The determinants of transverse tubular volume in resting skeletal muscle.

The transverse tubular (t)-system of skeletal muscle couples sarcolemmal electrical excitation with contraction deep within the fibre. Exercise, pathology and the composition of the extracellular fluid (ECF) can alter t-system volume (t-volume). T-volume changes are thought to contribute to fatigue, rhabdomyolysis and disruption of excitation-contraction coupling. However, mechanisms that underlie t-volume changes are poorly understood. A multicompartment, history-independent computer model of rat skeletal muscle was developed to define the minimum conditions for t-volume stability. It was found that the t-system tends to swell due to net ionic fluxes from the ECF across the access resistance. However, a stable t-volume is possible when this is offset by a net efflux from the t-system to the cell and thence to the ECF, forming a net ion cycle ECF→t-system→sarcoplasm→ECF that ultimately depends on Na(+)/K(+)-ATPase activity. Membrane properties that maximize this circuit flux decrease t-volume, including PNa(t) > PNa(s), PK(t) < PK(s) and N(t) < N(s) [P, permeability; N, Na(+)/K(+)-ATPase density; (t), t-system membrane; (s), sarcolemma]. Hydrostatic pressures, fixed charges and/or osmoles in the t-system can influence the magnitude of t-volume changes that result from alterations in this circuit flux. Using a parameter set derived from literature values where possible, this novel theory of t-volume was tested against data from previous experiments where t-volume was measured during manipulations of ECF composition. Predicted t-volume changes correlated satisfactorily. The present work provides a robust, unifying theoretical framework for understanding the determinants of t-volume.JAF was supported by a David Phillips Fellowship (BB/FO23863/1) awarded by the Biotechnology and Biological Sciences Research Council (UK). JS was supported by the Agency for Science, Technology and Research (Singapore) and a Caius Medical Association summer studentship from Gonville and Caius College, University of Cambridge.This is the final version. It was first published by Wiley at http://onlinelibrary.wiley.com/doi/10.1113/jphysiol.2014.281170/abstract

Radiomics-Based Texture Analysis of Ga-68-DOTATATE Positron Emission Tomography and Computed Tomography Images as a Prognostic Biomarker in Adults With Neuroendocrine Cancers Treated With Lu-177-DOTATATE

Purpose: Neuroendocrine tumors (NET) are rare cancers with variable behavior. A better understanding of prognosis would aid individualized management. The aim of this hypothesis-generating pilot study was to investigate the prognostic potential of tumor heterogeneity and tracer avidity in NET using texture analysis (TA) of 68Ga-DOTATATE positron emission tomography (PET) and non-enhanced computed tomography (CT) performed at baseline in patients treated with 177Lu-DOTATATE. It aims to justify a larger-scale study to evaluate its clinical value. Methods: The pretherapy 68Ga-DOTATATE PET-CT scans of 44 patients with metastatic NET (carcinoid, pancreatic, thyroid, head and neck, catecholamine-secreting, and unknown primary NET) treated with 177Lu-DOTATATE were analyzed retrospectively using commercially available texture analysis research software. Image filtration extracted and enhanced objects of different sizes (fine, medium, coarse), then quantified heterogeneity by statistical and histogram-based parameters (mean intensity, standard deviation, entropy, mean of positive pixels, skewness, and kurtosis). Regions of interest were manually drawn around up to five of the most 68Ga-DOTATATE avid lesions for each patient. 68Gallium uptake on PET was quantified as SUVmax and SUVmean. Associations between imaging and clinical markers with progression-free (PFS) and overall survival (OS) were assessed using univariate Kaplan-Meier analysis. Independence of the significant univariate markers of survival was tested using multivariate Cox regression analysis. Results: Measures of heterogeneity (higher kurtosis, higher entropy, and lower skewness) on coarse-texture scale CT and unfiltered PET images predicted shorter PFS (CT coarse kurtosis: p=0.05, PET entropy: p=0.01, PET skewness: p=0.03) and shorter OS (CT coarse kurtosis: p=0.05, PET entropy: p=0.01, PET skewness p=0.02). Conventional PET parameters such as SUVmax and SUVmean showed trends towards predicting outcome but were not statistically significant. Multivariate analysis identified that CT-TA (coarse kurtosis: HR=2.57, 95% CI=1.22–5.38, p=0.013) independently predicted PFS, and PET-TA (unfiltered skewness: HR=9.05, 95% CI=1.19–68.91, p=0.033) independently predicted OS. Conclusion: These preliminary data generate a hypothesis that radiomic analysis of neuroendocrine cancer on 68Ga-DOTATATE PET-CT may be of prognostic value and a valuable addition to the assessment of patients

Insights from echocardiography, magnetic resonance imaging, and microcomputed tomography relative to the mid-myocardial left ventricular echogenic zone.

Background: The anatomical substrate for the mid-mural ventricular hyperechogenic zone remains uncertain, but it may represent no more than ultrasound reflected from cardiomyocytes orientated orthogonally to the ultrasonic beam. We sought to ascertain the relationship between the echogenic zone and the orientation of the cardiomyocytes. Methods: We used 3D echocardiography, diffusion tensor imaging, and microcomputed tomography to analyze the location and orientation of cardiomyocytes within the echogenic zone. Results: We demonstrated that visualization of the echogenic zone is dependent on the position of the transducer and is most clearly seen from the apical window. Diffusion tensor imaging and microcomputed tomography show that the echogenic zone seen from the apical window corresponds to the position of the circumferentially orientated cardiomyocytes. An oblique band seen in the parasternal view relates to cardiomyocytes orientated orthogonally to the ultrasonic beam. Conclusions: The mid-mural ventricular hyperechogenic zone represents reflected ultrasound from cardiomyocytes aligned orthogonal to the ultrasonic beam. The echogenic zone does not represent a space, a connective tissue sheet, a boundary between ascending and descending limbs of a hypothetical helical ventricular myocardial band, nor an abrupt change in cardiomyocyte orientation

Insights from echocardiography, magnetic resonance imaging, and microcomputed tomography relative to the mid-myocardial left ventricular echogenic zone.

BACKGROUND: The anatomical substrate for the mid-mural ventricular hyperechogenic zone remains uncertain, but it may represent no more than ultrasound reflected from cardiomyocytes orientated orthogonally to the ultrasonic beam. We sought to ascertain the relationship between the echogenic zone and the orientation of the cardiomyocytes. METHODS: We used 3D echocardiography, diffusion tensor imaging, and microcomputed tomography to analyze the location and orientation of cardiomyocytes within the echogenic zone. RESULTS: We demonstrated that visualization of the echogenic zone is dependent on the position of the transducer and is most clearly seen from the apical window. Diffusion tensor imaging and microcomputed tomography show that the echogenic zone seen from the apical window corresponds to the position of the circumferentially orientated cardiomyocytes. An oblique band seen in the parasternal view relates to cardiomyocytes orientated orthogonally to the ultrasonic beam. CONCLUSIONS: The mid-mural ventricular hyperechogenic zone represents reflected ultrasound from cardiomyocytes aligned orthogonal to the ultrasonic beam. The echogenic zone does not represent a space, a connective tissue sheet, a boundary between ascending and descending limbs of a hypothetical helical ventricular myocardial band, nor an abrupt change in cardiomyocyte orientation

Getting into hot water:sick guppies frequent warmer thermal conditions

Ectotherms depend on the environmental temperature for thermoregulation and exploit thermal regimes that optimise physiological functioning. They may also frequent warmer conditions to up-regulate their immune response against parasite infection and/or impede parasite development. This adaptive response, known as ‘behavioural fever’, has been documented in various taxa including insects, reptiles and fish, but only in response to endoparasite infections. Here, a choice chamber experiment was used to investigate the thermal preferences of a tropical freshwater fish, the Trinidadian guppy (Poecilia reticulata), when infected with a common helminth ectoparasite Gyrodactylus turnbulli, in female-only and mixed-sex shoals. The temperature tolerance of G. turnbulli was also investigated by monitoring parasite population trajectories on guppies maintained at a continuous 18, 24 or 32 °C. Regardless of shoal composition, infected fish frequented the 32 °C choice chamber more often than when uninfected, significantly increasing their mean temperature preference. Parasites maintained continuously at 32 °C decreased to extinction within 3 days, whereas mean parasite abundance increased on hosts incubated at 18 and 24 °C. We show for the first time that gyrodactylid-infected fish have a preference for warmer waters and speculate that sick fish exploit the upper thermal tolerances of their parasites to self medicate

Research opportunities for argumentation in social networks

Nowadays, many websites allow social networking between their users in an explicit or implicit way. In this work, we show how argumentation schemes theory can provide a valuable help to formalize and structure on-line discussions and user opinions in decision support and business oriented websites that held social networks between their users. Two real case studies are studied and analysed. Then, guidelines to enhance social decision support and recommendations with argumentation are provided.This work summarises results of the authors joint research, funded by an STMS of the Agreement Technologies COST Action 0801, by the Spanish government grants [CONSOLIDER-INGENIO 2010 CSD2007-00022, and TIN2012-36586-C03-01] and by the GVA project [PROMETEO 2008/051].Heras Barberá, SM.; Atkinson, KM.; Botti Navarro, VJ.; Grasso, F.; Julian Inglada, VJ.; Mcburney, PJ. (2013). Research opportunities for argumentation in social networks. Artificial Intelligence Review. 39(1):39-62. doi:10.1007/s10462-012-9389-0S3962391Amgoud L (2009) Argumentation for decision making. Argumentation in artificial intelligence. Springer, BerlinAnderson P (2007) What is Web 2.0? Ideas, technologies and implications for education. JISC Iechnology and Standards Watch reportBentahar J, Meyer CJJ, Moulin B (2007) Securing agent-oriented systems: an argumentation and reputation-based approach. In: Proceedings of the 4th international conference on information technology: new generations (ITNG 2007), IEEE Computer Society, pp 507–515Buckingham Shum S (2008) Cohere: towards Web 2.0 argumentation. In: Proceedings of the 2nd international conference on computational models of argument, COMMA, pp 28–30Burke R (2002) Hybrid recommender systems: survey and experiments. User Model User-Adapt Interact 12:331–370Cartwright D, Atkinson K (2008) Political engagement through tools for argumentation. In: Proceedings of the second international conference on computational models of argument (COMMA 2008), pp 116–127Chesñevar C, McGinnis J, Modgil S, Rahwan I, Reed C, Simari G, South M, Vreeswijk G, Willmott S (2006) Towards an argument interchange format. Knowl Eng Rev 21(4):293–316Chesñevar CI, Maguitman AG, Gonzàlez MP (2009) Empowering recommendation technologies through argumentation. Argumentation in artificial intelligence. Springer, Berlin, pp 403–422García AJ, Dix J, Simari GR (2009) Argument-based logic programming. Argumentation in artificial intelligence. Springer, BerlinGolbeck J (2006) Generating predictive movie recommendations from trust in social networks. In: Proceedings of the fourth international conference on trust management, LNCS, vol 3986, 93–104Gordon T, Prakken H, Walton D (2007) The Carneades model of argument and burden of proof. Artif Intell 171(10–15):875–896Guha R, Kumar R, Raghavan P, Tomkins A (2004) Propagating trust and distrust. In: Proceedings of the 13th international conference on, World Wide Web, pp 403–412Heras S, Navarro M, Botti V, Julián V (2009) Applying dialogue games to manage recommendation in social networks. In: Proceedings of the 6th international workshop on argumentation in multi-agent aystems, ArgMASHeras S, Atkinson K, Botti V, Grasso F, Julián V, McBurney P (2010a) How argumentation can enhance dialogues in social networks. In: Proceedings of the 3rd international conference on computational models of argument, COMMA, vol 216, pp 267–274Heras S, Atkinson K, Botti V, Grasso F, Julián V, McBurney P (2010b) Applying argumentation to enhance dialogues in social networks. In: ECAI 2010 workshop on computational models of natural argument, CMNA, pp 10–17Karacapilidis N, Tzagarakis M (2007) Web-based collaboration and decision making support: a multi-disciplinary approach. Web-Based Learn Teach Technol 2(4):12–23Kim D, Benbasat I (2003) Trust-related arguments in internet stores: a framework for evaluation. J Electron Commer Res 4(2):49–64Kim D, Benbasat I (2006) The effects of trust-assuring arguments on consumer trust in internet stores: application of Toulmin’s model of argumentation. Inf Syst Rese 17(3):286–300Laera L, Tamma V, Euzenat J, Bench-Capon T, Payne T (2006) Reaching agreement over ontology alignments. In: Proceedings of the 5th international semantic web conference (ISWC 2006)Lange C, Bojãrs U, Groza T, Breslin J, Handschuh S (2008) Expressing argumentative discussions in social media sites. In: Social data on the web (SDoW2008) workshop at the 7th international semantic web conferenceLinden G, Smith B, York J (2003) Amazon.com recommendations: item-to-item collaborative filtering. IEEE Internet Comput 7(1):76–80Linden G, Hong J, Stonebraker M, Guzdial M (2009) Recommendation algorithms, online privacy and more. Commun ACM, 52(5)Mika P (2007) Ontologies are us: a unified model of social networks and semantics. J Web Semant 5(1):5–15Montaner M, López B, de la Rosa JL (2002) Opinion-based filtering through trust. In: Cooperative information agents VI, LNCS, vol 2446, pp 127–144Ontañón S, Plaza E (2008) Argumentation-based information exchange in prediction markets. In: Proceedings of the 5th international workshop on argumentation in multi-agent systems, ArgMASPazzani MJ, Billsus D (2007) Content-based recommendation systems. In: The adaptive web, LNCS, vol 4321, pp 325–341Rahwan I, Zablith F, Reed C (2007) Laying the foundations for a world wide argument web. Artif Intell 171(10–15):897–921Rahwan I, Banihashemi B (2008) Arguments in OWL: a progress report. In: Proceedings of the 2nd international conference on computational models of argument (COMMA), pp 297–310Reed C, Walton D (2007) Argumentation schemes in dialogue. In: Dissensus and the search for common ground, OSSA-07, volume CD-ROM, pp 1–11Sabater J, Sierra C (2002) Reputation and social network analysis in multi-agent systems. In: Proceedings of the 1st international joint conference on autonomous agents and multiagent systems, vol 1, pp 475–482Schafer JB, Konstan JA, Riedl J (2001) E-commerce recommendation applications. Data Min Knowl Discov 5:115–153Schafer JB, Frankowski D, Herlocker J, Sen S (2007) Collaborative filtering recommender systems. In: The adaptive web, LNCS, vol 4321, pp 291–324Schneider J, Groza T, Passant A (2012) A review of argumentation for the aocial semantic web. Semantic web-interoperability, usability, applicability. IOS Press, Washington, DCTempich C, Pinto HS, Sure Y, Staab S (2005) An argumentation ontology for distributed, loosely-controlled and evolvInG Engineering processes of oNTologies (DILIGENT). In: Proceedings of the 2nd European semantic web conference, ESWC, pp 241–256Toulmin SE (1958) The uses of argument. Cambridge University Press, Cambridge, UKTrojahn C, Quaresma P, Vieira R, Isaac A (2009) Comparing argumentation frameworks for composite ontology matching. in: Proceedings of the 6th international workshop on argumentation in multi-agent systems, ArgMASTruthMapping. http://truthmapping.com/Walter FE, Battiston S, Schweitzer F (2007) A model of a trust-based recommendation system on a social network. J Auton Agents Multi-Agent Syst 16(1):57–74Walton D, Krabbe E (1995) Commitment in dialogue: basic concepts of interpersonal reasoning. State University of New York Press, New York, NYWalton D, Reed C, Macagno F (2008) Argumentation schemes. Cambridge University Press, CambridgeWells S, Gourlay C, Reed C (2009) Argument blogging. Computational models of natural argument, CMNAWyner A, Schneider J (2012) Arguing from a point of view. 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Ethnic inequalities and pathways to care in psychosis in England: a systematic review and meta-analysis

© The Author(s). 2018Background: As part of a national programme to tackle ethnic inequalities, we conducted a systematic review and meta-analysis of research on ethnic inequalities in pathways to care for adults with psychosis living in England and/or Wales. Methods: Nine databases were searched from inception to 03.07.17 for previous systematic reviews, including forward and backward citation tracking and a PROSPERO search to identify ongoing reviews. We then carried forward relevant primary studies from included reviews (with the latest meta-analyses reporting on research up to 2012), supplemented by a search on 18.10.17 in MEDLINE, Embase, PsycINFO and CINAHL for primary studies between 2012 and 2017 that had not been covered by previous meta-analyses. Results: Forty studies, all conducted in England, were included for our updated meta-analyses on pathways to care. Relative to the White reference group, elevated rates of civil detentions were found for Black Caribbean (OR = 3.43, 95% CI = 2.68 to 4.40, n = 18), Black African (OR = 3.11, 95% CI = 2.40 to 4.02, n = 6), and South Asian patients (OR = 1.50, 95% CI 1.07 to 2.12, n = 10). Analyses of each Mental Health Act section revealed significantly higher rates for Black people under (civil) Section 2 (OR = 1.53, 95% CI = 1.11 to 2.11, n = 3). Rates in repeat admissions were significantly higher than in first admission for South Asian patients (between-group difference p < 0.01). Some ethnic groups had more police contact (Black African OR = 3.60, 95% CI = 2.15 to 6.05, n = 2; Black Caribbean OR = 2.64, 95% CI = 1.88 to 3.72, n = 8) and criminal justice system involvement (Black Caribbean OR = 2.76, 95% CI = 2.02 to 3.78, n = 5; Black African OR = 1.92, 95% CI = 1.32 to 2.78, n = 3). The White Other patients also showed greater police and criminal justice system involvement than White British patients (OR = 1.49, 95% CI = 1.03 to 2.15, n = 4). General practitioner involvement was less likely for Black than the White reference group. No significant variations over time were found across all the main outcomes. Conclusions: Our updated meta-analyses reveal persisting but not significantly worsening patterns of ethnic inequalities in pathways to psychiatric care, particularly affecting Black groups. This provides a comprehensive evidence base from which to inform policy and practice amidst a prospective Mental Health Act reform. Trial registration: CRD42017071663Peer reviewedFinal Published versio

Mobility properties of the Hermes transposable element in transgenic lines of Aedes aegypti

The Hermes transposable element has been used to genetically transform a wide range of insect species, including the mosquito, Aedes aegypti, a vector of several important human pathogens. Hermes integrations into the mosquito germline are characterized by the non-canonical integration of the transposon and flanking plasmid and, once integrated, Hermes is stable in the presence of its transposase. In an effort to improve the post-integration mobility of Hermes in the germline of Ae. aegypti, a transgenic helper Mos1 construct expressing Hermes transposase under the control of a testis-specific promoter was crossed to a separate transgenic strain containing a target Hermes transposon. In less than 1% of the approximately 1,500 progeny from jumpstarter lines analyzed, evidence of putative Hermes germline remobilizations were detected. These recovered transposition events occur through an aberrant mechanism and provide insight into the non-canonical cut-and-paste transposition of Hermes in the germ line of Ae. aegypti

Water quality and planktonic microbial assemblages of isolated wetlands in an agricultural landscape

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Wetlands 31 (2011): 885-894, doi:10.1007/s13157-011-0203-6.Wetlands provide ecosystem services including flood protection, water quality enhancement, food chain support, carbon sequestration, and support regional biodiversity. Wetlands occur in human-altered landscapes, and the ongoing ability of these wetlands to provide ecosystem services is lacking. Additionally, the apparent lack of connection of some wetlands, termed geographically isolated, to permanent waters has resulted in little regulatory recognition. We examined the influence of intensive agriculture on water quality and planktonic microbial assemblages of intermittently inundated wetlands. We sampled 10 reference and 10 agriculturally altered wetlands in the Gulf Coastal Plain of Georgia. Water quality measures included pH, alkalinity, dissolved organic carbon, nutrients (nitrate, ammonium, and phosphate), and filterable solids (dry mass and ash-free dry mass). We measured abundance and relative size distribution of the planktonic microbial assemblage (< 45 μm) using flow cytometry. Water quality in agricultural wetlands was characterized by elevated nutrients, pH, and suspended solids. Autotrophic microbial cells were largely absent from both wetland types. Heterotrophic microbial abundance was influenced by nutrients and suspended matter concentration. Agriculture caused changes in microbial assemblages forming the base of wetland food webs. Yet, these wetlands potentially support important ecological services in a highly altered landscape.Funding was provided by the Joseph W. Jones Ecological Research Center.2012-07-2

Mode equivalence and acceptability of tablet computer-, interactive voice response system-, and paper-based administration of the U.S. National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

Background PRO-CTCAE is a library of items that measure cancer treatment-related symptomatic adverse events (NCI Contracts: HHSN261201000043C and HHSN 261201000063C). The objective of this study is to examine the equivalence and acceptability of the three data collection modes (Web-enabled touchscreen tablet computer, Interactive voice response system [IVRS], and paper) available within the US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measurement system. Methods Participants (n = 112; median age 56.5; 24 % high school or less) receiving treatment for cancer at seven US sites completed 28 PRO-CTCAE items (scoring range 0–4) by three modes (order randomized) at a single study visit. Subjects completed one page (approx. 15 items) of the EORTC QLQ-C30 between each mode as a distractor. Item scores by mode were compared using intraclass correlation coefficients (ICC); differences in scores within the 3-mode crossover design were evaluated with mixed-effects models. Difficulties with each mode experienced by participants were also assessed. Results 103 (92 %) completed questionnaires by all three modes. The median ICC comparing tablet vs IVRS was 0.78 (range 0.55–0.90); tablet vs paper: 0.81 (0.62–0.96); IVRS vs paper: 0.78 (0.60–0.91); 89 % of ICCs were ≥0.70. Item-level mean differences by mode were small (medians [ranges] for tablet vs. IVRS = −0.04 [−0.16–0.22]; tablet vs paper = −0.02 [−0.11–0.14]; IVRS vs paper = 0.02 [−0.07–0.19]), and 57/81 (70 %) items had bootstrapped 95 % CI around the effect sizes within +/−0.20. The median time to complete the questionnaire by tablet was 3.4 min; IVRS: 5.8; paper: 4.0. The proportion of participants by mode who reported “no problems” responding to the questionnaire was 86 % tablet, 72 % IVRS, and 98 % paper. Conclusions Mode equivalence of items was moderate to high, and comparable to test-retest reliability (median ICC = 0.80). Each mode was acceptable to a majority of respondents. Although the study was powered to detect moderate or larger discrepancies between modes, the observed ICCs and very small mean differences between modes provide evidence to support study designs that are responsive to patient or investigator preference for mode of administration, and justify comparison of results and pooled analyses across studies that employ different PRO-CTCAE modes of administration. Trial registration NCT Clinicaltrials.gov identifier: NCT0215863