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Background Compared with women who are human immunodeficiency virus (HIV) negative, women with human immunodeficiency virus (WWH) have a higher human papillomavirus (HPV) prevalence and increased cervical cancer risk, emphasizing the need for effective cervical cancer screening in this population. The present study aimed to validate methylation markers ASCL1 and LHX8 for primary screening in a South African cohort of WWH. Methods In this post hoc analysis within the DIAgnosis in Vaccine And Cervical Cancer Screen (DiaVACCS) study, a South African observational multicenter cohort study, cervical scrape samples from 411 HIV-positive women were analyzed for hypermethylation of ASCL1 and LHX8 genes, HPV DNA, and cytology. Sensitivities, specificities, and positive and negative predictive values of primary methylation-based, HPV-based and cytology-based screening were calculated for the detection of cervical intraepithelial neoplasia of grade 3 or higher. Results Single markers ASCL1 and LHX8 resulted in a good performance for the detection of cervical intraepithelial neoplasia of grade 3 or higher, with sensitivities of 85.9% (95% confidence interval [CI], 78.2%–93.6%) and 89.7% (83.0%–96.5%), respectively, and specificities of 72.9% (67.3%–78.5%) and 75.0% (69.5%–80.5%). Combining markers ASCL1 and LHX8 resulted in a lower sensitivity compared with HPV testing (84.6% vs 93.6%, respectively; ratio, 0.90 [95% CI, .82–.99]) and a higher specificity (86.7% vs 78.3%; ratio 1.11 [1.02–1.20]) and reduced the referral rate from 46.8% to 33.4%. ASCL1/LHX8 methylation had a significantly higher sensitivity than cytology (threshold, high-grade intraepithelial squamous lesion or worse), (84.6% vs 74.0%, respectively; ratio, 1.16 [95% CI, 1.01–1.32]) and similar specificity (86.7% vs 91.0%; ratio, 0.95 [.90–1.003]). Conclusions Our results validate the accuracy of ASCL1/LHX8 methylation analysis for primary screening in WWH, which offers a full-molecular alternative to cytology- or HPV-based screening, without the need for additional triage testing.

Cervical cancer (CC) is one of the most preventable cancers; however, it is the leading cause of cancer-related female deaths in South Africa. This study aimed to compare the efficiency of recurren...

ObjectiveThe platform provided by human papillomavirus (HPV) vaccination for linked public health interventions to improve cervical cancer prevention remains incompletely explored. The Vaccine And Cervical Cancer Screen (VACCS) cross-sectional observation trials aimed to evaluate the efficacy of school-based HPV vaccination linked with maternal cervical cancer screening.MethodsGirls from 29 schools in two provinces in South Africa were invited in writing to receive HPV vaccination. Two approaches to informed consent were compared, namely an audiovisual presentation (VACCS1) and in written format (VACCS2). Markers of vaccine uptake and coverage were calculated, namely uptake among the invited and consented cohorts, and rates of completion and sufficient vaccination. Mothers and female guardians received educational material about cervical cancer, and either a self-sampling device or an invitation to attend existing screening facilities. Knowledge was assessed via structured questionnaires (before and after), and screening uptake was self-reported and directly assessed and compared between these approaches.ResultsVaccine acceptance among 5137 invited girls was similar for the two methods of consent; 99.3% of consented girls received a first dose; overall completion rate was 90.5%. More girls were vaccinated using a two-dose (974/1016 (95.9%)) than a three-dose regimen (1859/2030 (91.6%)). The questionnaire (n=906) showed poor maternal knowledge which improved significantly (pConclusionsSuccessful linking of primary health interventions to control cervical cancer was demonstrated. School-based HPV vaccination, linked to health education, self-sampling, and molecular screening resulted in significant improvements in knowledge and screening.

The inner $\sim$200 pc region of the Galaxy contains a 4 million M$_{\odot}$ supermassive black hole (SMBH), significant quantities of molecular gas, and star formation and cosmic ray energy densities that are roughly two orders of magnitude higher than the corresponding levels in the Galactic disk. At a distance of only 8.2 kpc, the region presents astronomers with a unique opportunity to study a diverse range of energetic astrophysical phenomena, from stellar objects in extreme environments, to the SMBH and star-formation driven feedback processes that are known to influence the evolution of galaxies as a whole. We present a new survey of the Galactic center conducted with the South African MeerKAT radio telescope. Radio imaging offers a view that is unaffected by the large quantities of dust that obscure the region at other wavelengths, and a scene of striking complexity is revealed. We produce total intensity and spectral index mosaics of the region from 20 pointings (144 hours on-target in total), covering 6.5 square degrees with an angular resolution of 4$"$,at a central frequency of 1.28 GHz. Many new features are revealed for the first time due to a combination of MeerKAT's high sensitivity, exceptional $u,v$-plane coverage, and geographical vantage point. We highlight some initial survey results, including new supernova remnant candidates, many new non-thermal filament complexes, and enhanced views of the Radio Arc Bubble, Sgr A and Sgr B regions. This project is a SARAO public legacy survey, and the image products are made available with this article., Comment: 29 pages, 15 figures, 3 tables, accepted for publication in the The Astrophysical Journal. Replacement arXiv version with higher quality figures

The radiosensitivity of haematopoietic stem and progenitor cells (HSPCs) to neutron radiation remains largely underexplored, notwithstanding their potential role as target cells for radiation-induced leukemogenesis. New insights are required for radiation protection purposes, particularly for aviation, space missions, nuclear accidents and even particle therapy. In this study, HSPCs (CD34+CD38+ cells) were isolated from umbilical cord blood and irradiated with 60Co γ-rays (photons) and high energy p(66)/Be(40) neutrons. At 2 h post-irradiation, a significantly higher number of 1.28 ± 0.12 γ-H2AX foci/cell was observed after 0.5 Gy neutrons compared to 0.84 ± 0.14 foci/cell for photons, but this decreased to similar levels for both radiation qualities after 18 h. However, a significant difference in late apoptosis was observed with Annexin-V+/PI+ assay between photon and neutron irradiation at 18 h, 43.17 ± 6.10% versus 55.55 ± 4.87%, respectively. A significant increase in MN frequency was observed after both 0.5 and 1 Gy neutron irradiation compared to photons illustrating higher levels of neutron-induced cytogenetic damage, while there was no difference in the nuclear division index between both radiation qualities. The results point towards a higher induction of DNA damage after neutron irradiation in HSPCs followed by error-prone DNA repair, which contributes to genomic instability and a higher risk of leukemogenesis.

IntroductionPositron emission tomography-computed tomography (PET-CT) imaging is commonly used to identify nodal involvement in locally advanced cervical carcinoma, but its appropriateness for that purpose among HIV-positive patients has rarely been studied. We analyzed PET-CT findings and subsequent treatment prescribed in patients with locally advanced cervical carcinoma in Cape Town, South Africa.MethodsWe identified a cohort of consecutive cervical carcinoma patients International Federation of Gynecology and Obstetrics (FIGO) stage IIB to IIIB at our cancer center who underwent a planning 18-fluorodeoxyglucose (18FDG) PET-CT scan from January 2015 through December 2018. Demographics, PET-CT findings, and subsequent treatment prescribed were recorded. Patients were selected for PET-CT only if they had no signs of distant disease on staging chest X-ray or abdominal ultrasound; were deemed suitable for radical chemoradiation by the multi-disciplinary team; and had normal renal function. HIV-positive patients ideally had to have been established on continuous antiviral therapy for more than 3 months and to have a CD4 cell count above 150 cells/μL. Small cell and neuroendocrine carcinoma cases were excluded from the study. Differences in demographic and clinical measures between HIV-positive and HIV-negative patients were evaluated by means of t-tests for continuous variables and χ2 tests for categorical variables.ResultsOver a 4 year period, 278 patients—192 HIV-negative (69.1%) and 86 HIV-positive (30.9%)—met the inclusion criteria. HIV-positive patients had a median CD4 count of 475 cells/µL (IQR 307–612 cells/µL). More than 80% of patients had pelvic nodal involvement, and more than 40% had uptake in common iliac and/or para-aortic nodes. Nodal involvement was not associated with HIV status. Fifty-four patients (19.4%) had at least one site of distant metastatic disease. Overall, 235 patients (84.5%) were upstaged following PET-CT staging scan. Upstaging was not associated with HIV status (HIV-negative 83.9% vs HIV-positive 87.2%; p=0.47). Ten patients who did not return for radiotherapy were excluded from the analysis. Following their PET-CT scan, treatment intent changed for 124 patients (46.3%): 53.6% of HIV-positive patients and 42.9% of HIV-negative patients (p=0.11).ConclusionWe found no differences between HIV-positive or HIV-negative patients in nodal involvement or occult metastases, and PET-CT imaging did not lead to, or justify, treatment differences between the two groups. Future studies will evaluate survival and correlation of upstaging with outcome.

CITATION: Butt, J. L. & Botha, M. H. 2019. Bone involvement in patients with cervical carcinoma: a single-institution cohort study. Southern African Journal of Gynaecological Oncology, 11(2): 31-37. doi:10.1080/20742835.2019.1702299

Background Cancer screening programs hold much potential for reducing the cervical cancer disease burden in developing countries. The aim of this study was to determine the feasibility of mobile health (mHealth) phone technology to improve management and follow-up of clients with cervical cancer precursor lesions. Methods A sequential mixed methods design was employed for this study. Quantitative data was collected using a cross-sectional survey of 364 women eligible for a Pap smear at public sector health services in Cape Town, South Africa. Information was collected on socio-demographic status; cell phone ownership and patterns of use; knowledge of cervical cancer prevention; and interest in Pap smear results and appointment reminders via SMS-text messages. Descriptive statistics, crude bivariate comparisons and logistic regression models were employed to analyze survey results. Qualitative data was collected through 10 in-depth interviews with primary health care providers and managers involved in cervical cancer screening. Four focus group discussions with 27 women attending a tertiary level colposcopy clinic were also conducted. Themes related to loss of mobile phones, privacy and confidentiality, interest in receiving SMS-text messages, text language and clinic-based management of a SMS system are discussed. Thematic analyses of qualitative data complemented quantitative findings. Results Phone ownership amongst surveyed women was 98% with phones mostly used for calls and short message service (SMS) functions. Over half (58%) of women reported loss/theft of mobile phones. Overall, there was interest in SMS interventions for receiving Pap smear results and appointment reminders. Reasons for interest, articulated by both providers and clients, included convenience, cost and time-saving benefits and benefits of not taking time off work. However, concerns were expressed around confidentiality of SMS messages, loss/theft of mobile phones, receiving negative results via SMS and accessibility/clarity of language used to convey messages. Responsibility for the management of a clinic-based SMS system was also raised. Conclusions Results indicated interest and potential for mHealth interventions in improving follow-up and management of clients with abnormal Pap smears. Health system and privacy issues will need to be addressed for mHealth to achieve this potential. Next steps include piloting of specific SMS messages to test feasibility and acceptability in this setting.

Objective Young women in South Africa are highly affected by sexually transmitted infections (STI), like C. trachomatis (CT) and N. gonorrhoeae (NG). We aimed to estimate the incidence of CT and NG, and its determinants, among young women from the Western Cape, South Africa, participating in an HPV vaccine trial (the EVRI study). Methods HIV-negative women aged 16–24 years were enrolled between October 2012 and July 2013. At enrolment and month 6 participants were screened for CT and NG (Anyplex CT/NG real-time detection method). A questionnaire on demographic and sexual history characteristics was completed at enrolment and month 7. Treatment for CT and/or NG was offered to infected participants. Incidence rates (IR) of CT and NG were estimated. Determinants of incident CT and NG infections were assessed using Poisson regression. Results 365 women were tested for CT and/or NG at least twice. Prevalence of CT and NG at baseline was 33.7% and 10.4%, respectively. Prevalence of co-infection with CT and NG was 7.1%. During 113.3 person-years (py), 48 incident CT infections were diagnosed (IR = 42.4 per 100 py, 95% confidence interval (CI) 31.9–56.2). Twenty-nine incident NG were diagnosed during 139.3 py (IR = 20.8 per 100 py, 95%CI 14.5–29.9). Prevalent CT infection at baseline was associated with incident CT (adjusted incidence rate ratio (aIRR) 5.8, 95%CI 3.0–11.23. More than three lifetime sex partners increased the risk for incident NG (3–4 partners aIRR = 7.3, 95%CI 2.1–26.0; ≥5 partners aIRR = 4.3, 95%CI 1.1–17.5). Conclusions The IR of bacterial STIs among young women in the Western Cape is very high. Besides being previously infected and a higher lifetime number of sex partners, no other risk factors were found for CT and NG, suggesting that the majority of these women were at risk. This indicates the need for intensified prevention of STIs as well as screening and treatment programs to increase sexual health in this region.

Disruption of mental functions in Alzheimer's disease (AD) and related disorders is accompanied by selective degeneration of brain regions. These regions comprise large-scale ensembles of cells organized into systems for mental functioning, however the relationship between clinical symptoms of dementia, patterns of neurodegeneration, and functional systems is not clear. Here we present a model of the association between dementia symptoms and degenerative brain anatomy using F18-fluorodeoxyglucose PET and dimensionality reduction techniques in two cohorts of patients with AD. This reflected a simple information processing-based functional description of macroscale brain anatomy which we link to AD physiology, functional networks, and mental abilities. We further apply the model to normal aging and seven degenerative diseases of mental functions. We propose a global information processing model for mental functions that links neuroanatomy, cognitive neuroscience and clinical neurology.

MeerKAT's large number of antennas, spanning 8 km with a densely packed 1 km core, create a powerful instrument for wide-area surveys, with high sensitivity over a wide range of angular scales. The MeerKAT Galaxy Cluster Legacy Survey (MGCLS) is a programme of long-track MeerKAT L-band (900-1670 MHz) observations of 115 galaxy clusters, observed for $\sim$6-10 hours each in full polarisation. The first legacy product data release (DR1), made available with this paper, includes the MeerKAT visibilities, basic image cubes at $\sim$8" resolution, and enhanced spectral and polarisation image cubes at $\sim$8" and 15" resolutions. Typical sensitivities for the full-resolution MGCLS image products are $\sim$3-5 {\mu}Jy/beam. The basic cubes are full-field and span 4 deg^2. The enhanced products consist of the inner 1.44 deg^2 field of view, corrected for the primary beam. The survey is fully sensitive to structures up to $\sim$10' scales and the wide bandwidth allows spectral and Faraday rotation mapping. HI mapping at 209 kHz resolution can be done at $0, Comment: 43 pages, 33 figures, 6 tables. Accepted for publication in Astronomy and Astrophysics

Objectives In South Africa, where HIV prevalence among adults is 18.9%, cervical carcinoma is the second most common malignancy in women. However, oncology services are considerably more accessible in South Africa than in many neighbouring countries. This study reports five-year overall survival in a cohort of HIV-positive and -negative cervix carcinoma patients undergoing primary radiotherapy at a single institution in South Africa. Methods Prospective cohort study of all locally advanced cervix carcinoma patients referred for radiotherapy (EBRT) from July 2007 to November 2011. Overall survival (OS) was the primary end-point. Results A total of 492 patients commenced treatment with radical intent, including 71 HIV-positive patients (14.4%) and 421 HIV-negative patients (85.6%). Of the 433 who were prescribed standard fractionation EBRT, 384 were prescribed concurrent platinum-based chemotherapy (88.7%). Fewer HIV-positive than HIV-negative patients (58.5% vs. 76.1%; p = 0.007) completed ≥4 cycles. The OS of HIV-negative patients was 49.5% (95%CI; 44.6%–54.4%) at 5 years. The OS of HIV-positive patients was significantly lower, 35.9% (95% CI; 23.9%–48.0%) at 5 years (p = 0.002). In our Cox models, factors affecting outcome were HIV infection, stage IIIB disease, presence of hydronephrosis, and delivery of concurrent chemotherapy. Conclusion In our large cohort, HIV-positive patients had poorer survival than HIV-negative patients, however nearly 40% survived 5 years, justifying provision of the best standard of care to HIV-positive patients with cervical carcinoma.

The incidence of cancer in pregnancy is increasing. The most frequent malignancies include breast and cervical cancers. Diagnosis may be complicated by late presentation. Imaging during pregnancy should consider risks to the fetus. Diagnostic work-up, including tumor markers, can be influenced by the physiology of pregnancy. Treatment of cancer can often be safely administered with good maternal and fetal outcomes. Chemotherapy, radiotherapy, and surgery must be adapted to the pregnancy state. Counselling and emotional support are an essential part of management.

Background. The impact of SARS-CoV-2 infection in pregnant women living with HIV (PLHIV) has not been described previously. Objectives. To describe the clinical presentation and outcomes of a cohort of women with high-risk pregnancies with confirmed COVID-19 to determine whether risk factors for disease severity and adverse outcomes of COVID-19 differed in pregnant women without HIV compared with PLHIV. Methods. We prospectively enrolled pregnant women with COVID-19 attending the high-risk obstetric service at Tygerberg Hospital, Cape Town, South Africa, from 1 May to 31 July 2020, with follow-up until 31 October 2020. Women were considered high risk if they required specialist care for maternal, neonatal and/or anaesthetic conditions. Common maternal or obstetric conditions included hypertensive disorders, morbid obesity (body mass index (BMI) ≥40 kg/m 2 ) and diabetes. Information on demographics, clinical features, and maternal and neonatal outcomes was collected and compared for PLHIV v. pregnant women without HIV. Results. One hundred women (72 without HIV and 28 PLHIV) with high-risk pregnancies had laboratory-confirmed COVID-19. Among the 28 PLHIV, the median (interquartile range) CD4 count was 441 (317 - 603) cells/µL, and 19/26 (73%) were virologically suppressed. COVID-19 was diagnosed predominantly in the third trimester (81%). Obesity (BMI ≥30 in n =61/81; 75%) and hypertensive disorders were frequent comorbidities. Of the 100 women, 40% developed severe or critical COVID-19, 15% required intensive care unit admission and 6% needed invasive ventilation. Eight women died, 1 from advanced HIV disease complicated by bacteraemia and urosepsis. The crude maternal mortality rate was substantially higher in women with COVID-19 compared with all other deliveries at our institution during this period (8/91 (9%) v. 7/4 058 (0.2%); p

Background: HPV antibodies are a marker of past exposure to the virus. Our objective was to assess HPV serostatus pre- and post-vaccination among HIV-negative women. Methods: Women aged 16â24 years old were randomized in a placebo controlled trial utilizing the 4-valent HPV (4vHPV) vaccine (NCT01489527, clinicaltrials.gov). Participants (n=389) received the 4vHPV vaccine or placebo following a three dose schedule. Sera were collected at Day 1 and Month 7 for assessment of HPV 6, 11, 16, and 18 neutralizing antibody levels using a multiplex competitive Luminex immunoassay (Merck) based on detecting the L1 capsid antigen for each HPV type. Results: Seroprevalence was 73% for HPV6, 47% for HPV11, 33% for HPV16, and 44% for HPV18. Seroprevalence for any HPV type did not significantly differ by age or lifetime number of partners. The majority of participants (64%) had two or more 4vHPV antibodies present at enrollment and 12% had antibodies to all four. Among women in the vaccine arm, those that were seropositive for HPV16 at enrollment had higher titers at month 7 compared to women that were seronegative for HPV16 at enrollment; this trend holds for the other HPV types as well. Seroconversion among baseline seronegative participants in the placebo group ranged from 5% for HPV16 to 23% for HPV6. Conclusion: HPV seroprevalence was high in this population, emphasizing the need to vaccinate prior to sexual debut. Keywords: HPV vaccine, EVRI, Seroprevalence, cLIA

ObjectiveTo estimate the prevalence and describe the patterns of concurrent human papillomavirus (HPV) and STIs and associated factors among HIV-negative young Western Cape, South African women participating in the Efficacy of HPV Vaccine to Reduce HIV Infection (EVRI) trial.MethodsHIV-negative women aged 16–24 years old were enrolled in the EVRI trial (NCT01489527) and randomised to receive the licensed four-valent HPV vaccine or placebo. At study entry, participants were clinically evaluated for five STIs: herpes simplex virus type 2 (HSV-2), chlamydia, gonorrhoea, syphilis and disease-causing HPV genotypes (6/11/16/18/31/33/35/39/45/51/52/56/58/59/68). Demographic and sexual history characteristics were compared among women with STI co-infections, single infection and no infection using Pearson χ2and Mann-Whitney tests. ORs were calculated to evaluate factors associated with STI co-infection prevalence.ResultsAmong 388 young women, STI co-infection prevalence was high: 47% had ≥2 concurrent STIs, 36% had a single STI and 17% had none of the five evaluated STIs. HPV/HSV-2 (26%) was the most prevalent co-infection detected followed by HPV/HSV-2/Chlamydia trachomatis(CT) (17%) and HPV/CT (15%). Co-infection prevalence was independently associated with alcohol use (adjusted OR=2.01, 95% CI 1.00 to 4.06) and having a sexual partner with an STI (adjusted OR=6.96, 95% CI 1.53 to 30.08).ConclusionsAmong high-risk young women from underserved communities such as in Southern Africa, a multicomponent prevention strategy that integrates medical and behavioural interventions targeting both men and women is essential to prevent acquisition of concurrent STI infections and consequent disease.Trial registration numberNCT01489527; Post-results.

Introduction/Background Self-sampling is an attractive addition to cervical screening programmes. It can remove barriers to testing as some women fear a gynaecological examination, and offers potential task shifting and resource savings for overburdened health care systems often in low resource settings. Methodology We performed a large cervical cancer screening study with ultimate objective to determine optimal screening algorithms for South African women. This interim analysis describes the experiences of a subset of women who were asked to fill in a questionnaire about the self-samplers. The aim was to compare user experiences of two different self-samplers in a South African public sector setting. 253 participants received a short education by the Health Care Worker (HCW), and were given either the Digene HC2 DNA Collection Device (Qiagen)or the Evalyn® Brush (Rovers Medical). Participant and HCW filled in a questionnaire afterwards. Results Analysis was done for 253 women. Mean age in group was 41.33 years (range [24–63], median 41 years). 82 women were in the Digene group, and 171 in the Evalyn group. HCWs reported more bleeding with the Digene vs. Evalyn users (37.9% vs. 20.4%). Both groups felt it was very or somewhat easy to use (98.8% vs. 94.2%). Women had little fear of using the devices, (61.0% vs 71.3%), and felt sure of how to use them. There was more bleeding reported by Digene vs Evalyn users (9.8% vs. 4.1%), and lastly, there was little pain experienced by users of either brush, 91.5% vs 93.6%. Conclusion In this cohort, both the self-samplers were well tolerated; there was more bleeding associated with use of the Digene device, both seen by participants and HCW, which will be analysed further once results are available. Self-sampling is feasible and acceptable in this public setting. Disclosure Rover BD donated Evalyn brushes for the study, and Qiagen provided digene collection devices, but neither were involved in preparing papers.

The Galactic Centre contains a supermassive black hole with a mass of 4 million suns within an environment that differs markedly from that of the Galactic disk. While the black hole is essentially quiescent in the broader context of active galactic nuclei, X-ray observations have provided evidence for energetic outbursts from its surroundings. Also, while the levels of star formation in the Galactic Centre have been approximately constant over the last few hundred Myr, there is evidence of elevated short-duration bursts, strongly influenced by interaction of the black hole with the enhanced gas density present within the ring-like Central Molecular Zone at Galactic longitude |l| < 0.7 degrees and latitude |b| < 0.2 degrees. The inner 200 pc region is characterized by large amounts of warm molecular gas, a high cosmic ray ionization rate, unusual gas chemistry, enhanced synchrotron emission, and a multitude of radio-emitting magnetised filaments, the origin of which has not been established. Here we report radio imaging that reveals bipolar bubbles spanning 1 degree x 3 degrees (140 parsecs x 430 parsecs), extending above and below the Galactic plane and apparently associated with the Galactic Centre. The structure is edge-brightened and bounded, with symmetry implying creation by an energetic event in the Galactic Centre. We estimate the age of the bubbles to be a few million years, with a total energy of 7 x 10^52 ergs. We postulate that the progenitor event was a major contributor to the increased cosmic-ray density in the Galactic Centre, and is in turn the principal source of the relativistic particles required to power the synchrotron emission of the radio filaments within and in the vicinity of the bubble cavities., 25 pages, 3 figures, 3 tables, authors' version of a Letter published in Nature on 11 September 2019

Objectives PET-CT imaging is commonly used as a staging tool to identify nodal involvement in locally advanced cervical carcinoma (LACC). The value of PET-CT for staging HIV-infected patients with locally advanced CC has not been previously described. We analyzed PET-CT findings in a cohort of patients with LACC in Cape Town, SA. Methods Patients with LACC FIGO Stage IIb or IIIB, and were referred, on the basis of stage and the availability of bookings, for PET-CT/radiotherapy planning CT from January 2015 to December 2018. A team of expert nuclear medicine physicians and radiologists reported the PET-CT examinations. Descriptive statistics and chi-squared tests were used to compare patients with and without HIV. Results A total of 286 patients underwent PET-CT. Eighty-nine patients (31.2%) were HIV-positive. Pelvic nodal involvement was notably found in 205 patients (72.4%), including 77.3% of those who had HIV and 70.3% of those who did not (p=0.22); para-aortic nodal disease in 114 patients (42.7% of HIV+ vs 38.8% HIV-, p=0.53); and distant disease in 55 patients (23.6% of HIV+ vs 17.3% HIV-; p=0.22). In total, 223 patients (79.3%), including 81.8% of patients without and 75.0% of patients with HIV (p=0.31), were prescribed standard fractionation EBRT. Twenty-two patients (7.8%) were prescribed hypofractionated EBRT, and 36 patients (12.8%) palliative therapy. Five patients (1.7%) did not return. Conclusions PET-CT imaging found no differences between LACC patients, with and without HIV, in nodal involvement or occult metastases and did not lead to, or justify, treatment differences.

We present the confusion-limited 1.28 GHz MeerKAT DEEP2 image covering one $\approx 68'$ FWHM primary beam area with $7.6''$ FWHM resolution and $0.55 \pm 0.01$ $\mu$Jy/beam rms noise. Its J2000 center position $\alpha=04^h 13^m 26.4^s$, $\delta=-80^\circ 00' 00''$ was selected to minimize artifacts caused by bright sources. We introduce the new 64-element MeerKAT array and describe commissioning observations to measure the primary beam attenuation pattern, estimate telescope pointing errors, and pinpoint $(u,v)$ coordinate errors caused by offsets in frequency or time. We constructed a 1.4 GHz differential source count by combining a power-law count fit to the DEEP2 confusion $P(D)$ distribution from $0.25$ to $10$ $\mu$Jy with counts of individual DEEP2 sources between $10$ $\mu$Jy and $2.5$ mJy. Most sources fainter than $S \sim 100$ $\mu$Jy are distant star-forming galaxies obeying the FIR/radio correlation, and sources stronger than $0.25$ $\mu$Jy account for $\sim93\%$ of the radio background produced by star-forming galaxies. For the first time, the DEEP2 source count has reached the depth needed to reveal the majority of the star formation history of the universe. A pure luminosity evolution of the 1.4 GHz local luminosity function consistent with the Madau & Dickinson (2014) model for the evolution of star-forming galaxies based on UV and infrared data underpredicts our 1.4 GHz source count in the range $-5 \lesssim \log[S(\mathrm{Jy})] \lesssim -4$., Comment: 20 pages, 18 figures. Accepted for publication in ApJ

Summary Objective The objective of this analysis was to assess human papillomavirus (HPV) infection persistence and incidence 7-months post-enrollment by HPV vaccine study arm (vaccine or placebo). Methods HIV-negative, sexually active women aged 16–24 years in the Western Cape, South Africa, were enrolled in the EVRI Trial and were randomized to receive 4-valent HPV vaccine or placebo. Cervical specimens were collected at enrollment and at the 7-month visit and were genotyped for HPV. HPV prevalence, persistence, and incidence were calculated. Prevalence ratios and odds ratios were calculated to assess factors associated with a prevalent and incident HPV infection. Results HPV incidence rates were marginally higher for the placebo group (n = 163) compared to the vaccine group (n = 169). A large proportion of the prevalent high-risk (HR-HPV) HPV types (49%) persisted over the 7-month period in both arms. Prevalent HR-HPV infection was significantly associated with a prevalent gonorrhea infection and detection of Herpes simplex type 2 antibodies. Incident HR-HPV infection was significantly associated with abnormal cervical cytology at enrollment and younger age. Conclusions Women living in geographic areas, such as southern Africa, at high-risk for HPV need to receive HPV vaccination at a very young age to maximally prevent infection and subsequent disease.

Background. An increase in vulvar cancer in young women is attributed to infection with oncogenic human papillomavirus (HPV). South Africa (SA) has a high prevalence of HPV, and it was therefore hypothesised that women with vulvar cancer here would be younger than in high-income countries (HICs). Objective. To describe age, cancer stage, treatment and outcome of patients with vulvar cancer at a tertiary referral centre in SA. Methods. In a retrospective observational study, patient records of women diagnosed with vulvar cancer between 2001 and 2014 were reviewed and demographic and surgical details captured. Histology results of vulvar biopsies and resected specimens were checked for HPV changes, koilocytes and usual-type vulval intraepithelial neoplasia. Patients were restaged using the International Federation of Gynecology and Obstetrics (FIGO) 2009 staging system to allow for comparison of outcomes. Five-year disease-specific survival probability curves were generated using Kaplan-Meier analysis. Results. The mean age of the 180 patients in the study was 52.5 years. Those who had documented HPV changes on histological specimens had a mean age of 50.4 years. More than 50% of the patients had advanced-stage disease, and 62.7% were treated with primary surgery. Five-year disease-specific survival probabilities were similar to those reported in the literature. Conclusions. Vulvar cancer should not be regarded as a disease of the elderly in SA, as women with vulvar cancer are 10 - 15 years younger than in HICs. A large proportion of patients present with advanced-stage disease. Health professionals should be alert to vulvar lesions, especially in women with abnormal Pap smears, to reduce the morbidity and mortality of this disease.

New radio (MeerKAT and Parkes) and X-ray (XMM-Newton, Swift, Chandra, and NuSTAR) observations of PSR J1622-4950 indicate that the magnetar, in a quiescent state since at least early 2015, reactivated between 2017 March 19 and April 5. The radio flux density, while variable, is approximately 100x larger than during its dormant state. The X-ray flux one month after reactivation was at least 800x larger than during quiescence, and has been decaying exponentially on a 111+/-19 day timescale. This high-flux state, together with a radio-derived rotational ephemeris, enabled for the first time the detection of X-ray pulsations for this magnetar. At 5%, the 0.3-6 keV pulsed fraction is comparable to the smallest observed for magnetars. The overall pulsar geometry inferred from polarized radio emission appears to be broadly consistent with that determined 6-8 years earlier. However, rotating vector model fits suggest that we are now seeing radio emission from a different location in the magnetosphere than previously. This indicates a novel way in which radio emission from magnetars can differ from that of ordinary pulsars. The torque on the neutron star is varying rapidly and unsteadily, as is common for magnetars following outburst, having changed by a factor of 7 within six months of reactivation., Comment: Published in ApJ (2018 April 5); 13 pages, 4 figures

Persistent HPV infection with an oncogenic strain of high-risk HPV is a necessary risk factor for the development of invasive cervical cancer. The improved understanding of the cytopathic effects of HPV led to the development of novel diagnostic and preventative tools. HPV manages to evade the immune response of the host. Oncogenic HPV infection does not progress to cancer in all infected individuals and certain variables make individuals more susceptible to the development of pre-malignant and malignant disease. The alpha HPV types are divided into high- and low-risk types according to their ability to cause malignant disease. HPV is mostly transmitted by mucosal contact and infects basal keratinocytes, most likely at a site of micro-trauma that exposes the basal layer to virus. The ability of low-risk HPV to disrupt cell proliferation is limited. In high-risk HPV infections, E6 and E7 are expressed early and strongly leading to accumulation of genetic changes that progress to cancer. The specific HPV type is the strongest factor associated with persistence and oncogenic potential. The concept of latency and reactivation may explain the re-emergence of HPV DNA detection many years after exposure. After a period of latency, reactivation of detectable HPV may follow immune suppression or hormonal changes.

Background Increasing resistance to cisplatin as well as the severity of the adverse effects limit the use of this drug, particularly at high doses. Evidence has implicated the importance of autophagy in cancer resistance as well as the fact that various chemotherapy agents induce autophagy in cancer cells. We therefore aimed to first assess the role of autophagy in cisplatin treatment and second to assess whether a nontoxic concentration of cisplatin, together with autophagy inhibition, is able to maintain its cancer-specific cytotoxic action. Methods Three human cervical cell lines were used: a noncancerous ectocervical epithelial cell line (Ect1/E6E7) and 2 cancerous cervical cell lines (HeLa and CaSki). Autophagy was monitored through the presence of the classical protein markers LC-3 II and p62 under basal and treatment conditions, and inhibited using bafilomycin and autophagy protein 5 (ATG5) siRNA under treatment conditions. Cell death was analyzed through examination of the apoptotic markers PARP and caspase-3 through Western blotting, as well as the Caspase-Glo assay to confirm caspase-3/7 activity. Cervical biopsies were analyzed for the presence of LC-3 using Western blotting and immunofluorescence to determine if a correlation between autophagic levels and the progression of the disease exists. Results Cervical cancer cells exhibit increased basal autophagic levels in comparison to the noncancerous counterparts. Cisplatin treatment enhanced autophagic activity in all 3 cell lines. Inhibition of this autophagic response together with cisplatin treatment leads to significant increases in cancer cell death. Expression profiles of LC-3 in normal, premalignant (low-grade and high-grade squamous intraepithelial lesion), and cancerous cervical tissue revealed that autophagy is significantly up-regulated in HSILs and carcinoma cervical tissue, which emphasized the role of autophagy in the progression of the disease. Conclusions The inhibition of autophagy improves the cytotoxicity of a nontoxic concentration of cisplatin and provides a promising new avenue for the future treatment of cervical cancer.

This study investigated sexual activity, knowledge of contraceptives use among females choosing termination of pregnancy (TOP) at a provincial clinic in South Africa. This was a quantitative and observational study in the form of a cross-sectional survey. A pre-tested self-administered questionnaire was used to collect data from 61 respondents who had terminated their pregnancies. Almost ninety-two (91.8%) percent of the respondents were single women between 18 and 27 years of age. Their level of education showed that 32% had completed high school, 28% were high school learners, 21.1% were tertiary education level learners and 1.8% had tertiary education. The frequency of sexual activity was mostly once a month (40%), followed by once a week (36.5%). Unemployment was high (36%), making the respondents dependent on government grants. Most of the women were aware of contraceptives methods (88.5%). The majority of the respondents (75.4%) have heard about emergency contraceptives (EC), while only 11.5% had never heard of contraceptives in general. The condom was the most popular method (54.1%), followed by the injection (45.9%). However, although 88.5% and 75.4% have heard of emergency contraceptives, their knowledge of contraceptives in general was very low. Contraceptives were used by 78.6% before termination of their pregnancy (TOP) and the most frequently used method was the injection at 36.6%. The respondents were the initiators of TOP. The researchers recommended that awareness of contraceptives should be promoted, and programmes aimed at changing the behaviour of sexually active females should be designed in order for them to make use of reproductive health services and family planning. Continuous education on sexual activities and contraceptives needs to be given to women visiting a reproductive health clinic. Policymakers should facilitate access to modern contraceptives and promote their effectiveness in all disadvantaged communities, thus addressing the root cause of the termination of unplanned pregnancies.

Ovarian cancers usually spread in four different ways: Trans peritoneal spread, direct invasion, lymphatic, and hematogenous. The primary way of metastasis of ovarian carcinoma is considered to be direct peritoneal dissemination in the abdominal cavity and serosa of bowel. Conversely, hematogenous dissemination is rare, and seldom leads to gastrointestinal metastasis. We report a case of a patient who was operated for an epithelial ovarian cancer and presented with small intestinal metastasis 8 months later. Vascular cancer emboli could be detected by microscopy. Immunohistochemistry tests proved the small intestinal metastasis originated from primary ovarian cancer.

The construction of the seven-dish Karoo Array Telescope (KAT-7) array in the Karoo region of the Northern Cape in South Africa was intended primarily as an engineering prototype for technologies and techniques applicable to the MeerKAT telescope. This paper looks at the main engineering and scientific highlights from this effort, and discusses their applicability to both MeerKAT and other next-generation radio telescopes. In particular, we found that the composite dish surface works well, but it becomes complicated to fabricate for a dish lacking circular symmetry; the Stirling cycle cryogenic system with ion pump to achieve vacuum works but demands much higher maintenance than an equivalent Gifford-McMahon cycle system; the ROACH (Reconfigurable Open Architecture Computing Hardware)-based correlator with SPEAD (Streaming Protocol for Exchanging Astronomical Data) protocol data transfer works very well and KATCP (Karoo Array Telescope Control Protocol) control protocol has proven very flexible and convenient. KAT-7 has also been used for scientific observations where it has a niche in mapping low surface-brightness continuum sources, some extended H I haloes and OH masers in star-forming regions. It can also be used to monitor continuum source variability, observe pulsars, and make Very Long Baseline Interferometry observations.

To determine factors that influence excision treatment outcome and recurrence of cervical squamous intraepithelial lesions (SIL) in women living with HIV infection, we analysed 1848 women who underwent excision treatment of cervical SIL at Tygerberg Hospital, Cape Town, South Africa. We compared treatment failure defined as presence of cervical intraepithelial neoplasia (CIN) I (presence of CIN I or higher at first follow-up after excision treatment) and post-excision recurrence of lesions (at one year or later) between women of HIV-positive, -negative or unknown status and examined factors associated with excision treatment outcome and recurrence. HIV-infected women experienced higher treatment failure than uninfected women (53.8% versus 26.9%, P< 0.001). At treatment failure, more HIV-infected women had low-grade squamous intraepithelial lesion (LSIL) compared with uninfected women (64.9% versus 37.3%, P < 0.001). Treatment failure did not differ with the type of excision used in HIV-infected women. HIV-infected women were more likely to experience recurrence of lesions after excision treatment than uninfected women (hazard ratio 1.95, 95% confidence interval [CI] 1.59-2.39; P < 0.001). Antiretroviral therapy (ART) initiated before excision biopsy had a strong protective effect against recurrence (hazard ratio 0.70, 95% CI 0.55-0.89; P = 0.006). Our data suggest that women with cervical SIL initiated on ART earlier may be expected to have better long-term excision treatment outcome. Close follow-up should be maintained after cervical excision treatment, especially in a setting of high HIV prevalence.

This study aimed to investigate the progression and persistence of low-grade squamous intraepithelial lesions (SILs) in human immunodeficiency virus (HIV)-infected women.Study participants for this retrospective cohort study were 1,720 women who had LSIL as their first abnormal Pap smear. A comparison of the survival of LSIL without progression to high-grade SIL as progression-free time and the survival of SIL without clearance of the lesion as persistence of SIL was done for women of HIV-positive, HIV-negative, or unknown status using the Kaplan-Meier method. Multivariable Cox proportional hazards regression model was applied to identify independent risk factors for disease progression or persistence.We found progression of LSIL not different between HIV groups but that persistence occurred more in HIV-positive women (63.8% vs 35.0%, p.001). For the HIV group, antiretroviral therapy that was started before the first LSIL was associated with decreased risk for progression compared with no antiretroviral therapy (hazard ratio = 0.66, 95% CI = 0.54-0.81, p.001). Antiretroviral therapy also improved clearance when corrected for excision treatment and age (hazard ratio = 1.71, 95% CI = 1.29-2.27, p.001). Excision of LSIL reduced the risk of progression. In HIV-negative women, progression was reduced from 54.7% to 0.0% (p.001), and from 46.9% to 6.4% in HIV-positive women (p.001). Excision also reduced persistence in HIV-negative women from 39.5% to 7.1% (p = .001), but for HIV-positive women, the effect was smaller (from 66.3% to 45.5%, p.001).Antiretroviral treatment reduced the risk for progression and persistence of LSIL in HIV-infected women.