bluuebunny/crossref_metadata_2025 huggingface dataset:
P036 Patients with learning disability, views on the use of a patient-held medication passport
Authors: Crook Joanne , Patel Deepa , Marvin Vanessa , Jubraj Barry
Published: June 2019

Aim

To establish the views of adolescent patients with learning disabilities and their carers, of the patient-held medication passport (My Medication Passport-MMP).

Methods

A questionnaire was devised to find out if patients/carers thought a patient-held record of their medications (the MMP) was useful and to suggest improvements as appropriate. The MMP is a patient-held record of medicines use available as a passport sized booklet.1 MMPs were distributed to patients and carers for them to read and review at a patient focus group. Ethics approval was not required for this study.

Results

20 questionnaires were sent and a total of 17 completed questionnaires were returned (85% response rate). 70% (n=12) of the questionnaires were completed by carers, 24% (n=4) by family members and 1% (n=1) by a patient. 100% (n=17) of carers/patients who reviewed the MMP found it useful. When asked about features they liked about MMP; Seven carers noted the MMP was easy to use; four carers felt MMP was a good way to keep (personal) medicines information up to date; with three further clarifying that it could be used as a ‘concise way of keep track (of medicines)’ and two specified they liked that ‘all the information is in one book’. When Patients/carers were asked for ways MMP could be improved; two carers asked for more space to document past medication, including an area to ‘keep track of the behaviours and how it is exhibited because of the medication’; one carer noted that ‘some youngsters would benefit from more visual learning’ and one asked for a version to be made available via app on smart phone. Limitations included a small sample with limited exposure to MMP. The patient group sampled may not be representative.

Conclusion

Passports as tools aim to help patients better manage their medicines and have been successfully used in a patient with learning disability.2 It is encouraging to see that this small group of patients with learning disability find the MMP useful. Suggested adaptations to MMP for this patient group included it being more visual, and having areas for past medication. Other trials of MMP have suggested that it may require a section surrounding medicines administration. Patients have since been directed to the MMP app which can be downloaded onto a smartphone. There are many opportunities for future work including conducting an evaluation of the MMP in use over time and across different sectors, and to determine what patients actually record in the MMP.

References

Barber S, et al. Evaluation of My Medication Passport: a patient-completed aide-memoire designed by patients, for patients, to help towards medicines optimisation. BMJ Open4(8). https://bmjopen.bmj.com/content/4/8/e005608

Jubraj B. Use of a medication passport in a disabled child seen across many care settings. BMJ Case Reports. 25 February 2015; http://casereports.bmj.com/content/2015/bcr-2014-208033Save
P040 Monitoring defibrotide usage in paediatric patients undergoing HSCT with known risk factors for developing VOD/SOS
Authors: Beirne Michelle , Butler Eileen , Fitzpatrick Michael
Published: June 2019

Aim

Defibrotide is licensed for the treatment of hepatic venous occlusive disease (VOD) following haematopoeitic stem cell transplant (HSCT). Up to April 2015 defibrotide was used as prophylaxis against VOD in our HSCT patients who were considered at high-risk for developing VOD. This practice was discontinued due to the lack of evidence of efficacy and increasing costs of the drug. The aims of this audit were to identify patients undergoing HSCT who had one or more risk factors for the development of VOD, to measure the incidence of VOD in this patient cohort after the discontinuation of prophylactic defibrotide and calculate the cost savings associated with the discontinuation of prophylaxis.

Methods

All patients who underwent HSCT between Oct 2015 and Dec 2016 were included. Patient’s medical records were reviewed and risk factors for VOD were identified. Risk factors for developing VOD post HSCT in our patient cohort were defined following a literature review of peer-reviewed papers identifying paediatric specific risk factors.1 2 These were namely: patients aged ≤2 years, patients receiving a second transplant, conditioning with IV busulfan ± cyclophosphamide, and previous treatment with gemtuzumab ozogamicin. The theoretical dose of defibrotide for patients with known risk factors was calculated based on their weight at start of conditioning and the duration of treatment was based on the number of days conditioning the patient received plus 30 days following the date of transplant. The cost of a theoretical course of defibrotide for these patients was calculated to determine cost savings.

Results

Of the 27 patients included in the study, 16 (59%) had one or more risk factors. The most common risk factor identified was conditioning with busulfan in patients ≤2 years of age (26% of patients). At present no patient post HSCT has developed VOD requiring treatment. One patient developed sub-clinical VOD which required no treatment and resolved spontaneously. Another patient received defibrotide as prophylaxis for VOD due to severe liver dysfunction prior to HSCT. There were substantial cost savings following the discontinuation of prophylactic defibrotide with a total of 2876 vials (180 vials/patient) saved during this time period.

Conclusion

This audit validates our decision to discontinue use of prophylactic defibrotide and reserve its use for treatment of early VOD.

References

Cheuk D, Wang P, Lee T, Chiang A, Ha S, Lau Y, Chan G. Risk factors and mortality predictors of hepatic veno-occlusive disease after pediatric hematopoietic stem cell transplantation. Bone Marrow Transplantation. 2007;40:935–944.

Mohty M, Malard F, Abecassis M, Aerts E, Alaskar A, Alijurf M, NiChonghaile M. Sinusoidal obstruction syndrome/veno- occlusive disease: current situation and perspectives- a position statement from the European Society for Blood and Marrow Transplantation (EBMT). 2015; Bone Marrow Transplantation. 2015;50:781–789.
P045 Value from your vitamins – optimising vitamin supplementation in children with cystic fibrosis
Authors: Turner Eleanor
Published: June 2019

Aim

To optimise fat soluble vitamin supplementation in children with CF in a tertiary children’s hospital and primary care. To compare supplementation of individual vitamins and supplementation with a new multivitamin preparation against national guidelines, cost and patient acceptability.1

Methods

Comparison of current practice (supplementation of individual vitamins) with a new multi-vitamin preparation, Paravit-CF. Form and dose of each of the fat soluble vitamins was compared against national CF Trust guidelines for nutrition.1 Cost of treatment per day was compared. Patient acceptability was explored by comparing medication burden and with a focus group made up of representatives from the CF multi-disciplinary team (MDT) including, consultants, specialist nurses, dieticians and a pharmacist.

Results

Current approach to vitamin supplementation is not in line with the CF Trust guidelines for nutrition. Supplementation with Paravit-CF preparations meets recommendations made in the CF Trust guidelines for nutrition for patients of all ages except for infants. Infants will receive vitamin A at higher doses than recommended. Cost of vitamin supplementation is reduced by approximately 50% when using Paravit-CF compared with current practice. Medication burden is reduced by more than 50% when using Paravit-CF compared with current practice. Main themes from the MDT focus group were that Paravit-CF liquid is colourless, taste free, odour free and can be mixed into food, all of which may aid compliance. Paravit-CF preparations also vegetarian friendly and comply with halal and kosher regulations. Unlike current practice, Paravit-CF does not offer flexibility in dosing of individual vitamins.

Conclusion

Fat soluble vitamin supplementation using Paravit-CF offers several advantages over supplementation of individual vitamins. Paravit-CF offers vitamin supplementation at doses in line with the recommendations made by the CF Trust, is cheaper and reduces the medication burden for patients. Locally, the decision has been made to switch to Paravit-CF as first line vitamin supplementation in children with CF. Future work is planned to assess clinical efficacy and financial impact of the switch.

Reference

Cystic Fibrosis Trust. Nutritional Management of Cystic Fibrosis. Second Edition. September 2016. Available from: https://www.cysticfibrosis.org.uk/the-work-we-do/clinical-care/consensus-documents (Accessed 10 July 2018)
Relative effectiveness of different forms of exercises for treatment of chronic low back pain: protocol for a systematic review incorporating Bayesian network meta-analysis
Authors: Gao Chengfei , Chen Guanghui , Yang Hui , Hua Zhen , Xu Peng , Wong Mansang , He Chengqi
Published: June 2019

Introduction

Exercise is considered as an effective intervention in the management of patients with chronic low back pain (cLBP). However, the relative effectiveness as well as the hierarchy of exercise interventions have not been well established, although various exercise options are available. Therefore, the present protocol proposes to conduct a network meta-analysis (NMA) aiming to evaluate the effectiveness of different forms of exercise for treatment of cLBP.

Methods and analysis

Medline, Embase, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature, the Cochrane Central Register of Controlled Trials, and the Physiotherapy Evidence Database will be searched to identify all randomised controlled trials that evaluate the effectiveness of exercise in the treatment of cLBP. There will be no restrictions on date or language. Two authors will screen the literature and extract data independently based on predesigned rules, and evaluate the risk of bias of included studies using the Cochrane Risk of Bias Tool. Disagreements will be resolved through discussion or consultation with a senior reviewer. The primary outcomes of this study will be pain relief and improvement in function or disability for all interventions. Traditional pairwise meta-analysis and Bayesian NMA will be conducted to compare the effectiveness of different exercise interventions. The ranking probabilities for all interventions will be estimated and the hierarchy of each intervention will be summarised as surface under the cumulative ranking curve. The quality of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation instrument.

Ethics and dissemination

Ethical approval and informed consent are not required since this is a protocol for a meta-analysis with no confidential personal data to be collected. The results of this NMA will be submitted to a peer-reviewed journal for publication.

PROSPERO registration number

CRD42018090576.
Conjunctival colonisation and antibiotic resistance of coagulase-negativeStaphylococcusafter cataract surgery: a 6-month longitudinal study at a medical centre in Taiwan
Authors: Kang Eugene Yu-Chuan , Hou Chiun-Ho , Huang Yhu-Chering , Hsiao Ching-Hsi
Published: June 2019

Objective

To explored 6-month longitudinal changes in conjunctival colonisation and antibiotic resistance profiles of coagulase-negativeStaphylococcus(CNS) after cataract surgery with 1 month tobramycin treatment.

Design

Prospective cohort study between 1 August 2012, and 31 July 2013.

Setting

A single medical centre in Taiwan.

Participants

A total of 128 Taiwanese patients with 46.9% of male participants.

Interventions

Samples from the conjunctival sacs of both operation (OP) and non-OP eyes were obtained separately before cataract surgery and at 1, 3 and 6 months after surgery. Tobramycin (0.3%) treatment was applied four times daily for 1 month postoperatively.

Main outcome measure

Identification of CNS isolates and their antibiotic susceptibility by using disk diffusion or E-test.

Results

CNS was detected in 24.2% of patients at baseline. During postoperative follow-up, the CNS colonisation rate did not decrease in either eye but showed an increasing trend in the OP eyes at 1 month (p=0.06). The colonisation rate showed no significant difference between the OP and non-OP eyes from baseline to a specific follow-up. We observed a significant increase (p<0.05) in resistance to tobramycin at 1 month and to ciprofloxacin at 3 months in the OP eyes and to trimethoprim/sulfamethoxazole at 1 month and 3 months and to oxacillin at 6 months in the non-OP eyes.

Conclusions

During the 6-month postoperative follow-up, 0.3% tobramycin administration failed to reduce CNS colonisation but increased resistance to several antibiotics. Postoperative antibiotic treatment may be replaced by other evidence-endorsed prophylactic routines.
Distinction between euthanasia and palliative sedation is clear-cut
Authors: Materstvedt Lars Johan
Published: June 2019

This article is a response to Thomas David Riisfeldt’s paper entitled ‘Weakening the ethical distinction between euthanasia, palliative opioid use and palliative sedation’. It is shown that as far as euthanasia and palliative sedation are concerned, Riisfeldt has not established that a common ground, or a similarity, between the two is the relief of suffering. Quite the contrary, this is not characteristic of euthanasia, neither by definition nor from a clinical point of view. Hence, the argument hinges on a conceptually and empirically erroneous premise and is accordingly a non-starter.
Intensive forest management — does it pay off financially on drained peatlands?
Authors: Ahtikoski Anssi , Hökkä Hannu
Published: June 2019

There are only a few studies focusing on the financial aspects of management regimes on peatland forests and even fewer studies investigating intensive management. Such studies, however, are urgently needed, particularly in Finland, where a considerable proportion of drained peatlands is reaching a phase requiring active management. An empirical data set derived from the 10th National Forest Inventory (NFI10) is applied for stand-level simulations (MOTTI stand simulator) until final cut. The data are a representative sample of the most common drained peatland site types and their current stand structures in Finland. Based on several different initial stand conditions, tree growth was projected according to four management regimes: (1) passive management (only one clearcut executed), (2) management according to prevailing silvicultural recommendations, (3) stand-level optimum without ditch network maintenance (DNM) and fertilization (FERT), and (4) stand-level optimum with DNM and FERT (intensive management). The intensive management regime financially outperformed the other management options distinctively, regardless of the climatic region, peatland site type, and initial stand structure. However, towards more harsh climatic conditions and a more barren site type, the financial difference between management options flattened out, and silvicultural recommendations even resulted in a higher mean annual increment (MAI) compared with intensive management.
Collaborative Recommendations using Hierarchical Clustering based on K-d Trees and Quadtrees
Authors: Das Joydeep , Majumder Subhashis , Gupta Prosenjit , Mali Kalyani
Published: June 2019

Majority of the e-commerce sites implement Recommender Systems (RS) to help users navigate through the large search space and assist their decision making process by suggesting products that the user may like. Collaborative Filtering (CF) is the most successful and widely used algorithm in the domain of RS. However, due to the exponential growth of the web in terms of both content and number of users, CF based RS face serious scalability issues. To alleviate this problem, we propose a clustering based CF approach using two hierarchical space partitioning data structures — K-d tree and Quadtree. We cluster or partition the users’ space of the system on the basis of user location and then use the resultant clusters for predicting ratings of a target user. Since the CF based recommendation algorithm is applied separately to the clusters and not on the entire rating data, it helps in bringing down the runtime of the algorithm substantially. We further measure spatial autocorrelation indices in the clusters to justify our clustering method. However, our objective is not only to reduce the runtime but also to maintain an acceptable recommendation quality. This requirement is rightly addressed by the proposed method which assures scalability, by processing very large datasets using the same computing resource. Moreover our proposed clustering scheme is oblivious of the underlying CF algorithm. Results from the extensive experiments conducted, show that our hierarchical clustering based recommendation approach reduces runtime of the standard CF algorithms by about 88%, 82%, 79% and 85% for MovieLens-100K, MovieLens-1M, Book-Crossing and TripAdvisor data respectively, while maintaining good recommendation quality.
EKEGWO: Enhanced Kernel-Based Exponential Grey Wolf Optimizer for Bi-Objective Data Clustering
Authors: Jadhav Amolkumar Narayan , N. Gomathi
Published: June 2019

The widespread application of clustering in various fields leads to the discovery of different clustering techniques in order to partition multidimensional data into separable clusters. Although there are various clustering approaches used in literature, optimized clustering techniques with multi-objective consideration are rare. This paper proposes a novel data clustering algorithm, Enhanced Kernel-based Exponential Grey Wolf Optimization (EKEGWO), handling two objectives. EKEGWO, which is the extension of KEGWO, adopts weight exponential functions to improve the searching process of clustering. Moreover, the fitness function of the algorithm includes intra-cluster distance and the inter-cluster distance as an objective to provide an optimum selection of cluster centroids. The performance of the proposed technique is evaluated by comparing with the existing approaches PSC, mPSC, GWO, and EGWO for two datasets: banknote authentication and iris. Four metrics, Mean Square Error (MSE), F-measure, rand and jaccord coefficient, estimates the clustering efficiency of the algorithm. The proposed EKEGWO algorithm can attain an MSE of 837, F-measure of 0.9657, rand coefficient of 0.8472, jaccord coefficient of 0.7812, for the banknote dataset.
A Mathematical Note on the Value Positivity for Matrix Game
Authors: Kreps Victoria , Matveenko Andrei
Published: June 2019

We give a criterion of positivity for the value of a matrix game. We use the criterion to investigate conditions of positivity of value for two classes of games: payoff matrices with all elements outside of the main diagonal having the same sign and symmetric payoff matrices.
Self-dual cyclic and quantum codes over ℤ2 × (ℤ2 + uℤ2)
Authors: Aydogdu Ismail , Abualrub Taher
Published: June 2019

In this paper, we introduce self-dual cyclic codes over the ring [Formula: see text]. We determine the conditions for any [Formula: see text]-cyclic code to be self-dual, that is, [Formula: see text]. Since the binary image of a self-orthogonal [Formula: see text]-linear code is also a self-orthogonal binary linear code, we introduce quantum codes over [Formula: see text]. Finally, we present some examples of self-dual cyclic and quantum codes that have good parameters.
Survey on Combinatorial Register Allocation and Instruction Scheduling
Authors: Lozano Roberto Castañeda , Schulte Christian
Published: June 2019

Register allocation (mapping variables to processor registers or memory) and instruction scheduling (reordering instructions to increase instruction-level parallelism) are essential tasks for generating efficient assembly code in a compiler. In the past three decades, combinatorial optimization has emerged as an alternative to traditional, heuristic algorithms for these two tasks. Combinatorial optimization approaches can deliver optimal solutions according to a model, can precisely capture trade-offs between conflicting decisions, and are more flexible at the expense of increased compilation time.

This article provides an exhaustive literature review and a classification of combinatorial optimization approaches to register allocation and instruction scheduling, with a focus on the techniques that are most applied in this context: integer programming, constraint programming, partitioned Boolean quadratic programming, and enumeration. Researchers in compilers and combinatorial optimization can benefit from identifying developments, trends, and challenges in the area; compiler practitioners may discern opportunities and grasp the potential benefit of applying combinatorial optimization.
A Machine-Learning Algorithm with Disjunctive Model for Data-Driven Program Analysis
Authors: Jeon Minseok , Jeong Sehun , Cha Sungdeok , Oh Hakjoo
Published: June 2019

We present a new machine-learning algorithm with disjunctive model for data-driven program analysis. One major challenge in static program analysis is a substantial amount of manual effort required for tuning the analysis performance. Recently, data-driven program analysis has emerged to address this challenge by automatically adjusting the analysis based on data through a learning algorithm. Although this new approach has proven promising for various program analysis tasks, its effectiveness has been limited due to simple-minded learning models and algorithms that are unable to capture sophisticated, in particular disjunctive, program properties. To overcome this shortcoming, this article presents a new disjunctive model for data-driven program analysis as well as a learning algorithm to find the model parameters. Our model uses Boolean formulas over atomic features and therefore is able to express nonlinear combinations of program properties. A key technical challenge is to efficiently determine a set of good Boolean formulas, as brute-force search would simply be impractical. We present a stepwise and greedy algorithm that efficiently learns Boolean formulas. We show the effectiveness and generality of our algorithm with two static analyzers: context-sensitive points-to analysis for Java and flow-sensitive interval analysis for C. Experimental results show that our automated technique significantly improves the performance of the state-of-the-art techniques including ones hand-crafted by human experts.
Text Analysis in Adversarial Settings
Authors: Gröndahl Tommi , Asokan N.
Published: June 2019

Textual deception constitutes a major problem for online security. Many studies have argued that deceptiveness leaves traces in writing style, which could be detected using text classification techniques. By conducting an extensive literature review of existing empirical work, we demonstrate that while certain linguistic features have been indicative of deception in certain corpora, they fail to generalize across divergent semantic domains. We suggest that deceptiveness as such leaves no
content-invariant stylistic trace
, and textual similarity measures provide a superior means of classifying texts as potentially deceptive. Additionally, we discuss forms of deception beyond semantic content, focusing on hiding author identity by
writing style obfuscation
. Surveying the literature on both author identification and obfuscation techniques, we conclude that current style transformation methods fail to achieve reliable obfuscation while simultaneously ensuring semantic faithfulness to the original text. We propose that future work in style transformation should pay particular attention to disallowing semantically drastic changes.
CSS Minification via Constraint Solving
Authors: Hague Matthew , Lin Anthony W. , Hong Chih-Duo
Published: June 2019

Minification is a widely accepted technique that aims at reducing the size of the code transmitted over the web. This article concerns the problem of semantic-preserving minification of Cascading Style Sheets (CSS)—the
de facto
language for styling web documents—based on merging similar rules.

The cascading nature of CSS makes the semantics of CSS files sensitive to the ordering of rules in the file. To automatically identify rule-merging opportunities that best minimise file size, we reduce the rule-merging problem to a problem concerning “CSS-graphs,” i.e., node-weighted bipartite graphs with a dependency ordering on the edges, where weights capture the number of characters.

Constraint solving plays a key role in our approach. Transforming a CSS file into a CSS-graph problem requires us to extract the dependency ordering on the edges (an NP-hard problem), which requires us to solve the selector intersection problem. To this end, we provide the first full formalisation of CSS3 selectors (the most stable version of CSS) and reduce their selector intersection problem to satisfiability of quantifier-free integer linear arithmetic, for which highly optimised SMT-solvers are available. To solve the above NP-hard graph optimisation problem, we show how Max-SAT solvers can be effectively employed. We have implemented our rule-merging algorithm and tested it against approximately 70 real-world examples (including examples from each of the top 20 most popular websites). We also used our benchmarks to compare our tool against six well-known minifiers (which implement other optimisations). Our experiments suggest that our tool produced larger savings. A substantially better minification rate was shown when our tool is used together with these minifiers.
Naming Content on the Network Layer
Authors: Mannes Elisa , Maziero Carlos
Published: June 2019

The Information-Centric Network (ICN) paradigm is a future Internet approach aiming to tackle the Internet architectural problems and inefficiencies, by swapping the main entity of the network architecture from hosts to content items. In ICN, content names play a central role: Each content gets a unique name at the network layer, and this name is used for routing the content over the network. This paradigm change potentially enables a future Internet with better performance, reliability, scalability, and suitability for wireless and mobile communication. It also provides new intrinsic means to deal with some popular attacks on the Internet architecture, such as denial of service. However, this new paradigm also represents new challenges related to security that need to be addressed, to ensure its capability to support current and future Internet requirements. This article surveys and summarizes ongoing research concerning security aspects of ICNs, discussing vulnerabilities, attacks, and proposed solutions to mitigate them. We also discuss open challenges and propose future directions regarding research in ICN security.
A Survey on Collecting, Managing, and Analyzing Provenance from Scripts
Authors: Pimentel João Felipe , Freire Juliana , Murta Leonardo , Braganholo Vanessa
Published: June 2019

Scripts are widely used to design and run scientific experiments. Scripting languages are easy to learn and use, and they allow complex tasks to be specified and executed in fewer steps than with traditional programming languages. However, they also have important limitations for reproducibility and data management. As experiments are iteratively refined, it is challenging to reason about each experiment run (or trial), to keep track of the association between trials and experiment instances as well as the differences across trials, and to connect results to specific input data and parameters. Approaches have been proposed that address these limitations by collecting, managing, and analyzing the provenance of scripts. In this article, we survey the state of the art in provenance for scripts. We have identified the approaches by following an exhaustive protocol of forward and backward literature snowballing. Based on a detailed study, we propose a taxonomy and classify the approaches using this taxonomy.
Multi-model Databases
Authors: Lu Jiaheng , Holubová Irena
Published: June 2019

The variety of data is one of the most challenging issues for the research and practice in data management systems. The data are naturally organized in different formats and models, including structured data, semi-structured data, and unstructured data. In this survey, we introduce the area of multi-model DBMSs that build a single database platform to manage multi-model data. Even though multi-model databases are a newly emerging area, in recent years, we have witnessed many database systems to embrace this category. We provide a general classification and multi-dimensional comparisons for the most popular multi-model databases. This comprehensive introduction on existing approaches and open problems, from the technique and application perspective, make this survey useful for motivating new multi-model database approaches, as well as serving as a technical reference for developing multi-model database applications.
Wide field of view quantitative imaging of cellular ATP release
Authors: Tan Ju Jing , Ponomarchuk Olga , Grygorczyk Ryszard , Boudreault Francis
Published: June 2019

Although several mechanical stressors promote ATP secretion from eukaryotic cells, few mechanosensitive pathways for ATP release have been precisely characterized and none have been clearly identified. To facilitate progress, we report here a wide field of view (∼20 × 20 mm sample area) imaging technique paired with a quantitative image analysis to accurately map the dynamics of ATP release from a cell population. The approach has been tested on A549 cells stretched at high initial strain rate (2–5 s−1) or swelled by hypotonic shock. The amount of ATP secreted in response to a series of five graded stretch pulses (5–37% linear deformation, 1-s duration at 25°C) changed nonmonotonically with respect to strain amplitude and was inhomogeneous across the cell monolayer. In a typical experiment, extracellular ATP density averaged 250 fmol/mm2, but the area of detectable signal covered only ∼40% of the cells. In some areas, ATP accumulation peaked around 900 fmol/mm2, which corresponded to an estimated concentration of 4.5 µM. The total amount of ATP released from the combined stretch pulses reached 384 ± 224 pmol/million cells ( n = 4). Compared with stretch, hypotonic shock (50%, 30°C) elicited a more homogeneous ATP secretion from the entire cell population but at a lower yield totaling 28 ± 12 pmol/million cells ( n = 4). The quantitative extracellular ATP mapping of several thousand cells at once, with this wide field of view imaging system, will help identify ATP release pathways by providing unique insights on the dynamics and inhomogeneities of the cellular ATP secretion that are otherwise difficult to assess within the smaller field of view of a microscope.
Oxidative stress pathways in pancreatic β-cells and insulin-sensitive cells and tissues: importance to cell metabolism, function, and dysfunction
Authors: Newsholme Philip , Keane Kevin N. , Carlessi Rodrigo , Cruzat Vinicius
Published: June 2019

It is now accepted that nutrient abundance in the blood, especially glucose, leads to the generation of reactive oxygen species (ROS), ultimately leading to increased oxidative stress in a variety of tissues. In the absence of an appropriate compensatory response from antioxidant mechanisms, the cell, or indeed the tissue, becomes overwhelmed by oxidative stress, leading to the activation of intracellular stress-associated pathways. Activation of the same or similar pathways also appears to play a role in mediating insulin resistance, impaired insulin secretion, and late diabetic complications. The ability of antioxidants to protect against the oxidative stress induced by hyperglycemia and elevated free fatty acid (FFA) levels in vitro suggests a causative role of oxidative stress in mediating the latter clinical conditions. In this review, we describe common biochemical processes associated with oxidative stress driven by hyperglycemia and/or elevated FFA and the resulting clinical outcomes: β-cell dysfunction and peripheral tissue insulin resistance.
Gut organoids: mini-tissues in culture to study intestinal physiology and disease
Authors: Almeqdadi Mohammad , Mana Miyeko D. , Roper Jatin , Yilmaz Ömer H.
Published: June 2019

In vitro, cell cultures are essential tools in the study of intestinal function and disease. For the past few decades, monolayer cellular cultures, such as cancer cell lines or immortalized cell lines, have been widely applied in gastrointestinal research. Recently, the development of three-dimensional cultures known as organoids has permitted the growth of normal crypt-villus units that recapitulate many aspects of intestinal physiology. Organoid culturing has also been applied to study gastrointestinal diseases, intestinal-microbe interactions, and colorectal cancer. These models are amenable to CRISPR gene editing and drug treatments, including high-throughput small-molecule testing. Three-dimensional intestinal cultures have been transplanted into mice to develop versatile in vivo models of intestinal disease, particularly cancer. Limitations of currently available organoid models include cost and challenges in modeling nonepithelial intestinal cells, such as immune cells and the microbiota. Here, we describe the development of organoid models of intestinal biology and the applications of organoids for study of the pathophysiology of intestinal diseases and cancer.
Deoxycholic acid activates colonic afferent nerves via 5-HT3 receptor-dependent and -independent mechanisms
Authors: Yu Yang , Villalobos-Hernandez Egina C. , Pradhananga Sabindra , Baker Corey C. , Keating Christopher , Grundy David , Lomax Alan E. , Reed David E.
Published: June 2019

Increased bile acids in the colon can evoke increased epithelial secretion resulting in diarrhea, but little is known about whether colonic bile acids contribute to abdominal pain. This study aimed to investigate the mechanisms underlying activation of colonic extrinsic afferent nerves and their neuronal cell bodies by a major secondary bile acid, deoxycholic acid (DCA). All experiments were performed on male C57BL/6 mice. Afferent sensitivity was evaluated using in vitro extracellular recordings from mesenteric nerves in the proximal colon (innervated by vagal and spinal afferents) and distal colon (spinal afferents only). Neuronal excitability of cultured dorsal root ganglion (DRG) and nodose ganglion (NG) neurons was examined with perforated patch clamp. Colonic 5-HT release was assessed using ELISA, and 5-HT immunoreactive enterochromaffin (EC) cells were quantified. Intraluminal DCA increased afferent nerve firing rate concentration dependently in both proximal and distal colon. This DCA-elicited increase was significantly inhibited by a 5-HT3 antagonist in the proximal colon but not in the distal colon, which may be in part due to lower 5-HT immunoreactive EC cell density and lower 5-HT levels in the distal colon following DCA stimulation. DCA increased the excitability of DRG neurons, whereas it decreased the excitability of NG neurons. DCA potentiated mechanosensitivity of high-threshold spinal afferents independent of 5-HT release. Together, this study suggests that DCA can excite colonic afferents via direct and indirect mechanisms but the predominant mechanism may differ between vagal and spinal afferents. Furthermore, DCA increased mechanosensitivity of high-threshold spinal afferents and may be a mechanism of visceral hypersensitivity.

NEW & NOTEWORTHY Deoxycholic acid (DCA) directly excites spinal afferents and, to a lesser extent, indirectly via mucosal 5-HT release. DCA potentiates mechanosensitivity of high-threshold spinal afferents independent of 5-HT release. DCA increases vagal afferent firing in proximal colon via 5-HT release but directly inhibits the excitability of their cell bodies.
Portal hyperperfusion after major liver resection and associated sinusoidal damage is a therapeutic target to protect the remnant liver
Authors: Kohler Andreas , Moller Per W. , Frey Sabrina , Tinguely Pascale , Candinas Daniel , Obrist Dominik , Jakob Stephan M. , Beldi Guido
Published: June 2019

Extended liver resection results in loss of a large fraction of the hepatic vascular bed, thereby causing abrupt alterations in perfusion of the remnant liver. Mechanisms of hemodynamic adaptation and associated changes in oxygen metabolism after liver resection and the effect of mechanical portal blood flow reduction were assessed. A pig model ( n = 16) of extended partial hepatectomy was established that included continuous observation for 24 h under general anesthesia. Pigs were randomly separated into two groups, one with a portal flow reduction of 70% compared with preoperative values, and the other as a control ( n = 8, each). In controls, portal flow [mean (SD)] increased from 74 (8) mL·min−1·100 g−1 preoperatively to 240 (48) mL·min−1·100 g−1 at 6 h after resection ( P < 0.001). Hepatic arterial buffer response was abolished after resection. Oxygen uptake per unit liver mass increased from 4.0 (1.1) mL·min−1·100 g−1 preoperatively to 7.7 (1.7) mL·min−1·100 g−1 8 h after resection ( P = 0.004). Despite this increase in relative oxygen uptake, total hepatic oxygen consumption (V̇o2) was not maintained, and markers of hypoxia and anaerobic metabolism were significantly increased in hepatocytes after resection. Reduced postoperative portal flow was associated with significantly decreased levels of aspartate aminotransferase and bilirubin and increased hepatic clearance of indocyanine green. In conclusion, major liver resection was associated with persistent portal hyperperfusion, loss of the hepatic arterial buffer response, decreased total hepatic V̇o2 and with increased anaerobic metabolism. Portal flow modulation by partial portal vein occlusion attenuated liver injury after extended liver resection.

NEW & NOTEWORTHY Because of continuous monitoring, the experiments allow precise observation of the influence of liver resection on systemic and local abdominal hemodynamic alterations and oxygen metabolism. Major liver resection is associated with significant and persistent portal hyperperfusion and loss of hepatic arterial buffer response. The correlation of portal hyperperfusion and parameters of liver injury and dysfunction offers a novel therapeutic option to attenuate liver injury after extended liver resection.
Heme oxygenase-2 protects against ischemic acute kidney injury: influence of age and sex
Authors: Nath Karl A. , Garovic Vesna D. , Grande Joseph P. , Croatt Anthony J. , Ackerman Allan W. , Farrugia Gianrico , Katusic Zvonimir S. , Belcher John D. , Vercellotti Gregory M.
Published: June 2019

Heme oxygenase (HO) activity is exhibited by inducible (HO-1) and constitutive (HO-2) proteins. HO-1 protects against ischemic and nephrotoxic acute kidney injury (AKI). We have previously demonstrated that HO-2 protects against heme protein-induced AKI. The present study examined whether HO-2 is protective in ischemic AKI. Renal ischemia was imposed on young and aged HO-2+/+ and HO-2−/− mice. On days 1 and 2 after renal ischemia, there were no significant differences in renal function between young male HO-2+/+ and HO-2−/− mice, between young female HO-2+/+ and HO-2−/− mice, or between aged female HO-2+/+ and HO-2−/− mice. However, in aged male mice, HO-2 deficiency worsened renal function on days 1 and 2 after ischemic AKI, and, on day 2 after ischemia, such deficiency augmented upregulation of injury-related genes and worsened histological injury. Renal HO activity was markedly decreased in unstressed aged male HO-2−/− mice and remained so after ischemia, despite exaggerated HO-1 induction in HO-2−/− mice after ischemia. Such exacerbation of deficiency of HO-2 protein and HO activity may reflect phosphorylated STAT3, as activation of this proinflammatory transcription factor was accentuated early after ischemia in aged male HO-2−/− mice. This exacerbation may not reflect impaired induction of nephroprotectant genes, since the induction of HO-1, sirtuin 1, and β-catenin was accentuated in aged male HO-2−/− mice after ischemia. We conclude that aged male mice are hypersensitive to ischemic AKI and that HO-2 mitigates such sensitivity. We speculate that this protective effect of HO-2 may be mediated, at least in part, by suppression of phosphorylated STAT3-dependent signaling.
Effects of reactive oxygen species on renal tubular transport
Authors: Gonzalez-Vicente Agustin , Hong Nancy , Garvin Jeffrey L.
Published: June 2019

Reactive oxygen species (ROS) play a critical role in regulating nephron transport both via transcellular and paracellular pathways under physiological and pathological circumstances. Here, we review the progress made in the past ~10 yr in understanding how ROS regulate solute and water transport in individual nephron segments. Our knowledge in this field is still rudimentary, with basic information lacking. This is most obvious when looking at the reported disparate effects of superoxide ([Formula: see text]) and H2O2 on proximal nephron transport, where there are no easy explanations as to how to reconcile the data. Similarly, we know almost nothing about the regulation of transport in thin descending and ascending limbs, information that is likely critical to understanding the urine concentrating mechanism. In the thick ascending limb, there is general agreement that ROS enhance transcellular reabsorption of NaCl, but we know very little about their effects on the paracellular pathway and therefore Ca2+ and Mg2+ transport. In the distal convoluted tubule, precious little is known. In the collecting duct, there is general agreement that ROS stimulate the epithelial Na+ channel.
The rhythm of memory: how breathing shapes memory function
Authors: Heck Detlef H. , Kozma Robert , Kay Leslie M.
Published: June 2019

The mammalian olfactory bulb displays a prominent respiratory rhythm, which is linked to the sniff cycle and is driven by sensory input from olfactory receptors in the nasal sensory epithelium. In rats and mice, respiratory frequencies occupy the same band as the hippocampal θ-rhythm, which has been shown to be a key player in memory processes. Hippocampal and olfactory bulb rhythms were previously found to be uncorrelated except in specific odor-contingency learning circumstances. However, many recent electrophysiological studies in both rodents and humans reveal a surprising cycle-by-cycle influence of nasal respiration on neuronal activity throughout much of the cerebral cortex beyond the olfactory system, including the prefrontal cortex, hippocampus, and subcortical structures. In addition, respiratory phase has been shown to influence higher-frequency oscillations associated with cognitive functions, including attention and memory, such as the power of γ-rhythms and the timing of hippocampal sharp wave ripples. These new findings support respiration’s role in cognitive function, which is supported by studies in human subjects, in which nasal respiration has been linked to memory processes. Here, we review recent reports from human and rodent experiments that link respiration to the modulation of memory function and the neurophysiological processes involved in memory in rodents and humans. We argue that respiratory influence on the neuronal activity of two key memory structures, the hippocampus and prefrontal cortex, provides a potential neuronal mechanism behind respiratory modulation of memory.
New advances regarding adaptation of the vestibulo-ocular reflex
Authors: Schubert Michael C. , Migliaccio Americo A.
Published: June 2019

This is a review summarizing the development of vestibulo-ocular reflex (VOR) adaptation behavior with relevance to rehabilitation over the last 10 years and examines VOR adaptation using head-on-body rotations, specifically the influence of training target contrast, position and velocity error signal, active vs. passive head rotations, and sinusoidal vs. head impulse rotations. This review discusses optimization of the single VOR adaptation training session, consolidation between repeated training sessions, and dynamic incremental VOR adaptation. Also considered are the effects of aging and the roles of the efferent vestibular system, cerebellum, and otoliths on angular VOR adaptation. Finally, this review examines VOR adaptation findings in studies using whole body rotations.
Pairing vagus nerve stimulation with tones drives plasticity across the auditory pathway
Authors: Borland Michael S. , Vrana Will A. , Moreno Nicole A. , Fogarty Elizabeth A. , Buell Elizabeth P. , Vanneste Sven , Kilgard Michael P. , Engineer Crystal T.
Published: June 2019

Previous studies have demonstrated that pairing vagus nerve stimulation (VNS) with sounds can enhance the primary auditory cortex (A1) response to the paired sound. The neural response to sounds following VNS-sound pairing in other subcortical and cortical auditory fields has not been documented. We predicted that VNS-tone pairing would increase neural responses to the paired tone frequency across the auditory pathway. In this study, we paired VNS with the presentation of a 9-kHz tone 300 times a day for 20 days. We recorded neural responses to tones from 2,950 sites in the inferior colliculus (IC), A1, anterior auditory field (AAF), and posterior auditory field (PAF) 24 h after the last pairing session in anesthetized rats. We found that VNS-tone pairing increased the percentage of IC, A1, AAF, and PAF that responds to the paired tone frequency. Across all tested auditory fields, the response strength to tones was strengthened in VNS-tone paired rats compared with control rats. VNS-tone pairing reduced spontaneous activity, frequency selectivity, and response threshold across the auditory pathway. This is the first study to document both cortical and subcortical plasticity following VNS-sound pairing. Our findings suggest that VNS paired with sound presentation is an effective method to enhance auditory processing.

NEW & NOTEWORTHY Previous studies have reported primary auditory cortex plasticity following vagus nerve stimulation (VNS) paired with a sound. This study extends previous findings by documenting that fields across the auditory pathway are altered by VNS-tone pairing. VNS-tone pairing increases the percentage of each field that responds to the paired tone frequency. This is the first study to document both cortical and subcortical plasticity following VNS-sound pairing.
Performance Analysis for Downlink MIMO-NOMA in Millimeter Wave Cellular Network with D2D Communications
Authors: Li Jianguo , Li Xiangming , Wang Aihua , Ye Neng
Published: June 2019

Enabling nonorthogonal multiple access (NOMA) in device-to-device (D2D) communications under the millimeter wave (mmWave) multiple-input multiple-output (MIMO) cellular network is of critical importance for 5G wireless systems to support low latency, high reliability, and high throughput radio access. In this paper, the closed-form expressions for the outage probability and the ergodic capacity in downlink MIMO-NOMA mmWave cellular network with D2D communications are considered, which indicates that NOMA outperforms TDMA. The influencing factors of performance, such as transmission power and antenna number, are also analyzed. It is found that higher transmission power and more antennas in the base station can decrease the outage probability and enhance the ergodic capacity of NOMA.