bluuebunny/crossref_metadata_2025 huggingface dataset:
The Primary Care Practice Improvement Tool (PC-PIT) process for organisational improvement in primary care: application by Australian Primary Health Networks
Authors: Borg Samantha J. , Crossland Lisa , Risk Jo , Porritt Julie , Jackson Claire L.
Published: March 2019

The Primary Care Practice Improvement Tool (PC-PIT) is an organisational performance improvement tool recently implemented by two Primary Health Networks (PHNs). This study explored barriers and facilitators to implementing the PC-PIT process at scale, from the initial introduction of the tool to completion of Plan-Do-Study-Act cycles with general practices. Using a qualitative design, in-depth, semi-structured interviews were conducted with 10 PHN staff to seek feedback on the delivery of the PC-PIT to general practices. Interview results were analysed using a grounded theory approach. The identification of barriers such as difficulty engaging practices and lack of report sharing with the PHNs will help streamline future implementation. The PC-PIT was highly compatible with existing quality improvement programs and offers enhanced opportunity to support capacity building and implementation of the Health Care Home model.
Baicalin improves IVM of pig oocytes and subsequent preimplantation embryo development by inhibiting apoptosis
Authors: Guo Qing , Xuan Mei-Fu , Luo Zhao-Bo , Wang Jun-Xia , Jin Song-Shan , Yin Xi-Jun , Kang Jin-Dan
Published: March 2019

Baicalin, a monomer of flavonoids extracted from dried roots of Scutellaria baicalensis, is used to treat female infertility. However, the effect of baicalin on oocyte maturation is unknown. In this study we investigated the effects of baicalin on the IVM of pig oocytes and subsequent embryo development following parthenogenetic activation (PA). We found that 0.1µgmL−1 baicalin significantly (P<0.05) increased the IVM rate of oocytes compared with the non-treatment (control) group by reducing levels of reactive oxygen species (ROS). In addition, the mRNA expression of genes related to nuclear maturation and cumulus cell expansion, mitochondrial membrane potential and ATP content was significantly (P<0.05) higher in baicalin-treated than control oocytes. To determine whether baicalin treatment during IVM of pig oocytes improves subsequent development of PA embryos, we measured the cleavage and blastocyst formation rates, as well as the number of cells per blastocyst. All these parameters were significantly (P<0.05) higher in the baicalin-treated than control group. In conclusion, this study demonstrates that baicalin improves pig oocyte maturation and subsequent embryo development invitro by inhibiting production of ROS and reducing apoptosis in oocytes.
Double-negative T cells remarkably promote neuroinflammation after ischemic stroke
Authors: Meng Hailan , Zhao Haoran , Cao Xiang , Hao Junwei , Zhang He , Liu Yi , Zhu Min-sheng , Fan Lizhen , Weng Leihua , Qian Lai , Wang Xiaoying , Xu Yun
Published: March 2019

Significance

In the present study, we found a significantly up-regulated CD3+CD4−CD8−T cell (double-negative T cell; DNT) population in the peripheral blood of patients with acute stroke compared with age-matched healthy subjects. Interestingly, infiltrating DNTs were mainly located close to microglia in the ischemic brain tissues of both stroke patients and middle cerebral artery occlusion mice. DNTs amplified the proinflammatory microglia and subsequently enhanced the neuroinflammation and exacerbated the brain injury after ischemic stroke. Mechanistically, DNT-intrinsic FasL and PTPN2 collaboratively regulate the level of CD86+microglia via production of TNF-α. Taken together, these data reveal that infiltrating DNTs are the critical driving force in promoting microglia-mediated neuroinflammation and ischemic brain injury.
Statistics of noisy growth with mechanical feedback in elastic tissues
Authors: Damavandi Ojan Khatib , Lubensky David K.
Published: March 2019

Significance

Tissue growth is often a noisy process, and control of this noise is vital to the integrity of growth and development. However, a basic theoretical understanding of how noise affects growth, especially in tissues with mechanical feedback, is lacking. Here, we consider the simplest model of stochastic tissue growth and show that it predicts nontrivial behavior for observable quantities like density correlations and the sizes of marked clones. The former, in particular, exhibits power laws analogous to those seen in models of the early universe, hinting at a hitherto unexplored richness in the physics of “inflationary embryology.”
Interleukin-37 monomer is the active form for reducing innate immunity
Authors: Eisenmesser Elan Z. , Gottschlich Adrian , Redzic Jasmina S. , Paukovich Natasia , Nix Jay C. , Azam Tania , Zhang Lingdi , Zhao Rui , Kieft Jeffrey S. , The Erlinda , Meng Xianzhong , Dinarello Charles A.
Published: March 2019

Interleukin-37 (IL-37), a member of the IL-1 family of cytokines, is a fundamental suppressor of innate and acquired immunities. Here, we used an integrative approach that combines biophysical, biochemical, and biological studies to elucidate the unique characteristics of IL-37. Our studies reveal that single amino acid mutations at the IL-37 dimer interface that result in the stable formation of IL-37 monomers also remain monomeric at high micromolar concentrations and that these monomeric IL-37 forms comprise higher antiinflammatory activities than native IL-37 on multiple cell types. We find that, because native IL-37 forms dimers with nanomolar affinity, higher IL-37 only weakly suppresses downstream markers of inflammation whereas lower concentrations are more effective. We further show that IL-37 is a heparin binding protein that modulates this self-association and that the IL-37 dimers must block the activity of the IL-37 monomer. Specifically, native IL-37 at 2.5 nM reduces lipopolysaccharide (LPS)-induced vascular cell adhesion molecule (VCAM) protein levels by ∼50%, whereas the monomeric D73K mutant reduced VCAM by 90% at the same concentration. Compared with other members of the IL-1 family, both the N and the C termini of IL-37 are extended, and we show they are disordered in the context of the free protein. Furthermore, the presence of, at least, one of these extended termini is required for IL-37 suppressive activity. Based on these structural and biological studies, we present a model of IL-37 interactions that accounts for its mechanism in suppressing innate inflammation.
Femtosecond covariance spectroscopy
Authors: Tollerud Jonathan Owen , Sparapassi Giorgia , Montanaro Angela , Asban Shahaf , Glerean Filippo , Giusti Francesca , Marciniak Alexandre , Kourousias George , Billè Fulvio , Cilento Federico , Mukamel Shaul , Fausti Daniele
Published: March 2019

Significance

Here we establish femtosecond covariance spectroscopy as a technique that uses ultrashort stochastic light pulses to measure nonlinear material responses. By using pulses with spectrally uncorrelated fluctuations we can leverage on the noise and consider each repetition of the experiment as a measurement under different conditions. In this limit we demonstrate that nonlinear processes in the sample can be retrieved by measuring the spectral correlations in different pulses. We validate the approach by studying stimulated Raman scattering in α-quartz. This concept can be applied to reveal low-energy modes of electronic, spin, and vibrational origin and adapted to different techniques and wavelength ranges, from optical to X-ray free-electron lasers, where strong stochastic fluctuations are unavoidable.
Weevilpgrp-lbprevents endosymbiont TCT dissemination and chronic host systemic immune activation
Authors: Maire Justin , Vincent-Monégat Carole , Balmand Séverine , Vallier Agnès , Hervé Mireille , Masson Florent , Parisot Nicolas , Vigneron Aurélien , Anselme Caroline , Perrin Jackie , Orlans Julien , Rahioui Isabelle , Da Silva Pedro , Fauvarque Marie-Odile , Mengin-Lecreulx Dominique , Zaidman-Rémy Anna , Heddi Abdelaziz
Published: March 2019

Long-term intracellular symbiosis (or endosymbiosis) is widely distributed across invertebrates and is recognized as a major driving force in evolution. However, the maintenance of immune homeostasis in organisms chronically infected with mutualistic bacteria is a challenging task, and little is known about the molecular processes that limit endosymbiont immunogenicity and host inflammation. Here, we investigated peptidoglycan recognition protein (PGRP)-encoding genes in the cereal weevilSitophilus zeamais’s association withSodalis pierantoniusendosymbiont. We discovered that weevilpgrp-lbgenerates three transcripts via alternative splicing and differential regulation. A secreted isoform is expressed in insect tissues under pathogenic conditions through activation of the PGRP-LC receptor of the immune deficiency pathway. In addition, cytosolic and transmembrane isoforms are permanently produced within endosymbiont-bearing organ, the bacteriome, in a PGRP-LC–independent manner. Bacteriome isoforms specifically cleave the tracheal cytotoxin (TCT), a peptidoglycan monomer released by endosymbionts.pgrp-lbsilencing by RNAi results in TCT escape from the bacteriome to other insect tissues, where it chronically activates the host systemic immunity through PGRP-LC. While such immune deregulations did not impact endosymbiont load, they did negatively affect host physiology, as attested by a diminished sexual maturation of adult weevils. Whereaspgrp-lbwas first described in pathogenic interactions, this work shows that, in an endosymbiosis context, specific bacteriome isoforms have evolved, allowing endosymbiont TCT scavenging and preventing chronic endosymbiont-induced immune responses, thus promoting host homeostasis.
Primate research and conservation in Malaysia.
Authors: Lappan S. , Ruppert N.
Published: March 2019

Malaysia is inhabited by ≥25 nonhuman primate species from five families, one of the most diverse primate faunas on earth. Unfortunately, most Malaysian primates are threatened with extinction due to habitat loss, degradation, and fragmentation, hunting and the synergies among these processes. Here, we review research on primates and issues related to their conservation in Malaysia. Despite the charisma and cultural importance of primates, the importance of primates in ecological processes such as seed dispersal, and the robust development of biodiversity-related sciences in Malaysia, relatively little research specifically focused on wild primates has been conducted in Malaysia since the 1980s. Forest clearing for plantation agriculture has been a primary driver of forest loss and fragmentation in Malaysia. Selective logging also has primarily negative impacts on primates, but these impacts vary across primate taxa, and previously-logged forests are important habitats for many Malaysian primates. Malaysia is crossed by a dense road network, which fragments primate habitats, facilitates further human encroachment into forested areas and causes substantial mortality due to road kills. Primates in Malaysia are hunted for food or as pests, trapped for translocation due to wildlife-human conflict and hunted and trapped for illegal trade as pets. Further research on the distribution, abundance, ecology and behavioural biology of Malaysian primates is needed to inform effective management plans. Outreach and education are also essential to reduce primate-human conflict and demand for primates as pets. Ultimately, researchers, civil organizations, governmental authorities and local and indigenous communities in Malaysia must work together to develop, promote and implement effective strategies for protecting Malaysian primates and their habitats.
Functions of banker plants for biological control of arthropod pests in protected culture.
Authors: Yano E.
Published: March 2019

Banker plant systems have been developed for the biological control of various pest species in protected culture. In such systems, non-crop plants, i.e. banker plants, are placed in the greenhouse and harbour alternative food and beneficials. The banker plant system is an effective strategy for biological control in greenhouses, with many benefits over the conventional release of beneficials. Moreover, they facilitate the reproduction of beneficials. However, the way banker plants function in this setting has not been clarified. The mechanisms of selection by beneficials between the banker plant, with its hosts or prey, and the crop plants, with its pests, is also not understood. The extent of selection of the banker plants by natural enemies may result in a lack of dispersal from the plants to crops and reduce pest control efficiency, because after selection of the banker plant, the natural enemy should disperse from it to the crop plant. There are many publications demonstrating the usefulness of banker plants as an alternative food source for the reproduction of beneficials. However, few publications have considered selection. Herein, we propose a theoretical basis for the banker plant system based on a consideration of its functions.
‘Goats eat where they are tied up’: illicit and habitual corruption in Mozambique
Authors: Tvedten Inge , Picardo Rachi
Published: March 2019

The article shows that corruption is structural and omnipresent in Mozambican society, effectively legitimising corrupt practices at all levels. Using an anthropological approach, it argues that small-scale corruption has the most immediate effects for the urban and rural poor and is so common that it has become an integrated part of daily life, or ‘habitual’. While most of the poor relate to corruption through tacit acceptance and acts of compliance, its practical implications are most severe for the very poorest, who cannot afford to take part in corrupt exchanges and are excluded from vital social relationships and social services.
Identification of a novel advanced glycation end product derived from lactaldehyde
Authors: Fujimoto Shiori , Murakami Yoto , Miyake Haruna , Hayase Fumitaka , Watanabe Hirohito
Published: March 2019

Advanced glycation end products (AGEs) are implicated in the development of diabetic complications via the receptor for AGEs (RAGE). We have reported that the 3-hydroxypyridinium (3HP)-containing AGEs derived from α-hydroxyaldehydes physically interact with RAGE and show cytotoxicity. Lactaldehyde (LA) is formed from a reaction between threonine and myeloperoxidase, but no LA-derived AGEs have been characterized. Here, we identify the structure and physiological effects of an AGE derived from LA. We isolated a novel 3HP derivative, 2-acetamido-6-(3-hydroxy-5-methyl-pyridin-1-ium-1-yl)hexanoate, named as N-acetyl-LAPL (lactaldehyde-derived pyridinium-type lysine adduct), from a mixture of LA with Nα-acetyl-L-lysine. LAPL was also detected in the LA-modified protein. LAPL elicited toxicity in PC12 neuronal cells, but the effect was suppressed by the soluble form of RAGE as a decoy receptor. Moreover, surface plasmon resonance-based analysis revealed that LAPL specifically binds to recombinant RAGE. These results indicate that LA generates an AGE containing the 3HP moiety and contributes to RAGE-dependent cytotoxicity.

Abbreviations: AGEs: advanced glycation end products; RAGE: receptor for advanced glycation end products; 3HP: 3-hydroxypyridinium; LA: lactaldehyde; LAPL: lactaldehyde-derived pyridinium-type lysine adduct; BSA: bovine serum albumin; GLAP: glyceraldehyde-derived pyridinium; MPO: myeloperoxidase; HFBA: heptafluorobutyric acid; TFA: trifluoroacetic acid; HPLC: high performance liquid chromatography; LC-ESI-QTOF-MS: liquid chromatography-electrospray ionization-quadrupole time-of-flight-mass spectrometry; NMR: nuclear magnetic resonance; LA-BSA: lactaldehyde-modified bovine serum albumin; PBS: phosphate buffered saline, GST, glutathione S-transferase; SPR: surface plasmon resonance; OP-lysine: 2-ammonio-6-(3-oxidopyridinium-1-yl)hexanoate; GLO1: glyoxalase 1; MG, methylglyoxal
Foiling Kamesian Belletristic Theory in Mid-Eighteenth-Century Scotland
Authors: Innocenti Beth
Published: March 2019

Two disciplinary stories told in mid-eighteenth-century Scotland omit an important plotline. One story is that university teaching of rhetoric transformed into belletristic criticism; another is that ideology and culture transformed to reorient rhetorical theorizing toward everyday practices by non-elites. Untold is a story of how familiar protagonists, such as Hugh Blair, clashed with antagonists, such as John Witherspoon, in the Church of Scotland. Telling that story from the antagonists’ perspectives shows that they reflected on how rhetoric ought to be practiced to manage disagreement in a democratic institution and used what amounted to Kamesian belletrism as a foil.
Dialoging with Bigger Thomas: A Reception History of Richard Wright’sNative Son
Authors: McCann Bryan J.
Published: March 2019

This essay develops a reception history of the Communist Party of the USA’s (CPUSA) responses to Richard Wright’s Native Son. Drawing on what Fiona Paton calls “cultural stylistics,” I argue that the voices residing in Native Son itself participated in the broader interpretive politics surrounding the novel. Specifically, Wright’s primary character, Bigger Thomas, functioned as a disruptive performance of blackness that revealed the limitations of communist orthodoxy for bringing expression to black subjectivity. I conclude by reflecting on the ways cultural stylistics poses salient ethical challenges to all of us who engage in the labor of critique.
Green economic efficiency in the Yangtze River Delta: spatiotemporal evolution and influencing factors
Authors: Wang Zhenbo , Wang Xinming , Liang Longwu
Published: March 2019

Based on economic-social-resource-environment perspective, which people’s welfare was considered compared with the traditional perspective, using SSU and PP model, spatial analysis method, spatial econometric model to study green economy efficiency (GRE) of 26 Cities in the Yangtze River Delta from 2005 to 2015. The results show the following: Corrected GRE is markedly lower than conventional efficiency; Stage characteristics are obvious of GRE. An overall spatial pattern has emerged of lower efficiency in the east and higher efficiency in the west, and exist clear signs of spatial agglomeration. The spatial Dubin model has abetter fitting effect. The biggest direct effect on local green economic efficiency and spatial spillover effects on nearby areas is proportion of tertiary industry.
Extraction of bioactive compounds fruit from Rhizophora mucronata using sonication method
Authors: Ernawati  , Suprayitno E , Hardoko  , Yanuhar U
Published: March 2019

Mangrove species Rhizopora mucronata fruit is currently widely used as a processed food ingredient. This aims of this research to determine the characteristics of fruit, phytochemical screening and rendement of extract in various solvents. Phytochemical research is qualitative descriptive using several reagents which include sample preparation, extraction, and phytochemical screening. From result of research got calculation of successive yield to extract methanol, ethyl acetate and n-hexane is 5,38%; 3.34% and 1.26%, The results of phytochemical screening of Rhizopora mucronata fruit extract on methanol solvent contain compounds: alkaloids, flavonoids, saponins, triterpenoids and tannins. In the ethyl acetate solvent contains compounds: alkaloids, triterpenoids, steroids and tannins. In the n-hexane solvent contain triterpenoid.
Current trends and open problems in arithmetic dynamics
Authors: Benedetto Robert , Ingram Patrick , Jones Rafe , Manes Michelle , Silverman Joseph , Tucker Thomas
Published: March 2019

Arithmetic dynamics is the study of number theoretic properties of dynamical systems. A relatively new field, it draws inspiration partly from dynamical analogues of theorems and conjectures in classical arithmetic geometry and partly frompp-adic analogues of theorems and conjectures in classical complex dynamics. In this article we survey some of the motivating problems and some of the recent progress in the field of arithmetic dynamics.
A pinch of salt: response of coastal grassland plants to simulated seawater inundation treatments
Authors: Hanley M E , Sanders S K D , Stanton H -M , Billington R A , Boden R
Published: March 2019

Background and Aims

The combination of rising sea levels and increased storm frequency and intensity is predicted to increase the severity of oceanic storm surge events and the impact of flooding on coastal ecosystems globally. Understanding how plant communities respond to this threat necessitates experiments involving plant immersion in saline water, but logistical issues and natural variation in seawater composition mean that pure NaCl solutions or marine aquarium salts (MS) are widely used. Nonetheless, their comparative impact on plant ecophysiology, and thus relevance to understanding real-world flooding scenarios, is unknown.

Methods

In the first of two experiments, we examined how six ecophysiological responses in white clover (Trifolium repens) varied when plants were subjected to five different inundation treatments: deionized water, natural seawater, an MS solution and two NaCl solutions. In a second experiment, we examined how immersion in deionized water, MS solution and natural seawater affected six European perennial herb species, three native to Spanish sand dunes, and three from British coastal grasslands.

Results

The two NaCl solutions induced exceptional Trifolium mortality, but responses varied little between MS and seawater treatments. In the second experiment, although leaf tissue necrosis and proline concentrations increased, and growth decreased compared with untreated controls, only one response in one species varied between MS and seawater treatments. Chemical speciation modelling revealed major variation in free Na+ and Cl− between NaCl solutions and seawater, but minor differences between MS and seawater.

Conclusions

We show that NaCl solutions are unsuitable surrogates to investigate plant response to elevated environmental salinity. Although responses to natural seawater and MS were consistent within species, there was notable between-species variation. Consequently, the first steps to elucidating how these species-specific responses influence coastal plant community recovery following storm surge can likely be achieved using commercial marine aquarium salts as substitutes for natural seawater.
Aggrescan3D standalone package for structure-based prediction of protein aggregation properties
Authors: Kuriata Aleksander , Iglesias Valentin , Kurcinski Mateusz , Ventura Salvador , Kmiecik Sebastian
Published: February 2019

Aggrescan3D (A3D) standalone is a multiplatform Python package for structure-based prediction of protein aggregation properties and rational design of protein solubility. A3D allows the re-design of protein solubility by combining structural aggregation propensity and stability predictions, as demonstrated by a recent experimental study. It also enables predicting the impact of protein conformational fluctuations on the aggregation properties. The standalone A3D version is an upgrade of the original web server implementation—it introduces a number of customizable options, automated analysis of multiple mutations and offers a flexible computational framework for merging it with other computational tools.

Availability and implementation

A3D standalone is distributed under the MIT license, which is free for academic and non-profit users. It is implemented in Python. The A3D standalone source code, wiki with documentation and examples of use, and installation instructions for Linux, macOS and Windows are available in the A3D standalone repository at https://bitbucket.org/lcbio/aggrescan3d.
VERA: agent-based modeling transmission of antibiotic resistance between human pathogens and gut microbiota
Authors: Glushchenko Oksana E , Prianichnikov Nikita A , Olekhnovich Evgenii I , Manolov Alexander I , Tyakht Alexander V , Starikova Elizaveta V , Odintsova Vera E , Kostryukova Elena S , Ilina Elena I
Published: February 2019

Motivation

The resistance of bacterial pathogens to antibiotics is one of the most important issues of modern health care. The human microbiota can accumulate resistance determinants and transfer them to pathogenic microbiota by means of horizontal gene transfer. Thus, it is important to develop methods of prediction and monitoring of antibiotics resistance in human populations.

Results

We present the agent-based VERA model, which allows simulation of the spread of pathogens, including the possible horizontal transfer of resistance determinants from a commensal microbiota community. The model considers the opportunity of residents to stay in the town or in a medical institution, have incorrect self-treatment, treatment with several antibiotics types and transfer and accumulation of resistance determinants from commensal microorganism to a pathogen. In this model, we have also created an assessment of optimum observation frequency of infection spread among the population. Investigating model behavior, we show a number of non-linear dependencies, including the exponential nature of the dependence of the total number of those infected on the average resistance of a pathogen. As the model infection, we chose infection with Shigella spp., though it could be applied to a wide range of other pathogens.

Availability and implementation

Source code and binaries VERA and VERA.viewer are freely available for download at github.com/lpenguin/microbiota-resistome. The code is written in Java, JavaScript and R for Linux platform.

Supplementary information

Supplementary data are available at Bioinformatics online.
On sparsity scales and covariance matrix transformations
Authors: Battey H S
Published: March 2019

We develop a theory of covariance and concentration matrix estimation on any given or estimated sparsity scale when the matrix dimension is larger than the sample size. Nonstandard sparsity scales are justified when such matrices are nuisance parameters, distinct from interest parameters, which should always have a direct subject-matter interpretation. The matrix logarithmic and inverse scales are studied as special cases, with the corollary that a constrained optimization-based approach is unnecessary for estimating a sparse concentration matrix. It is shown through simulations that for large unstructured covariance matrices, there can be appreciable advantages to estimating a sparse approximation to the log-transformed covariance matrix and converting the conclusions back to the scale of interest.
Scalp recorded spike ripples predict seizure risk in childhood epilepsy better than spikes
Authors: Kramer Mark A , Ostrowski Lauren M , Song Daniel Y , Thorn Emily L , Stoyell Sally M , Parnes McKenna , Chinappen Dhinakaran , Xiao Grace , Eden Uri T , Staley Kevin J , Stufflebeam Steven M , Chu Catherine J
Published: March 2019

In the past decade, brief bursts of fast oscillations in the ripple range have been identified in the scalp EEG as a promising non-invasive biomarker for epilepsy. However, investigation and clinical application of this biomarker have been limited because standard approaches to identify these brief, low amplitude events are difficult, time consuming, and subjective. Recent studies have demonstrated that ripples co-occurring with epileptiform discharges (‘spike ripple events’) are easier to detect than ripples alone and have greater pathological significance. Here, we used objective techniques to quantify spike ripples and test whether this biomarker predicts seizure risk in childhood epilepsy. We evaluated spike ripples in scalp EEG recordings from a prospective cohort of children with a self-limited epilepsy syndrome, benign epilepsy with centrotemporal spikes, and healthy control children. We compared the rate of spike ripples between children with epilepsy and healthy controls, and between children with epilepsy during periods of active disease (active, within 1 year of seizure) and after a period of sustained seizure-freedom (seizure-free, >1 year without seizure), using semi-automated and automated detection techniques. Spike ripple rate was higher in subjects with active epilepsy compared to healthy controls (P = 0.0018) or subjects with epilepsy who were seizure-free ON or OFF medication (P = 0.0018). Among epilepsy subjects with spike ripples, each month seizure-free decreased the odds of a spike ripple by a factor of 0.66 [95% confidence interval (0.47, 0.91), P = 0.021]. Comparing the diagnostic accuracy of the presence of at least one spike ripple versus a classic spike event to identify group, we found comparable sensitivity and negative predictive value, but greater specificity and positive predictive value of spike ripples compared to spikes (P = 0.016 and P = 0.006, respectively). We found qualitatively consistent results using a fully automated spike ripple detector, including comparison with an automated spike detector. We conclude that scalp spike ripple events identify disease and track with seizure risk in this epilepsy population, using both semi-automated and fully automated detection methods, and that this biomarker outperforms analysis of spikes alone in categorizing seizure risk. These data provide evidence that spike ripples are a specific non-invasive biomarker for seizure risk in benign epilepsy with centrotemporal spikes and support future work to evaluate the utility of this biomarker to guide medication trials and tapers in these children and predict seizure risk in other at-risk populations.
Postnatally Acquired Zika Virus Disease Among Children, United States, 2016–2017
Authors: Lindsey Nicole P , Porse Charsey C , Potts Emily , Hyun Judie , Sandhu Kayleigh , Schiffman Elizabeth , Cervantes Kimberly B , White Jennifer L , Mason Krystal , Owens Kamesha , Holsinger Caroline , Fischer Marc , Staples J Erin ,   Zika Virus Disease Enhanced Surveillance Working Group, Jilek Wendy , Brown Jennifer , Stevens Taryn , Tonzel Julius , Scott-Waldron Christine , Simonson Sean , Feldman Katherine , Brooks Richard , Galvin Megan , Scotland Sarah , Brown Catherine , Garafalo Kristin , Ojo Mojisola , Worthington Karen , Thomas Nadia , Jamro Erica , Long Jonah , Miller Barry , Arshadmansab Sepehr , Broussard Kelly , Evert Nicole , Broyhill Jim , Mircoff Elena
Published: March 2019

Background

The clinical findings among children with postnatally acquired Zika virus disease are not well characterized. We describe and compare clinical signs and symptoms for children aged <18 years.

Methods

Zika virus disease cases were included if they met the national surveillance case definition, had illness onset in 2016 or 2017, resided in a participating state, and were reported to the Centers for Disease Control and Prevention. Pediatric cases were aged <18 years; congenital and perinatal infections were excluded. Pediatric cases were matched to adult cases (18‒49 years). Clinical information was compared between younger and older pediatric cases and between children and adults.

Results

A total of 141 pediatric Zika virus disease cases were identified; none experienced neurologic disease. Overall, 28 (20%) were treated in an emergency department, 1 (<1%) was hospitalized; none died. Of the 4 primary clinical signs and symptoms associated with Zika virus disease, 133 (94%) children had rash, 104 (74%) fever, 67 (48%) arthralgia, and 51 (36%) conjunctivitis. Fever, arthralgia, and myalgia were more common in older children (12‒17 years) than younger children (1‒11 years). Arthralgia, arthritis, edema, and myalgia were more common in adults compared to children.

Conclusions

This report supports previous findings that Zika virus disease is generally mild in children. The most common symptoms are similar to other childhood infections, and clinical findings and outcomes are similar to those in adults. Healthcare providers should consider a diagnosis of Zika virus infection in children with fever, rash, arthralgia, or conjunctivitis, who reside in or have traveled to an area where Zika virus transmission is occurring.
Delays in referral from primary care are associated with a worse survival in patients with esophagogastric cancer
Authors: Arhi Chanpreet S , Markar S , Burns E M , Bouras G , Bottle A , Hanna G , Aylin P , Ziprin P , Darzi A
Published: March 2019

NICE referral guidelines for suspected cancer were introduced to improve prognosis by reducing referral delays. However, over 20% of patients with esophagogastric cancer experience three or more consultations before referral. In this retrospective cohort study, we hypothesize that such a delay is associated with a worse survival compared with patients referred earlier.

By utilizing Clinical Practice Research Datalink, a national primary care linked database, the first presentation, referral date, a number of consultations before referral and stage for esophagogastric cancer patients were determined. The risk of a referral after one or two consultations compared with three or more consultations was calculated for age and the presence of symptom fulfilling the NICE criteria. The risk of death according to the number of consultations before referral was determined, while accounting for stage and surgical management.

1307 patients were included. Patients referred after one (HR 0.80 95% CI 0.68–0.93 p = 0.005) or two consultations (HR 0.81 95% CI 0.67–0.98 p = 0.034) demonstrated significantly improved prognosis compared with those referred later. The risk of death was also lower for patients who underwent a resection, were younger or had an earlier stage at diagnosis. Those presenting with a symptom fulfilling the NICE criteria (OR 0.27 95% CI 0.21–0.35 p < 0.0001) were more likely to be referred earlier.

This is the first study to demonstrate an association between a delay in referral and worse prognosis in esophagogastric patients. These findings should prompt further research to reduce primary care delays.
European Crohn’s and Colitis Organisation Topical Review on Complementary Medicine and Psychotherapy in Inflammatory Bowel Disease
Authors: Torres Joana , Ellul Pierre , Langhorst Jost , Mikocka-Walus Antonina , Barreiro-de Acosta Manuel , Basnayake Chamara , Ding Nik John Sheng , Gilardi Daniela , Katsanos Konstantinos , Moser Gabriele , Opheim Randi , Palmela Carolina , Pellino Gianluca , Van der Marel Sander , Vavricka Stephan R
Published: February 2019

Patients with inflammatory bowel disease [IBD] increasingly use alternative and complementary therapies, for which appropriate evidence is often lacking. It is estimated that up to half of all patients with IBD use various forms of complementary and alternative medicine during some point in their disease course. Considering the frequent use of such therapies, it is crucial that physicians and patients are informed about their efficacy and safety in order to provide guidance and evidence-based advice. Additionally, increasing evidence suggests that some psychotherapies and mind–body interventions may be beneficial in the management of IBD, but their best use remains a matter of research. Herein, we provide a comprehensive review of some of the most commonly used complementary, alternative and psychotherapy interventions in IBD.
Sex-based differences in outcomes, 30-day readmissions, and costs following catheter ablation of atrial fibrillation: the United States Nationwide Readmissions Database 2010–14
Authors: Cheung Jim W , Cheng Edward P , Wu , Xian , Yeo Ilhwan , Christos Paul J , Kamel Hooman , Markowitz Steven M , Liu Christopher F , Thomas George , Ip James E , Lerman Bruce B , Kim Luke K
Published: March 2019

Aims

Although catheter ablation has emerged as an important therapy for patients with symptomatic atrial fibrillation (AF), there are limited data on sex-based differences in outcomes. We sought to compare in-hospital outcomes and 30-day readmissions of women and men undergoing AF ablation.

Methods and results

Using the United States Nationwide Readmissions Database, we analysed patients undergoing AF ablation between 2010 and 2014. Based on ICD-9-CM codes, we identified co-morbidities and outcomes. Multivariable logistic regression and inverse probability-weighting analysis were performed to assess female sex as a predictor of endpoints. Of 54 597 study patients, 20 623 (37.7%) were female. After adjustment for age, co-morbidities, and hospital factors, women had higher rates of any complication [adjusted odds ratio (aOR) 1.39; P < 0.0001], cardiac perforation (aOR 1.39; P = 0.006), and bleeding/vascular complications (aOR 1.49; P < 0.0001). Thirty-day all-cause readmission rates were higher for women compared to men (13.4% vs. 9.4%; P < 0.0001). Female sex was independently associated with readmission for AF/atrial tachycardia (aOR 1.48; P < 0.0001), cardiac causes (aOR 1.40; P < 0.0001), and all causes (aOR 1.25; P < 0.0001). Similar findings were confirmed with inverse probability-weighting analysis. Despite increased complications and readmissions, total costs for AF ablation were lower for women than men due to decreased resource utilization.

Conclusions

Independent of age, co-morbidities, and hospital factors, women have higher rates of complications and readmissions following AF ablation. Sex-based differences and disparities in the management of AF need to be explored to address these gaps in outcomes.
Investigator Engagement: Somewhat Radical Considerations on Practices to Improve Animal Care Program Compliance
Authors: Hankenson F Claire , Hallman Troy
Published: March 2019

The authors discuss approaches to bolster investigator engagement, inviting investigators to be partners within the Animal Care Program. Regulatory burden in animal research endeavors continues to be reviewed and critiqued; therefore, this article intends to encourage Animal Care Programs to promote transparency and incorporation of unique educational training initiatives to tailor and focus compliance efforts across research programs. Borrowing from concepts of patient engagement, adherence, and enrollment efforts within the medical profession, it is likely that gains in trust, understanding, and communication between stakeholders within animal programs can be achieved without excessive efforts to alter existing approaches. Institutions will continue to be challenged to balance animal welfare expectations with promotion of research missions. This article provides a framework for somewhat radical ideas, including the use of collaborative orientations, assistance with self-evaluations, timely self-reporting, and meaningful and directed trainings, that are all aimed to resonate in contemporary animal care programs and foster investigator engagement in ongoing compliance efforts.
Guideline attainment and morbidity/mortality rates in a large cohort of European haemodialysis patients (EURODOPPS)
Authors: Liabeuf Sophie , Sajjad Ayesha , Kramer Anneke , Bieber Brian , McCullough Keith , Pisoni Ron , Caskey Fergus , Combe Christian , Robinson Bruce M , Jager Kitty J , Massy Ziad A
Published: February 2019

Background

Haemodialysis patients experience a wide variety of intermediate complications, such as anaemia, hypertension and mineral bone disease (MBD). We aimed to assess the risk of death and hospital admissions as a function of the simultaneous attainment of different guideline targets (for hypertension, anaemia and MBD) in a large European cohort of dialysis patients.

Methods

EURODOPPS is part of the Dialysis Outcomes and Practice Patterns Study (DOPPS) international, prospective cohort study of adult, in-centre haemodialysis patients for whom clinical data are extracted from medical records. In the present analysis, 6317 patients from seven European countries were included between 2009 and 2011. The percentages of patients treated according to the international guidelines on anaemia, hypertension and MBD were determined. The overall degree of guideline attainment was considered to be high if four or all five of the evaluated targets were attained, moderate if two or three targets were attained, and low if fewer than two targets were attained. Fully adjusted multivariate Cox models were used to investigate the relationship of target attainment with mortality and first hospital admission.

Results

At baseline, the degree of target attainment was low in 1751 patients (28%), moderate in 3803 (60%) and high in 763 (12%). In the fully adjusted model using time-dependent covariates, low attainment was associated with higher all-cause mortality [hazard ratio (95% confidence interval) = 1.19 (1.05–1.34)] and high attainment was associated with lower all-cause mortality [0.82 (0.68–0.99)]. In a similar model that additionally accounted for death as a competing risk, low and high attainments were not associated with hospital admission.

Conclusion

In a large international cohort of dialysis patients, we have shown that more stringent application of guidelines is associated with lower mortality.
Predicting Cognitive Improvement in Normal Pressure Hydrocephalus Patients Using Preoperative Neuropsychological Testing and Cerebrospinal Fluid Biomarkers
Authors: McGovern Robert A , Nelp Taylor B , Kelly Kathleen M , Chan Andrew K , Mazzoni Pietro , Sheth Sameer A , Honig Lawrence S , Teich Andrew F , McKhann Guy M
Published: March 2019

BACKGROUND

Though it is well known that normal pressure hydrocephalus (NPH) patients can cognitively improve after ventriculoperitoneal shunting (VPS), one of the major dilemmas in NPH is the ability to prospectively predict which patients will improve.

OBJECTIVE

To prospectively assess preoperative predictors of postshunt cognitive improvement.

METHODS

This was a prospective observational cohort including 52 consecutive patients with approximately 1-yr follow-up. Patients underwent neuropsychological testing at baseline, postlumbar drainage, and postshunt. Cerebrospinal fluid (CSF) biomarkers and cortical biopsies were also collected to examine their relationship with postshunt cognitive improvement.

RESULTS

Rey Auditory Verbal Learning Test-L (RAVLT-L) was the only neuropsychological test to demonstrate statistically significant improvement both postlumbar drain and postshunt. Improvement on the RAVLT-L postlumbar drain predicted improvement on the RAVLT-L postshunt. Patients with biopsies demonstrating Aβ+ Tau+ had lower ventricular CSF Aβ42 and higher lumbar CSF pTau compared to Aβ– Tau– patients. A receiver operating curve analysis using lumbar pTau predicted Aβ+ Tau+ biopsy status but was not related to neuropsychological test outcome.

CONCLUSION

The RAVLT can be a useful preoperative predictor of postoperative cognitive improvement, and thus, we recommend using the RAVLT to evaluate NPH patients. CSF biomarkers could not be related to neuropsychological test outcome. Future research in a larger patient sample will help determine the prospective utility of CSF biomarkers in the evaluation of NPH patients.
Philosophy of Medicine
Authors: Broadbent Alex
Published: March 2019

Philosophy of Medicine seeks to answer two questions: (1) what is medicine? and (2) what should we think of it? The first question is motivated by the observation that medicine has existed and continues to exist in many different forms in different times and places. There is no activity or belief that is common to all medical traditions in all times and places. What, if anything, makes us count these activities as varieties of the same thing—namely, medicine? The book distinguishes the goal and business of medicine, arguing that the goal is cure, while the business of medicine cannot be, because medical traditions have been too hit-and-miss at achieving cure. The core medical competence is identified as engaging with the project of understanding the nature and causes of disease. A model of health is also required to say what medicine is, since health is part of its subject matter, and a novel theory of health as a secondary property is offered. In the second part of the book, the proper epistemic attitude to medicine is considered. Contrary to much contemporary work, the book argues against positions setting very rigid constraints on what counts as admissible evidence in forming beliefs either about whole traditions or about specific interventions. Thus both Evidence-Based Medicine and Medical Nihilism are rejected. Instead a view called Medical Cosmopolitanism is developed from Appiah’s corresponding work in ethics. The view is applied to alternative and non-Mainstream traditions, as well as to the project of decolonizing medicine.
Paracetamol and Pain Modulation by TRPV1, UGT2B15, SULT1A1 Genotypes: A Randomized Clinical Trial in Healthy Volunteers
Authors: Pickering Gisèle , Creveaux Isabelle , Macian Nicolas , Pereira Bruno
Published: March 2019

Background

The influence of the genetic polymorphism of enzymes and receptors involved in paracetamol metabolism and mechanism of action has not been investigated. This trial in healthy volunteers investigated the link between paracetamol pain relief and the genetic polymorphism of 23 enzymes and receptors.

Design

This randomized double-blind crossover controlled pilot study took place in the Clinical Pharmacology Department, University Hospital, Clermont-Ferrand, France. Forty-seven Caucasian volunteers were recruited. The trial consisted of two randomized sessions one week apart with oral paracetamol or placebo, and pain changes were evaluated with mechanical pain stimuli. The genetic polymorphism of 23 enzymes and receptors was studied, and correlations were made with pain relief. All tests are two-sided with a type I error at 0.05.

Results

Paracetamol was antinociceptive compared with placebo (222 ± 482 kPaxmin vs 23 ± 431 kPaxmin; P = 0.0047), and the study showed 30 paracetamol responders and 17 paracetamol nonresponders. Responders were characterized by TRPV1rs224534 A allele, UGT2B15rs1902023 TT genotype, and SULT1A1rs9282861 GG genotype (P < 0.05 for all). These findings confirm for the first time the involvement of a specific TRPV1 rs224534 variant in paracetamol antinociception. They also reveal a new antinociceptive role for specific variants of hepatic phase II enzymes associated with paracetamol metabolism.

Conclusions

The study warrants larger clinical trials on these potential genomic markers of paracetamol analgesia in patients. Confirmation of the present findings would open the way to effective individualized pain treatment with paracetamol, the most commonly used analgesic worldwide.
Squamous Cell Carcinoma following Epidermoid Cyst in the Buttock
Authors: Niimi Yosuke , Takeuchi Masaki , Isono Nobuo
Published: February 2019

In the field of plastic surgery, subcutaneous masses in the buttocks are frequently observed. However, squamous cell carcinoma (SCC) after epidermoid cyst, which appears in the presacral space, is extremely rare. This report described a case of a 71-year-old woman, who previously received a skin incision by a doctor for treating a cystic lesion in the buttock; she was diagnosed with SCC by preoperative biopsy at the authors’ department. In addition, computed tomography suspected that the tumor originated in the presacral space. Under general anesthesia, an extended resection of the malignant tumor with gastrointestinal surgery was performed. After resection, the defect of buttocks region was reconstructed with a V-Y advancement gluteus maximus myocutaneous flap. After pathological examination the tumor was diagnosed as SCC after epidermoid cyst; peplomycin sulfate at 50 mg/d was administered intramuscularly for 2 weeks as chemotherapy. No wound complications were observed after surgery, and no recurrence was noted for 5 years. For managing tumor in the gluteal region, a possibility of malignancy must be considered, and thorough radiographic studies must be pursued before surgery.