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Myelin is required for the function of neuronal axons in the central nervous system, but the mechanisms that support myelin health are unclear. Although macrophages in the central nervous system have been implicated in myelin health1, it is unknown which macrophage populations are involved and which aspects they influence. Here we show that resident microglia are crucial for the maintenance of myelin health in adulthood in both mice and humans. We demonstrate that microglia are dispensable for developmental myelin ensheathment. However, they are required for subsequent regulation of myelin growth and associated cognitive function, and for preservation of myelin integrity by preventing its degeneration. We show that loss of myelin health due to the absence of microglia is associated with the appearance of a myelinating oligodendrocyte state with altered lipid metabolism. Moreover, this mechanism is regulated through disruption of the TGFβ1–TGFβR1 axis. Our findings highlight microglia as promising therapeutic targets for conditions in which myelin growth and integrity are dysregulated, such as in ageing and neurodegenerative disease2,3.

Background We present a national data series to determine the incidence, outcomes and training opportunities for laparoscopic cholecystectomy among children Methods A retrospective cohort study was performed reviewing laparoscopic cholecystectomy performed at the three children’s hospitals in Scotland. Using the National Records Scotland Database mid-year population estimates; age and sex specific annual incidence rates of laparoscopic cholecystectomy were calculated between 1998-2015. Trends in the observed case mix were tested using univariate linear regression and students t-test. Results Between 1998–2015; 141 paediatric laparoscopic cholecystectomies were performed. The annual rate of cholecystectomy increased from 0.10/100,000 to 0.88/100,000 (p = 0.069). Sex specific incidences were identified; 0.00–0.90/100,000 (p = 0.098) in girls and 0.20–0.86/100,000 in boys (p = 0.28). Cholecystectomy was more frequent in girls (63%; p = 0.04). No major complications, defined as common bile duct injury or mortality were identified. Overall; 75% of cases were performed by consultants (n = 17 consultants, median = 5 cases, p Conclusion We have demonstrated that despite a low national case load (8 laparoscopic cholecystectomies per year) paediatric surgeons have been able to perform laparoscopic cholecystectomy safely without major morbidity.

Aim of the Study Few large series report outcomes for laparoscopic two-stage Fowler Stephens orchidopexy (LFSO). The aims were to evaluate testicular outcomes and to identify factors predictive of successful outcome. Method A retrospective case series of children undergoing laparoscopic surgery for impalpable testes between May 1996 and March 2018 was reviewed. Data were collected from case and operative records. The primary outcomes of interest were testicular atrophy or re-ascent. Regression analysis was conducted to identify factors predictive of successful outcome. Data was expressed as median (IQR). Results Of 279 patients (300 testes) undergoing laparoscopy for impalpable testis, 114 patients (128 testes) underwent LFSO. Eighty-five patients (96 testes) had adequate follow-up available (53 left; 43 right). Age at first stage was 19 (IQR 13–36) months. Fifteen children had relevant co-morbidities. Time between procedures was 7 (IQR 6–8) months. Longest follow-up available was 12.5 months (IQR 6.8–19.8). Atrophy occurred in 8 testes (8.3%), and ascent occurred in 6 (6.3%). No factors were significantly predictive of success, although a trend towards atrophy was seen amongst testes undergoing gubernacular division compared with a gubernaculum-sparing technique (p = 0.06; OR 3; 95% CI 0.97–9.3). Conclusion A successful outcome was seen amongst 82 of 96 testes (85%) undergoing LFSO, similar to previous reports. No factors were identified that significantly predicted outcome. Number of adverse outcomes was limited (hence possibility of type II error), and therefore preservation of the gubernaculum may reduce risk of testicular atrophy. Type of Study Prognosis Study. Level of Evidence Level IV.

Significance Sheep and goats (caprines) were domesticated in Southwest Asia, but how and in how many places remain open questions. Our analysis of caprine age and sex structures and related data reveal a local (endemic) domestication process at Aşıklı Höyük in Central Anatolia. Beginning ca. 10,400 y ago, caprine management segued through a series of viable systems over the next 1,000 y. The earliest stage simply involved capturing wild lambs and kids and growing them on site to supplement a broad-spectrum forager diet. Soon, low-level breeding began within the settlement along with catching and raising wild infants. By the end of the archaeological sequence, large numbers of animals were produced from captive herds, which gave rise to early domesticated forms., Sheep and goats (caprines) were domesticated in Southwest Asia in the early Holocene, but how and in how many places remain open questions. This study investigates the initial conditions and trajectory of caprine domestication at Aşıklı Höyük, which preserves an unusually high-resolution record of the first 1,000 y of Neolithic existence in Central Anatolia. Our comparative analysis of caprine age and sex structures and related evidence reveals a local domestication process that began around 8400 cal BC. Caprine management at Aşıklı segued through three viable systems. The earliest mode was embedded within a broad-spectrum foraging economy and directed to live meat storage on a small scale. This was essentially a “catch-and-grow” strategy that involved seasonal capture of wild lambs and kids from the surrounding highlands and raising them several months prior to slaughter within the settlement. The second mode paired modest levels of caprine reproduction on site with continued recruitment of wild infants. The third mode shows the hallmarks of a large-scale herding economy based on a large, reproductively viable captive population but oddly directed to harvesting adult animals, contra to most later Neolithic practices. Wild infant capture likely continued at a low level. The transitions were gradual but, with time, gave rise to early domesticated forms and monumental differences in human labor organization, settlement layout, and waste accumulation. Aşıklı was an independent center of caprine domestication and thus supports the multiple origins evolutionary model.

Metapopulation dynamics play a critical role in driving endemic persistence and transmission of childhood infections. The endemic threshold concept, also referred to as critical community size (CCS), is a key example and is defined as the minimum population size required to sustain a continuous chain of infection transmission. The concept is fundamental to the implementation of effective vaccine-based disease control programmes. Vaccination serves to increase endemic threshold population size, promoting disease fadeout and eventual elimination of infection. To date, empirical investigations of the relationship between vaccination and endemic threshold population size have tended to focus on isolated populations in island communities. Very few studies have examined endemic threshold dynamics in 'mainland' regional populations with complex hierarchical spatial structures and varying levels of connectivity between subpopulations. The present paper provides the first spatially explicit analysis of the temporal changes in endemic threshold populations for one vaccine-preventable childhood infection (pertussis) in two dynamic regions of England and Wales: Lancashire and South Wales. Drawing upon weekly disease records of the Registrar-General of England and Wales over a 30-year period (January 1940-December 1969) regression techniques were used to estimate the endemic threshold size for pertussis in the two study regions. Survival analyses were performed to compare disease fadeout duration and probability for both regions in the pre-vaccine and vaccine eras, respectively. Our findings reveal the introduction of mass vaccination led to a considerable increase in threshold size for both Lancashire (~387,333) and South Wales (~1,460,667). Significant growth in fadeout duration was observed in the vaccine era for pertussis non-hotspots in both regions, consistent with geographical synchronisation of epidemic activity. Regional differences in endemic threshold populations reflect significant regional variations in spatial connectivity, population dispersion and level of geographical isolation.

Shovakh cave is a late Middle Paleolithic cave site in Northern Israel, situated ca. 8 km from the Sea of Galilee. The Cave was originally was excavated by Sally Binford in 1962, and results of the analyses of its lithic assemblages played a major role in the then-raging Bordes-Binford debate, as well as in the initiation of the field of inquires known as “technological organization.” A renewed excavation in 2016 led to a better understanding of site formation at the cave and to a refined chrono-stratigraphic framework of the Middle Paleolithic occupations at the site. Here we present the results of the analyses of lithic and faunal assemblages combining material from both the original and renewed excavations at the site. Together with the results of the geoarcheological work, we are able to offer a refined reconstruction of the modes of occupation in the site as well as of its role within late MP settlement systems in the Levant. We show that during three periods of site occupation, settlements in Shovakh were mostly ephemeral, a rare phenomenon among the late MP cave sites. At the same time, the lithic and faunal assemblages suggest that the nature of these ephemeral occupations differed temporally and spatially. In each of these cases, the fitting scenario for Shovakh’s occupations is as a “transient camp,” used over short-term occupations.

Nineteen broken and complete bone fish hooks and six grooved stones recovered from the Epipaleolithic site of Jordan River Dureijat in the Hula Valley of Israel represent the largest collection of fishing technology from the Epipaleolithic and Paleolithic periods. Although Jordan River Dureijat was occupied throughout the Epipaleolithic (~20–10 kya the fish hooks appear only at the later stage of this period (15,000–12,000 cal BP). This paper presents a multidimensional study of the hooks, grooved stones, site context, and the fish assemblage from macro and micro perspectives following technological, use wear, residue and zooarchaeological approaches. The study of the fish hooks reveals significant variability in hook size, shape and feature type and provides the first evidence that several landmark innovations in fishing technology were already in use at this early date. These include inner and outer barbs, a variety of line attachment techniques including knobs, grooves and adhesives and some of the earliest evidence for artificial lures. Wear on the grooved stones is consistent with their use as sinkers while plant fibers recovered from the grooves of one hook shank and one stone suggest the use of fishing line. This together with associations between the grooved stones and hooks in the same archaeological layers, suggests the emergence of a sophisticated line and hook technology. The complexity of this technology is highlighted by the multiple steps required to manufacture each component and combine them into an integrated system. The appearance of such technology in the Levantine Epipaleolithic record reflects a deep knowledge of fish behavior and ecology. This coincides with significant larger-scale patterns in subsistence evolution, namely broad spectrum foraging, which is an important first signal of the beginning of the transition to agriculture in this region.

This paper investigates aquatic resource exploitation at the Late Natufian site (ca. 12,000 cal. BP) of Nahal Ein Gev II located 2 km east of the Sea of Galilee. Aquatic game, here fish and waterfowl, were an important component of the diverse small game resources that became important in the Late Epipaleolithic in Southwest Asia. We characterize local adaptations to the aquatic habitat and their economic and social implications at Nahal Ein Gev II. Taxonomic abundance and diversity, body-part representation, and fish body-size were investigated to evaluate the contribution of aquatic resources to human diets and butchery and transport strategies. Our results show that the residents of Nahal Ein Gev II were highly selective of the aquatic resources they captured and transported home. The hunters maximized foraging efficiency by nearly exclusively choosing the largest bodied species of fish and waterfowl and processing their carcasses to maximize meat utility before transporting them back to the site. The selectivity of these human foragers enables us to reconstruct rare details about the organization of forays for aquatic resources. When combined with evidence from other material classes from Nahal Ein Gev II and other sites, the results suggest that aquatic resource exploitation is only one of several specialized activities practiced at Nahal Ein Gev II. These along with other archaeological evidence provide evidence of task diversification that foreshadows the emergence of a more complex division of labor to come in the succeeding Neolithic period.

The central nervous system hosts parenchymal macrophages, known as microglia, and non-parenchymal macrophages, collectively termed border-associated macrophages (BAMs). Microglia, but not BAMs, were reported to be absent in mice lacking a conserved Csf1r enhancer: the fms-intronic regulatory element (FIRE). However, it is unknown whether FIRE deficiency also impacts BAM arrival and/or maintenance. Here, we show that macrophages in the ventricular system of the brain, including Kolmer's epiplexus macrophages, are absent in Csf1rΔFIRE/ΔFIRE mice. Stromal choroid plexus BAMs are also considerably reduced. During normal development, we demonstrate that intracerebroventricular macrophages arrive from embryonic day 10.5, and can traverse ventricular walls in embryonic slice cultures. In Csf1rΔFIRE/ΔFIRE embryos, the arrival of both primitive microglia and intracerebroventricular macrophages was eliminated, whereas the arrival of cephalic mesenchyme and stromal choroid plexus BAMs was only partially restricted. Our results provide new insights into the development and regulation of different CNS macrophage populations.

The external surface is the location of the majority of the bacteria associated with rotifers, since the number of bacteria culturable from homogenised rotifers by the spread-plate method was comparable to that visible on the external surface of the rotifers by scanning electron microscopy. Several methods of decontaminating rotifers were investigated. Most of the chemical agents tested were toxic to rotifers or were ineffective in reducing the rotifer bacterial load. A method is described whereby ultra-violet radiation caused a >99% reduction in the bacterial load without any apparent effect on the rotifers themselves.

This chapter examines the history and death-/memoria-related architecture and design of St John's Co-Cathedral in Malta. Its death-related art and architecture in the form of human bones and skulls, sepulchral monuments and burial slabs are examined, before discussing the relationship St John's has with dark tourism and pilgrimage.

Huntington's disease (HD) is an incurable neurodegenerative disorder caused by a trinucleotide (CAG) repeat expansion in the huntingtin gene (HTT). The R6/2 transgenic mouse model of HD expresses exon 1 of the human HTT gene with approximately 150 CAG repeats. R6/2 mice develop progressive behavioural abnormalities, impaired neurogenesis, and atrophy of several brain regions. In recent years, erythropoietin (EPO) has been shown to confer neuroprotection and enhance neurogenesis, rendering it a promising molecule to attenuate HD symptoms. In this study, the therapeutic potential of EPO was evaluated in female R6/2 transgenic mice. A single bilateral injection of a lentivirus encoding human EPO (LV-hEPO) was performed into the lateral ventricles of R6/2 mice at disease onset (8 weeks of age). Control groups were either untreated or injected with a lentivirus encoding green fluorescent protein (LV-GFP). Thirty days after virus administration, hEPO mRNA and protein were present in injected R6/2 brains. Compared to control R6/2 mice, LV-hEPO-treated R6/2 mice exhibited reduced hippocampal atrophy, increased neuroblast branching towards the dentate granular cell layer, and improved spatial cognition. Our results suggest that LV-hEPO administration may be a promising strategy to reduce cognitive impairment in HD.

Our compilation of zooarchaeological data from a series of important archaeological sites spanning the Epipaleolithic through Pre-Pottery Neolithic B periods in the Mediterranean Hills of the southern Levant contributes to major debates about the beginnings of ungulate management in Southwest Asia. The data support an onset of ungulate management practices by the Early PPNB (10,500–10,000 cal. BP), more than 500 years earlier than previously thought for this region. There is a clear developmental connection between reduced hunting intensity and the uptake of ungulate management, confirming that this process began in response to local, density-dependent demographic factors. The early process of goat domestication in the southern Levant appears to have been overwhelmingly local. This may have been true for cattle and pigs as well. Nevertheless, the loose synchrony of animal management trends across Southwest Asia was undoubtedly enabled by large-scale social networks that transmitted knowledge. The results add to growing evidence that animal management processes followed multiple regional evolutionary pathways within the Fertile Crescent.

The laparoscopic approach to tumour nephrectomy in children is controversial. We therefore reviewed our institution's cases of tumour nephrectomy (laparoscopic, open, and converted) to better understand which is suitable for this approach, what factors prevent it, and whether one can excise tumours greater than the CCLG recommendation of 300 ml.All tumour nephrectomies performed between 2002 and 2016 were identified using our surgical database. Further data were gathered from radiology and pathology databases. Those with nonrenal tumours or having a partial nephrectomy were excluded. Tumour maximum diameters, volumes, and ratios to contralateral kidneys were calculated. A Mann-Whitney U was used to compare the groups.Forty-three cases were included. Fifteen procedures were completed laparoscopically (35%), and a further 3 converted. The median age at surgery was 2.5 years (range 0-10) in the laparoscopic group and 2 years (range 0-15) in the open group. There was a significant difference (P0.05) between the laparoscopic and open groups for: median maximum diameter (10cm vs 12.25cm), median volume (155 ml vs 459 ml), maximum diameter ratio (1.22 vs 1.75), and volume ratio (3.8 vs 11.2).Tumours in the laparoscopic group were significantly smaller, but it was possible to excise tumours more than 300 ml. Difficulties in excision related to tumour size relative to the abdomen. Therefore, a ratio of tumour to contralateral kidney may be a better guide to safe excision than an overall volume cutoff. From our series, the laparoscopic approach is likely to be achievable if the volume ratio is ≤ 8.1.Level 3.

In many parts of the Mediterranean Basin, the Late Glacial was a dramatic time in terms of demographic, cultural, and technological change. One region that illustrates this especially well is southern Greece, where Upper Paleolithic lifeways transitioned to the Mesolithic with the onset of the Holocene. Previous archaeological research in this area has documented an intensification of meat resources as foragers widened their diet breadth to include more low-return prey animals, eventually shifting their focus to the Mediterranean Sea. In this paper, we synthesize and expand on these previous analyses by combining new data from Kephalari Cave with two other published sites in the Argolid (Peloponnese), Franchthi Cave and Klissoura Cave 1. These three sites provide an ideal case study for examining changes in meat procurement strategies because they have overlapping Upper Paleolithic and Mesolithic chronologies and are located within about 45 km of one another. We consider each of the sites within their local environmental contexts, including the contraction of the coastal plain and moving shorelines after the Last Glacial Maximum. Changes in the composition of ungulate prey track local environmental and ecological conditions. The use of low-return species supports an overall picture of resource intensification in the region over time. At Klissoura, the most inland of the three sites, small terrestrial prey increases over the course of the Upper Paleolithic, particularly in the Late Glacial, and until the site was abandoned in the Mesolithic. At both Franchthi and Kephalari, small game are abundant in all Upper Paleolithic layers, but there is no overall trend. However, fishing appears in the Upper Paleolithic (most likely the Gravettoid phase) of Kephalari and during the Epigravettian at Franchthi. Fishing increases dramatically in later layers at both sites. At Franchthi, this trend culminates in open-water fishing of large-bodied tunny in the Upper Mesolithic. Interestingly, the use of Klissoura declined at about the time that fishing became a critical part of the economy at Franchthi, and possibly Kephalari. These subsistence shifts reflect a combination of factors, including growing human populations on a regional level and local responses that included changes in mobility patterns and site use, and more diverse toolkits, as well as changes in Pleistocene shorelines that brought an additional ecosystem closer to two of the sites. These internal and external factors allowed foragers in southern Greece to successfully move into a new ecological niche at the end of the Pleistocene.

Aurochs played a prominent role in mortuary and feasting practices during the Neolithic transition in south-west Asia, although evidence of these practices is diverse and regionally varied. This article considers a new concentration of aurochs bones from the southern Levantine Pre-Pottery Neolithic site of Kfar HaHoresh, situating it in a regional context through a survey of aurochs remains from other sites. Analysis shows a change in the regional pattern once animal domestication began from an emphasis on feasting to small-scale practices. These results reveal a widely shared practice of symbolic cattle use that persisted over a long period, but shifted with the beginning of animal management across the region

Background: During murine kidney development, new cortical blood vessels form and pattern in cycles that coincide with cycles of collecting duct branching and the accompanying splitting of the cap mesenchyme (nephron progenitor cell populations that ‘cap' collecting duct ends). At no point in the patterning cycle do blood vessels enter the cap mesenchyme. We hypothesised that the exclusion of blood vessels from the cap mesenchyme may be controlled, at least in part, by an anti-angiogenic signal expressed by the cap mesenchyme cells. Results: We show that semaphorin-3f (Sema3f), a known anti-angiogenic factor, is expressed in cap mesenchymal cells and its receptor, neuropilin-2 (Nrp2), is expressed by newly forming blood vessels in the cortex of the developing kidney. We hypothesised that Sema3f/Nrp2 signalling excludes vessels from the cap mesenchyme. Genetic ablation of Sema3f and of Nrp2, however, failed to result in vessels invading the cap mesenchyme. Conclusions: Despite their complementary expression patterns, our data suggest that Sema3f and Nrp2 are dispensable for the exclusion of vessels from the cap mesenchyme during kidney development. These results should provoke additional experiments to ascertain the biological significance of Sema3f/Nrp2 expression in the developing kidney. This article is protected by copyright. All rights reserved.

Students often have little understanding of the role psychological science plays in informing us about the impact of human behavior when addressing climate change. We designed an assignment for a social psychology course based on Frantz and Mayer’s use of the decision tree model of helping behavior to identify the psychological barriers that reduce the likelihood that people will take action against climate change. Students identified one barrier and designed a persuasion or influence attempt to address that barrier. The assignment integrated social psychological topics in several areas (e.g., helping behavior, persuasion). A pretest–posttest design revealed that students’ knowledge of the role of psychological science in understanding climate change increased compared to a control class.

The proliferation, differentiation and survival of mononuclear phagocytes depend on signals from the receptor for macrophage colony-stimulating factor, CSF1R. The mammalian Csf1r locus contains a highly conserved super-enhancer, the fms-intronic regulatory element (FIRE). Here we show that genomic deletion of FIRE in mice selectively impacts CSF1R expression and tissue macrophage development in specific tissues. Deletion of FIRE ablates macrophage development from murine embryonic stem cells. Csf1rΔFIRE/ΔFIRE mice lack macrophages in the embryo, brain microglia and resident macrophages in the skin, kidney, heart and peritoneum. The homeostasis of other macrophage populations and monocytes is unaffected, but monocytes and their progenitors in bone marrow lack surface CSF1R. Finally, Csf1rΔFIRE/ΔFIRE mice are healthy and fertile without the growth, neurological or developmental abnormalities reported in Csf1r−/− rodents. Csf1rΔFIRE/ΔFIRE mice thus provide a model to explore the homeostatic, physiological and immunological functions of tissue-specific macrophage populations in adult animals., The lineage-specific receptor CSF1R controls macrophage development and homeostasis. Here the authors show that deletion of a conserved Csf1r enhancer (FIRE) selectively depletes brain microglia and resident macrophages in the epidermis, kidney, heart and peritoneum of otherwise healthy mice.

Keloid following circumcision has been described in the literature despite the rarity of its occurrence in penile skin. In this paper, we review the literature and report the successful management of post-circumcision keloid scarring in a 2-year-old boy. After circumcision a 2-year-old boy of African origin developed keloid scarring at the circumcision site. This was treated with three intralesional injections of triamcinolone acetate over 3 months, followed by surgical excision. There was no recurrence at 6 months after excision. To our knowledge this is the 12th case of keloid following paediatric circumcision described in the literature. There is a wide range of techniques described but all are recurrence free at 6 months following repeated intralesional triamcinolone acetate injection and surgical excision. While there is no current consensus in treating post-circumcision keloid, we find that intralesional injection followed by surgical excision provides an acceptable aesthetic result, which is recurrence free.

Wadi Madamagh, situated in the southern Levant, was occupied by humans during the Last Glacial Maximum (LGM; 26,500–19,000 years ago). The climatic and environmental conditions are reflected in the faunal assemblage, which derives from Late Upper Paleolithic and Early Epipaleolithic deposits. Zooarchaeological methods and a human behavioral ecology framework are applied to examine human hunting strategies, site occupation intensity, and population mobility. Taxonomic and skeletal representation reveal that the residents of Wadi Madamagh were efficient hunters who predominantly targeted prime-aged animals, namely wild goat (Capra aegagrus), and transported whole carcasses back to the site. The rarity of small game indicates that human hunters were able to rely nearly exclusively on wild goat populations for meat and did not need to shift down to less cost-effective small game resources. The presence of bezoar goat (Capra aegagrus), waterfowl, and aurochs (Bos primigenius) indicates that during the height of the LGM, the Petra region retained more moisture than today, and wetlands were located close to the site. Compared to contemporaneous sites in the region, the focus on wild goats is unusual but is not unexpected given the rocky, rugged landscape around Wadi Madamagh. In combination with other markers of site occupation intensity, the faunal assemblage suggests that Wadi Madamagh was home to repeated, light occupations over the course of millennia.

This study examined associations between level of sport participation, goal and sportspersonship orientations, and moral reasoning in sport and nonsport situations and orientation by sport participation interactions. Participants were individuals with elite (n = 176), high school (n = 183), and youth sport (n = 78) participation. When judging sport situations, individuals who participated in elite sports demonstrated poorer moral reasoning than those who participated in high school and youth sports. At low levels of sportspersonship, individuals who participated in youth sports demonstrated higher moral reasoning than those who participated in high school and elite sports. When judging nonsport situations, moral reasoning was positively related to positive sportspersonship and negatively related to ego orientation but did not differ by sport participation. Within sport, sport participation and goal and sportspersonship orientations play a critical role in moral reasoning. However, these orientations may b...

Ritual practice plays crucial social roles in human societies by communicating information about social status, calming tensions, and integrating communities. Although communication occurs through the act of ritual performance itself, the archaeological record rarely has the resolution to identify individual ritual actions. The high quality of preservation and recovery of a well-preserved grave of an unusual woman at the Late Natufian (12,000 cal BP) site of Hilazon Tachtit, Israel, enables the identification of multiple stages of a funerary ritual. These represent a variety of actions that allow glimpses into ritual performance as well as larger generalizations about Natufian ritual practice during this dynamic period at the beginning of the agricultural transition.