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International audience; The Peruvian coast experiences the largest interannual variability of sea surface temperature in the world due to the combined influence of the coastal upwelling and El Niño Southern Oscillation (ENSO). Although biological impacts of El Niño events have been widely reported, their effects on rocky intertidal communities remains largely unknown in Peru. Herein, we analyze the results of two biological surveys of rocky intertidal communities, conducted along 1400 km of the Peruvian coast. The first survey was conducted in 2015 yielding a snapshot of the distribution of rocky intertidal communities after 17 years of stable La Niña-like conditions. The second survey was carried in October 2017, after the 2015-16 and the 2017 El Niño events, which produced warm sea surface temperature (SST) anomalies up to 6 °C on the Peruvian coast. We find no changes throughout the latitudinal transect in taxonomic richness but an important turnover of species, especially marked in the transition zone (~4–8°S) between the Panamic and the Humboldt provinces. Temperature-related southward migration of species was evidenced in a few sites but did not explain the large-scale change in communities observed from 2015 to 2017, primarily driven by large changes in the distribution of a few ecologically important species across the Panamic and Humboldt provinces. A primary environmental impact on some ecologically key species likely triggered a chain of secondary impacts through ecological relationships which lead to a complex change independent from SST gradients. Further studies are needed to better characterize and disentangle the seasonal and interannual variability of the rocky intertidal communities and their drivers. When this interannual variability is integrated, the nine study sites show a highly persistent community structure determined by the latitudinal SST gradient along the Peruvian coast.

[EN] This study aims to identify the various forms of integration of olive-oil-producing small farms (OSFs) into food systems in four Southern European regions, as well as to identify the most beneficial strategies of integration. Drawing on data from the SALSA Project, the study has found that besides self-provision, OSFs are engaged in multiple types of integration, including reciprocity relations as well as relations with informal and formal markets. Multiple strategies with synergistic effects co-exist at the farm/farm household level. However, specific territorial resources are partially mobilized by actors? strategies; consequently, olive oil identities are valorized on the market to some extent, but less so through positive externalities. Therefore, the unrealized potential of localization of food systems in which OSFs operate is identified., This study draws on material from the Project "SALSA" ("Small farms, small food businesses and sustainable food security"). This project has received funding from the European Union's Horizon 2020 research and innovation programme, under grant agreement No 677363

In July 2020, the Florida Department of Health was alerted to three Candida auris bloodstream infections and one urinary tract infection in four patients with coronavirus disease 2019 (COVID-19) who received care in the same dedicated COVID-19 unit of an acute care hospital (hospital A). C. auris is a multidrug-resistant yeast that can cause invasive infection. Its ability to colonize patients asymptomatically and persist on surfaces has contributed to previous C. auris outbreaks in health care settings (1-7). Since the first C. auris case was identified in Florida in 2017, aggressive measures have been implemented to limit spread, including contact tracing and screening upon detection of a new case. Before the COVID-19 pandemic, hospital A conducted admission screening for C. auris and admitted colonized patients to a separate dedicated ward.

UNSTRUCTURED Type 1 diabetes (T1D) is one of the most common chronic childhood diseases, and its prevalence is rapidly increasing. The management of glucose in T1D is challenging, as youth must consider a myriad of factors when making diabetes care decisions. This task often leads to significant hyperglycemia, hypoglycemia, and glucose variability throughout the day, which have been associated with short- and long-term medical complications. At present, most of what is known about each of these complications and the health behaviors that may lead to them have been uncovered in the clinical setting or in laboratory-based research. However, the tools often used in these settings are limited in their ability to capture the dynamic behaviors, feelings, and physiological changes associated with T1D that fluctuate from moment to moment throughout the day. A better understanding of T1D in daily life could potentially aid in the development of interventions to improve diabetes care and mitigate the negative medical consequences associated with it. Therefore, there is a need to measure repeated, real-time, and real-world features of this disease in youth. This approach is known as ecological momentary assessment (EMA), and it has considerable advantages to in-lab research. Thus, this viewpoint aims to describe EMA tools that have been used to collect data in the daily lives of youth with T1D and discuss studies that explored the nuances of T1D in daily life using these methods. This viewpoint focuses on the following EMA methods: continuous glucose monitoring, actigraphy, ambulatory blood pressure monitoring, personal digital assistants, smartphones, and phone-based systems. The viewpoint also discusses the benefits of using EMA methods to collect important data that might not otherwise be collected in the laboratory and the limitations of each tool, future directions of the field, and possible clinical implications for their use.

Background: Additional safe and effective vaccines are needed to control the COVID-19 pandemic. Methods: HERALD is an ongoing phase 2b/3 randomised, observer-blinded, placebo-controlled clinical trial in ten countries in Europe and Latin America. SARS-CoV-2 naive adults were randomised 1:1 to receive two doses of CVnCoV mRNA vaccine candidate or placebo 28 days apart. Primary efficacy analysis included symptomatic COVID-19 more than 14 days after second dose. Solicited adverse events (AEs) were assessed in phase 2b participants and unsolicited AEs in all participants. The study is registered at ClinicalTrials.gov (NCT04652102). Findings: Between 11 December 2020 and 12 April 2021, 39 680 participants were randomised and 39 529 received CVnCoV (19 783) or placebo (19 746). Overall VE was 48·2% (95% CI: 31·0–61·4; 83/12 851 vs. 145/12 221 in CVnCoV and placebo recipients, respectively). Overall VE against moderate-to-severe COVID-19 was 70·7% (95% CI: 42·5–86·1; 12/12 851 vs. 37/12 211, respectively). In participants aged 18–60 years VE was 52·5% (95% CI: 36·2–64·8; 71/11 532 vs. 136/11 031, respectively). Too few cases occurred in participants aged ≥61 years (CVnCoV: 12, placebo: 9) precluding VE evaluation. Wild type SARS-CoV-2 was detected in 7/204 (3%) sequenced cases, with 14 variants being responsible for the other cases. Solicited adverse events, mostly systemic, were more common in CVnCoV recipients; 542/2002 CVnCoV recipients and 61/1980 placebo recipients reported grade 3 events. Unsolicited serious AEs were reported for 82/19 746 CVnCoV recipients and 66/19 746 placebo recipients; 8 and 2 SAEs, respectively were considered related to vaccination. Fatal SAEs were reported for 8 and 6 CVnCoV and placebo recipients. Interpretation: CVnCoV is efficacious in the prevention of COVID-19 of any severity and has an acceptable safety profile. Trial Registration: Study number: ClinicalTrials.gov Identifier: NCT04652102. Funding: This trial was funded by the German Federal Ministry of Education and Research (grant 01KI20703), and CureVac AG. Declaration of Interest: MB declares institutional funding from CureVac during the conduct of this study, from Janssen Vaccines, molecular partners, and Merck outside of the submitted work, and consulting fees from Janssen Vaccines. EJLDB, and MFMR, TO and XSL declare institutional funding from CureVac during the conduct of this study. LE, and LG declare institutional funding from CureVac during the conduct of this study and outside of the submitted work. CFL declares institutional funding from CureVac during the conduct of this study, and outside of the submitted work, and is a member of WHO Covid-19 Vaccine Effectiveness Working Group and WHO Product Development for Vaccines Advisory Committee (PDVAC). CL declares institutional funding from CureVac during the conduct of this study, and is a member of the of German Society of Infection board. ILR declares institutional funding from CureVac during the conduct of this study and from J &J, and OSE Immunotherapeutics outside of the submitted work. PGK declares institutional funding from CureVac during the conduct of this study, and is a member of the scientific advisory board for the HERALD clinical trial. VVRH declares institutional funding from CureVac during the conduct of this study, and speakers fees from Gilead outside of the submitted work. HJ declares consultant fees from CureVac, is the Medical Responsible Person for the HERALD clinical trial, and is co-chair of DSMB for the HERALD clinical trial. AK and PM are employed by CureVac, and hold stock options. OSK declares consultant fees from CureVac during the conduct of this study, and is a member of the DSMB for a CVnCoV phase 1 trial. TV declares consultant fees from CureVac during the conduct of this study, and consultant fees from CureVac, AstraZeneca, Pfizer, Johnson&Johnson, and Moderna outside of the submitted work. LO is employed by CureVac, and holds stock options, and is the holder of a pending patent. The other authors declare no competing interests. Ethical Approval: The trial protocol and amendments have been approved by the appropriate independent ethics committee or institutional review board at each study centre

In colorectal cancer (CRC), the prevalence of NRAS mutations (5–9%) is inferior to that of KRAS mutations (40–50%). NRAS mutations feature lately during tumour progression and drive resistance to anti-EGFR therapy in KRAS wild-type tumours. To elucidate specific functions of NRAS mutations in CRC, we expressed doxycycline-inducible G12D and Q61K mutations in the CRC cell line Caco-2. A focused phospho-proteome analysis based on the Bio-Plex platform, which interrogated the activity of MAPK, PI3K, mTOR, STAT, p38, JNK and ATF2, did not reveal significant differences between Caco-2 cells expressing NRASG12D, NRASQ61K and KRASG12V. However, phenotypic read-outs were different. The NRAS Q61K mutation promoted anchorage-independent proliferation and tumorigenicity, similar to features driven by canonical KRAS mutations. In contrast, expression of NRASG12D resulted in reduced proliferation and apoptosis. At the transcriptome level, we saw upregulation of cytokines and chemokines. IL1A, IL11, CXCL8 (IL-8) and CCL20 exhibited enhanced secretion into the culture medium. In addition, RNA sequencing results indicated activation of the IL1-, JAK/STAT-, NFκB- and TNFα signalling pathways. These results form the basis for an NRASG12D-driven inflammatory phenotype in CRC.

A pedagogical agent is an anthropomorphic virtual character used in an online learning environment for educational purposes. Pedagogical Agents fulfill a variety of educational purposes, for which they can have a high degree of adaptability, be very versatile, enable highly realistic simulations, focus on socio-cultural requirements of students, as well as having the ability to foster commitment, motivation and responsibility as well as improve learning and performance of cognitive subjects. In this work, we review the literature on Pedagogical Agents in order to identify and analyze them, as well as to evaluate the impact of the implementation of these systems in the field of pedagogy, considering also the different elements that they incorporate, such as: text, voice, 2D and 3D images, and human figures. The factors that drive the demands of new characteristics, functionalities and socio-cultural environments for the development of contemporary pedagogical agents are analyzed.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Esta tese discute sobre o papel da interação entre tecnologias ancestrais e digitais em duas experiências concretas, a Casa de Cultura Tainã e a Rede Mocambos para, reconhecer as trajetórias em suas práticas descolonizadoras, organizativas, comunicativas e de memória. Procura-se compreender os discernimentos e as práticas construídas pela Tainã e pela Rede e, assim, ampliar a discussão sobre o papel das tecnologias em contextos subalternizados. Estes saberes, concepções e práticas de uso, apropriação e integração das tecnologias por parte de excluídos têm muito que contribuir para concepções teóricas e com iniciativas práticas que pretendam fazer outras organizações. Para compreender esse construto comunitário, a pesquisa se apoia na perspectiva anticolonial da ação participativa e das histórias de vida, métodos que estão ancorados em princípios ético-políticos e epistemológicos que permitem que as estratégias de aproximação sejam de encontro, alteridade e dialogicidade crítica para apreender da experiência das comunidades. Portanto, adota-se uma perspectiva descolonizadora das tecnologias que procura entender as tecnologias no seu sentido possibilitador de autonomia, liberdade, autodeterminação das comunidades, consciência crítica, patrimônio da humanidade e reconhecimento da condição Ch’ixi. This doctoral thesis discusses the interaction role of ancestral and digital technologies in two concrete experiences, the Casa de Cultura Tainã and Rede Mocambos to recognize the trajectories effects on decolonizing, organizational, communicative and memory practices. This doctoral thesis seeks to understand the discernment and practices weave by Tainã and Rede and thus expand the discussion on technologies role in subalternized contexts. This knowledge, conceptions, usage practices, appropriation and technologies integration by excluded people have a lot to contribute with the theoretical conceptions develop in the academy and with practical initiatives that aim to make other organizations. In order to understand this community construct this research is based on the anticolonial perspective of participatory action and life stories, that are methods anchored in ethical-political and epistemological principles that allow proximity strategies to be of proximity, alterity and dialogically critical to apprehend from communities’ experience. Therefore a perspective of decolonizing technologies that seeks to understand technologies in its sense of autonomy enables, freedom, communities self-determination, critical awareness, humanity heritage and recognition of the Ch’ixi condition.

Summary: Oncoproteins such as the BRAFV600E kinase endow cancer cells with malignant properties, but they also create unique vulnerabilities. Targeting of BRAFV600E-driven cytoplasmic signaling networks has proved ineffective, as patients regularly relapse with reactivation of the targeted pathways. We identify the nuclear protein SFPQ to be synthetically lethal with BRAFV600E in a loss-of-function shRNA screen. SFPQ depletion decreases proliferation and specifically induces S-phase arrest and apoptosis in BRAFV600E-driven colorectal and melanoma cells. Mechanistically, SFPQ loss in BRAF-mutant cancer cells triggers the Chk1-dependent replication checkpoint, results in decreased numbers and reduced activities of replication factories, and increases collision between replication and transcription. We find that BRAFV600E-mutant cancer cells and organoids are sensitive to combinations of Chk1 inhibitors and chemically induced replication stress, pointing toward future therapeutic approaches exploiting nuclear vulnerabilities induced by BRAFV600E.

The most aggressive types of ovarian cancer is high-grade serous ovarian cancer (HGSOC), and the 5-year survival is less than 20%. Relapsed HGSOC patients often have enrichment of cancer stem cells (CSCs) with enhanced pro-survival and self-renewal capacity, suggesting a potential vulnerable population for effective targeted therapies with less toxicity. APOBEC3 proteins are a family of primate-specific DNA deaminases that catalyze cytidine to uracil (C-to-U) on single-strand DNA thereby introducing C-to-T/G point mutations. This important DNA modification is abundant in a wide array of cancer types including HGSOCs. However, the prevalence and significance of A3-induced DNA deamination in HGSOC CSC is currently unknown. We recently discovered that CSCs maintain a low A3-induced mutation burden. Using patient-sample derived spheroid culture and HGSOC cell lines, we found A3B was the only A3 members differentially expressed between CSC and non-CSC and the expression was significantly reduced in CSCs. In addition, inhibition of A3B leads to elevated frequency of CSCs and enhanced expression of the stemness factors. Important, our data suggest that DNA deaminase activity of A3B leads to induction of DNA damage thereby sensitizing HGSOC CSCs to PARPi. These novel insights suggest that DNA deamination plays a fundamental role in CSC biology and also raises the possibility that A3B activation may sensitize HGSOC CSCs to PARPi by promoting DNA damages. Citation Format: Jane isquith, Jessica Pham, Robert Phavong, Maria Rivera, Kathleen Fisch, Catriona Jamieson, Michael McHale, Ramez Eskander, Qingfei Jiang. DNA deaminase APOBEC3B regulates theresponse to PARP inhibitors of epithelial ovarian cancer stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 890.

Expression of the epidermal growth factor ligands amphiregulin (AREG) and epiregulin (EREG) is positively correlated with a response to EGFR-targeted therapies in colorectal cancer. Gene-body methylation sites, which show a strong inverse correlation with AREG and EREG gene expression, were identified in cell lines using targeted 454 FLX-bisulfite sequencing and SIRPH analyses for AREG/EREG promoters and intragenic CpGs. Upon treatment of colorectal cancer cells with 5-aza-2'-desoxycytidine, methylation decreases at specific intragenic CpGs accompanied by upregulation of AREG and EREG gene expression. The same AREG gene-body methylation was also found in human colorectal cancer samples and is independent of KRAS and NRAS mutations. Methylation is specifically decreased in the tumor epithelial compartment as compared to stromal tissue and normal epithelium. Investigation of a promoter/enhancer function of the AREG exon 2 region revealed a potential promoter function in reverse orientation. Retrospective comparison of the predictive power of AREG gene-body methylation versus AREG gene expression using samples from colorectal cancer patients treated with anti-EGFR inhibitors with complete clinical follow-up revealed that AREG expression is superior to AREG gene methylation. AREG and EREG genes undergo a complex regulation involving both intragenic methylation and promoter-dependent control.

Phenotypic plasticity in hatching age has been documented in many animals. A growing body of research indicates that embryos can rapidly hatch to escape egg-stage risk. However, fewer studies have tested whether selective tradeoffs in post-hatching stages favor trait plasticity. We assessed hatching plasticity and its benefits to the larval stage in five species of Neotropical glassfrogs (Centrolenidae). Glassfrog embryos develop on terrestrial vegetation and larvae in benthic stream sediments; thus hatching involves a dramatic habitat shift, when hatchlings must dive past stream fish to reach larval refuges. We found that all five species have extensive plasticity in hatching age and can delay hatching to more than double their minimum embryonic period. Along a stream in Panama, we found evidence that early hatching is induced by the risk of embryo predation, dehydration, and fungal infections. Differences in hatching timing were coupled with changes in hatchling phenotypes, such that younger hatchlings were smaller and less developed than older individuals. To assess locomotor function we measured diving speed, a key performance trait for newly hatched larvae. Older hatchlings dove 1.4–3.8 times faster than younger ones, which would reduce their exposure to predators in the water column. To assess the potential for exotrophic growth, we measured digestive system morphology and feeding onset across hatching ages. Younger hatchlings had intact yolk sacs and spent 4.5–6 days as larvae before feeding, while older hatchlings entered the water with well-developed guts and fed immediately. Therefore, while early hatching enables embryos to escape egg-stage risk, it is associated with initial performance costs and a lag before feeding in the larval stage. We recovered consistent results across multiple genera of glassfrogs, supporting that hatching plasticity is widespread, ancient, and has been maintained by shared selective trade-offs in this family.

Oxygen and carbon isotopes from herbivore teeth have previously been used as paleoenvironmental proxies. However, their use in white-tailed deer (Odocoileus virginianus) remains rare. Here, we present the results of analysis of sequential sub-samples from second and third molars of wild and non-wild deer from Georgia, United States in order to assess their application in humid subtropical climates. In wild deer, enamel carbonate δ18O corresponds broadly to the recorded precipitation δ18O over the 10-month period of tooth formation, capturing the rainfall seasonality across the physiogeographic regions of the state. Non-wild deer show significantly lower values compared to both measured and modeled δ18O precipitation. While δ13C in tooth enamel carbonate appears to reflect diet, it does not reflect seasonality in either population. The δ13C and δ15N from bone collagen values suggest that diet and source of drinking water influence the potential of white tailed deer tooth enamel carbonate to record the δ18O seasonality in the study area; therefore, special attention on the provenance of deer are necessary for obtaining accurate paleoclimate reconstruction.

Over the past 30 years, the number of US doctoral anthropology graduates has increased by about 70%, but there has not been a corresponding increase in the availability of new faculty positions. Consequently, doctoral degree-holding archaeologists face more competition than ever before when applying for faculty positions. Here we examine where US and Canadian anthropological archaeology faculty originate and where they ultimately end up teaching. Using data derived from the 2014–2015 AnthroGuide, we rank doctoral programs whose graduates in archaeology have been most successful in the academic job market; identify long-term and ongoing trends in doctoral programs; and discuss gender division in academic archaeology in the US and Canada. We conclude that success in obtaining a faculty position upon graduation is predicated in large part on where one attends graduate school.

CDC has updated the interim guidance for U.S. health care providers caring for pregnant women with possible Zika virus exposure in response to 1) declining prevalence of Zika virus disease in the World Health Organization's Region of the Americas (Americas) and 2) emerging evidence indicating prolonged detection of Zika virus immunoglobulin M (IgM) antibodies. Zika virus cases were first reported in the Americas during 2015-2016; however, the incidence of Zika virus disease has since declined. As the prevalence of Zika virus disease declines, the likelihood of false-positive test results increases. In addition, emerging epidemiologic and laboratory data indicate that, as is the case with other flaviviruses, Zika virus IgM antibodies can persist beyond 12 weeks after infection. Therefore, IgM test results cannot always reliably distinguish between an infection that occurred during the current pregnancy and one that occurred before the current pregnancy, particularly for women with possible Zika virus exposure before the current pregnancy. These limitations should be considered when counseling pregnant women about the risks and benefits of testing for Zika virus infection during pregnancy. This updated guidance emphasizes a shared decision-making model for testing and screening pregnant women, one in which patients and providers work together to make decisions about testing and care plans based on patient preferences and values, clinical judgment, and a balanced assessment of risks and expected outcomes.

The impact of electronic health record (EHR) immunization clinical alert systems on the delivery of other preventive services remains unknown. We assessed for spillover effects of an EHR immunization alert on delivery of 6 other preventive services, in children 18 to 30 months of age needing immunizations. We conducted a secondary data analysis, with additional primary data collection, of a randomized, historically controlled trial to improve immunization rates with EHR alerts, in an urban, primary care clinic. No significant differences were found in screening for anemia, lead, development, nutrition, and injury prevention counseling in children prompting EHR immunization alerts (n = 129), compared with controls (n = 135). Significant increases in oral health screening in patients prompting EHR alerts (odds ratio = 4.8, 95% CI = 1.8-13.0) were likely due to practice changes over time. An EHR clinical alert system targeting immunizations did not have a spillover effect on the delivery of other preventive services.

To evaluate fetal ultrasound and magnetic resonance imaging findings among a series of pregnant women with confirmed Zika virus infection to evaluate the signs of congenital Zika syndrome with respect to timing of infection.We conducted a retrospective case series of pregnant women referred to two perinatal clinics in Barranquilla and Ibagué, Colombia, who had findings consistent with congenital Zika syndrome and Zika virus infection confirmed in maternal, fetal, or neonatal samples. Serial ultrasound measurements, fetal magnetic resonance imaging results, laboratory results, and perinatal outcomes were evaluated.We describe 17 cases of confirmed prenatal maternal Zika virus infection with adverse fetal outcomes. Among the 14 symptomatic women, the median gestational age for maternal Zika virus symptoms was 10 weeks (range 7-14 weeks of gestation). The median time between Zika virus symptom onset and microcephaly (head circumference less than 3 standard deviations below the mean) was 18 weeks (range 15-24 weeks). The earliest fetal head circumference measurement consistent with microcephaly diagnosis was at 24 weeks of gestation. The earliest sign of congenital Zika syndrome was talipes equinovarus, which in two patients was noted first at 19 weeks of gestation. Common findings on fetal magnetic resonance imaging were microcephaly, ventriculomegaly, polymicrogyria, and calcifications.Our analysis suggests a period of at least 15 weeks between maternal Zika virus infection in pregnancy and development of microcephaly and highlights the importance of serial and detailed neuroimaging.

The selection and pre-treatment of a reliable organic fraction from which to acquire radiocarbon dates is fundamental to obtain accurate chronologies. Sampling from tropical lakes is particularly challenging given the adverse preservation conditions and diagenesis in these environments. Our research is the first to examine and quantify the differences between the radiocarbon date results from different carbon fractions and pretreatments from the same depths from a tropical lake sediment core (1.72 m long) located in north Australia to assess which one(s) are more reliable. Six different organic fractions (bulk organics, pollen concentrate, cellulose, stable polycyclic aromatic carbon (SPAC), charcoal >250 um and charcoal >63 um), for a total of 27 radiocarbon dates, were compared in six different depths along the core. Acid-base-acid (ABA), modified ABA (30 % hydrogen peroxide + ABA), 2chlorOx (a novel cellulose pre-treatment method) and hydrogen pyrolysis (hypy) were used to pre-treat the correspondent organic fractions. The oldest date is 31,295 calibrated years before present (cal yr BP) and the youngest is 2,048 cal yr BP, spanning 29,247 years. The smallest offset between the minimum and the maximum age in a given depth was found to be 975 years (between SPAC and charcoal >63 um) and the largest 16,527 years (between pollen concentrate and SPAC). The SPAC fractions pre-treated with hypy consistently yielded older ages compared to all other fraction in most cases, while bulk organics yielded consistently younger ones. The magnitude and consistency of the offsets and the physical and chemical properties of the tested organic fractions suggest that SPAC is the most reliable fraction to date in tropical lake sediments and that hypy successfully removes contamination sourced from exogenous carbon.

ITS (Intelligent Tutoring Systems) are integrated and complex systems, designed and developed using approaches and methods of artificial intelligence (AI), for the resolution of problems and requirements of the teaching/learning activities in the field of education and training of students and the workforce based in computers an web based emerging resources. These sys-tems can establish the level of student knowledge and the learning strategies used to improve the level of knowledge to support the detection and correction of student misconceptions. Their purpose is to contribute to the process of teaching and learning in a given area of knowledge, respecting the individuality of the student. In this paper, a review of intelligent tutorial systems (ITS) is presented, from the perspective of their application and usability in modern learning concepts. The methodology used was that of bibliographical review of classic works of the printed and digital literature in relation to ITS and e-Learning systems, as well as searches in diverse databases, of theses and works in universities and digital repositories. The main weakness of the research lies in the fact that the search was limited to documents published in the English, Spanish and Portuguese.

"The objective of the current study was to relate body mass index (BMI) and body condition score (BCS) in Pelibuey ewes in order to predict BMI based on a well-known method for estimating BCS. Body weight (BW), withers height (WH), body length (BL) and BCS were measured in 402 ewes. The relationships were investigated by regression models. The BMI and BCS had a strong relationship (r = 0.80, p < 0.001). The linear regression for predicting BMI from BCS was as follows: BMI (kg m-2) = 8.38 (± 0.189***) + 1.70 (± 0.064***) xBCS(R2 = 0.65, MSE: 2.56, RMSE: 1.60, p < 0.0001 and n = 402). In conclusion, BMI can be used as an indicator of the degree of obesity and body fat reserves in non-pregnant and non-lactating Pelibuey ewes under field conditions."

The importance of small farms is well established and recognized in developing countries, but far less is known about their role in Europe, where agriculture is largely industrialized. In this paper we use a comparative analysis of evidence from 15 European countries to assess the contribution of small farms to regional food production and availability, across geographies and products. We collected information about regional (NUTS-3) level production, trade and consumption of 91 products across 25 European regions using official statistics, expert interviews, and farm-level surveys. This information was used to develop product-specific systems maps which were coded and systematised. We then used a Random Forest algorithm to establish which system variables were more likely to explain variation along two dimensions: the contribution of small farms to regional production (i.e. proportion of regional production coming from small farms) and their contribution to regional food availability (i.e. proportion of their production that is consumed within the region). Our results suggest that the contribution of small farms to regional production is closely related to the relative abundance of small farms in the agricultural landscape, while their contribution to regional food availability is driven by structure of specific supply chains and the market linkages available to small farms, and in particular the degree of selfprovisioning and direct sales to consumers. These findings shed light on the relatively unknown word of European small farms, showing their importance in food production and availability, and providing new evidence to inform more effective policy for these often-neglected actors of the food system.

Background The Zika Contraception Access Network (Z-CAN) was designed to provide women in Puerto Rico who chose to delay or avoid pregnancy during the 2016–2017 Zika virus outbreak access to high-quality client-centered contraceptive counseling and the full range of reversible contractive methods on the same day and at no cost through a network of trained providers. We evaluated the implementation of Z-CAN from the patient perspective. Methods An online survey, administered to a subset of women served by the Z-CAN program approximately 2 weeks after their initial Z-CAN visit, assessed patient satisfaction and receipt of services consistent with select program strategies: receipt of high-quality client-centered contraceptive counseling, same-day access to the contraceptive method they were most interested in after counseling, and no-cost contraception. Results Of 3,503 respondents, 85.2% reported receiving high-quality client-centered contraceptive counseling. Among women interested in a contraceptive method after counseling (n = 3,470), most reported same-day access to that method (86.8%) and most reported receiving some method of contraception at no cost (87.4%). Women who reported receiving services according to Z-CAN program strategies were more likely than those who did not to be very satisfied with services. Women who received high-quality client-centered contraceptive counseling and same-day access to the method they were most interested in after counseling were also more likely to be very satisfied with the contraceptive method received. Conclusions A contraception access program can be rapidly implemented with high fidelity to program strategies in a fast-moving and complex public health emergency setting.

Background Childhood diarrhoea mortality has declined substantially in Peru in recent decades. We documented trends in childhood diarrhoea mortality from 1980 to 2015, along with trends in coverage of diarrhoea-related interventions and risk factors, to identify the main drivers of mortality reduction. Methods We conducted desk reviews on social determinants, policies and programmes, and diarrhoea-related interventions implemented during the study period. We reviewed different datasets on child mortality, and on coverage of diarrhoea-related interventions. We received input from individuals familiar with implementation of diarrhoea-related policies and programmes. We used the Lives Saved Tool (LiST) to help explain the reasons for the decline in diarrhoea mortality from 1980 to 2015 and to predict additional reduction with further scale up of diarrhoea-related interventions by 2030. Results In Peru under-five diarrhoea mortality declined from 23.3 in 1980 to 0.8 per 1000 livebirths in 2015. The percentage of under-five diarrhoea deaths as related to total under-five deaths was reduced from 17.8% in 1980 to 4.9% in 2015. Gross domestic product increased and poverty declined from 1990 to 2015. Access to improved water increased from 56% in 1986 to 79.3% in 2015. Oral rehydrating salts (ORS) use during an episode of diarrhoea increased from 3.6% in 1986 to 32% in 2015. Vertical programmes focused on diarrhoea management with ORS were implemented successfully in the 1980s and 1990s, and were replaced by integrated crosscutting interventions since the early 2000s. LiST analyses showed that about half (53.9%) of the reduction in diarrhoea mortality could be attributed to improved water, sanitation and hygiene, 25.0% to direct diarrhoea interventions and 21.1% to nutrition. The remaining mortality could be reduced by three-quarters by 2030 with improved diarrhoea treatment and further with enhanced breastfeeding practices and reduction in stunting. LiST does not take into account the role of social determinants. Conclusions The reduction of diarrhoeal under-five mortality in Peru can be explained by a combination of factors, including improvement of social determinants, child nutrition, diarrhoea treatment with ORS and prevention with rotavirus vaccine and increased access to water and sanitation. The already low rate of diarrhoea mortality could be further reduced by a number of interventions, especially additional use of ORS and zinc for diarrhoea treatment. Peru is a remarkable example of a country that was able to reduce childhood diarrhoea mortality by implementing interventions through vertical programmes initially, and afterwards through implementation of integrated multisectoral packages targeting prevalent illnesses and multi-causal problems like stunting.

This study is an attempt to assess the impact of small farms (SF) on the regional food product circulation of specific key products in selected, fragmented, agrarian regions in Poland and Portugal. The empirical study is based on the analysis of food product maps which were developed based on data from a survey conducted among owners of small farms and small food businesses at focus group meetings and workshops organized in 2017 and 2018 in the Nowotarski and Nowosądecki subregions in Poland and in the Alentejo Central and Oeste subregions in Portugal. Qualitative data analysis was conducted using uniform methodology. In each of the subregions, focus groups helped to confront the assumptions resulting from surveys and corroborate the flows and fluxes described in the developed food product maps. Data collected during focus groups were enriched by data gathered during regional workshops that focused on food system governance. It was concluded that food product maps indicate interesting relationship flows of small farmers’ products along the food system, highlighting the role of fluxes connecting small farmers with other actors regarding specific key products. Several similarities and disparities between regional KP production flows in the Portuguese and Polish subregions, based on the type of key product, the various distribution channels and farming capacities present in each subregion were observed.

Carbon and oxygen isotopes ratios from herbivore teeth have previously been used as paleo-environmental proxies in temperate zones. However, their utility in tropical zones remains uncertain. In this study, sequential sub-samples from white-tailed deer (

Zinc porphyrin-functionalized fullerene [C60] derivatives have been synthesized and usedto prepare titania-based composites. The electrochemical properties and HOMO andLUMO levels of the photosensitizers were determined by electrochemical measurements.Raman and IR techniques were used to study chemical groups present on the titaniasurface. Absorption properties of the composites were measured in the solid state bydiffuse reflectance UV-Vis spectra (DRS).

Recent findings on the contribution of smallholders to global food production and security challenge the values used in several reports of international organizations. The skewed distribution of the number of farms and the agricultural area by farm size may explain overestimations in small farms' food production. In fact, the highest values found in literature seem to be more strongly correlated to the total number of small farms than to the actual area they cover, suggesting errors in the estimation procedures. Additionally, a significant part of the small farms is not considered in official statistics, thus limiting the use of the data and also leading to underestimations. New efforts are thus needed to develop and apply methodologies to reduce the error and uncertainty of these estimates. In this paper we demonstrate the progress obtained by using a novel approach to provide new and more accurate estimates on the availability of food produced in small farms in 17 European regions (NUTS-3 level) distributed in 8 countries. Our assessment was carried out using two data sets: [1] data on crop area and production for a priori selected key products in each reference region, collected through questionnaires to small producers; [2] remote sensing-based products derived from Sentinel-1 and Sentinel-2 images, including crop type maps with ground-truth validation and small-scale farming systems probability maps. To reduce error propagation resulting from self-reported yield estimates, we used robust measures of central tendency based on Tukey's bi-weight function to compute the overall production in small farms in each region, minimizing the effect of outliers. The self-reported yields by small farmers were also compared with national and regional values of productivity per unit area and discussed in light of previous findings. Our results highlight not only the importance of small farms in the European context, but also their diversity in productivity levels. In addition to the novel methodological steps that underlie our study, which involve the combination of remote sensing data with data resulting from field surveys, the approach undertaken allows to better understand the contribution of small farmers to food security in each regional context, and the potential they have to support short food supply chains. Our findings can be key in supporting policy options that aim to enhance food security by reducing the EU footprint through strengthening and diversifying regional food systems.

Small farms are a key part of the system of food flows that happen outside of marketing channels, and which is a crucial source of food for to the most vulnerable part of the world population living in the rural or connected to the rural through family and other social links. Food Self-Provisioning (FSP) is the largest share of these informal flows. For Europe and European small farms today, the role of FSP is relatively un-known. In this paper we address the relative weight and relevance of extra-market arrangements in small farms in Europe, thus contributing to the understanding of the multi-dimensional role of small farms in the regional food system they are part of, and also in the wellbeing of their own household. The analysis is based on 739 face-to-face interviews to small farms, in 24 regions of Europe across a North-South and East-West gradient. We show evidence that FSP is important in all types of small farms, and even if all small farms are in some way linked to the market, they continue producing food which circulates outside the market and may be quite relevant for the farm household, as well as for strengthening social ties in the rural communities and rural-urban interactions.

Type 1 diabetes (T1D) is one of the most common chronic childhood diseases, and its prevalence is rapidly increasing. The management of glucose in T1D is challenging, as youth must consider a myriad of factors when making diabetes care decisions. This task often leads to significant hyperglycemia, hypoglycemia, and glucose variability throughout the day, which have been associated with short- and long-term medical complications. At present, most of what is known about each of these complications and the health behaviors that may lead to them have been uncovered in the clinical setting or in laboratory-based research. However, the tools often used in these settings are limited in their ability to capture the dynamic behaviors, feelings, and physiological changes associated with T1D that fluctuate from moment to moment throughout the day. A better understanding of T1D in daily life could potentially aid in the development of interventions to improve diabetes care and mitigate the negative medical consequences associated with it. Therefore, there is a need to measure repeated, real-time, and real-world features of this disease in youth. This approach is known as ecological momentary assessment (EMA), and it has considerable advantages to in-lab research. Thus, this viewpoint aims to describe EMA tools that have been used to collect data in the daily lives of youth with T1D and discuss studies that explored the nuances of T1D in daily life using these methods. This viewpoint focuses on the following EMA methods: continuous glucose monitoring, actigraphy, ambulatory blood pressure monitoring, personal digital assistants, smartphones, and phone-based systems. The viewpoint also discusses the benefits of using EMA methods to collect important data that might not otherwise be collected in the laboratory and the limitations of each tool, future directions of the field, and possible clinical implications for their use.

Zika virus infection during pregnancy can cause congenital microcephaly and brain abnormalities (1,2). Since 2015, Zika virus has been spreading through much of the World Health Organization's Region of the Americas, including U.S. territories. Zika virus is spread through the bite of Aedes aegypti or Aedes albopictus mosquitoes, by sex with an infected partner, or from a pregnant woman to her fetus during pregnancy.* CDC estimates that 41 states are in the potential range of Aedes aegypti or Aedes albopictus mosquitoes (3), and on July 29, 2016, the Florida Department of Health identified an area in one neighborhood of Miami where Zika virus infections in multiple persons are being spread by bites of local mosquitoes. These are the first known cases of local mosquito-borne Zika virus transmission in the continental United States.(†) CDC prevention efforts include mosquito surveillance and control, targeted education about Zika virus and condom use to prevent sexual transmission, and guidance for providers on contraceptive counseling to reduce unintended pregnancy. To estimate the prevalence of contraceptive use among nonpregnant and postpartum women at risk for unintended pregnancy and sexually active female high school students living in the 41 states where mosquito-borne transmission might be possible, CDC used 2011-2013 and 2015 survey data from four state-based surveillance systems: the Behavioral Risk Factor Surveillance System (BRFSS, 2011-2013), which surveys adult women; the Pregnancy Risk Assessment Monitoring System (PRAMS, 2013) and the Maternal and Infant Health Assessment (MIHA, 2013), which surveys women with a recent live birth; and the Youth Risk Behavior Survey (YRBS, 2015), which surveys students in grades 9-12. CDC defines an unintended pregnancy as one that is either unwanted (i.e., the pregnancy occurred when no children, or no more children, were desired) or mistimed (i.e., the pregnancy occurred earlier than desired). The proportion of women at risk for unintended pregnancy who used a highly effective reversible method, known as long-acting reversible contraception (LARC), ranged from 5.5% to 18.9% for BRFSS-surveyed women and 6.9% to 30.5% for PRAMS/MIHA-surveyed women. The proportion of women not using any contraception ranged from 12.3% to 34.3% (BRFSS) and from 3.5% to 15.3% (PRAMS/MIHA). YRBS data indicated that among sexually active female high school students, use of LARC at last intercourse ranged from 1.7% to 8.4%, and use of no contraception ranged from 7.3% to 22.8%. In the context of Zika preparedness, the full range of contraceptive methods approved by the Food and Drug Administration (FDA), including LARC, should be readily available and accessible for women who want to avoid or delay pregnancy. Given low rates of LARC use, states can implement strategies to remove barriers to the access and availability of LARC including high device costs, limited provider reimbursement, lack of training for providers serving women and adolescents on insertion and removal of LARC, provider lack of knowledge and misperceptions about LARC, limited availability of youth-friendly services that address adolescent confidentiality concerns, inadequate client-centered counseling, and low consumer awareness of the range of contraceptive methods available.

Purpose The purpose of this study is to compare the health of primary caregiving African American grandmothers with diabetes with African American women with diabetes who were not primary caregivers. Design Using a comparative, descriptive, cross-sectional design, 34 African American primary caregiving grandmothers were compared with 34 non-caregiving women with diabetes mellitus; women aged 55–75 years were recruited for this study throughout the central Arkansas. Methods To measure the overall health, data on blood pressure, body mass index measurements, HbA1c levels, total cholesterol, and urine protein and creatinine levels were collected from all the participants. Results Statistically significant differences between the caregivers and non-caregivers groups in systolic pressure ( t = −3.42, P = 0.001) and diastolic pressure ( t = −3.790, P = 0.000) and urine protein ( W = 294.00, P = 0.000) were noted. Additionally, a clinically significant difference in HbA1c was noted between groups. Conclusion Differences in systolic and diastolic pressures, urine protein, and clinically significant differences in HbA1c suggest that African American primary caregiving grandmothers with diabetes mellitus may have more difficulty in maintaining their diabetic health than non-caregiving African American women.

CDC has updated its interim guidance for U.S. health care providers caring for women of reproductive age with possible Zika virus exposure to include recommendations on counseling women and men with possible Zika virus exposure who are interested in conceiving. This guidance is based on limited available data on persistence of Zika virus RNA in blood and semen. Women who have Zika virus disease should wait at least 8 weeks after symptom onset to attempt conception, and men with Zika virus disease should wait at least 6 months after symptom onset to attempt conception. Women and men with possible exposure to Zika virus but without clinical illness consistent with Zika virus disease should wait at least 8 weeks after exposure to attempt conception. Possible exposure to Zika virus is defined as travel to or residence in an area of active Zika virus transmission ( http://www.cdc.gov/zika/geo/active-countries.html), or sex (vaginal intercourse, anal intercourse, or fellatio) without a condom with a man who traveled to or resided in an area of active transmission. Women and men who reside in areas of active Zika virus transmission should talk with their health care provider about attempting conception. This guidance also provides updated recommendations on testing of pregnant women with possible Zika virus exposure. These recommendations will be updated when additional data become available.

Consistent with global trends of infections due to multiple-drug resistant Gram-negative bacteria, we report the first official case of native mitral valve endocarditis due to multi-resistant Klebsiella Pneumonia Carbapenemase (KPC) producing Serratia marcescens. The patient underwent mitral valve replacement and was successfully treated with monotherapy ceftazidime-avibactam.

[EN] We propose a new typology of small farms in Europe using a multivariate analysis drawing from household surveys from 14 European countries. The variables to develop the types covered a range of characteristics from farmers' histories and motivations, to farm production, assets and labour, market linkages and access to support. The clustering analysis found five types of small farms, two with relatively weak commercial orientation (peasant and part-time farms) and three with relatively strong commercial orientation (diversified businesses, specialized businesses, and new enterprises). This typology provides a richer picture of the diversity and nature of small farming across Europe beyond assumptions about their role in subsistence and fragile household economies. We find evidence of entrepreneurship and strong market linkages as well as a range of motivations, including lifestyle options. Typologies such as the one presented here can help to better document and understand the role of small-scale farming in Europe, and provide an input for evidence-based policy making that can enhance their livelihoods and contribution., This work was carried out under the SALSA (Small farms, small food businesses and sustainable food and nutrition security) project, funded by the European Union - Horizon 2020 programme (Project ID: 677,363). We would like to thank Talis Tisenkopfs and two annonymous reviewers for comments on an earlier version of this article.

Recent discoveries indicate a genetic basis for high-altitude adaptation among human groups who have resided at high altitude for millennia, including Andeans, Tibetans, and Ethiopians. Yet, genetics alone does not explain the extent of variation in altitude-adaptive phenotypes. Current and past environments may also play a role, and one way to determine the effect of the environment is through the epigenome. To characterize if Andean adaptive responses to high altitude have an epigenetic component, we analyzed DNA methylation of the promoter region of EPAS1 and LINE-1 repetitive element among 572 Quechua individuals from high- (4,388 m) and low-altitude (0 m) in Peru. Participants recruited at high altitude had lower EPAS1 DNA methylation and higher LINE-1 methylation. Altitude of birth was associated with higher LINE-1 methylation, not with EPAS1 methylation. The number of years lived at high altitude was negatively associated with EPAS1 methylation and positively associated with LINE-1 methylation. We found four one-carbon metabolism SNPs (MTHFD1 rs2236225, TYMS rs502396, FOLH1 rs202676, GLDC rs10975681) that cumulatively explained 11.29% of the variation in average LINE-1 methylation. And identified an association between LINE-1 methylation and genome-wide SNP principal component 1 that distinguishes European from Indigenous American ancestry suggesting that European admixture decreases LINE-1 methylation. Our results indicate that both current and lifetime exposure to high-altitude hypoxia have an effect on EPAS1 and LINE-1 methylation among Andean Quechua, suggesting that epigenetic modifications may play a role in high-altitude adaptation.

Context The purpose of this paper is to synthesize and evaluate the evidence on the effectiveness of repeat teen pregnancy prevention programs offered in clinical settings. Evidence acquisition Multiple databases were searched for peer-reviewed articles published from January 1985 to April 2016 that included key terms related to adolescent reproductive health services. Analysis of these studies occurred in 2017. Studies were excluded if they focused solely on sexually transmitted disease/HIV prevention services, or occurred outside of a clinic setting or the U.S., Canada, Europe, Australia, or New Zealand. Inclusion and exclusion criteria further narrowed the studies to those that included information on at least one short-term (e.g., increased knowledge); medium-term (e.g., increased contraceptive use); or long-term (e.g., decreased repeat teen pregnancy) outcome, or identified contextual barriers or facilitators for providing adolescent-focused family planning services. Standardized abstraction methods and tools were used to synthesize the evidence and assess its quality. Only studies of clinic-based programs focused on repeat teen pregnancy prevention were included in this review. Evidence synthesis The search strategy identified 27,104 citations, 940 underwent full-text review, and 120 met the adolescent-focused family planning services inclusion criteria. Only five papers described clinic-based programs focused on repeat teen pregnancy prevention. Four studies found positive (n=2) or null (n=2) effects on repeat teen pregnancy prevention; an additional study described facilitators for helping teen mothers remain linked to services. Conclusions This review identified clinic-based repeat teen pregnancy prevention programs and few positively affect factors that may reduce repeat teen pregnancy. Access to immediate postpartum contraception or home visiting programs may be opportunities to meet adolescents where they are and reduce repeat teen pregnancy. Theme information This article is part of a theme issue entitled Updating the Systematic Reviews Used to Develop the U.S. Recommendations for Providing Quality Family Planning Services, which is sponsored by the Office of Population Affairs, U.S. Department of Health and Human Services.

Objectives. We estimated the number of women of reproductive age in need who would gain coverage for contraceptive services after implementation of the Affordable Care Act, the extent to which there would remain a need for publicly funded programs that provide contraceptive services, and how that need would vary on the basis of state Medicaid expansion decisions. Methods. We used nationally representative American Community Survey data (2009), to estimate the insurance status for women in Massachusetts and derived the numbers of adult women at or below 250% of the federal poverty level and adolescents in need of confidential services. We extrapolated findings to simulate the impact of the Affordable Care Act nationally and by state, adjusting for current Medicaid expansion and state Medicaid Family Planning Expansion Programs. Results. The number of low-income women at risk for unintended pregnancy is expected to decrease from 5.2 million in 2009 to 2.5 million in 2016, based on states’ current Medicaid expansion plans. Conclusions. The Affordable Care Act increases women’s insurance coverage and improves access to contraceptive services. However, for women who remain uninsured, publicly funded family planning programs may still be needed.

The developing human fetus is able to cope with the physiological reduction in oxygen supply occurring in utero. However, it is not known if microvascularization of the fetus is augmented when pregnancy occurs at high altitude. Fifty-three healthy term newborns in Puno, Peru (3,840 m) were compared with sea-level controls. Pre- and postductal arterial oxygen saturation (SpO2) was determined. Cerebral and calf muscle regional tissue oxygenation was measured using near infrared spectroscopy (NIRS). Skin microcirculation was noninvasively measured using incident dark field imaging. Pre- and postductal SpO2 in Peruvian babies was 88.1 and 88.4%, respectively, which was 10.4 and 9.7% lower than in newborns at sea level ( P < 0.001). Cerebral and regional oxygen saturation was significantly lower in the Peruvian newborns (cerebral: 71.0 vs. 74.9%; regional: 68.5 vs. 76.0%, P < 0.001). Transcutaneously measured total vessel density in the Peruvian newborns was 14% higher than that in the newborns born at sea level (29.7 vs. 26.0 mm/mm2; P ≤ 0.001). This study demonstrates that microvascular vessel density in neonates born to mothers living at high altitude is higher than that in neonates born at sea level.

Context When caring for an adolescent client, providers of contraceptive services must consider whether and how to encourage parent/guardian–child communication about the adolescent’s reproductive health. The objective of this systematic review was to summarize the evidence on the effectiveness of programs designed to increase parent–child communication about reproductive health. The review was used to inform national recommendations on quality family planning services. Data analysis occurred from mid-2011 through 2012. Evidence acquisition Several electronic bibliographic databases were used to identify relevant articles, including PubMed, CINAHL, PsycINFO, and Popline, published from January 1985 through February 2011. Evidence synthesis Sixteen articles met the inclusion criteria: all studies examined the impact on at least one medium- or short-term outcome, and two studies assessed the impact on teen pregnancy. One study examined the impact of a program conducted in a clinic setting; the remainder examined the impact of programs in community settings. All studies showed a positive impact on at least one short-term outcome, and 12 of 16 studies showed an increase in parent–child communication about reproductive health. Four of seven studies found an impact on sexual risk behavior. Conclusions Most programs increased parent–child communication, and several resulted in reduced sexual risk behavior of adolescents. This suggests that delivering a clinic-based program that effectively helps parents/guardians talk to their adolescent child(ren) about reproductive health, or referring parents/guardians to an evidence-based program in the community, may be beneficial. However, further rigorous research on delivery of these programs in clinical settings is needed.

The classic dynamic clamp technique uses a real-time electrical interface between living cells and neural simulations in order to investigate hypotheses about neural function and structure. One of the acknowledged drawbacks of that technique is the limited control of the cells' chemical microenvironment. In this manuscript, we use a novel combination of nanosensor and microfluidic technology and microfluidic and neural simulations to add sensing and control of chemical concentrations to the dynamic clamp technique. Specifically, we use a microfluidic lab-on-a-chip to generate distinct chemical concentration gradients (ions or neuromodulators), to register the concentrations with embedded nanosensors and use the processed signals as an input to simulations of a neural cell. The ultimate goal of this project is to close the loop and provide sensor signals to the microfluidic lab-on-a-chip to mimic the interaction of the simulated cell with other cells in its chemical environment.