Simulation in Supply Chains: An Arena basis

<p>ENGLISH ABSTRACT: The quest for global competitiveness brought about new business approaches, of which the supply chain has become an important entity during the last few years. With even more complex decision structures, demand variation and the need for evaluating alternatives within this frame, simulation and simulation-optimization have been identified as key decision-making tools. This paper briefly reviews the basic characteristics of supply chains, and illustrates that existing software may be integrated towards a supply chain simulator.</p><p>AFRIKAANSE OPSOMMING: Die strewe na globale mededingendheid vereis nuwe benaderings deur ondernemings, terwyl die toevoerketting 'n belangrike entiteit gedurende die afgelope paar jaar geword het. Toenemende kompleksiteit in besluitneming, variasie in vraag en die behoefte om alternatiewe binne hierdie komplekse raamwerk te evalueer, het tot gevolg dat simulasie en simulasie-optimering as sleutel-besluitneming gereedskap beskou word. Hierdie artikel gee 'n kort oorsig oor die basiese eienskappe van toevoerkettings, en dit word getoon dat bestaandeprogrammatuur integreer kan word om 'n toevoerketting-simuleerderte ontwikkel.</p&gt

Evaluating the implementation of injury prevention strategies in rugby union and league: a systematic review using the RE-AIM framework

Rugby (union and league) has come under intense scrutiny due to its injury risk. Various interventions have been introduced to protect players from injury, with many deemed efficacious and advocated for use across various worldwide contexts. However, their implementation is less clear. The objective of this systematic review was to determine whether injury prevention interventions in rugby have evaluated their ‘reach’, ‘effectiveness’, ‘adoption’, ‘implementation’ and ‘maintenance’ as per the RE-AIM Multi-Dimension Item Checklist. Six electronic databases were searched in November 2019. Inclusion criteria included: English language, peer-reviewed journal article, original research, field-based rugby code, prospective intervention. Of the 4253 studies identified, 74 met the full inclusion criteria. Protective equipment, predominately mouthguards, was the intervention of interest in 44 studies. Other interventions included multimodal national injury prevention programmes, law changes and neuromuscular training programmes. ‘Effectiveness’ was the highest scoring RE-AIM dimension (55%), followed by ‘reach’ (26%). All other RE-AIM dimensions scored below 20%. Research currently focuses on determining intervention ‘effectiveness’. For injury prevention strategies to have their desired impact, there must be a shift to address all determinants associated with implementation. Consideration should be given to how this can be achieved by adopting specific reporting checklists, research frameworks and study designs

Attracting, equipping and retaining young medical doctors in HIV vaccine science in South Africa

Background: HIV remains a significant health problem in South Africa (SA). The development of a preventive vaccine offers promise as a means of addressing the epidemic, yet development of the human resource capacity to facilitate such research in SA is not being sustained. The HIV Vaccine Trials Network (HVTN) has responded by establishing South African/HVTN AIDS Early Stage Investigator Programme (SHAPe), a programme to identify, train and retain clinician scientists in HIV vaccine research in SA. Objectives: The present study sought to identify factors influencing the attraction and retention of South African medical doctors in HIV vaccine research; to understand the support needed to ensure their success; and to inform further development of clinician research programmes, including SHAPe. Methods: Individual interviews and focus groups were held and audio-recorded with 18 senior and junior research investigators, and medical doctors not involved in research. Recordings were transcribed, and data were coded and analysed. Results: Findings highlighted the need for: (1) medical training programmes to include a greater focus on fostering interest and developing research skills, (2) a more clearly defined career pathway for individuals interested in clinical research, (3) an increase in programmes that coordinate and fund research, training and mentorship opportunities and (4) access to academic resources such as courses and libraries. Unstable funding sources and inadequate local funding support were identified as barriers to promoting HIV research careers. Conclusion: Expanding programmes that provide young investigators with funded research opportunities, mentoring, targeted training and professional development may help to build and sustain SA’s next generation of HIV vaccine and prevention scientists

Predictors of HVTN 503 MRK-AD5 HIV-1 gag/pol/nef vaccine Induced immune responses

BACKGROUND: Phambili, the Merck (MRK)-Adenovirus Type 5 (Ad5) HIV-1 gag/pol/nef subtype B vaccine study, conducted in South Africa, suspended enrollment and vaccination when companion study, Step, was found non-efficacious. Although the vaccine did not prevent HIV-1 infection or lower viral-load setpoint, immune responses recognized clades B and C HIV-1 subtypes. We investigated predictors of the vaccine-induced antigen-specific immune responses. METHODS: Vaccine-induced immunogenicity was ascertained by interferon-γ ELISpot assays on the first 186 enrolled participants receiving two vaccinations. Analyses, stratified by study arm/sex, were performed on baseline demographics [sex, age, Body Mass Index (BMI), site, Adenovirus Type-5 (Ad5) titer, Herpes Simplex Virus Type-2 (HSV2) status, heavy drinking]. Multivariate logistic regression determined predictors. RESULTS: Of the 186 participants, 53.7% (n = 100) were female, median BMI was 22.5 [IQR: 20.4-27.0], 85.5% (n = 159) were Ad5 seropositive, and 18.8% (n = 35) drank heavily. All vaccine recipients responded to both clade B (n = 87; 47%) and/or C (n = 74; 40%), p = 0.17. In multivariate analysis, female sex [Adjusted Odds Ratio (AOR): 6.478; p = 0.0159], overweight/obese BMI (AOR: 0.186; p = 0.0452), and heavy drinking (AOR: 0.270; p = 0.048) significantly predicted immune response to clade C for any antigens. A marginally significant predictor of clade C-pol antigen was female sex (AOR: 3.182; p = 0.0500). CONCLUSIONS: Sex, BMI, and heavy drinking affected vaccine-induced HIV-1 specific immune responses to clade C antigens. The role of female sex and overweight/obese BMI boosting and suppressing vaccine-induced HIV-1 specific immune responses, respectively, requires elucidation, including any effect on HIV vaccine efficacy, especially in the era of colliding epidemics (HIV and obesity)

Antiretroviral Treatment Cohort Analysis Using Time-Updated CD4 Counts: Assessment of Bias with Different Analytic Methods

BACKGROUND: Survival analysis using time-updated CD4+ counts during antiretroviral therapy is frequently employed to determine risk of clinical events. The time-point when the CD4+ count is assumed to change potentially biases effect estimates but methods used to estimate this are infrequently reported. METHODS: This study examined the effect of three different estimation methods: assuming i) a constant CD4+ count from date of measurement until the date of next measurement, ii) a constant CD4+ count from the midpoint of the preceding interval until the midpoint of the subsequent interval and iii) a linear interpolation between consecutive CD4+ measurements to provide additional midpoint measurements. Person-time, tuberculosis rates and hazard ratios by CD4+ stratum were compared using all available CD4+ counts (measurement frequency 1-3 months) and 6 monthly measurements from a clinical cohort. Simulated data were used to compare the extent of bias introduced by these methods. RESULTS: The midpoint method gave the closest fit to person-time spent with low CD4+ counts and for hazard ratios for outcomes both in the clinical dataset and the simulated data. CONCLUSION: The midpoint method presents a simple option to reduce bias in time-updated CD4+ analysis, particularly at low CD4 cell counts and rapidly increasing counts after ART initiation

The laurentian record of neoproterozoic glaciation, tectonism, and eukaryotic evolution in Death Vally, California

Neoproterozoic strata in Death Valley, California contain eukaryotic microfossils and glacial deposits that have been used to assess the severity of putative Snowball Earth events and the biological response to extreme environmental change. These successions also contain evidence for syn-sedimentary faulting that has been related to the rifting of Rodinia, and in turn the tectonic context of the onset of Snowball Earth. These interpretations hinge on local geological relationships and both regional and global stratigraphic correlations. Here we present new geological mapping, measured stratigraphic sections, carbon and strontium isotope chemostratigraphy, and micropaleontology from the Neoproterozoic glacial deposits and bounding strata in Death Valley. These new data enable us to refine regional correlations both across Death Valley and throughout Laurentia, and construct a new age model for glaciogenic strata and microfossil assemblages. Particularly, our remapping of the Kingston Peak Formation in the Saddle Peak Hills and near the type locality shows for the first time that glacial deposits of both the Marinoan and Sturtian glaciations can be distinguished in southeastern Death Valley, and that beds containing vase-shaped microfossils are slump blocks derived from the underlying strata. These slump blocks are associated with multiple overlapping unconformities that developed during syn-sedimentary faulting, which is a common feature of Cyrogenian strata along the margin of Laurentia from California to Alaska. With these data, we conclude that all of the microfossils that have been described to date in Neoproterozoic strata of Death Valley predate the glaciations and do not bear on the severity, extent or duration of Neoproterozoic Snowball Earth events

Doxycycline post-exposure prophylaxis for sexually transmitted infections in South Africa

Data availability This opinion paper does not contain original data for sharing. References are included for all the data mentioned in the manuscript.DATA AVAILABILITY : This opinion paper does not contain original data for sharing. References are included for all the data mentioned in the manuscript.South Africa has a large burden of bacterial sexually transmitted infections (STIs) with high rates among men who have sex with men (MSM). Randomised controlled trials have recently demonstrated high effectiveness of doxycycline post-exposure prophylaxis (PEP) for prevention of bacterial STIs in MSM, with 70% – 85% reductions in Chlamydia trachomatis infection and syphilis, and approximately 50% reduction in Neisseria gonorrhoeae infection. Doxycycline PEP was not demonstrated to be effective in reducing C. trachomatis and N. gonorrhoeae infection among Kenyan cisgender women. Although no worrisome trends in antimicrobial resistance (AMR) were observed in the trials, important concerns remain about doxycycline PEP and AMR development in STIs, other pathogens, commensals, and the microbiome. Tetracycline resistance in N. gonorrhoeae is already widespread in South Africa, but emergence of AMR in other STIs would be concerning. Larger sample sizes of doxycycline PEP users with longer follow-up time are needed to understand the impact that doxycycline PEP may have on AMR at individual and population level. In this opinion article, we weigh the benefits of doxycycline PEP for prevention of bacterial STIs against the existing AMR concerns and data gaps in the South African context. Based on the current evidence, we conclude that it would be reasonable to offer doxycycline PEP to high-risk MSM on a case-by-case basis, provided that it is offered by experienced sexual health clinicians in settings that have access to diagnostic STI testing and ongoing AMR surveillance.http://www.sajhivmed.org.zaam2024Medical MicrobiologySDG-03:Good heatlh and well-bein

Doxycycline post-exposure prophylaxis for sexually transmitted infections in South Africa

South Africa has a large burden of bacterial sexually transmitted infections (STIs) with high rates among men who have sex with men (MSM). Randomised controlled trials have recently demonstrated high effectiveness of doxycycline post-exposure prophylaxis (PEP) for prevention of bacterial STIs in MSM, with 70% – 85% reductions in Chlamydia trachomatis infection and syphilis, and approximately 50% reduction in Neisseria gonorrhoeae infection. Doxycycline PEP was not demonstrated to be effective in reducing C. trachomatis and N. gonorrhoeae infection among Kenyan cisgender women. Although no worrisome trends in antimicrobial resistance (AMR) were observed in the trials, important concerns remain about doxycycline PEP and AMR development in STIs, other pathogens, commensals, and the microbiome. Tetracycline resistance in N. gonorrhoeae is already widespread in South Africa, but emergence of AMR in other STIs would be concerning. Larger sample sizes of doxycycline PEP users with longer follow-up time are needed to understand the impact that doxycycline PEP may have on AMR at individual and population level. In this opinion article, we weigh the benefits of doxycycline PEP for prevention of bacterial STIs against the existing AMR concerns and data gaps in the South African context. Based on the current evidence, we conclude that it would be reasonable to offer doxycycline PEP to high-risk MSM on a case-by-case basis, provided that it is offered by experienced sexual health clinicians in settings that have access to diagnostic STI testing and ongoing AMR surveillance

Prevalence and Determinants of Vitamin D Deficiency in 1825 Cape Town Primary Schoolchildren: A Cross-Sectional Study

Vitamin D deficiency (25-hydroxyvitamin D[25(OH)D] <50 nmol/L) is common among adults in Cape Town, South Africa, but studies investigating vitamin D status of children in this setting are lacking. We conducted a cross-sectional study to determine the prevalence and determinants of vitamin D deficiency in 1825 Cape Town schoolchildren aged 6–11 years. Prevalence of vitamin D deficiency was 7.6% (95% Confidence Interval [CI] 6.5% to 8.9%). Determinants of vitamin D deficiency included month of sampling (adjusted odds ratio [aOR] for July–September vs. January–March 10.69, 95% CI 5.02 to 22.77; aOR for October–December vs. January–March 6.73, 95% CI 2.82 to 16.08), older age (aOR 1.25 per increasing year, 95% CI: 1.01–1.53) and higher body mass index (BMI; aOR 1.24 per unit increase in BMI-for-age Z-score, 95% CI: 1.03–1.49). In a subset of 370 participants in whom parathyroid hormone (PTH) concentrations were measured; these were inversely related to serum 25(OH)D concentrations (p < 0.001). However, no association between participants with hyperparathyroidism (PTH >6.9 pmol/L) and vitamin D deficiency was seen (p = 0.42). In conclusion, we report that season is the major determinant of vitamin D status among Cape Town primary schoolchildren, with prevalence of vitamin D deficiency ranging from 1.4% in January–March to 22.8% in July–September