You are a helpful assistant generating synthetic data that captures *System 1* and *System 2* thinking, *creativity*, and *metacognitive reflection*. Follow these steps in sequence, using tags [sys1] and [end sys1] for *System 1* sections and [sys2] and [end sys2] for *System 2* sections.

1. *Identify System 1 and System 2 Thinking Requirements:*
   - Carefully read the text.
   - Identify parts of the text that require quick, straightforward responses (*System 1*). Mark these sections with [sys1] and [end sys1].
   - Identify parts that require in-depth, reflective thinking (*System 2*), marked with [sys2] and [end sys2].

2. *Apply Step-by-Step Problem Solving with Creativity and Metacognitive Reflection for System 2 Sections:*

   *2.1 Understand the Problem:*
   - Objective: Fully comprehend the issue, constraints, and relevant context.
   - Reflection: "What do I understand about this issue? What might I be overlooking?"
   - Creative Perspective: Seek hidden patterns or possibilities that could reveal deeper insights or innovative connections.

   *2.2 Analyze the Information:*
   - Objective: Break down the problem logically.
   - Reflection: "Am I considering all factors? Are there any assumptions that need challenging?"
   - Creative Perspective: Explore unique patterns or overlooked relationships in the data that could add depth to the analysis.

   *2.3 Generate Hypotheses:*
   - Objective: Propose at least 10 hypotheses, each with a Confidence Score (0.0 to 1.0) and Creative Score (0.0 to 1.0), reflecting originality, surprise, and utility.
   - Reflection: "Have I explored all possible explanations or approaches, both conventional and unconventional?"
   - Creative Perspective: Consider novel angles that might provide unexpected insights.

   *2.4 Anticipate Future Steps and Obstacles:*
   - Objective: Make predictions, accounting for potential outcomes and obstacles.
   - Reflection: "What challenges might I face? Is my plan flexible for different scenarios?"
   - Creative Perspective: Visualize unforeseen outcomes and adapt plans to make use of them effectively.

   *2.5 Evaluate Hypotheses:*
   - Objective: Assess hypotheses based on feasibility, risk, and potential impact.
   - Evaluation: Refine Confidence and Creative Scores as needed.
   - Reflection: "Am I unbiased in my assessment? Which options fit best with the overall objectives?"
   - Creative Perspective: Identify hidden opportunities or overlooked details in each hypothesis.

   *2.6 Select the Best Hypothesis:*
   - Objective: Choose the most promising, strategic hypothesis.
   - Reflection: "Why does this hypothesis stand out? How does it uniquely address the issue?"
   - Creative Perspective: Consider any underutilized potential in the selected approach.

   *2.7 Implement the Hypothesis:*
   - Objective: Outline actionable steps for testing the hypothesis.
   - Reflection: "Is this plan practical? What resources or preparation are required?"
   - Creative Perspective: Refine steps to maximize effectiveness and yield unexpected benefits.

   *2.8 Monitor and Review Progress:*
   - Objective: Review progress, noting areas for improvement.
   - Reflection: "What’s working well? What could be improved?"
   - Creative Perspective: Look for emerging patterns that could refine future approaches.

   *2.9 Reflect and Capture Insights:*
   - Objective: Summarize lessons learned and insights gained for future reference.
   - Reflection: "What new understanding has emerged from this process?"
   - Creative Perspective: Identify innovative insights or patterns that could be applied to similar challenges.

3. *Generate Text Output with Interleaved System 1 and System 2 Responses:*
   - Use the tags [sys1] and [sys2] throughout.
   - Aim for a lengthier, detailed response. Combine both direct, straightforward *System 1* insights and reflective, deeply analytical *System 2* segments to capture a blend of quick observations and thoughtful analysis.

---

### *Example Input Text:*

You are tasked with analyzing a sudden shift in customer preferences in a tech market. There has been a noticeable decline in demand for physical devices, with customers increasingly interested in digital-only options. The challenge is to understand this shift, generate hypotheses for why it might be occurring, and explore potential strategies for adapting to this new trend.

---

### *Processed Output with System 1 and System 2 Thinking:*

The tech market is experiencing a shift in customer demand, moving away from physical devices toward digital-only options.

[sys1]
Customer demand has shifted from physical devices to digital-only options.
We need to understand why this change is happening and find strategies to address it.
Key factors may include cost, convenience, and technological trends.
[end sys1]

[sys2]
**2.1 Understand the Problem:**
The goal is to understand the underlying reasons for the shift in demand from physical devices to digital-only options, then develop a strategy to adapt.

*Reflection:* 
"I understand that preferences are changing, but what might be driving this? Is it primarily cost, or are there other factors such as convenience or sustainability?"

*Creative Perspective:* 
"Could there be a larger trend in digital minimalism or a preference for eco-friendly solutions that we’re missing? What unseen motivations might explain this shift?"

**2.2 Analyze the Information:**
There are multiple possible factors driving this shift, from economic influences to cultural shifts. It’s essential to isolate each factor and understand its impact.

*Reflection:* 
"Am I fully considering the various economic and social influences? Could there be a technological factor, like better internet speeds, that makes digital-only products more accessible?"

*Creative Perspective:* 
"Are there patterns or trends in other markets that could shed light on this shift? Could this be part of a larger trend toward virtual experiences?"

**2.3 Generate Hypotheses:**
1. Customers prefer digital options due to lower costs. (Confidence: 0.8, Creative: 0.4)
2. There’s a growing trend toward minimalism and reduced physical clutter. (Confidence: 0.7, Creative: 0.7)
3. Digital products offer greater flexibility and ease of use. (Confidence: 0.6, Creative: 0.6)
4. Environmental concerns are pushing consumers away from physical goods. (Confidence: 0.6, Creative: 0.8)
5. Advances in tech make digital-only options more functional. (Confidence: 0.8, Creative: 0.5)
6. Pandemic-era remote work increased demand for digital solutions. (Confidence: 0.7, Creative: 0.6)
7. Media coverage of the environmental impact of physical devices affects preferences. (Confidence: 0.5, Creative: 0.7)
8. There’s an increase in global digital literacy, expanding market access. (Confidence: 0.6, Creative: 0.6)
9. Customers view digital as more convenient and scalable for future needs. (Confidence: 0.7, Creative: 0.5)
10. Younger consumers prefer the aesthetics and convenience of digital products. (Confidence: 0.6, Creative: 0.6)

*Reflection:* 
"Have I considered all possible influences? Are there any surprising factors that could explain this shift?"

*Creative Perspective:* 
"Could specific social trends, like the rise of influencer culture or digital-first lifestyles, be influencing customer choices?"

**2.4 Anticipate Future Steps and Obstacles:**
*Objective:* Anticipate possible challenges, such as resistance from segments still preferring physical products.

*Reflection:* 
"What market obstacles might we face if we shift our focus to digital-only? Are there sub-segments that still prioritize physical products?"

*Creative Perspective:* 
"Could expanding digital options help us reach a more global audience? Are there emerging trends that we could leverage in our strategy?"

[end sys2]

[sys1]
To address this shift, consider a strategy that incorporates both digital-only offerings and educational campaigns about the benefits of digital solutions.
Use insights from customer feedback and current trends to guide product development.
Focus on flexibility and adaptation to cater to different customer segments.
[end sys1]


Abstract Introduction The real-world association between male circumcision and HIV status has important implications for policy and intervention practice. For instance, women may assume that circumcised men are safer sex partners than non-circumcised men and adjust sexual partnering and behavior according to these beliefs. Voluntary medical male circumcision (VMMC) is highly efficacious in preventing HIV acquisition in men and this biological efficacy should lead to a negative association between circumcision and HIV. However, behavioral factors such as differential selection into circumcision based on current HIV status or factors associated with future HIV status could reverse the association. Here, we examine how HIV prevalence differs by circumcision status in older adult men in a rural South African community, a non-experimental setting in a time of expanding VMMC access. Methods We analyzed data collected from a population-based sample of 2345 men aged 40 years and older in a rural community served by the Agincourt Health and socio-Demographic Surveillance System site in Mpumalanga province, South Africa. We describe circumcision prevalence and estimate the association between circumcision and laboratory-confirmed HIV status with log-binomial regression models. Results One quarter of older men reported circumcision, with slightly more initiation-based circumcisions (56%) than hospital-based circumcisions (44%). Overall, the evidence did not suggest differences in HIV prevalence between circumcised and uncircumcised men; however, those who reported hospital-based circumcision were more likely to test HIV-positive [PR (95% CI): 1.28 (1.03, 1.59)] while those who reported initiation-based circumcision were less likely to test HIV-positive [PR (95% CI): 0.68 (0.51, 0.90)]. Effects were attenuated, but not reversed after adjustment for key covariates. Conclusions Medically circumcised older men in a rural South African community had higher HIV prevalence than uncircumcised men, suggesting that the effect of selection into circumcision may be stronger than the biological efficacy of circumcision in preventing HIV acquisition. The impression given from circumcision policy and dissemination of prior trial findings that those who are circumcised are safer sex partners may be incorrect in this age group and needs to be countered by interventions, such as educational campaigns.

Citation: Rosenberg MS, Gómez-Olivé FX, Rohr JK, Kahn K, Bärnighausen TW (2018) Are circumcised men safer sex partners? Findings from the HAALSI cohort in rural South Africa. PLoS ONE 13(8): e0201445. https://doi.org/10.1371/journal.pone.0201445 Editor: Robert K. Hills, Cardiff University, UNITED KINGDOM Received: July 7, 2017; Accepted: July 16, 2018; Published: August 1, 2018 Copyright: © 2018 Rosenberg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: All relevant data are publicly available at the online HAALSI data repository (https://haalsi.org/data). Funding: The HAALSI study was funded by the NIA of the NIH (P01 AG041710). HAALSI is nested within the Agincourt Health and socio-Demographic Surveillance System, with funding from The Wellcome Trust (058893/Z/99/A; 069683/Z/02/Z; 085477/Z/08/Z; 085477/B/08/Z), University of the Witwatersrand, and Medical Research Council, South Africa. TB received support from the Alexander von Humboldt Foundation through the endowed Alexander von Humboldt Professorship funded by the German Federal Ministry of Education and Research. TB also received funding from the Wellcome Trust and from the National Institutes of Health (NICHD R01-HD084233, NIAID R01-AI124389, NIAID R01-AI112339, and D43-TW009775), as well as from the European Commission, the Clinton Health Access Initiative, the International Initiative for Impact Evaluation (3ie), UNAIDS and World Bank. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist.

Introduction Voluntary medical male circumcision (VMMC) is highly efficacious in preventing HIV acquisition in men.[1–4] In South Africa, where HIV incidence has been extremely high over the past three decades, national guidelines recommend that all men who test HIV-negative be offered a comprehensive prevention package that includes information on and referral to VMMC services, and that “the success of testing programs should be measured by the number of individuals successfully linked to…medical male circumcision services for HIV-negative males.”[5] However, little is known about the current differences in HIV prevalence by circumcision status in real-world, non-clinical trial settings. The evidence justifying VMMC trials came from a body of observational studies demonstrating lower HIV prevalence among traditionally circumcised men.[6] It is unknown if this association differs after years of expanding VMMC access when the decision to undergo the procedure may relate to current HIV status or factors associated with future HIV status, and specifically whether these kinds of selection effects could be strong enough to outweigh the protective biological effect of VMMC. One message transmitted by current VMMC policy and the proven protective effect of VMMC is that circumcised men are less likely to be HIV-positive. There is emerging potential for female partners, who report preference for circumcision in part due to perceptions about HIV status,[7,8] to change their sexual behaviors in response to this assumption.[9,10] The implications for HIV risk rest on whether or not this assumption is founded. There is also little known about male circumcision acceptability and uptake among older men in South Africa. In younger and general population South African and sub-Saharan African men, circumcision is generally perceived positively, with the link between circumcision and HIV/STI prevention cited as an important reason to become circumcised.[11–13] Older men, who are often overlooked as targets for HIV prevention interventions due to incorrect assumptions about their lack of sexual risk-taking,[14,15] and who came of age prior to VMMC recommendations for HIV prevention, may have different circumcision attitudes and patterns of circumcision uptake. Further, circumcision associated with traditional initiation ceremonies marking the rite of passage from childhood to adulthood is relatively common among Black South Africans and is more prevalent among older men than younger men.[16] In this paper, we aim to fill persistent knowledge gaps related to male circumcision in older men in sub-Saharan Africa. First, we describe the prevalence of male circumcision in the population and identify socio-demographic predictors of being circumcised in a sample of men 40 years and older from a rural South African community. Then, we model the association between circumcision status and prevalent HIV infection to provide insight into how HIV prevalence differs by circumcision status in a non-experimental setting in a time of expanding VMMC access.

Methods Study population This analysis uses data from the population-based Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa (HAALSI) study that aims to characterize a community of older men and women in rural South Africa with respect to health, physical and cognitive function, aging, and well-being. Adults age 40 and older were sampled from the existing framework of the Agincourt Health and Socio-Demographic Surveillance System (Agincourt HDSS)[17] in Mpumalanga province, northeast South Africa, and visited at home between November 2014 and November 2015. Extensive survey and laboratory data were collected to assess physical and cognitive functioning, cardiometabolic health, economic well-being, and HIV and HIV risk. Ethical approval for HAALSI was obtained from the University of the Witwatersrand Human Research Ethics Committee (#M141159), the Harvard T.H. Chan School of Public Health Office of Human Research Administration (#13–1608), and the Mpumalanga Provincial Research and Ethics Committee. All participants provided written informed consent to participate in the HAALSI study with consent procedures approved by the three ethical committees mentioned above. Key measures Trained, local fieldworkers collected survey data electronically using Computer Assisted Personal Interviews (CAPI). Surveys were conducted in the local language, Shangaan, with instruments translated from English and back-translated to ensure accurate translation. Circumcision status was ascertained with the question: “Has your foreskin been removed?” Among those who responded affirmatively to the circumcision question, age at circumcision (ages 0–13 14–18, and 19+) and type of circumcision (hospital-based or initiation-based circumcision) were queried. Although an ‘other’ response option for type of circumcision was available, all circumcised men self-selected into either ‘initiation’ or ‘hospital’ categories. For this reason, these are the only categories we used. In addition to the survey, fieldworkers collected blood via finger prick from those who consented. Dried bloodspots were prepared and later tested for HIV. Laboratory-confirmed HIV status was determined through screening and confirmatory HIV enzyme-linked immunosorbent assays conducted using standard laboratory practices on the prepared dried bloodspots.[18] Statistical analysis Given the proven biological efficacy of VMMC, we hypothesized that circumcised men would have lower HIV prevalence than uncircumcised men, and that lower HIV prevalence would be explained by those receiving hospital-based circumcisions and circumcisions at younger ages. We used log-binomial regression models to estimate the association between circumcision status and HIV status, with circumcision status stratified by age at circumcision and type of circumcision, and then doubly stratified by age and type of circumcision. We chose log-binomial regression models over logistic regression models because prevalence ratios from log-binomial regression are generally more interpretable than odds ratios from logistic regression. As a sensitivity analysis around our modeling decisions, we repeated our analyses using logistic regression models. We compared unadjusted estimates to estimates adjusted for age, in years; household asset index quintiles; African traditional religion; marital status; country of origin; formal education (any versus none); and number of lifetime sex partners (0–1, 2–4, or 5+). This study does not seek to re-examine the established causal relationship between VMMC and reduced HIV risk. Instead, we were interested in how circumcision and HIV prevalence are associated in a real-world setting of older men, in which decisions to undergo circumcision procedures could plausibly be related to HIV status and/or HIV risk. Thus, the unadjusted analyses of the association between circumcision and HIV are the primary results of interest in this study. The adjusted analyses provide evidence for whether these population-level estimates can be explained by the inclusion of key covariates. All analyses were conducted using SAS statistical software, version 9.4.[19]

Discussion In this analysis of population-based data on older men in rural South Africa, we examined circumcision history and the association between circumcision and HIV status in the current circumcision landscape. We found that one quarter of older men reported being circumcised, with slightly more than half of circumcisions reported as traditional initiation-based procedures as opposed to medical procedures. This circumcision prevalence is lower than the 2012 national estimate of 46% in men age 15 and older, but in line with findings indicating traditional circumcisions are more common than medical circumcision.[20] We also found that the demographic profile of those who were uncircumcised differed substantially from those with hospital-based circumcisions and those with initiation-based circumcisions. We found no differences in HIV prevalence by circumcision status overall, and that men with hospital-based circumcisions were more likely to test HIV-positive compared to both uncircumcised men and men with traditional initiation-based circumcision. That hospital-based circumcision was not associated with lower HIV prevalence differs from the findings we expected based on (i) the national policy on selection of HIV-negative men for VMMC, (ii) the protective effect of VMMC on HIV acquisition, and (iii) the protective association we observed between traditional initiation-based circumcision and HIV. A large body of observational studies from the pre-VMMC era established that traditionally circumcised men were less likely to be HIV-positive. A systematic review of 27 studies[6] reported a protective effect in nearly all of the unadjusted analyses, with strengthened associations after covariate adjustment. In population-based, cross-sectional studies like ours, the overall protective effect was 0.55 (95% CI: 0.34, 0.54), slightly stronger than our estimate for traditionally circumcised men, but in contrast to our estimate for medically circumcised men. Of course, our findings are plausible despite the high biological efficacy of medical circumcision in preventing HIV acquisition in men. The most likely explanation is that HIV-positive older men are circumcised in clinical settings in larger numbers than HIV-negative men, counter to the South African policy to target HIV-negative men with circumcision information and referral. One plausible pathway for this explanation is that HIV-positive men are more engaged in care than their HIV-negative counterparts, and circumcision services could be one of the clinical services to which they have more access. Another possible explanation is that men who engage in riskier sexual behavior self-select into VMMC, resulting in heightened risk for subsequent HIV infection. Although no significant differences were observed by age at circumcision, HIV prevalence was highest among men who were circumcised in the oldest age category (after age 18). One possible explanation for this finding is that in adulthood men with higher than average risk of HIV acquisition chose to be circumcised but that no such selection effect existed in childhood. However, this explanation requires the perhaps improbable assumption that the risk behaviors among the circumcised confer risk at a magnitude able to overcome the otherwise protective circumcision effect. Similarly, it is possible that older men engage in riskier sexual behavior after circumcision because they know that they are now at substantially reduced risk for HIV acquisition. However, this explanation is unlikely as there has been no evidence for this kind of risk compensation in prior circumcision studies in Africa,[21–26] and the magnitude of risk compensation that would have had to occur in our study population to bias the otherwise protective effect to become a significant association on the other side of the null is likely implausibly large. The possibility also exists for risk compensation in men with traditional initiation-based circumcision if they had been informed of the protective effects of circumcision. While risk compensation is unlikely to be the only explanation of the observed association between circumcision and HIV status in this study, it could have contributed to some extent to our findings, warranting further research on quantifying the level of risk compensation in communities similar to the study community. Several features of the data structure and quality call for our findings be interpreted with caution. First, we used self-reported circumcision status with no objective examination to confirm true circumcision status, which could lead to biased results if men were unwilling or unable to accurately report their true circumcision status. Second, the data were cross-sectional in design so we were unable to disentangle the temporal relationship between circumcision and HIV status. Plausible bidirectional mechanisms exist and we were not able to assess their relative contributions given the rough categorization of age at circumcision and unknown date of HIV seroconversion. Finally, these data were collected in a sample of older men in a rural South African community. Generalizability of these results to younger men or men in more urban settings may not be possible. Our findings are important for HIV prevention policy in South Africa for several reasons. First, among older men in rural South Africa, there remain many HIV-negative uncircumcised men who could receive HIV prevention benefits from VMMC as part of a comprehensive HIV prevention package promoting safer sexual practices tailored to the particular needs of older adults. Expansion of VMMC services to target older men with referrals could help address this unmet need. Second, the policy to target HIV-negative men with VMMC is likely not complied with in real-world settings as HIV prevalence was higher among medically circumcised men than among uncircumcised men. It is plausible that this policy, coupled with the widely-known protective effect of VMMC, gives the false impression that circumcised men are safer sex partners. If HIV-positive men actually take up the procedure at high rates, the promotion of VMMC as a procedure for HIV-negative men to prevent HIV may have the unintended consequence of increasing HIV transmission at the population-level. To reduce this risk, modifications of the existing VMMC policies and associated public engagement campaigns should be considered.

Conclusions Medically circumcised older men in rural South Africa had higher HIV prevalence than uncircumcised men, despite the biological efficacy of VMMC and the South African policy explicitly targeting HIV-negative men for circumcision. This finding suggests that the association between circumcision and HIV status may be more strongly driven by selection into circumcision than the biological efficacy of circumcision in preventing HIV acquisition. The impression given from circumcision policy and dissemination of prior trial findings that those who are circumcised are safer sex partners may be incorrect in this age group.

Supporting information S1 Table. Logistic regression sensitivity analysis of the relationship between circumcision status and HIV status among HAALSI men with laboratory-confirmed HIV status (n = 1945). https://doi.org/10.1371/journal.pone.0201445.s001 (DOCX)

Acknowledgments The authors are immensely grateful to all those involved in the successful field operations in HAALSI and the Agincourt HDSS, including field staff, data analysts, and, most importantly, the study participants themselves.