Traumatic brain injuries (TBI) and mental health or substance use disorders (MHSU) are global public health concerns due to their prevalence and impact on individuals and societies. However, care for individuals with TBI and MHSU remains fragmented with a lack of appropriate services and supports across the continuum of healthcare. This systematic review provided an evidence-based foundation to inform opportunities to mobilize and adapt existing resources to integrate care for individuals with TBI and MHSU by comprehensively summarizing existing integrated activities and reported barriers and facilitators to care integration. MEDLINE, EMBASE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, Sociological Abstracts, and Dissertations & Theses Global were independently reviewed by two reviewers based on pre-determined eligibility criteria. Data on the integration activity, level and type of integration, reported barriers and facilitators, and the strategies aligning with the World Health Organization’s (WHO) Framework on Integrated Person-Centred Care were extracted to form the basis for a narrative synthesis. Fifty-nine peer-reviewed articles were included, describing treatments (N = 49), programs (N = 4), or screening activities (N = 7). Studies discussing clinical integration at the micro- (N = 38) and meso- (N = 10) levels, service integration at the micro- (N = 6) and meso- (N = 5) levels, and functional integration at the meso-level (N = 1) were identified. A minority of articles reported on facilitators , barriers , or both (N = 6), related to integrating care. This review demonstrated that integrated TBI and MHSU care already exists across a range of levels and types. Given the finite and competing demands for healthcare resources, cognitive accommodations across treatment plans to facilitate integrated TBI and MHSU care should be considered. Multidisciplinary teams should also be explored to provide opportunities for education among health professionals so they can be familiar with TBI and MHSU.Trial registration: Prospero Registration: CRD42018108343. Traumatic brain injuries (TBI), mental health disorders, and substance use are global public health concerns due to their prevalence and impact on individuals and societies –4. TBI hWhile TBI and MHSU are significant concerns independently, many individuals with TBI also experience MHSU –12 and mIntegrated healthcare centred on the needs of the individuals, their families, and communities has been acknowledged by the World Health Organization (WHO) as a solution to address multi-morbidities and improve access to care and patient outcomes . In 2016Health services that are managed and delivered so that people receive a continuum of health promotion, disease prevention, diagnosis, treatment, disease-management, rehabilitation and palliative care services, coordinated across the different levels and sites of care within and beyond the health sector, and according to their needs throughout the life course [27 p.2].Crucially, it is widely acknowledged that health system or health service integration is highly complex and includes a range of strategies –32 that To the best of our knowledge, there is currently no systematic review on integrated care for individuals with TBI and MHSU, despite the prevalence of their co-occurrence, the interrelatedness of their symptoms, and the special considerations needed when they are comorbid. This is a significant gap in informing opportunities to integrate TBI and MHSU care. This systematic review aimed to summarize the current levels and types of integrated care for TBI and MHSU and identify the reported barriers and facilitators to integrated care for TBI and MHSU. Findings from this review provide an evidence-based foundation to inform opportunities to integrate person-centred healthcare for individuals with TBI and MHSU.BMJ Open [The protocol for this systematic review is published in the journal BMJ Open  and is hThe following databases were first searched in August 2018 for relevant articles. A second search was conducted in September 2020 to retrieve articles indexed since August 2018:MEDLINE In-Process and Other Non-Indexed Citations and MEDLINEEMBASEPsycINFOCINAHLCochrane Central Register of Controlled TrialsSociological AbstractsDissertations & These Global.S1 File presents the search strategy associated with each database.The search strategy was informed by published protocols and reviews on integrated healthcare –38, 40 aPeer-reviewed qualitative, quantitative, and mixed methods articles, as well as dissertations identified through our original search or through reference lists of included primary research articles and scoping or systematic reviews that met the following inclusion criteria were included in this systematic review:Describe or evaluate a policy, program, or intervention/treatment at the health service delivery level for individuals with TBI and MHSU; ORScreen or diagnosis for TBI in a mental health or substance use service setting; ORScreen or diagnosis for MHSU in a brain injury health service setting.Narrative or commentary articles, those that describe a theory or framework without primary data reported, and articles that examine a broader brain injured population  without specific mention of TBI were excluded. Furthermore, only articles published in or after 2013 were included in this review. It is acknowledged that integrated care predates the start date of our review; however, several factors informed our decision to only include articles published in 2013 or later. Almost 50% of the title and abstracts returned from this review’s search strategy were published in or after 2013 and a PubMed search of “traumatic brain injury” AND  showed an almost 100% increase in publications from 2013 to 2018. This suggests an increase in recognition and treatment of TBI in recent years as well as the growing acknowledgement of MHSU as a symptom or comorbidity of TBI. Thus, the inclusion of articles published in or after 2013 also captures more recent health service trends and provides a more contemporary review. However, we acknowledge that in limiting the search in this way we have missed relevant articles published prior to 2013.or MHSU. Consistent with the peer-reviewed protocol [All articles were independently assessed by at least two reviewers . At the title and abstract screen, articles were considered for the full-text screen if they described or evaluated a policy, program, or intervention/treatment at the health service delivery level for individuals with TBI protocol , a randoTable 1. As dissertations have not been formally peer-reviewed, they were not included in the narrative synthesis but described separately to capture early work, such as pilot studies, of integrated care that may not yet be published in peer-reviewed journals.A narrative synthesis, to critically analyze and report the peer-reviewed literature , was conAll articles meeting the inclusion criteria were assessed for risk of biases using quality assessment tools designed by methodologists from the National Institutes of Health and Research Triangle Institute International  or the CFig 1 presents the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) flow diagram for a detailed account of the search and screening results.A total of 12,439 articles were identified through the database searches. After duplicates were removed, 8,075 title and abstracts were screened, of which 958 were identified for full text review. Among these, 473 articles were published prior to 2013 and 57 were book chapters/abstracts and were excluded from further review. Of the remaining full text articles reviewed, four dissertations –48 and 5Table 2 presents study characteristics and integration activities of the included peer-reviewed studies with study citations. S1 Table presents key data extracted from these articles.Peer-reviewed articles were primarily conducted in the United States (81%). Thirty one percent of studies included all severity-levels of TBI; 22% did not specify TBI severity. PTSD and depression were the most commonly investigated MHSU . Many of the included studies (51%) focused on veterans, all of which were conducted in the United States. Except for case studies, which predominantly included a single sex or gender of participant, none of the included studies stratified results based on sex or gender. The most common types of integration activities were treatments/interventions (N = 49). Four studies reported on program implementation and seven studies described screening activities. One study described both screening and treatment activities, however, the type of treatment was not detailed in the study . Table 2S1 Table). Risk of bias associated with selection (N = 48), information (N = 41), performance (N = 33), and reporting (N = 17) were common due to the diverse study designs included in this review. As the aim of this review was to summarize existing integrated TBI and MHSU care rather than evaluate the outcome of the integrated activities, no studies were excluded based on their risk of bias. However, these biases were recognized in the narrative synthesis and discussion of the review.Risk of bias assessment was conducted for studies that reported a treatment or program : 21 randomized controlled trials (RCTs), 17 case studies/series studies, 7 before-after studies without a control, 6 observational cohort or cross-sectional studies, 2 qualitative studies, and 1 case-control study  at the level of individuals  (N = 38) or at the meso or sub-group/sub-population level (N = 10). Several studies discussed integration of different clinical services  at the micro (N = 6) and meso level (N = 5). One study described meso-level care that was both service and functional integration . None ofTable 4 presents more detailed reporting on alignment between WHO Framework Strategies and included articles.Almost all included studies (N = 51) described activities that involved engaging and empowering individuals and families . Coordinating services, aligning with WHO Framework Strategy 4, was the second most commonly described integration strategy, with six studies focusing on screening for TBI in MHSU settings or vice versa and 12 studies focused on coordination for individuals, one of which also considered coordination across sectors. Studies focusing on re-orienting the model of care , solely aligned with the strategy of innovating and/or incorporating new technologies (N = 7). Table 5 presents barriers and facilitators reported in the articles. An additional nine studies did not explicitly report barriers and facilitators to treatment activities but noted that compensatory strategies to address cognitive challenges associated with TBI were incorporated in the treatment design [A minority of studies (N = 15) reported on barriers or facilitators, approximately half of which solely discussed facilitators (N = 7). The remaining eight articles either discussed both barriers and facilitators (N = 6) or just barriers (N = 2). Common reported barriers included lack of education, limited access to care, and difficulties using or navigating technology. Commonly reported facilitators included engaging patients and families or caregivers, collaborating across disciplines, and incorporating compensatory strategies for addressing TBI-related cognitive challenges into treatment plans. t design , 84, 92.The four dissertations that met inclusion criteria were all completed at American Universities. One specifically focused on mild TBI , with thThis review is the first, to the best of our knowledge, to summarize existing levels and types of integrated care for individuals with TBI and MHSU and, where reported, the barriers and facilitators to integrated care. Fifty-nine peer-reviewed articles and four dissertations published in 2013 or later were identified that met our inclusion criteria. The majority of peer-reviewed articles and all dissertations discussed micro- or meso-level clinical integrations and a minority of peer-reviewed studies reported on service integration at these levels. None of the included studies discussed integrations at the macro-level or the level of populations or organizations, which may be reflected in grey literature, including government organization reports, rather than the peer-reviewed literature. Integration strategies from included peer-reviewed articles were mapped onto the WHO’s five strategies for integrated people-centred health services . Almost Like other reviews on integrated care –38, 40, Notably missing from the articles reporting on screening activities was any description of the outcome of the screening such as access to care or receipt of treatment. All screening studies included in this review aimed to identify the prevalence of TBI or MHSU or assess the feasibility of select tools to screen for TBI or MHSU. While screening and the receipt of a diagnosis may provide opportunities to access treatments, MHSU diagnosis may also be a barrier to TBI treatment. Indeed, some RCTs included in this review had exclusion criteria based on types of MHSU or severity of TBI , 107. AsThough only a subset of articles reported on barriers and facilitators, it is worth highlighting that many of those noted were complementary. For example, one study noted the geographical distance between care facilities as a barrier  and anotWhile this review’s goal was not to assess the efficacy of integration activities for individuals with TBI and MHSU , we did see a trend among included studies that we believe is worth noting. Specifically, almost all studies, regardless of integration activity, level, or type, reported positive outcomes. We recognize that this finding may be impacted by reporting and publication bias. Nonetheless, this supports the widely accepted notion that there is no ‘one size fits all’ approach to integrated care , 31. CliFinally, even though most studies aligned with the WHO Framework strategic approaches ‘Empowering and engaging people and communities’, none of the articles included in this review specifically addressed the needs of underserved or marginalized populations experiencing TBI and MHSU. The WHO Framework defines marginalized populations as comprising individuals who may not receive or access care due to barriers including but not limited to income, education, race/ethnicity, and gender . We acknSimilarly, while some studies included in this review successfully leveraged or incorporated technology  in the integrated activities, there was little consideration of the barriers related to technology use among underserved populations. Developers must be mindful of potential challenges associated with access to and use of technology among underserved populations to reduce the risk of furthering inequities in care for these individuals. Research that is co-produced with underserved populations according to their specific needs on integrating TBI and MHSU care is urgently needed. Finally, sex and gender considerations must be incorporated in all research, including the reporting of data stratified by sex or gender. Apart from case studies, which predominantly comprised participants of a single sex or gender, none of the articles in this review reported sex- or gender-stratified data. Furthermore, two studies reported findings on men and women but were described as ‘sex’ , 56 whilThis review is the first, to the best of our knowledge, to systematically review the peer-reviewed literature to identify existing integrated care for TBI and MHSU. The primary search strategy was supplemented with a secondary search to capture articles that describe integrated activities but do not explicitly describe their study as such . Similarly, the title and abstract screen was purposely broad to include articles on care for TBI or MHSU, recognizing that many abstracts may only describe data or refer to TBI or MHSU. Including these articles in the full-text screen reduced the risk of missing relevant articles.Limitations of this review include the risk of several forms of bias. As non-English language studies were excluded, integrated care in jurisdiction where English is not a primary language may be missed, limiting the comprehensiveness of this review. This review did not include a search of grey literature, meaning that non-peer-reviewed reports from institutions or health systems on their programs or services are missed in this review, which may explain the lack of integration activity at the macro-level. Indeed, notably absent were any studies focusing on strengthening governance and accountability (Strategy 2) or creating an enabling environment (Strategy 5). It is possible that research addressing these two strategies would be captured in organizational or other related grey literature that were not included in the search for this review. We recognize publication bias in this review, as unpublished results and non-peer-reviewed results were excluded, and the risk of biases including but not limited to selection, reporting, information, and performance bias, in studies that integrated treatments or programs for individuals with TBI and MHSU. These biases may contribute to the lack of studies reporting negative outcomes of integrated care. However, given that the goal of this review was to comprehensively summarize all integrated TBI and MHSU care and not to evaluate the impact of the integrated care, we believe the inclusion of study designs such as case studies/series and observational studies, in addition to RCTs, was appropriate. Finally, we acknowledge that the majority of studies included in this review were conducted in the United States and as such, findings may not be directly generalizable to other health systems or settings.Taken together, this review provides an overview of the current knowledge base of integrated care for TBI and MHSU, while highlighting areas needing future research. It also provides an evidence-based foundation to inform public health sector mobilization and adaptation of existing integrated care resources for individuals with TBI and MHSU. Integrated TBI and MHSU care already exists across a range of integration activities , levels (micro and meso), and types . Opportunities to facilitate the integration of TBI and MHSU care include embedding accommodations to address cognitive challenges experienced by individuals with TBI, including among facilities that are already providing therapy to individuals with MHSU or TBI, to facilitate access to care for individuals with TBI. Multidisciplinary teams, particularly within a single facility, should be explored as it may improve patient outcomes by addressing other sequelae of TBI and MHSU, supporting caregivers by addressing transportation barriers, and promoting education among health professionals so they can be familiar with TBI and MHSU. Finally, research co-produced with individuals with lived experience to understand the benefits and consequences of screening as well as research specifically with underserved populations to enable equitable access to healthcare and research are urgently needed.S1 File(PDF)Click here for additional data file.S1 Table(PDF)Click here for additional data file.


This study briefings the roles of Coriolis, and Lorentz forces on the dynamics of rotating nanofluids flow toward a continuously stretching sheet. The nanoparticles are incorporated because of their unusual qualities like upgrade the thermal transportation, which are very important in heat exchangers, modern nanotechnology, electronics, and material sciences. The primary goal of this study is to improve heat transportation. Appropriate similarity transformations are applied for the principal PDEs to transform into nonlinear dimensionless PDEs. A widely recognized Numerical scheme known as the Finite Element Method is employed to solve the resultant convective boundary layer balances. Higher input in the solvent fraction parameter has a rising effect on the primary velocity and secondary velocity magnitude, and decreasing impact on the distributions of temperature. It is seen that growing contributions of the Coriolis, and Lorentz forces cause to moderate the primary and secondary velocities, but the temperature and concentration functions show opposite trend. The concentration, temperature, and velocities distributions for suction case is prominently than that of injection case, but inverse trend is observed for local Nusselt and Sherwood numbers. These examinations are relevant to the field of plastic films, crystal growing, paper production, heat exchanger, and bio-medicine. The theoretical and experimental investigations confirm from the literature that the existence of nanoparticles in host fluid greatly affects the thermophysical properties of base fluids which exhibits poor conductivity properties3. The convective nanofluid heat transfer flow attracts numerous researchers due to their fascinating applications in every field of Science and Engineering. To name a few, the diamond and ceramic nanoparticles are used to upsurge the dielectric properties of the mineral oil, the fluid with nanoparticles can be used for direct absorption of the sunlight in solar collectors, the Zink and Titanium Oxide particles have antibacterial behavior and therefore which can be used for biomedical applications such as drug delivery and cancer therapy, and many more6. Ali et al.7 discussed convective unsteady hybrid nanofluid flow within an upright channel by using Laplace Transform (LT) technique, in which authors developed fractional Maxwell fluid model is developed by using Caputo fractional differential operator. Awais et al.8 considered nanofluid assisting and opposing flow for exploring the Lie group analysis numerically with Adams-Bash forth technique (ABT). Abdelmalek et al.9 considered Cauchy’s stress tensor for third-grade fluid to investigate the dissipative nanofluid flow past an elongating sheet by adopting built-in Matlab routine bvp4c. Farooq et al.10 adopted a modified Cattaneo–Christov mass and heat flu model for the numerical exploration of the Carreau nanofluid flow by horizontal stretching cylinder subject to the convective conditions. Subba Rao et al.11 studied the nanofluid (Buongiorno model) flow above the isothermal upright cone. There are some articles related to boundary layer flow along a nanoparticles14. The non-Newtonian fluids are technological importance. In nature, Boger fluids are also non-Newtonian fluids16.The fluids which are engineered by the homogeneous dispersion of metal and metallic oxide particles at the nanoscale are known as nanofluids18. Magnetic doubly stratified mixed convective flow with heat generation/absorption effects reported by Abbasi et al.19 and Alhussain et al.20 securitized numerically on Cattaneo-Christov flux model for the magneto nanofluid flow past a spinning cone embedded in an anisotropic permeable medium in the presence of cross-diffusion (Soret and Dufour), Navier slip, and Stefan blowing effects. The insight into significance of particles aggregation and carbon nanotube subject to rotating environment studied by Acharya et al.22. Jawad et al.23 obtained approximate analytical solutions using HAM for the energy irreversibility analysis on hydromagnetic nanofluid flow past a nonlinear elongating permeable sheet. Jamshed24 employed Keller Box Method (KBM) to study the MHD nanofluid flow past a nonlinearly stretching sheet with entropy generation and viscous dissipation effects.There have been rising fascination in the investigation of the impact of Lorentz force produced due to magnetic field because of its modern applications in fluid engineering, assembling of plastic materials, hot rolling, production of glass fiber, and medical treatment25. Chu et al.26 explored numerically on nanofluid flow past a bidirectional periodically moving surface in the presence of nonlinear radiation and heat source/sink effects by employing (HAM) Homotopy Analysis Method. Ali et al.18 employed GFEM  to explore the buoyant driven transient bio convective Maxwell nanofluid rotating 3D flow above the Riga plate with binary chemical reaction and activation energy. Ahmed et al.27 numerically investigated heat source/sink effects on stagnation point flow over stretching/shrinking rotating disk, Bilal et al.28 studied chemical reaction effects on magnetized nanofluid past a rotating cone with HAM, and khan et al.29 reported on the impact of heat source/sink effects subject to revised mass flu conditions for flow past rotating elongating cylinder. Ali et al.30 employed FEM to explore rotating Casson Carreau nanofluid flow over a sheet with Darcy–Forchheimer medium.In the recent years, the growing interest in the examination of Coriolis force effects on the dynamics of fluid flow over a stretching sheet because of several real applications in astrophysical and geophysical problems, hot rolling, fiber production, and centrifugal bio-reactor33 by employing GFEM with a weighted residual approach. The flow governing coupled highly nonlinear PDEs are solved by adopting a control volume approach by employing a Galerkin Finite Element Method35 with a weighted residual approach. The various flow field characteristics for numerous significant parameter changes are discussed and depicted pictorially. The computational results obtained through Matlab code blocks are corroborated with the existing literature and found to be a tolerable correlation. The friction factor, Nusselt number, and Sherwood number values are computed and documented in tabular form. This numerical study is relevant to the polymers, heat exchangers, bio-medicine, and astrophysical and geophysical problems.The scrupulous literature assessment cited above confirms that a little attention is made towards the Lorentz force embedded in Bogar nanofluid rotating flow past stretching surface under the influence of the Coriolis force and suction/injection, and present analysis is unique because of solvent fraction, Lorentz and Coriolis impact on dynamic of Bogar nanofluid. To the best of the author’s knowledge, all the cited reports are not deliberated on the elaborated problem. Therefore, the prime aim of the current investigation is to investigate the heat and mass transfer effects on transient hydromagnetic rotating nanofluid 3D flow with suction/injection effects. Very recently, the hydromagnetic boundary layer flow for both Newtonian and non-Newtonian nanofluid flow fields was investigated by numerous authorsTo observe the influence of Coriolis and Lorentz forces on the Boger fluid dynamics of temperature, fluid velocity, and concentration distributions with suction/injection?What is the effect of combine affect of Brownian motion, thermophoresis, Coriolis and Lorentz forces on the mass transfer rate, skin friction tensors, and heat transfer rate with suction/injection?Assess the Brownian motion, and thermophoresis parameters effect the temperature and tiny particles concentration profile?This study provide answers to below related scientific research questions: D rotating flow of nanofluid past a bidirectional stretching sheet is considered. The physical flow configuration and coordinate system of elaborated problem is shown in Fig. x along with velocity 30. The ambient concentration and temperature is 37:The transient magnetohydrodynamic 3C and T) are the tiny particles concentration, and temperature of fluid, :M), Prandtl number (Pr), Lewis number (Le), Brownian motion The complexity of elaborated problem is reduced by introducing the below similarity transformations On the base of finite element mesh, a variational formulation of the problem is performed.(ii)In above (i), the element equations are generated with the aid of approximation solution.(iii)Construct a stiffness matrix by using interpolation functions.After generation of the elements equation, we assembled all the generated elements equations through inter element continuity condition, and obtained a model which called global finite element model over a entire computational domain.The elaborated boundary conditions of the current problem are utilized on the obtained assembled equations.41, and Wang42. Further, in Table 43 and Shafique et al.44, and present FEM results for diverse values Finally, we solved the assembled equations iteratively. To justify the validity of finite element computations, a study for grid independence is conducted. The whole domain is divided into different mesh density of grids size, and observe no more variation after mentclass2pt{minimTo solve the Eqs.  to 14)  14) alon of Eqs. –15) red red18\doFor numerical computation, the plate length fixed at ith Eqs. –22) can can\docuHere entclass1pt{minimaHere, The develop finite-elements model of the equations is below:In this section, we show the significance of suction/injection on dynamics of Maxwell rotating fluid subject to Coriolis force, magnetohydrodynamic, and gyrotactic microorganism via finite element simulation. In each of the figures for these quantities, three sets of curves are drawn for varying values of suction/injection mentclass2pt{minimThe primary and secondary velocity distributions for different values of solvent fraction parameter, magnetic field parameter, rotation parameter, and unsteady parameter are portrayed in Figs. The sketches of M and The M, and rotation Le, and time dependent parameter M and Figure mentclasspt{minimasee Fig. a,b. The an increasing impact on the distributions of temperature and concentration.increase the magnitude of the velocity, temperature, and concentrations components reduce against the strength of injection.Higher input in the Coriolis and Lorentz has a decreasing effect on the primary velocity and secondary velocity magnitude, anddecreasing impact on the distributions of temperature.decrease the magnitude of Higher input in the solvent fraction parameter has a rising effect on the primary velocity and secondary velocity magnitude, anda negative effects on injection has a larger amount in injection case has larger Simultaneous increase in Brownian motion and thermophoresis parameters have an increasing impact on the distribution of temperature, andTiny particles concentration diminishes against incremented Lewis number, unsteady, and Brownian motion parameters and exhibits rise against thermophoresis.After successful computational struggle of parametric influence on the fluid dynamics, this study can be extend in future for Maxwell-nanofluid, Oldroyd-B nanofluid, comparative study between tangent-hyperbolic and Maxwell nanofluid, and viscoelastic Jeffrey’s nanofluids.In this report, the finite element analysis on the transient magnetohydrodynamic three-dimensional rotating flow of nanofluid flow past a bidirectional stretching sheet with suction/injection, Coriolis, and Lorentz forces has been explored numerically. Based on the observed analysis of outcomes, it is worth concluding that:


Assisted reproductive technology (ART) and previous Cesarean section (CS) are independently associated with the risk of adverse obstetric and perinatal outcomes in general. Few studies have focused on the association between adverse obstetric and perinatal outcomes and ART used in the high-risk population of women with previous CS.A retrospective cohort study including 14,099 women with a previous delivery and a subsequent delivery between April 2014 and April 2020 was conducted at our hospital. We assessed the risk of adverse obstetric and perinatal outcomes in pregnancies conceived by ART in women with previous CS, using log-binomial regression models.in vitro fertilization (IVF), whereas women with singletons conceived through cleavage-stage embryo transfer (ET) were at increased risk of gestational diabetes mellitus (GDM)  than those with singletons conceived through blastocyst–stage ET.In women with previous CS, ART singleton pregnancies were associated with an increased risk of maternal complications, such as pregnancy complications, placental anomalies of implantation, postpartum hemorrhage, and preterm birth (PTB), as compared to spontaneously conceived pregnancies. The implementation of ART and previous CS interacted in a synergistic manner to increase the likelihood of the placenta accreta spectrum in women with singleton pregnancies . In women with previous CS who underwent ART, women with singletons conceived through intracytoplasmic sperm injection were at increased risk of velamentous placenta  compared with those with singletons conceived through Pregnancies conceived through ART were at increased risk for adverse obstetric and perinatal outcomes in women who had previously delivered by CS, particularly for placental anomalies of implantation. In women with previous CS undergoing ART, IVF and blastocyst–stage ET may be a relatively safe treatment. It is well-documented that Cesarean section (CS) might increase the incidence of adverse obstetric and perinatal outcomes in subsequent conceptions, including persistent complete placenta previa, placental abruption, uterine Cesarean scar rupture, preterm birth (PTB), and low birth weight (LBW) . Thus, wThe present retrospective cohort study aimed to assess the prevalence of adverse obstetric and perinatal outcomes associated with ART in women with previous CS precisely and to elucidate how to implement ART safely in infertile women with a Cesarean scar.in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)–embryo transfer (ET), and frozen-thawed ET (FET). In women with a history of CS, pregnancies conceived through ART were assigned to the CS–ART group, whereas spontaneously conceived pregnancies were categorized into the CS–SC group. In women with a history of vaginal delivery (VD), pregnancies conceived through ART were assigned to the VD–ART group, whereas spontaneously conceived pregnancies were categorized into the VD–SC group.We conducted a retrospective cohort study, including all multipara women with a single previous full-term delivery and a subsequent delivery between April 2014 and April 2020 at the First Affiliated Hospital of Wenzhou Medical University. Obstetric and perinatal data of live newborns delivered after the 28th week of gestation were obtained from the delivery records. The exclusion criteria were as follows: (1) congenital uterine malformations, including uterus unicornis, uterus bicornis, septate uterus, and duplex uterus; (2) previous uterine myomectomy; and (3) stillbirths at current delivery. ART included Subsequently, the ART pregnancy group was divided into IVF and ICSI subgroups according to the fertilization mode, into the ET and FET subgroups according to different ET methods, and into blastocyst and cleavage-stage ET subgroups according to different embryo developmental stages. Using the unique personal identification number, all data were retrospectively collected from computer databases and stored in a deidentified database. Validation was performed on the data to check for errors and inconsistencies in documentation and coding.The study outcomes consisted of four parts: pregnancy complications, including gestational hypertension, preeclampsia, gestational diabetes mellitus (GDM); placental anomalies of implantation , includi2), and education level (≤ 9 and > 9 years). Other previous intrauterine operations included curettage, surgical termination of pregnancy, and evacuation of retained conception products. In the ART pregnancy group of women with previous CS, we compared the incidence of obstetric and perinatal complications between different fertilization modes, between different ET methods, and between different embryo developmental stages, to elucidate how to implement ART safely in infertile women with a Cesarean scar. For comparison between different fertilization modes, we additionally adjusted for ET methods and embryo developmental stages. For comparison between different ET methods, we additionally adjusted for fertilization modes and embryo developmental stages. For comparison between different embryo developmental stages, we additionally adjusted for fertilization modes and ET methods. For maternal outcomes, such as pregnancy complications, placental anomalies of implantation and other obstetric complications, as the dependent variable, the unit of analysis was the delivery. For perinatal outcomes as the dependent variable, the unit of analysis was the offspring. In addition, for perinatal outcomes in twin pregnancies, generalized estimating equations were used to account for the correlation between the twins of the same mother  stratified by birth plurality were assessed using log-binomial regression models. The adjusted risk ratios (aRRs) with 95% confidence intervals (CIs) for each outcome and the interaction models were calculated after controlling for maternal age at the time of delivery , interpregnancy interval  , other pe mother .In addition, we investigated the interaction between ART implementation and previous CS on the risk of obstetric and perinatal complications stratified by birth plurality, in which the VD–SC group were used as the reference group. The interaction measure between ART implementation and previous CS on the risk of obstetric and perinatal complications should only be used if the two exposure factors are risk factors for obstetric and perinatal outcomes. The relative excess risk due to interaction (RERI) along with 95%CI on the additive scale were calculated using the method described by All participants provided informed consent before undergoing routine treatment. Using the unique personal identification number, all data were retrospectively collected from computer databases and stored in a deidentified database. This study was approved by the ethics committee of the First Affiliated Hospital of Wenzhou Medical University (no. 2020–04) and performed according to the principles embodied in the Declaration of Helsinki.A total of 14,099 participants were included in the analysis . We idenThe maternal characteristics of singleton pregnancies and twin pregnancies are shown in In women with previous CS, ART singleton pregnancies were associated with an increased risk of gestational hypertension , GDM , velamentous placenta , placenta accreta spectrum , postpartum hemorrhage , and PTB , as compared to singletons in the CS–SC group .The implementation of ART and previous CS  are bothIn women with previous CS, twins born following ART had an increased risk of LBW  compared to twins in CS–SC group . PreviouAs shown in In this study, women with singletons in CS–ART group were at increased risk for adverse obstetric and perinatal outcomes when compared to those with singletons in CS–SC group. The risk was particularly increased for placental anomalies of implantation. In addition, the implementation of ART and previous CS interact synergistically to increase the likelihood of placenta accreta spectrum in women with singleton pregnancies. The obstetric and perinatal outcomes between different types of ART procedures used in women with previous CS were also examined: women with singletons conceived through ICSI were at increased risk of velamentous placenta compared with those with singletons conceived through IVF; whereas women with singletons conceived through cleavage-stage ET were at increased risk of GDM than those with singletons conceived through blastocyst-stage ET.Women with singletons in CS–ART group were associated with an increased risk of maternal complications, such as gestational hypertension, GDM, velamentous placenta, placenta accreta spectrum, postpartum hemorrhage, as well as PTB, as compared with those with singletons in CS–SC group. This finding was in line with several recent cohort studies, and a 2016 meta–analysis including 50 cohort studies that showed high relative risks for adverse obstetric and perinatal outcomes in the ART group as compared with the spontaneous conception group . NotablyThe current hypothesis for the development of placenta accreta spectrum is that of a secondary defect of the endometrial–myometrial interface, leading to a failure of normal decidualization in the area of the uterine scar, allowing abnormally deep placentation . Maternain vitro culture of the trophectoderm cell may contribute to abnormal production or function of various placenta secrete molecules  a lack of sufficient samples of twin pregnancies in women with previous CS; (2) most of the twins conceived naturally are monozygotic, while those conceived by ART are dizygotic. Therefore, the risk of adverse obstetric and perinatal outcomes in twin pregnancies conceived by ART compared with spontaneously conceived twins should be further studied, and conclusions should be drawn with caution.Our findings provide valuable information for estimating and improving the safety of pregnancies in women with a Cesarean scar who seek ART, and might be useful in decision-making for women and clinical doctors to balance the risks and benefits of a Cesarean delivery in the first and subsequent births. With an enlarged sample size , we could adjust for confounders to enhance statistical power and thereby could provide more precise and reliable risk estimates. Our analyzed data were collected from case notes at the time of delivery, which minimized selection and recall bias. Additionally, our study indicated that ART singletons in women with previous CS carry an increased risk of adverse obstetric and perinatal outcomes, which has been poorly investigated to date.This study had some limitations. The major weakness of this study lies in its retrospective nature and some confounders may be unavailable or unknown for adjustment. Although obstetric and perinatal outcomes during the first delivery may contribute to increased risks of adverse outcomes in the subsequent delivery, this information was only available in aggregated form in the delivery records for the second live birth. Therefore, there may have been residual confounding due to the lack of control for other potential confounding factors. It was difficult to confirm the indications for previous CS from the retrospective data. Further prospective studies are required to reduce the information bias. In addition, our database did not routinely record ultrasonographic features of Cesarean scar defect and therefore, we were unable to separately assess its role on obstetric and perinatal outcomes.In women with previous CS, clinicians should be aware of the increased risk of adverse obstetric and perinatal outcomes in pregnancies conceived by ART, particularly placental anomalies of implantation. Compared with other types of ART procedures, IVF and blastocyst-stage ET may be relatively safe for the high-risk population of women with previous CS who are undergoing ART.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.FJ: conceptualization and methodology. YL: data curation and writing—original draft preparation. QC: writing—reviewing and editing. XH: supervision. ZW: formal analysis and software. CC and HC: investigation. All authors contributed to the article and approved the submitted version.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. The handling editor declared a shared affiliation with two of the authors YL and FJ at time of review.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The COVID-19 pandemic has driven demand for integrated genomics, resulting in fast-tracked development of AusTrakka, Australia’s pathogen genomics platform. This facilitated rapid data sharing, democratised access to computational and bioinformatic resources and expertise, and achieved national real-time genomic surveillance. The COVID-19 pandemic has accelerated the demand for near real-time analysis and dissemination of pathogen genomic data. In this comment, the authors describe how Australia has developed and rolled out its SARS-CoV-2 genomics platform, AusTrakka, and used it to support public health action. Australia is a federation of states and territories, and public health laboratory activities have often been siloed between jurisdictional boundaries, hampering rapid genomic data sharing. This represents a major “missed opportunity” as pathogens do not respect borders and sharing of genomic information identifies and informs more rapid responses to infectious disease outbreaks3.The COVID-19 pandemic has highlighted the power of pathogen genomics to enhance infectious diseases surveillance and inform targeted public health responses4. In Australia, the pandemic also highlighted the need for an integrated public health genomics surveillance system.Recognising the significant opportunities afforded by pathogen genomics, there has been major government investments in the development and implementation of whole-genome sequencing (WGS), predominantly in high-income settings. The United Kingdom rapidly established the COVID-19 Genomics UK Consortium (COG-UK) and the United States government invested US$1.7 billion to expand genomics capacity for COVID-195. Its successes in earlier detection of outbreaks demonstrated that genomic data sharing could inform public health interventions5.In 2010, the GenomeTrakr network, established by the US Food and Drug Administration, was the first large-scale experiment that facilitated real-time genomic data sharing directly between laboratories from foodborne pathogens on a national level6. The national scope of activities covered by PHE allowed for national level integration of genomic and epidemiological data which meant challenges were around harmonisation of information systems and rapid reporting of data to referral laboratories.In the United Kingdom, Public Health England (PHE) invested heavily in centralised sequencing capacity, launching the PHE Pathogen Genomics Service in 2014https://irida.ca/) was developed. The IRIDA software operates independently for each public health laboratory with an interface to communicate between IRIDA database. The open-source nature of this platform enabled laboratories to establish genomic epidemiology capacity, however, the ability for laboratories to operate the software independently meant that there was no guarantee for real-time data sharing.Canada, like Australia, has a complex health system whereby each Canadian Province has its own public health laboratory. To facilitate real-time data sharing the Integrated Infectious Disease Analysis (IRIDA) project , comprised of representatives from public health laboratories across all jurisdictions in Australia and New Zealand, was established with an overarching aim to implement pathogen genomics in public health. AusTrakka was first proposed by the CDGN in 2016 as a system that would facilitate consistency in genomic data sharing and reporting to improve public health surveillance and response. The AusTrakka platform was developed and deployed by the Microbiological Diagnostic Unit Public Health Laboratory and governed by the CDGN. This platform was built by public health laboratories, for public health laboratories, ensuring that the architecture and the bioinformatics pipelines and analysis protocols were created within a National Association of Testing Authorities (NATA)/International Organization for Standardization (ISO) accredited public health laboratory environment.8 (iv) demand for investigation into ‘mystery cases’ detected despite restricted international travel, hotel quarantine policies and internal border closures; and (v) a strong desire for rapid detection and reporting of SARS-CoV-2 Variants of Concern in a nationally consistent way to inform public health control measures such as length of hotel quarantine and lockdowns. Subsequently, public and political demand for genomic investigation into essentially every case nationwide became an expectation that could only be met by rapid and open data sharing between health departments and public health laboratories. AusTrakka played a crucial role in facilitating genomic data sharing and providing national surveillance and ‘fine grain’ analyses, particularly into ‘mystery’ cases, revealing transmission within and between jurisdictions.The COVID-19 pandemic was the catalyst for further development and deployment of AusTrakka in 2020, with key factors leading to fast-tracking including: (i) national funding for COVID-19 genomics sequencing and analysis through CDGN and AusTrakka; (ii) expert advocacy that led to Commonwealth recognition of the importance of real-time genomics data for surveillance; (iii) early demonstrations of the utility of genomics for COVID-19 from some jurisdictions - landmark events including the genomic identification of a hotel quarantine breach being the single source of a large second wave in Victoria, Australia, which catapulted genomics into the public domain;AusTrakka is used by all public health laboratories in every jurisdiction in Australia and has extended to New Zealand. As public health laboratories upload new sequence data, the phylogenomic tree including all available sequences is updated. For SARS-CoV-2 a Maximum Likelihood tree is visualised, however the platform is able to visualise trees using any method. This tree is immediately accessible to public health laboratories to view their sequences in the national context. Given the sensitivity of this information, a specific framework for SARS-CoV-2 data sharing and analysis using AusTrakka was developed, formalising the endorsement from all jurisdictions to rapidly upload all SARS-CoV-2 sequence data to the AusTrakka platform. A multi-disciplinary and multi-jurisdictional AusTrakka team comprised of bioinformaticians, software engineers and genomic epidemiologists was established to support the development and operation Fig. .Fig. 1OvPublic health laboratories had varying degrees of sequencing and bioinformatics capacity, however, through the deployment of AusTrakka it became clear that equitable access was important to ensure a comprehensive national dataset and reduce potential biases in the data. To facilitate this, the dedicated AusTrakka team provides analysis, interpretation, and reporting support to jurisdictions with limited capacity. Implementing this centralised and collaborative system ensured harmonisation of analyses, consistent national reporting, and provides all public health laboratories with the same computational resources and capability. At a national level, AusTrakka provides a focal point for integrated SARS-CoV-2 genomic surveillance information for public health agencies: outputs include reporting against genomics surveillance indicators as part of the Australian Government Communicable Diseases Intelligence Report, weekly reporting of Variants of Concern and investigation into multi-jurisdictional outbreaks Fig. .The AusTrakka development process revealed significant gaps and opportunities in the national public health system, reflecting Australia’s status as a federation. Public health in Australia is a complex multi-levelled system, with each jurisdiction largely responsible for their own public health service delivery, creating barriers to rapid genomic data sharing. Genomic data is generated by the public health laboratories and epidemiological metadata is collected by the health departments. Through the deployment of AusTrakka the significant benefits of integrated genomic data sharing were highlighted, however some limitations were also revealed, including the lack of interoperability between surveillance systems at all levels and the fact custodianship of genomic and epidemiological data is managed by separate systems.A crucial element in the success of AusTrakka was its endorsement by, and compliance with, jurisdictional and federal governance structures for rapid data sharing between states and territories through a centralised platform. On 1 October 2020, AusTrakka was endorsed by the Australian Health Protection Principal Committee (AHPPC), the key decision-making committee for public health emergencies, however a key feature of this endorsement was ensuring access to the data was restricted to approved public health laboratories and agencies.1, detection of Variants of Concern in real-time and in silico testing of primers and probes to identify target failures that may impact diagnostic tests (Fig. AusTrakka streamlines genomic and epidemiological data sharing and enables fine-grained access controls of data between public health laboratories. Within 12 months from endorsement, more than 33,000 high-quality SARS-CoV-2 sequences had been uploaded to AusTrakka, equal to approximately 50% of all COVID-19 cases in Australia, from over 80 users across all public health laboratories. AusTrakka has informed public health decision making throught demonstration of inter-jurisdictional transmissions resulting in internal border closuresAusTrakka has transformed the way multi-jurisdictional infectious diseases outbreaks are investigated and managed in Australia, demonstrating that barriers to genomics data sharing and centralisation could be overcome. As genomics capacity continues to develop globally, AusTrakka has provided a roadmap for integrating pathogen genomics into public health systems. There are, however, significant differences in global access to genomics technologies, though the principles of robust data governance, and the need for systems for rapid data sharing and analysis, and equitable access to computational capacity to enable real-time pathogen genomics surveillance, universally applies. So far, AusTrakka has been used as a core public health tool, although it has potential to be a valuable resource for advancing genomics research that will be explored in future.It is imperative that the learnings and achievements experienced during the pandemic are sustained for the ongoing modernisation of infectious diseases surveillance and control. AusTrakka is adapting the approach to COVID-19 for other pathogens for broader public health impact, similar to that of the COG-UK, who have plans to forward the experience to the UK Health Security Agency to inform the development of a national pathogen genomics service. Sustained investment and engagement are critical to take full advantage of this enhanced genomics surveillance capability for other nationally notifiable pathogens that require close monitoring and targeted responses to reduce the public health, social and economic impacts of infectious diseases.


Effective responses to rapid environmental change rely on observations to inform planning and decision-making. Reviewing literature from 124 programs across the globe and analyzing survey data for 30 Arctic community-based monitoring programs, we compare top-down, large-scale program driven approaches with bottom-up approaches initiated and steered at the community level. Connecting these two approaches and linking to Indigenous and local knowledge yields benefits including improved information products and enhanced observing program efficiency and sustainability. We identify core principles central to such improved links: matching observing program aims, scales, and ability to act on information; matching observing program and community priorities; fostering compatibility in observing methodology and data management; respect of Indigenous intellectual property rights and the implementation of free, prior, and informed consent; creating sufficient organizational support structures; and ensuring sustained community members’ commitment. Interventions to overcome challenges in adhering to these principles are discussed. Local to global-scale transformational change in socioenvironmental systems , holders of Indigenous or local knowledge, or government agencies . In the context of observing or monitoring programs, coproduction may include codesign of observing systems, and comanagement of observing and systems operations.Indigenous knowledge. Understandings, skills, and worldviews developed by societies with centuries to millennia of interactions with their natural surroundings, and with potential to inform decision-making about fundamental aspects of day-to-day life. This knowledge is integral to a cultural context that includes language, systems of classification, resource use practices, social interactions, rituals, and spirituality  analysis  in Somaliland.Knowing the potential range of species is important for determining habitat requirements and conservation status and for informing decision-making. In many remote and inaccessible regions, information on wildlife is scant or does not exist. A solution in such regions may be to connect knowledge of local resource users with remote sensing of vegetation and species distribution models. In 2016 and 2017, Evangelista and colleagues  conducteGiven the nature of changes in Arctic socioenvironmental systems requiring community-level response and considering the disproportionately large number of CBM programs in the region table , we examIn the present article, we synthesize findings from this past report, combining them with a review of the global CBM literature completed for this publication and integrating findings from other case studies  Integrating Global Learning and Observations to Benefit the Environment (GLOBE) and NASA Assets (SIGNs) project uses a cocreated citizen science approach to craft local monitoring efforts that are motivated by input from elders and community leaders to address a pressing climate-related data need  have adopted ten international environmental agreements , forestry (47%), fisheries (40%), shipping (37%), tourism (37%), and mineral and hydrocarbon extraction (20%).Separate from the ten agreements, the UN SDG framework, adopted in 2015, has emerged as a key driver to enhance sustained observing and response at the global scale , we identify six broader aims, associated benefits, and challenges that derive from improved links between top-down and bottom-up observing approaches. Challenges that may prevent these benefits from being realized also are discussed and summarized in figure in situ observations are further advanced through careful selection of target monitoring or observing variables that serve a larger constituency and provide shared benefits . The ICC's work in documenting food security from an Inuit perspective lays a foundation on which observing system codesign—supported through global or regional-scale networks and alliances—can advance through the process of defining shared essential variables to implementation of observing and data networks. Therefore, the ICC food security framework can inform collaboration at the interface between CBM and global-scale satellite observing programs figure , leadingbiab018_Supplemental_FilesClick here for additional data file.


Wilson’s disease is an inherited disorder in which defective biliary excretion of copper leads to its accumulation, particularly in the liver and brain. Mutations in the ATP7B gene on chromosome 13 cause Wilson’s disease. If left untreated it will cause liver failure, neurological damage, and will be life threatening. It is considered a rare disease afflicting approximately 1 in 30,000 persons worldwide, although this rate is similar in the different countries some places show higher incidence rates. Since Costa Rica reports the highest number of cases per population, essential public health initiatives that promote wellbeing, prevent disease complications, and prolong life among the affected population have been carried out during the last decades. The most recent lead in this matter is the conformation of the Costa Rica’s National Alliance for Wilson’s disease whose main objective is to provide practical, operational, timely and relevant guidance to patients, families, and healthcare professionals in the region for early diagnosis and treatment. The development and implementation of the National Alliance for Wilson’s disease activities is crucial because it will reaffirm that early intervention and appropriate treatment, will reduce if not eliminate the burden of Wilson’s disease. Wilson’s disease (WD) also named hepatolenticular degeneration is a rare genetic disorder that causes excessive copper accumulation in the liver and brain and is fatal if not detected and treated . The disDespite the high incidence of WD in Costa Rica currently the relation between the number of deaths caused by hepatolenticular degeneration and the mortality by other liver diseases is not certain. Therefore a group of pioneers have been working together in the last years with the objective of studying profusely this disease and creating specific treatment and diagnosis guidelines for the region.“When approaching liver disease in Costa Rica; in patients under 30 years of age with chronic liver disease not secondary to alcohol consumption; the most likely diagnosis is Wilson’s disease.” Hevia-Urrutia M.D.Axiom of Wilson’s disease in Costa Rica:In 1970 Antillón-Salazar M.D. reported the first patient with WD in Costa Rica, a 17 year old man . Around On 1990, Herra et al., reported that between 1972 and 1989, 150 cases of WD were diagnosed in Costa Rica; of these 120 were treated at Hospital San Juan de Dios. Seven patients died of acute liver failure, hemolytic anemia, encephalopathy, gastrointestinal bleeding or kidney insufficiency [At the same moment, because of the high prevalence of WD in Costa Rica nationwide-inter-hospital working groups, consisting of medical microbiologists and pathologists, were established to analyze different diagnostic methods of copper metabolism for accuracy and effectiveness.Hevia-Urrutia M.D and a group of patients founded in 1989 the Costa Rican Association of Patients with Wilson’s Disease (A.C.O.P.A.W.) . The goaA major achievement was also obtained in 1989, during Oscar Arias Sanchez’s government. The Costa Rican congress declared WD a “National Interest Disease”, this ensure the adequate treatment  and management of patients by the Costa Rican Social Security National Health System (CCSS)  and the National Children’s Hospital (genetic screening).In order to achieve its objectives the National Alliance for WD has establish a network that activates upon new possible WD diagnoses. Each member of this coalition has different roles but work in collaboration during the whole process which starts with diagnosis confirmation. Once the diagnosis is established members become fully involve in the family screening, best treatment option determination and disease management. The members also determine in conjunction priority research projects related to WD, and develop educational activities like workshops, exercise prescription and referral and other decision-making tools; addressed for healthcare professionals. These precise and effective mechanisms of interaction and communication have shown great results in approaching and solving urgent cases of WD, particularly in cases of fulminant hepatic failure.The National Alliance for WD in Costa Rica aims to establish a Latin American Wilson’s disease network through the Latin American Hepatology Association (ALEH). This network will assist in the establishment of additional national alliances, centers and committees in other Latin American countries, to collaborate in the training of diagnostic, management and treatment protocols, along with providing educational and scientific support regarding WD.Currently the National Alliance for WD in Costa Rica considers the possible establishment of collaboration with a research group in Pamplona, Spain; that has developed a successful gene therapy for WD in animal models. For the future the creation of joint collaborations and programs with other organizations outside Costa Rica that perform similar actions as the National Alliance for Wilson’s Disease are in scope. These institutions include: Medlineplus , NationaBecause of the high prevalence of WD in Costa Rica current research is being conducted to improve diagnosis, management and treatment of WD patients. Some of the research initiatives include: new variations of D-penicillamine load tests to achieve earlier diagnosis, the significance of free copper levels in patients after diagnosis and during treatment, the use of medications such as tetrathiomolibdate in patients with neurological symptoms , long teThe liver is the first organ to be affected by the buildup of copper due to WD; however, patients are often misdiagnosed with infectious hepatitis. Excess copper can also produce psychiatric or neurologic symptoms , 23 whicCeruloplasmin (ferroxidase enzyme) which is normally lower than 200 mg/L. When ceruloplasmin is low, deficiency disorders may occur, including neurological symptoms like Menkes disease . Serum cSerum free copper, which is normally greater than 200 mcg/L.Hepatic copper, which is normally greater than 250 mcg/g dry weight.The presence of Kayser-Fleischer rings on slit-lamp examination. However rings may be absent in up to 50 % of patients with hepatic WD and most asymptomatic siblings, but present in other hepatic diseases such as primary biliary cirrhosis. In contrast, Kayser-Fleischer rings are present almost invariably in neurological WD  and in nEarly diagnosis and family screening of WD is fundamental, so treatment can be initiated before liver failure or neurological damage ensues. The 2001 International Meeting of Wilson’s disease, held in Leipzig, concluded that when evaluating a potential WD patient, these fundamental diagnostic elements should be included , 26:CeruWhile often the criteria of the Leipzig score are met , the comNowadays, the genetic diagnosis is also a feasible option, especially for family screening. The sequence analysis of ATP7B gene is clinically available to identify the mutations in the ATP7B gene on chromosome 13. However, the existence of more than 500 mutants makes the genetic testing laborious and expensive  and in aOnce a patient is identified with WD, their first and second degree relatives should undergo screening for WD through ceruloplasmin determination at the nephrology laboratory, which specializes in diagnosing copper metabolism abnormalities, including WD. Test results are available in a timely manner (less than 7 days).If ceruloplasmin level is low or normal-low, the result is reported to Hevia-Urrutia M.D. team and the individual will undergo 24-h urinary copper screening.In cases where both tests are abnormal or positive for WD, further diagnostic procedures such as a 24-h D-penicillamine challenge, liver biopsy, and genetic testing may take place.In Costa Rica, after a patient has been diagnosed it is essential that family members also get tested. The most successful WD detection and diagnostic method for family members of patients diagnosed with WD is as follows:Patients in Costa Rica diagnosed with WD (symptomatic and asymptomatic) are referred to a tertiary care level hospital and followed by specialists in gastroenterology and hepatology. Patients diagnosed with fulminant WD undergo an inter-hospital protocol for treatment of fulminant hepatic failure and liver transplant.Several drugs are available for the treatment of Wilson’s disease, including D-penicillamine, trientine, zinc, tetrathiomolybdate, and dimercaprol. These drugs are designed to remove excess copper and to prevent its accumulation. If treatment is initiated immediately after diagnosis, for both presymptomatic and symptomatic patients, deterioration can be avoided and life expectancy can be comparable to healthy subjects; of course, a patient must be compliant with their therapy. In Costa Rica, treatment with zinc during pregnancy and nursing is considered because of the teratogenic effects of chelating agents like D-penicillamine and trientine.Diet is an additional consideration and WD patients should avoid foods naturally high in copper including: chocolate, nuts, mushrooms, crustaceans, soy and gelatin, along with the use of cooking utensils containing copper. To ensure the safety of water flowing through copper pipes, water should run for a few minutes before drinking . The facWhile hepatolenticular degeneration is a rare disease worldwide, it is much more common in Costa Rica. Important advances relating the pathology have being made in the last decades through a series of actions and efforts in health policy, politics, and multidisciplinary work. One of the latest interventions is the foundation in 2015 of the National Alliance for Wilson’s disease.The ultimate goal of the Costa Rica’s National Alliance for Wilson’s disease is to promote awareness and early intervention of WD in a country un-proportionally afflicted with this deadly disease. Currently this initiative has begun implementing actions by evaluating guidelines for early diagnosis and adequate treatments, dissemination of relevant information on current research, legal issues and the support for WD patients and families; that have proof substantial reduction on Wilson’s disease affliction.The future prospects of the Costa Rican WD National Alliance is the establishment of international clinical and research collaborations with other Latin American countries, Europe and Japan. As well the development of relations with similar organizations like the Wilson Disease Centers of Excellence. These mutual benefit collaborative initiatives are the cornerstone for future diagnosis, treatment and management of WD.AASLD, American Association for the Study of Liver Diseases; ACOPAW, Costa Rican Wilson’s Disease Patient Association; ALEH, Latin American Hepatology Association; CCSS, Costa Rican Social Security National Health System; EASL, European Society for Liver Diseases; CLF, Canadian Liver Foundation; WD, Wilson’s disease; WDA, Wilson’s Disease Association


Our paper describes the overall framework and strategies that SMART-Africa team developed to strengthen capacity in three SSA countries  while focusing on its contextualization for the Kenyan school-community mental health settings. Methods to document the progress and impacts are also described.Children in Sub-Saharan Africa (SSA) experience high rates of mental health problems, and the region has limited access to mental health resources and research capacity to address the needs. Despite the success of numerous evidence-based interventions (EBIs) and emerging methodology from the field of implementation science for addressing child mental health needs, most EBIs and implementation science methodology have not been applied in SSA contexts. The SMART-Africa Center aims to address these child welfare, mental health, services, and EBI implementation research gaps by establishing a regional trans-disciplinary collaborative center and studying strategies to strengthening mental health system and implementation research capacity. The design of the system and research strengthening activities is guided by a SMART-Africa Capacity Building framework. Two areas of capacity are focused. Mental health system capacity focuses on building political wills, leadership, transdisciplinary partnership, and stakeholders’ global competency in evidence child mental health policy, intervention, and service implementation research. Implementation research capacity building focuses on building researchers’ implementation research competency by carrying out an EBI implementation research (using a Hybrid Type II effectiveness-implementation). For illustration purpose, we describe how the system strengthening strategies has been applied in Kenya, and how the mixed methods design applied to assess the value and impacts of the capacity building activities. Feedback data and evaluation data collection using qualitative and quantitative methods for both areas of capacity building are still ongoing. Data will be analyzed and compared across countries in 2020–2021.Our work has shown some feasibility of applying the theory-guided system strengthening model in improving child mental health service system and research capacity in one of the three SMART-Africa partnering countries. Our mental health landscape and resource mapping in Kenya also illustrated that capacity building in SSA countries involved complex dynamic, history, and some overlap efforts with multiple partnerships, and these are critical to consider in training activity and evaluation design. The burden of mental, neurological, and substance use (MNS) disorders account for 10–27% of the Global Burden of Disease , and halpolicy, legislation and health expenditure, only 44% of SSA countries have mental health policy or legislation. Most African countries spend less than 3% of government health expenditure on mental health, and most mental health expenditure (average 71%) is consumed by mental hospitals  adaptation, implementation, and evaluation research  is a SSA regional research center funded by the US National Institute of Mental Health (NIMH) in 2016. The Center aims to address social welfare and mental health needs of children in SSA by establishing a regional transdisciplinary collaborative to support system strengthening and implementation research capacity building. Guided by the global system, implementation, and leadership strategies described above and emerging lessons informed by literature and in consultation with our SSA partners, the SMART-African Center has developed a capacity building activity framework to guide the system changes across three SSA countries . The goals of this paper are to introduce the guiding framework and strategies of our approach for strengthening child mental health/welfare system and implementation research. For illustrative purposes, we describe how this framework has been applied in Kenya.In Kenya, 75% of population are young people (under 30 years of age), with 22% aged 10–19 and 49% under age 18 . Many chpolicy Kenya has a mental health plan and legislation developed in early 1990s. Kenyan Mental Health Policy, which provides for a framework on interventions for securing mental health systems reforms, was recently launched and offered key priorities from 2015 to 2030. This is in line with the Constitution of Kenya 2010, Vision 2030, the Kenya Health Policy (2014–2030) and the global commitments  (2010–2015) Initiatives, which aim to improve mental health outcomes as part of the Sustainable Development Goals (SDGs) , many researchers recognized the importance of integrating a mental health component and engaging multilevel stakeholders in health research to achieve greater public health impacts , Kenya has been a site of interest for many international development agencies for testing novel mental health policy, leadership, cost-effective and locally relevant interventions. For example, a collaboration between University of Nairobi (UON) and the University of Washington (UW), which builds on a 30-year HIV/AIDS research collaboration, has extended previous HIV research to include maternal and child mental health, gender-based violence, and HIV related substance abuse research. A number of our Kenyan collaborators are part of this collaboration, and their partnership has yielded a number of accomplishments that has advanced Kenya’s mental health research . Under t010–2015). Two, uns (SDGs) , a numbes (SDGs) . Some of impacts . Four, sresearch . Similarresearch .In sum, a decade of mental health research and capacity building efforts in Kenya highlight the numerous strengths that the Kenyan team bring to SMART-Africa Center. The landscape and resource mapping findings also illustrate how solid mental health research competency/capacity has already been established in Kenya and which can be transferred to child mental health implementation research. The findings also suggest that mental health partnerships and system strengthening are not new to the Kenyan investigation team, and their ability to develop efficient partnerships based on their prior experiences and lessons learned. Finally, child and adolescent mental health presents with greater challenges than adult mental health research as it requires involvement of several critical implementing partners like teachers, school, child protection and government, non-governmental and community stakeholders .The goals of this paper are to introduce the guiding framework and strategies of the SMART-Africa approach for strengthening child mental health/welfare system and implementation research. SMART-Africa is aimed to address service gaps and mental health needs of children in SSA by establishing a regional transdisciplinary collaborative to support system strengthening and implementation research capacity building. Given the child mental health system is underdeveloped, under resourced and limited implementation research has been carried out in Kenya on child mental health, our research offers an opportunity to study the feasibility and impact of the SMART-Africa approach in strengthening SSA countries’ child mental health system and implementation research capacity. In this paper, we describe how SMART-Africa framework has been applied in Kenya. We also describe how the mixed methods design is applied to assess the value and impacts of the capacity building activities.a capacity building framework  and Capacity Building Leads (from South Africa) developed ramework  that wouTo further map-out activities for two areas of capacity building (system and implementation research), the SMART-Africa US and South Africa leadership team designed a list of activities that are relevant to 4 categories of activities listed in mental health system capacity building, five activities centered on building political will, leadership, trans-discipline partnership teams, and general competency in evidence-based policy, intervention, and service implementation research are focused. Activity design for this area was driven by WHO recommended Comprehensive Mental Health Action and Service Pyramid frameworks  implementation project in three country sites is structured. As per our design, the activities listed target all aspects of child mental health system barriers listed above, but actual formats vary by countries.In ameworks , 2013 anameworks , 2013, aameworks . implemeMFG is a community driven and group-based evidence-based psychoeducational and support program that strengthens families to address child disruptive behavior problems or behavioral challenges. MFG utilizes a flexible implementation approach, which can be delivered by parent peers, community health workers, or social welfare/mental health professionals. It can also be implemented in diverse settings, such as social welfare, community-based organizations, schools. MFG was developed based on a body of evidence regarding the influence of parenting and quality of family life on youth behavioral challenges; and it targets multiple risk factors tied to poverty related stress and parenting. MFG focuses on six core areas of contents (4Rs-2Ss): Rules, Responsibility, Relationships, and Respectful Communication and Stress and Social Support. As families discuss their issues around these areas, children and adult caregivers learn to solve problems together and build each other’s capacities. The approach enables the high-risk problem behaviors to be understood and tackled but also provide some common learning around internalizing and externalizing disorders at home (We chose to adapt MFG for use in SSA because: 1) the EBI addresses one of the most common child mental health problems, disruptive behavioral disorders (DBDs), in the SSA region. Estimated prevalence of DBD in SSA and our study countries ranging from 12 to 33% ; 2) it h at home .To strengthen implementation research capacity and generate new effectiveness-implementation evidence in SSA, the same three-arm Hybrid Type II effectiveness-implementation research  and Reacrich expertise and resources from multidisciplinary scholarships from both the USA and African regions  to support the training. The team of experts from all participating countries have contributed to a range of capacity building activities such as mentorship, technical support, and offering workshop training. We recognize country level variations and each country’s strengths, but at the same time recognize local specific needs and local governments’ priority differences We allow capacity-building activities or stakeholder meeting discussion topics to vary based on the needs and priorities, and provide technical implementation methodology support or knowledge sharing. We also emphasize strength building, network learning, and SSA local stakeholder collaboration, which recognize each country’s unique mental health capacity strengths and experiences, and contribution to the network of knowledge. Our network learning approach draws on existing partnerships in the four countries to create child implementation science “laboratories”, which offers the opportunity to experiment both within and across country systems. Furthermore, to create efficient communication and learning opportunities, we utilize distance learning/communication technologies as well as group- and individual-based mentorship support and learning opportunities to share implementation science related knowledge and research skills. The eclectic use of multiple training methods , facilitate knowledge sharing and translation of skills to action across SSA countries and between US and SSA countries  already have substantial mental health epidemiological research competency and partnership experiences from prior health/mental health research capacity building projects, we structured learning opportunities specifically around child mental health, and build on the existing strengths and the Kenyan partnership team’s needs . Specifii) developing and managing a new policy-academic-NGO-community multi-stakeholder partnership that engage stakeholders from government , research, NGOs , schools , and communities (children and families) for child mental health policy and service research discussion; which would be an extension of prior broader mental health research network/collaboration; ii) implementation science methodology learning and applications to child mental health ; iii) developing an implementation collaboration structure  to effectively conducting and managing multi-components of implementation research projects; iv) new child mental health service and implementation research projects development ; v) child mental health resource development, testing, and sharing  that can be used broadly used in diverse Kenya contexts; and vi) strategies to strengthening school mental health evidence and service research to support school mental health policy decision and program design.Capacity building activities identified to be focused on for Kenyan team include : Familia Pamoja in Swahili and Families Together in English. The MFG implementation and evaluation research is ongoing. As described in th Year of research. The Kenyan team has prioritized a few areas of capacity building activities listed in Completing MFG Effectiveness-Implementation Research Activities and Evaluation Study. The Kenyan team is now focusing on Stage 2 capacity building activities by carrying out a MFG effectiveness-implementation study. We plan to complete the post MFG evaluation data collection, data analysis, and disseminate the findings in 2021.Policy-academic-NGO-community multi-stakeholder partnership and stakeholder engagement. This paper is the first step towards establishing a SMART-Africa Kenya conceptual and working model. We intend to invite stakeholder participation in refining the system strengthening conceptual model so that different technical working groups of the Ministries of Health, Education and Social Services can benefit from multi-sectoral partnerships on child mental health issues using a model sensitive to Kenyan’s needs.Further strengthening inter-ministerial collaboration on child mental health. The Kenyan Ministry of Health is in principle meant to provide technical support on mental health including child and adolescent mental health to other relevant Ministries including Education. There are few entry points around mental health and the programming remains regimented towards integrated special needs pupils - those experiencing developmental and neurocognitive disabilities. We plan to work collaboratively with the Ministries to build on each other’s capacities, train in child mental health issues and integrate EBIs like Familia Pamoja into their work.Developing psychoeducational materials for later dissemination. The team has developed psychoeducational materials with a view to strengthening the existing gaps through the use of simplified information sheets in control schools and community settings. These materials were developed by clinical psychology students under guidance from the team and proofread by psychiatrists, senior MOH and MOE program officers and teachers, and materials are ready for broader dissemination in Kenya.Engaging Basic Needs (the partnering NGO) on disseminating Familia Pamoja. The involvement of Basic Needs on MFG implementation and co-leading the implementation-effectiveness research is a strategic part of capacity building of SMART Kenya and the consortium as such. Basic Needs will also be playing an instrumental role in the future scale up of the MFG model.In Additional implementation focuses on testing Familia Pamoja. As this work develops further, the in-country team is also looking to explore and agree on gaps in mental health policy in Kenya and identify points of entry to strengthen Kenyan child mental health policy. In this work, the Kenyan Ministry of Health is very supportive. By utilizing expertise of the consortium, the effort is to produce epidemiological and policy relevant data that can provide pointers to sharpening guidelines and assessments for Kenyan children in school, home and community settings. Another element of this work is to explore and agree on appropriate interventions for Kenya’s school-based mental health system and the team is looking at different ways of bolstering multi-stakeholder foci  handbook will be specifically developed to provide local and credible referrals.Translating and adapting the manual. The Kenyan team intends to contextualize the manual and adapt it further by making amendments to Kiswahili, use of culturally specific terms, formatting that is user friendly and activities responsive to parent-child working together in groups.Further developing implementation strategies. We plan to compile lessons learned from stakeholders and MFG implementers and users, and developing additional implementation strategies for consideration in future MFG or school-based mental health service and implementation research.In addition to completing the activities, the Kenyan team is planning to gather additional feedback/satisfaction, acceptability, usefulness, partnership quality, and impact data  from participating stakeholders  in Year 5 to provide overall progress and lessons learned to inform future child and mental health implementation research. There are also a few activities have been identified to continue after the project end.This paper describes the applications of the child mental health system and implementation research capacity building framework developed by the SMART-African Center and implemented in the Kenyan contexts. As illustrated in the paper, we show some feasibility of applying this framework in one of the three SMART-Africa partnering countries. In addition, our mental health landscape and resource mapping in Kenya also illustrated that capacity building in SSA countries involved complex dynamic, history, and some overlap efforts with multiple partnerships, and these are critical to consider in training activity and evaluation design. For example, in the landscape/system context analysis, we illustrated that many Kenyan researchers have involved in global research capacity-building efforts and have gained solid mental health research competency/capacity that can be transferred to child mental health implementation research. Overlook these strengths and existing capacity building efforts may hinder the development of effective North-South research partnership. Our paper also illustrates that multiple research capacity-building and collaboration efforts are occurring concurrently in Kenya, which may pose challenges in evaluating impacts of the capacity building efforts. We plan to apply qualitative data collection method to unpack how the dynamic and history influence SMART-Africa US-Kenya partnership, and better understand what the unique contribution that SMART-Africa contributes to child mental health system and implementation research in Kenya.Although this study did not provide descriptions for applying the framework to other SMART-Africa partnering countries (in Uganda and Ghana), we anticipate the applicability of the framework  and desi


In late summer of 2020, we interviewed 45 senior leaders of social services and health care organizations serving older adults throughout Washington State about service demand, new challenges, and organizational adaptations. These organizations work with people made particularly vulnerable in the pandemic. A significant share reported that half or more of their clients live at or below the poverty line (54%), are people of color (29%), or have limited English language proficiency (20%). The state’s aging network leveraged strong partnerships, expertise, and community knowledge to provide trusted essential services to older Washingtonians and their caregivers. The role of trust as an enabler of emergency response and connection in the context of gentrification, the digital divide, employment loss, and language service gaps will be discussed, as will lack of trust as a barrier to service access, particularly for Latinx immigrant and migrant older adults.