Reactivation of a silenced H19 gene in human rhabdomyosarcoma by demethylation of DNA but not by histone hyperacetylation

BACKGROUND: The active copy of the imprinted gene H19 is turned off by inappropriate methylation in several pediatric tumors including Wilms' Tumour and embryonal rhabdomyosarcoma. H19 controls in cis the linked Insulin-like Growth Factor 2 (IGF2) gene, encoding an important growth factor. Recent work has suggested that methylation of a gene may lead to deacetylation of its associated histones and that silenced genes can be reactivated by increasing histone acetylation levels. RESULTS: Treatment of a rhabdomyosarcoma cell line which has a silent, methylated H19 gene with histone deacetylase (HDAC) inhibitors under conditions which gave maximal hyperacetylation of histone 4, both globally and at the H19 gene itself could not reactivate H19 or affect the active Insulin-like Growth Factor 2 (IGF2) gene, but caused clear up-regulation of the Tissue-type Plasminogen Activator (TPA) gene, a non-imprinted gene known to respond to changes in histone acetylation. In contrast, mild treatment of the cells with the methylation inhibitor 5-AzaC-2'-deoxycytidine (AzaC) on its own was able to reactivate H19. Combining AzaC treatment with HDAC inhibitors gave a reduced rather than enhanced reactivation. These findings were confirmed in mouse primary liver and kidney explants which maintain normal imprinting, where we also found that the silent Igf2 gene could not be reactivated by HDAC inhibitors. CONCLUSION: These results suggest that DNA methylation rather than histone acetylation is the primary determinant of silencing of H19 in rhabdomyosarcoma

Who, What, Where: an analysis of private sector family planning provision in 57 low- and middle-income countries.

OBJECTIVE: Family planning service delivery has been neglected; rigorous analyses of the patterns of contraceptive provision are needed to inform strategies to address this neglect. METHODS: We used 57 nationally representative Demographic and Health Surveys in low- and middle-income countries (2000-2013) in four geographic regions to estimate need for contraceptive services, and examined the sector of provision, by women's socio-economic position. We also assessed method mix and whether women were informed of side effects. RESULTS: Modern contraceptive use among women in need was lowest in sub-Saharan Africa (39%), with other regions ranging from 64% to 72%. The private sector share of the family planning market was 37-39% of users across the regions and 37% overall (median across countries: 41%). Private sector users accessed medical providers (range across regions: 30-60%, overall mean: 54% and median across countries 23%), specialised drug sellers (range across regions: 31-52%, overall mean: 36% and median across countries: 43%) and retailers (range across regions: 3-14%, overall mean: 6% and median across countries: 6%). Private retailers played a more important role in sub-Saharan Africa (14%) than in other regions (3-5%). NGOs and FBOs served a small percentage. Privileged women (richest wealth quintile, urban residents or secondary-/tertiary-level education) used private sector services more than the less privileged. Contraceptive method types with higher requirements (medical skills) for provision were less likely to be acquired from the private sector, while short-acting methods/injectables were more likely. The percentages of women informed of side effects varied by method and provider subtype, but within subtypes were higher among public than private medical providers for four of five methods assessed. CONCLUSION: Given the importance of private sector providers, we need to understand why women choose their services, what quality services the private sector provides, and how it can be improved. However, when prioritising one of the two sectors (public vs. private), it is critical to consider the potential impact on contraceptive prevalence and equity of met need

Calcitonin Gene Peptides: The Diagnostic Value of Measurement in Medullary Thyroid Carcinoma

The calcitonin gene encodes a family of peptides, at least three of which normally circulate in man: calcitonin (CT), a calcium-lowering hormone; katacalcin (KC), a peptide of unknown function; and calcitonin gene-related peptide (CGRP), a neuropeptide and potent vasodilator. In a study of 45 patients with medullary thyroid carcinoma (MTC), plasma CGRP was elevated in approximately 50% of cases. Furthermore, CGRP levels did not correlate with CT levels. However, plasma KC was elevated in all cases, with a good correlation with CT levels, as has been noted previously. Measurement of CT or KC appears to be superior to measurement of CGRP for the detection of MTC

Treatment, Services and Follow-up for Victims of Family Violence in Health Clinics in Maputo, Mozambique

Background: Family violence (FV) is a global health problem that not only impacts the victim, but the family unit, local community and society at large.Objective: To quantitatively and qualitatively evaluate the treatment and follow up provided to victims of violence amongst immediate and extended family units who presented to three health centers in Mozambique for care following violence.Methods: We conducted a verbally-administered survey to self-disclosed victims of FV who presented to one of three health units, each at a different level of service, in Mozambique for treatment of their injuries. Data were entered into SPSS (SPSS, version 13.0) and analyzed for frequencies. Qualitative short answer data were transcribed during the interview, coded and analyzed prior to translation by the principal investigator.Results: One thousand two hundred and six assault victims presented for care during the eight-week study period, of which 216 disclosed the relationship of the assailant, including 92 who were victims of FV. Almost all patients (90%) waited less than one hour to be seen, with most patients (67%) waiting less than 30 minutes. Most patients did not require laboratory or radiographic diagnostics at the primary (70%) and secondary (93%) health facilities, while 44% of patients received a radiograph at the tertiary care center. Among all three hospitals, only 10% were transferred to a higher level of care, 14% were not given any form of follow up or referral information, while 13% required a specialist evaluation. No victims were referred for psychological follow-up or support. Qualitative data revealed that some patients did not disclose violence as the etiology, because they believed the physician was unable to address or treat the violence-related issues and/or had limited time to discuss.Conclusion: Healthcare services for treating the physical injuries of victims of FV were timely and rarely required advanced levels of medical care, but there were no psychological services or follow-up referrals for violence victims. The healthcare environment at all three surveyed health centers in Mozambique does not encourage disclosure or self-report of FV. Policies and strategies need to be implemented to encourage patient disclosure of FV and provide more health system-initiated victim resources. [West J Emerg Med. 2011;12(3):348-353.

Asymmetric Unification: A New Unification Paradigm for Cryptographic Protocol Analysis

The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-642-38574-2_16We present a new paradigm for unification arising out of a technique commonly used in cryptographic protocol analysis tools that employ unification modulo equational theories. This paradigm relies on: (i) a decomposition of an equational theory into (R,E) where R is confluent, terminating, and coherent modulo E, and (ii) on reducing unification problems to a set of problems s=?ts=?t under the constraint that t remains R/E-irreducible. We call this method asymmetric unification. We first present a general-purpose generic asymmetric unification algorithm. and then outline an approach for converting special-purpose conventional unification algorithms to asymmetric ones, demonstrating it for exclusive-or with uninterpreted function symbols. We demonstrate how asymmetric unification can improve performanceby running the algorithm on a set of benchmark problems. We also give results on the complexity and decidability of asymmetric unification.S. Escobar and S. Santiago were partially supported by EU (FEDER) and the Spanish MEC/MICINN under grant TIN 2010-21062-C02-02, and by Generalitat Valenciana PROMETEO2011/052. The following authors were partially supported by NSF: S. Escobar, J. Meseguer, and R. Sasse under CNS 09-04749 and CCF 09- 05584; D. Kapur under CNS 09-05222; C. Lynch, Z. Liu, and C. Meadows under CNS 09-05378, and P. Narendran and S. Erbatur under CNS 09-05286. Part of the S. Erbatur’s work was supported while with the Department of Computer Science, University at Albany, and part of R. Sasse’s work was supported while with the Department of Computer Science, University of Illinois at Urbana-Champaign.Erbatur, S.; Escobar Román, S.; Kapur, D.; Liu, Z.; Lynch, CA.; Meadows, C.; Meseguer, J.... (2013). Asymmetric Unification: A New Unification Paradigm for Cryptographic Protocol Analysis. En Automated Deduction – CADE-24. Springer. 231-248. https://doi.org/10.1007/978-3-642-38574-2_16S231248IEEE 802.11 Local and Metropolitan Area Networks: Wireless LAN Medium Access Control (MAC) and Physical (PHY) Specifications (1999)Basin, D., Mödersheim, S., Viganò, L.: An on-the-fly model-checker for security protocol analysis. In: Snekkenes, E., Gollmann, D. (eds.) ESORICS 2003. LNCS, vol. 2808, pp. 253–270. Springer, Heidelberg (2003)Blanchet, B.: An efficient cryptographic protocol verifier based on Prolog rules. In: CSFW, pp. 82–96. IEEE Computer Society (2001)Bürckert, H.-J., Herold, A., Schmidt-Schauß, M.: On equational theories, unification, and (un)decidability. Journal of Symbolic Computation 8(1/2), 3–49 (1989)Comon-Lundh, H., Delaune, S.: The finite variant property: How to get rid of some algebraic properties. In: Giesl, J. (ed.) RTA 2005. LNCS, vol. 3467, pp. 294–307. Springer, Heidelberg (2005)Durán, F., Meseguer, J.: A Maude coherence checker tool for conditional order-sorted rewrite theories. In: Ölveczky, P.C. (ed.) WRLA 2010. LNCS, vol. 6381, pp. 86–103. Springer, Heidelberg (2010)Erbatur, S., Escobar, S., Kapur, D., Liu, Z., Lynch, C., Meadows, C., Meseguer, J., Narendran, P., Santiago, S., Sasse, R.: Effective symbolic protocol analysis via equational irreducibility conditions. In: Foresti, S., Yung, M., Martinelli, F. (eds.) ESORICS 2012. LNCS, vol. 7459, pp. 73–90. Springer, Heidelberg (2012)Erbatur, S., Escobar, S., Kapur, D., Liu, Z., Lynch, C., Meadows, C., Meseguer, J., Narendran, P., Sasse, R.: Asymmetric unification: A new unification paradigm for cryptographic protocol analysis. In: UNIF 2011 (2011), https://sites.google.com/a/cs.uni.wroc.pl/unif-2011/programEscobar, S., Sasse, R., Meseguer, J.: Folding variant narrowing and optimal variant termination. J. Log. Algebr. Program. 81(7-8), 898–928 (2012)Harju, T., Karhumäki, J., Krob, D.: Remarks on generalized post correspondence problem. In: Puech, C., Reischuk, R. (eds.) STACS 1996. LNCS, vol. 1046, pp. 39–48. Springer, Heidelberg (1996)Hopcroft, J.E., Motwani, R., Ullman, J.D.: Introduction to automata theory, languages, and computation - international edition, 2nd edn. Addison-Wesley (2003)Jouannaud, J.-P., Kirchner, H.: Completion of a set of rules modulo a set of equations. SIAM J. Comput. 15(4), 1155–1194 (1986)Liu, Z., Lynch, C.: Efficient general unification for XOR with homomorphism. In: Bjørner, N., Sofronie-Stokkermans, V. (eds.) CADE 2011. LNCS, vol. 6803, pp. 407–421. Springer, Heidelberg (2011)Liu, Z.: Dealing Efficiently with Exclusive OR, Abelian Groups and Homomorphism in Cryptographic Protocol Analysis. PhD thesis, Clarkson University (2012), http://people.clarkson.edu/~clynch/papers/Dissertation_of_Zhiqiang_Liu.pdfLowe, G., Roscoe, A.W.R.: Using CSP to detect errors in the TMN protocol. IEEE Transactions on Software Engineering 23, 659–669 (1997)Meseguer, J.: Conditional rewriting logic as a united model of concurrency. Theor. Comput. 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Taking stock: protocol for evaluating a family planning supply chain intervention in Senegal.

BACKGROUND: In Senegal, only 12% of women of reproductive age in union (WRAU) were using contraceptives and another 29% had an unmet need for contraceptives in 2010-11. One potential barrier to accessing contraceptives is the lack of stock availability in health facilities where women seek them. Multiple supply chain interventions have been piloted in low- and middle-income countries with the aim of improving contraceptive availability in health facilities. However, there is limited evidence on the effect of these interventions on contraceptive availability in facilities, and in turn on family planning use in the population. This evaluation protocol pertains to a supply chain intervention using performance-based contracting for contraceptive distribution that was introduced throughout Senegal between 2012 and 2015. METHODS: This multi-disciplinary research project will include quantitative, qualitative and economic evaluations. Trained researchers in the different disciplines will implement the studies separately but alongside each other, sharing findings throughout the project to inform each other's data collection. A non-randomised study with stepped-wedge design will be used to estimate the effect of the intervention on contraceptive stock availability in health facilities, and on the modern contraceptive prevalence rate among women in Senegal, compared to the current pull-based distribution model used for other commodities. Secondary data from annual Service Provision Assessments and Demographic and Health Surveys will be used for this study. Data on stock availability and monthly family planning consultations over a 4-year period will be collected from 200 health facilities in five regions to perform time series analyses. A process evaluation will be conducted to understand the extent to which the intervention was implemented as originally designed, the acceptability of third-party logisticians within the health system and potential unintended consequences. These will be assessed using monthly indicator data from the implementer and multiple ethnographic methods, including in-depth interviews with key informants and stakeholders at all levels of the distribution system, observations of third-party logisticians and clinic diaries. An economic evaluation will estimate the cost of the intervention, as well as its cost-effectiveness compared to the current supply chain model. DISCUSSION: Given the very limited evidence base, there is an important need for a comprehensive standardised approach to evaluating supply chain management, and distribution specifically. This evaluation will help address this evidence gap by providing rigorous evidence on whether private performance-based contracting for distribution of contraceptives can contribute to improving access to family planning in low- and middle-income countries

Breast cancer in lesbians and bisexual women: Systematic review of incidence, prevalence and risk studies

This article is made available through the Brunel Open Access Publishing Fund. © 2013 Meads and Moore; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: The UK Parliamentary Enquiry and USA Institute of Medicine state that lesbians may be at a higher risk of breast cancer but there is insufficient information. Lesbians and bisexual (LB) women have behavioural risk-factors at higher rates compared to heterosexuals such as increased alcohol intake and higher stress levels. Conversely, breast cancer rates are higher in more affluent women yet income levels in LB women are relatively low. This systematic review investigated all evidence on whether there is, or likely to be, higher rates of breast cancer in LB women. Methods: Cochrane library (CDSR, CENTRAL, HTA, DARE, NHSEED), MEDLINE, EMBASE, PsychINFO, CAB abstracts, Web of Science (SCI, SSCI), SIGLE and Social Care Online databases were searched to October 2013. Unpublished research and specific lesbian, gay and bisexual websites were checked, as were citation lists of relevant papers. Included were studies in LB populations reporting breast cancer incidence or prevalence rates, risk model results or risk-factor estimates. Inclusions, data-extraction and quality assessment were by two reviewers with disagreements resolved by discussion. Results: Searches found 198 references. No incidence rates were found. Nine studies gave prevalence estimates - two showed higher, four showed no differences, one showed mixed results depending on definitions, one had no comparison group and one gave no sample size. All studies were small with poor methodological and/or reporting quality. One incidence modelling study suggested a higher rate. Four risk modelling studies were found, one Rosner-Colditz and three Gail models. Three suggested higher and one lower rate in LB compared to heterosexual women. Six risk-factor estimates suggested higher risk and one no difference between LB and heterosexual women. Conclusions: The only realistic way to establish rates in LB women would be to collect sexual orientation within routine statistics, including cancer registry data, or from large cohort studies

Gridded and direct Epoch of Reionisation bispectrum estimates using the Murchison Widefield Array

We apply two methods to estimate the 21~cm bispectrum from data taken within the Epoch of Reionisation (EoR) project of the Murchison Widefield Array (MWA). Using data acquired with the Phase II compact array allows a direct bispectrum estimate to be undertaken on the multiple redundantly-spaced triangles of antenna tiles, as well as an estimate based on data gridded to the $uv$-plane. The direct and gridded bispectrum estimators are applied to 21 hours of high-band (167--197~MHz; $z$=6.2--7.5) data from the 2016 and 2017 observing seasons. Analytic predictions for the bispectrum bias and variance for point source foregrounds are derived. We compare the output of these approaches, the foreground contribution to the signal, and future prospects for measuring the bispectra with redundant and non-redundant arrays. We find that some triangle configurations yield bispectrum estimates that are consistent with the expected noise level after 10 hours, while equilateral configurations are strongly foreground-dominated. Careful choice of triangle configurations may be made to reduce foreground bias that hinders power spectrum estimators, and the 21~cm bispectrum may be accessible in less time than the 21~cm power spectrum for some wave modes, with detections in hundreds of hours.Comment: 19 pages, 10 figures, accepted for publication in PAS

Review-Electrode Kinetics and Electrolyte Stability in Vanadium Flow Batteries

Two aspects of vanadium flow batteries are reviewed: electrochemical kinetics on carbon electrodes and positive electrolyte stability. There is poor agreement between reported values of kinetic parameters; however, most authors report that kinetic rates are faster for VIV/VV than for VII/VIII. Cycling the electrode potential increases the rates of both reactions initially due to roughening but when no further roughening is observed, the VII/VIII and VIV/VV reactions are affected oppositely by the pretreatment potential. Anodic pretreatment activates the electrode for the VII/VIII reaction, and deactivates it for VIV/VV. Three states of the carbon surface are suggested: reduced and oxidized states R and O, respectively, both with low electrocatalytic activity, and an intermediate state M with higher activity. The role of surface functional groups and the mechanisms of electron transfer for the VII/VIII and VIV/VV reactions are still not well understood. The induction time for precipitation of V2O5 from positive electrolytes decreases with temperature, showing an Arrhenius-type dependence with an activation energy of 1.79 eV in agreement with DFT calculations based on a VO(OH)3 intermediate. It also decreases exponentially with increasing VV concentration and increases exponentially with increasing sulphate concentration. Both arsenate and phosphate are effective additives for improving thermal stability