The 1780s: global climate anomalies, floods, droughts, and famines

This handbook offers the first comprehensive, state-of-the-field guide to past weather and climate and their role in human societies. Bringing together dozens of international specialists from the sciences and humanities, this volume describes the methods, sources, and major findings of historical climate reconstruction and impact research. Its chapters take the reader through each key source of past climate and weather information and each technique of analysis; through each historical period and region of the world; through the major topics of climate and history and core case studies; and finally through the history of climate ideas and science. Using clear, non-technical language, The Palgrave Handbook of Climate History serves as a textbook for students, a reference guide for specialists and an introduction to climate history for scholars and interested readers

Prevalence and architecture of de novo mutations in developmental disorders.

The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

A signal of persistent Atlantic multidecadal variability in Arctic sea ice

Satellite data suggest an Arctic sea ice-climate system in rapid transformation, yet its long-term natural modes of variability are poorly known. Here we integrate and synthesize a set of multicentury historical records of Atlantic Arctic sea ice, supplemented with high-resolution paleoproxy records, each reflecting primarily winter/spring sea ice conditions. We establish a signal of pervasive and persistent multidecadal (~60–90 year) fluctuations that is most pronounced in the Greenland Sea and weakens further away. Covariability between sea ice and Atlantic multidecadal variability as represented by the Atlantic Multidecadal Oscillation (AMO) index is evident during the instrumental record, including an abrupt change at the onset of the early twentieth century warming. Similar covariability through previous centuries is evident from comparison of the longest historical sea ice records and paleoproxy reconstructions of sea ice and the AMO. This observational evidence supports recent modeling studies that have suggested that Arctic sea ice is intrinsically linked to Atlantic multidecadal variability. This may have implications for understanding the recent negative trend in Arctic winter sea ice extent, although because the losses have been greater in summer, other processes and feedbacks are also important

Correspondence

One of the few long instrumental records available for the Arctic is the Svalbard Airport composite series that hitherto began in 1911, with observations made on Spitsbergen, the largest island in the Svalbard Archipelago. This record has now been extended to 1898 with the inclusion of observations made by hunting and scientific expeditions. Temperature has been observed almost continuously in Svalbard since 1898, although at different sites. It has therefore been possible to create one composite series for Svalbard Airport covering the period 1898 2012, and this valuable new record is presented here. The series reveals large temperature variability on Spitsbergen, with the early 20th century warming as one striking feature: an abrupt change from the cold 1910s to the local maxima of the 1930s and 1950s. With the inclusion of the new data it is possible to show that the 1910s were colder than the years at the start of the series. From the 1960s, temperatures have increased, so the present temperature level is significantly higher than at any earlier period i

Landscapes of settlement in northern Iceland: Historical Ecology of human impact and climate fluctuation on the millennial scale

A thousand years ago Viking age voyagers crossed the grey waters of the North Atlantic, colonizing the Faroes, Iceland, Greenland, and Vinland between AD 800 and 1000. However, early transatlantic migration was not to have the historical impact of the later European re-discovery of North America, and by the 16th century the Scandinavian North Atlantic island communities had become either extinct or were marginalized colonies of continental states. Climate change and unintended human impact upon island ecosystems have long been proposed as root causes of the decline of the Norse Atlantic colonies, but interdisciplinary research had usually been restricted to short term investigations of single sites. In an attempt to better understand the complex interactions of culture and nature in early Iceland and to contribute a long term perspective to larger issues of sustainable resource use, soil erosion, and the historical ecology of global change, since 1996 the NABO research cooperative has mounted a sustained program of interdisciplinary collaboration focused upon 9th-13th century sites and landscapes in the highland interior lake basin of Mývatn. A multi-site, interdisciplinary, landscape based approach to human-environment interaction on the millennial scale has modified many early assumptions about human impact in the region, while documenting a case of 1200 year-old sustainable management of wildfowl and substantial internal exchange of marine products within 9th-10th century Iceland. Organizational background of the research cooperative and management lessons learned are also presented

Landscape of Familial Isolated and Young-Onset Pituitary Adenomas: Prospective Diagnosis in AIP Mutation Carriers.

Familial isolated pituitary adenoma (FIPA) due to aryl hydrocarbon receptor interacting protein (AIP) gene mutations is an autosomal dominant disease with incomplete penetrance. Clinical screening of apparently unaffected AIP mutation (AIPmut) carriers could identify previously unrecognized disease.This article is freely available via PubMed Central. Click on the 'Additional Link' above to access the full text