Nonpromoter methylation of the CDKN2A gene with active transcription is associated with improved locoregional control in laryngeal squamous cell carcinoma

We previously reported a novel association between CDKN2A nonpromoter methylation and transcription (ARF/INK4a) in human papillomavirus associated oropharyngeal tumors. In this study we assessed whether nonpromoter CDKN2A methylation in laryngeal squamous cell carcinomas (LXSCC) conferred a similar association with transcription that predicted patient outcome. We compared DNA methylation and ARF/INK4a RNA expression levels for the CDKN2A locus using the Illumina HumanMethylation27 beadchip and RT-PCR in 43 LXSCC tumor samples collected from a prospective study of head and neck cancer patients treated at Montefiore Medical Center (MMC). Validation was performed using RNAseq data on 111 LXSCC tumor samples from the Cancer Genome Atlas (TCGA). The clinical relevance of combined nonpromoter CDKN2A methylation and transcription was assessed by multivariate Cox regression for locoregional recurrence on a subset of 69 LXSCC patients with complete clinicopathologic data from the MMC and TCGA cohorts. We found evidence of CDKN2A nonpromoter hypermethylation in a third of LXSCC from our MMC cohort, which was significantly associated with increased ARF and INK4a RNA expression (Wilcoxon rank-sum, P = 0.007 and 0.003, respectively). A similar association was confirmed in TCGA samples (Wilcoxon rank-sum test P < 0.0001 for ARF and INK4a). Patients with CDKN2A hypermethylation or high ARF/INK4a expression were significantly less likely to develop a locoregional recurrence compared to those with neither of the features, independent of other clinicopatholgic risk factors (adjusted hazard ratio=0.21, 95% confidence interval:0.05-0.81). These results support the conclusion that CDKN2A nonpromoter methylation is associated with increased ARF and INK4a RNA expression, and improved locoregional control in LXSCC

Family planning in conflict: results of cross-sectional baseline surveys in three African countries

Background: Despite the serious consequences of conflict for reproductive health, populations affected by conflict and its aftermath face tremendous barriers to accessing reproductive health services, due to insecurity, inadequate numbers of trained personnel and lack of supplies. Family planning is often particularly neglected. Methods: In six conflict-affected areas in Sudan, northern Uganda and the Democratic Republic of Congo, household surveys of married or in-union women of reproductive age were conducted to determine baseline measures of family planning knowledge, attitudes and behaviors regarding contraception. Health facility assessments were carried out to assess baseline measures of family planning services availability. Data were double-entered into CSPro 3.2 and exported to SAS 9.2, which was used to calculate descriptive statistics. The studies' purposes were to guide program activities and to serve as a baseline against which program accomplishments could be measured. Results: Knowledge of modern contraceptive methods was low relative to other sub-Saharan African countries, and use of modern methods was under 4% in four sites; in two sites with prior family planning services it was 12% and 16.2%. From 30% to 40% of women reported they did not want a child within two years, however, and an additional 12% to 35% wanted no additional children, suggesting a clear need for family planning services. The health facilities assessment showed that at most only one-third of the facilities mandated to provide family planning had the necessary staff, equipment and supplies to do so adequately; in some areas, none of the facilities were prepared to offer such services. Conclusions: Family planning services are desired by women living in crisis situations when offered in a manner appropriate to their needs, yet services are rarely adequate to meet these needs. Refugee and internally displaced women must be included in national and donors' plans to improve family planning in Africa

Acquisition and Persistence of Human Papillomavirus 16 (HPV-16) and HPV-18 Among Men With High-HPV Viral Load Infections in a Circumcision Trial in Kisumu, Kenya

Background. Circumcision and lower human papillomavirus (HPV) viral loads in men are possibly associated with a reduced risk of HPV transmission to women. However, the association between male circumcision and HPV viral load remains unclear

La compilación de datos en situaciones de emergencia

A pesar de que la comunidad humanitaria reconoce que es necesario disponer de datos de buena calidad para la elaboración de programas y su seguimiento, las dificultades y las exigencias de las situaciones reales suelen conducir, con demasiada frecuencia, a la excusa de “no tenemos tiempo” o “es demasiado difícil”. Sin embargo, sin destinar tiempo y recursos a la compilación de datos de referencia y de control, las actividades de los proyectos no pueden basarse en pruebas sólidas procedentes de la evaluación de los programas

Challenges of collecting baseline data in emergency settings

Although the humanitarian community acknowledgesthe need for good quality data in programme design andmonitoring, the challenges and demands of field settingshave too often led to the argument that “we just don’thave time” or “it is too difficult”. Yet without the allocationof time and resources to the collection of baseline andmonitoring data, project activities cannot be groundedin strong evidence from programme evaluation

A qualitative study exploring child marriage practices among Syrian conflict-affected populations in Lebanon

Abstract Background Recent reports have suggested that child marriage among Syrians may be increasing as a result of displacement and conflict. This study sought to gather qualitative data about the factors that promote child marriage practices among Syrian refugees in Al Marj area in the Bekaa valley, Lebanon, where the majority of Syrian refugees have settled in Lebanon. The second aim of this study was to generate recommendations on how to mitigate the drivers and consequences of child marriage practices based on the findings. Methods Eight focus group discussions were conducted separately with married and unmarried young women and mothers and fathers of married and unmarried women. Furthermore, researchers conducted 11 key informant interviews with service providers and stakeholders to understand how conflict and displacement influenced marriage practices of Syrian refugees in Al Marj community. Results Although child marriage was a common practice in pre-conflict Syria, new factors seem to contribute to a higher risk of child marriage among Syrian refugees in Lebanon. Respondents cited conflict- and displacement-related safety issues and feeling of insecurity, the worsening of economic conditions, and disrupted education for adolescent women as driving factors. Service providers, young women, and parents also reported changes in some marriage practices, including a shorter engagement period, lower bride price, change in cousin marriage practices, and a reduced age at marriage. Conclusions Recommendations for interventions to mitigate the drivers of child marriage and its negative consequences should be built on a clear understanding of the local refugee context and the drivers of child marriage in refugee settings. Interventions should involve multiple stakeholders, they should be adjusted to target each specific context, age group and marital status. For these interventions to be effective, they should be addressed concurrently, and they should be delivered in a culturally sensitive and practical manner

Prioritizing programming to address the needs and risks of very young adolescents: a summary of findings across three humanitarian settings

Abstract Background Between 2013 and 2014, a series of qualitative and quantitative research efforts were undertaken in three conflict affected communities (Syrian refugees in the Bekaa Valley, Lebanon, Somali refugees in Kobe Refugee camp Ethiopia, and migrant communities from Myanmar settled in Tak Province, Thailand) that sought to understand the lived experiences of very young adolescents during emergencies. A research consortium that included the Women’s Refugee Commission, Johns Hopkins University, American University in Beirut, International Medical Corps in Ethiopia, Save the Children in Lebanon and the Adolescent Reproductive Health Network in Thailand convened around these activities. Methods The core research initiative, “Sexual and Reproductive Health Needs and Risks of Very Young Adolescents in Humanitarian Contexts” involved three phases of research: 1) A program needs assessment completed with key informants working on adolescent sexual and reproductive health in each context 2) qualitative research, that incorporated participatory approaches, with adolescents 10–16 years of age, and adults in the community in all three settings, and 3) A household survey with 10–14 year-olds in Ethiopia and Thailand. An additional phase of research was added in Lebanon and Ethiopia, to further explore the issue of child marriage which was a prominent experience identified within the core research initiative on very young adolescents. Results This research supplement, exploring the experiences during early adolescence, highlighted the crucial role of education, prominent experiences of insecurity, existing knowledge on body change and fertility, peer and family relationships among this age group, as well as concerns around child marriage (Lebanon and Ethiopia), child labor (Thailand), and gender roles. Conclusion Given the findings presented within this supplement, there are broad implications for work with very young adolescents by humanitarian actors in the settings where research was undertaken, and potentially, more broadly. Programs that promote health and well-being during early adolescence are critically needed in settings of conflict and displacement, and coordination among the diverse range of actors involved in such programming will be essential. Additionally, SRH programs for adolescents (10–14 years of age) in emergencies should include, at minimum, sensitive care for survivors of sexual violence, menstrual hygiene management, life skills, and fertility education. Humanitarian programs can better engage with parents, teachers, and community leaders as partners in the development and implementation of programs. Finally, fundamental rights to protection and education for all adolescents must be upheld

Online mass spectrometry of CE (SDS)-separated proteins by two-dimensional capillary electrophoresis

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) is the fundamental technique for protein separation by size. Applying this technology in capillary format, gaining high separation efficiency in a more automated way, is a key technology for size separation of proteins in the biopharmaceutical industry. However, unequivocal identification by online mass spectrometry (MS) is impossible so far, due to strong interference in the electrospray process by SDS and other components of the SDS-MW separation gel buffer. Here, a heart-cut two-dimensional electrophoretic separation system applying an electrically isolated valve with an internal loop of 20 nL is presented. The peak of interest in the CE (SDS) separation is transferred to the CZE-MS, where electrospray-interfering substances of the SDS-MW gel are separated prior to online electrospray ionization mass spectrometry. An online SDS removal strategy for decomplexing the protein-SDS complex is implemented in the second dimension, consisting of the co-injection of organic solvent and cationic surfactant. This online CE (SDS)-CZE-MS system allows MS characterization of proteoforms separated in generic CE (SDS), gaining additional separation in the CZE and detailed MS information. In general, the system can be applied to all kinds of proteins separated by CE (SDS). Here, we present results of the CE (SDS)-CZE-MS system on the analysis of several biopharmaceutically relevant antibody impurities and fragments. Additionally, the versatile application spectrum of the system is demonstrated by the analysis of extracted proteins from soybean flour. The online hyphenation of CE (SDS) resolving power and MS identification capabilities will be a powerful tool for protein and mAb characterization. Graphical abstract Two-dimensional capillary electrophoresis system hyphenated with mass spectrometry for the characterization of CE (SDS)-separated proteins. As first dimension, a generic and high MS-interfering CE (SDS) separation is performed for size separation. After heart-cut transfer of the unknown CE (SDS) protein peak, via a four-port nanoliter valve to a volatile electrolyte system as second dimension, interference-free mass spectrometric data of separated mAb fragments and soybean proteins are obtained

Pharmacological neuroenhancement and the ability to recover from stress – a representative cross-sectional survey among the German population

BACKGROUND: Pharmacological neuroenhancement (PNE) refers to the use of psychoactive substances without doctor’s prescription to enhance cognitive performance or to improve mood. Although some studies have reported that drugs for PNE are also being used to cope with stressful life situations, nothing is known about the relationship of PNE and resilience, i.e. the ability to recover from stress. This study aimed at investigating the relationship of PNE and resilience in the first representative population sample. METHODS: A cross-sectional survey in a representative sample of 1128 adults (age ≥ 18 yrs.) living in Germany was conducted. The use of PNE and related attitudes, perceptions and behaviours were assessed by structured interviews and self-report questionnaires. Stepwise logistic regression with backward elimination was conducted to identify potential risk factors for PNE use. RESULTS: Lifetime prevalence for the use of stimulating prescription drugs without medical indication was 4.3%, 10.2% for stimulating illicit drugs, 20.3% for mood modulating prescription drugs, and 23.4% for cannabis. Coping with stressful situations was more frequently reported as underlying motive for using stimulant or mood modulating prescription drugs than stimulating illicit drugs or cannabis. The individual perceived stress increased the risk of using stimulating prescription drugs (OR: 2.86; 95% Cl: 1.49–5.46) and the individual ability to recover from stress decreased the risk of using any substance for PNE and especially mood modulating prescription drugs (OR: .62; 95% Cl: .47–.81). CONCLUSIONS: The non-medical use of prescription drugs for PNE appears to be more prevalent in subjects who are less resilient to stress. Tailored resilience interventions that improve the ability to adapt to and recover from stressors may prevent the use of prescription medication for PNE. Further research should disentangle the association between psychological resilience and PNE as well as examine the efficacy of resilience interventions in the prevention of PNE

Understanding the unique experiences, perspectives and sexual and reproductive health needs of very young adolescents: Somali refugees in Ethiopia

Abstract Background Kobe Refugee camp hosts roughly 39,000 refugees displaced from Somalia during the 2011–2012 Horn of Africa Crisis. Sexual and reproductive health, as with the greater issues of health and well-being for adolescents displaced from this crisis remain largely unknown and neglected. In 2013, the Women’s Refugee Commission, Johns Hopkins University, and International Medical Corps in Ethiopia, implemented qualitative and quantitative research to explore the factors and risks that impact the health of very young adolescents (VYAs), those 10–14 years of age, in this setting. This paper presents findings from the qualitative effort. Methods Focus group discussions (FGD), incorporating community mapping and photo elicitation activities, were conducted with 10–12 and 13–14 year-olds to obtain information about their own perspectives, experiences and values. FGDs were also implemented with 15–16 year-olds and adults, to consider their perspectives on the sexual and reproductive health needs and risks of VYAs. Results This research identified several factors that were found to influence the health and well-being of VYAs in Kobe refugee camp, including newfound access to education and security, combined with gender divisions and parental communication around early SRH and puberty that remained intact from traditional Somali culture. Girls were found to face an additional risk of child marriage and early pregnancy exacerbated since displacement, which significantly limited their ability to access education and achieve future aspirations. Conclusion Findings from this study could help to inform future programs in Kobe and similar contexts involving long-term displacement from conflict, focusing on the health and development needs of VYAs. Future programs should consider the determinants of positive VYA health and development, including access to education, gender equity, and safety. By better understanding the unique experiences, perspectives and needs of VYAs, practitioners, policy makers and donors can invest in the individual and community assets that reinforce positive behaviors established in early adolescence, in order to achieve long-term SRH impacts