Force-velocity correlations in a dense, collisional, granular flow

We report measurements in a 2-dimensional, gravity-driven, collisional, granular flow of the normal force delivered to the wall and of particle velocity at several points in the flow. The wall force and the flow velocity are negatively correlated. This correlation falls off only slowly with distance transverse to the flow, but dies away on the scale of a few particle diameters upstream or downstream. The data support a picture of short-lived chains of frequently colliding particles that extend transverse to the flow direction, making transient load-bearing bridges that cause bulk fluctuations in the flow velocity. The time-dependence of these spatial correlation functions indicate that while the force-bearing structures are local in space, their influence extends far upstream in the flow, albeit with a time-lag. This leads to correlated velocity fluctuations, whose spatial range increases as the jamming threshold is approached.Comment: to be submitted for publicatio

Public health approach to prevent cervical cancer in HIV-infected women in Kenya : issues to consider in the design of prevention programs

Women living with HIV in Africa are at increased risk to be co-infected with Human Papilloma Virus (HPV), persistent high risk (HR) HPV infection and bacterial vaginosis (BV), which compounds HPV persistence, thereby increasing the risk for cervical dysplasia. New guidance from WHO in 2014 advocating for a "screen and treat" approach in resource poor settings is becoming a more widely recommended screening tool for cervical cancer prevention programs in such contexts. This review article summarizes the risk factors to be considered when designing a primary and secondary cervical prevention program in a post-vaccination era for HIV-infected women in Kenya. This review article is based on our prior research on the epidemiology of pHR/HR-HPV genotypes in HIV-infected women and CIN 2+ in Kenya and other sub-Saharan contexts. In order to contextualize the findings, a literature search was carried out in March 2017 by means of four electronic databases: PUBMED, EMBASE, SCOPUS, and PROQUEST. Risk factors for potential (pHR)/HR HPV acquisition, including CD4 count, HAART initiation, Female Sex Worker status (FSW) and BV need to be considered. Furthermore, there may be risk factors for abnormal cytology, including FSW status, multiple potential (p) HR/HR HPV genotypes, which may require that HIV-infected women be subjected to screening at more frequent intervals than the three year recommended by the WHO. The quadruple synergistic interaction between HIV, HPV and BV and its related cervicitis may need to be reflected within a larger prevention framework at the community level. The opportunities brought forth by the roll out of HAART could lead to task shifting of HIV-HPV-BV care to nurses, which may increase access in poorly-served areas

Distribution of human papillomaviruses and bacterial vaginosis in HIV positive women with abnormal cytology in Mombasa, Kenya

Background: HPV is the major etiological factor in the causal pathway for cervical cancer, which is the leading cancer among women in sub-Saharan Africa. HIV is associated with a higher prevalence and a broader range of high-risk HPV genotypes. Studies have shown a positive association between Bacterial vaginosis (BV) and HPV and HIV. Also, in African women, BV was found to be significantly associated with vaginal inflammation. The high prevalence of BV, HIV and HPV infections in the African continent makes elucidation of the interactions with one another of utmost public health interest. The aims of the current study are to examine the frequency of HPV genotypes and BV as well as their respective risk factors within an HIV infected population with abnormal cytology in the resource-constrained setting of Mombasa, Kenya and, secondly, highlight issues to consider for triple co-infection clinical management. Method: Cross-sectional analysis with a sample drawn from an ongoing cohort study. All consenting, non-pregnant HIV infected women, between 18 and 50 years of age, without a history of cervical cancer or hysterectomy, between November 2005 and April 2006 were screened for HR HPV DNA in Mombasa, Kenya. 1 out of 4 HIV positive women fulfilled the criteria by having SIL (24.9 %). 600 HIV infected women were tested to reach a cohort of 74 HIV women with abnormal cytology. To assess which factors were associated with HR HPV, crude statistical analysis was performed through logistic regression. Results: Bacterial vaginosis (BV) was found in 46 women out of 74 (62.2 %). Cervicitis was diagnosed in 15 % of women (n = 11), of which 8 had BV. The most prevalent HPV genotypes were HPV 16 (33.8), HPV 53 (24.3) and HPV 18 (17.6 %), while 65 % of the participants had multiple genotype infection. Statistically significant associations between CD4 counts = 350 mu l and HPV 16 adjusted for age (OR = 2.9; 95 % CI: 1.0-8.3; p = 0.05). A borderline statistically significant association was observed between BV and HPV58 (crude OR = 4.1, 95 % CI: 0.8-21.0; p = 0.07). Conclusion: The most prevalent HPV genotypes observed were HPV 16, HPV 53, and HPV 18, which have a combined prevalence of 76 %. Our results show that a triage based on CD4 count should start at CD4 count >= 350 mu l as our study suggests that HPV 16 are more prevalent when women are moderately immunosuppressed. Given the high prevalence of HPV 53 in a HIV infected population with abnormal cytology, its cervical carcinoma genesis potential as a stand-alone genotype and as well as its synergism with multiple infections should be investigated. The new WHO guideline in resource-poor settings to rescreen women for HPV within ten years may be more effective if BV and cervicitis management become a major component for HIV-HPV management

Uptake of three doses of HPV vaccine by primary school girls in Eldoret, Kenya : a prospective cohort study in a malaria endemic setting

Background: All women are potentially at risk of developing cervical cancer at some point in their life, yet it is avoidable cause of death among women in Sub- Saharan Africa with a world incidence of 530,000 every year. It is the 4th commonest cancer affecting women worldwide with over 260,000 deaths reported in 2012. Low resource settings account for over 75% of the global cervical cancer burden. Uptake of HPV vaccination is limited in the developing world. WHO recommended that 2 doses of HPV vaccine could be given to young girls, based on studies in developed countries. However in Africa high rates of infections like malaria and worms can affect immune responses to vaccines, therefore three doses may still be necessary. The aim of this study was to identify barriers and facilitators associated with uptake of HPV vaccine. Methods: A cross-sectional survey was conducted at Eldoret, Kenya involving 3000 girls aged 9 to 14 years from 40 schools. Parents/guardians gave consent through a questionnaire. Results: Of all 3083 the school girls 93.8% had received childhood vaccines and 63.8% had a second HPV dose, and 39. 1% had a third dose. Administration of second dose and HPV knowledge were both strong predictors of completion of the third dose. Distance to the hospital was a statistically significant risk factor for non-completion (P: 0.01). Conclusions: Distance to vaccination centers requires a more innovative vaccine-delivery strategy and education of parents/guardians on cervical screening to increase attainment of the HPV vaccination

Effects of malaria/helminthic coinfections on cervical cancer progression among sub Saharan African women on highly active antiretroviral therapy : a scoping review

In Africa, the HIV prevalence in rural areas has begun to reach levels estimated within urban settings, where women are also more at risk for both malaria and intestinal parasitic infections. The objective of this review is to assess whether concomitant infections with malaria and/or helminthic diseases have an impact on cervical disease progression in women on HAART. This scoping review was conducted in August 2018. To conduct this scoping review, we searched the relevant studies in electronic databases such as PUBMED, Global Health, EMBASE, CINAHL and SCOPUS published in the year between 1960 and 2018 using the following search terms HAART AND malaria OR Helminth and Female OR women. Eight studies qualified for this review. The literature underscores the need for women on HAART with multiple co-infections to use adjuncts to retain immune recovery and undetectable HIV viral load, to reduce risk of cervical disease progression. A trend for higher risk of CIN3+ in HIV+ women reporting recent malarial infection was observed in one study. Given the public health impact of synergistic interactions between malaria and helminthic infections in HIV/HPV co-infected women on HAART, it is urgent that these interactions are elucidated

Human papilloma virus correlates of high grade cervical dysplasia in HIV-infected women in Mombasa, Kenya: a cross-sectional analysis

Background: Women living with HIV are at increased risk to be co-infected with HPV, persistent high-risk (HR) human papillomavirus (HPV) infection and increased HR HPV viral load, which make them more at risk for cervical cancer. Despite their inherent vulnerability, there is a scarcity of data on potential high risk (pHR) and HR HPV genotypes in HIV- infected women with cervical dysplasia and HPV-type specific viral load in this population in Sub Saharan Africa. The aim of this analysis of HIV-infected women was to explore the virological correlates of high-grade cervical dysplasia (CIN 2+) in HIV-infected women, thereby profiling HPV genotypes. Method: This analysis assesses baseline data obtained from a cohort study of 74 HIV-infected women with abnormal cytology attending a Comprehensive Care Centre for patients with HIV infection in Mombasa, Kenya. Quantitative real-time PCR was used for HPV typing and viral load. Results: CIN 2 was observed in 16% (12/74) of women, CIN 3 in 23% (17/74), and, invasive cervical carcinoma (ICC) in 1% (1/74) of women. In women with CIN 3+, HPV 16 (44%), HPV 56 (33%), HPV 33 and 53 (HPV 53 (28%) were the most prevalent genotypes. HPV 53 was observed as a stand-alone HPV in one woman with ICC. A multivariate logistic regression adjusting for age, CD4 count and HPV co-infections suggested the presence of HPV 31 as a predictor of CIN 2+ (adjusted odds ratio [aOR]:4.9; p = 0.05; 95% (Confidence Interval) [CI]:1.03-22.5). Women with CIN2+ had a significantly higher viral log mean of HPV 16, (11.2 copies/ 10,000 cells; 95% CI: 9.0-13.4) than with CIN 1. Conclusion: The high prevalence of HPV 53 in CIN 3 and as a stand-alone genotype in the patient with invasive cervical cancer warrants that its clinical significance be further revisited among HIV-infected women. HPV 31, along with elevated means of HPV 16 viral load were predictors of CIN 2 + 

Associations between highly active antiretroviral therapy and the presence of HPV, premalignant and malignant cervical lesions in sub-Saharan Africa, a systematic review : current evidence and directions for future research

Objectives: In sub-Saharan Africa, substantial international funding along with evidence-based clinical practice have resulted in an unparalleled scale-up of access to antiretroviral treatment at a higher CD4 count. The role and timing of highly active antiretroviral therapy (HAART) in mediating cervical disease remains unclear. The aim of this article is to systematically review all evidence pertaining to Africa and identify research gaps regarding the epidemiological association between HAART use and the presence of premalignant/malignant cervical lesions. Method: Five databases were searched until January 2017 to retrieve relevant literature from sub-Saharan Africa. Publications were included if they addressed prevalence, incidence or clearance of human papillomavirus (HPV) infection in women undergoing HAART as well as cytological or histological neoplastic abnormalities. Results: 22 studies were included, of which seven were prospective studies. Women receiving HAART are less likely to develop squamous intraepithelial lesions (SILs). There is evidence that duration of HAART along with the CD4 count may reduce the prevalence of high-risk HPV (HR-HPV), suggesting that without HAART, severe immunosuppression increases the risk of becoming or remaining infected with HR-HPV. Furthermore, according to existent literature, the CD4 count, rather than HAART coverage or its duration, plays a central role in the prevalence of cervical intraepithelial neoplasia (CIN) 2 and CIN 3. Conclusion: Our findings suggest a positive impact of HAART duration, in conjunction and interaction with CD4 count, on reducing the prevalence of HR-HPV. The greatest treatment effect might be seen among women starting at the lowest CD4 count, which may have a more instrumental role in cervical oncogenesis than either HAART use or the treatment duration on the prevalence of CIN 2 and CIN 3. There is still insufficient evidence to show a clear association between HAART coverage and the incidence of invasive cervical cancer. Enhanced surveillance on the impact of HAART treatment is crucial

Epidemiology of HPV Genotypes among HIV Positive Women in Kenya: A Systematic Review and Meta-Analysis

Background: There is a scarcity of data on the distribution of human papillomavirus (HPV) genotypes in the HIV positive population and in invasive cervical cancer (ICC) in Kenya. This may be different from genotypes found in abnormal cytology. Yet, with the advent of preventive HPV vaccines that target HPV 16 and 18, and the nonavalent vaccine targeting 90% of all ICC cases, such HPV genotype distribution data are indispensable for predicting the impact of vaccination and HPV screening on prevention. Even with a successful vaccination program, vaccinated women will still require screening to detect those who will develop ICC from other High risk (HR) HPV genotypes not prevented by current vaccines. The aim of this review is to report on the prevalence of pHR/HR HPV types and multiple pHR/HR HPV genotypes in Kenya among HIV positive women with normal, abnormal cytology and ICC. Methods: PUBMED, EMBASE, SCOPUS, and PROQUEST were searched for articles on HPV infection up to August 2nd 2016. Search terms were HIV, HPV, Cervical Cancer, Incidence or Prevalence, and Kenya. Results: The 13 studies included yielded a total of 2116 HIV-infected women, of which 89 had ICC. The overall prevalence of pHR/HR HPV genotypes among HIV-infected women was 64% (95%CI: 50%-77%). There was a borderline significant difference in the prevalence of pHR/HR HPV genotypes between Female Sex workers (FSW) compared to non-FSW in women with both normal and abnormal cytology. Multiple pHR/HR HPV genotypes were highly prominent in both normal cytology/HSIL and ICC. The most prevalent HR HPV genotypes in women with abnormal cytology were HPV 16 with 26%, (95%CI: 23.0%-30.0%) followed by HPV 35 and 52, with 21% (95%CI: 18%-25%) and 18% (95%CI: 15%-21%), respectively. In women with ICC, the most prevalent HPV genotypes were HPV 16 (37%; 95%CI: 28%-47%) and HPV 18 (24%; 95%CI: 16%-33%). Conclusion: HPV 16/18 gains prominence as the severity of cervical disease increases, with HPV 16/18 accounting for 61% (95%CI: 50.0%-70.0%) of all ICC cases. A secondary prevention program will be necessary as this population harbors multiple pHR/HR HPV co-infections, which may not be covered by current vaccines. A triage based on FSW as an indicator may be warranted