Priority for the Worse Off and the Social Cost of Carbon

The social cost of carbon (SCC) is a monetary measure of the harms from carbon emission. Specifically, it is the reduction in current consumption that produces a loss in social welfare equivalent to that caused by the emission of a ton of CO2. The standard approach is to calculate the SCC using a discounted-utilitarian social welfare function (SWF)—one that simply adds up the well-being numbers (utilities) of individuals, as discounted by a weighting factor that decreases with time. The discounted-utilitarian SWF has been criticized both for ignoring the distribution of well-being, and for including an arbitrary preference for earlier generations. Here, we use a prioritarian SWF, with no time-discount factor, to calculate the SCC in the integrated assessment model RICE. Prioritarianism is a well-developed concept in ethics and theoretical welfare economics, but has been, thus far, little used in climate scholarship. The core idea is to give greater weight to well-being changes affecting worse off individuals. We find substantial differences between the discounted-utilitarian and non-discounted prioritarian SCC

Genomic mining of prokaryotic repressors for orthogonal logic gates

Genetic circuits perform computational operations based on interactions between freely diffusing molecules within a cell. When transcription factors are combined to build a circuit, unintended interactions can disrupt its function. Here, we apply 'part mining' to build a library of 73 TetR-family repressors gleaned from prokaryotic genomes. The operators of a subset were determined using an in vitro method, and this information was used to build synthetic promoters. The promoters and repressors were screened for cross-reactions. Of these, 16 were identified that both strongly repress their cognate promoter (5- to 207-fold) and exhibit minimal interactions with other promoters. Each repressor-promoter pair was converted to a NOT gate and characterized. Used as a set of 16 NOT/NOR gates, there are >10[superscript 54] circuits that could be built by changing the pattern of input and output promoters. This represents a large set of compatible gates that can be used to construct user-defined circuits.United States. Air Force Office of Scientific Research (Award FA9550-11-C-0028)American Society for Engineering Education. National Defense Science and Engineering Graduate Fellowship (32 CFR 168a)United States. Defense Advanced Research Projects Agency. Chronical of Lineage Indicative of Origins (N66001-12-C-4016)United States. Office of Naval Research (N00014-13-1-0074)National Institutes of Health (U.S.) (GM095765)National Science Foundation (U.S.). Synthetic Biology Engineering Research Center (SA5284-11210

Genetic and Proteomic Approaches to Identify Cancer Drug Targets

While target-based small-molecule discovery has taken centre-stage in the pharmaceutical industry, there are many cancer-promoting proteins not easily addressed with a traditional target-based screening approach. In order to address this problem, as well as to identify modulators of biological states in the absence of knowing the protein target of the state switch, alternative phenotypic screening approaches, such as gene expression-based and high-content imaging, have been developed. With this renewed interest in phenotypic screening, however, comes the challenge of identifying the binding protein target(s) of small-molecule hits. Emerging technologies have the potential to improve the process of target identification. In this review, we discuss the application of genomic (gene expression-based), genetic (short hairpin RNA and open reading frame screening), and proteomic approaches to protein target identification

Principles of genetic circuit design

Cells navigate environments, communicate and build complex patterns by initiating gene expression in response to specific signals. Engineers seek to harness this capability to program cells to perform tasks or create chemicals and materials that match the complexity seen in nature. This Review describes new tools that aid the construction of genetic circuits. Circuit dynamics can be influenced by the choice of regulators and changed with expression 'tuning knobs'. We collate the failure modes encountered when assembling circuits, quantify their impact on performance and review mitigation efforts. Finally, we discuss the constraints that arise from circuits having to operate within a living cell. Collectively, better tools, well-characterized parts and a comprehensive understanding of how to compose circuits are leading to a breakthrough in the ability to program living cells for advanced applications, from living therapeutics to the atomic manufacturing of functional materials.National Institute of General Medical Sciences (U.S.) (Grant P50 GM098792)National Institute of General Medical Sciences (U.S.) (Grant R01 GM095765)National Science Foundation (U.S.). Synthetic Biology Engineering Research Center (EEC0540879)Life Technologies, Inc. (A114510)National Science Foundation (U.S.). Graduate Research FellowshipUnited States. Office of Naval Research. Multidisciplinary University Research Initiative (Grant 4500000552

Basic science of osteoarthritis

Osteoarthritis (OA) is a prevalent, disabling disorder of the joints that affects a large population worldwide and for which there is no definitive cure. This review provides critical insights into the basic knowledge on OA that may lead to innovative end efficient new therapeutic regimens. While degradation of the articular cartilage is the hallmark of OA, with altered interactions between chondrocytes and compounds of the extracellular matrix, the subchondral bone has been also described as a key component of the disease, involving specific pathomechanisms controlling its initiation and progression. The identification of such events (and thus of possible targets for therapy) has been made possible by the availability of a number of animal models that aim at reproducing the human pathology, in particular large models of high tibial osteotomy (HTO). From a therapeutic point of view, mesenchymal stem cells (MSCs) represent a promising option for the treatment of OA and may be used concomitantly with functional substitutes integrating scaffolds and drugs/growth factors in tissue engineering setups. Altogether, these advances in the fundamental and experimental knowledge on OA may allow for the generation of improved, adapted therapeutic regimens to treat human OA.(undefined

Strategies of a parasite of the ant–Acacia mutualism

Mutualisms can be exploited by parasites—species that obtain resources from a partner but provide no services. Though the stability of mutualisms in the presence of such parasites is under intensive investigation, we have little information on life history traits that allow a species to be a successful mutualist or rather a parasite, particularly in cases where both are closely related. We studied the exploitation of Acacia myrmecophytes by the ant, Pseudomyrmex gracilis, contrasting with the mutualistic ant Pseudomyrmex ferrugineus. P. gracilis showed no host-defending behavior and had a negative effect on plant growth. By preventing the mutualist from colonization, P. gracilis imposes opportunity costs on the host plant. P. gracilis produced smaller colonies with a higher proportion of alates than did the mutualist and thus showed an “r-like” strategy. This appears to be possible because P. gracilis relies less on host-derived food resources than does the mutualist, as shown by behavioral and stable isotope studies. We discuss how this system allows the identification of strategies that characterize parasites of mutualisms

Parental Monitoring During Early Adolescence Deters Adolescent Sexual Initiation: Discrete-Time Survival Mixture Analysis

We used discrete-time survival mixture modeling to examine 5,305 adolescents from the 1997 National Longitudinal Survey of Youth regarding the impact of parental monitoring during early adolescence (ages 14–16) on initiation of sexual intercourse and problem behavior engagement (ages 14–23). Four distinctive parental-monitoring groups were identified and labeled as “High,” “Increasing,” “Decreasing,” and “Low”. About 68% of adolescents received a high level of parental monitoring from ages 14 to 16 (High), 6 and 9% respectively exhibited an accelerated (Increasing) and a decelerated trajectory (Decreasing), and 17% had consistently low parental monitoring (Low). Relative to participants in the Low group, adolescents in the High group delayed sexual initiation by 1.5 years. Males, relative to females, were more likely to have had a low trajectory of parental monitoring, and were more likely to initiate sexual intercourse before age 14. In contrast to White Adolescents, Hispanics and Blacks were less likely to receive High parental monitoring, and had a higher rate of early sexual initiation before age 14. The study demonstrates the temporal relationship of parental monitoring with adolescent sexual initiation from a longitudinal perspective. An increase of parental monitoring across ages is accompanied with a decrease of sexual risk. The continual high level of parental monitoring from ages 14 to 16 also mitigated the risk of engagement in substance use and delinquent behaviors from ages 14 to 23

Sociocultural Determinants of Teenage Childbearing Among Latinas in California

Objectives U.S. Latinas have a persistently high rate of teenage childbearing, which is associated with adverse outcomes for both mother and child. This study was designed to investigate the roles of socioeconomic factors and acculturation in teenage childbearing in this population. Methods Logistic regression was used to analyze the association of measures of acculturation (language spoken at home, nativity, and age at immigration) and respondents’ parents’ education with age at first birth in a stratified sample of post-partum women in California. Results The unadjusted odds ratio for teenage birth for Latinas versus non-Latina Whites was 5.2 (95% CI 4.1–6.6). Nativity was not significantly associated with teen birth, but speaking Spanish at home was positively associated and immigrating at a later age was negatively associated with teen birth. Overall, these measures of acculturation accounted for 17% (95% CI 8–28%) of the difference in odds of teen birth between Latinas and non-Latina Whites. Higher levels of education among respondents’ parents had differentially protective effects across the racial/ethnic groups. Controlling for disparities in respondents’ parents’ education without changing its differential effects across racial/ethnic groups reduced the odds ratio for Latinas compared to non-Latina Whites by 30% (95% CI 14–60%). Conclusion These findings call into question common assumptions about the protective effect of acculturation on teen fertility and suggest that improving childhood socioeconomic factors among Latinas may decrease teen childbearing

Randomised controlled trial of a supervised exercise rehabilitation program for colorectal cancer survivors immediately after chemotherapy: study protocol

Background Colorectal cancer (CRC) diagnosis and the ensuing treatments can have a substantial impact on the physical and psychological health of survivors. As the number of CRC survivors increases, so too does the need to develop viable rehabilitation programs to help these survivors return to good health as quickly as possible. Exercise has the potential to address many of the adverse effects of CRC treatment; however, to date, the role of exercise in the rehabilitation of cancer patients immediately after the completion of treatment has received limited research attention. This paper presents the design of a randomised controlled trial which will evaluate the feasibility and efficacy of a 12-week supervised aerobic exercise program (ImPACT Program) on the physiological and psychological markers of rehabilitation, in addition to biomarkers of standard haematological outcomes and the IGF axis. Methods/Design Forty CRC patients will be recruited through oncology clinics and randomised to an exercise group or a usual care control group. Baseline assessment will take place within 4 weeks of the patient completing adjuvant chemotherapy treatment. The exercise program for patients in the intervention group will commence a week after the baseline assessment. The program consists of three supervised moderate-intensity aerobic exercise sessions per week for 12 weeks. All participants will have assessments at baseline (0 wks), mid-intervention (6 wks), post-intervention (12 wks) and at a 6-week follow-up (18 wks). Outcome measures include cardio-respiratory fitness, biomarkers associated with health and survival, and indices of fatigue and quality of life. Process measures are participants' acceptability of, adherence to, and compliance with the exercise program, in addition to the safety of the program. Discussion The results of this study will provide valuable insight into the role of supervised exercise in improving life after CRC. Additionally, process analyses will inform the feasibility of implementing the program in a population of CRC patients immediately after completing chemotherapy

Quality of life among Latina breast cancer patients: a systematic review of the literature

Introduction The Latino population is the most rapidly growing ethnic minority in the United States and Latinas have higher rates of advanced breast cancer and more rigorous treatments than White women. However, the literature lacks reviews on quality of life among this population of breast cancer patients. Methods A systematic review of the breast cancer quality of life (QOL) literature was conducted among studies that provided a comparison of mental, physical, social, or sexual QOL between Latinas and other racial/ethnic groups. Of the 375 studies reviewed, 20 quantitative studies and two qualitative studies met criteria for inclusion. Results Latinas were more likely to report poor mental, physical, and social QOL, relative to non-Latinas. Only four studies assessed sexual QOL, making it difficult to draw any conclusions. Of these four QOL domains, the largest disparity was found in the area of mental health in which Latinas reported poorer QOL compared to non-Latina Whites and Blacks. Discussion/conclusions Most quantitative studies revealed either that Latinas consistently evidenced significantly lower QOL than non-Latinas on all measures (6 studies) or reported mixed findings in which Latinas generally demonstrated significantly worse QOL on most, but not all, measures (12 studies) included in the study. Explanatory mechanisms including socio-demographic, treatment-related, and culturally-relevant factors are discussed. Implications for research design, measurement, and clinical work are also included. Implications for cancer survivors Although not entirely consistent, data suggest that Latina breast cancer survivors on average experience worse QOL than non-Latina Whites. Understanding ethnic differences in QOL among breast cancer survivors can inform interventions targeted at improving health status for Latinas