Human papilloma virus genotype distribution and risk factor analysis amongst reproductive aged women in urban Gambia

Purpose. Cervical cancer is the most frequently diagnosed female cancer in The Gambia, representing approximately 30% of cases. In 2014, the quadrivalent human papilloma virus (HPV) vaccine was introduced, which offers protection against HPV genotypes 6, 11, 16 and 18. To evaluate the potential effectiveness of this vaccine, genotype distribution and risk factor analysis were assessed. Methodology. Endocervical samples (n=232) were collected from women aged 20-49 years residing in urban Gambia. A questionnaire was administered to capture socio-demographic and cervical cancer risk factors. HPV detection and genotyping was performed by PCR amplification of the L1 major capsid gene and analysis of sequenced PCR products. Results/ Key Findings. The prevalence of HPV was 12% (28/232) and the high risk (HR) genotype HPV 52 (5/28) was the most prevalent genotype. HR-HPV sequences had high identity (≥ 90 %) to isolates which originated from America, Europe and Asia but not from Africa. Half (14/28) of participants were co-infected with Ureaplasma urealyticum/parvum, which increases the risk of progression to cervical cancer. Female genital mutilation and the use of hormone contraception for >5 years were identified as potential risk factors for HPV infection. Ethnicity-associated differences were also noted; participants of the Fula ethnic group had a higher prevalence of HR-HPV infection (31.3%) compared to the Mandinka (18.8%) and Wollof (12.5%) groups. Conclusion. These data may have a significant public health impact as the HPV quadrivalent vaccine may be of limited value if the circulating non-HPV 16/18 HR-genotypes are responsible for cytological abnormalities of the cervix

Cancer in The Gambia: 1988–97

We describe the incidence of cancer in The Gambia over a 10-year period using data collected through the Gambian National Cancer Registry. Major problems involved with cancer registration in a developing country, specifically in Africa are discussed. The data accumulated show a low overall rate of cancer incidence compared to more developed parts of the world. The overall age standardized incidence rates (ASR) were 61.0 and 55.7 per 100 000 for males and females, respectively. In males, liver cancer was most frequent, comprising 58% of cases (ASR 35.7) followed by non-Hodgkin lymphoma, 5.4% (ASR 2.4), lung 4.0%, (ASR 2.8) and prostate 3.3% (ASR 2.5) cancers. The most frequent cancers in females were cervix uteri 34.0% (ASR 18.9), liver 19.4% (ASR 11.2), breast 9.2% (ASR 5.5) and ovary 3.2% (ASR 1.6). The data indicate that cancers of the liver and cervix are the most prevalent cancers, and are likely to be due to infectious agents. It is hoped that immunization of children under 1 year against hepatitis B will drastically reduce the incidence of liver cancer in The Gambia. © 2001 Cancer Research Campaign http://www.bjcancer.co

The gravity duals of SO/USp superconformal quivers

We study the gravity duals of SO/USp superconformal quiver gauge theories realized by M5-branes wrapping on a Riemann surface ("G-curve") together with a Z_2-quotient. When the G-curve has no punctures, the gravity solutions are classified by the genus g of the G-curve and the torsion part of the four-form flux G_4. We also find that there is an interesting relation between anomaly contributions from two mysterious theories: T_{SO(2N)} theory with SO(2N)^3 flavor symmetry and \tilde{T}_{SO(2N)} theory with SO(2N) x USp(2N-2)^2 flavor symmetry. The dual gravity solutions for various SO/USp-type tails are also studied.Comment: 27 pages, 13 figures; v2 minor corrections, typos corrected, Figure 13 replaced, references adde

KDM6A Lysine Demethylase Directs Epigenetic Polarity of MDSCs during Murine Sepsis

Sepsis-induced myeloid-derived suppressor cells (MDSCs) increase mortality risk. We previously identified that long non-coding RNA Hotairm1 supports myeloid precursor shifts to Gr1+CD11b+ MDSCs during mouse sepsis. A major unanswered question is what molecular processes control Hotairm1 expression. In this study, we found by a genetic deletion that a specific PU.1-binding site is indispensable in controlling Hotairm1 transcription. We then identified H3K4me3 and H3K27me3 at the PU.1 site on the Hotairm1 promoter. Controlling an epigenetic switch of Hotairm1 transcription by PU.1 was histone KDM6A demethylase for H3K27me3 that derepressed its transcription with possible contributions from Ezh2 methyltransferase for H3K27me3. KDM6A knockdown in MDSCs increased H3K27me3, decreased H3K4me3, and inhibited Hotairm1 transcription activation by PU.1. These results enlighten clinical translation research of PU.1 epigenetic regulation as a potential sepsis immune-checkpoint treatment site

Holographic Entanglement Entropy at Finite Temperature

Using a holographic proposal for the entanglement entropy we study its behavior in various supergravity backgrounds. We are particularly interested in the possibility of using the entanglement entropy as way to detect transitions induced by the presence horizons. We consider several geometries with horizons: the black hole in $AdS_3$, nonextremal Dp-branes, dyonic black holes asymptotically to $AdS_4$ and also Schwarzschild black holes in global $AdS_p$ coordinates. Generically, we find that the entanglement entropy does not exhibit a transition, that is, one of the two possible configurations always dominates.Comment: v3: 31 pp, ten figures, modified to match version accepted by IJMP

A double blind randomised controlled trial comparing standard dose of iron supplementation for pregnant women with two screen-and-treat approaches using hepcidin as a biomarker for ready and safe to receive iron.

BACKGROUND: Until recently, WHO recommended daily iron supplementation for all pregnant women (60 mg/d iron combined with 400ug/d folic acid) where anaemia rates exceeded 40 %. Recent studies indicate that this may pose a risk to pregnant women. Therefore, there is a need to explore screen-and-treat options to minimise iron exposure during pregnancy using an overall lower dosage of iron that would achieve equivalent results as being currently recommended by the WHO. However, there is a lack of agreement on how to best assess iron deficiency when infections are prevalent. Here, we test the use of hepcidin a peptide hormone and key regulator of iron metabolism, as a potential index for 'safe and ready to receive' iron. DESIGN/METHODS: This is a 3-arm randomised-controlled proof-of-concept trial. We will test the hypothesis that a screen-and-treat approach to iron supplementation using a pre-determined hepcidin cut-off value of <2.5 ng/ml will achieve similar efficacy in preventing iron deficiency and anaemia at a lower iron dose and hence will improve safety. A sample of 462 pregnant women in rural Gambia will be randomly assigned to receive: a) UNU/UNICEF/WHO international multiple micronutrient preparation (UNIMMAP) containing 60 mg/d iron (reference arm); b) UNIMMAP containing 60 mg/d iron but based on a weekly hepcidin screening indicating if iron can be given for the next 7 days or not; c) or UNIMMAP containing 30 mg/d iron as in (b) for 12 weeks in rural Gambia. The study will test if the screen-and-treat approach is non-inferior to the reference arm using the primary endpoint of haemoglobin levels at a non-inferiority margin of 0.5 g/dl. Secondary outcomes of adverse effects, compliance and the impact of iron supplementation on susceptibility to infections will also be assessed. DISCUSSION: This trial is expected to contribute towards minimising the exposure of pregnant women to iron that may not be needed and therefore potentially harmful. If the evidence in this study shows that the overall lower dosage of iron is non-inferior to 60 mg/day iron, this may help decrease side-effects, improve compliance and increase safety. The potential for the use of hepcidin for a simple point-of-care (PoC) diagnostic for when it is most safe and effective to give iron may improve maternal health outcomes. TRIAL REGISTRATION: ISRCTN21955180

Involving community health workers in disease-specific interventions: perspectives from The Gambia on the impact of this approach

Background The Community Health Worker (CHW) programme is recognised as key for providing healthcare to communities, particularly in remote locations. CHWs are usually volunteers, nominated by their communities and trained to provide basic care and prevention for common illnesses. However, differences in disease-specific programmes aimed at meeting national agenda and perceived health needs of the community raises questions about the best approach to maximise the potential of this workforce. Methods This was an explorative qualitative study, ancillary to a larger trial on a malaria control intervention. In July 2017, 40 semi-structured interviews were conducted with 17 village health workers (VHWs), four community health nurses who supervise VHWs, and 19 key informants from the community. Analysis was concurrent to data collection and carried out using a deductive process for thematic analysis, with the aid of NVivo 11 Qualitative Analysis Software. Results There were three key aspects of the VHW role identified in this setting; (1) to give health advice; (2) to treat and refer patients; and (3) to support environmental cleaning. The VHWs’ involvement in the clinical trial impacted their role in several ways. Overall, this was perceived very positively by the community and the VHWs since it improved access to medication and training on how to treat malaria. However, involvement was also perceived to increase VHWs’ workload, and placed more emphasis on malaria over other common illnesses, creating a shift in the balance of their role between disease prevention and treatment. Conclusions VHWs are essential for the successful delivery of disease-specific activities at the community level. However, involving them in these activities has important implications for their everyday role. If carefully managed, it has the potential to improve their capacity to screen and treat specific diseases such as malaria

Beyond LLM in M-theory

The Lin, Lunin, Maldacena (LLM) ansatz in D = 11 supports two independent Killing directions when a general Killing spinor ansatz is considered. Here we show that these directions always commute, identify when the Killing spinors are charged, and show that both their inner product and resulting geometry are governed by two fundamental constants. In particular, setting one constant to zero leads to AdS7 x S4, setting the other to zero gives AdS4 x S7, while flat spacetime is recovered when both these constants are zero. Furthermore, when the constants are equal, the spacetime is either LLM, or it corresponds to the Kowalski-Glikman solution where the constants are simply the mass parameter.Comment: 1+30 pages, footnote adde

Serum Hepcidin Concentrations Decline during Pregnancy and May Identify Iron Deficiency: Analysis of a Longitudinal Pregnancy Cohort in The Gambia.

Background: Antenatal anemia is a risk factor for adverse maternal and fetal outcomes and is prevalent in sub-Saharan Africa. Less than half of antenatal anemia is considered responsive to iron; identifying women in need of iron may help target interventions. Iron absorption is governed by the iron-regulatory hormone hepcidin.Objective: We sought to characterize changes in hepcidin and its associations with indexes of iron stores, erythropoiesis, and inflammation at weeks 14, 20, and 30 of gestation and to assess hepcidin's diagnostic potential as an index of iron deficiency.Methods: We measured hemoglobin and serum hepcidin, ferritin, soluble transferrin receptor (sTfR), and C-reactive protein (CRP) at 14, 20, and 30 wk of gestation in a cohort of 395 Gambian women recruited to a randomized controlled trial. Associations with hepcidin were measured by using linear regression, and hepcidin's diagnostic test accuracy [area under the receiver operating characteristic curve (AUCROC), sensitivity, specificity, cutoffs] for iron deficiency at each time point was analyzed.Results: The prevalence of anemia increased from 34.6% at 14 wk of gestation to 50.0% at 20 wk. Hepcidin concentrations declined between study enrollment and 20 wk, whereas ferritin declined between 20 and 30 wk of gestation. The variations in hepcidin explained by ferritin, sTfR, and CRP declined over pregnancy. The AUCROC values for hepcidin to detect iron deficiency (defined as ferritin <15 μg/L) were 0.86, 0.83, and 0.84 at 14, 20, and 30 wk, respectively. Hepcidin was superior to hemoglobin and sTfR as an indicator of iron deficiency.Conclusions: In Gambian pregnant women, hepcidin appears to be a useful diagnostic test for iron deficiency and may enable the identification of cases for whom iron would be beneficial. Hepcidin suppression in the second trimester suggests a window for optimal timing for antenatal iron interventions. Hemoglobin does not effectively identify iron deficiency in pregnancy. This trial was registered at www.isrctn.com as ISRCTN49285450