Community engagement for the Voluntary Medical Male Circumcision (VMMC) program: an analysis of key stakeholder roles to promote a sustainable program in Zambia [version 2; peer review: 1 approved, 2 approved with reservations]

Background: Within the Voluntary Medical Male Circumcision (VMMC) programme, community engagement has been central in facilitating the acceptance of VMMC, especially in non-circumcising communities. We used the case of the development of community engagement plans for sustainability of VMMC in Zambia to illustrate diversity of stakeholders, their power, roles, and strategies in community engagement. Methods: Data were collected using document review, in-depth interviews (n=35) and focus group discussions (n=35) with community stakeholders, health workers, health centre committees, counsellors, teachers, community volunteers and parents/caregivers. Data were analysed using thematic analysis. The analysis was guided by the power and interest model. Results: Differences were noted between the rural and urban sites in terms of power/influence and interest rating of community stakeholders who could be involved in the sustainability phase of the VMMC response in Zambia. For example, in the urban setting, neighbourhood health committees (NHCs), health workers, leaders of clubs, community health workers (CHWs), radio, television and social media platforms were ranked highest. From this list, social media and television platforms were not highly ranked in rural areas. Some stakeholders had more sources of power than others. Forms or sources of power included technical expertise, local authority, financial resources, collective action (action through schools, churches, media platforms, other community spaces), and relational power.   Key roles and strategies included strengthening and broadening local coordination systems, enhancing community involvement, promoting community-led monitoring and evaluation, through the use of locally recognised communication spaces and channels, facilitating ownership of VMMC, and improving local accountability processes in VMMC activities. Conclusions: By consulting with the most relevant stakeholders, and considering community needs in programme development, the VMMC programme may be able to leverage the community structures and systems to reduce long term demand generation costs for VMMC and increase the acceptability and frequency of male circumcision

Métodos para la identificación del antígeno de histocompatibilidad HLA-B27: comparación de cuatro protocolos técnicos

Introducción: La asociación del HLA-B27 y las Espondiloartritis, ha hecho evidente que la tipificación del HLA-B27 sea considerada como un apoyo en el diagnóstico de estas enfermedades. Los métodos más empleados para la determinación del antígeno HLA-B27 en los laboratorios clínicos y en investigación son: la microlinfocitotoxicidad (MCTX), la citometría de flujo digital (CMFd), la citometría de flujo análoga (CMFa) y la reacción en cadena de la polimerasa con primers de secuencia específicos (PCR-SSP).Objetivo: Comparar MCTX con la CMFd, la CMFa con la CMFd, y la técnica de CMFd frente a PCR-SSP.Métodos para la identificación del antígeno de histocompatibilidad hla-b27 Métodos: Se analizaron 4109 solicitudes de HLA-B27 en población con manifestaciones sugestivas de EAS remitidas entre 2009 y 2012 al Hospital Militar Central y al Instituto de Referencia Andino. Se evaluaron las frecuencias obtenidas por Chi cuadrado (X2); para estimar la concordancia metodológica se utilizó el Coeficiente de Correlación Intraclase (CCI). Los análisis se realizaron con el paquete estadístico SPSS V18.Resultados: Al evaluar 467 datos por la técnica de CMFa frente a PCR-SSP, la CMFa mostró 239 resultados entre positivos y en rango indeterminado, de los cuales, luego de ser confirmados PCRSSP, solo 213 demostraron la expresión de HLA-B27 (p<0.05). Se obtuvieron 208 resultados realizados por CMFd y PCR-SSP simultáneamente, observándose una alta correspondencia entre estas técnicas (p<0.05). Para evaluar la concordancia entre la MCTX y CMFd se analizaron 34 datos,revelando un 100% de correspondencia entre esta dos metodologías CCI=1,p<0.05).Conclusión: La citometría de flujo digital es un método rápido que presenta un desempeño altamente confiable para la identificación de HLA-B27, resultados que se recomiendan confirmar por PCR SSP

The telomere bouquet facilitates meiotic prophase progression and exit in fission yeast

During meiotic prophase, chromosome arrangement and oscillation promote the pairing of homologous chromosomes for meiotic recombination. This dramatic movement involves clustering of telomeres at the nuclear membrane to form the so-called telomere bouquet. In fission yeast, the telomere bouquet is formed near the spindle pole body (SPB), which is the microtubule organising centre, functionally equivalent to the metazoan centrosome. Disruption of bouquet configuration impedes homologous chromosome pairing, meiotic recombination and spindle formation. Here, we demonstrate that the bouquet is maintained throughout meiotic prophase and promotes timely prophase exit in fission yeast. Persistent DNA damages, induced during meiotic recombination, activate the Rad3 and Chk1 DNA damage checkpoint kinases and extend the bouquet stage beyond the chromosome oscillation period. The auxin-inducible degron system demonstrated that premature termination of the bouquet stage leads to severe extension of prophase and consequently spindle formation defects. However, this delayed exit from meiotic prophase was not caused by residual DNA damage. Rather, loss of chromosome contact with the SPB caused delayed accumulation of CDK1-cyclin B at the SPB, which correlated with impaired SPB separation. In the absence of the bouquet, CDK1-cyclin B localised near the telomeres but not at the SPB at the later stage of meiotic prophase. Thus, bouquet configuration is maintained throughout meiotic prophase, by which this spatial organisation may facilitate local and timely activation of CDK1 near the SPB. Our findings illustrate that chromosome contact with the nuclear membrane synchronises meiotic progression of the nucleoplasmic chromosomes with that of the cytoplasmic SPB.the European Research Council and Cancer Research U

Overcoming platinum-acquired resistance in ovarian cancer patient-derived xenografts

Background: Epithelial ovarian cancer is the most lethal gynecological cancer and the high mortality is due to the frequent presentation at advanced stage, and to primary or acquired resistance to platinum-based therapy. Methods: We developed three new models of ovarian cancer patient-derived xenografts (ovarian PDXs) resistant to cisplatin (cDDP) after multiple in vivo drug treatments. By different and complementary approaches based on integrated metabolomics (both targeted and untargeted mass spectrometry-based techniques), gene expression, and functional assays (Seahorse technology) we analyzed and compared the tumor metabolic profile in each sensitive and their corresponding cDDP-resistant PDXs. Results: We found that cDDP-sensitive and -resistant PDXs have a different metabolic asset. In particular, we found, through metabolomic and gene expression approaches, that glycolysis, tricarboxylic acid cycle and urea cycle pathways were deregulated in resistant versus sensitive PDXs. In addition, we observed that oxygen consumption rate and mitochondrial respiration were higher in resistant PDXs than in sensitive PDXs under acute stress conditions. An increased oxidative phosphorylation in cDDP-resistant sublines led us to hypothesize that its interference could be of therapeutic value. Indeed, in vivo treatment of metformin and cDDP was able to partially reverse platinum resistance. Conclusions: Our data strongly reinforce the idea that the development of acquired cDDP resistance in ovarian cancer can bring about a rewiring of tumor metabolism, and that this might be exploited therapeutically

Characterization of hydrogenated amorphous silicon sensors on polyimide flexible substrate

Hydrogenated amorphous silicon (a-Si:H) is a material having an intrinsically high radiation hardness that can be deposited on flexible substrates like Polyimide. For these properties a-Si:H can be used for the production of flexible sensors. a-Si:H sensors can be successfully utilized in dosimetry, beam monitoring for particle physics (x-ray, electron, gamma-ray and proton detection) and radiotherapy, radiation flux measurement for space applications (study of solar energetic particles and stellar events) and neutron flux measurements. In this paper we have studied the dosimetric x-ray response of n-i-p diodes deposited on Polyimide. We measured the linearity of the photocurrent response to x-rays versus dose-rate from which we have extracted the dosimetric x-ray sensitivity at various bias voltages. In particular low bias voltage operation has been studied to assess the high energy efficiency of these kind of sensor. A measurement of stability of x-ray response versus time has been shown. The effect of detectors annealing has been studied. Operation under bending at various bending radii is also shown