bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct measurement of the magnetocaloric effect on micrometric Ni-Mn-(In,Sn) ribbons by the mirage effect under pulsed magnetic field
Authors: Cugini F. , Orsi D. , Brück E. , Solzi M.
Published: December 2018

In this work, we report on the direct measurement of the magnetic field induced temperature change in a series of micrometric thick ribbons of Ni-Mn-In-Sn Heusler alloys, performed with an innovative experimental technique based on the thermo-optical “Mirage Effect.” The technique combines very fast measurement time, 1 T pulsed magnetic field in the millisecond range, and contactless temperature detection. These features make the technique ideal for the characterization of thin samples with a thickness down to a few micrometers. In this work, we demonstrate this by directly measuring the magnetocaloric effect (MCE) of micrometric-thick ribbons of Heusler alloys at the Curie transition, which was tuned on a wide temperature range by varying the Sn to In ratio. The direct test of the MCE in thin samples is fundamental for the development of refrigerant elements with a large heat-transfer coefficient and for the design of solid state micro devices for cooling and energy harvesting.
Fabrication of Ag@AgCl with Enhanced Plasmonic Photocatalysis Performance via a Deep Eutectic Solvent
Authors: Ge Jianhua , Chen Yuchong , Xu Jing , Liu Yujie , Zhang Long , Zha Fugeng
Published: December 2018

The plasmonic photocatalyst Ag@AgCl was successfully prepared through a facile solvothermal method via a deep eutectic solvent (DES), which is composed of choline chloride and urea. X-Ray diffraction, scanning electron microscopy, energy-dispersive X-ray, element-mapping, X-ray photoelectron spectroscopy, N2 absorption–desorption, and UV-vis diffuse reflectance techniques were adopted to analyse the performance of the plasmonic photocatalyst. Characterisation results indicated that the DES not only served as a solvent and Cl source, but also as a reductant. Meanwhile, the probable mechanism for the formation of Ag@AgCl is discussed, which revealed a visible light enhanced photocatalytic property for the degradation of benzidine. Furthermore, the photocatalyst showed no decrease in its catalytic activity even after five cycles of operation. Finally, a possible photocatalytic oxidation mechanism of Ag@AgCl is proposed.
What information is important for accredited exercise physiologists to facilitate change in clients living with type 2 diabetes mellitus?
Authors: Zimmermann Alisa K. , Barnett Fiona
Published: December 2018

Accredited Exercise Physiologists (AEPs) prescribe exercise and physical activity interventions for people living with type 2 diabetes mellitus (T2DM). During initial consultations, AEPs face the challenge of collecting enough information to facilitate behaviour change and adherence to treatment recommendations. The objective of this research is to explore the initial consultation practices of AEPs with clients living with T2DM and resultant recommendations provided to clients to promote long-term adherence. This study was an exploratory descriptive qualitative study. Twenty-one AEPs who currently practice in the Townsville Region participated in focus groups or semi-structured interviews. Data were analysed using a thematic and triangulation approach. Results revealed that an interview style consultation is standard practice, which varied based on experience of the AEP. Interviewing techniques facilitating behaviour change were under-utilised, especially among less-experienced AEPs who focused on the medical information. Assessment of the psychosocial wellbeing of the client living with T2DM by AEPs was limited. AEPs recommended that group exercise sessions yielded greater success for clients adopting physical activity. It is recommended that new graduate AEPs develop greater confidence in strategies of gathering information to facilitate behaviour change in clients with T2DM. A mentorship program could ensure the continued development of new graduate AEPs through the transfer of knowledge and skills.
Sperm output and body condition are maintained independently of hibernation in an endangered temperate amphibian
Authors: Poo Sinlan , Hinkson Kristin M. , Stege Edward
Published: December 2018

Hibernation is an integral part of the life history of species living in seasonal environments. However, our knowledge about the link between hibernation and reproductive success in amphibians remains limited, which poses an obstacle for critical conservation efforts. To fill this gap, we quantified the effects of captive hibernation on sperm quality, sperm quantity and body condition in an endangered anuran, the Wyoming toad (Anaxyrus baxteri), and used naturally hibernated wild toads as a standard for comparison. We hypothesised that hibernation is essential for optimal sperm output but is detrimental to body condition. Sperm collection was performed using assisted reproductive technologies for both captive and wild toads. Contrary to our hypotheses, no differences were observed in sperm metrics (total number of cells, concentration, motility and viability) or in body condition across captive treatment groups (0, 30 or 60 days of hibernation). Moreover, no difference was found between sperm metrics of captive toads and wild toads. These unexpected findings suggest that hibernation may not be an essential process for spermiation in A. baxteri while using exogenous hormones, and illustrate the potential of temperate amphibians to adapt to varying environmental conditions during winter months.
Amelioration of sperm immobilisation factor-induced infertility by bacterial antigenic determinants cross-reacting with spermatozoa
Authors: Thaper Deepali , Rahi Deepak K. , Prabha Vijay
Published: December 2018

A strain of Staphylococcus aureus, capable of invitro immobilisation of human and mouse spermatozoa, was already present in our laboratory. Therefore, in the present study, the factor responsible (sperm immobilisation factor, SIF) was isolated and purified. It was found to compromise not only motility, but also viability, morphology and Mg2+-ATPase activity of mouse spermatozoa. Also, SIF (250μgmL−1), when administered intravaginally in female BALB/c mice before mating, showed 100% contraceptive effect. Moreover, fluorescein isothiocyanate-labelled SIF was also found to bind mouse spermatozoa and various motile as well as non-motile bacteria, indicating the presence of common SIF-binding receptors on spermatozoa and bacteria. Further, to demonstrate molecular mimicry, the amelioration of SIF-induced impairment of sperm function by a SIF-binding bacterial receptor was compelling. For this, the SIF-binding receptor from Escherichia coli (E-SBR) was purified and evaluated for its ameliorative effect on SIF-induced sperm impairment invitro and invivo. Interestingly, upon the addition of mouse spermatozoa to SIF pre-incubated with E-SBR, an ameliorative effect against SIF-induced impairment of sperm function could be observed through analysis of normal sperm parameters (motility, viability, morphology, Mg2+-dependent ATPase levels). E-SBR also blocked binding of labelled SIF to spermatozoa and bacteria and alleviated SIF-induced infertility in female BALB/c mice. This provided evidence for molecular similarities between bacteria and spermatozoa, owing to which anti-bacterial antibodies cross-reacting with spermatozoa might be produced and infertility might follow.
Awareness of and attitudes to sexually transmissible infections among gay men and other men who have sex with men in England: a qualitative study
Authors: Datta Jessica , Reid David , Hughes Gwenda , Mercer Catherine H. , Wayal Sonali , Weatherburn Peter
Published: December 2018

Background
Rates of sexually transmissible infections (STIs) have increased over recent years among gay men and other men who have sex with men (MSM) in England and Wales. HIV diagnoses remain high in this group and men with diagnosed HIV are disproportionally affected by STIs. MSM are therefore a priority for health promotion efforts to reduce STIs. Understanding awareness of and attitudes towards STIs is essential in developing health promotion interventions to reduce prevalence. Methods: Eight focus group discussions (FGDs) with a total of 61 MSM in four English cities included a ranking exercise to gauge how ‘scary’ participants thought 11 STIs are. The exercise sought insights into participants’ awareness of, knowledge about and attitudes towards STIs and blood-borne viruses (BBVs). FGDs were audio-recorded, transcribed and data analysed thematically. Results: All groups ranked HIV and Hepatitis C virus (HCV) as the scariest infections, and the majority ranked syphilis and herpes as highly scary. Scabies was ranked as the least scary by most groups. Rankings were dependent on how well informed participants felt about an infection, its transmission mechanisms, health affect and the availability of vaccines and treatment. Personal experience or that of friends influenced perceptions of particular infections, as did their prevalence, treatment options, visibility of symptoms and whether an STI could be cleared from the body. Conclusions: The study findings suggest that, although some MSM are well informed, there is widespread lack of knowledge about the prevalence, modes of transmission, health implications and treatment regimens of particular STIs.
A sexual rejection peptide: potential use for controlling mouse overpopulation
Authors: Osakada Takuya , Itakura Takumi , Kenmochi Ryo , Touhara Kazushige
Published: December 2018

Exocrine gland-secreting peptide 22 (ESP22) is a 10-kDa protein secreted in tears of juvenile mice. ESP22 inhibits sexual behaviors in adults, leading to a reduction in reproduction rate. We herein identified the 24 amino acid sequence within ESP22 that was essential for exhibiting sexual rejection activity. This synthesizable peptide can be useful for controlling mouse overpopulation.
A concavity condition for existence of a negative value in Neumann-Poincaré spectrum in three dimensions
Authors: Ji Yong-Gwan , Kang Hyeonbae
Published: December 2018

It is proved that if a bounded domain in three dimensions satisfies a certain concavity condition, then the Neumann-Poincaré operator on either the boundary of the domain or its inversion in a sphere has a negative value in its spectrum. The concavity condition is quite simple, and is satisfied if there is a point on the boundary at which the Gaussian curvature is negative.
Burnside groups and 𝑛-moves for links
Authors: Miyazawa Haruko , Wada Kodai , Yasuhara Akira
Published: December 2018

M. K. Da̧bkowski and J. H. Przytycki introduced thennth Burnside group of a link, which is an invariant preserved bynn-moves. Using this invariant, for an odd primepp, they proved that there are links which cannot be reduced to trivial links viapp-moves. It is generally difficult to determine ifppth Burnside groups associated to a link and the corresponding trivial link are isomorphic. In this paper, we give a necessary condition for the existence of such an isomorphism. Using this condition we give a simple proof for their results that concernpp-move reducibility of links.
On an observation of Sibony
Authors: Chakrabarti Debraj
Published: December 2018

It is shown that if the boundary of a Reinhardt domain in

C

n

\mathbb {C}^n

contains the origin, then the origin has a neighborhood to which each holomorphic function on the domain which is infinitely many times differentiable up to the boundary extends holomorphically.
Histones predate the split between bacteria and archaea
Authors: Alva Vikram , Lupas Andrei N
Published: December 2018

Motivation

Histones form octameric complexes called nucleosomes, which organize the genomic DNA of eukaryotes into chromatin. Each nucleosome comprises two copies each of the histones H2A, H2B, H3 and H4, which share a common ancestry. Although histones were initially thought to be a eukaryotic innovation, the subsequent identification of archaeal homologs led to the notion that histones emerged before the divergence of archaea and eukaryotes.

Results

Here, we report the detection and classification of two new groups of histone homologs, which are present in both archaea and bacteria. Proteins in one group consist of two histone subunits welded into single-chain pseudodimers, whereas in the other they resemble eukaryotic core histone subunits and show sequence patterns characteristic of DNA binding. The sequences come from a broad spectrum of deeply-branching lineages, excluding their genesis by horizontal gene transfer. Our results extend the origin of histones to the last universal common ancestor.

Supplementary information

Supplementary data are available at Bioinformatics online.
miRDeep-P2: accurate and fast analysis of the microRNA transcriptome in plants
Authors: Kuang Zheng , Wang Ying , Li Lei , Yang Xiaozeng
Published: December 2018

Motivation

Two major challenges arise when employing next-generation sequencing methods to comprehensively identify microRNAs (miRNAs) in plants: (i) how to minimize the false-positive inheritable to computational predictions and (ii) how to minimize the computational time required for analyzing the miRNA transcriptome in plants with complex and large genomes.

Results

We updated miRDeep-P to miRDeep-P2 (miRDP2) by employing a new filtering strategy and overhauling the algorithm. miRDP2 has been tested against miRNA transcriptomes in plants with increasing genome sizes that included Arabidopsis, rice, tomato, maize and wheat. Compared with miRDeep-P and several other computational tools, miRDP2 processes next-generation sequencing data with superior speed. By incorporating newly updated plant miRNA annotation criteria and developing a new scoring system, the accuracy of miRDP2 outperformed other programs. Taken together, our results demonstrate miRDP2 as a fast and accurate tool for analyzing the miRNA transcriptome in plants.

Availability and implementation

The miRDP2 are freely available from https://sourceforge.net/projects/mirdp2/.

Supplementary information

Supplementary data are available at Bioinformatics online.
The power of participatory story mapping: Advancing equitable development in disadvantaged neighbourhoods
Authors: Lung-Amam Willow S , Dawkins Casey
Published: December 2018

Community developers and planners have long recognized the value of storytelling to engage communities. Yet, in working with disadvantaged communities, they are often challenged to meaningfully engage residents and uncover place values that can help drive community development strategies. In a case study of Langley Park, Maryland, a neighborhood comprised of largely low-income Latino immigrants facing potential displacement from a new transit line, this article investigates the potential of new story mapping techniques and technologies to assist communities in leveraging everyday place meanings and values to advance greater equity in the process of neighborhood redevelopment. It demonstrates how participatory story mapping can empower traditionally marginalized voices and encourage more complex place narratives within community development and planning.
Radiation Risks of Uterine Cancer in Atomic Bomb Survivors: 1958–2009
Authors: Utada Mai , Brenner Alina V , Preston Dale L , Cologne John B , Sakata Ritsu , Sugiyama Hiromi , Sadakane Atsuko , Grant Eric J , Cahoon Elizabeth K , Ozasa Kotaro , Mabuchi Kiyohiko
Published: December 2018

Background

Ionizing radiation is known to be capable of causing cancer of many organs, but its relationship with uterine cancer has not been well characterized.

Methods

We studied incidence of uterine cancer during 1958–2009 among 62 534 female atomic bomb survivors. Using Poisson regression analysis, we fitted excess relative risk (ERR) models to uterine cancer rates adjusted for several lifestyle and reproductive factors. Person-years at risk were also adjusted for the probability of prior hysterectomy, because it could affect the subsequent risk of uterine cancer. We assessed the modifying effect of age and other factors on the radiation risk. For analysis of the modifying effect of age at radiation exposure around menarche, we compared the radiation risk for several exposure-age categories as well as using parametric models.

Results

There were 224 uterine corpus cancers and 982 cervical cancers. We found a significant association between radiation dose and risk of corpus cancer (ERR per Gray [ERR/Gy] = 0.73, 95% confidence interval [CI] = 0.03 to 1.87) but not for cervical cancer (ERR/Gy = 0.00, 95% CI = −0.22 to 0.31). For corpus cancer, we found statistically significant heterogeneity in ERR/Gy by age (Pheterogeneity = .001) with elevated risk for women exposed to radiation between ages 11 and 15 years (ERR/Gy = 4.10, 95% CI = 1.47 to 8.42) and no indication of a radiation effect for exposures before or after this exposure-age range.

Conclusions

The current data suggest that uterine corpus is especially sensitive to the carcinogenic effect of radiation exposure occurring during the mid-pubertal period preceding menarche. There is little evidence for a radiation effect on cervical cancer risk.
External Equity Financing Shocks, Financial Flows, and Asset Prices
Authors: Belo Frederico , Lin Xiaoji , Yang Fan
Published: December 2018

We develop a dynamic model with time variation in external equity financing costs and show that variation in these costs is important for the model to quantitatively capture the joint dynamics of firms’ asset prices, real quantities, and financial flows in the U.S. economy. Growth firms and high investment firms are less risky in equilibrium, because they can substitute more easily debt financing for equity financing when it becomes more costly to raise external equity, which are high marginal utility states. Using a model-implied proxy of aggregate equity issuance cost shocks, we provide empirical support for the model’s economic mechanism.

Received August 7, 2017; editorial decision September 24, 2018 by Editor Stijn Van Nieuwerburgh. Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online
Innate lymphoid cells in asthma: pathophysiological insights from murine models to human asthma phenotypes
Authors: Jonckheere Anne-Charlotte , Bullens Dominique M.A. , Seys Sven F.
Published: December 2018

Purpose of review

The current review describes the role of different types of innate lymphoid cells (ILCs) in the pathogenesis of asthma inflammatory phenotypes by linking findings from murine asthma models with human studies. Novel treatment options are needed for patients with steroid-insensitive asthma. Strategies targeting ILCs, or their upstream or downstream molecules are emerging and discussed in this review.

Recent findings

In eosinophilic asthma, ILCs, and especially type 2 ILCs (ILC2s), are activated by alarmins such as IL-33 upon allergen triggering of the airway epithelium. This initiates IL-5 and IL-13 production by ILC2, resulting in eosinophilic inflammation and airway hyperreactivity. Type 3 ILCs (ILC3s) have been shown to be implicated in obesity-induced asthma, via IL-1β production by macrophages, leading ILC3 and release of IL-17. ILC1s might play a role in severe asthma, but its role is currently less investigated.

Several studies have revealed that ILC2s play a role in the induction of eosinophilic inflammation in allergic and nonallergic asthmatic patients mainly via IL-5, IL-13, IL-33 and thymic stromal lymphopoietin. Knowledge on the role of ILC3s and ILC1s in asthmatic patients is lagging behind. Further studies are needed to support the hypothesis that these other types of ILCs contribute to asthma pathogenesis, presumably in nonallergic asthma phenotypes.
Risk Factors for New-Onset Atrial Fibrillation in Patients With Sepsis: A Systematic Review and Meta-Analysis
Authors: Bosch Nicholas A. , Cohen David M. , Walkey Allan J.
Published: December 2018

Objective:

Atrial fibrillation frequently develops in patients with sepsis and is associated with increased morbidity and mortality. Unfortunately, risk factors for new-onset atrial fibrillation in sepsis have not been clearly elucidated. Clarification of the risk factors for atrial fibrillation during sepsis may improve our understanding of the mechanisms of arrhythmia development and help guide clinical practice.

Data Sources:

Medline, Embase, Web of Science, and Cochrane CENTRAL.

Study Selection:

We conducted a systematic review and meta-analysis to identify risk factors for new-onset atrial fibrillation during sepsis.

Data Extraction:

We extracted the adjusted odds ratio for each risk factor associated with new-onset atrial fibrillation during sepsis. For risk factors present in more than one study, we calculated pooled odds ratios (meta-analysis). We classified risk factors according to type and quantified the factor effect sizes. We then compared sepsis-associated atrial fibrillation risk factors with risk factors for community-associated atrial fibrillation.

Data Synthesis:

Forty-four factors were examined as possible risk factors for new-onset atrial fibrillation in sepsis, 18 of which were included in meta-analyses. Risk factors for new-onset atrial fibrillation included demographic factors, comorbid conditions, and most strongly, sepsis-related factors. Sepsis-related factors with a greater than 50% change in odds of new-onset atrial fibrillation included corticosteroid use, right heart catheterization, fungal infection, vasopressor use, and a mean arterial pressure target of 80–85 mm Hg. Several cardiovascular conditions that are known risk factors for community-associated atrial fibrillation were not identified as risk factors for new-onset atrial fibrillation in sepsis.

Conclusions:

Our study shows that risk factors for new-onset atrial fibrillation during sepsis are mainly factors that are associated with the acute sepsis event and are not synonymous with risk factors for community-associated atrial fibrillation. Our results provide targets for future studies focused on atrial fibrillation prevention and have implications for several key areas in the management of patients with sepsis such as glucocorticoid administration, vasopressor selection, and blood pressure targets.
Pembrolizumab in the treatment of advanced/metastatic melanoma: a single-center institution experience
Authors: Cimminiello Carolina , Indini Alice , Di Guardo Lorenza , Prisciandaro Michele , Randon Giovanni , Tolomio Elena , De Braud Filippo , Del Vecchio Michele
Published: December 2018

Pembrolizumab is an anti-programmed cell death-1 monoclonal antibody, currently representing the first-line treatment for advanced melanoma. Apart from registration trials, there is a paucity of data on its effectiveness and safety in a real-world setting. We retrospectively analyzed patients with metastatic melanoma treated at our institution in the context of an Expanded Access Program. Survival outcomes were assessed using Kaplan–Meier and Cox hazard models. Overall, 42 melanoma patients were treated. BRAF status was wild type in 30 (71%) patients and mutated in 12 (29%). Twelve (29%) patients received pembrolizumab as the II line treatment, the other 30 (71%) as at least III line treatment. One (2%) patient experienced complete response, six (14%) partial response, and seven (17%) stable disease; 39 (93%) patients had disease progression. Median progression-free survival and overall survival were 2.4 (range: 0.2–46.5) and 5.5 months (range: 0.2–47.1), respectively. Results of the multivariate analysis showed that performance status [hazard ratio (HR): 7.10; 95% confidence interval (CI): 2.73–18.4; P<0.001] and the number of previous therapeutic lines (HR: 1.84; 95% CI: 1.08–3.13; P=0.025) influenced progression-free survival. Similarly, performance status (HR: 6.14; 95% CI: 2.44–15.4; P<0.001) and the number of previous lines (HR: 2.04; 95% CI: 1.17–3.56; P=0.012) influenced overall survival. Fourteen (33%) patients reported immune-related adverse events. Three (7%) patients discontinued treatment due to immune-related adverse events onset. At present eight (19%) patients are still alive and one patient is still on treatment. Despite the limitations related to the size and characteristics of this report, our experience confirms the use of pembrolizumab for advanced melanoma in a real-life setting.
Concurrent Radiation and Immunotherapy
Authors: Amin Neha P. , Remick Jill , Agarwal Manuj , Desai Nina A. , Bergom Carmen , Simone Charles B.
Published: December 2018

Objective:

The objective of this study was to report on US radiation oncologists’ (ROs) practice patterns and perceptions of concurrent radiation (RT) and immunotherapy (IT) (CRI).

Methods:

A 22-question survey was emailed to radiation oncologists in February 2018. CRI was defined as RT completed within 1 week before initial IT infusion through 4 weeks after final IT infusion.

Results:

Of the 323 respondents from 45 states, 88% had experience treating a patient with CRI, including 51% private and 48% academic physicians. The most common reason for not offering CRI was concerns of increased toxicity (50%). Although 84% to 94% of respondents did not change RT dose, more ROs decreased dose when treating central structures (chest/abdomen/pelvis) versus noncentral structures (brain/head and neck/extremities): 13% to 15% versus 4% to 8%, P<0.001. The majority (58% to 80%) of respondents would not delay RT from last IT infusion. Moderate and significant actual toxicities were rare (medical intervention 6%, hospitalization/death <1%). 97.5% of ROs did not routinely prescribed prophylactic steroids for CRI. More ROs believed CRI with SBRT/SRS versus palliative RT had better local control (35% vs. 25%, P<0.05) and higher rates of abscopal responses (41% vs. 25%, P<0.01).

Conclusions:

Despite concerns for toxicity, ROs with CRI experience reported minimal toxicities. Most ROs do not alter RT dose, use prophylactic steroids, or delay starting RT from last IT infusion. Uncertainty remains about improved local control outcomes and abscopal responses from CRI, with a perception that concurrent SBRT offers better outcomes than palliative RT. These survey results may help guide ROs until more definitive data are available.
Bisphosphonate-loaded Bone Cement as a Local Adjuvant Therapy for Giant Cell Tumor of Bone
Authors: Greenberg David D. , Lee Francis Y.
Published: December 2018

Background:

Historically, nontargeted adjuvant therapies such as liquid nitrogen, phenol, argon beam, and alcohol have been applied locally after curettage of giant cell tumors (GCT) in the extremities. Systemic bisphosphonates (BP) and denosumab have emerged as osteoclast-targeting therapies because osteoclast-like giant cells, responsible for aggressive bone resorption, are susceptible to BP or denosumab. However, such drugs may cause systemic side effects. We examined the effects of an alternative intraoperative local delivery of BP on GCTs.

Materials and Methods:

In total, 17 patients with GCTs underwent extended surgical curettage procedures consisting of high-speed burring, traditional adjuvant therapy, and application of BP-loaded polymethylmethacrylate bone cement. Clinical data and follow-up radiographs were reviewed to investigate local recurrence (LR) rate and complications in a retrospective manner.

Results:

There were 6 males and 11 females (mean age, 33.7 y). There were no cases of pulmonary metastases. Patient follow-up ranged from 1 to 12 years. There was 1 LR during the follow-up period for an LR rate of 5.9%. The mean final Musculoskeletal Tumor Society (MSTS) score was 29. There were no systemic or localized avascular necrosis or atypical fractures related to BPs noted.

Conclusions:

BP-loaded polymethylmethacrylate is a targeted local adjuvant therapy that is feasible, safe, and may reduce LRs while alleviating the risk of systemic side effects of BPs such as avascular necrosis of jaw and atypical femur fractures. Future prospective randomized clinical trials will strengthen the level of evidence of this proposed targeted therapy.

Level of Evidence:

Therapeutic level IV—see instructions for authors for a complete description of evidence.
Simultaneous Quantification of 13 Cannabinoids and Metabolites in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry in Adult Epilepsy Patients
Authors: Roslawski Michaela J. , Remmel Rory P. , Karanam Ashwin , Leppik Ilo E. , Marino Susan E. , Birnbaum Angela K.
Published: December 2018

Background:

A sensitive, robust method was developed and validated to quantitate 13 major natural cannabinoid parent and metabolite compounds in human plasma at or below 0.5 ng/mL.

Methods:

A liquid chromatography tandem mass spectrometry method was developed and validated to measure 13 cannabinoid compounds: cannabidiol (CBD), cannabidiolic acid, cannabidivarin, cannabinol, cannabigerol, cannabigerolic acid, cannabichromene, Δ9-tetrahydocannabinol (THC), Δ9-tetrahydrocannabinolic acid A (THCA), Δ9-tetrahydrocannabivarin (THCV), 11-hydroxy-Δ9-tetrahydrocannbinol (11-OH-THC), 11-nor-9-carboxy-Δ9-tetrahydrocannbinol (THC-COOH), and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol glucuronide (THC-COOH-glu). Samples (200 µL) were extracted through protein precipitation and separated with a Kinetex EVO C18 column and a 65%–95% gradient of methanol and 0.2% ammonium hydroxide/H2O at a flow rate of 0.4 mL/min. Samples were obtained from patients with epilepsy receiving cannabis for the treatment of seizures.

Results:

The extracted lower limit of quantification was 0.05 ng/mL for CBD, cannabidivarin, cannabinol, and 11-OH-THC; 0.10 ng/mL for cannabidiolic acid, cannabigerol, cannabichromene, cannabigerolic acid, THC, THCA, and THCV; and 0.50 ng/mL for THC-COOH and THC-COOH-glu. Mean quality control intraday accuracy and precision for all analytes ranged 96.5%–104% and 2.7%–4.9%, respectively, whereas interday accuracy and precision ranged 98%–103.3% and 0.2%–3.6%, respectively. An absolute matrix effect was observed for some analytes, however, with minimal relative matrix effect. Lack of nonspecific drug binding to extraction glass and plasticware was verified. Patient CBD levels ranged from 0.135 to 11.13 ng/mL.

Conclusions:

The validated method met FDA guidelines for bioanalytical assays precision and accuracy criteria. The assay reliably confirmed the use of particular medical cannabis formulations in patient samples as well as reliably measured low CBD concentrations from single-dose CBD exposure.
Rapid Quantitation of Flecainide in Human Plasma for Therapeutic Drug Monitoring Using Liquid Chromatography and Time-of-Flight Mass Spectrometry
Authors: Rahman Mohammed , Couchman Lewis , Povstyan Valentyna , Bainbridge Verity , Kipper Karin , El-Nahhas Toqa , Johnston Atholl , Holt David
Published: December 2018

Background:

Measurement of flecainide is useful to optimize dosage and minimize risks of toxicity. Furthermore, there is a need for urgent sample analysis when flecainide is used in transplacental therapy for fetal tachycardia. To this end, we have developed and validated a rapid assay for the measurement of flecainide in human plasma or serum, using a small sample volume (50 µL).

Methods:

After a simple deproteination with zinc sulfate and methanol, prepared samples were injected onto a short (30 mm) analytical column and eluted using a rapid gradient elution. Detection was performed using time-of-flight mass spectrometry. Flecainide was quantified using flecainide-D4 as internal standard, with both compounds extracted from the total ion chromatogram using a ±5 ppm extraction window based on the theoretical m/z values for the protonated ions.

Results:

The assay was linear over a putative therapeutic range (100–1500 mcg/L). Between- and within-assay imprecision and accuracy were <4.6% and 94.8%–110.0%, respectively. Matrix effects were minimal and were compensated for by flecainide-D4. There were no effects due to hemolysis or lipemia, and no carryover was apparent. Total analysis time was just 1.2 minutes (72 seconds).

Conclusions:

We have developed and validated a rapid method for the analysis of flecainide. The method is particularly suited for flecainide therapeutic drug monitoring, when analyzing samples from mothers receiving flecainide for the treatment of fetal tachycardia.
Translational highlights in breast cancer research and treatment: recent developments with clinical impact
Authors: Fasching Peter A. , Schneeweiss Andreas , Kolberg Hans-Christian , Ettl Johannes , Fehm Tanja N. , Overkamp Friedrich , Lüftner Diana
Published: December 2018

Purpose of review

Over the last decades the time which is needed to translate a preclinical finding or idea in the clinic has reduced continuously. Especially but not only for breast cancer the number of tested drugs and targeted pathways have increased immensely. In addition, the introduction of immune-oncological treatments has further advanced the possibilities for future treatments. This review focuses on recent developments in the prevention and treatment of breast cancer including results from major clinical trials and recent conferences.

Recent findings

Many pathways involved in the progression or treatment of breast cancer have been also identified in the cause and pathogenesis of breast cancer. Therefore, breast cancer risk can be described in much more detail, possibly leading to new prevention strategies. In breast cancer treatment the introduction of PARP inhibitors has begun. Recent trials will lead to a better understanding whether PI3K inhibitors can be developed for application in the clinic and first large randomized trials show the superiority of anti PD-1/PD-L1 treatments.

Treatment strategies which were developed over the last decade are moving rapidly into the clinical use. The understanding of treatment targets and involved side effects will be important for the safe implementation of these treatments into routine practice.
Cyclin-dependent kinase 4/6 inhibitors: what have we learnt across studies, therapy situations and substances
Authors: Banys-Paluchowski Malgorzata , Krawczyk Natalia , Paluchowski Peter
Published: December 2018

Purpose of review

Cyclin-dependent kinases (CDK) are key regulatory enzymes that control cell cycle and cell division. In the recent years, new therapeutic options selectively targeting CDK 4 and 6 have shown promising clinical activity in several solid tumors. Since 2015, three CDK 4/6 inhibitors have been approved for treatment of hormone receptor-positive HER2-negative metastatic breast cancer: palbociclib, ribociclib and abemaciclib. These drugs share a common mechanism of action and have been evaluated in studies with a similar design. The following review gives a clinical overview of the CDK 4/6 inhibitors in breast cancer therapy and highlight current study data with regard to their antitumor efficacy and toxicities.

Recent findings

In clinical trials in the first-line and later-line setting, palbociclib, ribociclib and abemaciclib in combination with endocrine therapy significantly prolonged progression-free survival. The most common adverse events during treatment with CDK 4/6 inhibitors are neutropenia, fatigue and gastrointestinal symptoms.

CDK 4/6 inhibitors represent a valuable treatment option for patients with metastatic hormone receptor-positive HER2-negative breast cancer. Although the clinical efficacy of the three agents seems similar, their toxicity profiles differ. Therefore, the choice of a CKD 4/6 inhibitor depends on patient's characteristics and individual preferences.

Video abstract

In the video, the author describes the content of the review and present the main topics discussed in the article (http://links.lww.com/COOG/A44).
A Multicenter Study Evaluating the Risk Factors and Outcomes of Repeat Descemet Stripping Endothelial Keratoplasty
Authors: Thompson Jordan M. , Truong Alexander H. , Stern Hudson D. , Djalilian Ali , Cortina M. Soledad , Tu Elmer Y. , Johnson Paula , Verdier David D. , Rafol Lorene , Lubeck David , Spektor Tatyana , Jorgensen Colin , Rubenstein Jonathan B. , Majmudar Parag A. , Talati Rushi , Basti Surendra , Feder Robert , Sugar Alan , Mian Shahzad I. , Balasubramanian Neelam , Sandhu Jasmin , Gaynes Bruce I. , Bouchard Charles S.
Published: December 2018

Purpose:

Descemet stripping endothelial keratoplasty (DSEK), currently the most common procedure for managing corneal endothelial dysfunction, may be repeated following DSEK failure from a variety of causes. This multicenter study reports the risk factors and outcomes of repeat DSEK.

Methods:

This was an institutional review board-approved multicenter retrospective chart review of patients who underwent repeat DSEK. Twelve surgeons from 5 Midwest academic centers and 3 private practice groups participated. The Eversight Eye Bank provided clinical indication and donor graft data. We also assessed the role of the learning curve by comparing cohorts from the first and second 5-year periods.

Results:

A total of 121 eyes from 121 patients who underwent repeat DSEK were identified. The average age of the patients was 70 ± 12 years. The most common indication for repeat DSEK was late endothelial graft failure without rejection (58%, N = 63). Average preoperative and 12-month postoperative repeat DSEK corrected distance visual acuities were 20/694 and 20/89, respectively. Visual acuity outcomes, endothelial cell density, and cell loss did not significantly vary between the 2 cohorts. Initial graft rebubble rates for the first and second cohorts were 51% and 25%. The presence of glaucoma, prior glaucoma surgery, or a history of penetrating (full thickness) keratoplasty did not significantly affect visual outcomes. The median, mean, and range of intraocular pressures before repeat DSEK were 15.0, 15.7, and 6 to 37 mm Hg, respectively. Patients with higher intraocular pressures before repeat DSEK had improved postoperative corrected distance visual acuities.

Conclusions:

Repeating DSEK improves vision following failed or decompensated DSEK surgery. Higher preoperative repeat DSEK IOPs were associated with improved visual outcomes, and initial graft rebubble rates, which decreased over time, were likely due to surgeon experience.
Outcomes of Combined Ahmed Glaucoma Valve and Trabeculectomy Revision With Adjunctive Antimetabolite
Authors: Lin Mark , Alizadeh Reza , Law Simon K.
Published: December 2018

Purpose:

Evaluate the intraocular pressure (IOP) control in combined Ahmed Glaucoma Valve (AGV) implantation and trabeculectomy revision with adjunctive antimetabolite compared with AGV alone in patients who failed prior trabeculectomy.

Methods:

Consecutive cases of combined AGV implantation and trabeculectomy revision with adjunctive antimetabolite (combined group) after January 3, 2014 were case-matched to cases of AGV implantation alone (AGV-alone group) before January 3, 2014. Primary outcome measures were qualified success with stratified IOP targets based on criteria: (A) IOP≤18 mm Hg and 20% IOP reduction; (B) IOP≤15 mm Hg and 25% IOP reduction; (C) IOP≤12 mm Hg and 30% IOP reduction, and hypertensive phase (HP) rate. Secondary outcome measures were 1-year postoperative IOP and number of glaucoma medications and complications.

Results:

Twenty eyes (20 patients) in each group were included. Cumulative success for combined group and AGV-alone group at 1-year were: 74.0% versus 59.2% (criterion A, P=0.221), 61.9% versus 49.5% (B, P=0.183), and 54.2% versus 30.0% (C, P=0.033), respectively. In total, 50% (10 eyes) in the AGV-alone group developed HP compared with 15% (3 eyes) in the combined group (P=0.041). At 1-year follow-up, combined group had statistically significantly lower IOP than AGV-alone group (10.1±4.4, 13.3±2.9 mm Hg, respectively; P=0.028). There were no cases of bleb-related infections, choroidal effusion or hemorrhage, persistent hypotony, or hypotony maculopathy in either group.

Conclusions:

Combining AGV implantation with trabeculectomy revision with antimetabolite was associated with better tonometric success compared with AGV implantation alone in patients with previously failed trabeculectomy, particularly when a low IOP target (≤12 mm Hg) is required. Revised trabeculectomy may provide complimentary outflow facility to AGV.
Changes in Intraocular Pressure and Angle Status After Phacoemulsification in Primary Angle Closure Hypertension
Authors: Selvan Harathy , Angmo Dewang , Tomar Ankit S. , Yadav Suresh , Sharma Arpit , Dada Tanuj
Published: December 2018

Purpose:

To study the change in intraocular pressure (IOP) and angle status after phacoemulsification in a cohort of primary angle closure hypertension (PACHT) patients.

Setting:

Tertiary Eye Care, India.

Design:

Prospective interventional case-series.

Methods:

Case-series of 18 eyes of 18 patients. Preoperative biometry including axial length, anterior chamber depth (ACD), lens thickness, and central corneal thickness were studied. Preoperative and postoperative IOP, number of topical glaucoma medications, angle swept source optical coherence tomography (SS-OCT) parameters of nasal and temporal angle opening distance, trabecular iris space area, scleral spur angle, lens vault and circumferential iridotrabecular contact (ITC) were studied and their correlations derived.

Results:

The mean preoperative IOP, 31±6 mm Hg, decreased to 14±1 mm Hg at 6-months postoperative period, P<0.001, a fall by 58±14%. The number of glaucoma medications reduced from 4(3-5) to 2(1-3), P<0.001. All SS-OCT studied parameters denoted significant angle widening postsurgery. The ITC% reduced from 52(16-100) to 19(0-97), P<0.001. The preoperative ITC showed moderate to strong correlation with all preoperative nasal and temporal angle parameters. It also showed moderate positive correlation with percentage fall in IOP at 1-month postoperative period. The preoperative ACD showed significant negative correlation with preoperative and postoperative ITC.

Conclusions:

PACHT patients benefit significantly from cataract surgery with marked angle widening, IOP reduction and a decrease in the number of glaucoma medications. The SS-OCT derived circumferential iridotrabecular contact index can be used as the single best parameter to indicate the preoperative angle status and predict postoperative change in IOP, as against the numerous single section measured angle parameters.
Determining Optic Nerve Cupping Using Optical Coherence Tomography (OCT) Versus a New Electronic Mobile Device
Authors: Sarmento Andrea G.L. , Sarmento Adriano , Souza Luiz L. , Oliveira Luiz A. , Rios Marcus F.R. , Domingues Thiago A.L. , Paula Jayter S. , Lira Rodrigo P.C.
Published: December 2018

Purpose:

We present a new device that may aid in glaucoma screening. The vertical cup-to-disc ratio (CDR) obtained from a new electronic mobile device (EMD) was compared with that obtained from a spectral-domain optical coherence tomography. In addition, results from examiner’s evaluations were compared with the results mentioned above.

Methods:

A single-masked study was performed to evaluate the CDR results from 110 eyes from 110 subjects whose ages ranged between 18 and 60 years (39±13 y old), of whom 66 (60%) were female individuals. Vertical CDR was analyzed 5 times with each device in a single visit and evaluated by 3 different ophthalmologists. The Spearman correlation test and Bland-Altman analysis were used to evaluate the correlation and agreement between methods.

Results:

The CDR average using spectral-domain optical coherence tomography was 0.47±0.04, whereas the CDR average using EMD was 0.42±0.02. The clinical evaluation resulted in an average of 0.34±0.27. The Spearman test showed a strong correlation between vertical CDR obtained with both devices (r=0.8319; P<0.0001) and between EMD and the examiners (r=0.7156; P>0.001). Bland-Altman analysis showed good agreement between both devices as well as between EMD and the examiners (95% limits of agreement from −0.20 to 0.10 and from −0.15 to 0.30, respectively).

Conclusions:

We present a low-cost, reliable EMD that may serve as an alternative to subjectively measuring vertical CDR in face-to-face consultations and hence increase the general public’s access to glaucoma screening. This may be especially useful for patients who live in remote areas.
Transconjunctival Compression Sutures for an Overfiltering Bleb Following Subconjunctival Gel Stent Insertion for Glaucoma
Authors: Karaconji Tanya , Naqvi Salman , Mercieca Karl
Published: December 2018

Low intraocular pressure and hypotony secondary to overfiltration is a recognized complication after trabeculectomy, particularly when augmented with antimetabolites such as 5-fluorouracil and mitomycin C. The relatively recent introduction of minimally invasive glaucoma surgery such as the ab interno XEN 45 (Allergan, Ireland) subconjunctival gel implant has heralded a new era of glaucoma drainage surgery where postoperative complications may be less and surgical recovery quicker. However, any effective glaucoma filtering procedure will always carry the risk of inducing hypotony. We describe the case of an 84-year-old white gentleman who underwent right eye XEN implantation for refractory primary open-angle glaucoma who subsequently developed persistent hypotony secondary to an overfiltering bleb. The complication was successfully treated with a modified transconjunctival bleb compression suture technique. To our knowledge, this has not been previously described in the literature and may help the glaucoma specialist deal effectively and relatively noninvasively with this rare but potentially challenging minimally invasive glaucoma surgery complication.
Conditioned pain modulation in rodents can feature hyperalgesia or hypoalgesia depending on test stimulus intensity
Authors: Tansley Shannon N. , Macintyre Leigh C. , Diamond Laura , Sotocinal Susana G. , George Nicole , Meluban Lee , Austin Jean-Sebastien , Coderre Terence J. , Martin Loren J. , Mogil Jeffrey S.
Published: December 2018

The counterirritation phenomenon known as conditioned pain modulation, or diffuse noxious inhibitory control in animals, is of increasing interest due to its utility in predicting chronic pain and treatment response. It features considerable interindividual variability, with large subsets of pain patients and even normal volunteers exhibiting hyperalgesia rather than hypoalgesia during or immediately after receiving a conditioning stimulus. We observed that mice undergoing tonic inflammatory pain in the abdominal cavity (the conditioning stimulus) display hyperalgesia, not hypoalgesia, to noxious thermal stimulation (the test stimulus) applied to the hindpaw. In a series of parametric studies, we show that this hyperalgesia can be reliably observed using multiple conditioning stimuli (acetic acid and orofacial formalin), test stimuli (hindpaw and forepaw-withdrawal, tail-withdrawal, hot-plate, and von Frey tests) and genotypes (CD-1, DBA/2, and C57BL/6 mice and Sprague-Dawley rats). Although the magnitude of the hyperalgesia is dependent on the intensity of the conditioning stimulus, we find that the direction of effect is dependent on the effective test stimulus intensity, with lower-intensity stimuli leading to hyperalgesia and higher-intensity stimuli leading to hypoalgesia.