Reflections on Gravettian firewood procurement near the Pavlov Hills, Czech Republic

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordThis paper draws attention to firewood as a natural resource that was gathered, processed and consumed on a daily basis by Palaeolithic groups. Using Gravettian occupation of the Pavlovsk� Hills as a case study (dated to around 30,000 years BP), we investigate firewood availability using archaeological, palaeoenvironmental and ecological data, including making inferences from charcoal in Pavlovian hearths. The collated evidence suggests that while dead wood was likely readily available in woodland areas where humans had not recently foraged, longer term occupations - or repeated occupation of the same area by different groups - would have quickly exhausted naturally occurring supplies. Once depleted, the deadwood pool may have taken several generations (~40-120 years) to recover enough to provide fuel for another base camp occupation. Such exhaustion of deadwood supplies is well attested ethnographically. Thus, we argue that Pavlovian groups likely managed firewood supplies using methods similar to those used by recent hunter-gatherers: through planned geographic mobility and by deliberately killing trees years in advance of when wood was required, so leaving time for the wood to dry out. Such management of fuel resources was, we argue, critical to human expansion into these cold, hitherto marginal, ecologies of the Upper Palaeolithic.AJEP is grateful to The Leverhulme Trust that funded this research, which was undertaken as part of the project Seasonality, Mobility and Storage in Palaeolithic hunting societies (RPG-2013-318)

Reindeer prey mobility and seasonal hunting strategies in the late Gravettian mammoth steppe

This is the final version. Available on open access from Springer via the DOI in this recordData availability: The original datasets generated during the current study are available as Excel spreadsheets from the corresponding author on reasonable request.Reindeer are part of the faunal suite that dominated central Europe during the last glacial cycle. Their importance to Late Gravettian hunters as prey and a source of raw materials (hide, bone, antler) is well attested, however the context of Late Gravettian reindeer predation is lesser understood. This paper presents an investigation of human and reindeer predator-prey interactions at the Late Gravettian kill-butchery site of Lubná VI, Czech Republic. We reconstruct seasonal mobility (87Sr/86Sr, δ18O), diet (δ13C, δ15N) and season of death (dental cementum) of up to nine reindeer prey, to inform on the strategic choices made by Late Gravettian hunters. Results indicate that most hunted reindeer lived year-round in the foothills of the Bohemian-Moravian highlands near where Lubná is located, at altitudes between ~ 200–450 m above present sea level, while a smaller number showed evidence of seasonal migration between this area and the open plains of the Elbe river corridor (Bohemian Cretaceous basin). No evidence for long distance migration of reindeer was detected, indicating that productive local environments were supporting reindeer herds within a single annual territory. Meanwhile, areas higher than ~ 450 m above present sea level were avoided entirely by all analysed individuals, consistent with these areas being topographic barriers to movement due to climate severity. We conclude that hunters visited Lubná as part of a logistically-organised subsistence strategy, deliberately targeting reindeer in late autumn when fat supplies, hides and antler are in prime condition knowing that they would reliably encounter their prey at this location.National Science Center, PolandUniversity of Exete

System-Agnostic Clinical Decision Support Services: Benefits and Challenges for Scalable Decision Support

System-agnostic clinical decision support (CDS) services provide patient evaluation capabilities that are independent of specific CDS systems and system implementation contexts. While such system-agnostic CDS services hold great potential for facilitating the widespread implementation of CDS systems, little has been described regarding the benefits and challenges of their use. In this manuscript, the authors address this need by describing potential benefits and challenges of using a system-agnostic CDS service. This analysis is based on the authors’ formal assessments of, and practical experiences with, various approaches to developing, implementing, and maintaining CDS capabilities. In particular, the analysis draws on the authors’ experience developing and leveraging a system-agnostic CDS Web service known as SEBASTIAN. A primary potential benefit of using a system-agnostic CDS service is the relative ease and flexibility with which the service can be leveraged to implement CDS capabilities across applications and care settings. Other important potential benefits include facilitation of centralized knowledge management and knowledge sharing; the potential to support multiple underlying knowledge representations and knowledge resources through a common service interface; improved simplicity and componentization; easier testing and validation; and the enabling of distributed CDS system development. Conversely, important potential challenges include the increased effort required to develop knowledge resources capable of being used in many contexts and the critical need to standardize the service interface. Despite these challenges, our experiences to date indicate that the benefits of using a system-agnostic CDS service generally outweigh the challenges of using this approach to implementing and maintaining CDS systems

Phenotypic insights into ADCY5-associated disease

BACKGROUND: Adenylyl cyclase 5 (ADCY5) mutations is associated with heterogenous syndromes: familial dyskinesia and facial myokymia; paroxysmal chorea and dystonia; autosomal-dominant chorea and dystonia; and benign hereditary chorea. We provide detailed clinical data on 7 patients from six new kindreds with mutations in the ADCY5 gene, in order to expand and define the phenotypic spectrum of ADCY5 mutations. METHODS: In 5 of the 7 patients, followed over a period of 9 to 32 years, ADCY5 was sequenced by Sanger sequencing. The other 2 unrelated patients participated in studies for undiagnosed pediatric hyperkinetic movement disorders and underwent whole-exome sequencing. RESULTS: Five patients had the previously reported p.R418W ADCY5 mutation; we also identified two novel mutations at p.R418G and p.R418Q. All patients presented with motor milestone delay, infantile-onset action-induced generalized choreoathetosis, dystonia, or myoclonus, with episodic exacerbations during drowsiness being a characteristic feature. Axial hypotonia, impaired upward saccades, and intellectual disability were variable features. The p.R418G and p.R418Q mutation patients had a milder phenotype. Six of seven patients had mild functional gain with clonazepam or clobazam. One patient had bilateral globus pallidal DBS at the age of 33 with marked reduction in dyskinesia, which resulted in mild functional improvement. CONCLUSION: We further delineate the clinical features of ADCY5 gene mutations and illustrate its wide phenotypic expression. We describe mild improvement after treatment with clonazepam, clobazam, and bilateral pallidal DBS. ADCY5-associated dyskinesia may be under-recognized, and its diagnosis has important prognostic, genetic, and therapeutic implications. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

Mucociliary and long-term particle clearance in airways of patients with immotile cilia

Spherical monodisperse ferromagnetic iron oxide particles of 1.9 μm geometric and 4.2 μm aerodynamic diameter were inhaled by seven patients with primary ciliary dyskinesia (PCD) using the shallow bolus technique, and compared to 13 healthy non-smokers (NS) from a previous study. The bolus penetration front depth was limiting to the phase1 dead space volume. In PCD patients deposition was 58+/-8 % after 8 s breath holding time. Particle retention was measured by the magnetopneumographic method over a period of nine months. Particle clearance from the airways showed a fast and a slow phase. In PCD patients airway clearance was retarded and prolonged, 42+/-12 % followed the fast phase with a mean half time of 16.8+/-8.6 hours. The remaining fraction was cleared slowly with a half time of 121+/-25 days. In healthy NS 49+/-9 % of particles were cleared in the fast phase with a mean half time of 3.0+/-1.6 hours, characteristic of an intact mucociliary clearance. There was no difference in the slow clearance phase between PCD patients and healthy NS. Despite non-functioning cilia the effectiveness of airway clearance in PCD patients is comparable to healthy NS, with a prolonged kinetics of one week, which may primarily reflect the effectiveness of cough clearance. This prolonged airway clearance allows longer residence times of bacteria and viruses in the airways and may be one reason for increased frequency of infections in PCD patients

The Morningside Initiative: Collaborative Development of a Knowledge Repository to Accelerate Adoption of Clinical Decision Support

The Morningside Initiative is a public-private activity that has evolved from an August, 2007, meeting at the Morningside Inn, in Frederick, MD, sponsored by the Telemedicine and Advanced Technology Research Center (TATRC) of the US Army Medical Research Materiel Command. Participants were subject matter experts in clinical decision support (CDS) and included representatives from the Department of Defense, Veterans Health Administration, Kaiser Permanente, Partners Healthcare System, Henry Ford Health System, Arizona State University, and the American Medical Informatics Association (AMIA). The Morningside Initiative was convened in response to the AMIA Roadmap for National Action on Clinical Decision Support and on the basis of other considerations and experiences of the participants. Its formation was the unanimous recommendation of participants at the 2007 meeting which called for creating a shared repository of executable knowledge for diverse health care organizations and practices, as well as health care system vendors. The rationale is based on the recognition that sharing of clinical knowledge needed for CDS across organizations is currently virtually non-existent, and that, given the considerable investment needed for creating, maintaining and updating authoritative knowledge, which only larger organizations have been able to undertake, this is an impediment to widespread adoption and use of CDS. The Morningside Initiative intends to develop and refine (1) an organizational framework, (2) a technical approach, and (3) CDS content acquisition and management processes for sharing CDS knowledge content, tools, and experience that will scale with growing numbers of participants and can be expanded in scope of content and capabilities. Intermountain Healthcare joined the initial set of participants shortly after its formation. The efforts of the Morningside Initiative are intended to serve as the basis for a series of next steps in a national agenda for CDS. It is based on the belief that sharing of knowledge can be highly effective as is the case in other competitive domains such as genomics. Participants in the Morningside Initiative believe that a coordinated effort between the private and public sectors is needed to accomplish this goal and that a small number of highly visible and respected health care organizations in the public and private sector can lead by example. Ultimately, a future collaborative knowledge sharing organization must have a sustainable long-term business model for financial support

The binding of Varp to VAMP7 traps VAMP7 in a closed, fusogenically inactive conformation.

SNAREs provide energy and specificity to membrane fusion events. Fusogenic trans-SNARE complexes are assembled from glutamine-contributing SNAREs (Q-SNAREs) embedded in one membrane and an arginine-contributing SNARE (R-SNARE) embedded in the other. Regulation of membrane fusion events is crucial for intracellular trafficking. We identify the endosomal protein Varp as an R-SNARE-binding regulator of SNARE complex formation. Varp colocalizes with and binds to VAMP7, an R-SNARE that is involved in both endocytic and secretory pathways. We present the structure of the second ankyrin repeat domain of mammalian Varp in complex with the cytosolic portion of VAMP7. The VAMP7-SNARE motif is trapped between Varp and the VAMP7 longin domain, and hence Varp kinetically inhibits the ability of VAMP7 to form SNARE complexes. This inhibition will be increased when Varp can also bind to other proteins present on the same membrane as VAMP7, such as Rab32-GTP

Inside the guts of wood-eating catfishes: can they digest wood?

To better understand the structure and function of the gastrointestinal (GI) tracts of wood-eating catfishes, the gross morphology, length, and microvilli surface area (MVSA) of the intestines of wild-caught Panaque nocturnus, P. cf. nigrolineatus “Marañon”, and Hypostomus pyrineusi were measured, and contrasted against these same metrics of a closely related detritivore, Pterygoplichthys disjunctivus. All four species had anatomically unspecialized intestines with no kinks, valves, or ceca of any kind. The wood-eating catfishes had body size-corrected intestinal lengths that were 35% shorter than the detritivore. The MVSA of all four species decreased distally in the intestine, indicating that nutrient absorption preferentially takes place in the proximal and mid-intestine, consistent with digestive enzyme activity and luminal carbohydrate profiles for these same species. Wild-caught Pt. disjunctivus, and P. nigrolineatus obtained via the aquarium trade, poorly digested wood cellulose (<33% digestibility) in laboratory feeding trials, lost weight when consuming wood, and passed stained wood through their digestive tracts in less than 4 h. Furthermore, no selective retention of small particles was observed in either species in any region of the gut. Collectively, these results corroborate digestive enzyme activity profiles and gastrointestinal fermentation levels in the fishes’ GI tracts, suggesting that the wood-eating catfishes are not true xylivores such as beavers and termites, but rather, are detritivores like so many other fishes from the family Loricariidae

Incremental value of the CT coronary calcium score for the prediction of coronary artery disease

Objectives:: To validate published prediction models for the presence of obstructive coronary artery disease (CAD) in patients with new onset stable typical or atypical angina pectoris and to assess the incremental value of the CT coronary calcium score (CTCS). Methods:: We searched the literature for clinical prediction rules for the diagnosis of obstructive CAD, defined as≥50% stenosis in at least one vessel on conventional coronary angiography. Significant variables were re-analysed in our dataset of 254 patients with logistic regression. CTCS was subsequently included in the models. The area under the receiver operating characteristic curve (AUC) was calculated to assess diagnostic performance. Results:: Re-analysing the variables used by Diamond & Forrester yielded an AUC of 0.798, which increased to 0.890 by adding CTCS. For Pryor, Morise 1994, Morise 1997 and Shaw the AUC increased from 0.838 to 0.901, 0.831 to 0.899, 0.840 to 0.898 and 0.833 to 0.899. CTCS significantly improved model performance in each model. Conclusions:: Validation demonstrated good diagnostic performance across all models. CTCS improves the prediction of the presence of obstructive CAD, independent of clinical predictors, and should be considered in its diagnostic work-up. © 2010 The Author(s)

The Salmonella effector SseJ disrupts microtubule dynamics when ectopically expressed in Normal Rat Kidney cells

Salmonella effector protein SseJ is secreted by Salmonella into the host cell cytoplasm where it can then modify host cell processes. Whilst host cell small GTPase RhoA has previously been shown to activate the acyl-transferase activity of SseJ we show here an un-described effect of SseJ protein production upon microtubule dynamism. SseJ prevents microtubule collapse and this is independent of SseJ's acyl-transferase activity. We speculate that the effects of SseJ on microtubules would be mediated via its known interactions with the small GTPases of the Rho family