While some research training programs have considered the importance of mentoring in inspiring professionals to engage in translational research, most evaluations emphasize outcomes specific to academic productivity as primary measures of training program success. The impact of such training or mentoring programs on stakeholders and local community organizations engaged in translational research efforts has received little attention. The purpose of this evaluation is to explore outcomes other than traditional academic productivity in a translational research graduate certificate program designed to pair graduate students and behavioral health professionals in collaborative service-learning projects.Semi-structured qualitative interviews with scholars, community mentors, and academic mentors were conducted regarding a translational research program to identify programmatic impacts. Interviews were transcribed and coded by the research team to identify salient themes related to programmatic outcomes.Results are framed using the Translational Research Impact Scale which is organized into three overarching domains of potential impact: (1) research-related impacts, (2) translational impacts, and (3) societal impacts. This evaluation demonstrates the program’s impact in all three domains of the TRIS evaluation framework. Graduate certificate participants (scholars) reported that gaining experience in applied behavioral health settings added useful skills and expertise to their present careers and increased their interest in pursuing translational research. Scholars also described benefits resulting from networks gained through participation in the program, including valuable ties between the university and community behavioral health organizations.This evaluation of the outcomes of a graduate certificate program providing training in translational research highlights the need for more community-oriented and practice-based measures of success. Encouraging practitioner involvement in translational research is vital to translate knowledge into practice and to enable practice-based needs to inform research and policy. A more flexible approach to measuring programmatic success in research training programs can help bridge the knowledge translation gap. Translational research aims to improve individual and population health outcomes by bringing evidence-based knowledge into clinical and public health practice , 2. HealTraining in translational research has thus far demonstrated positive results. Targeting graduate students for mentoring has been shown to influence graduate students’ career development trajectories. Long-term mentoring also encourages support of mentees to continue to evolve their academic research careers . Many evIn this paper, the authors present an evaluation of a National Institute on Drug Abuse (NIDA)-funded translational research training program, the Institute for Translational Research Education in Adolescent Drug Abuse (“the Institute”), aimed at engaging graduate-level scholars and behavioral health practitioners in substance abuse translational research. The Institute engages new researchers in combining substance abuse research with evidence-based approaches to implementation. Such a training program has potentially substantial public health impacts given the sizable gap between the demand for implementation of high-quality evidence-based programs and the number of researchers focusing in this area , 16.Glasgow et al.  called fOne of the most challenging aspects of implementing evidence into practice is that implementation stakeholders  rarely have the skills to interpret and implement new research into practice . In thisGraduate Certificate in Translational Research in Adolescent Behavioral Health Program. Implementation is not only relevant for academically based researchers but also has a pragmatic relevance for those who practice in the field. The intention of including both master’s and doctoral students in the Institute is to expose a broader range of professionals to the implications for translational research and implementation science in working agencies.The central aim of the Institute is to develop innovative, applied research skills among behavioral health researchers and practitioners through a collaborative service-learning-focused approach. Institute scholars complete service-learning translational research and implementation science studies in collaboration with academic and community mentors and community behavioral health organization partners as part of the Service-learning studies are defined as research carried out as a service to the program. Scholars were expected to approach their projects based on what community mentors describe as the greatest need in their organization. The graduate certificate provided additional training for scholars, in most cases, outside of the requirements for their degree program. The program was designed as a graduate certificate to be available to enrolled graduate students and also available to community members seeking additional certification and/or knowledge for their current job. Additionally, making the program an official graduate certificate of the university created a sustainable program beyond grant funding.Interested applicants applied to the Institute by submitting a personal statement, resume, two letters of recommendation, and official transcripts. Members of the Executive Committee then reviewed the applicants collectively and made final decisions regarding admission to the program. The Institute Executive Committee included the multiple principal investigators for the Institute and the project director who were responsible for the Institute’s design, implementation, and evaluation.Two groups of mentors (academic and community) contributed to the delivery of the curriculum. The academic mentors provided support in research design and analysis, while the community mentors provided hands-on experience and real-world interpretations. Community agencies interested in participating in the Institute met with members of the Executive Committee to determine fit for the program, including the commitment to scholar project length and providing a community mentor at their site. Academic mentors were selected at the university based on areas of expertise that were applicable to the proposed research projects.Annual Research and Policy Conference on Child, Adolescent and Young Adult Behavioral Health where they participate in a networking event with community mentors and academic mentors. Scholars then rank preferences for projects, and the Executive Committee reviews scholar preferences and mentor expertise and places the scholars and mentors into their respective research teams. During the last semester of the program, graduating scholars also attend the conference (cited above) to present findings from their applied research studies. For additional information about the Institute, see the website, http://www.usf.edu/cbcs/cfs/itre/index.aspx [The graduate certificate program (15 credits) requires four continuous semesters, a total of 18 months, to complete. Scholars complete online coursework on adolescent behavioral health, translational research methods, and community-based participatory research, while also completing their in-person service-learning research project. During the first semester, scholars attend the dex.aspx , 20.As part of the triadic mentoring relationship, scholars have the opportunity to gain experience in improving community readiness, uptake, and successful implementation of new programs and practices. Academic mentors provide experience in methodologies of data collection, research and evaluation methods, community consultation, and problem solving, while community partners provide the practical application possibilities and pitfalls of accomplishing such changes.Measures for gauging the success of the program beyond academic productivity include real-world implementation and community outcomes. These measures are considered a step toward a more comprehensive understanding of the impact of translational research training on both scholars and community behavioral health organizations.The purpose of this evaluation is to explore outcomes of the Institute beyond academic productivity in order to highlight areas of impact and suggest potential next steps in the field of translational research. The Translational Research Impact Scale (TRIS), developed by Dembe et al. , provideThe Institute engages in ongoing process and outcomes evaluation in its efforts to inform practitioners and future researchers about the field of translational research and implementation science. The current study reports evaluation measures completed to date with the first two cohorts of scholars enrolled in the graduate certificate program. Evaluation is mainly focused on cohort #1 scholars, for whom information about career trajectory and longer term impact has already been collected. Cohort #1 included a Masters of Social Work student, six Masters of Public Health students, four employees of community agencies, two doctoral students in public health, and one doctoral student in criminology. Insights from cohort #2 scholars (similar in background), as well as academic and community mentors, are also included.Cohort #1 scholars (completed Institute participation in May 2014) were interviewed 1 year after completion of the Institute graduate certificate program. Questions focused on long-term outcomes of participation in the Institute, including current career, current interests and engagement in translational research, dissemination and research activities, and other themes of interest. Cohort #2 scholars (completed Institute participation in May 2015) were interviewed about their experiences in the Institute and plans for future research, career aspirations, and beliefs about how the Institute influenced their careers and professional aspirations overall.For each cohort, Institute scholars were matched with a community partner organization focused on behavioral health in order to complete the translational research and implementation science study. For cohort #1, five community behavioral health organizations agreed to host a team of scholars and provide an on-site community mentor to work directly with scholars on the conceptualization and implementation of the translational research study. The on-site community mentor provided oversight on the nature and scope of the project, while also assisting the scholars with ongoing data collection and analysis activities. For cohort #2, all but one of the original five agencies continued their involvement with the Institute.In addition to being paired with a community mentor, scholars were also paired with academic mentors, forming a triadic mentoring relationship. Academic mentors were tasked with providing consultation and oversight of research methodology including qualitative and quantitative approaches for data collection and analysis. In particular, academic mentors provided oversight on methodology in order to ensure the service-learning translational research studies best matched the needs of the behavioral health organizations. Academic mentors were paired with teams of scholars whose proposed research studies matched at least one of their areas of research expertise.The purpose of this evaluation was to assess longer term impacts of the Institute on scholars as well as from the perspectives of academic mentors and community partners. This evaluation was approved by the University of South Florida Institutional Review Board and participants provided verbal consent to participate. Semi-structured qualitative interviews were audio recorded and transcribed verbatim. A member of the Executive Committee trained the interviewers. Interviewers conducted practice interviews with Institute staff and met to discuss issues that arose in order to align strategies prior to conducting the interviews.n = 33) was sufficient for the purposes of this evaluation.Sample size was limited by the total number of people participating in the Institute program. In contrast to quantitative sampling in which large numbers of participants are required to achieve significance, relatively small numbers, as few as twelve in some instances, of participants are typically needed in qualitative research to achieve what is referred to as “thematic saturation” –24. Themcareer aspirations, (2) current career, (3) dissemination activities, (4) education activities/aspirations, (5) grant-writing activities/aspirations, and (6) influence of the Institute on Scholars’ lives overall. The importance of networks gained through Institute participation was added as an emergent theme of central interest to scholars and community mentors. Two coders met multiple times to discuss coding and establish reliability. This reliability procedure was intended to critically reflect on disagreements and improve analytical consistency, not to measure percentage of agreement [All interview transcripts were coded manually using both inductive and deductive approaches –26 for tgreement , 28. Quagreement –31. InvoAfter initial coding and analysis, the Translational Research Impact Scale (TRIS)  was usedInstitute scholars were recruited from health- and social-services-related graduate academic disciplines, programs, and fields, such as criminal justice, education, nursing, psychology, public health, behavioral health, rehabilitation and mental health counseling, and social work. Of the fifteen scholars in cohort #1, twelve agreed to be interviewed for this evaluation. Of the twelve scholars in cohort #2, seven agreed to be interviewed for this evaluation.Community mentors were full-time employees at local or regional child and adolescent behavioral health service agencies. We use behavioral health service agencies to refer to organizations that provided mental health, substance use, and/or educational programs, in this case specific to children and adolescents. Three of the agencies provided direct behavioral health services. One agency disseminates and evaluates an evidence-based curriculum focused on preventing substance abuse. The final agency was the social work services division of a local county school system. All five community mentors representing participating community behavioral health service agencies participated in the 2014 evaluation. Three out of the four community mentors participated in the 2015 evaluation.Of the academic mentors, two were psychologists with backgrounds working with community and school-based mental health intervention programs. One academic mentor had a background in mental health policy and social/health psychology and extensive experience working with community behavioral health agencies on evaluation projects. Another academic mentor was a sociologist with expertise in behavioral health statistics. All six of the academic mentors involved with the cohort #1 scholars participated in interviews during the 2014 evaluation. Three of the four academic mentors involved with the cohort #2 scholars participated in interviews during the 2015 evaluation.Using the domains of the TRIS framework   identification of research needs, (2) development of innovative methods, (3) improvement of research conduct and/or management strategies, (4) improvements in analysis and synthesis of results, (5) increases in the number of grant submissions and publications among translational researchers, (6) new, marketable discoveries, and (7) successes in research dissemination to appropriate audiences. Table Domain 1, A range of new research networks and collaborations were formed as a result of collaborative mentoring and community-based participatory research studies conducted as part of the Institute graduate certificate program. Community mentors, representing five different community behavioral health organizations collaborated with Institute scholars on community-based applied research studies. Although some individuals had prior relationships with the Institute’s faculty, community mentors and academic mentors reported improved collaborative relationships as a result of the Institute service-learning component .The triangular research mentoring relationship, including scholars, academic mentors, and community mentors, reportedly influenced scholars’ success and helped them develop and refine competencies in public health and translational research . One yeaTo date, four cohorts of scholars have created and implemented applied research studies in collaboration with community mentors. The service-learning studies that were completed have positively impacted the operations of participating community organizations . The traIn the context of translational research, individual mentoring can be difficult and thus not conducive to collaborative training. The Institute developed a collaborative mentoring approach to address this challenge and provided broader training to scholars as well as offering beneficial service-learning research to community behavioral health organizations . EmphasiInclusion of community mentors and practice-oriented scholars led to widespread diffusion of understanding of the techniques involved in conducting and implementing translational research. Scholars reported giving presentations to local policymakers and community organizations. Those scholars working for health organizations also reported bringing techniques learned from participating in the Institute into their work and educating their colleagues on the value of evaluation.Five scholars from cohort #1 reported presenting study results at national conferences. Several manuscripts are in preparation, authored by scholars and mentors from cohorts #1 and #2. Thus far, one manuscript has been published by an Institute scholar team . ScholarSometimes we get really wrapped up in formal research, in publishing and getting our names on things. That kind of left a bitter taste about that, not specifically from the Institute just like in general through my master’s program. I think maybe that’s why I’ve been not as involved or like eager to go to conferences or eager to be in the American Public Health Association or anything, just because I feel like we end up getting kind of really lost in that. I’m much more of like a one-on-one kind of person, like hands-on on the ground type work. (Cohort #1 Scholar)One scholar noted that over-emphasis on academic productivity can frustrate practice-oriented scholars and de-emphasize outcomes that are of importance to community organizations such as programmatic development or sharing results with other providers.Annual Research and Policy Conference on Child, Adolescent, and Young Adult Behavioral Health). Disseminating project results at this conference created an opportunity to speak to both academic- and community-based audiences.To balance the different outcomes valued by academia versus community organizations, one key outcome for all projects included in the Institute was a presentation at a national conference held in Tampa, FL  incorporation of discoveries from bench science into human or animal studies, (2) incorporation of clinical trial results into clinical or practical guidelines, (3) recruitment and preparation of new translational researchers, and (4) improvement in evidence-based health care service and delivery, patient outcomes, and positive health behaviors, as a result of research translation. Table Domain 2, The Institute’s inclusion of graduate students and working professionals from a range of health- and social-services-focused disciplines resulted in a diverse cohort of professionals trained in translational research methodology not only from the university but also from community agencies. Whereas transdisciplinary research across university departments is important in furthering research and translation, members of community-based organizations involved in implementation also benefit from training in translational research and implementation science methods. As earlier Institute-focused publications describe, the processual development of the Institute, including a community agency network and a translational research training program, have contributed toward the goal of increasing the number of people working in health care who have been trained to understand the importance of evidence translation and research , 20, 32.social impacts, includes potential impact areas such as (1) strengthening and refining of health-related policies and procedures, (2) improvements in community health, empowerment, and economic conditions to reduce health disparities, and (3) development of new community-based participatory programs and partnerships geared toward effective and meaningful implementation. For illustrative quotes related to societal impacts resulting from Institute projects, see Table Domain 3, . While most scholars did not continue to collaborate with the community mentors after graduating from the program, the community mentors continued partnerships with the university through ongoing service-learning projects with new cohorts of Institute scholars. Rather than attempts to create new behavioral health programs, the Institute’s training program was designed to train new researchers as well as make meaningful contributions to the function and applicability of existing behavioral health programs. Scholars have presented study outcomes and insights to local policymakers and community behavioral health organizations. Such presentations contribute to participatory decision-making and policy development. Community mentors described impacts to their organizations in terms of understanding the value of applied research and collaboration with the University, as well as of the need for adaptation and innovation of their ongoing operations.Service-learning applied research studies completed as part of the Institute’s graduate certificate and training program were collaboratively designed and implemented by scholars and community mentors and academic mentors. The emphasis on mutual benefit was designed to ensure the sustainability of community-based behavioral health programs and partnershipsExamples of outcomes from service-learning translational research projects completed as part of the Institute’s graduate certificate program include the following: (1) development of a training for providers focused on appropriate mechanisms to adapt a school-based evidence-based practice curriculum; (2) implementation of a professional development training program focused on mental health counseling; and (3) identifying facilitators and barriers to integrating primary care and behavioral health services.The Institute’s emphasis on community-university partnerships with a community-based participatory research foundation was designed to broadly impact child and adolescent behavioral health issues . CommuniAt the time of the evaluation, cohort #1 scholars were employed in a range of behavioral health organizations and university departments. Current careers included the following: technical assistants on health focused grant projects; reporting and analytics for a health care organization; senior qualitative analyst for a health care organization; administrator for a substance-abuse-focused organization; curriculum development and implementation specialist for a substance abuse outreach organization; manager for a children’s special needs organization; and research fellow for a federal healthcare organization.As noted above, one of the most challenging aspects of implementing evidence into practice is that implementation stakeholders  rarely have the skills to interpret and implement new research into practice . Part ofImplementing a multi-component, applied service-learning research experience, in addition to education or perhaps curriculum-based translational research, holds the potential to expand the public health and behavioral health workforce in needed areas , 35. To Fortunately, there are resources available to encourage translation of research into practice. The National Collaborating Centre for Methods and Tools  has deveTraining and mentoring new researchers in implementation science and in translational research are increasingly emphasized in health equity research, as evidenced by the many current programs in existence for training both students and faculty members , 39–41. This paper is limited by the self-reported nature of the qualitative data collected. Qualitative investigation is well-suited, however, to providing in-depth information about participants’ experiences. For the purpose of this evaluation, qualitative interviews were intended to elicit information about stakeholder experiences in the Institute. Although this paper does not provide a comprehensive evaluation of the Institute, these findings about Institute scholar experiences and the need for alternative measures of success will likely be of interest to similar current and future educational training programs in translational research , 39–41. Over the course of this evaluation, the authors identified several drawbacks in emphasizing academic measures of productivity rather than community outcomes in evaluating translational research training programs. Common measures, such as numbers of grant applications and awards, are less revealing of success when applied to practice-oriented graduate and professional degree programs and community organizations. In this paper, the use of the TRIS domains to identify areas of potential impact suggests ways of broadening measures of success in the context of a translational research educational training program designed for graduate students, community partners, and academic mentors. This triadic, applied approach to translational research training has potential to broaden the reach of translational research in several ways. After participating in training programs, researchers are better prepared to work in interdisciplinary environments and to successfully implement evidence-based programs in applied community practice settings. Further, training not only graduate students but also members of stakeholder organizations can facilitate improved communication and understanding and lead to stronger community/university partnerships.


In the literature, there is growing evidence that subfertile patients who conceived after infertility treatments have an increased risk of pregnancy and perinatal complications and this is particularly true for patients who conceived through use of high technology infertility treatments. Moreover, high technology infertility treatments include many concomitant clinical and biological risk factors. This review aims to summarize in a systematic fashion the current evidence regarding the relative effect of the different procedures for high technology infertility treatments on the risk of adverse pregnancy and perinatal outcome. A literature search up to August 2016 was performed in IBSS, SocINDEX, Institute for Scientific Information, PubMed, Web of Science and Google Scholar and an evidence-based hierarchy was used to determine which articles to include and analyze. Data on prepregnancy maternal factors, low technology interventions, specific procedures for male factor, ovarian tissue/ovary and uterus transplantation, and chromosomal abnormalities and malformations of the offspring were excluded. The available evidences were analyzed assessing the level and the quality of evidence according to the Oxford Centre for Evidence-Based Medicine guidelines and the Grading of Recommendations Assessment, Development, and Evaluation system, respectively. Current review highlights that every single procedure of high technology infertility treatments can play a crucial role in increasing the risk of pregnancy and perinatal complications. Due to the suboptimal level and quality of the current evidence, further well-designed studies are needed. Throughout the years, it has always been clear to scientists that the primary endpoint in reproductive medicine was the healthy baby and that all other endpoints would be considered only a surrogate , 2. The Notwithstanding these limitations, more and more data available in the literature seem to demonstrate that pregnancy following infertility treatments are at higher risk of adverse pregnancy and perinatal outcomes when compared with those after natural conception (NC) independently from scientific approach , and thiAlthough systematic reviews with and/or without meta-analysis have been published on specific topics, at the moment no comprehensive review is available in the literature, discussing the impact on maternal and perinatal outcome of each element and/or clinical/biological choice which comprise the high technology infertility treatments. Based on these considerations, the aim of the current document was to comprehensively review in a systematic fashion the hitherto published evidences regarding the effects of high technology infertility treatments on the obstetric risk of patients with female and couple infertility. The effects on the risk of chromosomal abnormalities and malformations of the offspring was not a study aim.The methodology used for the current systematic review consisted of searching all available articles for each specific issue to explore the relationship between high technology infertility treatments and pregnancy and perinatal complications. High technology infertility treatments were considered as all interventions for fertility enhancement including manipulation of female gametes. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement  was follMultiple strategies were used to search and identify relevant demographic, epidemiological, clinical and experimental studies. Sociological online libraries , Institute for Scientific Information, PubMed, Web of Science and Google Scholar were consulted. Only articles written in English were considered. The search was conducted independently by two authors (S.P. and S.S.). The literature available up to August 2016 was captured, including all available studies which reported data about the relationship between each fertility technique and the related obstetric and perinatal complications, matching every intervention with every potential obstetric disorder and perinatal health impact, as shown in Table The available evidence about the relationship between high technology infertility treatments and adverse obstetric and perinatal outcomes was analyzed assessing the level of evidence according to the Oxford Centre for Evidence-Based Medicine (OCEM)-Levels of Evidence 2011 guidelines  and the Figure Many data from systematic reviews with and without meta-analyses have demonstrated that ART singletons are at increased risk of pregnancy and perinatal complications. In 2004, an initial systematic review of controlled studies found a relative risk of 3.27 (95 % CI 2.03 to 5.28) for early-preterm birth (EPTB) (< 32 weeks) in singleton pregnancies from assisted conceptions . SingletThe most recently published meta-analysis about the risk of pregnancy-related complications and adverse perinatal outcomes in singleton pregnancies obtained with ART involves 50 cohort studies for a total of 161,370 ART singleton compared with 2,280,241 NC singleton pregnancies . This meInitial systematic reviews with meta-analyses , 17 demoA recent meta-analysis including 39 cohort studies explored the risk of adverse pregnancy outcomes in ART conceptions compared with NC in a sample of 146,008 multiple births . ART werIn all meta-analytic data , 22, 23 One way to overcome the zygosity as confounder could be to perform comparisons restricted to different-sex twin pairs in order to exclude all the monochorionic twins. To this regard, a recent meta-analysis  includinAn excellent meta-analysis of individual data from RCTs demonstrated that the elective single embryo transfer (SET) is less effective (of about 50 %) than double embryo transfer (DET) in women aged more than 33 years but not in younger, and that the odds of a multiple live birth in women randomized to eSET were significantly smaller than for women who received DET . After eIrrespective of the risk related to the multiple pregnancies, the number of embryos transferred can be an independent and potential factor influencing the obstetric and perinatal outcomes. Available data were very heterogeneous showing better perinatal outcomes , 31 or nIn singletons with a ‘vanishing co-twin’, the risk of PTB  and of other adverse perinatal outcomes (aOR ranging from 1.73 to 2.88) was significantly higher than in singletons from a single gestation . The obsA well designed retrospective study on a very large cohort of 252,994 singleton deliveries evaluated the pregnancy and perinatal outcomes, adjusted for confounders such as fertility treatment and maternal age, in VTS in comparison with those recorded in singletons and dichorionic twins . VTS wasIn comparison with children born after natural-cycle IVF, IVF children conceived after stimulation with clomiphene citrate (CC) and with CC plus gonadotropins had a higher risk of LBW . On the 2) levels on the day of the human chorionic gonadotropin (hCG) trigger were closely related to the risks of SGA and PE in singleton pregnancies [2 levels; the elective cryopreservation of all embryos with subsequent thawed ET reduced significantly the risk of PE , and to deliver SGA infants  as compared with the patients who had fresh ET [The ovarian response to COH has been also related to pregnancy complications. A recent observational United Kingdom (UK) study  on 402,1gnancies , 52. Thufresh ET . Howeverfresh ET –56. In lfresh ET , even iffresh ET .Finally, the hitherto published literature regarding the relation between OHSS and pregnancy complications is limited and controversial . This diIn a first systematic review with meta-analysis , the risAt the moment, the most complete data on maternal and child health adjusted for confounders were from a large retrospective cohort study  comparinAn important issue observed in the studies comparing the transfer of embryos at blastocyst vs. cleavage state was the discrepancy between the increased incidence in PTB and the similar incidence of LBW neonates in singletons . RegardiOn the other hand, a recent retrospective registry study   after frozen-thawed ET than after fresh ET . A studyThe frozen-thawed embryo cycles showed an increased association with PIH/PE  , similarThe risk of post-term birth , LGA , and macrosomia  also increased , 89. Of Recently, a national register-based controlled cohort study with further meta-analysis was designed in order to clarify whether the “large baby syndrome” was caused by intrinsic maternal factors or related to the freezing/thawing procedures . In ordeA recent retrospective UK cohort study  analyzedFinally, two retrospective recent cohort studies suggest that frozen cycles are associated with a reduction of the incidence of ectopic pregnancies and monozygotic twins , 101. SpInitially, there were some safety concerns about old vitrification procedures because the use of very high concentrations of cryoprotectants required to optimize the efficacy could induce toxic effects . New vitSpecific data on the influence of oocyte vitrification on obstetric risk are few and poorly reported, and head-to-head studies are lacking. A systematic review intercepted only uncontrolled or case reports reporting very limited data on the health of the newborns from vitrified and slow frozen oocytes. Also successive studies  reportedOnly in 2014, a retrospective cohort study  comparedComparable gestational age at delivery, weight at birth, and congenital anomaly rate were observed analyzing 435 blastocyst vitrification cycles using an open system, with the fresh oocyte control cycles . Other rOne retrospective, single-center study of children born after day 3 ET from fresh, slow frozen or vitrified embryos showed that the incidence of PIH/PE, GDM, placenta previa and abruptio placenta were similar in all groups . SpecifiNo difference in almost all pregnancy and perinatal/neonatal outcomes was observed in a Swedish retrospective study  comparinThe largest and most recent population-based cohort study compared obstetric and perinatal outcomes of 16,845, 2,766 and 6,537 clinical pregnancies, and 13,049, 2,065 and 4,955 live deliveries of fresh, slow frozen and vitrified blastocysts . SingletAn interesting retrospective study  analyzedAny adverse effects of the IVM procedure on pregnancy and perinatal outcomes are a partially unknown field of research. From a mechanicistic point of view, IVM could affect the oocyte development, as any intervention in the growth phase could affect oocyte maturation, fertilization and subsequent embryo development . On the A systematic review  of head-Although many studies on the safety of IVM are available in the literature, all have a retrospective design, very small sample sizes, and are not controlled and include a number of biases and (unadjusted) confounders. Obviously a high prevalence of PCOS cases in these studies could influence the results , 127. InAlthough hatching of the blastocyst is a crucial step for embryo implantation, and the failure to hatch can be considered one of limiting factors of the embryo development, the artificial disruption of the zona pellucida (assisted hatching) can potentially affect embryo competence and, thus, increase the risk of pregnancy complications. Although each technique used for assisted hatching can potentially exert specific effects on maternal and perinatal/neonatal health, very few data are available in literature about the effects of assisted hatching on obstetric and perinatal outcomes.In a double-blind RCT , no effeFinally, the use of assisted hatching has been associated with an increased incidence of monozygotic twinning . MoreoveThe European Society of Human Reproduction and Embryology (ESHRE) PGD Consortium reported that pregnancies and babies born after ICSI/PGD are not different from pregnancies obtained and babies born after ICSI treatment . SimilarA recent study  comparedA very recent retrospective cohort study, using data from the U.S. National ART Surveillance System on fresh autologous cycles with blastocyst transfer, compared 97,069 non-PGD procedures with other 9,833 PGD procedures demonstrating the influence on perinatal outcome of the specific indication for PGD . SpecifiNotwithstanding these available scientific data, definitive conclusions on the safety of the PGD cannot be drawn since couples undergoing PGD are usually fertile and in good health, data on fetal/perinatal growth and weight can be biased by timing of the biopsy, extended embryo culture, type of ET, etc., and long-term data on offspring are totally lacking. To this regard, a recent retrospective questionnaire analysis  showed aInitial studies on OD populations, aiming to assess their obstetric and perinatal risk, had as crucial confounders advanced maternal age and the high rate of multiple pregnancies and VTS –143. In An increased risk of obstetric complications, such as first trimester vaginal bleeding, PE, PIH, PTB and cesarean delivery, was reported after OD, although hypertensive disorders seem to be the most frequent one , 149. WiFive meta-analyses on pregnancy complications and perinatal outcomes after OD cycles are available in the literature –155. UnfFinally, the last systematic review with meta-analysis  includedOne of the largest and better controlled cohort study published on perinatal outcomes of children born after OD included 375 OD babies, and clinical data compared with three control cohorts of children, i.e. NC  and born after either IVF  or ICSI  . An incrSparse available data in the literature seems to suggest an increased risk of hypertensive disorders during pregnancy, with a specific increase of the PE risk, in nulliparous and in multiparous pregnancies with changed paternity , 160. InVery little is known about the relationship between embryo donation and pregnancy and perinatal complications. In fact, available data can be extrapolated from infertile populations who conceived after mixed procedures of gamete and embryo donations . At the A systematic review on gestational surrogacy has been very recently published, and the pregnancy and perinatal outcomes of gestational carriers compared, when possible, with those of standard IVF and OD cycles . The incDespite the level and the quality of the current evidence it is generally suboptimal due to the presence of biases, confounders and limitations in study design Table , currentIdeally, the knowledge of the pathogenesis of the increased risk of pregnancy and perinatal complications in women who receive high technology infertility treatments and of the specific mechanisms of action could be crucial for preventing them. Unfortunately, few data are available regarding the biological explanations of that increased risk. Many mechanisms have been hypothesized and regard the alterations of the early placentation including not only alterations in endometrial receptivity, genetic and epigenetic mechanisms of implantation, invasion and growth of the trophoblast but also genetic and/or epigenetic alterations of oocyte/embryos due to biological manipulations , and immunological intolerance in case of OD because the fetal genome is allogenic to the carrier , 165–167th week of gestation) are related with a risk lower of VLBW neonates , LBW neonates , and preterm birth  [However, from the clinical point of view, the priority is not to precisely estimate the amount of the obstetric risk but to recognize the presence of one or more risk factors , to correct those modifiable and to strictly follow the resulting pregnancies with appropriate prenatal cares. In fact, the delay in receiving prenatal care increased the PTB risk, while more-frequent use of prenatal care significantly improved the birth weight among pregnancies at high risk including subfertile women . Recentlctively) . That daAt the moment, well established strategies to identify, follow and manage infertile patients and/or patients who have receive an infertility treatment are lacking and only few papers suggest potential strategies of management consisting in a generic close pregnancy monitoring and diagnostic testing , 157. PhSubfertile women who conceived after the use of high technology infertility treatments are at increased risk of pregnancy complications, and every single/specific step and/or procedure can play an independent and crucial role. Thus, all infertile patients scheduled for high technology infertility treatments should be clearly informed of that increased obstetric and perinatal risk in case of pregnancy, regardless of multiple pregnancy. A careful preconceptional counselling aimed to optimize the general health status of the pre-pregnant women is needed , identifying and treating modifiable reproductive disorders  and, fin


Phoca vitulina richardii). The availability and spatial distribution of glacier ice in the fjords is likely a key environmental variable that influences the abundance and distribution of selected marine mammals; however, the amount of ice and the fine-scale characteristics of ice in fjords have not been systematically quantified. Given the predicted changes in glacier habitat, there is a need for the development of methods that could be broadly applied to quantify changes in available ice habitat in tidewater glacier fjords. We present a case study to describe a novel method that uses object-based image analysis (OBIA) to classify floating glacier ice in a tidewater glacier fjord from high-resolution aerial digital imagery. Our objectives were to (i) develop workflows and rule sets to classify high spatial resolution airborne imagery of floating glacier ice; (ii) quantify the amount and fine-scale characteristics of floating glacier ice; (iii) and develop processes for automating the object-based analysis of floating glacier ice for large number of images from a representative survey day during June 2007 in Johns Hopkins Inlet (JHI), a tidewater glacier fjord in Glacier Bay National Park, southeastern Alaska. On 18 June 2007, JHI was comprised of brash ice (2 (SD = 2.6 m2). We estimate the total area (± uncertainty) of iceberg habitat in the fjord to be 455,400 ± 123,000 m2. The method works well for classifying icebergs across scenes (classification accuracy of 75.6%); the largest classification errors occur in areas with densely-packed ice, low contrast between neighboring ice cover, or dark or sediment-covered ice, where icebergs may be misclassified as brash ice about 20% of the time. OBIA is a powerful image classification tool, and the method we present could be adapted and applied to other ice habitats, such as sea ice, to assess changes in ice characteristics and availability.Tidewater glaciers are glaciers that terminate in, and calve icebergs into, the ocean. In addition to the influence that tidewater glaciers have on physical and chemical oceanography, floating icebergs serve as habitat for marine animals such as harbor seals ( Tidewater glaciers, or glaciers that terminate in the ocean, are a prominent landscape feature in southeastern and south-central Alaska and play an important role in landscape and ecosystem processes. Changes in tidewater glaciers are cyclical in nature, with advance rates typically an order of magnitude slower and occurring over much longer time periods than retreats e.g., ,2). Thou. Thou2])Phoca vitulina richardii) to rest, whelp, nurse young, molt, and avoid predators )Herein, we present a case study with glacier ice habitat in an Alaskan tidewater glacier fjord to describe a novel method that uses OBIA to quantify the amount and fine-scale characteristics of glacier ice from high resolution aerial imagery. Our primary objective was to develop a semi-automated method to estimate ice habitat from high spatial resolution airborne imagery collected of floating glacier ice in a tidewater glacier fjord. Specifically, we (i) developed workflows and rule sets to classify airborne imagery of glacier ice using object-based image analysis; (ii) quantified the amount and fine-scale characteristics of floating glacier ice in the fjord; (iii) developed processes for automating the object-based analysis of ice for a large number of digital images; and (iv) present results describing ice characteristics and accuracy assessments of classification from a representative survey day during June 2007. The described method could be applied to ice habitats, including sea ice, in subpolar and polar regions, that are used by other pagophilic species.Aerial surveys were conducted under NOAA Fisheries Marine Mammal Protection Act permit #358-1787-01, and scientific permits issued by Glacier Bay National Park.2 of marine waters )Eumetopias jubatus) in Alaska, dugongs (Dugong dugon) in nearshore marine habitats in Australia, and penguins and pinnipeds in Antarctic [The OBIA technique that we have described could also be applied to imagery collected by unmanned Aerial System (UASs), which are relatively new low-cost platforms that can be used to quantify wildlife and the habitats that they use. For example, UASs have been successfully used to photograph several species and their habitats in remote regions including Steller sea lions (ntarctic –44.Ursus maritimus).This study demonstrates that OBIA is a method that can be used to assess the availability of glacier ice for seals and for quantifying the fine-scale characteristics of ice in tidewater glacier fjords. An understanding of the amount and fine-scale features of icebergs will be essential for assessing how future changes in glacier calving rates may influence ice habitat that is used by harbor seals in tidewater glacier fjords. The method described here can be applied in future studies to assess seasonal and inter-annual changes in the availability of icebergs, and also used to provide quantitative estimates of iceberg characteristics that can be used in habitat and population trend models for harbor seals or other pagophilic species. The approach we have presented could be broadly applied to quantify iceberg characteristics in other tidewater glacier fjords, as well as other ice habitats such as sea ice, in order to investigate the effects of changing ice cover on other pagophilic species such as penguins and polar bears (


Each person differs from the next by an average of over 3 million genetic variations in their DNA. This genetic diversity is responsible for many of the interindividual differences in food preferences, nutritional needs, and dietary responses between humans. The field of nutrigenetics aims to utilize this type of genetic information in order to personalize diets for optimal health. One of the most well-studied genetic variants affecting human dietary patterns and health is the lactase persistence mutation, which enables an individual to digest milk sugar into adulthood. Lactase persistence is one of the most influential Mendelian factors affecting human dietary patterns to occur since the beginning of the Neolithic Revolution. However, the lactase persistence mutation is only one of many mutations that can influence the relationship between dairy intake and disease risk. The purpose of this review is to summarize the available nutrigenetic literature investigating the relationships between genetics, dairy intake, and health outcomes. Nonetheless, the understanding of an individual’s nutrigenetic responses is just one component of personalized nutrition. In addition to nutrigenetic responses, future studies should also take into account nutrigenomic responses , and phenotypic/characteristic traits , as these factors all interact with diet to influence health. The fields of nutrigenetics and nutrigenomics both aim to elucidate how the genome interacts with nutrition to influence health. They differ in that nutrigenetics focuses on how gene variants influence responses to diet, while nutrigenomics focuses on how diet affects gene expression. The intended end goals of these sciences, which both fall under the umbrella of nutritional genomics, are to improve health through the application of personalized nutrition . At presThe vast majority of genetic variants that have nutrigenetic consequences are loss of function mutations in which the ability to properly digest or metabolize dietary compounds are diminished. LP stands apart from the majority of monogenic mutations in that it is a gain of function mutation in which the ability to break down lactose into adulthood is gained. Nutrigenetic loss of function mutations tend to restrict or reduce dietary options, but LP does the opposite and increases the available number of dietary options that can be digested. This ability has resulted in LP becoming one of the strongest positive selective pressures in human history , reinforLP polymorphisms have occurred independently in Northern Europe, Africa and the Middle East. This dominant trait provided these populations with the ability to greatly expand their cuisines and improve their access to energy, nutrients, and dietary sources of potable water ,10. LP gThe LCT-13910 C > T single nucleotide polymorphism (SNP) at intron 13 is the most prevalent and most studied LP polymorphism. Traditionally, a person with two CC alleles is considered to be lactose intolerant, also known as lactase non-persistent (lactase activity <10 units/g protein) . A majorThe study of nutrigenetics is expanding rapidly as researchers are now investigating the polygenic nature of several disease states. In fact, only a small percentage of obesity cases have been shown to be monogenic . Rather,In agreement with the epidemiological data, several nutrigenetic studies of mixed design which did measure dairy intake also found the LCT-13910 C > T SNP to be correlated with higher dairy intake and BMI ,18,19,22Overweight and obesity increase the risk for cardiometabolic disorders such as metabolic syndrome, CVD, and type 2 diabetes (T2D). The majority of dairy intake studies have consistently provided evidence of neutral or protective associations related to metabolic syndrome risk factors  and chronic diseases such as CVD and T2D ,39,40,41A study of 551 participants of European descent found that the LCT-13910 C > T polymorphism in combination with higher dairy intake could increase the risk for metabolic syndrome, but only in women . These fA Mendelian randomization study of over 20,000 participants from multiple racial and ethnic groups including American  and Spanish populations assessed the relationship between a different and less commonly studied LP polymorphism (the MCM6-rs3754686 polymorphism at intron 15). The researchers found no associations between LP and CVD or total mortality rates . The resEpidemiological studies have provided mixed results regarding dairy intake and cancer risk ,48,49,50Large prospective cohort studies and meta-analyses provide evidence for protective associations of dairy intake on colorectal cancer that often depend on the type and amount of dairy products consumed ,51,52; hProstate cancer is one of the most common cancers in men . In contRelatively few nutrigenetic studies have been conducted on LP status, dairy intake, and cancer types residing outside of the digestive or reproductive systems. A recent study in nearly 23,000 Swedish adults with lactose intolerance found a decreased risk of lung, breast, and ovarian cancers compared to individuals who were lactose tolerant . The autTotal dairy intake , dairy pResearchers investigating the relationships between milk intake, LP status, and bone health in 258 postmenopausal women from Austria found that LP genotype influenced BMD and bone fractures . The CC Recent investigations into the associations between LP status, dairy intake, and health outcomes have provided nuanced findings that are moderated by factors including LP genotype, the type and amount of dairy product consumed, age, gender, body weight, and the specific pathology of the disease being assessed. Additionally, numerous other variables such as mutations in non-LP genes, whole dietary patterns, and environmental factors affect the nutrigenetic relationship between lactase persistence, dairy intake, and health. The science of nutrigenetics is quickly moving beyond the single candidate gene approach, and it is becoming clear that LP mutations are not the only mutations that have the potential to moderate the relationships between dairy intake and disease.In addition to lactose, dairy products contain a diverse set of constituents  that can affect human health. The digestion, metabolism, transport, and excretion of these compounds are all dependent on gene products . Therefore, genetic variants that result in altered metabolic and hormonal gene products may influence the relationship between dairy intake and disease risk. The gene variants that have been studied so far in relation to dairy intake include polymorphisms in genes related to lipid metabolism, hormone receptor function, and vitamin D receptor function .Saturated fat is one of the most commonly studied dietary compounds in relation to genetic polymorphisms and health, primarily having to do with cholesterol levels and CVD risk . SaturatA gene-candidate study involving 2000 ethnically diverse participants (Americans of Northern European ancestry and Americans of Puerto Rican origin) was conducted to determine the interactions between an apolipoprotein A2 gene (APOA2) gene variant, dairy product intake, and BMI . In thisA year-long randomized trial of 161 Spanish adults investigated the relationship between dairy fat intake and 14 SNPs within nine different candidate lipid metabolism genes . The parIn addition to lipid metabolism SNPs, hormone and hormone receptor SNPs have also been studied in the context of dairy intake and health outcomes. Researchers from the InterAct Consortium investigated the relationships between incretin hormone SNPs, whey-containing dairy intake, and risk for T2D in 18,638 European adults . Whey-coA gene-candidate study involving 945 European adults at high risk for CVD from the PREDIMED-Valencia Study was conducted to determine if a particular genetic polymorphism in the somatostatin receptor 2 (SSTR2) gene interacts with dietary or anthropometric variables . Among oStudies on vitamin D receptor (VDR) polymorphisms and dairy intake have provided key insights into how different polymorphisms in the same gene interact with diet to influence health outcomes. Indeed, while one VDR polymorphism might affect receptor-binding activity, another might pertain to receptor binding strength or substrate affinity. These differences can affect how the receptors will interact with dietary constituents, and in turn will affect how those dietary constituents are absorbed, transported, metabolized, and excreted.A 12-week long intervention study investigated the relationships between VDR FokI polymorphism, vitamin D fortified dairy intake, and inflammatory and antioxidative markers in 140 Iranian subjects with T2D ,67. SubjA similar 12-week long study was conducted by the same researchers to determine the relationships between a different VDR polymorphism (Cdx2 polymorphism), vitamin D fortified yogurt intake, and central obesity in 60 Iranian subjects with T2D . The subWhen multiple VDR polymorphism  and dairy intake were investigated in relation to colorectal cancer recurrence in 480 subjects from the United Kingdom , only ceIn combination with the findings from LP and dairy intake studies, studies on non-LP gene variants and dairy intake provide convincing evidence that an array of gene variants are responsible for significant interindividual variations in dietary intake patterns and metabolic responses. Many of these gene–diet interactions converge to influence body weight, cardiometabolic disease risks, cancer risk and bone health. Further findings from the investigations of gene–dairy–disease interactions will contribute greatly to the development of more genetically informed and personalized recommendations regarding dairy product intake and disease risk management.A major aim of personalized nutrition is to turn a person’s nutrigenetic and nutrigenomic information into highly specific dietary advice that can be used to improve or maintain health. This type of dietary advice has the potential to revolutionize the fields of nutrition and healthcare. However, at present, the science of personalized nutrition is just scratching the surface of its potential, and we must be careful not to label it a panacea before proving its efficacy. While this review of nutrigenetic studies has focused solely on one food group and a few select genetic mutations, it has clearly shown the complexities of understanding and utilizing the information gathered from studies of gene–diet interactions. Nutrigenetic studies that have included data on dairy intake provide mixed results on health outcomes. Many of these studies show that LP is associated with higher dairy intake and BMI, but they also tend to show that LP and higher dairy intake are not consistently associated with cardiometabolic disease risk, certain types of cancer occurrence, or bone health. Nutrigenetic studies investigating the effects of polymorphisms in genes related to lipid metabolism, hormone receptor function, and vitamin D receptor function also show mixed results and the potential for differential sensitivity between genotypes to the health effects of dairy food intake. More research is necessary on polygenic and multifactorial relationships in the context of diet and disease. In the end, these nutrigenetic relationships are likely dependent on many other factors besides the individual SNPs tested, such as the type and amount of dairy product consumed, gender, age, ethnicity, and other genetic mutations that affect the metabolism, transport, or storage of nutrients in the body.The interindividual variation between humans is on the magnitude of millions of SNPs, so the insights gained from a limited focus on a few SNPs having to do with dairy intake reveal only a small part of a person’s nutrigenetic story. Furthermore, additional research is needed on the relationships between different gene variants and their abilities to interact and influence each other in antagonistic, additive, or synergistic ways. In summary, nutrigenetic research which is focused on the relationships between single SNPs (of which there are millions) and single food groups (which may be comprised of a diverse array of products with varying combinations and amounts of nutrients and bioactives), may provide great insights into improving the science of personalized nutrition. However, this type of research is only part of the personalized nutrition equation. Nutrigenomic responses  to different types and amounts of dairy products, along with microbiome data, and phenotypic/characteristic traits  must also be accounted for, since these factors can all interact with the diet to influence health.


We analysed observations from 31 neighbourhood parks, with each parkmapped into smaller target areas for study, across five US cities generatedusing the System for Observing Play and Recreation in the Community (SOPARC). Inareas where at least two people were observed, less than one-third(31.6%) were populated with at least one white and one non-white person.Park areas that were supervised, had one or more people engaged in vigorousactivity, had at least one male and one female present, and had one or moreteens present were significantly more likely to involve interracial groups(p<0.01 for each association). Observations in parks located ininterracial neighbourhoods were also more likely to involve interracial groups(p<0.05). Neighbourhood poverty rate had a significant and negativerelationship with the presence of interracial groups, particularly inneighbourhoods that are predominantly non-white. Additional research is neededto confirm the impact of these interactions. Urban planning and public healthpractitioners should consider the health benefits of interracial contact in thedesign and programming of neighbourhood parks. Urban parks have held a prominent place in city planning, landscapearchitecture, and public health scholarship for well over a century . Recent Before describing data collection and analysis methods, we review literaturefrom four distinct areas of scholarship that together create the conceptual andmethodological foundation for our research: (1) urban planning and landscapearchitecture’s history of promoting urban parks as democratic public spacesthat foster cohesion between groups of different socio-economic and ethnicbackground; (2) research on social interaction, social cohesion, and intergroupcontact in public spaces and green spaces within leisure studies and environmentaland social psychology; (3) public health research on chronic exposure to prejudiceand institutional racism as primary contributors to racial health disparities; and(4) recent public health research utilizing systematic social observations andenvironmental audits of outdoor public spaces including neighbourhood parks. Byborrowing from these distinct areas of scholarship, we present a conceptualframework and suggestions for measurement and research design that highlight andtest the underappreciated public health benefits of people coming together acrossrace and ethnicity in neighbourhood parks.th century (As the world undergoes a third major period of urbanization (Angel 2011),local governments are adopting new types of parks and green space strategies.This includes creation of rail trails and greenways, retrofitting landfills,cemeteries, rooftops, and parking areas, covering highways and reservoirs,sharing schoolyards, closing roads, and creating urban farms and communitygardens . There i century .thcentury parks movement developed in response to the negative impact of urbanindustrialization on physical health, mental health, and social bonds  andmeta-analyses demonstrate consistent and relatively large and positive effects of intergroupcontact on prejudice and intergroup conflict across age groups, settings, andcountries (Pettigrew 2016). These positive effects of intergroup contact are notlimited to the group members who are directly involved in the interaction butextend to the larger group by impacting norms . Fewer studies have applied intergroup contact theory to urban publicplaces such as neighbourhood parks. One study by The Within public health literature, concern about the role of urbanneighbourhood parks in racial health disparities has focused on lack of physicalaccess to parks, disproportionate exposure to park disamenities, and racialdisparities in park use by people of color .The patPublic health research has focused on the human health implications ofparks primarily as sites for promoting physical activity  Howfrequently are people across racial groups present in the same section of parksat the same time? (2) What are the characteristics of park areas and parkactivities that correlate with the co-presence of park users across racialgroups? And (3) What neighbourhood characteristics in which parks are locatedare correlated with the co-presence of park users across racial groups? We useour results to highlight they ways that urban planners and public healthprofessionals can work deliberately to design and program neighbourhood parks tomaximize their public health impact. Our analysis of who is coming into contactin parks has important implications for understanding and, potentially,improving interracial and interethnic relations. This is especially timely inlight of the ethnic confrontation that is entangled with contemporaryglobalization and urbanization around the world, and within the United States,the “Age of Ferguson” and Black Lives Matter movement .The System for Observing Play and Recreation in the Community (SOPARC) is avalidated direct observation tool for assessing use of park and recreation areas,including park users’ physical activity levels, gender, activity types, andestimated age and ethnicity groupings . SOPARC Observations were made using SOPARC at 31 neighbourhood parks across fivedifferent US cities during the spring, summer and fall between 2008 and 2010.Researchers from Albuquerque, NM, Columbus, OH, Chapel Hill/Durham, NC, andPhiladelphia, PA selected six parks each and researchers from Los Angeles CAselected seven neighbourhood parks from areas with different racial/ethnic andincome composition. Some but not all parks included a recreation center andfull-time staff. Trained staff observed all areas of each park at fourrandomly-selected 1-hour intervals between 7am and 8pm on two randomly selectedweekdays and two randomly-selected weekend days over at least 3 seasons of the year. The timOverall park size was calculated as a continuous variable (in acres).Each park was mapped and divided into discrete target areas to make observationsmore manageable. The type of facilities present  were documented for each targetarea. Two staff rotated around the park, systematically observing each targetarea and identifying whether it was physically accessible ,empty, organized (scheduled sporting event or exercise class), and supervised bypark staff, coach, volunteer, or teacher.Observations were coded based on the total number of people present,whether at least one male and one female was present, only males were present,or only females were present and whether any children, teens, adults or seniorswere present. Based on data collected in the field, all observations were latercoded as interracial or not based on whether at least one white and onenon-white person were present in the same target area at the same time.Interracial was defined exclusively as the simultaneous presence of someonewhite and someone non-white in the same target area. We chose to operationalizeinterracial this way because whites represented the largest (Columbus and ChapelHill/Durham) or second largest demographic group in all of the cities. Also, historically racial/ethnicconflict in the United States has been defined largely in the context of whiteprivilege and white supremacy that categorizes all non-whites as“other” .ResearcStaff identified the number of males and number of females beingsedentary or standing without moving (heretofore referred to as sedentary),moderately active , or vigorously active. SOPARC has also beenshown to have high levels of inter-rater reliability for physical activitylevels . They alThe neighbourhood racial/ethnic and income characteristics of each parkwere determined using 2000 US Census data for block groups with centroids withinhalf a mile of park boundaries for parks in all cities other than ChapelHill/Durham where block groups with centroids within 0.8 mile were used becauseof much lower population densities. The population density and the percent ofneighbourhood residents who were white, Black/African American, andHispanic/Latino and living in poverty were determined for all parks.Neighbourhoods were then identified as having a high interracial mix  or mediuminterracial mix ., and as having a high poverty (poverty rate greater than25% or not) or low poverty (poverty rate less than 15% or not).Poverty rate was measured as a continuous variable for the GEE model.Descriptive statistics were generated to compare the timing ofobservations, characteristics pf park target areas, and characteristics of parkactivities across cities and neighbourhoods. Generalized Estimating Equations(GEE) were used to analyse the SOPARC data. GEE models are appropriate given theclustered nature of the sample  andmultiple observations taking place on the same day in the same park in the samecity.This research protocol was approved by the Institutional Review Boardsof the University of Pennsylvania, RAND Corporation, The Ohio State University,University of North Carolina, and Behavioral Health Research Center of theSouthwest/PIRE.Of the 43,706 observations made across the 31 parks, only 7,352(16.8%) included two or more people present in the same target area at thesame time. Less than one-third of these observations (31.6%) included atleast one white and one non-white person. The frequently of observations ofinterracial groups varied by city, with the highest rate (40.5%) in ChapelHill and the lowest (23.6%) in Philadelphia. There were also significantdifferences across cities in the age and gender of park participants and the amountof sedentary behavior, walking, vigorous activity, and supervised activity see.Through the multivariate GEE analysis , a numbeNeighbourhood characteristics showed some interesting associations, as well.Neighbourhoods with high and medium racial mix were significantly more likely tohave park users across racial group co-present  than racially homogenous neighbourhoods in their communityparks. Poverty level of a neighbourhood had a significant and complex relation,through the interaction with the percentage of white population in theneighbourhood. In a white-majority neighbourhood , poverty level was not significantly associated with inter-racialgrouping. In a neighbourhood with a relatively low percent of white residents , poverty level had a significant and negativeassociation . On the other hand, thepercentage of white population always had a significant and positive associationregardless of the local poverty level. For example, in a relatively high-incomeneighbourhood with 10% households in poverty, every percentage point ofwhite population had an estimated log odds ratio of .02 (p=.0004) for inter-racialgrouping. In a relatively low-income neighbourhood with 30% households inpoverty, the log odds ratio for inter-racial grouping is .04 (p=.0001). Differencesamong cities were not significant in the multivariate model when controlling for thepercent poverty and racial composition of the area around the park, suggesting thelack of unobserved confounders for the outcome of interest besides poverty,racial/ethnicity structure, and their interaction.Extensive observation across five cities, three seasons, and 31neighborhoods reveal that only a fraction of target areas in neighbourhood parks arepopulated by two or more people at any given time, and in less than one-third of thepopulated areas those park users represented different racial groups, defined as atleast one white and one non-white person. Still, we identified 2123 instances wherepeople of different racial groups were co-present, suggesting that neighbourhoodparks can potentially serve as places that promote intergroup contact. While ourresults speak only to co-presence, and not necessarily “contact” asdescribed by Allport, they provide some quantitative evidence that applyinginterracial contact theory to understanding psychosocial pathways between park useand human health is worthwhile. Furthermore, our research shows that certain parks,park users, and neighbourhood characteristics make the co-presence of park usersacross racial groups—and potentially interracial contact—more orless likely. Some of these, like neighbourhood racial/ethnic and income composition,cannot be changed easily, while others, such as whether males and females andchildren are present at the same time or activities are supervised, are modifiable.To understand the impact of these empirical results on intergroup contact, we turnfirst to the modifiable factors where there are the greatest opportunities forintervention.The factor that can potentially be modified most easily is the supervisionof specific activities in parks. Supervision might take the form of a coach,referee, park staff person, or an adult who represents some level of authority andprovides a certain amount of oversight. While having full-time staff atneighbourhood parks may be financially unrealistic in all communities, volunteersincluding summer high school and college interns, graduate students and faculty, City YeUnlike the supervision of park activities, neighbourhood racial/ethnic andincome composition—which also holds a considerable influence on whetherpeople across racial groups are co-present—are not easily modifiable. Theneighbourhood parks with the most observations including people across racial groupswere located in areas of relatively low poverty and majority but not exclusivelywhite populations. The one exception was a park in Los Angeles that had a moderatepoverty rate (18.3%) and no majority racial/ethnic population butsignificant white and Latino populations. The neighbourhood parks with the highestpoverty rates and largest Black/African American populations were least likely tohave people across racial groups co-present. This does not preclude interventionsfocused on increasing the amount of supervised activities in neighbourhood parks;having supervised activities makes vigorous physical activity more likely even wheninterracial contact is unlikely. But deliberate efforts to promote interracialcontact are most likely to be successful in areas of low and moderate poverty andwith at least some racial/ethnic mix. That parks in areas with even non-majorityBlack/African-American populations are unlikely to have much interracial contactdemonstrates the high levels of white prejudice that need to be reversed. Theseresults demonstrate yet another way that the persistence and co-occurrence ofracial/ethnic and income segregation at the neighbourhood level can reinforce healthdisparities by making intergroup contact in parks unlikely .The strengths of this research include the large sample of observations fromneighbourhood parks across five different cities and different racial/ethnic andincome composition. No previous published study has analysed such a large number ofobservations as an objective measure of the co-presence of racial groups. While theparks were not selected at random, the days of the weeks and times of the day whenobservations were conducted were selected randomly, and observations were conductedover three seasons, depending upon the city, allowing for some generalizability offindings across US cities.The limitations of this analysis are important to acknowledge. Operationallydefining interracial as involving white and non-white park users likelyunderestimates the true amount of interracial activity, which could includeco-presence in park areas among non-white groups such as Asians, Blacks/AfricanAmericans, and Latinos that could also have important health implications. Thisbinary approach to defining interracial also masks important historical differencesin how Hispanic/Latinos and Asians are perceived and treated by whites as forms ofdiscrimination between minority groups (Research on intergroup contact frequently emphasizes the conditions thatfacilitate positive effects, such as the presence of authority to support bothgroups. We may be able to infer that supervision of park activities constitutes thisauthority, but we know nothing about the nature of thoseinteractions—including the amount of civility, engagement, friendship, orconflict—through observations using the conventional SOPARC measure. Furtherresearch is needed to investigate the nature of the interactions among people acrossracial groups and their impact on individual attitudes and behaviours. Adaptationsto SOPARC might include new considerations of the verbal language, body language,tone of voice, eye contact, physical contact, and other characteristics of theinteraction among park users. Or, on the model of th Century with high expectations and democratic ideals, even ifthey may not have been intended to challenge white prejudice and institutionalracism. The potential for neighbourhood parks and other outdoor, green public spacesto promote interracial contact represents an important and underappreciated pathwaylinking urban design and human health. Urban planning must meet this mandate forrealizing the promise of neighbourhood parks by more carefully theorizing,designing, maintaining and then activating these public spaces to achieve equity andhealth.This study calls on researchers across disciplines to consider more broadlythe contributions of parks to public health beyond physical activity and thepsychosocial benefits of exposure to nature. Urban parks were purposefully designedin the 19


PDGF system in the context of GBM intra- and intertumoral heterogeneity is lacking in the literature, this study aims at characterising PDGF expression in different histologically-defined GBM regions as well as investigating correlation of these genes expression with parameters related to poor prognosis. Z-score normalised expression values of PDGF subunits from multiple slices of 36 GBMs, alongside with clinical and genomic data on those GBMs patients, were compiled from Ivy Glioblastoma Atlas Project – Allen Institute for Brain Science data sets. PDGF subunits show differential expression over distinct regions of GBM and PDGF family is heterogeneously expressed among different brain lobes affected by GBM. Further, PDGF family expression correlates with bad prognosis factors: age at GBM diagnosis, Phosphatase and Tensin Homolog deletion and Isocitrate Dehydrogenase 1 mutation. These findings may aid on clinical management of GBM and development of targeted curative therapies against this devastating tumour.Glioblastoma Multiforme (GBM) is the most frequent and lethal primary brain cancer. Due to its therapeutic resistance and aggressiveness, its clinical management is challenging. Platelet-derived Growth Factor (PDGF) genes have been enrolled as drivers of this tumour progression as well as potential therapeutic targets. As detailed understanding of the expression pattern of  Therefore, efforts have been directed to the characterisation of the molecular and genetic profile of this high grade glioma and the discovery of therapeutic markers that may be the targets of a more specific and effective clinical approach3.Glioblastoma multiforme (GBM) is the most frequent and the worst type of glioma, in terms of therapeutic resistance, aggressiveness and associated short life expectancy. At present, management of GBMs is based on surgical resection followed by chemotherapy and/or radiotherapy, which is invasive, comes with unwanted side effects, and does not prevent the tumour from being significantly recurrent5. Of clinical importance, PDGF system expression and genetic profiles have been reported as prognostic factors and valid therapeutic response biomarkers for a number of cancers, such as sarcomas and breast cancer, and these properties are also been investigated on brain tumors6.In this context, Platelet-derived Growth Factors (PDGF) constitute a family of six subunits assembled into heterodimer and homodimer ligands and tyrosine kinase receptors, which are enrolled in physiological embryogenesis, haematopoiesis, neuroprotection and glial cell development besides of being identified as part of the GBM molecular panel. These genes have been described as drivers of GBM growth and metastasis, for their role in the dedifferentiation of glial cells into stem cells, the epithelial to mesenchymal transition, the activation of cancer-associated fibroblasts as well as the intratumoral stimulation of angiogenesis, lymphangiogenesis and immunosuppression7. Further, heterogeneity is a hallmark of GBM8 and is thought not to be appreciated by current diagnostic and assessment method of single biopsy and whole tissue analysis of a GBM9. This is likely to give a poor perspective of how is the tumour molecular panel configured and how its already well-described biomarkers are distributed in each single tumour block, which has a direct negative impact on the development of successful targeted therapies.For their prominent influence in GBM development, and in keeping with the perspective of molecular-based curative treatments of this tumour, PDGF genes have been suggested as GBM therapeutic targets and clinical trials have been performed with inhibitors of tyrosine kinase receptors such as Imatinib, which showed only limited beneficial effects. Treatment failure may be attributed to the lack of specificity of these inhibitors as to PDGF receptorshttp://glioblastoma.alleninstitute.org/] is a scientific initiative that investigates the expression of selected genes on different histological regions of GBM blocks, gathers genomic profile and clinical data of the correspondent patients/donors and publishes this valuable resource in the free-access online platforms of Allen Brain Atlas and Ivy GAP Clinical and Genomic Database. In the present study, PDGF system expression data is compiled from those databases with the aim to characterise these genes distribution in different histological regions of a GBM, so that more specific curative strategies against this tumour may be devised. Moreover, PDGF expression is studied regarding clinical parameters that influence life expectancy of GBM patients, to evaluate the potential role of those genes as prognostic factors in GBM.To motivate further research on GBM, the Ivy Glioblastoma Atlas Project . Z-score normalised expression values of PDGF subunits were downloaded from the Anatomic Structures RNA-Sequencing data set of the online Allen Brain Atlas . Gene expression data available in this open access atlas was obtained by RNA sequencing technique, applied to the seven GBM histological structures that were isolated by laser micro-dissection in each histological section of tumour blocks: Leading Edge, Infiltrating Tumour, Cellular Tumour, Perinecrotic Zone, Pseudopalisading Cells around Necrosis, Hyperplastic Blood Vessels in Cellular Tumour and Microvascular Proliferation. All values are described to be processed through post-hoc data normalisation followed by TbT normalisation. More detailed description on the methodology of gene expression data production is available on the Technical White Paper: Overview – 2015, accessible in glioblastoma.alleninstitute.org. Additionally, extensive clinical and genomic data of the patients recruited for the study are available in the online Ivy GAP Clinical and Genomic Database  and were gathered and tabulated.PDGFA, PDGFB, PDGFC, PDGFD, PDGFRA, PDGFRB) were analysed with regard to variables such as GBM histological structure, clinical parameters and genomic data. GraphPad Prism version 7.00 for Windows, GraphPad Software, La Jolla California USA (www.graphpad.com) was used for graphical representation and statistical analysis. Differences between two sample groups were assessed by Mann-Whitney test, whereas multiple comparisons were evaluated by Kruskal-Wallis test followed by Dunn’s Multiple Comparisons test. Values were assessed as medians and correlations were considered statistically significant if p value <0.05.Gene expression values of PDGF subunits (The datasets analysed during the current study are from the © 2015 Allen Institute for Brain Science - Ivy Glioblastoma Atlas Project, available in: glioblastoma.alleninstitute.org and ivygap.swedish.org/home.Supplementary Information


The purpose of the present systematic and critical review was to assess the findings and to identify the gaps in the literature concerning gay and bisexual fathers. A comprehensive search of relevant literature using electronic databases and reference lists for articles published until December 2016 was conducted. A total of 63 studies, spanning from 1979 to 2016, were collected. More than half of the studies were published after 2011 and the overwhelming majority were conducted in the United States. Nine themes were identified in the studies reviewed: (1) Pathways to fatherhood; (2) Motivations for fatherhood; (3) Parenting experiences and childrearing; (4) Family life and relationship quality; (5) Gender and father identities and gender-role orientation; (6) Disclosure of sexual identity; (7) Social climate; (8) Father's psychosocial adjustment; and (9) Children's psychosocial adjustment. It was found that research on gay fatherhood appears to be more heterogeneous than on lesbian motherhood, perhaps because of the variety of pathways to parenthood . Two-father families are becoming more visible in research on sexual minority parenting and gradually transforming the conceptualization of parenting in family research. Research on families headed by gay/lesbian parents started in the late 1970's, after important milestones in gender equality had been accomplished by the feminist and the gay liberation movements  and reference lists for articles published until December 2016. In addition, to identify other studies not easily accessible or less cited, expert researchers in the field were contacted. Further article searches were conducted in key reference journals in the field, namely the Journal of GLBT Family Studies and the Journal of Homosexuality. Searches included all possible combinations of the following terms: “gay,” “homosexual,” “same-gender,” “same-sex” with “father,” “parentThe main inclusion criterion was that articles reported original empirical data on gay fathers and/or children of gay fathers. A further criterion was that articles were published in peer-reviewed scientific journals until December of 2016. Exclusion criteria included review articles, studies with only lesbian parented families, and articles that simply combined lesbian-mother and gay- father families in one sample. Considering the dearth of studies about gay fatherhood, all studies including gay fathers and children of gay fathers were selected, regardless of family configuration, living arrangements, study design, or study objectives. The quality of the studies was not systematically assessed, as there was wide variation among them in terms of study designs, methods employed, sampling procedures, and, importantly, date of publication (1979–2016). However, a critical examination of the strengths and limitations of the studies was undertaken as part of the review. Our wide inclusion criteria enabled us to achieve a better overview of research on gay fathers and assess the state of the art in this sparse field.A coding scheme based on the literature was developed to systematize the information collected from the reviewed studies. Two researchers separately coded the findings from each study, and the two coding schemes were compared and discussed. Inter-coder reliability was 90%, and a final list of themes was achieved after resolving the discrepancies.A total of 63 studies that fulfilled the inclusion criteria were collected  were qualitative (including interviews and focus groups), 25 (40%) were quantitative, and only three studies employed mixed-methods. Regarding data collection, the overwhelming majority of studies were based on convenience and/or purposive samples (91%), namely through contacts within the LGBT community. Looking at the samples, the studies collectively recorded 1,837 gay or bisexual fathers with 532 sons and daughters. Samples sizes varied between 3 and 739 fathers, parenting between 36 and 179 children. Most of the samples were composed by middle-class, highly educated, and predominantly white fathers, although compared with earlier research some recent studies with larger samples were able to capture a wider diversity in fathers' sociodemographic characteristics.A variety of parenting and kinship arrangements were identified in the samples studied. Slightly over a quarter of the studies recruited participants who had become fathers via diverse routes, and 16% were adoptive gay and bisexual fathers. Older studies focused on gay or bisexual fathers who had conceived their children within the context of a heterosexual relationship before coming out as gay or bisexual. More recent studies sampled a broader array of kinship arrangements involving gay and bisexual fathers, including adoption, surrogacy, step parenting, sperm donation to lesbian couples, and co-parenting arrangements with heterosexual women  focused only on fathers themselves, although some also enquired into children's development. We were able to group the research questions into the following nine themes to better review the reported findings: (1) Pathways to fatherhood; (2) Motivations for fatherhood; (3) Parenting experiences and childrearing; (4) Family life and relationship quality; (5) Gender and father identities and gender-role orientation; (6) Disclosure of sexual identity; (7) Social climate; (8) Father's psychosocial adjustment; and (9) Children's psychosocial adjustment. Notably, only one out of the nine research themes focused on children. Next, we review research under these themes of research questions.post-heterosexual divorce families and intentional families  woman also has offered gay men opportunities for creating a family  gay men referred to similar motivations across different studies . Furthermore, in Skeen and Robinson's sample most gay fathers had grown up in families with both their mother and father present and seemed to appreciate stability of family relationships during their childhood. Further corroborating evidence was reported in Power et al.'s study , in whicIn two recent studies, gay fathers presented higher levels of subjective well-being  and a stronger sense of personal growth and purpose compared to both childless gay men and heterosexual fathers  sampled gay and bisexual fathers who had children within a prior heterosexual relationship before coming-out. In contrast, contemporary studies have shed new light on diverse pathways to parenthood for gay men, namely through adoption, surrogacy, step parenting, co-parenting, and sperm donation (Tornello and Patterson, non-traditional families grow up to identify as heterosexual, despite having increased opportunities for consideration of different sexual identities (Tasker, Compared to the many studies of lesbian mothers that have mostly focused on their children's development, very few studies of gay or bisexual fathers have (see, for example, Tasker,  Tasker, .Regarding both gay fathers' and their children's psychosocial adjustment profiles, the reviewed studies have revealed that both fathers and children were generally well-adjusted. Gay fathers have reported that their children did not show any social, psychological or emotional problems (Barrett and Tasker, Most intriguing is the way in which children of gay fathers seem to have accepted the revelation of their father's sexual identity in spite of public concerns about this. Some children already knew about their father's sexual identity, some were surprised, while for others it was a gradual process through which the overwhelming majority accepted and welcomed the revelation (Barrett and Tasker, Regarding childrearing, gay and bisexual men clearly felt the need to justify their parental quality and efficacy, even in more recent studies. Since their effectiveness and capability as parents are constantly being questioned by society, gay and bisexual fathers like lesbian mothers may feel under more pressure to report a healthier parent–child relationship compared with heterosexual parents (Crowl et al., innate desire to become parents. Gay youth and young adults have indicated a high level of desire and motivation for parenthood (Riskind and Patterson, In terms of motivations for having children, gay fathers have reported similar motivations to heterosexual fathers, and a strong seemingly family (Tornello and Patterson, Gay and bisexual fathers have suffered discrimination not only from society in general but also from other gay men (Patterson and Tornello, gay baby boom came much later and more slowly than the lesbian baby boom (Patterson, Furthermore, gay couples have faced more challenges in planning to have children in comparison to lesbian couples due to their reproductive circumstances. The literature on lesbian and gay parented families largely reflects families created through donor insemination by lesbian women. Other planned parenting arrangements such as adoption, fostering, or surrogacy require a greater effort from prospective parents (Patterson and Tornello, family needs to be further explored and discussed. Same-gender parented families and their children are often confronted with unique challenges due to social stigma (Stacey and Biblarz, degendered redefinition of fathering, the process of sexual identity revelation and the process of normalizing same-gender relationships and family life.Comparative studies were necessary to demonstrate that children raised by lesbian and gay parents are not negatively affected in their psychosocial development by their parents' sexual orientation, and that lesbian and gay men are as capable as heterosexuals in parenting and childrearing (Crowl et al., Because there are fewer studies on gay parenting, one of the main criticisms of the field is focused on the non-representativeness of samples, particularly when considering the diversity in gay father family configurations Tasker, . We arguFurthermore, the vast majority of the samples have been collected through convenience or purposive sampling, although some studies have now successfully recruited samples through assisted reproduction clinics and surrogacy and adoption agencies. Purposive and convenience sampling ought to be acknowledged as a methodological limitation on the representativeness of family configurations within gay father families. Nevertheless, despite the common use of convenience samples, our review showed that the findings were corroborated in different studies and in different countries, which is indicative of external validity.Gay father populations are somewhat small but diverse which calls for a high level of methodological sophistication to overcome the barriers in sampling. Although, there is no conclusive evidence that gay men's pathways to parenthood are more diverse than those of heterosexual parents, researchers need to explore the qualitative differences inherent to this specific, extremely complex and non-homogeneous group. In short, researcher methodologies “will need to be considerably more refined than they have tended to be over the last 50 years” (Barrett and Tasker, Another important consideration regards children's psychosocial development. Few studies have explored the psychological and social adjustment of children raised by gay and bisexual fathers. One of the core aspects of child development is attachment, specifically the role of the main caregiver as a secure base who allows children to organize their behavior, feel secure and learn about their environment (Posada et al., Gay fathers are still seen more negatively and judged more harshly than lesbian mothers because society in general perceives them as undermining traditional gender roles. Consequently, gay men are perceived as being less capable of parenting well-adjusted children than are lesbians (McLeod et al., PAC, FAC, and IL: conception of the work; PAC and FAC: acquisition of data; PAC and FAC: data analysis; PAC, FAC, FS-Q, and FT: interpretation of data; PAC, FAC, FT, FS-Q, and IL: drafting the manuscript; final approval of the version to be published; agreement to be accountable for all aspects of the work.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.