 30%.

Conclusions

Mood instability and impulsivity are common in people with anxiety disorders. Anxiety disorders are associated with impulsivity largely because of the association between mood instability and impulsivity. Mood instability may contribute to non‐suicidal self‐injury and binge eating/purging in people with anxiety disorders. Treatments for mood instability in addition to standard anxiety disorder treatment may reduce impulsivity, non‐suicidal self‐injury, and binge eating/purging in people with anxiety disorders.

Practitioner points

Many patients with anxiety disorders experience mood instability, which is associated with impulsivity, non‐suicidal self‐injury, and binge eating/purging.

Treating mood instability alongside anxiety may help reduce impulsivity, non‐suicidal self‐injury, and binge eating/purging in people with anxiety disorders.
Recurrent oral ulcerations following heart transplant in a pediatric patient: A diagnostic dilemma
Authors: Asmar Namir , Geerlinks Ashley V. , Laxer Ronald M. , Tse Shirley M. L. , Dipchand Anne , Punnett Angela
Published: July 2018

Oral ulceration is a non‐specific clinical finding with many potential causes. The persistence of oral ulcers in the context of a patient post–SOT is concerning for PTLD. There is growing evidence that SOT recipients may also be at higher risk of autoimmune diseases. This case report describes a pediatric patient with persistent oral ulcers after heart transplant, who underwent an extensive workup for PTLD, including repeat investigations, with a subsequent diagnosis of Behçet's disease.
Ex vivo liver resection and autotransplantation with cardiopulmonary bypass for hepatoblastoma in children: A case report
Authors: Shi Shu‐Jun , Wang Deng‐Liang , Hu Wei , Peng Fei , Kang Quan
Published: July 2018

Some primary and secondary liver carcinomas cannot be resected using a conventional approach due to their size, location, or major vascular invasion. The aim of this study was to explore the application of ex vivo liver resection and autotransplantation for complicated HB in children. A 1.5‐year‐old girl with HB after repeated chemotherapy was analyzed. In this patient, tumor invasion includes the IV, V, and VIII liver segments, and thrombosis formed in the inferior vena cava and right atrium. It is difficult to obtain complete tumor resection using conventional hepatectomy. The patient was treated via ex vivo liver resection and autotransplantation, and tumor thrombus in the inferior vena cava and right atrium was removed via cardiopulmonary bypass. Operative methods and precautions were analyzed during and after the operation. The operation was completed successfully within 8 hours, and the liver's cold ischemia time was 190 minutes. The patient recuperated successfully, and the liver's function and AFP levels gradually tended to normalize 2 weeks after the operation. Ultrasonic examination revealed that the blood flow velocity of the hepatic vein, portal vein, and hepatic artery was good. The patient recovered and was discharged 3 weeks after the operation. Ex vivo liver resection and autotransplantation have great application value for complicated HB in children that is not suitable for conventional hepatic lobectomy.