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Knowing the cost of specific health and social care services is crucial information for making decisions about what support is provided to those who need help, assisting service providers to plan for the future of their services, and more generally for allocating scarce resources and budgets. To support resourcing decisions, the Unit Cost Programme has been carried out by the Personal Social Services Research Unit (PSSRU) at the University of Kent. They produced the annual cost estimates for the delivery of health and social care services for 29 years. Lesley Curtis, a Senior Research Fellow at PSSRU led the Unit Costs of Health and Social Care programme, alongside Jennifer Beecham, Ann Netten and Amanda Burns. In 2020, Karen Jones, Co-Director of PSSRU, led the programme for two years. The annual publication is freely available online. The work is underpinned by three key principles: 1. The provision of robust, consistent estimates of costs based on economic theory and reflecting the long-run marginal opportunity cost. 2. Comprehensive coverage of available health and social care services, reflective of new service developments. 3. Clarity and accessibility in the presentation of cost estimates. The annual volume included nationally-applicable costs for around 80 health and adult social care services (NHS, local authority, private and voluntary) as well as at least three articles by academics and practitioners each year. Unit costs represents the total expenditure incurred to produce one unit of output in health and social care. For example, the cost of one hour of a nurse or GP’s time, or a face-to-face appointment with a social worker or perhaps a speech therapist. It could also be a week in a residential care or nursing home or the cost of a day care attendance. The consistency, comprehensiveness and robustness of what was produced over time has seen the volumes become a cornerstone of economic evaluations and a resource to inform deliberations among decision-ma

Social media platforms capture and trade consumer data for analysis, user profiling and for sale to interested parties and is used extensively in marketing. To collect, store, process and resell this data, they are legally required to obtain informed consent. However, users may agree to consent without the ability to comprehend the consequences of what that consent means. In this article we examine the complexity of privacy policies and raise ethical concerns about the ability of users to comprehend their consent actions. Using readability scores and reading fluency instruments, we analyzed the accessibility of privacy policies from a major social media platform (Meta) and a smaller platform (Twitter). Findings indicate that due to reading fluency and document length it is unlikely all users, especially minors, can authorize the consent actions which raises ethical concerns. Practical implications for managers and policy makers are also discussed and regulators may need to review users’ access to platforms where they lack the ability to comprehend their consent actions.

Social media platforms capture and trade consumer data for analysis, user profiling and for sale to interested parties and is used extensively in marketing. To collect, store, process and resell this data, they are legally required to obtain informed consent. However, users may agree to consent without the ability to comprehend the consequences of what that consent means. In this article we examine the complexity of privacy policies and raise ethical concerns about the ability of users to comprehend their consent actions. Using readability scores and reading fluency instruments, we analyzed the accessibility of privacy policies from a major social media platform (Meta) and a smaller platform (Twitter). Findings indicate that due to reading fluency and document length it is unlikely all users, especially minors, can authorize the consent actions which raises ethical concerns. Practical implications for managers and policy makers are also discussed and regulators may need to review users’ access to platforms where they lack the ability to comprehend their consent actions.

Knowing the cost of specific health and social care services is crucial information for making decisions about what support is provided to those who need help, assisting service providers to plan for the future of their services, and more generally for allocating scarce resources and budgets. To support resourcing decisions, the Unit Cost Programme has been carried out by the Personal Social Services Research Unit (PSSRU) at the University of Kent. They produced the annual cost estimates for the delivery of health and social care services for 29 years. Lesley Curtis, a Senior Research Fellow at PSSRU led the Unit Costs of Health and Social Care programme, alongside Jennifer Beecham, Ann Netten and Amanda Burns. In 2020, Karen Jones, Co-Director of PSSRU, led the programme for two years. The annual publication is freely available online. The work is underpinned by three key principles: 1. The provision of robust, consistent estimates of costs based on economic theory and reflecting the long-run marginal opportunity cost. 2. Comprehensive coverage of available health and social care services, reflective of new service developments. 3. Clarity and accessibility in the presentation of cost estimates. The annual volume included nationally-applicable costs for around 80 health and adult social care services (NHS, local authority, private and voluntary) as well as at least three articles by academics and practitioners each year. Unit costs represents the total expenditure incurred to produce one unit of output in health and social care. For example, the cost of one hour of a nurse or GP’s time, or a face-to-face appointment with a social worker or perhaps a speech therapist. It could also be a week in a residential care or nursing home or the cost of a day care attendance. The consistency, comprehensiveness and robustness of what was produced over time has seen the volumes become a cornerstone of economic evaluations and a resource to inform deliberations among decision-ma

This paper explores processes of urban park creation from the mid-1800s to show how ‘green lungs’ and ‘green liberty’ shaped the health geography of the modern city. Tracking this story across a transatlantic canvas (using examples from London, Paris, New York and Montreal), it looks at how ideas around fresh air, exercise and greenery sat within municipal designs for a functional metabolic landscape, what I call somatic urbanism. Plotting the historical contours of the park as a landscape of health has two main uses. Firstly, it usefully connects the worlds of medicine and environment to show how debates about industrialism, modernity, sanitation and social reform found common ground. Secondly, in a contemporary world where ventilation issues have been highlighted by the coronavirus pandemic and municipal authorities grapple with anthropogenic challenges, it argues that historical studies of health and environment assume a vital importance in shaping the future of sustainable cities.

This paper explores processes of urban park creation from the mid-1800s to show how ‘green lungs’ and ‘green liberty’ shaped the health geography of the modern city. Tracking this story across a transatlantic canvas (using examples from London, Paris, New York and Montreal), it looks at how ideas around fresh air, exercise and greenery sat within municipal designs for a functional metabolic landscape, what I call somatic urbanism. Plotting the historical contours of the park as a landscape of health has two main uses. Firstly, it usefully connects the worlds of medicine and environment to show how debates about industrialism, modernity, sanitation and social reform found common ground. Secondly, in a contemporary world where ventilation issues have been highlighted by the coronavirus pandemic and municipal authorities grapple with anthropogenic challenges, it argues that historical studies of health and environment assume a vital importance in shaping the future of sustainable cities.

"Karen’s vignette shows how delving into environmental histories through text can reveal influences, propagated over time that shape our understanding of landscape. Often, these concepts, conveyed by words like ‘naturalness’ or ‘wildness’, are used without the writer necessarily being aware of their complex histories. But words can also be used deliberately, to change the way we think about a place." (taken from the text in the book after this section)

Immune dysregulation has been noted consistently in individuals with autism spectrum disorder (ASD) and their families, including the presence of autoantibodies reactive to fetal brain proteins in nearly a quarter of mothers of children with ASD versus <1% in mothers of typically developing children. Our lab recently identified the peptide epitope sequences on seven antigenic proteins targeted by these maternal autoantibodies. Through immunization with these peptide epitopes, we have successfully created an endogenous, antigen-driven mouse model that ensures a constant exposure to the salient autoantibodies throughout gestation in C57BL/6J mice. This exposure more naturally mimics what is observed in mothers of children with ASD. Male and female offspring were tested using a comprehensive sequence of behavioral assays, as well as measures of health and development highly relevant to ASD. We found that MAR-ASD male and female offspring had significant alterations in development and social interactions during dyadic play. Although 3-chambered social approach was not significantly different, fewer social interactions with an estrous female were noted in the adult male MAR-ASD animals, as well as reduced vocalizations emitted in response to social cues with robust repetitive self-grooming behaviors relative to saline treated controls. The generation of MAR-ASD-specific epitope autoantibodies in female mice prior to breeding created a model that demonstrates for the first time that ASD-specific antigen-induced maternal autoantibodies produced alterations in a constellation of ASD-relevant behaviors.

Gender stereotypes are prevalent in education, as is all spheres of society. Gender stereotypes squash talent, limit educational experiences and achievement and corrode aspirations - which in turn can limit professional opportunities and prospects. This book supports you to recognise and challenge gender stereotypes in educational settings and in your own practice. It iincules practical guidance and strategies.

Immune dysregulation has been noted consistently in individuals with autism spectrum disorder (ASD) and their families, including the presence of autoantibodies reactive to fetal brain proteins in nearly a quarter of mothers of children with ASD versus <1% in mothers of typically developing children. Our lab recently identified the peptide epitope sequences on seven antigenic proteins targeted by these maternal autoantibodies. Through immunization with these peptide epitopes, we have successfully created an endogenous, antigen-driven mouse model that ensures a constant exposure to the salient autoantibodies throughout gestation in C57BL/6J mice. This exposure more naturally mimics what is observed in mothers of children with ASD. Male and female offspring were tested using a comprehensive sequence of behavioral assays, as well as measures of health and development highly relevant to ASD. We found that MAR-ASD male and female offspring had significant alterations in development and social interactions during dyadic play. Although 3-chambered social approach was not significantly different, fewer social interactions with an estrous female were noted in the adult male MAR-ASD animals, as well as reduced vocalizations emitted in response to social cues with robust repetitive self-grooming behaviors relative to saline treated controls. The generation of MAR-ASD-specific epitope autoantibodies in female mice prior to breeding created a model that demonstrates for the first time that ASD-specific antigen-induced maternal autoantibodies produced alterations in a constellation of ASD-relevant behaviors.

It has been estimated that autism spectrum disorder (ASD) now affects 1 in 59 children in the United States. Although the cause(s) of ASD remain largely unknown, it is becoming increasingly apparent that ASD can no longer be defined simply as a behavioral disorder, but is in effect a rather complex and highly heterogeneous biological disorder. Up until recently the brain was thought to be "immune privileged." However, it is now known that the immune system plays critical roles in the development and functioning of the brain throughout life. Recent evidence from multiple investigators has illustrated the deleterious role that dysregulation of the maternal immune system during gestation can play in the manifestation of changes in neurodevelopment, resulting in the development of neurobehavioral disorders such as ASD. One potential etiologic pathway through which the maternal immune system can interfere with neurodevelopment is through maternal autoantibodies that recognize proteins in the developing fetal brain. This mechanism of pathogenesis is now thought to lead to a subphenotype of ASD that has been termed maternal autoantibody related (MAR) ASD. This review provides an overview of the current research implicating the presence of brain-reactive maternal autoantibodies as a risk factor for MAR ASD.

Natural selection produces cognitive systems that are well designed for solving ancestral adaptive problems. For a group-living species like our own, this principle implies that interacting with others will be regulated by sophisticated cognitive systems. Here we explain how evolutionary game theory is used to identify ancestral problems of social interaction and what counted as adaptive solutions to these problems during our evolutionary past. We start with a detailed examination of selection pressures that shape mechanisms for interacting with kin; these specify an envelope of conditions in which selection favors (i) acting with beneficence toward kin and (ii) avoiding sexual contact with kin. By combining these analyses with knowledge of how our hunter-gatherer ancestors lived, evolutionary psychologists were able to develop and test hypotheses about the computational design of systems regulating interaction with kin. These cognitive adaptations produce intuitions about how we ought to treat kin and how kin ought to treat us—moral intuitions about duties of beneficence and sexual prohibitions. We then consider selection for cooperation with unrelated individuals and how this differs from interactions with kin. Topics include the evolution of cooperation by partner control (punishment) versus partner choice; collective action; and the role of luck versus effort in sharing. Research guided by these theories suggests that selection has produced adaptations that generate different moral inferences in each of these domains. Capturing this moral diversity may require normative theories that embrace moral pluralism—brands of ethical intuitionism, moral sentimentalism, or virtue ethics.

Immunoglobulin G (IgG) autoantibodies reactive to fetal brain proteins in mothers of children with ASD have been described by several groups. To understand their pathologic significance, we developed a mouse model of maternal autoantibody related ASD (MAR-ASD) utilizing the peptide epitopes from human autoantibody reactivity patterns. Male and female offspring prenatally exposed to the salient maternal autoantibodies displayed robust deficits in social interactions and increased repetitive self-grooming behaviors as juveniles and adults. In the present study, neuroanatomical differences in adult MAR-ASD and control offspring were assessed via high-resolution ex vivo magnetic resonance imaging (MRI) at 6 months of age. Of interest, MAR-ASD mice displayed significantly larger total brain volume and of the 159 regions examined, 31 were found to differ significantly in absolute volume (mm3) at an FDR of <5%. Specifically, the absolute volumes of several white matter tracts, cortical regions, and basal nuclei structures were significantly increased in MAR-ASD animals. These phenomena were largely driven by female MAR-ASD offspring, as no significant differences were seen with either absolute or relative regional volume in male MAR-ASD mice. However, structural covariance analysis suggests network-level desynchronization in brain volume in both male and female MAR-ASD mice. Additionally, preliminary correlational analysis with behavioral data relates that volumetric increases in numerous brain regions of MAR-ASD mice were correlated with social interaction and repetitive self-grooming behaviors in a sex-specific manner. These results demonstrate significant sex-specific effects in brain size, regional relationships, and behavior for offspring prenatally exposed to MAR-ASD autoantibodies relative to controls.

Immunoglobulin G (IgG) autoantibodies reactive to fetal brain proteins in mothers of children with ASD have been described by several groups. To understand their pathologic significance, we developed a mouse model of maternal autoantibody related ASD (MAR-ASD) utilizing the peptide epitopes from human autoantibody reactivity patterns. Male and female offspring prenatally exposed to the salient maternal autoantibodies displayed robust deficits in social interactions and increased repetitive self-grooming behaviors as juveniles and adults. In the present study, neuroanatomical differences in adult MAR-ASD and control offspring were assessed via high-resolution ex vivo magnetic resonance imaging (MRI) at 6 months of age. Of interest, MAR-ASD mice displayed significantly larger total brain volume and of the 159 regions examined, 31 were found to differ significantly in absolute volume (mm3) at an FDR of <5%. Specifically, the absolute volumes of several white matter tracts, cortical regions, and basal nuclei structures were significantly increased in MAR-ASD animals. These phenomena were largely driven by female MAR-ASD offspring, as no significant differences were seen with either absolute or relative regional volume in male MAR-ASD mice. However, structural covariance analysis suggests network-level desynchronization in brain volume in both male and female MAR-ASD mice. Additionally, preliminary correlational analysis with behavioral data relates that volumetric increases in numerous brain regions of MAR-ASD mice were correlated with social interaction and repetitive self-grooming behaviors in a sex-specific manner. These results demonstrate significant sex-specific effects in brain size, regional relationships, and behavior for offspring prenatally exposed to MAR-ASD autoantibodies relative to controls.

Attachment theory and research are drawn upon in many applied settings, including family courts, but misunderstandings are widespread and sometimes result in misapplications. The aim of this consensus statement is, therefore, to enhance understanding, counter misinformation, and steer family-court utilisation of attachment theory in a supportive, evidence-based direction, especially with regard to child protection and child custody decision-making. This article is divided into two parts. In the first part, we address problems related to the use of attachment theory and research in family courts, and discuss reasons for these problems. To this end, we examine family court applications of attachment theory in the current context of the best-interest-of-the-child standard, discuss misunderstandings regarding attachment theory, and identify factors that have hindered accurate implementation. In the second part, we provide recommendations for the application of attachment theory and research. To this end, we set out three attachment principles: the child's need for familiar, non-abusive caregivers; the value of continuity of good-enough care; and the benefits of networks of attachment relationships. We also discuss the suitability of assessments of attachment quality and caregiving behaviour to inform family court decision-making. We conclude that assessments of caregiver behaviour should take center stage. Although there is dissensus among us regarding the use of assessments of attachment quality to inform child custody and child-protection decisions, such assessments are currently most suitable for targeting and directing supportive interventions. Finally, we provide directions to guide future interdisciplinary research collaboration., La teoría y la investigación sobre el apego se utilizan en muchos contextos aplicados, incluidos los juzgados de familia, pero hay malentendidos muy extendidos y que a veces dan lugar a aplicaciones erróneas. El objetivo de este documento de consenso es, por lo tanto, mejorar la comprensión, contrarrestar la desinformación y dirigir el uso de la teoría del apego por parte de los juzgados de familia en la dirección de un apoyo basado en la evidencia, especialmente en lo que respecta a la protección de niñas y niños y las decisiones sobre su custodia. El artículo se divide en dos partes. En la primera abordamos los problemas relacionados con el uso de la teoría y la investigación sobre apego en los juzgados de familia, analizando las causas de tales problemas. Para ello examinamos las aplicaciones de la teoría del apego en los juzgados de familia en el marco del concepto de interés superior de niños y niñas, analizamos los malentendidos relacionados con la teoría del apego e identificamos los factores que han obstaculizado su adecuada aplicación. En la segunda parte ofrecemos recomendaciones para la aplicación de la teoría y la investigación sobre apego. Para ello establecemos tres principios del apego: la necesidad de niñas y niños de cuidadoras y cuidadores habituales que no maltraten, el valor de la continuidad de cuidados de calidad suficientemente buena y los beneficios de las redes de relaciones de apego. También analizamos la idoneidad de las evaluaciones de los estilos de apego y del comportamiento de los cuidadores para fundamentar la toma de decisiones de los juzgados de familia. Llegamos a la conclusión de que las evaluaciones de quienes cuidan deberían ocupar un lugar central. Aunque no hay consenso entre nosotros sobre el uso de las evaluaciones del estilo de apego para fundamentar las decisiones sobre custodia y protección infantil, dichas evaluaciones son actualmente las más adecuadas para orientar y dirigir las intervenciones de apoyo. Por último, prop

Immunoglobulin G (IgG) autoantibodies reactive to fetal brain proteins in mothers of children with ASD have been described by several groups. To understand their pathologic significance, we developed a mouse model of maternal autoantibody related ASD (MAR-ASD) utilizing the peptide epitopes from human autoantibody reactivity patterns. Male and female offspring prenatally exposed to the salient maternal autoantibodies displayed robust deficits in social interactions and increased repetitive self-grooming behaviors as juveniles and adults. In the present study, neuroanatomical differences in adult MAR-ASD and control offspring were assessed via high-resolution ex vivo magnetic resonance imaging (MRI) at 6 months of age. Of interest, MAR-ASD mice displayed significantly larger total brain volume and of the 159 regions examined, 31 were found to differ significantly in absolute volume (mm3) at an FDR of <5%. Specifically, the absolute volumes of several white matter tracts, cortical regions, and basal nuclei structures were significantly increased in MAR-ASD animals. These phenomena were largely driven by female MAR-ASD offspring, as no significant differences were seen with either absolute or relative regional volume in male MAR-ASD mice. However, structural covariance analysis suggests network-level desynchronization in brain volume in both male and female MAR-ASD mice. Additionally, preliminary correlational analysis with behavioral data relates that volumetric increases in numerous brain regions of MAR-ASD mice were correlated with social interaction and repetitive self-grooming behaviors in a sex-specific manner. These results demonstrate significant sex-specific effects in brain size, regional relationships, and behavior for offspring prenatally exposed to MAR-ASD autoantibodies relative to controls.

BackgroundPerinatal exposure to air pollution and immune system dysregulation are two factors consistently associated with autism spectrum disorders (ASD) and other neurodevelopmental outcomes. However, little is known about how air pollution may influence maternal immune function during pregnancy.ObjectivesTo assess the relationship between mid-gestational circulating levels of maternal cytokines/chemokines and previous month air pollution exposure across neurodevelopmental groups, and to assess whether cytokines/chemokines mediate the relationship between air pollution exposures and risk of ASD and/or intellectual disability (ID) in the Early Markers for Autism (EMA) study.MethodsEMA is a population-based, nested case-control study which linked archived maternal serum samples collected during weeks 15-19 of gestation for routine prenatal screening, birth records, and Department of Developmental Services (DDS) records. Children receiving DDS services for ASD without intellectual disability (ASD without ID; n = 199), ASD with ID (ASD with ID; n = 180), ID without ASD (ID; n = 164), and children from the general population (GP; n = 414) with no DDS services were included in this analysis. Serum samples were quantified for 22 cytokines/chemokines using Luminex multiplex analysis technology. Air pollution exposure for the month prior to maternal serum collection was assigned based on the Environmental Protection Agency's Air Quality System data using the maternal residential address reported during the prenatal screening visit.ResultsPrevious month air pollution exposure and mid-gestational maternal cytokine and chemokine levels were significantly correlated, though weak in magnitude (ranging from - 0.16 to 0.13). Ten pairs of mid-pregnancy immune markers and previous month air pollutants were significantly associated within one of the child neurodevelopmental groups, adjusted for covariates (p < 0.001). Mid-pregnancy air pollution was not associated with any neurod

BackgroundPerinatal exposure to air pollution and immune system dysregulation are two factors consistently associated with autism spectrum disorders (ASD) and other neurodevelopmental outcomes. However, little is known about how air pollution may influence maternal immune function during pregnancy.ObjectivesTo assess the relationship between mid-gestational circulating levels of maternal cytokines/chemokines and previous month air pollution exposure across neurodevelopmental groups, and to assess whether cytokines/chemokines mediate the relationship between air pollution exposures and risk of ASD and/or intellectual disability (ID) in the Early Markers for Autism (EMA) study.MethodsEMA is a population-based, nested case-control study which linked archived maternal serum samples collected during weeks 15-19 of gestation for routine prenatal screening, birth records, and Department of Developmental Services (DDS) records. Children receiving DDS services for ASD without intellectual disability (ASD without ID; n = 199), ASD with ID (ASD with ID; n = 180), ID without ASD (ID; n = 164), and children from the general population (GP; n = 414) with no DDS services were included in this analysis. Serum samples were quantified for 22 cytokines/chemokines using Luminex multiplex analysis technology. Air pollution exposure for the month prior to maternal serum collection was assigned based on the Environmental Protection Agency's Air Quality System data using the maternal residential address reported during the prenatal screening visit.ResultsPrevious month air pollution exposure and mid-gestational maternal cytokine and chemokine levels were significantly correlated, though weak in magnitude (ranging from - 0.16 to 0.13). Ten pairs of mid-pregnancy immune markers and previous month air pollutants were significantly associated within one of the child neurodevelopmental groups, adjusted for covariates (p < 0.001). Mid-pregnancy air pollution was not associated with any neurod

Vitamin D is essential for several physiological functions and biological processes. Increasing levels of maternal vitamin D are required throughout pregnancy as a unique source of vitamin D for the fetus, and consequently maternal vitamin D deficiency may result in several adverse outcomes in newborns. However, the genetic regulation of vitamin D in pregnancy and at birth is not yet well understood. We performed genome-wide association studies of maternal midgestational serum-derived and neonatal blood-spot-derived total 25-hydroxyvitamin D from a case-control study of autism spectrum disorder (ASD). We identified one fetal locus (rs4588) significantly associated with neonatal vitamin D levels in the GC gene, encoding the binding protein for the transport and function of vitamin D. We also found suggestive cross-associated loci for neonatal and maternal vitamin D near immune genes, such as CXCL6-IL8 and ACKR1 We found no interactions with ASD. However, when including a set of cases with intellectual disability but not ASD (N = 179), we observed a suggestive interaction between decreased levels of neonatal vitamin D and a specific maternal genotype near the PKN2 gene. Our results suggest that genetic variation influences total vitamin D levels during pregnancy and at birth via proteins in the vitamin D pathway, but also potentially via distinct mechanisms involving loci with known roles in immune function that might be involved in vitamin D pathophysiology in pregnancy.

Martha Jane Canary, popularly known as Calamity Jane, was the pistol-packing, rootin’ tootin’ “lady wildcat” of the American West. Brave and resourceful, she held her own with the men of America’s most colorful era and became a celebrity both in her own right and through her association with the likes of Wild Bill Hickok and Buffalo Bill Cody. In this engaging account, Karen Jones takes a fresh look at the story of this iconic frontierswoman. She pieces together what is known of Canary’s life and shows how a rough and itinerant lifestyle paved the way for the scattergun, alcohol-fueled heroics that dominated Canary’s career. Spanning Canary’s rise from humble origins to her role as “heroine of the plains” and the embellishment of her image over subsequent decades, Jones shows her to be feisty, eccentric, transgressive—and very much complicit in the making of the myth that was Calamity Jane.

High-throughput complementary DNA sequencing technologies have advanced our understanding of transcriptome complexity and regulation. However, these methods lose information contained in biological RNA because the copied reads are often short and modifications are not retained. We address these limitations using a native poly(A) RNA sequencing strategy developed by Oxford Nanopore Technologies. Our study generated 9.9 million aligned sequence reads for the human cell line GM12878, using thirty MinION flow cells at six institutions. These native RNA reads had a median length of 771 bases, and a maximum aligned length of over 21,000 bases. Mitochondrial poly(A) reads provided an internal measure of read-length quality. We combined these long nanopore reads with higher accuracy short-reads and annotated GM12878 promoter regions to identify 33,984 plausible RNA isoforms. We describe strategies for assessing 3' poly(A) tail length, base modifications and transcript haplotypes.

Natural selection produces cognitive systems that are well designed for solving ancestral adaptive problems. For a group-living species like our own, this principle implies that interacting with others will be regulated by sophisticated cognitive systems. Here we explain how evolutionary game theory is used to identify ancestral problems of social interaction and what counted as adaptive solutions to these problems during our evolutionary past. We start with a detailed examination of selection pressures that shape mechanisms for interacting with kin; these specify an envelope of conditions in which selection favors (i) acting with beneficence toward kin and (ii) avoiding sexual contact with kin. By combining these analyses with knowledge of how our hunter-gatherer ancestors lived, evolutionary psychologists were able to develop and test hypotheses about the computational design of systems regulating interaction with kin. These cognitive adaptations produce intuitions about how we ought to treat kin and how kin ought to treat us—moral intuitions about duties of beneficence and sexual prohibitions. We then consider selection for cooperation with unrelated individuals and how this differs from interactions with kin. Topics include the evolution of cooperation by partner control (punishment) versus partner choice; collective action; and the role of luck versus effort in sharing. Research guided by these theories suggests that selection has produced adaptations that generate different moral inferences in each of these domains. Capturing this moral diversity may require normative theories that embrace moral pluralism—brands of ethical intuitionism, moral sentimentalism, or virtue ethics.

High-throughput complementary DNA sequencing technologies have advanced our understanding of transcriptome complexity and regulation. However, these methods lose information contained in biological RNA because the copied reads are often short and modifications are not retained. We address these limitations using a native poly(A) RNA sequencing strategy developed by Oxford Nanopore Technologies. Our study generated 9.9 million aligned sequence reads for the human cell line GM12878, using thirty MinION flow cells at six institutions. These native RNA reads had a median length of 771 bases, and a maximum aligned length of over 21,000 bases. Mitochondrial poly(A) reads provided an internal measure of read-length quality. We combined these long nanopore reads with higher accuracy short-reads and annotated GM12878 promoter regions to identify 33,984 plausible RNA isoforms. We describe strategies for assessing 3' poly(A) tail length, base modifications and transcript haplotypes.

Karen Henson Jones était sur le chemin convenu de la réussite dans le monde des affaires, lorsqu'un soudain problème cardiaque à l'âge de 30 ans l'a projetée au seuil de la mort. Durant une expérience hors du commun, elle a dû faire un choix entre quitter son corps ou revenir sur Terre. Quand son souhait de continuer à vivre lui a été accordé, Karen a forcément été confrontée à la vie qu'elle avait vécue jusque-là.Avec chaleur, émerveillement et intelligence, Au c?ur des miracles nous amène avec elle dans un voyage inspirant à travers l'Inde, l'Italie, le Bhoutan et la Terre Sainte d'Israël, en quête d'un sens plus profond à la vie. En explorant le pouvoir de la méditation, la science médicale occidentale, les doctrines transformatrices de la réincarnation et les enseignements de Jésus, Karen nous encourage à saisir et à profter des immenses possibilités de notre moi spirituel.

Karen Henson Jones était sur le chemin convenu de la réussite dans le monde des affaires, lorsqu'un soudain problème cardiaque à l'âge de 30 ans l'a projetée au seuil de la mort. Durant une expérience hors du commun, elle a dû faire un choix entre quitter son corps ou revenir sur Terre. Quand son souhait de continuer à vivre lui a été accordé, Karen a forcément été confrontée à la vie qu'elle avait vécue jusque-là.Avec chaleur, émerveillement et intelligence, Au c?ur des miracles nous amène avec elle dans un voyage inspirant à travers l'Inde, l'Italie, le Bhoutan et la Terre Sainte d'Israël, en quête d'un sens plus profond à la vie. En explorant le pouvoir de la méditation, la science médicale occidentale, les doctrines transformatrices de la réincarnation et les enseignements de Jésus, Karen nous encourage à saisir et à profter des immenses possibilités de notre moi spirituel.

BACKGROUND:The immune system plays a fundamental role in development during pregnancy and early life. Alterations in circulating maternal and neonatal immune mediators have been associated with pregnancy complications as well as susceptibility to autoimmune and neurodevelopmental conditions in later life. Evidence suggests that the immune system in adults not only responds to environmental stimulation but is also under strong genetic control. METHODS:This is the first genetic study of > 700 mother-infant pairs to analyse the circulating levels of 22 maternal mid-gestational serum-derived and 42 neonatal bloodspot-derived immune mediators (cytokines/chemokines) in the context of maternal and fetal genotype. We first estimated the maternal and fetal genome-wide SNP-based heritability (h2g) for each immune molecule and then performed genome-wide association studies (GWAS) to identify specific loci contributing to individual immune mediators. Finally, we assessed the relationship between genetic immune determinants and ASD outcome. RESULTS:We show maternal and neonatal cytokines/chemokines displaying genetic regulation using independent methodologies. We demonstrate that novel fetal loci for immune function independently affect the physiological levels of maternal immune mediators and vice versa. The cross-associated loci are in distinct genomic regions compared with individual-specific immune mediator loci. Finally, we observed an interaction between increased IL-8 levels at birth, autism spectrum disorder (ASD) status, and a specific maternal genotype. CONCLUSIONS:Our results suggest that maternal and fetal genetic variation influences the immune system during pregnancy and at birth via distinct mechanisms and that a better understanding of immune factor determinants in early development may shed light on risk factors for developmental disorders.

BACKGROUND:The immune system plays a fundamental role in development during pregnancy and early life. Alterations in circulating maternal and neonatal immune mediators have been associated with pregnancy complications as well as susceptibility to autoimmune and neurodevelopmental conditions in later life. Evidence suggests that the immune system in adults not only responds to environmental stimulation but is also under strong genetic control. METHODS:This is the first genetic study of > 700 mother-infant pairs to analyse the circulating levels of 22 maternal mid-gestational serum-derived and 42 neonatal bloodspot-derived immune mediators (cytokines/chemokines) in the context of maternal and fetal genotype. We first estimated the maternal and fetal genome-wide SNP-based heritability (h2g) for each immune molecule and then performed genome-wide association studies (GWAS) to identify specific loci contributing to individual immune mediators. Finally, we assessed the relationship between genetic immune determinants and ASD outcome. RESULTS:We show maternal and neonatal cytokines/chemokines displaying genetic regulation using independent methodologies. We demonstrate that novel fetal loci for immune function independently affect the physiological levels of maternal immune mediators and vice versa. The cross-associated loci are in distinct genomic regions compared with individual-specific immune mediator loci. Finally, we observed an interaction between increased IL-8 levels at birth, autism spectrum disorder (ASD) status, and a specific maternal genotype. CONCLUSIONS:Our results suggest that maternal and fetal genetic variation influences the immune system during pregnancy and at birth via distinct mechanisms and that a better understanding of immune factor determinants in early development may shed light on risk factors for developmental disorders.

Several groups have described the presence of fetal brain-reactive maternal autoantibodies in the plasma of some mothers whose children have autism spectrum disorder (ASD). We previously identified seven autoantigens targeted by these maternal autoantibodies, each of which is expressed at significant levels in the developing brain and has demonstrated roles in typical neurodevelopment. To further understand the binding repertoire of the maternal autoantibodies, as well as the presence of any meaningful differences with respect to the recognition and binding of these ASD-specific autoantibodies to each of these neuronal autoantigens, we utilized overlapping peptide microarrays incubated with maternal plasma samples obtained from the Childhood Autism Risk from Genetics and Environment (CHARGE) Study. In an effort to identify the most commonly recognized (immunodominant) epitope sequences targeted by maternal autoantibodies for each of the seven ASD-specific autoantigens, arrays were screened with plasma from mothers with children across diagnostic groups (ASD and typically developing (TD)) that were positive for at least one antigen by western blot (N = 67) or negative control mothers unreactive to any of the autoantigens (N = 18). Of the 63 peptides identified with the discovery microarrays, at least one immunodominant peptide was successfully identified for each of the seven antigenic proteins using subsequent selective screening microarrays. Furthermore, while limited by our relatively small sample size, there were peptides that were distinctly recognized by autoantibodies relative to diagnosis For example, reactivity was observed exclusively in mothers of children of ASD towards several peptides, including the LDH-B peptides DCIIIVVSNPVDILT (9.1% ASD vs. 0% TD; odds ratio (95% CI) = 6.644 (0.355-124.384)) and PVAEEEATVPNNKIT (5.5% ASD vs. 0% TD; odds ratio (95% CI) = 4.067 (0.203-81.403)).These results suggest that there are differences in the binding repertoire b

The overall aim of the study is to: 1. Determine the range of activities being funded by the BCF, including the scale of the various schemes covered by the fund. 2. Assess the implementation and potential outcomes of the BCF based on the processes and mechanisms being put in place, given local circumstances. This assessment would include indentifying enablers and inhibitors to implementation. 3. Estimate the impact of different levels and types of BCF expenditure on system-level outcome indicators.

We investigate how other high-income countries have thought about and implemented changes to their funding systems for health and social care to better meet the challenges ahead. This paper is part of a broader project funded by the Health Foundation, which aims to identify a range of feasible options for the future funding of health and social care in the four countries of the UK, and assess the relative (un-)attractiveness of different funding approaches to the general public. The research reported here examines trends and innovations in health and social care funding in a selection of high-income countries. We focus on where the money to pay for care comes from, not on how it is then spent. Drawing on a review of the literature and interviews with 30 key informants in a range of high-income countries, we explore current thinking on the options for funding health care and social care. Our aim is to add to the evidence base and improve the quality of the debate, rather than make recommendations. Specifically, we: • provide examples of funding configurations for health and social care, as well as changes that have been implemented, or are being considered, in a range of high income countries • explore the drivers of recent or planned health and social care funding changes and reforms and the contexts within which decisions around funding were taken • highlight key points that can inform the range of conceivable options for funding health care and social care in the four countries of the UK. Overall we find that: • most reviewed countries fund health care primarily from public sources, such as taxation and mandatory health insurance, while social care often relies to a comparatively greater extent on individuals paying privately • health and social care funding reforms tend to be incremental rather than radical, are path-dependent, and are catalysed by changes in economic conditions rather than by rising demand for care • high-income countries have taken diverse appr

New machinery, factory systems and a burgeoning population made the nineteenth century the era of the city. It also represented the coming of age of the city park. Across Europe and North America, elite spaces were opened to public access and new areas dedicated as ‘parks for the people.’ This paper offers a brief tour of green spaces across three iconic metropolitan sites – London, Paris and New York - to consider how the axioms of recreation, industrial modernity and public health operated in specific urban contexts. Of particular note is the fact that park planners embraced an holistic vision, often articulated via bodily metaphors, that incorporated both social and environmental aspects: thus behind apparently nostalgic visions for a pre-industrial bucolic greenery lay irrefutably modern approaches to urban planning that presaged twenty and twenty-first century holistic experiments in garden cities and ‘living homes.’ Also central to this study is the idea of the park as a liminal space and an eminently readable landscape: an evolving site of translation, negotiation and transformation that highlights the fertile ground of cross-disciplinary study and the benefits of a complex ecological history that involves close examination of place, action and imagery

This paper tracks human-animal entanglements through one particular species, Canis lupus, the wolf, with a view to exploring how this contested predator might be used to unpack normative assumptions about wildlife science, conservation practice and storytelling. The focus of attention here is on Yellowstone National Park and the century-long struggle to eradicate and then restore the wolf based on the shifting rubrics of science and environmental ethics. The ‘wild heart’ of North America and an epicentre of scientific and popular environmental mythology, Yellowstone presents a useful terrain (both material and contextual) in which to theorise the wolf as an environmental agent and explore its special provenance within an evolving narrative of ecological science. More specifically, the landmark story of restor(y)ation that played out in the national park serves to illuminate the complex web of temporality, narrative and memory that frames our configurations of animal agency. Wiped out in the late nineteenth and early twentieth century and ruminated on in the interwar period, the wolf was returned to ancestral haunts in the 1990s (to great fanfare) as a charismatic poster animal for environmental consciousness and a vital ‘missing link’ in the psychological and biotic fabric of the landscape. Ornamented with what conservationist Aldo Leopold famously called a ‘fierce green fire,’ the wolf became a carrier animal for Yellowstone’s environmental memory, transporting with it the fates of other threatened species and the promise of an enlightened Ecological Age. Beneath this teleological tale of expanding biological knowledge and ethical awakening lies a convoluted (and interesting) story that reveals the sinuous connections between the material and the imagined animal as well as the challenges and the complexities of reading non-human traces.

The general approach of the current report – in line with process evaluation methods (Moore et al., 2015) – was to learn from (a) the experience of organisational representatives with responsibility for personal health budget policy and practice; and (b) budget holders since the national pilot programme and also (by way of some contrast) from the experiences of new budget holders. In particular, we sought to infer key mechanisms of effect, and reflect on the contexts in which they operated (Pawson and Tilly, 2007). Together, mechanisms and context help us understand why we saw the outcomes of personal health budgets that were found in the national evaluation, and conjecture on how changing context – specifically, post-pilot operation of the policy – might have an impact. Based on the studies to date, the following process factors were expected to be important in determining the success of personal health budgets: * Different budget-setting process * Support planning and review process * The development of the range of services available and availability of providers * The extent of integration between health and social care We explored these issues using a process evaluation approach that involved interviews with both organisational representatives – i.e. people charged with implementing personal health budgets – and with budget holders. Semi-structured interviews were conducted, with topics framed around the hypothesised process factors. Audio-files of the interviews were transcribed verbatim and were analysed using software NVivo 10 for Windows (QSR International Pty Ltd).

This chapter destabilizes the conventional narrative of smoking guns and masculine heroism in the construction of America’s frontier mythology to explore how western women seized the agency of firearms for themselves. More specifically, I look here at two prominent characters in the ‘winning of the West’ – Martha Canary (Calamity Jane) and Annie Oakley - to examine how two women came to take on the mantle of gun-toting heroines and how their stage presence added colour and contest to the frontier story. Both pointed, firstly, to a tradition of firearms use among pioneer women for whom skill with a rifle promised security and sustenance in remote climes. Moreover (and this is the principal focus here) the gun became a critical prop in the theatrical routines of Oakley and Canary as they developed their own cultures of celebrity in the latter years of the 1800s

The Medieval Review, (dlps) baj9928.0804.020, (tmr) 08.04.20, http://quod.lib.umich.edu/t/text/accesspolicy.html

The primary aim of this IIASC study is to develop outcome indicators that better reflect the contributions made by adult social care. Specifically, the IIASC study aims to identify a way by which data collected from the ASCS and SACE could be used to generate a measure of ‘added value’ reflecting the impact of support provided by LAs on social care-related outcomes. The IIASC study collected in-depth information from service users and carers across 22 local authorities (LAs) in England. By including a wide range of measures of social care service use and non-service-related factors, the study aims to identify the best adjustment methodology to ensure a fair comparison between organisations and over time, and to provide recommendations for the use of this measure and the supplementary items to be collected in the ASCS and SACE. The study does not aim to address theoretical questions on the use of outcome measures in adult social care.

The fourth in a series of four blogs which introduce the key elements of the MAX toolkit. The MAX toolkit has been developed to support local authority staff to make more use of data collected by the Adult Social Care Survey (ASCS) and Personal Social Services Survey of Adult Carers in England (PSS SACE or Carers’ Survey) for local performance improvement activities (e.g. service delivery, commissioning). The current blog provides an overview of the barriers to reporting survey data and the general reporting preferences of report-recipients (e.g. managers, commissioners) identified during earlier research activities and consultations with local authority staff, and introduces the reporting element of the MAX toolkit.

The third in a series of four blogs which introduce the key elements of the MAX toolkit. The MAX toolkit has been developed to support local authority staff to make more use of data collected by the Adult Social Care Survey (ASCS) and Personal Social Services Survey of Adult Carers in England (PSS SACE or Carers’ Survey) for local performance improvement activities (e.g. service delivery, commissioning). The current blog discusses the potential benefits of conducting further analysis and provides a brief introduction to the analysis and interpretation element of the MAX toolkit.

The second in a series of four blogs which introduce the key elements of the MAX toolkit. The MAX toolkit has been developed to support local authority staff to make more use of data collected by the Adult Social Care Survey (ASCS) and Personal Social Services Survey of Adult Carers in England (PSS SACE or Carers’ Survey) for local performance improvement activities (e.g. service delivery, commissioning). The current blog discusses the potential benefits of stakeholder engagement for analysts and decision-makers associated with the surveys, and provides an overview of the engagement tools included in the MAX toolkit.

The first in a series of four blogs which introduce the key elements of the MAX toolkit. The MAX toolkit has been developed to support local authority staff to make more use of data collected by the Adult Social Care Survey (ASCS) and Personal Social Services Survey of Adult Carers in England (PSS SACE or Carers’ Survey) for local performance improvement activities (e.g. service delivery, commissioning). The current blog provides an overview of the findings from earlier research activities and consultations with local authority staff and discusses the challenges associated with developing appropriate support.