Bernard-Soulier syndrome (BSS) is a rare, autosomal recessive platelet function disorder which is commonly mistaken for idiopathic thrombocytopenic purpura (ITP).The report includes seven cases of BSS that have been diagnosed and treated as ITP for a long time.Between 2006 and 2016, data of seven BSS patients who have long been diagnosed and treated as ITP were collected and analyzed.Two patients were males and 5 were females. The patient's age range was between one day and four years at the onset of symptoms. Easy bruising, nose bleeds and mucocutaneous bleeding were the most frequent symptoms. Bleeding attacks of the gum, gastrointestinal tract and menorrhagia also occurred and in one case bleeding in the injection site of the first vaccination was reported. In 6 patients, parents were relatives and in three cases, there was a family history of low platelet counts. Variable thrombocytopenia, prolonged bleeding time (BT), and large platelets with increased bone marrow megakaryocyte were seen in all cases. Most patients were treated with steroids, Intravenous immunoglobulin (IVIG), and some with IV anti-D, Azathioprine, Danazol, Rituximab. Splenectomy was performed in one case. In supplementary tests the platelet aggregation to ristocetin was absent and GPIb expression level by flow cytometry method was lower than 10%.BSS should always be considered in differential diagnosis of ITP especially in persistent and refractory ITP. GlanzmaIn this study were collected clinical and laboratory data of 7 children less than 18 years at Seyed- al - Shohada Hospital in Isfahan, Iran since 2006 to 2016 which were diagnosed and treated as chronic ITP for a several years but due to lack of response to the treatment and clinical suspicion they were re-examined by supplementary tests and the BSS diagnosis is given to them. Demographic and general clinical data including age, sex, time of first bleeding, age of BSS diagnosis, type of bleeding signs and symptoms and family history of low platelet count, abnormal bleeding and consanguineous marriage were collected from patient files. The results of their laboratory findings included platelets count, mean platelet volume, presence of giant platelet in peripheral smear, IVY bleeding time and prothrombin time, activated partial thromboplastin time, level of fibrinogen, vWF antigen and vWF activity, FXIII screening , platelet function tests, bone marrow aspiration and biopsy and flow cytometry were recorded and analyzed.Demographic, clinical and laboratory findings and performed treatments in patients are summarized respectively, in Variable thrombocytopenia, prolonged bleeding time (BT), and large platelets with increased bone marrow megakaryocyte were present in all cases. In supplementary tests the platelet aggregation to ristocetin was absent and GPIb expression level was lower than 10% of control values . Most paIn present study we reported seven patients with Bernard-Soulier syndrome which had been treated and followed-up a  long time as ITP, but due to the lack of response to ITP treatments and clinical suspicion, they were re-examined and finally platelet aggregation tests and flow cytometric studies disclose the diagnosis. BSS is a rare, genetically inherited bleeding disorder which is due to its rarity, less consider in patients with thrombocytopenia and often misdiagnosed with ITP , 17. TheThe other clue which can help in the diagnosis of BSS and other hereditary thrombocytopenia from ITP is the presence of low platelet count in other family members , 20. ITPIn addition to clinical signs and symptoms, laboratory findings can also helpful in differentiating ITP and BSS. Prolonged bleeding time especially its inconsistency with platelet count , the pre ITP is usually a self- limited disease and majority of patients will improve within 6 months. Furthermore 20-30% of affected children may develop chronic ITP (lasting for more than 12 months). Intravenous immunoglobulin (IVIG), corticosteroids or anti-D immunoglobulin is first line therapy and splenectomy, immunosuppressive therapy or rituximab are in the second line for these patients. In recent years, thrombopoietin (TPO) receptor agonists (romiplostim and eltrombopag) are used in refractory chronic ITP . Lack of response to these therapies that are usually used for ITP treatment is one of the most important factors which should be suspected to diagnosis . In our In cconclusion based on the very close similarities of BSS with ITP, this disease should always be considered in differential diagnosis of ITP especially in persistent and refractory ITP.


In recent years, blood coagulation monitoring has become crucial to diagnosing causes of hemorrhages, developing anticoagulant drugs, assessing bleeding risk in extensive surgery procedures and dialysis, and investigating the efficacy of hemostatic therapies. In this regard, advanced technologies such as microfluidics, fluorescent microscopy, electrochemical sensing, photoacoustic detection, and micro/nano electromechanical systems (MEMS/NEMS) have been employed to develop highly accurate, robust, and cost-effective point of care (POC) devices. These devices measure electrochemical, optical, and mechanical parameters of clotting blood. Which can be correlated to light transmission/scattering, electrical impedance, and viscoelastic properties. In this regard, this paper discusses the working principles of blood coagulation monitoring, physical and sensing parameters in different technologies. In addition, we discussed the recent progress in developing nanomaterials for blood coagulation detection and treatments which opens up new area of controlling and monitoring of coagulation at the same time in the future. Moreover, commercial products, future trends/challenges in blood coagulation monitoring including novel anticoagulant therapies, multiplexed sensing platforms, and the application of artificial intelligence in diagnosis and monitoring have been included. This circulating blood is also a significant source of information on in vivo coagulation parameters, hypercoagulability, and alterations in fibrinolysis. Blood coagulation involving a blood fluid to become a solid clot is critical to stop bleeding when an injury occurs inside or outside of the body. However, abnormalities in blood coagulation such as hypercoagulability can cause excessive blood clots and vein blockage, leading to stroke  also have significant functions in blood clotting and its disorders . The therapeutic or conventional INR ranges are between 2.0 to 3.0. INR levels above 4.9 are examined as critical values and increasing the risk of bleeding. As an alternative, a narrow INR range lower than 2.0 (1.5 to 1.9) is used to reduce bleeding risks and so improve the safety profile of anticoagulation  tests for coagulation monitoring with the help of various activators, play an important role in detecting bleeding disorders and monitoring of anticoagulant drugs. Prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), Prothrombinase induced clotting time (PiCT) are the most useful tests to investigate patients with coagulopathies and drug monitoring  is desired  compared to conventional coagulation tests (40–60 min). POC INR devices can also be used in pre-hospital emergency services to provide fast and reliable results for patients suspected of coagulation factor deficiencies , effective attenuation coefficient (μeff), and the thermoacoustic efficiency (Γ) parameters  and a detection limit of 0.33 nM.One of the big advantages of the fluorescent imaging is that it enables visualization of the dynamics of blood clot, analysis of blood coagulation with different fluorescent probes, and multiplexed sensing in the blood coagulation process. Fluorescent labeling techniques have drastically improved thrombosis monitoring by using fluorophores to track clot molecules and cells for quantitative measurement of multiple targets simultaneously. Dudek et al. described clotting time assay by fluorescent probing to detect onset of fibrin clot formation with high accuracy  is one of the widely known acoustic wave devices which has been widely used in bio/chemical sensors for ethanol gas sensing  based detection has been used for real time monitoring of circulating clots, blood coagulation monitoring in tissue  from 0 to 2 IU/ml heparin in plasma and blood samples were reported.Photoacoustic imaging is based on the laser-induced acoustic vibrations in tissue which inherits both the advantages of deep penetration of acoustic waves and high contrast of optical imaging  activation leads to the blood clot, electrochemical sensing of this enzyme is also widely used for the thrombin clotting time measurement 2(PO4)12] including approximately up to 20 wt% of the inorganic phase of human bone. WH consists of Ca2+, Mg2+, and in vivo experiment . For instance, Acticoat™ produces wound dressing consists of silver nanoparticle wich can be released to the wound. Electrospun nanofibers  devices for standard diagnostic blood clotting tests such as PT/INR, and APTT tests, (2) devices which measure directly the viscoelastic properties of clotting blood. in vitro physiological and pathophysiological processes closer to in vivo conditions than other homogeneous global tests. The parameters extracted from clot growth curve are: Tlag (the time to the start of clot growth); Vi  and V (stationary) spatial clot growth rates ; and CS (the clot size at 30 min after coagulation activation). Two other important parameters may also be measured: the maximum optical density of the formed clot (D), which characterizes the clot quality, and the time of appearance of spontaneous clots in the sample (Tsp)  and machine learning, algorithms that can track multiple parameters simultaneously throughout a treatment/diagnosis and find out patient specific patterns that can aid in pinpointing proper treatment or underlying causes will become one of the biggest developments in coagulation measurement technologies in the upcoming years , studying effects of the drugs, and checking the risks in surgeries for the patients is highly demanded. Viscoelastic assessments, optical (scattering and fluorescent imaging), and electrical impedance measurement are frequently used for both evaluating pharmacological treatments and diagnosing the blood coagulation abnormalities. Recent advances in microfluidic technology has enabled the researchers to simulate the blood coagulation process in physiological conditions and study the events in the molecular level. Moreover, the fluorescent imaging and targeting different particles with fluorescent probes in microfluidic channels facilitate understanding of the interactions and origin of defects with a remote, accurate, and multiplexed manner. Other platforms like centrifugal microfluidic devices can be used for future multiplexed analysis of blood as it facilitates the separation of different blood components. Moreover, we discussed different nanostructured materials for the detection and treatment blood coagulation purposes which helps developing future monitoring and control of hemostasis at the same time in MM, AE, and OY wrote the article, read, and approved the final version of the manuscript.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.


Our objectives were (1) to systematically map the contours of the European evidence base on labour trafficking, identifying its key characteristics, coverage, gaps, strengths and weaknesses and (2) to synthesise key scientific research.We took a two-phase approach: a systematic map followed by a detailed synthesis of key scientific research evidence. Our search strategy included 15 databases, hand searches of additional journals, backwards searches, snowball searches and expert recommendations. We identified and screened 6106 records, mapped 152 and synthesised eight.Overall, the literature was limited and fragmented. Reports produced by official agencies dominated; academic authorship and peer-reviewed outputs were comparatively rare. Few publications met minimum scientific standards. Qualitative designs outweighed quantitative ones. Publications typically described trafficking’s problem profile and/or discussed interventions; they rarely assessed trafficking’s impacts or evaluated interventions. Even among the key scientific research, the quality of evidence was variable and often low. Particular weaknesses included poor methods reporting, unclear or imprecise results and conclusions not properly grounded in the data. The synthesised studies were all exploratory, also sharing other design features. Common themes identified included: poor treatment of victims; diversity of sectors affected and commonalities among victims; inadequacies of current responses; and barriers to interventions.There is a lack of high-quality studies into European labour trafficking. Methodological opacity, insufficient rigour and publication in non-indexed locations impede the identification, assessment and synthesis of evidence. Adherence to higher reporting standards would further the field’s development and particular research gaps should be addressed.The online version of this article (10.1007/s11292-017-9321-3) contains supplementary material, which is available to authorized users. Human trafficking, sometimes known as modern slaverySystematic reviews of any aspect of the trafficking literature are rare; notable exceptions have focused on trafficking’s health impacts , the predominance of purely descriptive work, methodological opacity, weak research design , sampling biases (a common shortcoming when working with hidden populations), ill-founded inferences, a tendency to be emotionally and/or politically charged and lack balance, and poor-quality statistics  , as recommended for reviews like ours that deal with broad topics and poorly-charted domains What can we learn from key scientific research evidence about the scale, nature and impacts of labour trafficking affecting Europe and on-the-ground counter-measures? (Synthesis)We defined ‘human trafficking’ in accordance with international law as:the recruitment, transportation, transfer, harbouring or receipt of persons, by means of the threat or use of force or other forms of coercion, of abduction, of fraud, of deception, of the abuse of power or of a position of vulnerability or of the giving or receiving of payments or benefits to achieve the consent of a person having control over another person, for the purpose of exploitation. Exploitation shall include, at a minimum, the exploitation of the prostitution of others or other forms of sexual exploitation, forced labour or services, slavery or practices similar to slavery, servitude or the removal of organs.  and/or within the household (domestic servitude). Our review definition of labour trafficking was that implicitly used in the UK for data collection and case monitoring : exploitation of any bodily labour except sexual services and domestic servitude. This definition covers labour in both legal and illegal industries but excludes domestic servitude. Analysis of UK trafficking data has revealed statistically significant differences between victims of domestic servitude and labour trafficking , Malta, Moldova, Monaco, Montenegro, Netherlands, Norway, Poland, Portugal, Romania, Russian Federation, San Marino, Serbia, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, Ukraine and the UK.We defined ‘Europe’ as all European Union (EU) member states, candidates and potential candidates plus additional countries not affiliated with the EU but located within the geographical territory commonly understood as Europe . The full list of countries covered is:Ethical approval was not required for this project. We registered our review prospectively in the PROSPERO International Prospective Register of Systematic Reviews  to ensure external scrutiny, draw on their diverse perspectives and experiences and maximise the review’s relevance and practical application Continental Europe DatabaseCriminal Justice DatabaseEast Europe, Central Europe DatabaseERIC (Education Resources Information Center)IBSS NCJRS  Abstracts DatabaseProquest theses and dissertationsPsycINFOPsycEXTRASCOPUSSocial Policy and PracticeSocial Science DatabaseSociological AbstractsWeb of Science.We used varied and complementary search strategies, designed to retrieve relevant publications from both the academic and grey literatures. First, we ran keyword searches of the following fifteen databases: Brown Journal of World Affairs; Criminology and Public Policy; Policing: A Journal of Policy and Practice; Health and Human Rights; International Health; and Journal of Immigrant and Minority Health. Third, we ran backwards searches on the contents of two major bibliographies we found that catalogued publications on human trafficking  indexed in the above databases. They were:The range of issues that labour trafficking encompasses and the lack of definitional consistency and clarity meant we needed broad and varied search terms. Our search terms Appendix  were desWe uploaded search results to specialist systematic review software (EPPI 4 Reviewer). Most of our results came from database searches and were returned in a format suited to screening on title and abstract; this worked as an initial sift before full text screening. Results from other sources typically lacked abstracts and so we proceeded directly to full text screening. We used the sequence of inclusion criteria detailed in Table n = 216) of the total records screened on title and abstract. The results indicated strong consistency between coders  of texts. A comparison of the exact codes assigned showed a high degree of consistency between coders (86%).We mapped the full texts using a detailed data extraction form Appendix . A singlThe systematic map highlighted the methodological weaknesses of the literature, which influenced how we targeted our synthesis. We selected studies for inclusion using the criteria in Table Eight publications met the inclusion criteria for synthesis. They varied in their design, methods and foci and included substantial qualitative material. Consequently, we designed our data extraction form Appendix  to be brGiven the anticipated nature of the literature, we chose to assess the quality of the studies based on the best methodological approach possible under the circumstances of their designs, rather than the risk of bias inherent in these designs in the first place  was the same and there was 88% overall agreement between coders. All discrepancies, none of which were larger than one point, were discussed and resolved.reported in the publications. It remains a possibility that at least some of the publications with underdeveloped or missing methods section were less methodologically weak in practice than in their reporting.We present results from the systematic map and synthesis in turn. We use examples from publications to substantiate certain findings: these were selected for context and illustrative purposes and are neither exhaustive nor intended to ‘name and shame’. Our coding was necessarily based on what was Although the empirical evidence base on labour trafficking is underdeveloped, the issue has been addressed in the context of numerous and diverse European countriesn = 105) of publications appeared from January 2009 to July 2015 (approximately 40% of the study period). During screening, we noted that certain countries’ annual reports of human trafficking originally dealt exclusively with sex trafficking: in Sweden and the Netherlands, for example, labour trafficking was first included respectively in the ninth  and multiple countries . There were striking methodological gaps in 9% of publications (n = 13) around precisely which countries were covered in all or part of their enquiries. Finally, multiple-country enquiries generally dealt with each country in isolation and international comparative analyses were rare: notable exceptions include Rijken . Reports were by far the most common publication format, accounting for 77% (n = 117) of the sample. The remainder was comprised of books or book chapters , theses  and miscellaneous formats . We noted that reports were often extremely long: the median was 84 pages (interquartile range of 112) and the longest ran to 644 pages.There were remarkably few journal articles in the sample: just 12% (n = 5340), they contributed just 25% (n = 38) of the publications mapped. Most  came instead from backwards searches, snowballing and requests to stakeholders.A related issue was publication in non-indexed locations; although the database searches yielded the vast majority of our initial results  featured the combination of a literature review and other non-scientific enquiry.Figure n = 18) of publications contained anything that met our definition of scientific research, despite the standards for this being fairly rudimentary  in design than exclusively quantitative . Although mixed methods enquiries were common , within them, qualitative methods dominated and the quantitative contribution rarely exceeded the description of basic numerical data. Again highlighting the methodological weaknesses of the overall evidence base, 11% (n = 16) of publications contained insufficient information even to establish whether the design was qualitative, quantitative or both.Far more of the publications were exclusively qualitative  and/or a discussion of interventions .n = 10) or of interventions . Five of those that assessed labour trafficking’s impacts met our criteria for scientific research, including a small but noteworthy set of studies addressing health impacts  since it limits their external validity.Second, all studies used non-random sampling. This is particularly noteworthy for those studies involving quantitative enquiries    , we made sure to pilot our codebooks, assess for inter-rater reliability (results showed good consistency) and encourage the coders to seek a second opinion where unsure. We double-coded the quality assessment of the studies in the synthesis. Some of the coding categories in the rest of the synthesis were open-ended and narrative in nature. Although unavoidable, as they are appropriate to the review of qualitative literature, such categories introduce greater subjectivity and with it a risk of bias. For validation and quality control, a second coder reviewed and commented on the main coder’s outputs here.Despite increased prioritisation of labour trafficking in European counter-trafficking policy and practice de Jonge , our resWhile publication in a journal does not guarantee quality, the peer-review process is widely seen as a quality-control measure that promotes rigour and transparency. Yet, the majority of mapped publications were reports: a format that is generally neither well-indexed nor subject to rigorous quality control. The preponderance of grey literature raises concerns about the visibility, accessibility and quality of the evidence on labour trafficking. Digestibility is another consideration: the tendency towards very lengthy publications may limit their dissemination, consumption and, ultimately, impact.The knowledge-production process was dominated by official agencies, with comparatively little input from academics and other independent parties. Of course, different authorships have different strengths. Robust outputs from practitioners, for example, can capitalise on valuable experiential knowledge and hard-to-access data and sources. In contrast, obvious advantages to academic outputs include the expectation of impartiality, rigorous methods training, strong analytical skills and research experience. The scarcity of academic research may reflect difficulties in securing data access, an oft-cited barrier to trafficking research Feingold .n = 18) of mapped publications met our basic criteria for scientific research. It seems that the problem is less that there is too little information, although there are certainly major gaps, and more that so much of it risks being lost because it exists in states not conducive to meaningful appraisal and synthesis. Many publications that fell short of the inclusion criteria for our synthesis contained material that was interesting, empirically-rich and informative   model of problem-oriented policing  merits further attention. The severity of labour trafficking was reflected both in its association with symptoms of ill health and more general accounts of extremely poor living and working conditions. While it remains to be seen whether and how the experiences and impacts of labour trafficking diverge from, say, sex trafficking, these results speak to a clear need for investment in both support services for victims of labour trafficking and targeted preventative activity. Numerous perceived barriers to intervention were highlighted, ranging from limited awareness to unmet training needs and widespread corruption. While their actual impact was not assessed, it would be useful to consider these factors when designing and evaluating interventions. The results suggest labour trafficking can affect a diverse range of legal and illegal industries. A more differentiated approach to researching and responding to labour trafficking that takes into account similarities and differences between sectors could prove useful in future. Finally, the overlaps between labour trafficking and other labour market issues  highlight the importance of situating research on and responses to labour trafficking within a broader spectrum of interrelated matters: labour trafficking should not be reduced to a criminal justice issue alone  reviews of and commentaries on other aspects to the human trafficking literature. Similar complaints about methodological opacity, lack of rigour, failure to acknowledge and account for limitations and skews in focus and methods have been heard repeatedly for over a decade , responses have rarely been evidence-based and the literature remains notoriously weak


A timely convergence of many factors, including gene‐editing technologies, machine learning, nanomedicine, and artificial intelligence, is making it tremendously exciting to be an engineer at the interface of medicine. This is further fueled by the recognition that we need bold strategies to tackle health care challenges across the world including ways to prevent autism and Alzheimer's, making medicines economical, and speeding up the process of translation. Bringing perspectives from across the spectrum of stakeholders is critical to speeding up translation. Engineers are well positioned be an enabling community in this regard. Recognizing this opportunity, the American Institute of Chemical Engineers (AIChE) and Society of Biological Engineers (SBE) launched this journal and the conference series starting in 2016. The second conference in this series was held in Minneapolis on the heels of the annual AIChE meeting from October 28–29 (Co‐chairs: Ali Khademhosseini and Efie Kokkoli), featuring exciting talks and posters covering focus areas such as stem cells/regenerative medicine, immunoengineering, regulatory aspects, biopharmaceuticals and gene/drug delivery. These are being highlighted in this issue edited by Rangaramanujam Kannan (Johns Hopkins Medicine) and Samir Mitragotri (Harvard).William Kaemmerer reviews the landscape and outlines the challenges for the field to make a bigger impact, including the need for manufacturing capacity improvements for viral vectors. Vargasan and Anselmo review the opportunities for the next generation microbe‐based therapies that are undergoing clinical translation, including genetically‐engineered microbes. Sharma, Kannan and coworkers describe an example of defining the nanoproduct and enabling the translation from lab scale to manufacturing of the first dendrimer‐drug conjugate for the systemic treatment of neuroinflammation in CNS disorders, undergoing human trials. Jarvis, Mitragotri and coworkers underscore the importance of understanding the physiological stability of ligand‐modified nanoparticles. Using microfluidic devices, they illustrate how endothelial cell contact, conjugation chemistry, and vascular flow parameters and conjugation can modify surface ligands on nanoparticle surfaces.2017 marked the year when multiple gene therapy products were successful. Knapp, Whitehead and coworkers describe the approach of delivering RNAi cocktails using lipid nanoparticles for the eventual treatment of Mantle cell lymphoma, with significant potential in aggressive tumors. Monroe, Flexner and Cui define the next challenges associated with antiretroviral therapy, not only preventing viral replication and progression to AIDS, but killing the latent virus. The potential of nanoparticle‐based systems in improving tissue penetration and targeting of the latent virus, enabling reduce drug doses at lower dosing frequency are explored. Hou, Chen and coworkers describe what could the new wave of T‐cell immunotherapy approaches where a new class of TGFβ—promoting chimeric antigen receptor T‐cells can play a key role in adoptive T‐cell therapy. They underscore the importance of understanding the interaction between these cells and the effector and regulatory T‐cells. Howsman, Hahn and coworkers describe a multivariate technique that can enable early diagnosis of autism spectrum disorders and provide biochemical understanding of the disease.In many ways, the articles in the first of the two conference special issues, and the BTM conference highlighted the rich variety and depth of perspectives bioengineers can bring to important health issues, through their collaborations with physicians, regulators and investors. We may be at the tipping point where such perspectives can accelerate translation of discoveries, human impacting health meaningfully.


The objective of this effort is to gather data to tailor interventions appropriately. Greater understanding of the correlates of socioeconomic status and obesogenic dietary behaviors was the focus of this manuscript. Using multistage sampling, women with varied education levels completed a baseline assessment in a longitudinal study of women aged 30 to 50 years. This study was conducted in low-SES areas of South King County, Washington State. This study included 530 Caucasian and 510 Hispanic women. Fruit and vegetable consumption was positively associated and soft drink consumption inversely associated with the level of education in Caucasian women. In contrast, percentage calories from fat was positively associated with the level of education in Hispanic women. In Hispanic women, level of education interacted significantly with food security in relation to percentage calories from fat, and with eating norms in relation to soft drink consumption. Neighborhood presence of ethnic food stores was associated with outcomes for Hispanic women, but for Caucasians, presence of fast food restaurants was important. Education was consistently associated with two of the three obesogenic dietary behaviors studied among Caucasian women. Education played a moderating role in the associations of food security and eating norms, independent of area level food availability, in two of three obesogenic dietary behaviors studied. However, these patterns differed for Hispanic women, indicating the need for more research into important variables to support change in Hispanic women. Women of differing ethnic groups did not respond similarly to environmental conditions and policy-relevant surroundings. These data have meaning for considering urban policy that impacts obesity levels in the population. Obesity occurs disproportionately in women of lower socioeconomic status (SES), especially in industrialized countries . The SESDietary behaviors associated with both obesity and excess energy intake include: low consumption of fruits and vegetables , high coPsychosocial factors are relevant individual-level predictors of human behavior because they are characteristics of an individual that are influenced by the social and physical environments and may help explain relationships between SES and behavior . HoweverThe price of food has been found to be one significant barrier to accessing healthy food ,11. PercPerceived personal and social norms around healthy eating and weight has been associated with dietary behaviors ,11 and oThe evidence for an association between greater access to healthy food outlets and healthier diets and lower levels of obesity is mixed ,21,22,23With respect to environmental variables, Ding and colleagues recently published a paper that evaluated the association of several individual and neighborhood activity-related variables with multiple physical activity behaviors . They syThe purpose of this paper is to explore the association of multiple individual and environmental variables and their interaction with selected psychosocial variables on obesogenic dietary behaviors in a sample of women recruited for SES diversity. First, we identified the relationship between socioeconomic status and these individual-level variables. We considered models, using an approach modified from Ding et al., 2012  to identThe Socioeconomic Status and Obesity Study (The SESO Study) enrolled Hispanic and Caucasian women in primarily low-SES areas of South King County, Washington during 2010–2012 to evaluate associations between SES and obesity. The study was designed to test three specific mediating pathways between SES and obesity including: (1) access to material resources in the neighborhood; (2) the psychosocial context; and (3) the stress process ,28. Thesn = 143 block-groups). These methods are detailed elsewhere [Women were recruited into the SESO study using population-based sampling methods where the first stage involved selecting U.S. Census block-groups within Seattle with a high representation of Hispanics, low education and low income as determined by the 2000 U.S. Census , 4% with some college through post-bachelor course or training, and 50% with a Master’s or doctoral or professional degree were randomly sampled to join the study, due to the larger numbers of eligible Caucasian women. Socioeconomic status. For this analysis, we defined socioeconomic status at the individual-level by years of education in five categories for Caucasian women  and six categories for Hispanic women (did not go to school or grade school (1–4 years), grade school (5–8 years), some high school, high school diploma or GED, vocational school/some college/Associates degree, college graduate/Baccalaureate degree or higher). These differences in coding were due to the large differences in distribution between Hispanic and Caucasian women in this sample. Education was treated as a continuous variable.Unaffordability of food. Perceptions of fruit and vegetable affordability, and the affordability of food in general, were measured with a modified version of Disball and colleagues’  instrumePerceived food insecurity. Food insecurity was measured and scored according to the United States Department of Agriculture food security adult module . ParticiPerceived availability of grocery stores/areas for exercise. Availability of grocery markets and areas designed for exercise were each assessed with one item modified from the Neighborhood Environment Walkability Scale (NEWS) . ParticiEating Norms. Measures of eating norms were created based on the work of Christakis, Fowler and colleagues  that invWeight-related Norms. Weight norms were assessed based on published work by Christakis, Fowler and colleagues . Two queFood management. Food management was measured according to Dickin and colleague’s  six-itemObjective environment: availability of neighborhood food outlets. Neighborhood was defined by geocoding the participants address and forming a concentric circle with a radius of 0.5 miles. The density of food outlets were enumerated within this buffer using geospatial data from University of Washington’s Urban Form Laboratory. Geocoded addresses of food establishments were based on food permit data from the Seattle King County Health Department and were verified via cross-checking with online business directories. Categorizations of food outlets extracted included: food stores , ethnic grocery stores, and fast food or “quick-serve” restaurants  ,34.regular or diet)?); and (3) % energy consumed as fat from the 24-h dietary recalls [We identified three obesogenic behaviors as dependent measures for these analyses. They included: (1) daily fruit and vegetable consumption , a singl recalls  as a nutParticipants provided demographic information including ethnicity (Hispanic/non-Hispanic), highest level of education completed, age at baseline data collection, level of acculturation, marital status, highest level of education achieved, total family income, and employment status.Descriptive and summary statistics were calculated for participants’ demographic characteristics. Descriptive statistics were calculated on the three dependent variables including percentage calories consumed from fat, daily fruit and vegetable consumption, and soft drink consumption, as well as all associated variables, by education and ethnicity.Multi-level linear regression models with a random block group effect were used to estimate associations between SES  and dietary behaviors  to account for participant clustering in neighborhoods . Each mon = 6 Hispanic and n = 10 Caucasian) and women with missing data for the variables of interest were excluded from the sample for analyses (n = 1002 (509 Hispanic and 493 Caucasian). We calculated a response rate of 46% using methods articulated from AAPOR [Pregnant women  and consumed more soft drinks (p < 0.001). The same pattern of behaviors did not hold true for Hispanic women. Hispanic women reported higher levels of fat consumption in the higher three education categories, with significant differences across education level (p = 0.01).p < 0.01). Food management, fruit/vegetable affordability, and food affordability judgments differed across education level for Caucasians (p’s < 0.001). In all cases, higher SES Caucasians reported less obesogenic psychosocial association variables. Finally, weight and eating norms differed across education levels for Caucasian women (p’s < 0.001), with higher weight norms for lower education levels and lower eating norms for lower education levels. For Hispanic women, food unaffordability, food management, and grocery/activity access scores differed across education levels (p’s < 0.001) and so did social norms for eating (p’s < 0.001), in the same direction as for Caucasian women.We set out to test interactions between environmental and individual-level variables relevant to obesity in Caucasian and Hispanic women. Education is clearly related to fruit and vegetable consumption, mostly for Caucasian women. For Caucasian women, the effect of education was in the hypothesized direction across the five categories, showing an inverse relationship between education and healthy eating. For Hispanic women, the relationship was more complex and not consistent across dependent variables. This finding has been noted in the literature, as Hispanic women’s education levels do not relate consistently and linearly to their BMI . FurtherThe modeling of psychosocial variables, neighborhood-level variables, and interactions helped us to identify patterns of findings that might lead to modifiable relationships of elements of behavior and environment with obesogenic dietary behaviors. Again, the patterns differed by ethnicity. For Caucasian women, eating norms and food management levels, and to a lesser extent, food insecurity and food affordability perceptions were all related to obesogenic behaviors. For Hispanic women, eating norms was the only consistent psychosocial variable related to obesogenic behaviors. One possible explanation for these patterns is that the levels of some of these variables were different between the two cohorts. In general, Hispanic women had different food insecurity ratings and lower food management and affordability ratings, possibly pushing Hispanic women into a part of the distribution for these variables that is simply underserved and therefore, does not vary enough to see differences.Weak or no associations were observed between many neighborhood-level variables and obesogenic dietary variables. There were two consistent exceptions to this general finding: The association between the presence of ethnic food stores and fruit and vegetable consumption for Hispanic women and the positive association between presence of fast food restaurants and both percentage calories from fat and soft drink consumption in Caucasians. Regarding the finding in Hispanic women, this could be of critical importance for future studies that attempt to increase fruit and vegetable consumption among Hispanic women, who might need access to fruits and vegetables that they recognize and feel comfortable with. There is some evidence for the presence of food outlet subtypes as differently related to different groups of adults and children’s behaviors  and so tThis study has several design qualities that limit the generalizability of the findings. First, the Hispanic and Caucasian women were sampled from the same neighborhoods, and so the interpretation of the findings is limited to women who reside in more integrated neighborhoods. All neighborhoods in Seattle are not so integrated, and the extent of integration has been related to other health and risk outcomes in previous research ,42. FutuThis study does include strengths that enhance the value of its findings. It is unusual in that it was explicitly designed to include women of all SES levels, to enable the evaluation of education on obesity related variables. Therefore, we were able to analyze these data across educational levels with some samples in each important cell, although the sizes did get small in some of the lower SES levels for non-Hispanic white women. It is a sample selected based on household location and not completely through convenience or volunteering, thus increasing the nonbiased selection of participants. Finally, it includes cohorts of two different ethnic groups, thereby increasing our ability to understand the role of SES in women from many diverse backgrounds.In summary, education is consistently associated with two of the three obesogenic dietary behaviors studied among Caucasian women and for these women, education plays a moderating role in the associations of food security and eating norms, independent of area level food availability, in two of three obesogenic dietary behaviors studied. For Hispanic women, there were a few individual variables that related to obesogenic dietary behaviors, but the neighborhood presence of ethnic food stores consistently related to these behaviors and could be a direction for future investigation and public health practice. Considering these findings when creating or modifying policies related to area-level obesogenic policies, laws, and regulations makes sense in the context of urban planning.


To evaluate body water volumes and cardiac output in each trimester of pregnancies complicated with hypertension and/or poor fetal growth, relative to uncomplicated pregnancy.In this semi-longitudinal cohort study, a standardised non-invasive maternal hemodynamics assessment in first, second or third trimester was performed in 1068 women with uncomplicated pregnancy (UP), 75 with early onset (EPE) and 117 with late onset preeclampsia (LPE), 139 with gestational hypertension (GH), 129 with small for gestational age (SGA) neonates and 43 with essential hypertension (EH). Women with hypertension or SGA were included prior to onset of symptoms or at diagnosis of disease; 46% of women (758/1631) were assessed in ≥ 2 trimesters. Impedance cardiography and spectrum analysis were used to measure cardiac output, total body water (TBW), extracellular (ECW) and intracellular water (ICW). A linear mixed model was used for inter-trimestrial comparison of parity-, age- and BMI-corrected values within and between groups.For all pregnancies, TBW is higher in each consecutive trimester, mainly due to increasing fraction of ECW (ECW%). Compared to first trimester UP, ECW and ECW% are higher in EPE whereas TBW, ECW and ICW are lower in SGA. Compared to inter-trimestrial differences in UP, abnormal changes for body water volumes are observed in GH, EPE and LPE and for CO in EPE and LPE. Changes in EH are not different from UP.This study is the first to show that concomitant gestational changes of ECW and CO are different from UP already in preclinical stages of pregnancies complicated with hypertension and/or poor fetal growth, except EH. This finding highlights the relevance of early gestational assessment of maternal body fluid status in pregnancies at risk for hypertension or poor fetal growth. A woman’s total body water volume is estimated at around 55% of her body weight. Two third of this volume is intracellular fluid and the remaining third is located extracellularly in the intravascular, interstitial and transcellular compartments . All fluA rise of maternal cardiac output and plasma volume, in association with a generalised vasodilation and reduced total peripheral resistance, are well known features of normal gestational physiology. It is also known that pregnancies, complicated with hypertension or poor fetal growth, present with inadequate maternal cardiovascular adaptations.Associations between maternal cardiac function and volume homeostasis have been reported in both normotensive and hypertensive pregnant women , and abnEthical approval by the Comité Medische Ethiek Ziekenhuis Oost Limburg, Genk was obtained before study onset  and informed consent was obtained before inclusion. Women with apparently normotensive singleton pregnancies at random gestational ages, presenting at the obstetric ultrasound scanning clinic of Ziekenhuis Oost-Limburg Genk, Belgium, as well as women referred to the Maternal-Feal-Medicine Department of the same hospital with suspected new-onset hypertension in ambulatory or hospital setting, were invited to participate in an observational study on maternal cardiovascular functioning between 2011–2017, as part of the ongoing Hasselt University Research Project of Maternal Venous Hemodynamics. When included in first or second trimester, women were asked for repeat measurements in consecutive trimesters. Three periods of assessment were considered in the statistical analysis: women included in the first trimester (< 15 weeks), second trimester (15+0 to 27+6 weeks) and third trimester (≥ 28 weeks). Per trimester, only 1 measurement per pregnancy was included. At birth, data on gestational outcome was categorized according to the criteria revised by the International Society for Studies of Hypertension in Pregnancy (ISSHP) . The catBioimpedance cardiography and spectrum analaysis were applied according to a standardized protocol with known inter- and intra-observer correlations as reported in previous publications , 31, in The Non-Invasive Continuous Cardiac Output Monitor  was used for automated blood pressure measurements on the right arm and with an appropriate cuff width at standard time points as reported . ICG anaThe body composition and fluid balance were measured by a multiple frequency bioelectrical impedance analyser  in supine position with stretched arms and legs, without socks or shoes [An independent t-test at 5% significance level was used for intergroup comparison of continuous demographic data. Chi-square test was used for categorical demographic variables. Normality was checked via Shapiro-Wilk. Data were presented as mean ± SD or n (%).Linear Mixed Models for repeated measurements were used to calculate differences in cardiovascular and volume parameters between UP and EPE/LPE/GH/EH/SGA. A random patient effect was used to correct for the correlation between trimestrial measurements of a pregnancy, due to intrasubject repeated measures. Fixed effects of trimester and outcome, as well as their interaction term were specified. The fixed effects structure was simplified by using a significance level of 5%. Analyses were done in SAS . A correction for demographical influences  on the cardiovascular parameters was implemented in the linear mixed model. Corrections for multiple testing were not implemented.In the ongoing Hasselt University Research Project of Maternal Venous Hemodynamics, a total of 1763 women were assessed between 2011–2017, and categorized according to gestational outcome as shown in the flow chart . In thesPatient demographics are shown in 2). CO is higher in each consecutive trimester of UP, and this is not observed in any of the other groups. A similar trend is observed for CI in EPE, LPE and GH, but not in GH and SGA. An overall lack of rise in CO or CI is observed in EPE and LPE.Detailed information on patient’s demographics and impedance measurements of volumes and cardiac output are attached as supplement in The most important findings of this study are that (1) all pregnancies show an increase of body water volumes, irrespective of outcome and body composition, and (2) typical features of abnormal volume regulation are observed in pregnancies with abnormal outcome, such as a persistently low fraction of TBW, ECW and ICW in SGA pregnancies, a lack of CO increase in EPE and LPE, and severely, moderately and mildly discrepant evolutions of CO and ECW MoM values in EPE, LPE and GH respectively. No differences are found between UP and EH.The strengths of this study are the large numbers of included subjects and assessments, all performed according to a rigid standard protocol , and theSeveral reports mention an increase of body water volume in every pregnant woman, a process in which the relative rise of ECW rise is larger than of ICW , 24. TheOur data show that first trimester TBW volume is abnormally low in SGA pregnancies. This observation is in line with other reports on plasma volume, a component of TBW, that repeatedly has been reported lower in SGA pregnancies , 38. ThiReduced plasma volume expansion in EPE has been reported , as wellAnother important observation of this study is the striking similarity of body water volumes and cardiac output in every gestational trimester of UP and EH without superimposed PE. As such, body water homeostasis may be an important predictive discriminator between normal and abnormal outcome of pregnancies in women with essential hypertension. This observation needs confirmation from more targeted research.Finally, our data add to the growing body of evidence that, despite the reported limitations, the bio-impedance technology is a very simple method to assess body volume changes at every stage of pregnancy, which offers perspectives towards a potentially valuable and easily applicable technology in screening and management of GHD.We conclude from our observations presented in this report that body water volume increases in every pregnant woman, starting from first trimester abnormal values in EPE and SGA, or becoming abnormal in later stages of LPE and GH. BIA is a useful and easy to perform method to evaluate these body volume changes. These data invite to further explore BIA volume measurements as a new tool in screening and management of GHD and/or SGA.S1 Table(PDF)Click here for additional data file.


Previous studies on the effects of greenspace exposure on health are largely based on static contextual units, such as residential neighborhoods, and other administrative units. They tend to ignore the spatiotemporal dynamics of individual daily greenspace exposure and the mediating effects of specific activity type . Therefore, this study examines individual daily greenspace exposure while taking into account people’s daily mobility and the mediating role of physical activity between greenspace exposure and health. Specifically, using survey data collected in Guangzhou, China, and high-resolution remote sensing images, individual activity space for a weekday is delineated and used to measure participants’ daily greenspace exposure. Structural equation modeling is then applied to analyze the direct effects of individual daily greenspace exposure on health and its indirect effects through the mediating variable of physical activity. The results show that daily greenspace exposure directly influences individual health and also indirectly affects participants’ health status through physical activity. With respect to the total effects, daily greenspace exposure helps improve participants’ mental health and contributes to promoting their social health. It also helps improve participants’ physical health, although to a lesser extent. In general, the higher the daily greenspace exposure, the higher the physical activity level and the better the overall health . Economic growth and urbanization can bring better living conditions, various opportunities , and challenges . In the process, however, environmental problems are becoming increasingly serious, including a dramatic decrease in greenspace. Many urban dwellers today do not have easy access to and contact with various forms of greenspace , including natural and artificial greenspace, which has negative impacts on human health and sustainable development in urban areas . A reporUrban greenspace has been associated with a wide range of health benefits. Decades of research has examined the direct effects of greenspace on people’s physical and mental health based on fixed contextual or areal units . Some researchers suggested that residential green environment can help to regulate microclimate , purify Previous research mainly focuses on the direct effects of greenspace on physical and mental health. Recently, the literature on greenspace and individual health has expanded to consider its effects on people’s physical activity. Although urban inhabitants typically benefit from superior access to medical technology, health care, and other services, these benefits are offset by their sedentary lifestyle and lack of physical activity ,29. InadHowever, previous studies have rarely paid attention to the influence of daily greenspace exposure on social health and social interaction. Generally, the above studies analyzed the effects of greenspace on one or two dimension(s) of health  through the mediator of physical activity, but the different effects of greenspace on different dimensions of health were ignored. Thus, this paper focuses on the direct and indirect effects of objectively measured greenspace on three dimensions of health , and compares the different effects of greenspace on these health dimensions. Considering the definition of “greenspace” in previous studies that only includes “vegetation coverage” as too narrow, this paper extends the concept of “greenspace” to the broader notion of “greenspace exposure” by adding an activity dimension according to the concept of “environmental exposure science.” Greenspace exposure in this study encompasses the quantity, quality, and accessibility of greenspace for a person to meet the needs for a better urban environment and recreational activities in the actual geographic areas of his or her daily life. Among the indicators of greenspace selected in this paper, green vegetation contributes to improving the natural environment. Physical activity sites can provide more structured environments for social interactions and physical activity . In addiIn addition, some qualitative and quantitative studies examined the relationship between the environment and health using fixed geographic or contextual units based on buffer areas around individuals’ residences ,37,38 orBased on such considerations, this study takes advantage of the methods of human mobility research and constructs a conceptual framework for modeling the health benefit of individual daily greenspace exposure. A structural equation model is used to analyze the causal mechanisms among daily greenspace exposure, physical activity, and individual health based on questionnaire survey data and objectively measured data . Meanwhile, individual activity space is considered when analyzing how greenspace exposure influence people’s health behaviors and outcomes. Specifically, the article seeks to address the following questions: Is there any relationship among daily greenspace exposure, physical activity and individual health from the perspective of human mobility and the uncertain geographic context problem? Does individual daily greenspace exposure directly affect health, and does it also indirectly affect health through the mediating role of physical activity? How do specific elements of daily greenspace exposure and physical activity influence the different dimensions of individual health? This paper seeks to enrich and deepen our knowledge of health geography and spatiotemporal behaviors. Moreover, it has theoretical and practical value for urban planning, informing greenspace construction programs and strategies for achieving global environmental health. Recent studies have examined the relationship among greenspace, physical activity and health, indicating that physical activity may play a partly intermediate role in this relationship ,53,54. T2. The urbanization rate of Guangzhou reached 86.14% with a permanent population of about 14.5 million and a gross domestic product (GDP) of 2150.315 billion RMB in 2017 [2 in area, and they include historical blocks, danwei communities, commercial housing, affordable housing and informal housing. These residential blocks are located in seven of the central, transitional and marginal districts of the city, which include Liwan, Yuexiu, Tianhe, Haizhu, Baiyun, Panyu and Huangpu Districts , and supported by grants from the National Natural Science Foundation of China (41522104), and all participants gave informed consent. Respondents in the survey were proportionally selected from the adult residents in the 11 selected residential blocks in Guangzhou based on the size of the permanent population of each block reported in the Sixth National Census of China. Each questionnaire was administered by a trained interviewer in a face-to-face interview with a participant, and it took about 30–40 min to fill out. A total of 1003 valid and usable questionnaires were finally obtained. Individual-level data items solicited through the questionnaires include personal characteristic (demographic and socioeconomic characteristics), residential and employment information, physical activity, self-reported health conditions, social interactions, and activity logs. (i) Demographic and socioeconomic characteristics—Demographic indicators solicited through the questionnaires include gender, age, and marital status. The proportions of males and females in the sample are quite balanced. The proportion of young people (between the age of 19 and 44) is noticeably higher . In addition, education level and personal monthly income, which are highly related to socioeconomic status, were also obtained from the participants.(ii) Physical activity indicators—Physical activity level was assessed mainly by their duration, frequency, and intensity ,37. The MOS 36-Item Short-Form Health Survey  [World Health Organization’s Five Well-Being Indexes (WHO-5) [Social Cohesion and Trust Scale [Social Wellbeing Scale [Social Support List-Interactions (SSL-I) [(iii) Health indicators—The definition of health by the WHO in 1948 is “A state of complete physical, mental and social well-being and not merely the absence of disease or infirmity.” Thus, this study focuses on the three dimensions of physical health, mental health, and social health . Physica, and 7) , which h (WHO-5) , which hst Scale , Social ng Scale  and Soci (SSL-I) ), and th (SSL-I) ,65. All Activity space, which is the area containing all locations where an individual undertakes his or her daily activities ,66, is uGreenspace data used in this study were automatically extracted and calculated from remote sensing images covering Guangzhou in November 2015 using ENVI 5.2  and ArcGIS 10.3 . These remote sensing images, with a spatial resolution of 2 m, are obtained from the Gao Fen-1 (GF-1) satellite, the first satellite of China’s High-Resolution Earth Observation System (CHEOS). Using these remote sensing images, three objective indicators  used in previous studies ,37 were nth activity space buffer, and so on; nth activity space, and so on; (1) Vegetation coverage: This is the time-weighted proportion of the area of vegetation that is within the activity space buffers of a participant.nth activity space buffer, and so on; (2) Physical activity site coverage: This is the time-weighted proportion of the area of physical activity sites  that can be accessed within a participant’s activity space buffers.nth activity site to its nearest greenspace in the nth activity space buffer, and so on; n is the number of activity space buffer. These three greenspace exposure indicators were used in this study to capture various forms of greenspace exposure for the participants. (3) Accessibility to the nearest greenspace: This is the average of the sum of the distances between each activity site of a participant to the nearest greenspace in the respective activity space buffers.As a powerful method for examining the causal relationships among a set of variables, structural equation modeling has been widely used in the literature of health geography ,73. It cBefore constructing the structural equation model (SEM), the reliability and validity of the variables were verified by using Cronbach’s Alpha and factor analysis in order to make the model results more convincing. The results suggest that variables selected in this study have a relatively high reliability (Cronbach’s Alpha is 0.726 (≥0.700)) and validity (Kaiser-Meyer-Olkin (KMO) is 0.779 (>0.700) and Sig. is 0.000 (<0.05)). Given that this study focuses mainly on the direct effects of greenspace exposure on health and the indirect effects of greenspace exposure on health through physical activity, personal characteristics are taken mainly as control variables in the SEM . Greenspp < 0.05). As shown in p > 0.05; H1 and H7 are invalid). Thus, the effect of greenspace exposure on physical health and the effect of physical activity on social health are both considered 0.00 in further analysis. The specific effect relationships between the latent variables are shown in The SEM is constructed and revised using AMOS 21.0. It is found that the SEM presented in The correlation coefficients between greenspace exposure and its measured variables  are 0.70, 0.87 and 0.08 respectively , suggestp < 0.01)  are 0.83, 0.14, and 0.82, respectively , suggest < 0.01) . It is s < 0.01) . Physica < 0.01) . HoweverAs shown in The total effects (direct effects + indirect effects) of daily greenspace exposure on physical health, mental health, and social health are 0.018, 0.228, and 0.17, respectively , all of Among the three dimensions of health, daily greenspace exposure level has the most obvious effect on mental health. This indicates that daily greenspace exposure plays a primary role in improving participants’ mental health, likely through an increase in the quantity and quality of greenspace in their activity space. Specifically, people could release stress and tension, mitigate negative emotions and create a relaxed and pleasant mental state through frequent contact with greenspace. Although daily greenspace exposure has the lowest indirect effect on social health, its total effect on social health is second, due to its higher direct effect. This suggests that natural environment provides more opportunities for people to engage in physical activity with families and neighbors, which promotes interpersonal relationships, fosters social interactions, strengthens community cohesion, and enhances individual well-being. Notably, daily greenspace exposure has the lowest total effect on physical health, due to the fact that its direct effect on physical health is the lowest. The main reason resulting in its lowest direct effect on physical health is that this study only considers the coverage of greenspace and ignores other factors, such as the diversity of plant species, landscaping design and layout, and so on. In contrast, the indirect effect of daily greenspace exposure on physical health is higher, indicating that promoting physical health through physical activity may yield better outcomes than relying on the direct effects. For instance, greenspace with high accessibility and attractive surroundings can help stimulate people’s interest in physical activity, which in turn reduces the incidence of diseases and helps maintain health through higher levels of physical activity. Urban greenspace planning is a crucial issue in the context of rapid urbanization and sustainable development, as greenspace helps to support physical activity and improve individual health outcomes. Recent research has underlined the importance of planning and management of greenspace, especially in megacities, due to the huge populations and scarcity of space ,77,78.Urban greenspace exposure makes a great contribution to counteracting people’s sedentary lifestyle, increasing their physical activity and improving their health status. However, there is a general underestimation of the value of daily greenspace exposure in urban planning and park management in China. Therefore, conducting research in this area and applying the findings to improve the planning and design of greenspace in urban areas has great significance to urban sustainability and healthy living. In order to further promote the beneficial influence of greenspace on health outcomes, residents should be advised to heighten their environmental protection consciousness and increase their utilization rate of greenspace. In addition, urban planners should take more measures in constructing greenspace and building ecological cities so as to increase people’s greenspace exposure. These specific measures include increasing the proportion of greenspace in urban areas, and promoting supporting facilities and services like seats and outdoor exercise or fitness equipment. Finally, relevant government departments should establish and improve laws and regulations to protect public health through constructing a green environment for promoting health and formulating and implementing health education action plan. One limitation of this research is that greenspace exposure indicators included only objectively measured variables, which precluded the ability to draw conclusions about the influence of subjective assessment of greenspace exposure on health. Subjective assessment should be coupled with objectively measured data in future studies, such as the evaluation of the quantity and quality of one’s activity space, the utilization rate of greenspace and subjective assessment of sanitary condition. Another limitation of this study relates to the survey of mental health, which only reflects the overall state of mind in the recent period. However, mental state  and emotions  will also change momentarily depending on different events that people experience in their daily life. Future research may shed new light on the moderating effects of greenspace exposure on changes in people’s mental states that are affected by the stressful events or daily emergencies they experience. For instance, respondents may be asked to wear global positioning systems (GPS) to track their movement patterns in a more objective manner and list all activities they are engaged in and how they felt during each activity through responding to real-time prompts based on ecological momentary assessment (EMA) methods. In future work, conducting studies with these additional components has potential to help improve research results. The objective of this study is to examine the relationship between daily greenspace exposure and individual health from the point of view of human mobility and the uncertain geographic context problem. The results indicate that daily greenspace exposure directly influences participants’ health and indirectly affects their health status through the mediating effect of physical activity. Specifically, the direct effect of daily greenspace exposure on mental health is more significant than its direct effect on social health, while such direct effect on physical health is not obvious. The indirect effect of daily greenspace exposure on mental health is similar to that on physical health, but such indirect effect on social health is not remarkable. In addition, the total effect of daily greenspace exposure on mental health is more obvious than its total effect on social health. However, the total effect of daily greenspace exposure on physical health is not significant. On the whole, a higher level of individual daily greenspace exposure in the study area is related to better physical activity and overall health. Daily greenspace exposure primarily helps to improve participants’ mental health and relieve their negative feelings, and then promote their social health and strengthen social cohesion, and enhance their physical health and reduce the incidence of diseases to a lesser extent.


What are consensus components of a framework for humanitarian surgical response in modern conflict zones?This survey study using responses from 35 participants in the Stanford Humanitarian Surgical Response in Conflict Working Group suggests that humanitarian responses include both care of traumatic injury and emergency surgical needs of the population. Lessons from civilian and military trauma systems as well as humanitarian settings were translated into a tiered continuum of response from patient presentation through rehabilitation.Evidence suggests that modern trauma systems save lives but providing this standard of care in insecure conflict settings places new burdens on humanitarian systems; the framework presented herein integrates advances in surgical care to these environments. Armed conflict in the 21st century poses new challenges to a humanitarian surgical response, including changing security requirements, access to patients, and communities in need, limited deployable surgical assets, resource constraints, and the requirement to address both traumatic injuries as well as emergency surgical needs of the population. At the same time, recent improvements in trauma care and systems have reduced injury-related mortality. This combination of new challenges and medical capabilities warrants reconsideration of long-standing humanitarian surgery protocols.To describe a consensus framework for surgical care designed to respond to this emerging need.An international group of 35 representatives from humanitarian agencies, US military, and academic trauma programs was invited to the Stanford Humanitarian Surgical Response in Conflict Working Group to engage in a structured process to review extant trauma protocols and make recommendations for revision.The working group’s method adapted core elements of a modified Delphi process combined with consensus development conference from August 3 to August 5, 2018.Lessons from civilian and military trauma systems as well as recent battlefield experiences in humanitarian settings were integrated into a tiered continuum of response from point of injury through rehabilitation. The framework addresses the security and medical requirements as well as ethical and legal principles that guide humanitarian action. The consensus framework includes trained, lay first responders; far-forward resuscitation/stabilization centers; rapid damage control surgical access; and definitive care facilities. The system also includes nontrauma surgical care, injury prevention, quality improvement, data collection, and predeployment training requirements.Evidence suggests that modern trauma systems save lives. However, the requirements of providing this standard of care in insecure conflict settings places new burdens on humanitarian systems that must provide both emergency and trauma surgical care. This consensus framework integrates advances in trauma care and surgical systems in response to a changing security environment. It is possible to reduce disparities and improve the standard of care in these settings. This study provides consensus guidelines on humanitarian surgical response formulated by representatives from international government and nongovernmental organizations for military and civilian populations in combat sites. This unprecedented battlefield survival was the result of a purposeful commitment to coordinate advances in trauma care with immediate frontline intervention and rapid transport to facilities with escalating surgical capabilities. The survival rate of individuals after battlefield injury has more than doubled when compared with the Vietnam War.2 Advances were both technical  and systems-based .3 An integrated continuum of care from the point of injury (POI) through rehabilitation included the following levels:An essential component of this improved trauma capability has been the rapid stabilization of the injured and their managed evacuation through a tiered system of care, each with escalating and increasingly specialized medical capabilities. The US military’s commitment to such a system took the form of the Joint Trauma System, which coupled rapid tiered response with data registries, ongoing performance improvement, and the development and implementation of clinical practice guidelines.Role 1–tactical combat casualty care, in which frontline personnel perform hemorrhage control, resuscitation, and airway protection measures proximate to the POI;Role 2–time and distance gaps from the POI to definitive surgical care, which are bridged via forward surgical teams capable of providing damage control resuscitation and surgery before rapid evacuation;Role 3–combat support hospitals, which provide the highest level of care in the conflict zone. After stabilization, casualties are moved out of the country to definitive care facilities; andRole 4–well-resourced definitive care facilities, which are located away from the conflict zone.4 In contrast, the humanitarian response in conflict settings not only has to provide trauma care but also emergency surgical care to the affected population. Providing humanitarian care in insecure environments poses major pragmatic and ethical challenges. Protracted intrastate conflicts that use siege warfare, the use of explosive weapons in densely populated urban settings, and the targeting of health facilities and other essential infrastructure  can cause high levels of civilian mortality.6 This context also poses obstacles to the establishment of advanced trauma systems by humanitarian actors. Of particular concern are the positioning of humanitarian medical personnel close to the front lines, the control of evacuation pathways for casualties, secure supply chains, adequate human resources, and most fundamentally, the safety of patients and humanitarian personnel.The successes of military trauma systems demonstrate the potential of advanced trauma management, and many of these advances have been successfully adopted into civilian trauma settings.7 Partly in response to this event, in 2013, the World Health Organization published what is called the Blue Book, a set of guidelines that established a framework of overarching standards for teams operating in sudden-onset disasters.8 Similar guidelines for the humanitarian response to conflict do not currently exist. The health response to the Battle of Mosul, Iraq, in 2016-2017 raised serious concerns regarding the deployment of humanitarian medical personnel under the direct protection of Iraqi security forces.9 The Mosul experience and the subsequent fighting in Raqqa, Syria, also raised concerns regarding military-civilian coordination and the responsibilities of militaries for the evacuation and care of civilian casualties.Several events have underscored the need to revise humanitarian protocols. The 2010 earthquake in Haiti exposed the inadequate training and coordination of emergency medical personnel, which resulted in care that has been described as “medically shameful.”10 humanitarian organizations increasingly have become the major providers of medical care in areas of violent conflict. Humanitarian response to conflict is dissimilar from disaster and current World Health Organization Blue Book guidelines do not give adequate guidance. Unarmed humanitarian medical groups must operate in insecure environments and personnel must also adhere to the principles of humanity, neutrality, impartiality, and independence—requirements that place special demands on humanitarian systems.12 Civilian population needs differ from those of military personnel. Moreover, the military focus on frontline stabilization and rapid evacuation of patients is particularly difficult to implement in humanitarian settings. Unless these challenges are addressed, these dynamics can lead to high rates of preventable death and disability.While responsibility for frontline care of the wounded should rest first with the parties to the conflict,In response to these concerns, the Stanford Humanitarian Surgical Response in Conflict Working Group was established on March 20, 2018, to reevaluate the humanitarian medical response to conflict. The Group’s deliberations culminated in an in-person convening from August 3 to August 5, 2018, which produced a consensus framework for humanitarian trauma systems in conflict settings. The framework’s goal was to translate the progress made by trauma systems to the pragmatic realities of humanitarian medical provision in areas of violent conflict.Thirty-five participants were invited to the Stanford Humanitarian Surgical Response in Conflict Working Group. Contributors were selected on the basis of sector expertise, organization leadership, publication record in trauma care, trauma systems development, and humanitarian surgical care. This multinational group included senior representatives from civilian and military trauma systems, international humanitarian nongovernmental organizations, such as Médecins Sans Frontières, Samaritan’s Purse, International Committee of the Red Cross, World Health Organization, and academic trauma system and research centers. The group’s charge was to design a consensus framework for a new model for surgical humanitarian response, translating advances in combat casualty care to the modern humanitarian context. The first iteration of this framework was designed for protracted urban conflict, such as that seen in Syria and Iraq, with the understanding that this schema could be adapted to different humanitarian contexts in the future.13 Group members received a compilation of current protocols, resource lists, and relevant health services research on humanitarian and military trauma care in conflict settings. Documents were circulated electronically for feedback and voting. At each stage, input was synthesized and incorporated into revised documents that were recirculated for review. Members had the opportunity to comment, dissent, and revise their opinion after viewing the blinded results of others’ feedback. In addition, the group organizer prepared a final set of documents based on all feedback that served as the basis for discussion at the in-person convening.The working group’s process incorporated core elements of a modified Delphi process combined with formal consensus development methods with iterative rounds of inclusive, anonymized input leading to a transparent derivation of final decisions.14 The Stanford University Institutional Review Board determined that this research does not involve human subjects and therefore waived the need for informed consent.From August 3 to 5, 2018, a 3-day, in-person convening occurred at Stanford University, Stanford, California. The proceedings consisted of presentations on the perspectives and practices of the represented organizations, as well as small-group design activities and entire-group discussion for transparent consensus building. No round proceeded until the objections of all members had been solicited, addressed, and resolved through discussion and consensus voting, and formal consensus had been achieved.The objective of this framework is to provide a standardized approach to minimize preventable death and disability of people with surgical needs during conflict. This population includes patients with conflict-related violent injury as well as other surgical needs, such as obstructed labor, soft-tissue infections, nonviolent trauma, and intra-abdominal emergencies. Similar to the Joint Trauma System, this proposed framework consists of an integrated tiered chain of care with continuity from POI to definitive treatment and rehabilitation as well as systemwide advances .15 In the humanitarian context, training civilian first responders should minimize responder risk and maximize opportunities to improve POI care. Basic skills should include (1) safe scene management , (2) airway protection through jaw-thrust and chin-lift maneuvers and lateral trauma position for transportation,16 (3) bleeding control with manual compression and wound packing, (4) protecting the injured from the environment, and (5) rapid transportation of the injured to care. Bystander tourniquet application is not recommended, as transport may be prolonged and misapplied tourniquets may be ineffectual or harmful.17 Spine immobilization should also be avoided given prolonged transport times, reliance on makeshift transport, potential loss of airway, and difficulty managing complex spinal injury in this context.18 Interventions for cardiopulmonary arrest are not recommended, as individuals with no pulse do not survive in this environment.Expansion of tactical combat casualty care to all service members enabled the US military to decrease preventable prehospital deaths.20 Trauma first responders would complete identical training of the basic community responders and receive advanced training in (1) triage including identification of individuals who died or had injuries incompatible with life, (2) basic fracture immobilization, (3) preparation of casualties for transport, and (4) logistical options for transport adapted to the local context. In addition, trauma first responders ideally should provide ongoing community education and conflict first-aid training.More advanced training of a subset of community first responders could improve trauma outcomes in low-resource settings.21 Surgical procedures are not performed at this site.The trauma stabilization point (TSP) is proposed as the first site of care staffed by trained medical  personnel. The TSP’s primary function is to provide far-forward emergency resuscitation and stabilization and must be capable of functioning in resource-constrained environments. The objective at this site is to control hemorrhage, manage airway emergencies, and initiate timely transfer to a higher level of care.By moving medical capabilities as close to the POI as possible, the TSP represents a significant change from most humanitarian responses. The role and location of the TSP must be continuously reassessed in light of conflict dynamics and security considerations. The utility of TSPs may be limited in certain contexts, particularly where fighting is sporadic or front lines are poorly defined. The potential contribution of the TSP is contingent on the presence of a system of care meeting the following requirements: (1) adequate transport, (2) capability to maintain care en route, and (3) transfer to a receiving facility able to provide more-advanced care.22 Early hemorrhage control allows patients to survive; in addition, the triage category can be downstaged, as in the example of extremity hemorrhage.The TSP would be the first site of medical triage influenced by patient injury and use of resources. The reciprocity between hemorrhage control and triage has been well recognized in the military trauma system of care. Life-saving measures for survivable injuries prioritizing circulation and control of massive hemorrhage with nonsurgical management of airway emergencies have been reported to decrease preventable deaths.23 TSPs would ideally be located within 10 minutes of the POI. Given contextual constraints, the goal should be within 20 minutes. Therefore, rapid patient evacuation is an essential component of the TSP. The TSP services should include (1) hemorrhage control via tourniquets and/or placement of a pelvic binder; (2) resuscitation, including tranexamic acid administration, intravenous and intraosseous line placement, and crystalloid infusion; (3) initial management of chest injury causing airway or circulatory compromise via decompression of the pleural space, application of chest seals, and insertion of pleural drains; (4) initial management of life-threatening infection via resuscitation and antibiotic administration as well as wound irrigation and debris removal; and (5) pain control. Owing to poor long-term prognosis, resuscitation of pulseless patients and emergency resuscitative thoracotomy should not be performed. The advisability of initiating invasive procedures at this site is contingent on the ability to sustain care beyond the TSP. Only patients requiring a higher level of care should be transferred to the definitive facility. The TSP is not intended to serve as a site of primary care or management of nontraumatic medical or surgical needs. In addition, definitive management and discharge of patients with non–life-threatening injury should be provided at the TSP, including acute wound and closed fracture management, pain management, and tetanus prevention. By consensus, context-specific recommendations for TSP personnel, which is a controversial subject,13 fell outside the group’s mandate.Based on military data,24 Transfusion capability, which may be possible through walking blood banks, would augment the TSP. However, although desirable, blood transfusion at the TSP is currently not available in most settings.Early component or whole blood transfusion has been reported to improve survival in patients with hemorrhagic shock and is the equalizer for long transport times to a higher level of care.After stabilization at the TSP, patients in need of additional care should be transported to a definitive care facility. This site would be the first point at which surgical care will be provided and must be capable of treating injuries as well as emergency surgical and obstetrical conditions. These facilities require significant investment in material and human resources to provide quality care. Minimum essential procedures provided at this site are presented in Box 1. Imaging: radiography and ultrasonographyFracture management (open and closed)Management of spinal cord or column injuriesDefinitive surgical burn careOperative treatment of abdominal and obstetrical surgical emergenciesOpen skull fracture managementAmputation and fasciotomyHerniorrhaphy Emergency genitourinary proceduresComplex wound closure and skin graftEnucleationOperative management of fractured mandibleLocal or rotational flapDefinitive vascular reconstructionComplex surgical treatment of wounds and infectionRegional, spinal, and general anesthesia with intubationTransfusion servicesComplex perioperative careIntermediate level of care above wardPostanesthesia care unitPalliative care Imaging: ultrasonographyDiagnostic peritoneal lavage or aspirationClosed fracture managementConservative management of spinal cord or column injuriesEmergency burn escharotomy and acute burn managementBasic neck explorationSuprapubic tube placementTemporary vascular stabilization including shuntOpen skull fracture managementAmputation and fasciotomyOperative treatment of abdominal and obstetrical surgical emergenciesSurgical treatment of wounds and infectionRegional, spinal, and general anesthesia with intubationPostanesthesia recovery in operating suiteBasic transfusion servicesPain and symptom managementVentilatorsIntensive care unit nursing staffCentral venous cathetersCardiac monitoringIV inotropesCardiothoracicNeurosurgicalReconstructiveaThis facility would provide damage control surgery en route to definitive surgery as needed.bAn advanced capability package can be used to increase the complexity and scope of surgery performed in the definitive care facilities by providing specialist surgeons and critical care services.25 should optimally receive surgical care within 45 minutes but no longer than 60 minutes after leaving the TSP. For those with less-critical conditions , this timeline extends to surgery within 4 hours optimally but no more than 6 hours. Although these timelines are ambitious in insecure environments, similar transport times have been achieved in other resource-constrained settings.26 Emergency abdominal and obstetric procedures could also be done at this site if timely transfer to the definitive site is not possible within a time frame that maximizes survival (An innovation proposed by this group is the contingency facility. This facility should provide damage control surgery en route to definitive care as needed. Situations dictating the need for a contingency site include (1) the pace and volume of incoming casualties, (2) anticipated surge in casualties, (3) ability to provide timely damage-control surgery, and (4) other threats to the survival gains made at the TSP. Patients with critical status survival . ContingAnother proposed innovation is a standardized advanced capability package that can be used by definitive care facilities to provide higher-level specialty surgical and critical care. The advanced capability package would consist of personnel with specialized surgical training  and equipment , which could be integrated into the core platform as circumstances permit.27Despite resource limitations, the system should seek to improve functional outcomes by including basic reconstructive and rehabilitative services . HoweverA significant percentage of patients who experience blast and explosion injuries require amputation. It is critical for surgeons to consider function in the creation of the residual limb. Of equal importance is training in adaptive devices, safe transfer techniques, and physiotherapy for residual limb preparation. When feasible, the provision of adequate prostheses would permit patients to regain additional function. At present there are few organizations with the means to provide and maintain prosthetics in these settings. Efforts should be made to establish international networks and allocate funds for prosthesis provision and follow-up.Burn injuries are common in both conflict and low-income contexts. Therefore, acute burn care, reconstruction, and rehabilitation are critical functions to prevent death and disability. Mental health services should be an integral part of care and follow-up planning at acute care facilities. In addition, reconstruction of congenital disorders and other complex non–conflict-related conditions should be deferred during active conflict given resource constraints.In addition to the technical requirements and competencies necessary at each level of care, there are features that should be integrated within the system to optimize care. These features include predeployment education, injury prevention, data collection, and quality improvement.29 Humanitarian medical teams are unarmed and may come under fire if operating near the front line or, increasingly, are directly targeted. Attempts to reconcile the dual imperatives of safety and rapid medical intervention have proven controversial.30 Placing humanitarian medical personnel under the protection of combatant forces challenges the long-standing humanitarian principles of neutrality and independence, which are in part designed to enhance humanitarian access and safety.11 Although these tensions are unresolved, it remains important to distinguish humanitarian activities from other forms of assistance associated with “interest-conflicted” parties, which may include the host state. Efforts to document attacks on medical personnel and/or zones established to care for the wounded and sick and hold perpetrators accountable should be strongly supported.32The ability for humanitarian organizations to provide surgical care proximate to the time of injury is complicated by security and access constraints.33 Special attention should be paid to the principle of impartiality, which requires that assistance be provided based on medical need regardless of a patient’s political affiliation or preinjury combatant status.11 Counter-terrorism strategies can conflict with medical impartiality, and potential conflicts should be managed with an understanding of international humanitarian law and informed anticipation of these pressures. Standardized, pragmatic educational materials for medical personnel and predeployment checklists may prove useful  may improve their reach. Population safeguards, such as early warning systems and egress assistance, may also prove to be useful.Injury prevention may provide additional opportunities to reduce preventable death and disability .34 Preve37 A clinical data collection system is foundational for understanding the evolving epidemiology of surgical disease in conflict and for improving the quality of response.Advances in trauma systems development have been predicated on the ability to evaluate data from trauma registries such as the Department of Defense Trauma Registry and American College of Surgeons National Trauma Data Bank.39 Desired data elements include the geographic place of injury, clinical complications, functional status at disposition and, if possible, measures of long-term patient outcomes. If multiple organizations are involved, responsibilities for data collection and analysis should be clearly defined and occur at consistent points throughout the system. The registration and transmission of data must use security safeguards to protect the identity of the patient, maintain patient safety, and link individual records across the continuum of care. To minimize the task burden and maximize utility, data collection should be completed electronically and include a limited number of elements at each site. In addition, systematic data analysis should be undertaken in real time to ensure immediate feedback and response refinement in a rapidly changing environment.The recommended minimum data that should be collected at each point of care and coordinated among all actors are outlined in Box 3. Patient demographic information Mechanism and anatomic location of injuryEstimated time of injuryTime of arrival at each point of careMode of transport to point of careVital signs25 and Kampala Trauma Score38Triage categoryProcedures performedDisposition outcome Time of dispositionIntended destination at dispositionGeographic place of injury (if not risking patient safety)Clinical complicationsInformation about the patient’s basic functional status at dispositionAny available data about long-term patient outcomesThis framework presents minimum standards for humanitarian surgical response in areas beset by armed conflict. Even in high-risk security and resource-constrained conflict settings there exists a realistic potential to prevent death and disability. Adapting advances in trauma systems to the humanitarian context could also improve outcomes in the care of other surgical emergencies.41 This framework builds on this evidence, optimizing rapid intervention to manage the leading causes of death, hemorrhage, and airway compromise. Military and civilian communities have approached these challenges by developing coordinated systems of trauma care that match the nature and urgency of patient needs with provision of escalating surgical capabilities. Communication between system components is also essential to facilitate clinical standards, transitions of care, data collection, and quality improvement.The implementation of trauma systems has consistently reported reduction of preventable death and disability in both military as well as civilian environments.There are significant challenges to the implementation of this framework; however, its utility is based on providing a basic blueprint that can be adapted for different conflict settings. The Stanford Working Group also identified areas for further consideration, including (1) standardized technical and contextual training for personnel deployed to conflict settings, (2) development of a uniform data registry with embedded quality improvement capabilities, and (3) a system for communication and coordination of care between all actors working in the zone of conflict, as collaboration between all medical actors is critical to the success of a surgical care system.Ideally, the principles used to establish military and civilian trauma systems should be applied to the humanitarian care of patients in conflict zones. Organized trauma systems save lives and have become the standard of care; as such, it is vital for all actors to extend these benefits to populations in conflict.