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The interpretation of archaeological features often requires a combined methodological approach in order to make the most of the material record, particularly from sites where this may be limited. In practice, this requires the consultation of different sources of information in order to cross validate findings and combat issues of ambiguity and equifinality. However, the application of a multiproxy approach often generates incompatible data, and might therefore still provide ambiguous results. This paper explores the potential of a simple digital framework to increase the explanatory power of multiproxy data by enabling the incorporation of incompatible, ambiguous datasets in a single model. In order to achieve this, Bayesian confirmation was used in combination with decision trees. The results of phytolith and geochemical analyses carried out on soil samples from ephemeral sites in Jordan are used here as a case study. The combination of the two datasets as part of a single model enabled us to refine the initial interpretation of the use of space at the archaeological sites by providing an alternative identification for certain activity areas. The potential applications of this model are much broader, as it can also help researchers in other domains reach an integrated interpretation of analysis results by combining different datasets.

Palegawra cave, alongside its neighbouring Zarzi, has been an emblematic site of the Epipalaeolithic (Zarzian) cultural horizon in the NW Zagros of Southwest Asia ever since its first exploration in 1951 by Bruce Howe and Robert Braidwood in the context of the Iraq-Jarmo project. At the time scientific excavation, sampling and analysis methods were either under-developed or did not exist. In this paper we present the first results of new excavations at Palegawra conducted in 2016-2017 by the Eastern Fertile Crescent (EFEC) project, a research collaboration of the University of Liverpool and the Sulaymaniyah Directorate of Antiquities and Heritage. Our research has produced the first radiometric evidence pushing back the chronology of the NW Zagros Epipalaeolithic to the Last Glacial Maximum, thus fully aligning it with Epipalaeolithic facies until now known only from the Levant and the south Anatolian coast. We have also unearthed, for the first time in the Palaeolithic of the Zagros, direct archaeobotanical evidence for hitherto elusive Zarzian plant exploitation and the vegetation of the NW Zagros piedmont zone from the LGM to the end of the Lateglacial (~19,600-13,000 cal BP). The new Palegawra chronology alongside our detailed studies of its material culture and faunal and botanical assemblages suggest that the prevailing Epipalaeolithic habitation pattern in the NW Zagros (centred on generalised persistent occupations of small caves and rock-shelters alongside task-oriented ephemeral open-air campsites) remained an enduring characteristic of the Zarzian horizon throughout this period. The Palegawra data clearly show that neither resource levels and climate conditions nor geographic and/or cultural isolation provide adequate explanations for the stability and longevity of Zarzian lifeways during this long timespan. More fieldwork is required, including the discovery, excavation and intensive sampling of other Zarzian sites, for reaching a data-informed understanding of the nature and evolution of the NW Zagros Epipalaeolithic.Palegawra cave, alongside its neighbouring Zarzi, has been an emblematic site of the Epipalaeolithic (Zarzian) cultural horizon in the NW Zagros of Southwest Asia ever since its first exploration in 1951 by Bruce Howe and Robert Braidwood in the context of the Iraq-Jarmo project. At the time scientific excavation, sampling and analysis methods were either under-developed or did not exist. In this paper we present the first results of new excavations at Palegawra conducted in 2016-2017 by the Eastern Fertile Crescent (EFEC) project, a research collaboration of the University of Liverpool and the Sulaymaniyah Directorate of Antiquities and Heritage. Our research has produced the first radiometric evidence pushing back the chronology of the NW Zagros Epipalaeolithic to the Last Glacial Maximum, thus fully aligning it with Epipalaeolithic facies until now known only from the Levant and the south Anatolian coast. We have also unearthed, for the first time in the Palaeolithic of the Zagros, direct archaeobotanical evidence for hitherto elusive Zarzian plant exploitation and the vegetation of the NW Zagros piedmont zone from the LGM to the end of the Lateglacial (~19,600-13,000 cal BP). The new Palegawra chronology alongside our detailed studies of its material culture and faunal and botanical assemblages suggest that the prevailing Epipalaeolithic habitation pattern in the NW Zagros (centred on generalised persistent occupations of small caves and rock-shelters alongside task-oriented ephemeral open-air campsites) remained an enduring characteristic of the Zarzian horizon throughout this period. The Palegawra data clearly show that neither resource levels and climate conditions nor geographic and/or cultural isolation provide adequate explanations for the stability and longevity of Zarzian lifeways during this long timespan. More fieldwork is required, including the discovery, excavation and intensive sampling of other Zarzian sites, for reaching a data-informed understanding of the nature and evolution of the NW Zagros Epipalaeolithic.

This paper explores the explanations for, and consequences of, the early appearance of food production outside the Fertile Crescent of Southwest Asia, where it originated in the 10th/9th millennia cal BC. We present evidence that cultivation appeared in Central Anatolia through adoption by indigenous foragers in the mid ninth millennium cal BC, but also demonstrate that uptake was not uniform, and that some communities chose to actively disregard cultivation. Adoption of cultivation was accompanied by experimentation with sheep/goat herding in a system of low-level food production that was integrated into foraging practices rather than used to replace them. Furthermore, rather than being a short-lived transitional state, low-level food production formed part of a subsistence strategy that lasted for several centuries, although its adoption had significant long-term social consequences for the adopting community at Boncuklu. Material continuities suggest that Boncuklu’s community was ancestral to that seen at the much larger settlement of Çatalhöyük East from 7100 cal BC, by which time a modest involvement with food production had been transformed into a major commitment to mixed farming, allowing the sustenance of a very large sedentary community. This evidence from Central Anatolia illustrates that polarized positions explaining the early spread of farming, opposing indigenous adoption to farmer colonization, are unsuited to understanding local sequences of subsistence and related social change. We go beyond identifying the mechanisms for the spread of farming by investigating the shorter- and longer-term implications of rejecting or adopting farming practices.

Introduction It has been increasingly recognised that the impact of Ataxia extends beyond physical and motor symptomology. However, it is less known whether self-reported non-motor and ataxia symptom severity varies across ataxias of differing aetiology, which would have important implications for providing more targeted treatment. Aim This study aimed to investigate the impact of ataxia aetiology (hereditary, acquired or idiopathic) on self-reported depression, anxiety, fatigue, cognitive deficits, and ataxia symptom severity. Comparisons were also made between the ataxia sample as a whole and a neurologically healthy control group. Method Responses were collected using a cross-sectional online survey to recruit a national UK sample of people with ataxia. Results The study recruited 110 participants with ataxia (hereditary = 51, acquired = 16, idiopathic = 43) and 32 healthy controls. No significant differences were found across study variables for different causes of ataxia. However, participants with ataxia did report significantly higher levels of depression, anxiety, fatigue, cognitive deficits, and ataxia symptom severity compared to healthy controls. Conclusion This study found that participants with ataxia self-reported increased non-motor symptoms compared to healthy controls, which was a generally homogenous experience across different causes of ataxia. There was also considerable comorbidity of symptoms which requires further exploration. This study highlights the need for early assessment and intervention to address these non-motor symptoms in ataxia populations.

The dynamic regulation of actin polymerization plays crucial roles in cell morphology and endocytosis. The mechanistic details of these processes and the proteins involved are not fully understood, especially in neurons. PICK1 is a PDZ–BAR-domain protein involved in regulated AMPA receptor (AMPAR) endocytosis in neurons. Here, we demonstrate that PICK1 binds filamentous (F)-actin and the actin-nucleating Arp2/3 complex, and potently inhibits Arp2/3-mediated actin polymerization. RNA interference (RNAi) knockdown of PICK1 in neurons induces a reorganization of the actin cytoskeleton resulting in aberrant cell morphology. Wild-type PICK1 rescues this phenotype, but a mutant PICK1, PICK1 W413A , that does not bind or inhibit Arp2/3 has no effect. Furthermore, this mutant also blocks NMDA-induced AMPAR internalization. This study identifies PICK1 as a negative regulator of Arp2/3-mediated actin polymerization that is critical for a specific form of vesicle trafficking, and also for the development of neuronal architecture.

The house mouse ( Mus musculus ) represents the extreme of globalization of invasive mammals. However, the timing and basis of its origin and early phases of dispersal remain poorly documented. To track its synanthropisation and subsequent invasive spread during the develoment of complex human societies, we analyzed 829 Mus specimens from 43 archaeological contexts in Southwestern Asia and Southeastern Europe, between 40,000 and 3,000 cal. BP, combining geometric morphometrics numerical taxonomy, ancient mitochondrial DNA and direct radiocarbon dating. We found that large late hunter-gatherer sedentary settlements in the Levant, c. 14,500 cal. BP, promoted the commensal behaviour of the house mouse, which probably led the commensal pathway to cat domestication. House mouse invasive spread was then fostered through the emergence of agriculture throughout the Near East 12,000 years ago. Stowaway transport of house mice to Cyprus can be inferred as early as 10,800 years ago. However, the house mouse invasion of Europe did not happen until the development of proto urbanism and exchange networks — 6,500 years ago in Eastern Europe and 4000 years ago in Southern Europe — which in turn may have driven the first human mediated dispersal of cats in Europe.

The wild population of the African lion Panthera leo continues to decline, requiring alternate conservation programs to be considered. One such program is ex situ reintroduction. Prior to release, longterm monitoring and assessment of behavior is required to determine whether prides and coalitions behave naturally and are sufficiently adapted to a wild environment. Social network analysis （SNA） can be used to provide insight into how the pride as a whole and individuals within it, function. Our study was conducted upon 2 captive-origin prides who are part of an ex situ reintroduction program, and 1 wild pride of African lion. Social interactions were collected at all occurrence for each pride and categorized into greet, social grooming, play, and aggression. Betweenness centrality showed that offspring in each pride were central to the play network, whereas degree indicated that adults received （indegree） the greatest number of overall social interactions, and the adult males of each pride were least likely to initiate （outdegree） any interactions. Through the assessment of individual centrality and degree values, a social keystone adult female was identified for each pride. Social network results indicated that the 2 captive-origin prides had formed cohesive social units and possessed relationships and behaviors comparable with the wild pride for the studied behaviors. This study provided the first SNA comparison between captive-bred origin and a wild pride of lions, providing valuable information on individual and pride sociality, critical for determining the success of prides within an ex situ reintroduction program.

The authors present a new type of communal and monumental structure from the earliest Neolithic in western Asia. A complement to the decorated stone pillars erected at Göbekli Tepe in the north, ‘Wadi Faynan 16 Structure O75’ in the southern Levant is a ritualised gathering place of a different kind. It serves to define wider western Asia as an arena of social experiment in the tenth millennium BC, one in which community seems to take precedence over economy.

The Effect of Evening Alcohol Consumption on Next-Morning Glucose Control in Type 1 Diabetes Benjamin C. Turner , MRCP 1 , Emma Jenkins , BSC 1 , David Kerr , MD, FRCP 1 , Robert S. Sherwin , MD 2 and David A. Cavan , MD, FRCP 1 1 Bournemouth Diabetes and Endocrine Centre, Royal Bournemouth Hospital, Bournemouth, U.K. 2 Yale University School of Medicine, New Haven, Connecticut Abstract OBJECTIVE —Alcohol is associated with acute hypoglycemia in patients with type 1 diabetes. After drinking alcohol in the evening, delayed hypoglycemia has also been described, although its cause is unknown. We performed a controlled study to investigate this phenomenon. RESEARCH DESIGN AND METHODS —We admitted six men with type 1 diabetes (aged 19–51 years, HbA 1c 7.0–10.3%) on two occasions, from 5:00 p.m . to 12:00 noon the following day. They received regular insulin injections before standardized meals, at 6:00 p.m. and 8:00 a.m ., and a basal insulin infusion (0.15 mU · kg −1 · min −1 ) from 11:00 p.m . They drank either dry white wine (0.75 g/kg alcohol) or mineral water at 9:00 p.m. over 90 min. Blood glucose, alcohol, insulin, cortisol, growth hormone, and glucagon levels were measured. RESULTS —Blood ethanol reached a mean (SEM) peak of 19.1 (1.2) mmol/l and was undetectable by 8:00 a.m . There were no significant differences in evening or overnight blood glucose levels between the studies. In the morning, fasting and postprandial blood glucose levels were significantly lower after consumption of wine (postprandial peak 8.9 [1.7] vs. 15 [1.5] mmol/l, P < 0.01), and from 10:00 a.m ., five subjects required treatment for hypoglycemia (nadir 1.9–2.9 mmol/l). None of the subjects had hypoglycemia after consumption of water. After consumption of wine, growth hormone secretion was significantly reduced between midnight and 4:00 a.m . (area under the curve 2.1 [1.1] vs. 6.5 [2.1] μg · l –1 · h –1 , P = 0.04). There were no differences in insulin or other hormone levels. CONCLUSIONS —In type 1 diabetes, moderate consumption of alcohol in the evening may predispose patients to hypoglycemia after breakfast the next morning. This is associated with reduced nocturnal growth hormone secretion. Patients should be informed of this risk and advised regarding appropriate preventative measures. AUC, area under the curve FFA, free fatty acid Footnotes Address correspondence and reprint requests to Dr. Benjamin C. Turner, Diabetes and Endocrine Day Centre, 6/F North Wing, St. Thomas’ Hospital, Lambeth Palace Rd., London, SE1 7EH U.K. E-mail: ben.turner{at}gstt.sthames.nhs.uk Received for publication 13 February 2001 and accepted in revised form 8 August 2001. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

Abstract Aims Tight junction protein zonula occludens protein 2 (ZO-2) is a member of the membrane-associated guanylate kinases protein family known to be expressed at tight junctions of epithelial and endothelial cells and at adherens junctions (AJs) in cardiomyocytes. Little is known about ZO-2 expression and function in the human heart. Here, we examinedthe hypothesis that chronic hypoxia down-regulates ZO-2 expression in human myocardium and cultured rat cardiomyocytes. Methods and results Patients with a diagnosis of cyanotic (n = 10) or acyanotic (n = 10) Tetralogy of Fallot undergoing surgical repair were used to examine ZO-2 messenger RNA and protein expression by real time-PCR, immunohistochemistry, and western blotting. A model of cultured rat cardiomyocytes wasused to measure ZO-2 and AJ proteins levels in response to hypoxia and to investigate ZO-2 cellular localization. We showed that ZO-2 is expressed in myocardial tissue in acyanotic and cyanotic children with congenital heart defects. ZO-2 was specifically down-regulated in cyanotic myocardium at both the messenger RNA and protein levels when compared with acyanotic patients. This specific down-regulation can be mimicked in cultured rat cardiomyocytes by treating them with hypoxic conditions confirming that ZO-2 gene down-regulation is specifically due to cyanosis. Furthermore, in addition to its cytoplasmic expression, ZO-2 showed nuclear expression in cultured rat cardiomyocytes suggesting potential role in transcription regulation. Conclusions Hypoxia down-regulates ZO-2 expression in both cyanotic patient's myocardium and cultured rat cardiomyocytes. This down-regulation suggest an involvement of ZO-2 in cardiac remodelling of AJs in cyanotic children and may explain the greater susceptibility of cyanotic patients to corrective heart surgery.