bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Advances in Photodecarboxylations Involving Phthalimides
Authors: Mumtaz Saira , Robertson Mark J. , Oelgemöller Michael
Published: August 2018

Owing to their favourable photophysical and electrochemical properties, phthalimides undergo a variety of highly efficient photodecarboxylation reactions. These transformations have been applied to the synthesis of macrocyclic compounds as well as bioactive addition adducts. N-Acetoxyphthalimides are versatile precursors to imidyl and alkyl radicals through photodecarboxylation and have subsequently been used for a variety of coupling reactions. The generally mild reaction conditions make these reactions attractive for green chemical applications. The process protocols were successfully transferred to novel photoreactor devices, among these falling film or continuous flow reactors.
Expect the unexpected: a new large species of Marionia (Heterobranchia : Nudibranchia : Tritoniidae) from western Europe
Authors: Almón Bruno , Pérez Jacinto , Caballer Manuel
Published: August 2018

The target species of this work is a large tritonid nudibranch, relatively common in Galician waters (north-western Spain), where it has been regularly observed since the year 2000. To date, this species has been misidentified as Tritonia hombergii, a species from northern latitudes, because of its remarkable size. On the other hand, the external anatomy of the specimens from north-western Spain resembles that of Marionia blainvillea, a species common in the Mediterranean. To untangle the real taxonomic identity of the species, a detailed anatomical study was performed, revealing several morphological differences that has led us to consider the Galician specimen as new to science. A phylogenetic analysis was conducted for both 16S and COI genes to try to establish its systematic position in relation with other taxa. Marionia gemmii, sp. nov. differs from all known Tritoniidae in the size, colour pattern, number of velar processes, presence of stomach plates, radular formula, the shape of spawning masses and even in its feeding habits. The phylogenetic results support the comprehensive morphological analysis and also make it clear that most tritoniid genera currently recognised are not monophyletic and that a major systematic revision of the family is needed. http://zoobank.org/urn:lsid:zoobank.org:pub:91332872-9020-4D06-8B1C-2E7654D54E1A
Associations between economic dependence, sexual behaviours, and sexually transmitted infections among young, Black, gay, bisexual and other men who have sex with men living with and without HIV in Jackson, Mississippi, USA
Authors: Closson Kalysha , Smith Rachel Vickers , Olarewaju Gbolahan , Crosby Richard
Published: August 2018

Background In the USA, young Black gay, bisexual or other men who have sex with men (YBMSM) bear the largest burden of HIV incidence. The aim of this study is to examine the independent associations between economic dependency on a sexual partner and several HIV risk behaviours and sexual health outcomes among YBMSM living in Jackson, Mississippi, USA. Methods: Baseline data from 589 YBMSM, with a median age of 22.0 years (IQR = 15–25) participating in a brief sex-positive HIV and STI prevention intervention, were used to measure the association between six sexual behaviours, sexually transmissible infections (STIs) status at baseline and economic dependence. Bivariate χ2 associations were tested and regression models adjusted for education level (≤ high school), employment and HIV-status. Results: In regressions, of the six sexual behaviours reported in the last 90 days and six STIs tested at baseline, economically dependent YBMSM were more likely to report condomless anal receptive sex (aOR = 2.19, 95%CI = 1.25–3.83), ≥3 partners as a top (aOR = 1.99, 95%CI = 1.17–340), ≥3 sex partners as a bottom (aOR = 2.07, 95%CI = 1.24–3.45), ≥3 sex acts as a bottom (aOR = 2.10, 95%CI = 1.16–3.82) and testing positive for oral gonorrhoea (aOR = 2.39, 95%CI = 1.18–4.83) after controlling for HIV status, employment and education. Conclusions: Interventions should consider how poverty, unemployment and economic dependence interact to influence relationship power imbalances, condom use and sexual positioning agency, and sexual health for key populations of MSM.
Ocean currents and herbivory drive macroalgae-to-coral community shift under climate warming
Authors: Kumagai Naoki H. , García Molinos Jorge , Yamano Hiroya , Takao Shintaro , Fujii Masahiko , Yamanaka Yasuhiro
Published: August 2018

Significance

Global degradation of coral reefs and macroalgal beds can have ecosystem-wide implications for biodiversity, ecological functioning, and ocean resources. However, recent studies in warm temperate zones have documented community shifts from macroalgae to corals, signaling a potential mechanism for coral conservation under climate warming. Here, we present evidence that warming, aided by the dominant poleward-flowing current system, is facilitating the expansion of tropical corals and herbivorous fishes into existing temperate Japanese macroalgae communities, which are contracting faster than they are expanding. Furthermore, our results suggest future climate change may exacerbate this process, potentially compromising the long-term stability of these communities. Future conservation of these communities might require of a more proactive management toward climate adaptation.
Decreasing fire season precipitation increased recent western US forest wildfire activity
Authors: Holden Zachary A. , Swanson Alan , Luce Charles H. , Jolly W. Matt , Maneta Marco , Oyler Jared W. , Warren Dyer A. , Parsons Russell , Affleck David
Published: August 2018

Significance

Wildfires have profound impacts on forested ecosystems and rural communities. Increases in area burned by wildfires in the western United States have been widely attributed to reduced winter snowpack or increased summer temperatures. Trends in precipitation have previously been dismissed as has their feedback to regional temperature trends. We show that declines in summer precipitation and wetting rain days have likely been a primary driver of increases in wildfire area burned. Understanding the climatic drivers of fire activity is important for informing forest management. Our findings are consistent with future climate projections, which predict further decreases in summer precipitation and longer dry periods between rain events across much of the West.
Aberrant early endosome biogenesis mediates complement activation in the retinal pigment epithelium in models of macular degeneration
Authors: Kaur Gulpreet , Tan Li Xuan , Rathnasamy Gurugirijha , La Cunza Nilsa , Germer Colin J. , Toops Kimberly A. , Fernandes Marie , Blenkinsop Timothy A. , Lakkaraju Aparna
Published: August 2018

Significance

The first lines of communication between cells and the environment are early endosomes, which sort incoming cargo to regulate cell health. Endosomal abnormalities are seen in neurodegenerative diseases, yet the molecular mechanisms remain obscure. Here, using human donor cells and disease models, we demonstrate that excess ceramide promotes expansion of early endosomes in the retinal pigment epithelium (RPE), a primary site of injury in Stargardt and age-related maculopathies. Complement C3 uptake into enlarged endosomes and subsequent cleavage is associated with abnormal mechanistic target of rapamycin activity. Decreasing ceramide using Food and Drug Administration-approved drugs corrects endosomal defects and prevents C3 activation. Our studies establish how organelles modulate RPE complement activity, and identify ceramide as a drug target for macular degenerations.
Status-quo management of marine recreational fisheries undermines angler welfare
Authors: Abbott Joshua K. , Lloyd-Smith Patrick , Willard Daniel , Adamowicz Wiktor
Published: August 2018

Significance

Marine recreational fisheries are culturally and economically important around the world. However, they often suffer from management that promotes short seasons, congestion, wasteful allocations of fish, and overfishing. We use survey data from anglers taking trips on for-hire vessels in the US Gulf of Mexico to estimate the magnitude of economic benefits squandered by current management. We find a minimum of $139/y of benefits per angler could be realized under appropriate management reforms. These rights-based approaches would improve angler benefits by increasing flexibility to fish year round—improving access while establishing greater accountability for fish harvest. Extending similar reforms worldwide could generate billions of dollars of benefits to anglers and related sectors.
Recycling of Golgi glycosyltransferases requires direct binding to coatomer
Authors: Liu Lin , Doray Balraj , Kornfeld Stuart
Published: August 2018

Significance

The mammalian Golgi contains numerous glycosyltransferases that continuously recycle from late cisternae to earlier cisternae in COPI vesicles to maintain their steady-state localization in this organelle. How the glycosyltransferases are incorporated into these vesicular carriers is poorly understood. Here, we show that the N-cytoplasmic tails (N-tails) of a subset of these type II transmembrane proteins bind directly to two of the seven subunits of COPI coatomer. These glycosyltransferases share a common amino acid motif in their N-tails. The importance of these interactions is illustrated by mucolipidosis III patients with missense mutations within the N-tail motif of GlcNAc-1-phosphotransferase that impair binding to the COPI subunits, resulting in the mislocalization of this transferase to lysosomes.
Fabrication of icephobic aluminium surfaces by atmospheric plasma jet polymerisation
Authors: Jafari Reza , Momen Gelareh , Eslami Esmaeil
Published: August 2018

Atmospheric plasma treatment followed by a plasma polymerisation coating produced an aluminium surface having high water repellency and icephobicity. We varied the plasma parameters and the amount of hexamethyldisiloxane precursor to optimise surface hydrophobicity. The static contact and sliding angles of the surface reached 163° and <1°, respectively. Furthermore, the prepared surfaces remained superhydrophobic after seven days of immersion in acid–base media as well as after five icing/de-icing cycles.
Agency, power, modernity: A manifesto for social theory
Authors: Reed Isaac Ariail , Weinman Michael
Published: August 2018

In this article, we propose a new direction for social theory, based on a distinction between action and agency, a reconsideration of sociological theories of power, and a rereading of the transition to modernity. Drawing on Aristotle, Carole Pateman, Hannah Arendt, and Ernst Kantorowicz, we propose a conceptual model of power centred on the sending and binding of another to be one's agent in the world, and the varying representation of this relation and what it excludes. This approach allows a different understanding of modernity than is offered by accounts of power derived from the work of Pierre Bourdieu and Michel Foucault. With reference to the French Revolution and twentieth and twenty-first century presidential politics in the USA, we manifest the utility of the framework for the construction of a research programme in historical and political sociology.
hCALCRL mutation causes autosomal recessive nonimmune hydrops fetalis with lymphatic dysplasia
Authors: Mackie Duncan I. , Al Mutairi Fuad , Davis Reema B. , Kechele Daniel O. , Nielsen Natalie R. , Snyder Joshua C. , Caron Marc G. , Kliman Harvey J. , Berg Jonathan S. , Simms John , Poyner David R. , Caron Kathleen M.
Published: August 2018

We report the first case of nonimmune hydrops fetalis (NIHF) associated with a recessive, in-frame deletion of V205 in the G protein–coupled receptor, Calcitonin Receptor-Like Receptor (hCALCRL). Homozygosity results in fetal demise from hydrops fetalis, while heterozygosity in females is associated with spontaneous miscarriage and subfertility. Using molecular dynamic modeling and in vitro biochemical assays, we show that the hCLR(V205del) mutant results in misfolding of the first extracellular loop, reducing association with its requisite receptor chaperone, receptor activity modifying protein (RAMP), translocation to the plasma membrane and signaling. Using three independent genetic mouse models we establish that the adrenomedullin–CLR–RAMP2 axis is both necessary and sufficient for driving lymphatic vascular proliferation. Genetic ablation of either lymphatic endothelial Calcrl or nonendothelial Ramp2 leads to severe NIHF with embryonic demise and placental pathologies, similar to that observed in humans. Our results highlight a novel candidate gene for human congenital NIHF and provide structure–function insights of this signaling axis for human physiology.
Phenotypic plasticity in Periplaneta americana photoreceptors
Authors: Frolov Roman V. , Immonen Esa-Ville , Saari Paulus , Torkkeli Päivi H. , Liu Hongxia , French Andrew S.
Published: August 2018

Plasticity is a crucial aspect of neuronal physiology essential for proper development and continuous functional optimization of neurons and neural circuits. Despite extensive studies of different visual systems, little is known about plasticity in mature microvillar photoreceptors. Here we investigate changes in electrophysiological properties and gene expression in photoreceptors of the adult cockroach, Periplaneta americana, after exposure to constant light (CL) or constant dark (CD) for several months. After CL, we observed a decrease in mean whole-cell capacitance, a proxy for cell membrane area, from 362 ± 160 to 157 ± 58 pF, and a decrease in absolute sensitivity. However, after CD, we observed an increase in capacitance to 561 ± 155 pF and an increase in absolute sensitivity. Small changes in the expression of light-sensitive channels and signaling molecules were detected in CD retinas, together with a substantial increase in the expression of the primary green-sensitive opsin (GO1). Accordingly, light-induced currents became larger in CD photoreceptors. Even though normal levels of GO1 expression were retained in CL photoreceptors, light-induced currents became much smaller, suggesting that factors other than opsin are involved. Latency of phototransduction also decreased significantly in CL photoreceptors. Sustained voltage-activated K+ conductance was not significantly different between the experimental groups. The reduced capacitance of CL photoreceptors expanded their bandwidth, increasing the light-driven voltage signal at high frequencies. However, voltage noise was also amplified, probably because of unaltered expression of TRPL channels. Consequently, information transfer rates were lower in CL than in control or CD photoreceptors. These changes in whole-cell capacitance and electrophysiological parameters suggest that structural modifications can occur in the photoreceptors to adapt their function to altered environmental conditions. The opposing patterns of modifications in CL and CD photoreceptors differ profoundly from previous findings in Drosophila melanogaster photoreceptors.
Unconventional lattice dynamics in few-layer h-BN and indium iodide crystals*
Authors: Hu Gan , Huang Jian-Qi , Wang Ya-Ning , Yang Teng , Dong Bao-Juan , Wang Ji-Zhang , Zhao Bo , Ali Sajjad , Zhang Zhi-Dong
Published: August 2018

Unusual quadratic dispersion of flexural vibrational mode and red-shift of Raman shift of in-plane mode with increasing layer-number are quite common and interesting in low-dimensional materials, but their physical origins still remain open questions. Combining ab initio density functional theory calculations with the empirical force-constant model, we study the lattice dynamics of two typical two-dimensional (2D) systems, few-layer h-BN and indium iodide (InI). We found that the unusual quadratic dispersion of flexural mode frequency on wave vector may be comprehended based on the competition between atomic interactions of different neighbors. Long-range interaction plays an essential role in determining the dynamic stability of the 2D systems. The frequency red-shift of in-plane Raman-active mode from monolayer to bulk arises mainly from the reduced long-range interaction due to the increasing screening effect.
Numerical Simulation of the Airflow Characteristics of Drying by Ground Air Film
Authors: Yu-lan Zheng , Xiao-yong Peng
Published: August 2018

According to the interference and coupling characteristics among sub-systems of the chassis of the forklift truck, the the neutral network inverse system method of the non-linear system is applied for the decoupling control of the active rear steering (ARS) and the direct yaw moment control (DYC) of the forklift truck. Based on the analysis of the reversibility of the chassis system, a back propagation neutral network reverse system model is set to decouple the chassis system into two independent pseudo-linear system; A PD closed loop controller is designed to comprise a composite controller with the neutral network reverse system and the simulation is performed for verification. The simulation result shows that the decoupling control strategy with the neutral network reverse system can eliminate the interference and coupling among sub-systems of the chassis and thus enhances the status tracking and operating stability of forklift trucks.
Topology of real Schläfli six-line configurations on cubic surfaces and in ℝℙ³
Authors: Finashin Sergey , Zabun Remzi̇ye Arzu
Published: August 2018

A famous configuration of 27 lines on a non-singular cubic surface in

P

3

\mathbb {P}^3

contains remarkable subconfigurations, and in particular the ones formed by six pairwise disjoint lines. We study such six-line configurations in the case of real cubic surfaces from a topological viewpoint, as configurations of six disjoint lines in the real projective 3-space, and show that the condition that they lie on a cubic surface implies a very special property of homogeneity. This property distinguishes them in the list of 11 deformation types of configurations formed by six disjoint lines in

R
P

3

\mathbb {RP}^3

.
The existence and population connectivity of Icelandic spring-spawning herring over a 50-year collapse period
Authors: Óskarsson Guðmundur J
Published: August 2018

In the late 1960s, two local herring stocks and one seasonal migratory herring stock in Icelandic waters collapsed primarily due to overfishing. While the stocks of Icelandic summer-spawning herring (ISSH) and Norwegian spring-spawning herring (NSSH) have recovered, Icelandic spring-spawning herring (ISPH) has not. The main objective of this work is to explore the existence of ISPH and identify potential signs of recovery. Analyses were based on samples from the autumn fishery and survey data from 1962 to 2016. In the autumn, local ISSH and ISPH cohabitated and mixed in the main fishery, where sampled fish were categorized into stocks on basis of maturity stage. The results indicate that the proportion of ISPH was in the range of 13–33% in the 1960s while below 5% and on average 1.4% during 1970–2016. Several year classes of ISPH exhibit notable differences from the general low levels and caused a slight increase in ISPH spawning-stock biomass for corresponding years. An increase in proportion of generally old ISPH around 2004 and 2013 occurred simultaneously with the reappearances of NSSH in the feeding areas east and north of Iceland, respectively. Altogether, it supports earlier suggestions that ISPH might require immigration from NSSH to recover, as these were considered closely related stocks. This is consistent with the source-sink theoretical model of stock size regulation.
Hemorrhagic and Cystic Brain Metastases Are Associated With an Increased Risk of Leptomeningeal Dissemination After Surgical Resection and Adjuvant Stereotactic Radiosurgery
Authors: Press Robert H , Zhang Chao , Chowdhary Mudit , Prabhu Roshan S , Ferris Matthew J , Xu Karen M , Olson Jeffrey J , Eaton Bree R , Shu Hui-Kuo G , Curran Walter J , Crocker Ian R , Patel Kirtesh R
Published: August 2018

BACKGROUND

Brain metastases (BM) treated with surgical resection and focal postoperative radiotherapy have been associated with an increased risk of subsequent leptomeningeal dissemination (LMD). BMs with hemorrhagic and/or cystic features contain less solid components and may therefore be at higher risk for tumor spillage during resection.

OBJECTIVE

To investigate the association between hemorrhagic and cystic BMs treated with surgical resection and stereotactic radiosurgery and the risk of LMD.

METHODS

One hundred thirty-four consecutive patients with a single resected BM treated with adjuvant stereotactic radiosurgery from 2008 to 2016 were identified. Intracranial outcomes including LMD were calculated using the cumulative incidence model with death as a competing risk. Univariable analysis and multivariable analysis were assessed using the Fine & Gray model. Overall survival was analyzed using the Kaplan-Meier method.

RESULTS

Median imaging follow-up was 14.2 mo (range 2.5-132 mo). Hemorrhagic and cystic features were present in 46 (34%) and 32 (24%) patients, respectively. The overall 12- and 24-mo cumulative incidence of LMD with death as a competing risk was 11.0 and 22.4%, respectively. On multivariable analysis, hemorrhagic features (hazard ratio [HR] 2.34, P = .015), cystic features (HR 2.34, P = .013), breast histology (HR 3.23, P = .016), and number of brain metastases >1 (HR 2.09, P = .032) were independently associated with increased risk of LMD.

CONCLUSION

Hemorrhagic and cystic features were independently associated with increased risk for postoperative LMD. Patients with BMs containing these intralesion features may benefit from alternative treatment strategies to mitigate this risk.
Treading the Front-Line: Tartanization and Police–Academic Partnerships
Authors: Martin Denise , Wooff Andrew
Published: August 2018

Recognized as an International Leader in the development of Police Academic Collaborations, the Scottish Institute of Police Research has had a key role in contributing to evidence-based approaches in policing, supporting a strategic approach to innovation, as well as, contributing to education, professional development, and organizational learning. The aim of this article is to examine the particular relevance of this partnership in shaping both the recent professionalization and educational agenda of policing in Scotland. It will critically explore these collaborative efforts, particularly in relation to the development of Higher Educational Routes into the service and suggest that while there are benefits to this partnership approach, a co-operative rather than collaborative style emerged in this specific case study. The potential reasons for this co-operative approach as well as the implications for the development of Higher Education routes for police officers in Scotland will be discussed.
Calcium/calmodulin–dependent protein kinase IV (CaMKIV) activation contributes to the pathogenesis of experimental colitis via inhibition of intestinal epithelial cell proliferation
Authors: Cunningham Kellie E. , Novak Elizabeth A. , Vincent Garret , Siow Vei Shaun , Griffith Brian D. , Ranganathan Sarangarajan , Rosengart Matthew R. , Piganelli Jon D. , Mollen Kevin P.
Published: August 2018

The incidence and prevalence of inflammatory bowel disease (IBD) are increasing worldwide. IBD is known to be multifactorial, but inflammatory signaling within the intestinal epithelium and a subsequent failure of the intestinal epithelial barrier have been shown to play essential roles in disease pathogenesis. CaMKIV is a multifunctional protein kinase associated with inflammation and cell cycle regulation. CaMKIV has been extensively studied in autoimmune diseases, but a role in idiopathic intestinal inflammation has not been described. In this study, active CaMKIV was highly expressed within the intestinal epithelium of humans with ulcerative colitis and wild‐type (WT) mice with experimental induced colitis. Clinical disease severity directly correlates with CaMKIV activation, as does expression of proinflammatory cytokines and histologic features of colitis. In WT mice, CaMKIV activation is associated with increases in expression of 2 cell cycle proarrest signals: p53 and p21. Cell cycle arrest inhibits proliferation of the intestinal epithelium and ultimately results in compromised intestinal epithelial barrier integrity, further perpetuating intestinal inflammation during experimental colitis. Using a CaMKIV null mutant mouse, we demonstrate that a loss of CaMKIV protects against murine DSS colitis. Small molecules targeting CaMKIV activation may provide therapeutic benefit for patients with IBD.—Cunningham, K. E., Novak, E. A., Vincent, G., Siow, V. S., Griffith, B. D., Ranganathan, S., Rosengart, M. R., Piganelli, J. D., Mollen, K. P. Calcium/calmodulin‐dependent protein kinase IV (CaMKIV) activation contributes to the pathogenesis of experimental colitis via inhibition of intestinal epithelial cell proliferation. FASEB J. 33, 1330–1346 (2019). www.fasebj.org
The disrupted balance between hair follicles and sebaceous glands inHoxc13‐ablated rabbits
Authors: Deng Jichao , Chen Mao , Liu Zhiquan , Song Yuning , Sui Tingting , Lai Liangxue , Li Zhanjun
Published: August 2018

Pure hair and nail ectodermal dysplasia 9 (ECTD‐9) is an autosomal recessive genetic disease caused by mutation ofHOXC13and is characterized by hypotrichosis and nail dystrophy in humans. Unlike patients with ECTD‐9,Hoxc13‐mutated mice and pigs do not faithfully recapitulate the phenotype of hypotrichosis, so there is a limited understanding of the molecular mechanism ofHoxc13‐mediated hypotrichosis in animal models and clinically. Here, the homozygousHoxc13−/−rabbits showed complete loss of hair on the head and dorsum, whereas hypotrichosis in the limbs and tail were determined in theHoxc13−/−rabbits. In addition, reduced hair follicles (HFs) while the enlarged and increased number of sebaceous glands (SGs) were also found in theHoxc13−/−rabbits, showing that the disrupted balance between HFs and SGs may respond to hypotrichosis of ECTD‐9 in an animal model and clinically. Therefore, our findings demonstrate thatHoxc13−/−rabbits can be used as a model for human ECTD‐9, especially to understand the pathologic mechanism of hypotrichosis. Moreover, the disrupted balance between HFs and SGs, especially in theHoxc13−/−rabbits, can be used as an ideal animal model for dermatology ailments, such as acne and hypotrichosis, in preclinical studies.—Deng, J., Chen, M., Liu, Z., Song, Y., Sui, T., Lai, L., Li, Z. The disrupted balance between hair follicles and sebaceous glands inHoxc13‐ablated rabbits. FASEB J. 33, 1226–1234 (2019).www.fasebj.org
CE: Managing Stable COPD: An Evidence-Based Approach
Authors: O'Dell Amy , Diegel-Vacek Lauren , Burt Leah , Corbridge Susan
Published: August 2018

Chronic obstructive pulmonary disease (COPD) affects as many as 16 million Americans and is expected to be the third leading cause of death worldwide by 2020. To increase awareness of COPD, encourage related research, and improve care of patients with this chronic disease, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) was launched in 1998 and published an evidence-based report on COPD prevention and management strategies in 2001 that has been revised regularly. The fourth major revision, which was published in 2017 and revised in 2018, includes significant changes related to COPD classification, as well as to pharmacologic, nonpharmacologic, and comorbidity management. The authors discuss the changes to the GOLD recommendations and, using a patient scenario, explain their application to clinical practice.
Core Clerkship Grading: The Illusion of Objectivity
Authors: Hauer Karen E. , Lucey Catherine R.
Published: August 2018

Core clerkship grading creates multiple challenges that produce high stress for medical students, interfere with learning, and create inequitable learning environments. Students and faculty alike succumb to the illusion of objectivity—that quantitative ratings converted to grades convey accurate measures of the complexity of clinical performance.

Clerkship grading is the first high-stakes assessment within medical school and occurs just as students are newly immersed full-time in an environment in which patient care supersedes their needs as learners. Students earning high marks situate themselves to earn entry into competitive residency programs and selective specialties. However, there is no commonly accepted standard for how to assign clerkship grades, and the process is vulnerable to imprecision and bias. Rewarding learners for the speed with which they adapt inherently favors students who bring advantages acquired before medical school and discounts the goal of all learners achieving competence.

The authors propose that, rather than focusing on assigning core clerkship grades, assessment of student performance should incorporate expert judgment of learning progress. Competency-based medical education is predicated on the articulation of stepwise expectations for learners, with the support and time allocated for each learner to meet those expectations. Concurrently, students should ideally review their own performance data with coaches to self-assess areas of relative strength and areas for further growth. Eliminating grades in favor of competency-based assessment for learning holds promise to engage learners in developing essential patient care and teamwork skills and to foster their development of lifelong learning habits.
Translational Sepsis Research: Spanning the Divide
Authors: Lewis Anthony J. , Lee Janet S. , Rosengart Matthew R.
Published: August 2018

Objective:

Our knowledge of the molecular mechanisms of sepsis has attained exponential growth. Yet, the pillars of its care remain antibiotics, fluid resuscitation, and physiologic support of failing organ systems. The inability to bring biologic breakthroughs to the bedside is not for lack of effort. Over 60 clinical trials of novel therapies, each heavily supported by the momentum of biologic data suggesting clinical utility, have been conducted and have failed to identify benefit. This mass of “negative” clinical data abut an equally towering mound of knowledge of sepsis biology, which collectively have led investigators to ask, “what happened?”

Data Sources:

Review of published scientific literature via MEDLINE searches using key terms related to the article topics.

Study Selection:

Original articles, review articles, and systematic reviews were considered.

Data Extraction:

Articles were selected for inclusion based upon author consensus.

Data Synthesis:

Here, we present a synthetic review of some of the challenges in translating experimental animal models of sepsis to the bedside. We commence with the concept that the heterogeneity in the kinetics of the sepsis response serves as an important, often underappreciated but surmountable, source of translational impedance. Upon this groundwork, we discuss distinctions between animal experimentation and clinical trial design in the elements for hypothesis testing: cohort selection, power and sample size, randomization and blinding, and timing of intervention. From this concept, we develop a contextual framework for advancing the paradigm of animal-based investigations to facilitate science that transitions from molecule to medicine.

Conclusions:

A persistent divide exists between the laboratory and clinical research arenas, which may be addressable via systematic targeting of identified translational gaps.
T lymphocytes as therapeutic arsenal for patients with hematological malignancies
Authors: Montoro Juan , Piñana José L. , Sanz Jaime , Guerreiro Manuel
Published: August 2018

Purpose of review

We present an overview of the clinically available immunotherapeutic platforms centered on T cell lymphocytes for the treatment of hematological malignancies with a special focus on the advances achieved since 2017.

Recent findings

The most promising strategies of T cell therapies are based on the infusion of unmanipulated donor lymphocytes, antigen-specific T cells, ex-vivo genetically modified T cells or in-vivo manipulation of T cells using antibodies (bispecific and checkpoint inhibitors). To select the most appropriate option for a specific patient, is important to understand not only each platform-specific biological mechanisms, clinical activity and toxicities but also their intrinsic differences. In this extremely fast-growing field, to keep track of recent advances is a hard and challenging task for a hematologist. Therefore, we aimed to provide a global integrative review of T-cell-based immunotherapies, essential to ascertain their optimal place and timing in our daily clinical practice.

We highlight recent advances and discuss future directions of T-cell-based immunotherapies entering the common clinical practice in hematology.
Diffuse low-grade glioma, oncological outcome and quality of life: a surgical perspective
Authors: Duffau Hugues
Published: August 2018

Purpose of review

Because diffuse low-grade glioma (DLGG) is constantly migrating in the brain until malignant transformation, the historic wait-and-watch attitude was replaced by an early therapeutic management. Moreover, advances in cognitive neurosciences allowed an improved understanding of neuroplasticity reactional to DLGG growth. Here, the aim is to reevaluate the role of surgery regarding both oncological and functional outcomes.

Recent findings

Recent data evidenced the significant benefit of maximal well tolerated resection on survival and quality of life (QoL). By removing a diffuse neoplastic disease up to eloquent neural networks identified by intraoperative awake mapping and cognitive monitoring, overall survival is about the double compared with biopsy, whereas the rate of severe persistent deficits was significantly reduced. Postoperative QoL may even be improved owing to functional rehabilitation and epilepsy control.

Early and functional mapping-guided surgery is currently the first treatment in DLGG. Surgical resection(s) should be integrated in a global personalized management that must be tailored to the brain connectome of each patient. To optimize the oncofunctional balance, the next step is a screening, to detect and to treat DLGG patients earlier, and to increase the rate of ‘supramarginal excision’ in the setting of a ‘prophylactic connectomal neurooncological surgery’.
Inhibition of epidermal growth factor receptor improves antitumor efficacy of vemurafenib in BRAF-mutant human melanoma in preclinical model
Authors: Kenessey István , Kramer Zsófia , István Lilla , Cserepes Mihály T. , Garay Tamás , Hegedűs Balázs , Dobos Judit , Tímár József , Tóvári József
Published: August 2018

Oncogenic activation of the epidermal growth factor receptor (EGFR) signaling pathway occurs in a variety of tumor types, albeit in human melanoma, the contribution of EGFR is still unclear. The potential role of EGFR was analyzed in four BRAF-mutant, one NRAS-mutant and one wild-type NRAS-BRAF-carrying human melanoma cell lines. We have tested clinically available reversible tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib, irreversible EGFR-TKI pelitinib and a reversible experimental compound PD153035 on in-vitro proliferation, apoptosis, migration as well as in-vivo metastatic colonization in a spleen-liver model. The presence of the intracellular domain of EGFR protein and its constitutive activity were demonstrated in all cell lines. Efficacies of EGFR-TKIs showed significant differences, and irreversible inhibition had the strongest antitumor potential. Compared with BRAF-mutant cells, wild-type BRAF was associated with relative resistance against gefitinib. In combination with gefitinib, selective mutant BRAF-inhibitor vemurafenib showed additive effect in all BRAF-mutant cell lines. Treatment of BRAF-mutant cells with gefitinib or pelitinib attenuated in-vitro cell migration and in-vivo colonization. Our preclinical data suggest that EGFR is a potential target in the therapy of BRAF-mutant malignant melanoma; however, more benefits could be expected from irreversible EGFR-TKIs and combined treatment settings.
Osteopenia and fractures associated with long-term therapy with MEK inhibitors
Authors: Dumas Marc , Laly Pauline , Gottlieb Jérémy , Vercellino Laetitia , Paycha Frédéric , Bagot Martine , Baroudjian Barouyr , Madelaine Isabelle , Basset-Seguin Nicole , Eftekhari Pirayeh , Pagès Cécile , Lebbé Céleste , Lioté Frédéric
Published: August 2018

Targeted therapies have markedly improved the survival of patients with melanoma. We report the case of two patients with advanced melanoma controlled by long-term MEK inhibitor or combination of BRAF and MEK inhibitors, who developed fractures related to severe osteopenia. A 48-year-old woman was treated by pimasertib after the failure of two lines of chemotherapy, and a 42-year-old man was treated by an association of BRAFi (dabrafenib) and MEKi (trametinib) after the failure of one line of chemotherapy. During follow-up, both complained of buttock pain, revealing primary fractures of the pelvis and lumbar vertebra. In both patients, none had osteoporosis risk factors; DEXA scan revealed osteopenia, and analysis ruled out metastatic bone lesion or secondary osteoporosis. Zoledronic acid, cholecalciferol (vitamin D3), oral calcium, and pain killers were introduced, leading to no further bone event. Numerous pathways are involved in the homeostasis of bone turnover, and the effect of tyrosine kinase inhibitors on those pathways is not well known yet. The absence of usual causes of osteoporosis or metastatic bone lesion and kinetics of symptoms lead us to suggest that MEK inhibitors were responsible for the development of osteoporosis. To the best of our knowledge, this is the first report of fractures associated with osteopenia in patients treated with MEKi. Long-term survival owing to new targeted treatment could be associated with yet underestimated adverse effects such as osteopenia/osteoporosis that could impair patient’s quality of life and should be investigated.
Short-term exposure to air pollution might exacerbate autoimmune diseases
Authors: Faustini Annunziata , Renzi Matteo , Kirchmayer Ursula , Balducci Maria , Davoli Marina , Forastiere Francesco
Published: August 2018

Background:

Mortality and cardiorespiratory diseases are well-documented effects of atmospheric pollutants. Because epigenetic mechanisms are identified as interaction factors between environmental exposures and gene expression, as well as pathogenic factors of impaired immune tolerance, it seems relevant to study autoimmune diseases in relation to air pollution.

Methods:

To study whether daily increases of particulate matter (PM10, PM2.5) and nitrogen dioxide (NO2) are associated with exacerbations of autoimmune diseases, a total of 23,898 residents of Rome (Italy) who were diagnosed in 2003–2014 with Hashimoto thyroiditis, systemic lupus erythematosus, rheumatoid arthritis, psoriasis, and multiple sclerosis were enrolled. Exacerbations were defined as subsequent hospitalizations for the initial disease or its complications, or a different autoimmune disease, and as dose increases or time reductions between drug prescriptions for autoimmune diseases. Data were analyzed for 2006–2014. Daily concentrations of PM10, PM2.5, and NO2 in Rome were available from a fixed monitoring network, during 2006–2014. A time-stratified case-crossover study was carried out.

Results:

All air pollutants were associated with more frequent changes than usual in treatment for all autoimmune diseases; the greatest increases in risk were observed for PM2.5 (10 μg/m3 increase) in thyroiditis (3.31% [2.21%, 4.2%]), lupus (3.55% [0.70%, 6.49%]), arthritis (4.93% [2.11%, 7.83%]), and psoriasis (4.04% [0.21%, 8.01%]). No associations were observed for hospitalizations for all studied diseases, whereas changes toward lower corticosteroids’ dose in multiple sclerosis and less effective corticosteroids’ forms in psoriasis were observed.

Conclusions:

PM2.5 and NO2 might exacerbate autoimmune diseases. As detected with treatment changes especially in younger patients.
The “Paper Roll”: A Simple but Useful Tool for Minimal Invasive Mitral Valve Repair Surgery
Authors: Wisser Wilfried , Stelzmüller Marie-Elisabeth
Published: August 2018

During minimal invasive mitral valve repair, excessive valve tissue, as in myxomatous or Barlow disease, might be cumbersome to analyze and treat the subvalvular mitral valve apparatus. We developed a new, adaptive, flexible, and easy-to-use technique for better visualization of the subvalvular apparatus. After visualization of the mitral valve, a simple sterile paper ruler was curled up to a roll 1 cm in diameter and inserted through the mitral valve. By means of two endo forceps, the paper roll was uncurled to the desired diameter, thus pushing the valve leaflets away, allowing for a direct view onto the subvalvular apparatus. This technique was successfully used in 34 consecutive patients (mean ± SD age = 57.2 ± 11.5 years; 22 male). The calculated risk score for additive EuroScore, logistic EuroScore, and EuroScore II was 4 ± 2, 3.2 ± 2.1, and 2.5 ± 5.4, respectively. No patient died within the first 30 days. All patients presented mitral valve insufficiency grade 0 to 1 postoperatively. Artificial chords were implanted in all patients (3.6 ± 1.8 chords per patient). This simple, adaptive, and cheap technique facilitates the approach to the subvalvular apparatus, especially in patients with myxomatous or Barlow disease. The ease of use allows for prompt approach to the papillary muscles and quick removal.
Magna Ease versus Trifecta Early Hemodynamics
Authors: Yanagawa Bobby , Tam Derrick Y. , Hong Kathryn , Mazine Amine , Bagai Akshay , Shahbaz Nazgol Kafaei , Ouzounian Maral , Verma Subodh
Published: August 2018

Objective

This meta-analysis compares the early echocardiographic outcomes of aortic valve replacement using the two most commonly implanted stented bioprostheses.

Methods

We searched MEDLINE and EMBASE databases until 2017 for studies comparing Magna or Magna Ease (Edwards Lifesciences, Irvine, CA USA) versus Trifecta (St Jude Medical, St. Paul, MN USA) aortic bioprosthetic valves. A random-effects meta-analysis was performed for the primary outcome of mean gradient on echocardiography and secondary outcomes of effective orifice area, indexed effective orifice area, and in-hospital mortality.

Results

There were two randomized controlled trial, three matched, and six unmatched retrospective observational studies with 2119 patients [median reported follow-up = 6 months (interquartile range = 6 to 12)]. The Magna/Magna Ease valve was associated with higher early mean gradient (mean difference = 4.09, 95% confidence interval = 3.48 to 4.69, P < 0.0001) and smaller effective orifice area (mean difference = 0.30, 95% confidence interval = −0.38 to −0.22, P < 0.0001). There were no differences in 30-day mortality between Magna/Magna Ease and Trifecta (relative risk = 1.01, 95% confidence interval = 0.41 to 2.50, P = 1.0).

Conclusions

Trifecta may offer a small hemodynamic advantage compared with the Magna/Magna Ease valve with no differences in early mortality. Long-term follow-up is required to determine whether these differences persist and translate into differences in clinical outcomes.
Can We Improve Physical Health Monitoring for Patients Taking Antipsychotics on a Mental Health Inpatient Unit?
Authors: Ross Elyse , Barnett Rebecca , Tudhope Rebecca , Vasudev Kamini
Published: August 2018

Background

Patients with severe mental illness are at risk of medical complications, including cardiovascular disease, metabolic syndrome, and diabetes. Given this vulnerability, combined with metabolic risks of antipsychotics, physical health monitoring is critical. Inpatient admission is an opportunity to screen for medical comorbidities. Our objective was to improve the rates of physical health monitoring on an inpatient psychiatry unit through implementation of an electronic standardized order set.

Methods

Using a clinical audit tool, we completed a baseline retrospective audit (96 eligible charts) of patients aged 18 to 100 years, discharged between January and March 2012, prescribed an antipsychotic for 3 or more days. We then developed and implemented a standard electronic admission order set and provided training to inpatient clinical staff. We completed a second chart audit of patients discharged between January and March 2016 (190 eligible charts) to measure improvement in physical health monitoring and intervention rates for abnormal results.

Results

In the 2012 audit, thyroid-stimulating hormone (TSH), blood pressure, blood glucose, fasting lipids, electrocardiogram (ECG), and height/weight were measured in 71%, 92%, 31%, 36%, 51%, and 75% of patients, respectively. In the 2016 audit, TSH, blood pressure, blood glucose, fasting lipids, ECG, and height/weight were measured in 86%, 96%, 96%, 64%, 87%, and 71% of patients, respectively. There were statistically significant improvements (P < 0.05) in monitoring rates for blood glucose, lipids, ECG, and TSH. Intervention rates for abnormal blood glucose and/or lipids (feedback to family doctor and/or patient, consultation to hospitalist, endocrinology, and/or dietician) did not change between 2012 and 2016.

Conclusions

Electronic standardized order set can be used as a tool to improve screening for physical health comorbidity in patients with severe mental illness receiving antipsychotic medications.
Diagnosis, Surgical Management, and Postoperative Care for the Neonate With Sacrococcygeal Teratoma
Authors: Miller Lori , Dunn Stefanie
Published: August 2018

Background

Neonatal sacrococcygeal teratoma is rare occurring in approximately one in 35,000 live births with a female predominance (3:1–4:1 ratio). It is an unusual tumor that develops before birth and arises from embryologically multipotent cells from the Hensen node, which is located in the coccyx. Sacrococcygeal teratomas generally present in two distinct fashions: newborns with large predominately external masses, which are noted in utero or at the time of delivery and are rarely malignant, and older infants and young children presenting with tumors predominately confined to the pelvis with a much higher rate of malignancy. Most sacrococcygeal teratomas are now diagnosed prenatally because of the routine obstetric ultrasonagraphy. An abnormally sized uterus is typically the first sign that a sacrococcygeal teratoma may be present. The increased-sized uterus can be due to a massive tumor or polyhydramnios. Less common presentations include maternal preeclampsia. Newborns generally present with the mass protruding from the sacral region. If detected prenatally, the neonate should be considered for abdominal delivery if the mass is greater than 5 cm in size. In addition, some develop in utero high-output cardiac failure resulting in fetal hydrops and may be candidates for in utero resection. When a prenatally diagnosed sacrococcygeal teratoma is associated with fetal hydrops, the tumor can become life-threatening to both mother and baby. A classification system has been devised by Altman et al. in 1974 and is still used today. Sacrococcygeal teratomas are categorized according to their location and severity. Type I tumors are predominately external. Type II tumors present with both internal and external components. Type III tumors are predominately hidden in the pelvis with a very small external portion. Type IV tumors are entirely hidden within the pelvis. The recommended treatment of a sacrococcygeal teratoma is complete removal of the tumor by surgery performed soon after the birth. Unfortunately, there is a significant recurrence rate of 10%–20% even with complete resection. Long-term follow-up is needed, as there is a risk of malignancy and reoccurrence. Postoperative follow-up is needed during the first several years of life as bowel and bladder functions can be affected. Children should be followed through potty training to ensure that bowel and bladder functions are normal.