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Chickens were among the first domesticates introduced by Europeans to North America, where they quickly became established. Morphometric analyses of chicken remains from sites in eastern Canada and the Northeastern USA demonstrate that founding populations likely came from several different types of chicken. Comparison of these data with English medieval and post-medieval assemblages reveals that continued selection for larger body size in both populations resulted in larger chickens. However, the physical proportions of these birds remained consistent across time and space until the nineteenth century, when breeders began producing specialized laying, broiler, and show birds with exaggerated characteristics.

Little is known about the early history of the chicken (Gallus gallus domesticus), including the timing and circumstances of its introduction into new cultural environments. To evaluate its spatio-temporal spread across Eurasia and north-west Africa, the authors radiocarbon dated 23 chicken bones from presumed early contexts. Three-quarters returned dates later than those suggested by stratigraphy, indicating the importance of direct dating. The results indicate that chickens did not arrive in Europe until the first millennium BC. Moreover, a consistent time-lag between the introduction of chickens and their consumption by humans suggests that these animals were initially regarded as exotica and only several centuries later recognised as a source of ‘food’.

Heterozygous activating variants in platelet-derived growth factor, beta (PDGFRB) are associated with phenotypes including Kosaki overgrowth syndrome (KOGS), Penttinen syndrome and infantile myofibromatosis (IM). Here, we present three new cases of KOGS, including a patient with a novel de novo variant c.1477A > T p.(Ser493Cys), and the oldest known individual age 53 years. The KOGS phenotype includes characteristic facial features, tall stature, scoliosis, hyperelastic thin skin, lipodystrophy, variable intellectual and neurological deterioration, and abnormalities on brain imaging. Long-term outcome is unknown. Our cases confirm the phenotypic spectrum includes progressive flexion contractures, camptodactyly, widely spaced teeth, and constriction rings. We also propose novel occasional features including craniosynostosis, ocular pterygia, anterior chamber cleavage syndrome, early osteoporosis, increased pigmentation, recurrent haematomas, predisposition to cellulitis, nail dystrophy, carpal tunnel syndrome, recurrent hypoglycaemia in infancy, joint dislocation, and splenomegaly. Importantly, we report fusiform aneurysm of the basilar artery in two patients. Complications include thrombosis and stroke in the oldest reported patient and fatal rupture at the age of 21 in the patient with the novel variant. We conclude that cerebrovascular complications are part of the phenotypic spectrum of KOGS and KOGS-like disorders and suggest vascular imaging is indicated in these patients.

Determining the age of bird remains after the cessation of growth is challenging due to the absence of techniques such as tooth eruption and wear available for mammals. Without these techniques, it is difficult to reconstruct hunting strategies, husbandry regimes, and wider human–animal relationships. This paper presents a new method, developed from a collection (n = 71) of known-age specimens of domestic fowl (Gallus gallus domesticus L. 1758), for assessing age based on the fusion and size of the tarsometatarsal spur. Using this method, we reconstruct the demographics of domestic fowl from Iron Age to Early Modern sites in Britain to reveal the changing dynamics of human–domestic fowl relationships. We highlight the advanced age that cockerels often attained in their early history and how their life expectancies have subsequently declined.

BRWD3 has been described as a cause of X-linked intellectual disability, but relatively little is known about the specific phenotype. We report the largest BRWD3 patient series to date, comprising 17 males with 12 distinct null variants and two partial gene deletions. All patients presented with intellectual disability, which was classified as moderate (65%) or mild (35%). Behavioral issues were present in 75% of patients, including aggressive behavior, attention deficit/hyperactivity and/or autistic spectrum disorders. Mean head circumference was +2.8 SD (2.8 standard deviations above the mean), and mean BMI was +2.0 SD (in the context of a mean height of +1.3 SD), indicating a predominant macrocephaly/obesity phenotype. Shared facial features included a tall chin, prognathism, broad forehead, and prominent supraorbital ridge. Additional features, reported in a minority (

Sotos syndrome is an overgrowth-intellectual disability (OGID) syndrome caused by NSD1 pathogenic variants and characterized by a distinctive facial appearance, an intellectual disability, tall stature and/or macrocephaly. Other associated clinical features include scoliosis, seizures, renal anomalies, and cardiac anomalies. However, many of the published Sotos syndrome clinical descriptions are based on studies of children; the phenotype in adults with Sotos syndrome is not yet well described. Given that it is now 17 years since disruption of NSD1 was shown to cause Sotos syndrome, many of the children first reported are now adults. It is therefore timely to investigate the phenotype of 44 adults with Sotos syndrome and NSD1 pathogenic variants. We have shown that adults with Sotos syndrome display a wide spectrum of intellectual ability with functioning ranging from fully independent to fully dependent. Reproductive rates are low. In our cohort, median height in adult women is +1.9 SD and men +0.5 SD. There is a distinctive facial appearance in adults with a tall, square, prominent chin. Reassuringly, adults with Sotos syndrome are generally healthy with few new medical issues; however, lymphedema, poor dentition, hearing loss, contractures and tremor have developed in a small number of individuals.

Overgrowth-intellectual disability (OGID) syndromes are characterized by increased growth (height and/or head circumference ≥+2 SD) in association with an intellectual disability. Constitutive EED variants have previously been reported in five individuals with an OGID syndrome, eponymously designated Cohen-Gibson syndrome and resembling Weaver syndrome. Here, we report three additional individuals with constitutive EED variants, identified through exome sequencing of an OGID patient series. We compare the EED phenotype with that of Weaver syndrome (56 individuals), caused by constitutive EZH2 variants. We conclude that while there is considerable overlap between the EED and EZH2 phenotypes with both characteristically associated with increased growth and an intellectual disability, individuals with EED variants more frequently have cardiac problems and cervical spine abnormalities, boys have cryptorchidism and the facial gestalts can usually be distinguished.

Trastornos del espectro autista; Prueba genética Trastorns de l'espectre autista; Prova genètica Autism spectrum disorders; Genetic testing Witteveen-Kolk syndrome (OMIM 613406) is a recently defined neurodevelopmental syndrome caused by heterozygous loss-of-function variants in SIN3A. We define the clinical and neurodevelopmental phenotypes related to SIN3A-haploinsufficiency in 28 unreported patients. Patients with SIN3A variants adversely affecting protein function have mild intellectual disability, growth and feeding difficulties. Involvement of a multidisciplinary team including a geneticist, paediatrician and neurologist should be considered in managing these patients. Patients described here were identified through a combination of clinical evaluation and gene matching strategies (GeneMatcher and Decipher). All patients consented to participate in this study. Mean age of this cohort was 8.2 years (17 males, 11 females). Out of 16 patients ≥ 8 years old assessed, eight (50%) had mild intellectual disability (ID), four had moderate ID (22%), and one had severe ID (6%). Four (25%) did not have any cognitive impairment. Other neurological symptoms such as seizures (4/28) and hypotonia (12/28) were common. Behaviour problems were reported in a minority. In patients ≥2 years, three were diagnosed with Autism Spectrum Disorder (ASD) and four with Attention Deficit Hyperactivity Disorder (ADHD). We report 27 novel variants and one previously reported variant. 24 were truncating variants; three were missense variants and one large in-frame gain including exons 10–12. Funding for the project was provided by the Wellcome Trust and by grants from the Netherlands Organization for Health Research and Development (ZonMw grant 91718310 and the Dutch Scientific Organization (NWO, grant NWA 1160.18.320). WKC is supported by grants from SFARI and the JPB Foundation

Malan syndrome is an overgrowth disorder described in a limited number of individuals. We aim to delineate the entity by studying a large group of affected individuals. We gathered data on 45 affected individuals with a molecularly confirmed diagnosis through an international collaboration and compared data to the 35 previously reported individuals. Results indicate that height is > 2 SDS in infancy and childhood but in only half of affected adults. Cardinal facial characteristics include long, triangular face, macrocephaly, prominent forehead, everted lower lip and prominent chin. Intellectual disability is universally present, behaviorally anxiety is characteristic. Malan syndrome is caused by deletions or point mutations of NFIX clustered mostly in exon 2. There is no genotype-phenotype correlation except for an increased risk for epilepsy with 19p13.2 microdeletions. Variants arose de novo, except in one family in which mother was mosaic. Variants causing Malan and Marshall-Smith syndrome can be discerned by differences in the site of stop codon formation. We conclude that Malan syndrome has a well recognizable phenotype that usually can be discerned easily from Marshall-Smith syndrome but rarely there is some overlap. Differentiation from Sotos and Weaver syndrome can be made by clinical evaluation only. This article is protected by copyright.

Item does not contain fulltext CHD8 has been reported as an autism susceptibility/intellectual disability gene but emerging evidence suggests that it additionally causes an overgrowth phenotype. This study reports 27 unrelated patients with pathogenic or likely pathogenic CHD8 variants (25 null variants, two missense variants) and a male:female ratio of 21:6 (3.5:1, p < .01). All patients presented with intellectual disability, with 85% in the mild or moderate range, and 85% had a height and/or head circumference >/=2 standard deviations above the mean, meeting our clinical criteria for overgrowth. Behavioral problems were reported in the majority of patients (78%), with over half (56%) either formally diagnosed with an autistic spectrum disorder or described as having autistic traits. Additional clinical features included neonatal hypotonia (33%), and less frequently seizures, pes planus, scoliosis, fifth finger clinodactyly, umbilical hernia, and glabellar hemangioma (

BACKGROUND: Ultrarare Marshall-Smith and Malan syndromes, caused by changes of the gene nuclear factor I X (NFIX), are characterised by intellectual disability (ID) and behavioural problems, although questions remain. Here, development and behaviour are studied and compared in a cross-sectional study, and results are presented with genetic findings. METHODS: Behavioural phenotypes are compared of eight individuals with Marshall-Smith syndrome (three male individuals) and seven with Malan syndrome (four male individuals). Long-term follow-up assessment of cognition and adaptive behaviour was possible in three individuals with Marshall-Smith syndrome. RESULTS: Marshall-Smith syndrome individuals have more severe ID, less adaptive behaviour, more impaired speech and less reciprocal interaction compared with individuals with Malan syndrome. Sensory processing difficulties occur in both syndromes. Follow-up measurement of cognition and adaptive behaviour in Marshall-Smith syndrome shows different individual learning curves over time. CONCLUSIONS: Results show significant between and within syndrome variability. Different NFIX variants underlie distinct clinical phenotypes leading to separate entities. Cognitive, adaptive and sensory impairments are common in both syndromes and increase the risk of challenging behaviour. This study highlights the value of considering behaviour within developmental and environmental context. To improve quality of life, adaptations to environment and treatment are suggested to create a better person-environment fit.

A significant proportion of children with learning disability will have an underlying genetic cause. The genetic aetiology of learning disability is broad and includes chromosomal abnormalities, copy number variants, single gene, mitochondrial and imprinting disorders. New genetic technologies are increasing the likelihood that a diagnosis will be made in a child with a learning disability. This provides information on prognosis and complications, thereby facilitating optimal management for the child and genetic counselling for the family. Here we provide an overview of the genetics of learning disability and a clinical approach to investigating a child with a learning disability. The clinical features and management of a number of specific genetic conditions of particular relevance to paediatricians are described.

Two articulating chicken bones from a feast deposit, dated to the 16th century, from Chester, exhibit lesions consistent with the skeletal disorder chondrodystrophy. While this form of dwarfism has many potential causes, it is also consistent with the presentation of the 'creeper' mutation. In this paper we describe and undertake a differential diagnosis of the two articulating chicken bones, and consider the wider significance of this find in 16th-century Britain. The appearance of these lesions, along with the widespread size increase in chickens, the rise of early modern publications concerning chicken husbandry, and contemporary observations that dwarf fowl were luxury foods, provide indirect support for this diagnosis and adds to the growing body of knowledge regarding the unintended health impact of selective breeding.

Dyskeratosis congenita (DC) and related syndromes are inherited, life-threatening bone marrow (BM) failure disorders, and approximately 40% of cases are currently uncharacterized at the genetic level. Here, using whole exome sequencing (WES), we have identified biallelic mutations in the gene encoding poly(A)-specific ribonuclease (PARN) in 3 families with individuals exhibiting severe DC. PARN is an extensively characterized exonuclease with deadenylation activity that controls mRNA stability in part and therefore regulates expression of a large number of genes. The DC-associated mutations identified affect key domains within the protein, and evaluation of patient cells revealed reduced deadenylation activity. This deadenylation deficiency caused an early DNA damage response in terms of nuclear p53 regulation, cell-cycle arrest, and reduced cell viability upon UV treatment. Individuals with biallelic PARN mutations and PARN-depleted cells exhibited reduced RNA levels for several key genes that are associated with telomere biology, specifically TERC, DKC1, RTEL1, and TERF1. Moreover, PARN-deficient cells also possessed critically short telomeres. Collectively, these results identify a role for PARN in telomere maintenance and demonstrate that it is a disease-causing gene in a subset of patients with severe DC.

Beckwith-Wiedemann syndrome (BWS), a human genomic imprinting disorder, is characterized by phenotypic variability that might include overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycaemia, lateralized overgrowth and predisposition to embryonal tumours. Delineation of the molecular defects within the imprinted 11p15.5 region can predict familial recurrence risks and the risk (and type) of embryonal tumour. Despite recent advances in knowledge, there is marked heterogeneity in clinical diagnostic criteria and care. As detailed in this Consensus Statement, an international consensus group agreed upon 72 recommendations for the clinical and molecular diagnosis and management of BWS, including comprehensive protocols for the molecular investigation, care and treatment of patients from the prenatal period to adulthood. The consensus recommendations apply to patients with Beckwith-Wiedemann spectrum (BWSp), covering classical BWS without a molecular diagnosis and BWS-related phenotypes with an 11p15.5 molecular anomaly. Although the consensus group recommends a tumour surveillance programme targeted by molecular subgroups, surveillance might differ according to the local health-care system (for example, in the United States), and the results of targeted and universal surveillance should be evaluated prospectively. International collaboration, including a prospective audit of the results of implementing these consensus recommendations, is required to expand the evidence base for the design of optimum care pathways. Beckwith-Wiedemann syndrome (BWS), a human genomic imprinting disorder, is characterized by phenotypic variability that might include overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycaemia, lateralized overgrowth and predisposition to embryonal tumours. Delineation of the molecular defects within the imprinted 11p15.5 region can predict familial recurrence risks and the risk (and type) of embryonal tumour. Despite recent advances in knowledge, there is marked heterogeneity in clinical diagnostic criteria and care. As detailed in this Consensus Statement, an international consensus group agreed upon 72 recommendations for the clinical and molecular diagnosis and management of BWS, including comprehensive protocols for the molecular investigation, care and treatment of patients from the prenatal period to adulthood. The consensus recommendations apply to patients with Beckwith-Wiedemann spectrum (BWSp), covering classical BWS without a molecular diagnosis and BWS-related phenotypes with an 11p15.5 molecular anomaly. Although the consensus group recommends a tumour surveillance programme targeted by molecular subgroups, surveillance might differ according to the local health-care system (for example, in the United States), and the results of targeted and universal surveillance should be evaluated prospectively. International collaboration, including a prospective audit of the results of implementing these consensus recommendations, is required to expand the evidence base for the design of optimum care pathways.

Beckwith-Wiedemann syndrome (BWS), a human genomic imprinting disorder, is characterized by phenotypic variability that might include overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycaemia, lateralized overgrowth and predisposition to embryonal tumours. Delineation of the molecular defects within the imprinted 11p15.5 region can predict familial recurrence risks and the risk (and type) of embryonal tumour. Despite recent advances in knowledge, there is marked heterogeneity in clinical diagnostic criteria and care. As detailed in this Consensus Statement, an international consensus group agreed upon 72 recommendations for the clinical and molecular diagnosis and management of BWS, including comprehensive protocols for the molecular investigation, care and treatment of patients from the prenatal period to adulthood. The consensus recommendations apply to patients with Beckwith-Wiedemann spectrum (BWSp), covering classical BWS without a molecular diagnosis and BWS-related phenotypes with an 11p15.5 molecular anomaly. Although the consensus group recommends a tumour surveillance programme targeted by molecular subgroups, surveillance might differ according to the local health-care system (for example, in the United States), and the results of targeted and universal surveillance should be evaluated prospectively. International collaboration, including a prospective audit of the results of implementing these consensus recommendations, is required to expand the evidence base for the design of optimum care pathways.

An archaeological strip, map and record exercise on behalf of the Environment Agency was undertaken as part of the Easington Wetlands Project. The excavations revealed earlier prehistoric activity, probably representing seasonal occupation at times of the year when intermittently available resources were abundant. This activity is dated by predominantly later Neolithic and early Bronze Age flints, two Bronze Age radiocarbon dates and later Bronze Age pottery. A Romano-British field system that may have had Iron Age origins was also identified. The pottery assemblage suggests the field system was in use up to the fourth century ad.

The original Wembley Stadium in London was built in the mid-1920s for the British Empire Exhibition, subsequently becoming the national football stadium and a centre for national sport in the UK. Following its use as one of the venues for the 1948 Olympic Games, two monumental plaques, later known as ‘The Olympic Roll of Honour’, were commissioned from sculptor Hugo Powell to commemorate the names of the gold medal winners. The plaques were set within the concrete walls to either side of the Royal Tunnel entrance. When the stadium was demolished in 2003, the plaques were extracted, conserved and stored until a suitable home could be found for them—a lengthy process that significantly affected the conservation programme. The conservators were able to meet Powell and gain unique insights into the context, design and manufacture of the plaques. The plaques have finally been returned to Wembley, in time for a new London Olympics, as part of an exhibition display within the new stadium.

Angioedema is an uncommon, yet morbid, adverse reaction to recombinant tissue plasminogen activator (rtPA) administration for ischemic stroke. Orolingual edema may preclude completion of rtPA therapy and cause potential airway compromise. Few case reports and case series have examined the incidence of angioedema and anaphylaxis related to this common stroke therapy. We report a case of orolingual edema and bleeding in a patient who received rtPA for acute ischemic stroke who was concurrently on an angiotension-converting enzyme inhibitor and discuss the pathophysiology of this reaction.

Studies to discover novel, potent and selective oxytocin antagonists are reported. Combinatorial libraries designed to find novel replacements of fragments of oxytocin antagonist L-371,257, identified pyrimidine, thiazole, indole and benzofuran as potential alternatives to the benzoic acid moiety of L-371,257. Additional investigations identified indole and benzofuran derivatives with potent oxytocin antagonist activity.

Studies to discover novel, potent and selective oxytocin antagonists are reported. Combinatorial libraries designed to find novel replacements of fragments of oxytocin antagonist L-371,257, identified pyrimidine, thiazole, indole and benzofuran as potential alternatives to the benzoic acid moiety of L-371,257. Additional investigations identified indole and benzofuran derivatives with potent oxytocin antagonist activity.

Background: Sociodemographic characteristics of frequent attenders in general practice are known. It is not known whether frequent attendance is linked to specific diseases.Objective: To investigate whether frequent consultation in primary care is related to specific morbidities and whether this relationship is influenced by the general practice which the patient attends.Design: One-year survey of consultation data.Setting: Nine general practices in North Staffordshire, UK.Participants: 1000 adults aged 18 years and over who had consulted primary care at least once during the study year were randomly selected from each practice and grouped into frequent (high and very high), medium and low frequency consulters.Main outcome measures: Type of morbidity coded at each consultation and number of repeat consultations for each morbidity (based on Read Code Chapters).Results: All morbidity Chapters were associated with frequent consultation. Frequent consultation was also associated with repeated consultation within most morbidities. Stronger associations were seen with mental disorders, blood disorders, circulatory disorders, digestive disorders, endocrine diseases and with causes of injury and poisoning. Some variation between practices in the morbidities associated with frequent consultation were apparent; particularly for skin diseases and unspecified conditions.Conclusions: Frequent consulters in primary care are not restricted to particular groups of morbidities. There is some aspect of frequent consultation that is a characteristic of individuals regardless of the symptoms with which they consult. Some morbidities are more prominent than others in this group of consulters, and this may help guide practice policies and future research into frequent consulters.

Introduction Provision of 7-day specialist palliative care services in all care settings has been identified as a key standard for statutory sector providers for a number of years. In 2009, in response to the recommendations of the All Wales Palliative Care Review and the Palliative Care Implementation Board, a Ministerial Letter was issued throughout Wales, requiring implementation of 7-day working for specialist palliative care. Aim This paper will firstly, discuss the development of partnership working between a statutory sector specialist palliative care team (SPCT) and independent sector Hospice to deliver 7 day access to specialist palliative care assessment and intervention, across all healthcare settings; secondly, it will discuss the benefits for patients, families, services, the wider health community and economy. Method The SPCT Clinical Nurse Specialists (CNS) base their service from the Hospice at weekends and Bank Holidays, where out of hour9s advice calls from primary and secondary care have historically been received. This decision was made to support safe lone working, governance, access to medical and hospice support for CNS9s, and streamline access to the service. Results Evaluation of this initiative provides evidence of: ▶Closer integration and team working ▶Rapid access to specialist palliative care, across primary and secondary care, improving outcomes and experiences for patients and their families, and increasing quality and standards of care ▶Access to hospice inpatient admission for patients requiring urgent transfer into a specialist palliative care bed, at weekends and Bank Holidays ▶Prevention of unscheduled acute hospital admissions ▶Support for providers of general palliative care, throughout primary and secondary care. Conclusion Partnership working between the SPCT and Hospice has enabled an innovative approach to the delivery of 7 day working that benefits patients, their families, and service providers.

This literature review explores the research on the clinical presentation of childhood-onset schizophrenia (COS) that was conducted in the period 1994–2004. A literature search was done using Internet search engines and psychological databases to collect English-language journal articles from 1994 onwards. Research indicates that COS is a stable diagnosis. Generally, there is a clear history of premorbid abnormalities, an insidious onset and a deteriorating course. For the majority of cases there seems to be a poor outcome. Despite the limitations in the research conducted thus far, findings provide important insights into COS and several possibilities for future research.

INTRODUCTION: Migrant Chinese constitute a significant and increasing proportion of New Zealand women. They have lower rates of participation in breast cancer screening than other New Zealanders, but reasons for this are unknown. The aim of this study was to investigate factors affecting Chinese women’s understanding of, and access to, breast health services, to better understand reasons for low participation in screening and their experiences of breast cancer clinic care. METHODS: The participants were 26 Chinese migrant women – 19 recruited in the community and seven recruited from 17 eligible women attending a breast clinic between 2008 and 2010 in Wellington, New Zealand. The design was that of a qualitative study, using semi-structured interviews and thematic content analysis. FINDINGS: There were low levels of awareness about the national breast screening programme and limited engagement with preventive primary care services. Concerns about privacy and a range of communication difficulties were identified that related to oral language, lack of written information in Chinese, and limited understanding about Chinese perceptions of ill health and traditional Chinese medicine by New Zealand health professionals. CONCLUSION: Addressing communication barriers for Chinese migrant women has the potential to raise awareness about breast cancer and breast health, and to increase successful participation in breast cancer screening. Greater efforts are needed to ensure this group has an understanding of, and is engaged with a primary care provider. Such efforts are key to improving health for this growing sector of the New Zealand population. KEYWORDS: Breast cancer; Chinese; mammography; mass screening; New Zealand