Search

By August, 2021, South Africa had been affected by three waves of SARS-CoV-2; the second associated with the beta variant and the third with the delta variant. Data on SARS-CoV-2 burden, transmission, and asymptomatic infections from Africa are scarce. We aimed to evaluate SARS-CoV-2 burden and transmission in one rural and one urban community in South Africa.We conducted a prospective cohort study of households in Agincourt, Mpumalanga province (rural site) and Klerksdorp, North West province (urban site) from July, 2020 to August, 2021. We randomly selected households for the rural site from a health and sociodemographic surveillance system and for the urban site using GPS coordinates. Households with more than two members and where at least 75% of members consented to participate were eligible. Midturbinate nasal swabs were collected twice a week from household members irrespective of symptoms and tested for SARS-CoV-2 using real-time RT-PCR (RT-rtPCR). Serum was collected every 2 months and tested for anti-SARS-CoV-2 antibodies. Main outcomes were the cumulative incidence of SARS-CoV-2 infection, frequency of reinfection, symptomatic fraction (percent of infected individuals with ≥1 symptom), the duration of viral RNA shedding (number of days of SARS-CoV-2 RT-rtPCR positivity), and the household cumulative infection risk (HCIR; number of infected household contacts divided by the number of susceptible household members).222 households (114 at the rural site and 108 at the urban site), and 1200 household members (643 at the rural site and 557 at the urban site) were included in the analysis. For 115 759 nasal specimens from 1200 household members (follow-up 92·5%), 1976 (1·7%) were SARS-CoV-2-positive on RT-rtPCR. By RT-rtPCR and serology combined, 749 of 1200 individuals (62·4% [95% CI 58·1-66·4]) had at least one SARS-CoV-2 infection episode, and 87 of 749 (11·6% [9·4-14·2]) were reinfected. The mean infection episode duration was 11·6 days (SD 9·0; range 4-137). Of 662 RT-rtPCR-confirmed episodes (14 days after the start of follow-up) with available data, 97 (14·7% [11·9-17·9]) were symptomatic with at least one symptom (in individuals aged19 years, 28 [7·5%] of 373 episodes symptomatic; in individuals aged ≥19 years, 69 [23·9%] of 289 episodes symptomatic). Among 222 households, 200 (90·1% [85·3-93·7]) had at least one SARS-CoV-2-positive individual on RT-rtPCR or serology. HCIR overall was 23·9% (195 of 817 susceptible household members infected [95% CI 19·8-28·4]). HCIR was 23·3% (20 of 86) for symptomatic index cases and 23·9% (175 of 731) for asymptomatic index cases (univariate odds ratio [OR] 1·0 [95% CI 0·5-2·0]). On multivariable analysis, accounting for age and sex, low minimum cycle threshold value (≤30 vs30) of the index case (OR 5·3 [2·3-12·4]) and beta and delta variant infection (vs Wuhan-Hu-1, OR 3·3 [1·4-8·2] and 10·4 [4·1-26·7], respectively) were associated with increased HCIR. People living with HIV who were not virally supressed (≥400 viral load copies per mL) were more likely to develop symptomatic illness when infected with SAR-CoV-2 (OR 3·3 [1·3-8·4]), and shed SARS-CoV-2 for longer (hazard ratio 0·4 [95% CI 0·3-0·6]) compared with HIV-uninfected individuals.In this study, 565 (85·3%) SARS-CoV-2 infections were asymptomatic and index case symptom status did not affect HCIR, suggesting a limited role for control measures targeting symptomatic individuals. Increased household transmission of beta and delta variants was likely to have contributed to successive waves of SARS-CoV-2 infection, with more than 60% of individuals infected by the end of follow-up.US CDC, South Africa National Institute for Communicable Diseases, and Wellcome Trust.

Determine if spinal curvatures, deformities, as well as level of disability (due to back pain) changes with aging in adults with bilateral spastic cerebral palsy after receiving orthopedic interval surgery approach treatment in childhood.Consecutive case-series SETTING: Urban South Africa PARTICIPANTS: Twenty-seven ambulatory adults with cerebral palsy MAIN OUTCOME MEASURES: Spinal curvatures (scoliosis, thoracic kyphosis and lumbar lordosis) and deformities (spondylolysis and spondylolisthesis) were determined with X-rays, while the level of disability was assessed with the Oswestry Disability Index.The prevalence of spinal abnormalities were: 30% scoliosis (mild:30°), 0% thoracic hyperkyphosis, 15% lumbar hyperlordosis, 0%; spondylolysis, and 0% spondylolisthesis. No changes in scoliosis and lumbar lordosis angles were observed, while the change in thoracic kyphosis angle was smaller than the minimal clinically important difference and moved closer toward the norm-values for typically developing adults. Level of disability remained similar with 63% reporting minimal disability, 26% moderate disability and 11% severe disability. No associations with spinal curvatures were found.No clinically meaningful changes in spinal curvatures, deformities and level of disability due to pain were seen during the 6 years follow-up period in adults with cerebral palsy who have been treated with interval surgery approach in childhood.

BACKGROUND: Sub-Saharan Africa is undergoing an epidemiologic transition from infectious diseases to cardiovascular diseases. From 2014 to 2019, sociodemographic surveillance was performed in a large cohort in rural South Africa. METHODS: Disease prevalence and incidence were calculated using inverse probability weights. Poisson regression was used to identify disease predictors. The percentage of individuals with controlled ( RESULTS: Compared with 2014 (n=5059), study participants in 2019 (n=4176) had similar rates of obesity (mean body mass index, 27.5±10.0 versus 27.0±6.5) but higher smoking (9.1% versus 11.5%) and diabetes (11.1% versus 13.9%). There was no significant increase in hypertension prevalence (58.4% versus 59.8%; age adjusted, 64.3% versus 63.3%), and there was a significant reduction in mean systolic blood pressure (138.0 versus 128.5 mm Hg; P CONCLUSIONS: The hypertension prevalence and incidence are plateauing in this aging cohort. There was a statistically and clinically significant decline in mean blood pressure and a substantial increase in individuals with controlled hypertension on medication. The prevalence of cardiometabolic risk factors did not decrease over time, suggesting that the blood pressure decrease is likely due to increased medication access and adherence, promoted by local health systems.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections may be underestimated because of limited access to testing. We measured SARS-CoV-2 seroprevalence in South Africa every 2 months during July 2020–March 2021 in randomly selected household cohorts in 2 communities. We compared seroprevalence to reported laboratory-confirmed infections, hospitalizations, and deaths to calculate infection–case, infection–hospitalization, and infection–fatality ratios in 2 waves of infection. Post–second wave seroprevalence ranged from 18% in the rural community children

Background Orthopaedic surgery is commonly performed in children with cerebral palsy (CP) and spastic diplegia to improve functional mobility. However, no research has quantified levels of accomplishment and satisfaction in daily activities and participation long-term after surgery. Therefore, this study aimed to investigate 1) the level of accomplishment and satisfaction of life habits in adults with CP, 2) whether there were differences between Gross Motor Function Classification System (GMFCS) levels, and 3) associations with contextual factors, functional level and frequency of pain. Methods Levels of accomplishment and satisfaction in activity and participation were assessed using the Life-Habits 3.1 questionnaire in 30 adults with CP and spastic diplegia who received the first orthopaedic intervention more than 15 years ago (age: median [interquartile range (IQR)] = 27:8 [21:7–33:8] y:mo; GMFCS level I/II/III: n = 15/11/4). GMFCS and Functional Mobility Scale (FMS) assessed mobility over 5 m, 50 m and 500 m. Participants reported frequency of back pain and pain in the lower and upper limb. Results On average 63% of the participants were independent and faced no difficulties in the accomplishment of all life habits. Difficulties were mostly experienced for ‘mobility’, ‘housing’ and ‘recreation’ (all 61%). Participants were overall satisfied, with lowest scores for ‘employment’ (13% dissatisfied). Between the GMFCS levels, accomplishment scores of participants with level I were significantly higher than level II. In addition, negative associations were found between accomplishment of life habits and GMFCS level, FMS, and pain on spinal level. Conclusion Levels of accomplishment and satisfaction were relatively high among adults with CP who underwent orthopaedic interventions during childhood. However, negative associations between accomplishment levels and level of functioning and back pain argue for rehabilitation programs specialized on these factors. This information is imperative for physicians and allied health care professionals to guide adults with CP during ageing.

Monitoring treatment response is an important precaution in spinal tuberculosis (TB), particularly when the condition was clinically diagnosed rather than bacteriologically confirmed and when drug susceptibility testing was not performed. Conventional monitoring measures have limitations and there is a need for favourable alternatives. Therefore, this study aimed to investigate changes in immune biomarkers over the course of treatment for spinal TB and to compare these responses to the conventional monitoring measure, erythrocyte sedimentation rate (ESR).Patients with spinal TB were recruited from a tertiary hospital in the Western Cape, South Africa, and provided blood samples at 0, 3, 6, 9 and 12 months of TB treatment. Blood samples were analysed for ESR, using standard techniques, and for 19 cytokines, using a multiplex platform. Changes in ESR and cytokine levels were investigated using a mixed model ANOVA and Least Significant Difference post-hoc testing.Twenty-six patients with spinal TB were included in the study although only fifteen remained in follow-up at 12 months. Seven biomarkers changed significantly over the course of treatment (CRP, Fibrinogen, IFN-γ, Ferritin, VEGF-A, ApoA1 and NCAM, p 0.01) with a further three showing a strong trend towards change (CCL1, CXCL9 and GDF-15, 0.05 ≥ p ≤ 0.06). Responsive biomarkers could be approximately grouped according to patterns of progressive, initial or delayed change. ESR performed similarly to CRP, Fibrinogen and IFN-γ with all showing significant decreases between 0, 6 and 12- months of treatment. Individual ESR responses were variable.Individual ESR responses may be unreliable and support the investigation of multi-marker approaches to evaluating treatment response in spinal TB. Biomarkers of treatment response identified in the current study require validation in a larger study, which may also incorporate aspects such as evaluating biomarkers within the first week of treatment and the inclusion of a healthy control group.

BackgroundBy August 2021, South Africa experienced three SARS-CoV-2 waves; the second and third associated with emergence of Beta and Delta variants respectively.MethodsWe conducted a prospective cohort study during July 2020-August 2021 in one rural and one urban community. Mid-turbinate nasal swabs were collected twice-weekly from household members irrespective of symptoms and tested for SARS-CoV-2 using real-time reverse transcription polymerase chain reaction (rRT-PCR). Serum was collected every two months and tested for anti-SARS-CoV-2 antibodies.ResultsAmong 115,759 nasal specimens from 1,200 members (follow-up rate 93%), 1976 (2%) were SARS-CoV-2-positive. By rRT-PCR and serology combined, 62% (749/1200) of individuals experienced ≥1 SARS-CoV-2 infection episode, and 12% (87/749) experienced reinfection. Of 662 PCR-confirmed episodes with available data, 15% (n=97) were associated with ≥1 symptom. Among 222 households, 200 (90%) had ≥1 SARS-CoV-2-positive individual. Household cumulative infection risk (HCIR) was 25% (213/856). On multivariable analysis, accounting for age and sex, index case lower cycle threshold value (OR 3.9, 95%CI 1.7-8.8), urban community (OR 2.0,95%CI 1.1-3.9), Beta (OR 4.2, 95%CI 1.7-10.1) and Delta (OR 14.6, 95%CI 5.7-37.5) variant infection were associated with increased HCIR. HCIR was similar for symptomatic (21/110, 19%) and asymptomatic (195/775, 25%) index cases (p=0.165). Attack rates were highest in individuals aged 13-18 years and individuals in this age group were more likely to experience repeat infections and to acquire SARS-CoV-2 infection. People living with HIV who were not virally supressed were more likely to develop symptomatic illness, and shed SARS-CoV-2 for longer compared to HIV-uninfected individuals.ConclusionsIn this study, 85% of SARS-CoV-2 infections were asymptomatic and index case symptom status did not affect HCIR, suggesting a limited role for control measures targeting symptomatic individuals. Increased household transmission of Beta and Delta variants, likely contributed to successive waves, with >60% of individuals infected by the end of follow-up.Research in contextEvidence before this studyPrevious studies have generated wide-ranging estimates of the proportion of SARS-CoV-2 infections which are asymptomatic. A recent systematic review found that 20% (95% CI 3%-67%) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections remained asymptomatic throughout infection and that transmission from asymptomatic individuals was reduced. A systematic review and meta-analysis of 87 household transmission studies of SARS-CoV-2 found an estimated secondary attack rate of 19% (95% CI 16-22). The review also found that household secondary attack rates were increased from symptomatic index cases and that adults were more likely to acquire infection. As of December 2021, South Africa experienced three waves of SARS-CoV-2 infections; the second and third waves were associated with circulation of Beta and Delta variants respectively. SARS-CoV-2 vaccines became available in February 2021, but uptake was low in study sites reaching 5% fully vaccinated at the end of follow up. Studies to quantify the burden of asymptomatic infections, symptomatic fraction, reinfection frequency, duration of shedding and household transmission of SARS-CoV-2 from asymptomatically infected individuals have mostly been conducted as part of outbreak investigations or in specific settings. Comprehensive systematic community studies of SARS-CoV-2 burden and transmission including for the Beta and Delta variants are lacking, especially in low vaccination settings.Added value of this studyWe conducted a unique detailed COVID-19 household cohort study over a 13 month period in South Africa, with real time reverse transcriptase polymerase chain reaction (rRT-PCR) testing twice a week irrespective of symptoms and bimonthly serology. By the end of the study in August 2021, 749 (62%) of 1200 individuals from 222 randomly sampled households in a rural and an urban community in South Africa had at least one confirmed SARS-CoV-2 infection, detected on rRT-PCR and/or serology, and 12% (87/749) experienced reinfection. Symptom data were analysed for 662 rRT-PCR-confirmed infection episodes that occurred >14 days after the start of follow-up (of a total of 718 rRT-PCR-confirmed episodes), of these, 15% (n=97) were associated with one or more symptoms. Among symptomatic indvidiausl, 9% (n=9) were hospitalised and 2% (n=2) died. Ninety percent (200/222) of included households, had one or more individual infected with SARS-CoV-2 on rRT-PCR and/or serology within the household. SARS-CoV-2 infected index cases transmitted the infection to 25% (213/856) of susceptible household contacts. Index case ribonucleic acid (RNA) viral load proxied by rRT-PCR cycle threshold value was strongly predictive of household transmission. Presence of symptoms in the index case was not associated with household transmission. Household transmission was four times greater from index cases infected with Beta variant and fifteen times greater from index cases infected with Delta variant compared to wild-type infection. Attack rates were highest in individuals aged 13-18 years and individuals in this age group were more likely to experience repeat infections and to acquire SARS-CoV-2 infection within households. People living with HIV (PLHIV) who were not virally supressed were more likely to develop symptomatic illness when infected with SARS-CoV-2, and shed SARS-CoV-2 for longer when compared to HIV-uninfected individuals.Implications of all the available evidenceWe found a high rate of SARS-CoV-2 infection in households in a rural community and an urban community in South Africa, with the majority of infections being asymptomatic in individuals of all ages. Asymptomatic individuals transmitted SARS-CoV-2 at similar levels to symptomatic individuals suggesting that interventions targeting symptomatic individuals such as symptom-based testing and contact tracing of individuals tested because they report symptoms may have a limited impact as control measures. Increased household transmission of Beta and Delta variants, likely contributed to recurrent waves of COVID-19, with >60% of individuals infected by the end of follow-up. Higher attack rates, reinfection and acquisition in adolescents and prolonged SARS-CoV-2 shedding in PLHIV who were not virally suppressed suggests that prioritised vaccination of individuals in these groups could impact community transmission.

Background: Single-event multilevel surgery (SEMLS) approach is regarded as the golden standard in developed countries to improve gait and functional mobility in children with cerebral palsy (CP). However, this approach is not always feasible in developing countries. Therefore, orthopedic surgery based on an interval surgery approach (ISA) is still commonly used in developing countries, although little is known about the long term outcomes of an ISA. Therefore, the aim of this study was to describe the gait patterns of adults with CP, who have been treated with ISA, which started more than 15 years ago. Materials and Methods: Thirty adults with CP and spastic diplegia, who received ISA treatment 21.6–33.7 years ago, were recruited for this study and participated in three-dimensional gait analysis. Twenty kinematic and nondimensional temporal-distance parameters were captured, while the overall gait deviation index (GDI) was also calculated. Data of the adults with CP were compared to normative data of typically developing (TD) adults. Results: Although all adults with CP were still ambulant, their gait parameters significantly differed from TD adults, with a lower GDI in the adults with CP. The CP gait patterns were characterized by excessive hip flexion and hip internal rotation as well as a stiff-knee gait. Conclusion: Although different to TD adults, the gait patterns observed in the adult with CP treated with ISA is in line with other studies. Gait patterns suggest that derotation osteotomies potentially could have improved the long term gait patterns. Although SEMLS might be the preferred treatment method, potentially resulting in better outcomes, ISA can also be used to treat children with CP in developing countries as India and South Africa, where a SEMLS approach is not always feasible.

BackgroundSARS-CoV-2 infections may be underestimated due to limited testing access, particularly in sub-Saharan Africa. South Africa experienced two SARS-CoV-2 waves, the second associated with emergence of variant 501Y.V2. In this study, we report longitudinal SARS-CoV-2 seroprevalence in cohorts in two communities in South Africa.MethodsWe measured SARS-CoV-2 seroprevalence two monthly in randomly selected household cohorts in a rural and an urban community (July 2020-March 2021). We compared seroprevalence to laboratory-confirmed infections, hospitalisations and deaths reported in the districts to calculate infection-case (ICR), infection-hospitalisation (IHR) and infection-fatality ratio (IFR) in the two waves of infection.FindingsSeroprevalence after the second wave ranged from 18% (95%CrI 10-26%) and 28% (95%CrI 17-41%) in children InterpretationThe second wave was associated with a shift in age distribution of cases from individuals aged to 35-59 to individuals at the extremes of age, higher attack rates in the rural community and a higher IFR in the urban community. Approximately 95% of SARS-CoV-2 infections in these two communities were not reported to the national surveillance system, which has implications for contact tracing and infection containment.FundingUS Centers for Disease Control and PreventionResearch in contextEvidence before this studySeroprevalence studies provide better estimates of SARS-CoV-2 burden than laboratory-confirmed cases because many infections may be missed due to restricted access to care and testing, or differences in disease severity and health-care seeking behaviour. This underestimation may be amplified in African countries, where testing access may be limited. Seroprevalence data from sub-Saharan Africa are limited, and comparing seroprevalence estimates between countries can be challenging because populations studied and timing of the study relative to country-specific epidemics differs. During the first wave of infections in each country, seroprevalence was estimated at 4% in Kenya and 11% in Zambia. Seroprevalence estimates in South African blood donors is estimated to range between 32% to 63%. South Africa has experienced two waves of infection, with the emergence of the B.1.351/501Y.V2 variant of concern after the first wave. Reported SARS-CoV-2 cases may not be a true reflection of SARS-CoV-2 burden and specifically the differential impact of the first and second waves of infection.Added value of this studyWe collected longitudinal blood samples from prospectively followed rural and urban communities, randomly selected, household cohorts in South Africa between July 2020 and March 2021. From 668 and 598 individuals included from the rural and urban communities, respectively, seroprevalence was found to be 7% (95%CrI 5-9%) and 27% (95%CrI 23-31%), after the first wave of infection, and 26% (95%CrI 22-29%) and 41% (95%CrI 37-45%) after the second wave, in rural and urban study districts, respectively. After standardising for age, we estimated that only 5% of SARS-CoV-2 infections were laboratory-confirmed and reported. Infection-hospitalisation ratios in the urban community were higher in the first (2.01%, 95%CI 1.57-2.57%) and second (2.29%, 95%CI 1.63-3.94%) wave than the rural community where there was a 0.75% (95%CI 0.49-1.41%) and 0.66% (95%CI 0.50-0.98%) infection-hospitalisation ratio in the first and second wave, respectively.When comparing the infection fatality ratios for the first and second SARS-CoV-2 waves, at the urban site, the ratios for both in-hospital and excess deaths to cases were significantly higher in the second wave (0.36%, 95%CI 0.28-0.57% in-hospital and 0.51%, 95%CI 0.34-0.93% excess deaths), compared to the first wave in-hospital (0.17%, 95%CI 0.15-0.20%) and excess (0.13%, 95%CI 0.10-0.17%) fatality ratios, pImplications of all the available evidenceIn South Africa, the overall prevalence of SARS-CoV-2 infections is substantially underestimated, resulting in many cases being undiagnosed and without the necessary public health action to isolate and trace contacts to prevent further transmission. There were more infections during the first wave in the urban community, and the second wave in the rural community. Although there were less infections during the second wave in the urban community, the infection-fatality ratios were significantly higher compared to the first wave. The lower infection-hospitalisation ratio and higher excess infection-fatality ratio in the rural community likely reflect differences in access to care or prevalence of risk factors for progression to severe disease in these two communities. In-hospital infection-fatality ratios for both communities during the first wave were comparable with what was experienced during the first wave in India (0.15%) for SARS-CoV-2 confirmed deaths. To our knowledge, these are the first longitudinal seroprevalence data from a sub-Saharan Africa cohort, and provide a more accurate understanding of the pandemic, allowing for serial comparisons of antibody responses in relation to reported laboratory-confirmed SARS-CoV-2 infections within diverse communities.

Objectives 18F-Fluorodeoxyglucose (FDG) Positron Emission Tomography- Computed Tomography (PET/CT) scans can be used to assess healing following treatment for spinal tuberculosis (TB) but have limited accessibility and high cost. This study investigated the association between immune biomarkers and FDG-PET/CT activity after ≥9 months of treatment for spinal TB. Methods Patients who had completed ≥9 months of treatment for spinal TB were recruited from a major hospital in the Western Cape, South Africa. Participants underwent a FDG-PET/CT scan and FDG- PET/CT activity was quantified for all spinal and extra-spinal sites. Participants also provided a blood sample, which was evaluated for 19 cytokines along with erythrocyte sedimentation rate (ESR). Correlations and multiple regression analyses were used to investigate the association between biomarkers and PET/CT measures. Results Twenty-eight patients were recruited, of whom 24 (86%) had spinal and/or extra-spinal FDG-PET/CT activity. In the strongest multiple regression model, CXCL10/IP-10, VEGFA, IFN-γ, CRP and Factor D/Adipsin explained 52% of the variation in overall maximal FDG uptake. Conventional monitoring marker ESR showed no significant association with PET/CT measures. Conclusions The current findings offered encouragement that biomarkers to predict FDG-PET/CT activity may show some promise and identified candidate biomarkers for further investigation in this regard.

Background:Although adverse drug reactions resulting from the use of nevirapine (NVP) are well described in adults (estimated frequency of 6% – 10%), it has previously been considered less common in children (0.3% – 1.4%). Stock-outs of antiretroviral agents occur frequently in South Africa and result in interruptions in therapy and drug substitutions. Objectives:To report on a case series of paediatric patients who suffered cutaneous drug reactions to NVP at rates not previously described in children. Method:We describe a retrospective observational case series of six children living with HIV who developed Stevens-Johnson Syndrome (SJS) following exposure to NVP because of a prolonged stock-out of efavirenz 200 mg tablets in South Africa. Results:Of the 392 paediatric patients receiving antiretroviral therapy at the institution, 172 were affected by the efavirenz stock-out. Of these, 85 children were changed to NVP of which six developed NVP-induced SJS (7.1% incidence rate). The median time between initiating NVP and developing symptoms was 27 days (range 12–35 days). All patients responded well to NVP cessation and symptomatic treatment. One patient was referred for specialist care. Two patients were successfully rechallenged with efavirenz after developing SJS and three continued lopinavir/ritonavir. Conclusions:This is the second largest case series of NVP-induced SJS in children to date and raises the possibility that the incidence of SJS in children may be higher than previously described. Further research is required to explore the risk factors associated with NVP-induced SJS in children. This case series highlights the negative impact of drug stock-outs on patient health outcomes.

Background Insight into the day-to-day challenges faced by adults living with Cerebral Palsy (CP) in low-to-middle income countries (LMICs) will enable support towards healthy aging in this population. Objectives To determine changes in level of pain, functional mobility and accomplishment as well as satisfaction in daily life of ambulant adults with CP living in a LMIC over a six-year period, compared to typically developed (TD) adults. In addition, to determine associations with individual characteristics. Methods Twenty-eight adults with CP and spastic diplegia (median [interquartile ranges] age = 39.0 [34.0–45.7] years; Gross Motor Function Classification System level I/II/III: n = 11/12/5) participated in this study, together with 28 matched TD adults. Levels of accomplishment and satisfaction were assessed with the Life-Habits questionnaire, functional mobility was determined with the Functional Mobility Scale and (back, lower and upper limb) pain frequency was gauged with a standardized questionnaire. Results Life-Habits accomplishment and satisfaction scores of adults with CP remained unchanged during the six-year follow-up, with 79% being independent and 100% satisfied. Functional mobility decreased and related to the total accomplishment score. No change in pain frequency was observed, but adults with CP experienced more pain than their peers. Back pain was significantly associated with the total satisfaction score. Conclusions Relative high levels of accomplishment and satisfaction and no change in pain frequency were noted during a six-year follow-up study of adults with CP living in a LMIC. The importance of exercise/rehabilitation programs to reduce pain and maintain functional mobility in persons aging with CP was highlighted.

We demonstrate the flexibility and ease of use of C++ algorithmic differentiation (AD) tools based on overloading to numerical patterns (kernels) arising in computational finance. While adjoint methods and AD have been known in the finance literature for some time, there are few tools capable of handling and integrating with the C++ codes found in production. Adjoint methods are also known to be very powerful but to potentially have infeasible memory requirements. We present several techniques for dealing with this problem and demonstrate them on numerical kernels which occur frequently in finance. We build the discussion around our own AD tool dco/c++ which is designed to handle arbitrary C++ codes and to be highly flexible, however the sketched concepts can certainly be transferred to other AD solutions including in-house tools. An archive of the source code for the numerical kernels as well as all the AD solutions discussed can be downloaded from an accompanying website. This includes documentation for the code and dco/c++. Trial licences for dco/c++ are available from NAG.

The purpose of this study was to determine the incidence of spinal deformities in ambulant adults with cerebral palsy (CP) and spastic diplegia, more than 15 years after orthopaedic interval surgery approach (ISA) treatment, and its relationship to contextual factors, level of pain and physical status. Spinal X-rays, pain (Oswestry Disability Index (ODI) and location/frequency) questionnaires and physical examination assessing lower extremity muscle strength (Medical Research Council scale), motor control (selectivity scale) and muscle tone (Ashworth score) were conducted in 30 adults with spastic diplegic CP. Mild scoliosis (curve 12–22°) was determined in eight (28%) participants. Hyperkyphosis (> 50°) was reported in two (7%) and lumbar hyperlordosis (> 60°) in five (17%) participants. Pain was most commonly reported at cervical (n = 19, 63%) and lumbosacral (n = 18, 60%) area, resulting in ‘moderate disability’ for six (20%) and ‘severe disability’ for one (3%) participant. Most apparent physical abnormalities determined were hip abduction weakness and increased rectus femoris muscle tone. Regarding correlations, no relations were found for scoliosis curvature, but kyphosis curvature was related to females, ODI scores (lifting and sitting) and increased muscle tone of ankle plantar flexor muscles, lordosis curvature to passive hip extension mobility, and hip flexors and ankle plantar flexors muscle tone. Adults with spastic diplegic CP who received their first orthopaedic intervention more than 15 years ago (based on ISA) showed similar incidence of spinal deformities as reported in the younger CP population, suggesting stability of spinal curvature into adulthood. These slides can be retrieved under Electronic Supplementary Material.

In this paper we discuss the challenges and optimisations opportunities when solving a large number of small, equally sized discretised PDEs on regular grids. We present an extension of the OPS (Oxford Parallel library for Structured meshes) embedded Domain Specific Language, and show how support can be added for solving multiple systems, and how OPS makes it easy to deploy a variety of transformations and optimisations. The new capabilities in OPS allow to automatically apply data structure transformations, as well as execution schedule transformations to deliver high performance on a variety of hardware platforms. We evaluate our work on an industrially representative finance simulation on Intel CPUs, as well as NVIDIA GPUs.

Background Trichoepithelioma (TE) is a benign adnexal neoplasm derived from basal cells in the hair follicle. Solitary TE occurs sporadically as opposed to the multiple familial variant that presents as an autosomal dominant genodermatosis. The solitary variant can be confused with basal cell carcinoma both clinically and histologically. Multiple familial TEs are a cosmetically disfiguring condition with limited satisfactory treatment options. Method Skin biopsies diagnosed as TE from January 1, 2001, to December 31, 2011, were retrieved from the archives of the Division of Anatomical Pathology (University of Stellenbosch and National Health Laboratory Service, Cape Town, South Africa). Clinical and demographic data were retrieved from the patient records at Tygerberg Academic Hospital. Data of patients with solitary TE and multiple TE were compared. Results Thirty-three biopsy specimens were collected from 30 patients. Twenty patients had solitary TE, nine patients had multiple TEs, and one patient had multiple linear TEs. Multiple TEs started to develop in patients at an average age of 17.3 years. Three patients in the study had tumoral TE with a diameter greater than 20 mm. One patient had TE associated with a basal cell carcinoma. Multiple TEs were commonly misdiagnosed clinically as tuberous sclerosis and showed a cribriform histopathological tumor pattern in 80% of cases as compared to only 10% of solitary TEs. Conclusion The current study was confined to a cohort of patients, in the Western Cape Province of South Africa, whose ethnic and geographic origins were not available. The extrapolation of findings from this study to the rest of the South African population may not be valid. A cribriform growth pattern occurs in the majority of cases of multiple TEs.

BACKGROUND Ultraviolet (UV) radiation is the most important environmental risk factor for the development of nonmelanoma skin cancer (NMSC). UV radiation is, however, also vital in the formation of vitamin D in humans. Strict sun protection advised to skin cancer patients may lead to vitamin D deficiency, yet vitamin D may have a protective effect against cancer formation. OBJECTIVES The primary aim was to determine whether patients with nonmelanoma skin cancer at our institution were vitamin D deficient. METHODS 25-Hydroxyvitamin D (25[OH]D) levels were determined in 109 patients with a diagnosis of basal cell carcinoma (BCC) and/or squamous cell carcinoma (SCC) during the summer and winter of 2015 at the Tygerberg Academic Hospital in Cape Town, South Africa. Associations between clinical and epidemiological data and the 25(OH)D level results were investigated. Vitamin D deficiency was defined as total 25(OH)D levels

Calibration of stochastic local volatility (SLV) models to their underlying local volatility model is often performed by numerically solving a two-dimensional non-linear forward Kolmogorov equation. We propose a novel finite volume (FV) discretization in the numerical solution of general 1D and 2D forward Kolmogorov equations. The FV method does not require a transformation of the PDE. This constitutes a main advantage in the calibration of SLV models as the pertinent PDE coefficients are often nonsmooth. Moreover, the FV discretization has the crucial property that the total numerical mass is conserved. Applying the FV discretization in the calibration of SLV models yields a non-linear system of ODEs. Numerical time stepping is performed by the Hundsdorfer-Verwer ADI scheme to increase the computational efficiency. The non-linearity in the system of ODEs is handled by introducing an inner iteration. Ample numerical experiments are presented that illustrate the effectiveness of the calibration procedure., 29 pages, 14 figures

Aim The aim of this study was to explore the physical status and gait patterns of children with spastic diplegia secondary to human immunodeficiency virus encephalopathy (HIVE). Method A cross-sectional study was conducted on children diagnosed with HIVE and spastic diplegia. Sociodemographic and clinical background information was obtained, followed by three-dimensional gait analysis (3DGA) and a physical examination including assessments of muscle tone, strength, motor control, contractures, and bony deformities of the lower extremities. Results Fourteen children (eight males, six females; mean age 5y 8mo [SD 9mo], range 4y 4mo–6y 10mo) were studied. The cohort was divided into two groups based on distinctive gait patterns. Nine participants in group I showed only limited abnormalities. Group II displayed a more pathological gait pattern including stiff knee and equinus ankle abnormalities. Results of 3DGA, as with the physical examination outcomes, showed increased impairments from proximal to distal (except for hip extension). Interpretation This study provides a first description of distinctive gait patterns and related physical characteristics of children with HIVE and spastic diplegia. Further research is necessary.

Introduction. This paper examines the persistent problematic issue of engaging business students in teaching computer programming. Studies continue to document challenges in teaching computer programming and various methods have been proposed with varying degrees of success. From an educator’s perspective, the concern is how to engage students to enable the effective delivery of computer programming principles to the students. From a student’s perspective, how they experience the computer programming course will leave students with good programming habits, the ability to learn on their own and a favourable impression of the field of Information Systems as a profession.Method. The study used a case study design in which a survey and interviews were conducted among 138 students currently registered for a second year computer programming course at large urban University in South Africa. Three instructors involved in teaching the class were also interviewed to gauge their perspectives in relation to those offered by the students.Results. Our findings refutes the notion that the popular use of computer games in social contexts implies that they can be used successfully for teaching computer programming to business students. This allowed us, as educators in a position of power over students, to reflect on our intentions when re-designing curricula.Discussion and Conclusion. We suggest that while teaching innovations should be linked to a broader theme reflexive practice of experimentation; educators should encourage feedback from other stakeholders to foster ‘reflexive competence’, a desired property for transformation of curricula.

Publisher Summary Random number generation is a key component of many forms of simulation, and fast parallel generation is particularly important for the naturally parallel Monte Carlo simulations that are used extensively in computational finance and many areas of computational science and engineering. This chapter discusses the parallelization of three very popular random number generators. In each case, the random number sequence that is generated is identical to that produced on a CPU by the standard sequential algorithm. The key to the parallelization is that each CUDA thread block generates a particular block of numbers within the original sequence, and to do this step, it needs an efficient skip-ahead algorithm to jump to the start of its block. Although there is much in common in the underlying mathematical formulation of these three generators, there are also very significant differences owing to differences in the size of the state information required by each generator. The Intel random number generators are contained in the vector statistical library (VSL). This library is not multithreaded, but is thread safe and contains all the necessary skip-ahead functions to advance the generators' states. The way in which consideration of the number of registers required, the details of data dependency in advancing the state, and the desire for memory coalescence in storing the output lead to different implementations in the three cases is of most importance.

Assuming that the stock price $Z=(Z_t)_{0\leq t\leq T}$ follows a geometric Brownian motion with drift $\mu\in\mathbb{R}$ and volatility $\sigma>0$, and letting $M_t=\max_{0\leq s\leq t}Z_s$ for $t\in[0,T]$, we consider the optimal prediction problems \[V_1=\inf_{0\leq\tau\leq T}\mathsf{E}\biggl(\frac{M_T}{Z_{\tau}}\biggr)\quadand\quad V_2=\sup_{0\leq\tau\leq T}\mathsf{E}\biggl(\frac{Z_{\tau}}{M_T}\biggr),\] where the infimum and supremum are taken over all stopping times $\tau$ of $Z$. We show that the following strategy is optimal in the first problem: if $\mu\leq0$ stop immediately; if $\mu\in (0,\sigma^2)$ stop as soon as $M_t/Z_t$ hits a specified function of time; and if $\mu\geq\sigma^2$ wait until the final time $T$. By contrast we show that the following strategy is optimal in the second problem: if $\mu\leq\sigma^2/2$ stop immediately, and if $\mu>\sigma^2/2$ wait until the final time $T$. Both solutions support and reinforce the widely held financial view that ``one should sell bad stocks and keep good ones.'' The method of proof makes use of parabolic free-boundary problems and local time--space calculus techniques. The resulting inequalities are unusual and interesting in their own right as they involve the future and as such have a predictive element., Comment: Published in at http://dx.doi.org/10.1214/08-AAP566 the Annals of Applied Probability (http://www.imstat.org/aap/) by the Institute of Mathematical Statistics (http://www.imstat.org)

where the infimum is taken over all stopping times τ of B . Reducing the optimal prediction problem to a parabolic free-boundary problem and making use of local time-space calculus techniques, we show that the following stopping time is optimal: τ∗ = inf { 0 ≤ t ≤ 1 | S t −B t ≥ b(t) } where b : [0, 1] → IR is a continuous decreasing function with b(1) = 0 that is characterised as the unique solution to a nonlinear Volterra integral equation. This also yields an explicit formula for V∗ in terms of b . If μ = 0 then there is a closed form expression for b . This problem was solved in [14] and [4] using the method of time change. The latter method cannot be extended to the case when μ 6= 0 and the present paper settles the remaining cases using a different approach. It is also shown that the shape of the optimal stopping set remains preserved for all Levy processes.