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/SummaryCerebral small vessel disease (SVD) affects the small vessels in the brain and is a leading cause of stroke and dementia. Emerging evidence supports a role of the extracellular matrix (ECM), at the interface between blood and brain, in the progression of SVD pathology but this remains poorly characterized.To address ECM role in SVD, we developed a co-culture model of mural and endothelial cells using human induced pluripotent stem cells from patients withCOL4A1/A2SVD-related mutations. This model revealed that these mutations induce apoptosis, migration defects, ECM remodelling and transcriptome changes in mural cells. Importantly, these mural cell defects exert a detrimental effect on endothelial cells tight junctions through paracrine actions.COL4A1/A2models also express high levels of matrix metalloproteinases (MMP) and inhibiting MMP activity partially rescues the ECM abnormalities and mural cell phenotypic changes. These data provide a basis for targeting MMP as a therapeutic opportunity in SVD.HighlightsA novel human iPSC-derived model of genetic SVD due to collagen IV (COL4A1/A2) mutations is describedMural cells expressingCOL4A1/A2mutations have prominent ECM abnormalities as seen in patients and mouse models and contribute to endothelial cells defectsECM and endothelial cells abnormalities can be rescued by MMP inhibition in theCOL4A1/A2model

Efficient and effective methods for converting human induced pluripotent stem cells (iPSC) into differentiated derivatives are critical for performing robust, large-scale studies of development and disease modelling, and for providing a source of cells for regenerative medicine. Here, we describe a 14-day neural differentiation protocol which allows for the scalable, simultaneous differentiation of multiple iPSC lines into cortical neural stem cells (NSCs). We currently employ this protocol to differentiate and compare sets of engineered iPSC lines carrying loss of function alleles in developmental disorder associated genes, alongside isogenic wildtype controls. Using RNA sequencing (RNA-Seq), we can examine the changes in gene expression brought about by each disease gene knockout, to determine its impact on neural development and explore mechanisms of disease. The 10-day Neural Induction period uses the well established dual-SMAD inhibition approach combined with Wnt/β-Catenin inhibition to selectively induce formation of cortical NSCs. This is followed by a 4-day Neural Maintenance period facilitating NSC expansion and rosette formation, and NSC cryopreservation. We also describe methods for thawing and passaging the cryopreserved NSCs, which are useful in confirming their viability for further culture. Routine implementation of ICC Quality Control confirms the presence of PAX6-positive and/or FOXG1-positive NSCs and the absence of OCT4-positive iPSCs after differentiation. RNA-Seq, flow cytometry, immunocytochemistry (ICC) and RT-qPCR provide additional confirmation of robust presence of NSC markers in the differentiated cells. The broader utility and application of our protocol is demonstrated by the successful differentiation of wildtype iPSC lines from five additional independent donors. This paper thereby describes an efficient method for the production of large numbers of high purity cortical NSCs, which are widely applicable for downstream research into developmental mechanisms, further differentiation into postmitotic cortical neurons, or other applications such as large-scale drug screening experiments.

Human induced pluripotent stem cells (hiPSC) offer a tractable system to model the blood-brain barrier (BBB). Here we detail the assembly of a triple co-culture hiPSC-BBB model, using hiPSC-derived brain microvascular endothelial cells (BMEC), astrocytes, and mural cells (MC). Transendothelial electrical resistance (TEER) and sodium fluorescein (NaFl) permeability can be used to test the barrier properties. The model has applications in studying BBB-related pathology and for drug screening.

Background Effectiveness of end-of-shift patient handover between nurses may be impacted by poor communication. This can be improved with the use of information tools, either electronic or paper-based. Few studies have investigated the activities that support patient handover, and fewer have explored how several of these tools used together affects the handover process. Purpose The aim of this study was to understand coordination challenges in end-of-shift patient handover between nurses and the influence of multiple information tools used in that context. Methodology A qualitative methodology to investigate phenomena in an acute care hospital in the United States was used in this study. Semistructured interviews were used to elicit insights from 16 nurses. Data were analyzed by coding three types of task dependencies (prerequisite, simultaneous, and shared) and three information tools (electronic medical records [EMRs], Kardex, and printouts of EMR data). Results In preparation for a handover, nurses were burdened by ensuring that information in the EMR was correct and complete. A one-sheet Kardex was the tool nurses in the study preferred, because the essential information was at hand and it provided structure to the communication. Printouts of EMR data were often physically cumbersome and not useful in their current form, although they may be useful for communicating anomalous data. Conclusion This study provides insights regarding the challenges of care coordination in end-of-shift patient handover between nurses and the usages of a variety of information tools in preparation for handover, as well as the actual handover process. Practice implications Multiple interrelated information tools may be used to support patient handover. Health leaders should focus efforts on further advancing protocols for end-of-shift nurse handovers. Health system designers should design information tools to align them with their defined purpose in the handover process. Future work should consider both the information needs of nurses and the goal of improving nurse workflows.

ObjectiveHospice at Home (HAH) services aim to enable patients to be cared for and die at home, if that is their choice and achieve a ‘good death’. A national survey, in 2017, aimed to describe and compare the features of HAH services and understand key enablers to service provision.MethodsService managers of adult HAH services in the ‘Hospice UK’ and National Association for Hospice at Home directories within England were invited to participate. Information on service configuration, referral, staffing, finance, care provision and enablers to service provision were collected by telephone interview.ResultsOf 128 services invited, 70 (54.7%) provided data. Great diversity was found. Most services operated in mixed urban/rural (74.3%) and mixed deprivation (77.1%) areas and provided hands-on care (97.1%), symptom assessment and management (91.4%), psychosocial support (94.3%) and respite care (74.3%). Rapid response (within 4 hours) was available in 65.7%; hands-on care 24 hours a day in 52.2%. Charity donations were the main source of funding for 71.2%. Key enablers for service provision included working with local services (eg, district nursing, general practitioner services), integrated health records, funding and anticipatory care planning. Access to timely medication and equipment was critical.ConclusionThere is considerable variation in HAH services in England. Due to this variation it was not possible to categorise services into delivery types. Services work to supplement local care using a flexible approach benefitting from integration and funding. Further work defining service features related to patient and/or carer outcomes would support future service development.

Subject to colonial incursions for centuries, Taiwan has long struggled to define itself. Even today, after the May 2016 inauguration of President Tsai Ing-wen of the independence-supporting Democratic Progressive Party, the island is once again wracked by debate over its status: Is it an independent nation, or a province of China? Which aspects of its complex history should be seized upon to define its present and future? By some definitions “postnational,” modern Taiwan people are actively shaping their citizen-identities based on social experience and economic and cultural reality rather than unwieldy and outdated ideological constructs. In this essay I look at two recent English-language novels set in Taiwan, Francie Lin’s The Foreigner and Julie Wu’s The Third Son, which feature Taiwanese American protagonists who struggle with personal and cultural history in coming to terms with their own complex identity. Approaching these characters as “postnational” figures, I find ways in which their experience can be seen to parallel Taiwan’s own uncertain and dynamic situation.

Pregnant women living in or traveling to areas with local mosquito-borne Zika virus transmission are at risk for Zika virus infection, which can lead to severe fetal and infant brain abnormalities and microcephaly (1). In February 2016, CDC recommended 1) routine testing for Zika virus infection of asymptomatic pregnant women living in areas with ongoing local Zika virus transmission at the first prenatal care visit, 2) retesting during the second trimester for women who initially test negative, and 3) testing of pregnant women with signs or symptoms consistent with Zika virus disease (e.g., fever, rash, arthralgia, or conjunctivitis) at any time during pregnancy (2). To collect information about pregnant women with laboratory evidence of recent possible Zika virus infection* and outcomes in their fetuses and infants, CDC established pregnancy and infant registries (3). During January 1, 2016-April 25, 2017, U.S. territories† with local transmission of Zika virus reported 2,549 completed pregnancies§ (live births and pregnancy losses at any gestational age) with laboratory evidence of recent possible Zika virus infection; 5% of fetuses or infants resulting from these pregnancies had birth defects potentially associated with Zika virus infection¶ (4,5). Among completed pregnancies with positive nucleic acid tests confirming Zika infection identified in the first, second, and third trimesters, the percentage of fetuses or infants with possible Zika-associated birth defects was 8%, 5%, and 4%, respectively. Among liveborn infants, 59% had Zika laboratory testing results reported to the pregnancy and infant registries. Identification and follow-up of infants born to women with laboratory evidence of recent possible Zika virus infection during pregnancy permits timely and appropriate clinical intervention services (6).

‭Southern California’s hidden treasures include two church interiors containing elements designed by Alfredo Ramos Martinez (1871–1946). This Mexican-born artist trained in France, returned to take an activist role in Mexican revolutionary culture, and migrated to the United States in 1929. For sixteen years, his talents were in demand among members of the Hollywood elite. In 1934, he produced the fresco murals at the Santa Barbara Cemetery Chapel, a jewel of Spanish Revival architecture. His images crossed over traditional boundaries between the sacred and the profane. He created odes to human rights and suffering humanity, depicting Christ and his mother as indigenous peasants with dark-skinned New World ethnicity. A decade later in 1946, Ramos sketched designs for his final projects at St. John the Evangelist Church in Los Angeles: a series of stained glass windows representing fourteen multiethnic saints as well as incomplete oil painted Stations of the Cross that recall his earlier pictures of suffering humanity. The architectural setting—a modernist church with stripped-down forms and materials of concrete, steel, and neon—announces a radically transformed post-war industrial culture. The contrast of these two aesthetics, the Spanish Revival and the modernist, demonstrates an evolution in liturgical forms as Californians came to grips with global migrations and an evolving modernist identity.‬

Imperial British India is the point of origin for protagonists in both Frances Hodgson Burnett’s The Secret Garden (1911) and Rudyard Kipling’s The Jungle Books (1894–1895), two influential children’s stories in which late Victorian notions of childhood education and nature converge with those of national and imperial identity. In Burnett’s The Secret Garden, Mary Lennox, orphaned in colonial India, is restored to health only as she is “schooled” in the English countryside. Kipling, meanwhile, finds the imperial setting a fine and fitting place to raise his hero Mowgli. In both cases the young protagonists develop physically, spiritually and socially in classrooms of nature outside or parallel to mainstream culture. This paper follows the different “escapes” offered characters in these works, while tracing the contours of class structure, gender, family relations, educational standards and imperial identity as experienced in the last decades of the nineteenth century.

In her article "Mapping Memory in Tran's Vietnamerica" Mary Goodwin explores the use of maps, landscape paintings, and other topographic images in Gia-Bao Tran's graphic memoir chronicling the "postmemory" of the US-American son of wartime refugees. Tran's family immigrated to the United States in 1975 following the fall of Saigon. Tran knew nothing of his parents' hardships and struggle to escape Vietnam until he returned for relatives' funerals in his 20s. Similar to Spiegelman's Maus, Vietnamerica is a mixed-media memoir containing photographs, maps, and comics in various styles. Following Hirsch's lead in demonstrating the special historical value of photographs in Maus, Goodwin argues for the unique value of the maps and landscape visuals Tran uses to relate Vietnam's history and his family's experiences. The medium of the graphic novel presents its own challenges as auto/biography and historical record and topographic images introduce a complication in juxtaposing the "real" public world with the personal and individual. Thus Vietamerica becomes an ever-shifting kaleidoscope of perspective on a multi-dimensional history of war, exile, and personal struggles to come to terms with cultural and familial identity.

This is the first reported case of psychotic illness following pediatric cardiac transplantation. The case highlights diagnostic issues, and indicates a need for monitoring the psychological effects of cardiac transplantation in children.

This paper is based upon our experience as a psychosocial team working on the paediatric heart/heart-lung (H/HLT) programme for the last 10 years. During this time more than 350 children have been assessed, 240 have been put onto an active waiting list and 160 have had transplants. The essence of this paper is a detailed description of the multidisciplinary and comprehensive approach to children who are being considered for heart or heart-lung transplantation, and their families. The key issues of which we have become aware are: creating a therapeutic alliance; listening to and involving the children; involving the wider network; understanding the family's illness narrative and their individual belief systems, including issues of culture, ethnicity and spirituality; acknowledging and addressing the power imbalance between the child/family and professional. (Int J Psych Clin Pract 2000; 4:93-99).

Sex-role stereotyping in advertising has been a controversial issue in the past decade. While studies have shown a disproportionate use of males in authority roles, little research has been done to examine the effects on consumers' self-efficacies. Results from this research indicate that, contrary to expectations, females had higher confidence in their purchase decisions after viewing stereotypical television advertisements. Social implications for advertisers and marketers are discussed.

For pregnant women, lactating mothers, infants, children, and adolescents, adequate nutrition is vital for attaining growth, promoting development, and maintaining health and wellbeing. Projected demographic trends support the continuing nutrition needs of these target groups. Because of the "baby boom" following World War II, the female population in childbearing age, which has increased rapidly since 1970, will continue to increase from 48 million to between 55 and 57 million women by 1990. As a result, births for the 1980s will be above the current level of nearly 3.3 million and could easily reach 4 million. Between 1978 and 1990, the following changes are expected among the child population: the number of oneto four-yearolds are expected to increase slightly from 15 million to around 19 million; the fiveto thirteen-year-olds will increase slightly from 31 million to about 33 million; and the fourteento seventeen-year-olds will experience a significant decrease from 16 million to between 12 and 13 million. In addition, women appear to be having their first babies at a later age; birth rates for teenagers, 15 to 17 years of age, are decreasing; and more women are receiving prenatal care earlier in pregnancy. Although infant mortality rates have declined, there are still significant differences among racial groups; e.g., the proportion of low-birth-weight infants born to black women is nearly twice as high as the proportion born to white women. Low-birth-weight babies have higher mortality rates and are more likely to suffer from handicapping conditions. There is ample evidence that higher weight gain in pregnancy is related to higher birth weight. Dental problems still affect large numbers of children as do obesity and other nutrition-related problems, such as iron-deficiency anemia.