Reproduction and production in a social context: Group size, reproductive skew and increasing returns.

Evolutionary success requires both production (acquisition of food, protection and warmth) and reproduction. We suggest that both may increase disproportionately as group size grows, reflecting 'increasing returns' or 'group augmentation benefits', raising fitness in groups that cooperate in production and limit reproduction to one or a few high fertility females supported by non-reproductives, with high reproductive skew. In our optimisation theory both Allee effects (when individual fitness increases with group size or density) and reproductive skew arise when increasing returns determine optimal group size and proportion of reproductive females. Depending on which of food or maternal time is more important for reproduction, evolutionary trajectories of lineages may (1) reach a boundary constraint where only one female reproduces in a period (as with African wild dogs) or (2) reach a boundary where all females reproduce during their lifetimes but only during an early life stage (human menopause) or a late life stage (birds with non-dispersing helpers), where stage length optimises the proportion of females that is reproductive at any time or (3) reach the intersection of these boundary constraints where a single reproductive female is fully specialised in reproduction (as with eusocial insects). We end with some testable hypotheses.

Intergenerational resource sharing and mortality in a global perspective.

Resource sharing has always been a central component of human sociality. Children require heavy investments in human capital; during working years, help is needed due to illness, disability, or bad luck. While hunter-gatherer elders assisted their descendants, more recently, elderly withdraw from work and require assistance as well. Willingness to share has been critically important for our past evolutionary success and our present daily lives. Here, we document a strong linear relationship between the public and private sharing generosity of a society and the average length of life of its members. Our findings from 34 countries on six continents suggest that survival is higher in societies that provide more support and care for one another. We suggest that this support reduces mortality by meeting urgent material needs, but also that sharing generosity may reflect the strength of social connectedness, which itself benefits human health and wellbeing and indirectly raises survival.

Demographic perspectives on the mortality of COVID-19 and other epidemics.

To put estimates of COVID-19 mortality into perspective, we estimate age-specific mortality for an epidemic claiming for illustrative purposes 1 million US lives, with results approximately scalable over a broad range of deaths. We calculate the impact on period life expectancy (down 2.94 y) and remaining life years (11.7 y per death). Avoiding 1.75 million deaths or 20.5 trillion person years of life lost would be valued at $10.2 to $17.5 trillion. The age patterns of COVID-19 mortality in other countries are quite similar and increase at rates close to each country's rate for all-cause mortality. The scenario of 1 million COVID-19 deaths is similar in scale to that of the decades-long HIV/AIDS and opioid-overdose epidemics but considerably smaller than that of the Spanish flu of 1918. Unlike HIV/AIDS and opioid epidemics, the COVID-19 deaths are concentrated in a period of months rather than spread out over decades.

Data-driven contact network models of COVID-19 reveal trade-offs between costs and infections for optimal local containment policies.

While several non-pharmacological measures have been implemented for a few months in an effort to slow the coronavirus disease (COVID-19) pandemic in the United States, the disease remains a danger in a number of counties as restrictions are lifted to revive the economy. Making a trade-off between economic recovery and infection control is a major challenge confronting many hard-hit counties. Understanding the transmission process and quantifying the costs of local policies are essential to the task of tackling this challenge. Here, we investigate the dynamic contact patterns of the populations from anonymized, geo-localized mobility data and census and demographic data to create data-driven, agent-based contact networks. We then simulate the epidemic spread with a time-varying contagion model in ten large metropolitan counties in the United States and evaluate a combination of mobility reduction, mask use, and reopening policies. We find that our model captures the spatial-temporal and heterogeneous case trajectory within various counties based on dynamic population behaviors. Our results show that a decision-making tool that considers both economic cost and infection outcomes of policies can be informative in making decisions of local containment strategies for optimal balancing of economic slowdown and virus spread.

Disposition and metabolism of the G protein-coupled receptor 40 agonist TAK-875 (fasiglifam) in rats, dogs, and humans.

The absorption, distribution, metabolism, and excretion of fasiglifam were investigated in rats, dogs, and humans. The absolute oral bioavailability of fasiglifam was high in all species (>76.0%). After oral administration of [14C]fasiglifam, the administered radioactivity was quantitatively recovered and the major route of excretion of radioactivity was via feces in all species. Fasiglifam was a major component in the plasma and feces in all species. Its oxidative metabolite (M-I) was observed as a minor metabolite in rat and human plasma (<10% of plasma radioactivity). In human plasma, hydroxylated fasiglifam (T-1676427), the glucuronide of fasiglifam (fasiglifam-G), and the glucuronide of M-I were detected as additional minor metabolites (<2% of plasma radioactivity). None of these metabolites were specific to humans. Fasiglifam-G was the major component in the rat and dog bile. In vitro cytochrome P450 (CYP) and uridine diphosphate glucuronosyltransferase (UGT) reaction phenotyping indicated that oxidation (to form M-I and T-1676427) and glucuronidation of fasiglifam are mainly mediated by CYP3A4/5 and UGT1A3, respectively. Fasiglifam and fasiglifam-G are substrates of BCRP and Mrp2/MRP2, respectively. Glucuronidation of fasiglifam-G was found to be the predominant elimination pathway of fasiglifam in all species tested, including humans.

Clinical Benefit in Response to Palbociclib Treatment in Refractory Uterine Leiomyosarcomas with a Common CDKN2A Alteration.

BACKGROUND: Uterine leiomyosarcoma (uLMS) responds poorly to conventional chemotherapeutic agents, and personalized therapies have yet to be systematically explored. Comprehensive genomic profiling (CGP) can identify therapeutic targets and provide insight into the biology of this highly aggressive tumor. We report a case of uLMS treated with the CGP-matched therapy palbociclib, a CDK4/6 inhibitor, with sustained clinical benefit in this rare and deadly malignancy. MATERIALS AND METHODS: This study analyzed 279 clinically advanced/recurrent uLMS samples. Median patient age was 54 years (range, 23-83 years). DNA was extracted from 40 µm of formalin-fixed, paraffin-embedded sections, and CGP was performed on hybridization-captured, adaptor ligation-based libraries for up to 405 cancer-related genes plus introns from up to 31 genes frequently rearranged in cancer. Sequencing data were analyzed for base pair substitutions, insertions/deletions, copy number alterations, and rearrangements. RESULTS: CGP shows that 97.1% of uLMS harbor at least one alteration, and approximately 57% harbor alterations in one or more therapeutically targetable pathways. CDKN2A mutations that inactivate p16INK4a were identified in 11% of uLMS. We report the first demonstration of clinical benefit in response to palbociclib treatment for a uLMS patient with a CDKN2A mutation, resulting in disease stabilization and significant symptom reduction. CONCLUSION: A patient with uLMS harboring a CDKN2A mutation experienced clinical benefit from treatment with palbociclib, and genomic analysis of 279 uLMS samples revealed that 19% of patients had mutations affecting the cyclin-dependent kinase (CDK) pathway. These observations provide a rationale for a clinical trial investigating treatment with CDK pathway inhibitors for uLMS harboring relevant genomic alterations. The Oncologist 2017;22:416-421Implications for Practice: Comprehensive genomic profiling (CGP) of individuals with uterine leiomyosarcoma (uLMS) indicates that nearly 20% of patients may harbor a mutation affecting the cyclin-dependent kinase (CDK) pathway. The case presented demonstrates that a CDK inhibitory drug may provide clinical benefit to such individuals. Given the lack of curative therapies for uLMS, CGP could be performed on all cases of advanced uLMS and a CDK inhibitor could be recommended (preferably as part of a clinical trial) for individuals harboring a mutation in the CDK pathway.

Versatile Tool for the Analysis of Metal-Protein Interactions Reveals the Promiscuity of Metallodrug-Protein Interactions.

Metallodrug-protein interactions contribute to their therapeutic effect (even when DNA is the dominant target), side-effects and are implicit in drug resistance. Here, we provide mass spectrometric-based evidence to show that metallodrug interactions with proteins are considerably more complex than current literature would suggest. Using native-like incubation and electrospray conditions together with an automated tool we designed for exhaustive mass spectra matching, the promiscuity of binding of cisplatin to ubiquitin is revealed, with 14 different binding sites observed. There is a binding preference to negatively charged sites on the protein, consistent with the cationic nature of the cisplatin adduct following aquation. These results have implications in metallodrug development and beyond to the toxicological effects of metal ions more generally.

Biochemical and biophysical characterization of ruthenation of BRCA1 RING protein by RAPTA complexes and its E3 ubiquitin ligase activity.

RAPTA compounds, ([Ru(η6-arene)(PTA)Cl2], PTA = 1,3,5-triaza-7-phosphaadamantane), have been reported to overcome drug resistance in cisplatin resistant cells. However, the exact mechanism of these complexes is still largely unexplored. In this study, the interaction of some RAPTA compounds with the N-terminal fragment of the BRCA1 RING domain protein was investigated. The binding of the RAPTA compounds to the BRCA1 protein resulted in a release of Zn2+ ions in a dose and time dependent manner, as well as thermal alteration of ruthenated-BRCA1 proteins. Electron Transfer Dissociation (ETD) fragmentation mass spectrometry revealed the preferential binding sites of the RAPTA complexes on the BRCA1 zinc finger RING domain at a similar short peptide stretch, Cys24Lys25Phe26Cys27Met28Leu29 and Lys35 (residues 44-49 and 55 on full length BRCA1). Changes in the conformation and binding constants of ruthenium-BRCA1 adducts were established, resulting in inactivation of the RING heterodimer BRCA1/BARD1-mediated E3 ubiquitin ligase function. These findings could provide mechanistic insight into the mode of action of RAPTA complexes for on tested BRCA1 model protein.

The Differential Distribution of RAPTA-T in Non-Invasive and Invasive Breast Cancer Cells Correlates with Its Anti-Invasive and Anti-Metastatic Effects.

Nanoscale secondary ion mass spectrometry (NanoSIMS) combined with transmission electron microscopy (TEM) can be a powerful approach to visualize the exact distribution of drugs at the sub-cellular level. In this work, we exploit this approach to identify the distribution and localisation of the organometallic ruthenium(II)-arene drug Ru(η6-C6H5Me)(pta)Cl2, termed RAPTA-T, in MDA-MB-231 and MCF-7 human breast cancer cells. These cell lines have been chosen because the former cell lines are highly invasive and resistant to most chemotherapeutic agents and the latter ones are very sensitive to hormonal-based therapies. In the MDA-MB-231 cells, RAPTA-T was found to predominantly localise on the cell membrane and to a lesser extent in the nucleolus. These findings are consistent with the previously reported anti-metastatic properties of RAPTA-T and the observation that once internalized RAPTA-T is associated with chromatin. RAPTA-T shows a lack of membrane accumulation on the non-invasive MCF-7 cells, which correlates well with its selective anti-metastatic properties on invasive cell lines.

HOW THE GROWING GAP IN LIFE EXPECTANCY MAY AFFECT RETIREMENT BENEFITS AND REFORMS.

Older Americans have experienced dramatic gains in life expectancy in recent decades, but an emerging literature reveals that these gains are accumulating mostly to those at the top of the income distribution. We explore how growing inequality in life expectancy affects lifetime benefits from Social Security, Medicare, and other programs and how this phenomenon interacts with possible program reforms. We first project that life expectancy at age 50 for males in the two highest income quintiles will rise by 7 to 8 years between the 1930 and 1960 birth cohorts, but that the two lowest income quintiles will experience little to no increase over that time period. This divergence in life expectancy will cause the gap between average lifetime program benefits received by men in the highest and lowest quintiles to widen by $130,000 (in $2009) over this period. Finally we simulate the effect of Social Security reforms such as raising the normal retirement age and changing the benefit formula to see whether they mitigate or enhance the reduced progressivity resulting from the widening gap in life expectancy.

Work readiness of pharmacy graduates: An exploratory study.

Introduction: The recent global pandemic of Covid-19 caused various disruptions. Among them were face-to-face teaching and learning activities being switched to virtual sessions in accordance with health authorities recommendations. The impact of these changes on work readiness of pharmacy graduates is unknown. Aim: This study aims to determine the impact of pharmacy graduate's work readiness, particularly those that had their studies disrupted from the pandemic. Methods: Practicing pharmacists with supervisory experience were interviewed on their opinions on work readiness of early career and intern pharmacists. Specifically, they were asked to comment on work readiness of pharmacy graduates who had their later stage of pharmacy education impacted by the pandemic. Data was transcribed verbatim and thematically analysed. This was also supplemented with quantitative data from graduating students in 2020 and 2021 using the Work Readiness Scale. Results: Qualitative feedback showed four themes related to workforce readiness: work competence, social intelligence, personal characteristics, and organizational acumen. Preceptors interviewed noted differences in communication abilities when interacting with patients. However, this improved with time. Quantitative data collected from graduates via the validated Work-Readiness Scale also showed a more positive agreement towards perceived work readiness. These graduates were comfortable with using technology as they had used these extensively in their learning during the pandemic and thus was comfortable in adopting digital health tools in their practice. Conclusion: Although graduates reported to be work ready, there were gaps in communication skills and confidence levels when interacting with patients, as reported by supervising preceptors. Graduates also described this sense of 'missing out' from not having the opportunity to attend face-to-face activities like their originally planned hospital placements and how it impacted their choice of career. As pharmacists continue to play vital roles as members of the broader healthcare workforce, both in clinical and nonclinical settings, learnings from this study should be considered in designing educational activities to train and develop the workforce of the future.

On the evolution of intergenerational division of labor, menopause and transfers among adults and offspring.

We explain how upward transfers from adult children to their elderly parents might evolve as an interrelated feature of a deepening intergenerational division of labor. Humans have a particularly long period of juvenile dependence requiring both food and care time provided mainly by younger and older adults. We suggest that the division of labor evolves to exploit comparative advantage between young and old adults in fertility, childcare and foraging. Eventually the evolving division of labor reaches a limit when the grandmother's fertility reaches zero (menopause). Continuing, it may hit another limit when the grandmother's foraging time has been reduced to her subsistence needs. Further specialization can occur only with food transfers to the grandmother, enabling her to reduce her foraging time to concentrate on additional childcare. We prove that this outcome can arise only after menopause has evolved. We describe the conditions necessary for both group selection (comparative steady state reproductive fitness) and individual selection (successful invasion by a mutation), and interpret these conditions in terms of comparative advantages.

Perspectives on opportunities and challenges in a predominantly flipped classroom-based pharmacy curriculum: A qualitative study.

INTRODUCTION: To adapt to flipped classroom pedagogy in universities, factors such as the amount of the program that is flipped, students' pre-existing educational experiences, and cultural background may influence adjusting to the approach. We investigated students' perspectives across four years of a predominantly flipped classroom-based pharmacy curriculum in a low to middle income country. METHODS: We conducted five semi-structured focus groups with 18 pharmacy students from years one to four of the bachelor of pharmacy program at Monash University Malaysia where students came from different pre-university backgrounds. Focus group recordings were transcribed verbatim and thematically analysed. Interrater reliability was performed to ascertain reliability of themes. RESULTS: Three major themes were identified. Firstly, students cited issues moving past the initial barrier when starting flipped classrooms in terms of education background impacting adaptability and how/why they eventually adapted. Another theme was how flipped classrooms helped development of life skills such as adaptability, communication, teamwork, self-reflection, and time management. The final theme was on requiring a sufficient safety net and support system in flipped classrooms that included well designed pre-classroom materials and well-implemented feedback mechanisms. CONCLUSIONS: We have identified students' perspectives on the benefits and challenges associated with a predominantly flipped classroom pharmacy curriculum in a low to middle income country setting. We suggest using scaffolding and effective feedback approaches to guide the implementation of flipped classrooms successfully. This work can aid future educational designers in preparation and supporting a more equitable learning experience regardless of student background.

Remote extemporaneous compounding lab practical for pharmacy students during the COVID-19 pandemic.

BACKGROUND AND PURPOSE: Due to COVID-19 movement restrictions, institutes of higher learning had to deliver pharmacy curricula remotely. One major challenge was teaching practical lab skills, such as extemporaneous compounding, remotely due to the need for hands-on learning and its associated logistical requirements. EDUCATIONAL ACTIVITY AND SETTING: We present the approach to remote extemporaneous compounding teaching taken by three pharmacy schools: Monash University Malaysia, University of Michigan, and University of Maryland. Prior to delivery, students were either supplied with or asked to procure a set of easily accessible ingredients and equipment to conduct the extemporaneous practicals from home. We conducted lessons remotely using both synchronous and asynchronous delivery, and demonstrated, taught, and assessed practical lab skills using video conferencing modalities. FINDINGS: We successfully conducted remote teaching of extemporaneous compounding, where similar learning outcomes to the face-to-face implementation were achieved. At Monash University Malaysia, > 90% of students responding to the post-activity surveys found the remote extemporaneous sessions useful for their learning, and qualitative comments supported these views. Mean scores from the remote extemporaneous labs in 2021 were similar to those when conducted physically in 2019, supporting the effectiveness of the approach. The different approaches attempted by the three institutions highlighted the flexibility in implementation that can be considered to achieve similar outcomes. SUMMARY: Combining technology-based approaches with synchronous and asynchronous teaching and learning methods can successfully deliver extemporaneous compounding skills remotely.

Sexual dimorphism and sexual selection: a unified economic analysis.

We develop a life history model with two sexes, and study the optimal energy allocation strategy of males and females. We join Darwin and others in suggesting that the origin of sexual dimorphism and sexual selection is the difference between male and female reproduction costs. Due to this assumed cost difference, the resulting Bellman equations of gene dynamics in our two-sex life history model imply a large "energy surplus" on the part of males. This allows the male form to devote energy to the development of some costly male traits that help the males to compete for access to females. These costly male traits are sexually dimorphic. Using this life history model, we are able to explain important features of sexual dimorphism, as well as why males often transfer less to their offspring than do females, and why only females have a menopause.

Cultural adaptation and validation of instruments for measuring the flipped classroom experience.

INTRODUCTION: In 2017, a revamped bachelor of pharmacy program was introduced at Monash University and incorporated a predominantly flipped classroom-based pedagogy. The attitudes and preferences of students towards this program had yet to be assessed using a reliable instrument. Since no instrument was readily available, the objective of this study was to identify, contextualize, and validate a suitable instrument. METHODS: We conducted a literature search to identify and adapt a validated instrument. Cognitive interviews were conducted to examine students' understanding of scales and definitions of items. The instrument was then evaluated by education experts for further refinement. The reliability of the final instrument was assessed in a cohort of students, and unsuitable items were removed. RESULTS: Students had issues understanding the scales and specific terms used in the original instrument, potentially due to differences in terminologies used in the university's context and variance in English proficiency levels and exposure. In the preference domain, wording of the instrument to present exclusively traditional classroom or exclusively flipped classroom statements greatly influenced its reliability. This could be due to exposure of students to a predominantly flipped classroom environment since inception. The final instrument optimized in this study had α = 0.85, 0.86, and 0.9 for the pre-activities, in-class lectures, and in-class workshops attitude domains, respectively, and α = 0.73 for the preference domain. CONCLUSIONS: Our study highlights the necessity of contextualizing instruments to fit the local context in which they are administered and provides key recommendations when conducting such adaptations.

A Community-Based Pancreatic Cancer Screening Study in High-Risk Individuals: Preliminary Efficacy and Safety Results.

INTRODUCTION: Pancreatic cancer (PC) screening recommendations have been based on studies performed solely at high-volume academic centers. To make PC screening more widely available, community-based efforts are essential. We implemented a prospective PC screening study in the community of Fairfield County, CT, and report our early safety and efficacy results. METHODS: Eligible individuals were enrolled into an investigator-initiated study and underwent a baseline and 3 annual magnetic resonance imagings/magnetic resonance cholangiopancreatographies (MRIs/MRCPs) with gadolinium, biannual blood donations for biobanking, and assessments for anxiety and depression. All MRIs were presented at a multidisciplinary board to determine whether further investigation was warranted. RESULTS: Seventy-five individuals have been enrolled and 201 MRIs performed over a 2.6-year average length of follow-up. Abnormal pancreatic findings (predominantly small cysts) were detected in 58.7% of the participants. Among these, 6.7% underwent endoscopic ultrasound, with 1 case complicated by postprocedural pancreatitis. One surgical resection was performed on a 4.7-cm intraductal papillary mucinous neoplasm with a focus on low-grade pancreatic intraepithelial neoplasia. One incidental finding of fibrosing mediastinitis was detected. Anxiety and depression scores decreased over the course of this study from 21.4% to 5.4% and 10.7% to 3.6%, respectively. DISCUSSION: This preliminary report supports the feasibility of performing MRI/magnetic resonance cholangiopancreatographies-based PC screening as part of a clinical trial in a community setting. A longer follow-up is needed to better assess safety and efficacy. To the best of our knowledge, this is the first report from a community-based PC screening effort ( clinicaltrials.gov ID: NCT03250078).

Effectiveness and acceptability of a computerized decision support system using modified Wells criteria for evaluation of suspected pulmonary embolism.

STUDY OBJECTIVE: Ready availability of computed tomography (CT) angiography for evaluation of pulmonary embolism in emergency departments (EDs) is associated with a dramatic increase in the number of CT angiography tests. The aims of this study are to determine whether a validated prediction algorithm embedded in a computerized decision support system improves the positive yield rate of CT angiography for pulmonary embolism and is acceptable to emergency physicians. METHODS: This study was conducted as a prospective interventional study with a retrospective preinterventional comparison group. RESULTS: The implementation of the computerized physician order entry-based computerized decision support system was associated with an overall increase in the positivity rate of from 8.3% (95% confidence interval [CI] 4.9% to 12.9%) preintervention to 12.7% (95% CI 8.6% to 17.7%) postintervention, with a difference of 4.4% (95% CI -1.4% to 10.1%). A total of 404 patients were eligible for inclusion. Physician nonadherence to the computerized decision support system occurred in 105 (26.7%) cases. Fifteen patients underwent CT angiography despite low Wells score and negative D-dimer result, all of whose results were negative for pulmonary embolism. Emergency physicians did not order CT angiography for 44 patients despite high pretest probability, with one receiving a diagnosis of pulmonary embolism on a subsequent visit and another, of DVT. When emergency physicians adhered to the computerized decision support system for the evaluation of suspected pulmonary embolism, a higher yield of CT angiography for pulmonary embolism occurred, with 28 positive results of 168 CT angiography tests (16.7%; 95% CI 11.4% to 23.2%) and a difference compared with preintervention of 8.4% (95% CI 1.7% to 15.4%). Physicians cited the time required to apply the computerized decision support system and a preference for intuitive judgment as reasons for not adhering to the computerized decision support system. CONCLUSION: Use of an evidence-based computerized physician order entry-based computerized decision support system for the evaluation of suspected pulmonary embolism was associated with a higher yield of CT angiography for pulmonary embolism. The computerized decision support system, however, was poorly accepted by emergency physicians (partly because of increased computer time), leading to possibly selective use, reducing the effect on overall yield, and leading to removal of the computerized decision support system from the computer order entry. These findings emphasize the importance of facilitation of rule-based decisionmaking in the ED and attentiveness to the complex demands placed on emergency physicians.

Sociality, selection, and survival: simulated evolution of mortality with intergenerational transfers and food sharing.

Why do humans survive so long past reproductive age, and why does juvenile mortality decline after birth, both contrary to the classic theory of aging? Previous work has shown formally that intergenerational transfers can explain both these patterns. Here, simulations confirm those results under weaker assumptions and explore how different social arrangements shape life-history evolution. Simulated single-sex hunter-gatherers survive, forage, reproduce, and share food with kin and nonkin in ways guided by the ethnographic literature. Natural selection acts on probabilistically occurring deleterious mutations. Neither stable population age distributions nor homogeneous genetic lineages are assumed. When food is shared only within kin groups, an infant death permits reallocation of its unneeded food to the infant's kin, offsetting the fitness cost of the death and weakening the force of selection against infant mortality. Thus, evolved infant mortality is relatively high, more so in larger kin groups. Food sharing with nonkin reduces the costs to kin of child rearing, but also reduces the resources recaptured by kin after an infant death, so evolved infant mortality is lower. Postreproductive adults transfer food to descendants, enhancing their growth and survival, so postreproductive survival is selected. The force of selection for old-age survival depends in complicated ways on the food-sharing arrangements. Population-level food sharing with nonkin leads to the classic pattern of constant low mortality up to sexual maturity and no postreproductive survival.

Welfare and Generational Equity in Sustainable Unfunded Pension Systems.

Using stochastic simulations we analyze how public pension structures spread the risks arising from demographic and economic shocks across generations. We consider several actual and hypothetical sustainable PAYGO pension structures, including: (1) versions of the US Social Security system with annual adjustments of taxes or benefits to maintain fiscal balance; (2) Sweden's Notional Defined Contribution system and several variants developed to improve fiscal stability; and (3) the German system, which also includes annual adjustments to maintain fiscal balance. For each system, we present descriptive measures of uncertainty in representative outcomes for a typical generation and across generations. We then estimate expected utility for generations based on simplifying assumptions and incorporate these expected utility calculations in an overall social welfare measure. Using a horizontal equity index, we also compare the different systems' performance in terms of how neighboring generations are treated.While the actual Swedish system smoothes stochastic fluctuations more than any other and produces the highest degree of horizontal equity, it does so by accumulating a buffer stock of assets that alleviates the need for frequent adjustments. In terms of social welfare, this accumulation of assets leads to a lower average rate of return that more than offsets the benefits of risk reduction, leaving systems with more frequent adjustments that spread risks broadly among generations as those most preferred.