Block of nicotinic acetylcholine receptors by philanthotoxins is strongly dependent on their subunit composition

Philanthotoxin-433 (PhTX-433) is an active component of the venom from the Egyptian digger wasp, Philanthus triangulum. PhTX-433 inhibits several excitatory ligand-gated ion channels, and to improve selectivity two synthetic analogues, PhTX-343 and PhTX-12, were developed. Previous work showed a 22-fold selectivity of PhTX-12 over PhTX-343 for embryonic muscle-type nicotinic acetylcholine receptors (nAChRs) in TE671 cells. We investigated their inhibition of different neuronal nAChR subunit combinations as well as of embryonic muscle receptors expressed in Xenopus oocytes. Whole-cell currents in response to application of acetylcholine alone or co-applied with PhTX analogue were studied by using two-electrode voltage-clamp. α3β4 nAChRs were most sensitive to PhTX-343 (IC50=12 nM at −80 mV) with α4β4, α4β2, α3β2, α7 and α1β1γδ being 5, 26, 114, 422 and 992 times less sensitive. In contrast α1β1γδ was most sensitive to PhTX-12 along with α3β4 (IC50values of 100 nM) with α4β4, α4β2, α3β2 and α7 being 3, 3, 26 and 49 times less sensitive. PhTX-343 inhibition was strongly voltage-dependent for all subunit combinations except α7, whereas this was not the case for PhTX-12 for which weak voltage dependence was observed. We conclude that PhTX-343 mainly acts as an open-channel blocker of nAChRs with strong subtype selectivity

Exploring the effectiveness of the output-based aid voucher program to increase uptake of gender-based violence recovery services in Kenya: a qualitative evaluation

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: Few studies in Africa have explored in detail the ability of output-based aid (OBA) voucher programs to increase access to gender-based violence recovery (GBVR) services. Methods: A qualitative study was conducted in 2010 and involved: (i) in-depth interviews (IDIs) with health managers, service providers, voucher management agency (VMA) managers and (ii) focus group discussions (FGDs) with voucher users, voucher non-users, voucher distributors and opinion leaders drawn from five program sites in Kenya. Results: The findings showed promising prospects for the uptake of OBA GBVR services among target population. However, a number of factors affect the uptake of the services. These include lack of general awareness of the GBVR services vouchers, lack of understanding of the benefit package, immediate financial needs of survivors, as well as stigma and cultural beliefs that undermine reporting of cases or seeking essential medical services. Moreover, accreditation of only hospitals to offer GBVR services undermines access to the services in rural areas. Poor responsiveness from law enforcement agencies and fear of reprisal from perpetrators also undermine treatment options and access to medical services. Low provider knowledge on GBVR services and lack of supplies also affect effective provision and management of GBVR services. Conclusions: The above findings suggest that there is a need to build the capacity of health care providers and police officers, strengthen the community strategy component of the OBA program to promote the GBVR services voucher, and conduct widespread community education programs aimed at prevention, ensuring survivors know how and where to access services and addressing stigma and cultural barriers.The Bill and Melinda Gates Foundatio

An assessment of opportunities and challenges for public sector involvement in the maternal health voucher program in Uganda

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: Continued inequities in coverage, low quality of care, and high out-of-pocket expenses for health services threaten attainment of Millennium Development Goals 4 and 5 in many sub-Saharan African countries. Existing health systems largely rely on input-based supply mechanisms that have a poor track record meeting the reproductive health needs of low-income and underserved segments of national populations. As a result, there is increased interest in and experimentation with results-based mechanisms like supply-side performance incentives to providers and demand-side vouchers that place purchasing power in the hands of low-income consumers to improve uptake of facility services and reduce the burden of out-of-pocket expenditures. This paper describes a reproductive health voucher program that contracts private facilities in Uganda and explores the policy and implementation issues associated with expansion of the program to include public sector facilities. Methods: Data presented here describes the results of interviews of six district health officers and four health facility managers purposefully selected from seven districts with the voucher program in southwestern Uganda. Interviews were transcribed and organized thematically, barriers to seeking RH care were identified, and how to address the barriers in a context where voucher coverage is incomplete as well as opportunities and challenges for expanding the program by involving public sector facilities were investigated. Results: The findings show that access to sexual and reproductive health services in southwestern Uganda is constrained by both facility and individual level factors which can be addressed by inclusion of the public facilities in the program. This will widen the geographical reach of facilities for potential clients, effectively addressing distance related barriers to access of health care services. Further, intensifying ongoing health education, continuous monitoring and evaluation, and integrating the voucher program with other services is likely to address some of the barriers. The public sector facilities were also seen as being well positioned to provide voucher services because of their countrywide reach, enhanced infrastructure, and referral networks. The voucher program also has the potential to address public sector constraints such as understaffing and supply shortages.Conclusions: Accrediting public facilities has the potential to increase voucher program coverage by reaching a wider pool of poor mothers, shortening distance to service, strengthening linkages between public and private sectors through public-private partnerships and referral systems as well as ensuring the awareness and buy-in of policy makers, which is crucial for mobilization of resources to support the sustainability of the programs. Specifically, identifying policy champions and consulting with key policy sectors is key to the successful inclusion of the public sector into the voucher program

Protocol for stage 1 of the GaP study (Genetic testing acceptability for Paget's disease of bone): an interview study about genetic testing and preventive treatment: would relatives of people with Paget's disease want testing and treatment if they were available?

BACKGROUND: Paget's disease of bone (PDB) is characterised by focal increases in bone turnover, affecting one or more bones throughout the skeleton. This disrupts normal bone architecture and causes pain, deformity, deafness, osteoarthritis, and fractures. Genetic factors are recognised to play a role in PDB and it is now possible to carry out genetic tests for research. In view of this, it is timely to investigate the clinical potential for a programme of genetic testing and preventative treatment for people who have a family history of PDB, to prevent or delay the development of PDB. Evidence from non-genetic conditions, that have effective treatments, demonstrates that patients' beliefs may affect the acceptability and uptake of treatment. Two groups of beliefs (illness and treatment representations) are likely to be influential. Illness representations describe how people see their illness, as outlined in Leventhal's Self-Regulation Model. Treatment representations describe how people perceive potential treatment for their disease. People offered a programme of genetic testing and treatment will develop their own treatment representations based on what is offered, but the beliefs rather than the objective programme of treatment are likely to determine their willingness to participate. The Theory of Planned Behaviour is a theoretical model that predicts behaviours from people's beliefs about the consequences, social pressures and perceived control over the behaviour, including uptake of treatment. METHODS/DESIGN: This study aims to examine the acceptability of genetic testing, followed by preventative treatment, to relatives of people with PDB. We aim to interview people with Paget's disease, and their families, from the UK. Our research questions are: 1. What do individuals with Paget's disease think would influence the involvement of their relatives in a programme of genetic testing and preventative treatment? 2. What do relatives of Paget's disease sufferers think would influence them in accepting an offer of a programme of genetic testing and preventative treatment? DISCUSSION: Our research will be informed by relevant psychological theory: primarily the Self-Regulation Model and the Theory of Planned Behaviour. The results of these interviews will inform the development of a separate questionnaire-based study to explore these research questions in greater detail

Extension of adrenocortical carcinoma into the right atrium – echocardiographic diagnosis: A case report

BACKGROUND: Adrenocortical carcinoma is a rare, highly malignant tumor. Cardiac involvement of the tumor is very rare. Echocardiography facilitates the evaluation of the cardiac involvement of the tumor. CASE PRESENTATION: We describe a patient with an adrenal tumor. Transthoracic echo showed its extension into the right atrium. Accordingly, a combined abdominal and cardiac operation was performed, monitored by transesophageal echocardiography. CONCLUSION: This case highlights the importance of echocardiography in revealing the cardiac involvement by this tumor and in planning the operative procedure

Passerine Birds Breeding under Chronic Noise Experience Reduced Fitness

Background Fitness in birds has been shown to be negatively associated with anthropogenic noise, but the underlying mechanisms remain obscure. It is however crucial to understand the mechanisms of how urban noise impinges on fitness to obtain a better understanding of the role of chronic noise in urban ecology. Here, we examine three hypotheses on how noise might reduce reproductive output in passerine birds: (H1) by impairing mate choice, (H2) by reducing territory quality and (H3) by impeding chick development. Methodology/Principal Findings We used long-term data from an island population of house sparrows, Passer domesticus, in which we can precisely estimate fitness. We found that nests in an area affected by the noise from large generators produced fewer young, of lower body mass, and fewer recruits, even when we corrected statistically for parental genetic quality using a cross-fostering set-up, supporting H3. Also, individual females provided their young with food less often when they bred in the noisy area compared to breeding attempts by the same females elsewhere. Furthermore, we show that females reacted flexibly to increased noise levels by adjusting their provisioning rate in the short term, which suggests that noise may be a causal factor that reduces reproductive output. We rejected H1 and H2 because nestbox occupancy, parental body mass, age and reproductive investment did not differ significantly between noisy and quiet areas. Conclusions/Significance Our results suggest a previously undescribed mechanism to explain how environmental noise can reduce fitness in passerine birds: by acoustically masking parent–offspring communication. More importantly, using a cross-fostering set-up, our results demonstrate that birds breeding in a noisy environment experience significant fitness costs. Chronic noise is omnipresent around human habitation and may produces similar fitness consequences in a wide range of urban bird species

Surgical resectability of pancreatic adenocarcinoma: CTA

Imaging studies play an important role in the diagnosis and management of patients with pancreatic adenocarcinoma. Computed tomography (CT) is the most widely available and best validated modality for imaging these patients. Meticulous technique following a well-designed pancreas protocol is essential for maximizing the diagnostic efficacy of CT. After the diagnosis of pancreatic adenocarcinoma is made, the key to management is staging to determine resectability. In practice, staging often entails predicting the presence or absence of vascular invasion by tumor, for which several radiologic grading systems exist. With advances in surgical techniques, the definition of resectability is in evolution, and it is crucial that radiologists have an understanding of the implications of findings that are relevant to the determination of resectability

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration