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Purpose Contemporary trauma resuscitation prioritizes control of bleeding and uses major haemorrhage protocols (MHPs) to prevent and treat coagulopathy. We aimed to determine whether augmenting MHPs with Viscoelastic Haemostatic Assays (VHA) would improve outcomes compared to Conventional Coagulation Tests (CCTs). Methods This was a multi-centre, randomized controlled trial comparing outcomes in trauma patients who received empiric MHPs, augmented by either VHA or CCT-guided interventions. Primary outcome was the proportion of subjects who, at 24 h after injury, were alive and free of massive transfusion (10 or more red cell transfusions). Secondary outcomes included 28-day mortality. Pre-specified subgroups included patients with severe traumatic brain injury (TBI). Results Of 396 patients in the intention to treat analysis, 201 were allocated to VHA and 195 to CCT-guided therapy. At 24 h, there was no difference in the proportion of patients who were alive and free of massive transfusion (VHA: 67%, CCT: 64%, OR 1.15, 95% CI 0.76–1.73). 28-day mortality was not different overall (VHA: 25%, CCT: 28%, OR 0.84, 95% CI 0.54–1.31), nor were there differences in other secondary outcomes or serious adverse events. In pre-specified subgroups, there were no differences in primary outcomes. In the pre-specified subgroup of 74 patients with TBI, 64% were alive and free of massive transfusion at 24 h compared to 46% in the CCT arm (OR 2.12, 95% CI 0.84–5.34). Conclusion There was no difference in overall outcomes between VHA- and CCT-augmented-major haemorrhage protocols.

The ability of sensory networks to transiently store information on the scale of seconds can confer many advantages in processing time-varying stimuli. How a network could store information on such intermediate time scales, between typical neurophysiological time scales and those of long-term memory, is typically attributed to persistent neural activity. An alternative mechanism which might allow for such information storage is through temporary modifications to the neural connectivity which decay on the same second-long time scale as the underlying memories. Earlier work that has explored this method has done so by emphasizing one attractor from a limited, pre-defined set. Here, we describe an alternative, a Transient Attractor network, which can learn any pattern presented to it, store several simultaneously, and robustly recall them on demand using targeted probes in a manner reminiscent of Hopfield networks. We hypothesize that such functionality could be usefully embedded within sensory cortex, and allow for a flexibly-gated short-term memory, as well as conferring the ability of the network to perform automatic de-noising, and separation of input signals into distinct perceptual objects. We demonstrate that the stored information can be refreshed to extend storage time, is not sensitive to noise in the system, and can be turned on or off by simple neuromodulation. The diverse capabilities of transient attractors, as well as their resemblance to many features observed in sensory cortex, suggest the possibility that their actions might underlie neural processing in many sensory areas.

Superconducting phase fluctuations are often associated with the pseudogap phase of the copper-oxide superconductors. However, the same fluctuations exist in the overdoped part of the phase diagram where the pseudogap is absent, suggesting that phase fluctuations are independent of the pseudogap In underdoped cuprate superconductors, phase stiffness is low and long-range superconducting order is destroyed readily by thermally generated vortices (and anti-vortices), giving rise to a broad temperature regime above the zero-resistive state in which the superconducting phase is incoherent 1 , 2 , 3 , 4 . It has often been suggested that these vortex-like excitations are related to the normal-state pseudogap or some interaction between the pseudogap state and the superconducting state 5 , 6 , 7 , 8 , 9 , 10 . However, to elucidate the precise relationship between the pseudogap and superconductivity, it is important to establish whether this broad phase-fluctuation regime vanishes, along with the pseudogap 11 , in the slightly overdoped region of the phase diagram where the superfluid pair density and correlation energy are both maximal 12 . Here we show, by tracking the restoration of the normal-state magnetoresistance in overdoped La 2− x Sr x CuO 4 , that the phase-fluctuation regime remains broad across the entire superconducting composition range. The universal low phase stiffness is shown to be correlated with a low superfluid density 1 , a characteristic of both underdoped and overdoped cuprates 12 , 13 , 14 . The formation of the pseudogap, by inference, is therefore both independent of and distinct from superconductivity.

Aortic calcification is an important independent predictor of future cardiovascular events. We performed a genome-wide association meta-analysis to determine SNPs associated with the extent of abdominal aortic calcification ( n  = 9,417) or descending thoracic aortic calcification ( n  = 8,422). Two genetic loci, HDAC9 and RAP1GAP , were associated with abdominal aortic calcification at a genome-wide level ( P  < 5.0 × 10 −8 ). No SNPs were associated with thoracic aortic calcification at the genome-wide threshold. Increased expression of HDAC9 in human aortic smooth muscle cells promoted calcification and reduced contractility, while inhibition of HDAC9 in human aortic smooth muscle cells inhibited calcification and enhanced cell contractility. In matrix Gla protein–deficient mice, a model of human vascular calcification, mice lacking HDAC9 had a 40% reduction in aortic calcification and improved survival. This translational genomic study identifies the first genetic risk locus associated with calcification of the abdominal aorta and describes a previously unknown role for HDAC9 in the development of vascular calcification. Genome-wide analyses identify variants near HDAC9 associated with abdominal aortic calcification and other cardiovascular phenotypes. Functional work shows that HDAC9 promotes an osteogenic vascular smooth muscle cell phenotype, enhancing calcification and reducing contractility.

Let $B_n$ denote the classical braid group on $n$ strands and let the mixed braid group$B_{m,n}$ be the subgroup of $B_{m+n}$ comprising braids for which the first $m$ strands form the identity braid. Let $B_{m,\\infty}=\\bigcup_nB_{m,n}$. We describe explicit algebraic moves on $B_{m,\\infty}$ such that equivalence classes under these moves classify oriented links up to isotopy in a link complement or in a closed, connected, oriented three-manifold. The moves depend on a fixed link representing the manifold in $S^3$. More precisely, for link complements the moves are the two familiar moves of the classical Markov equivalence together with ‘twisted’ conjugation by certain loops $a_i$. This means premultiplication by $a_i^{-1}$ and postmultiplication by a ‘combed’ version of $a_i$. For closed three-manifolds there is an additional set of ‘combed’ band moves that correspond to sliding moves over the surgery link. The main tool in the proofs is the one-move Markov theorem using $L$-moves (adding in-box crossings). The resulting algebraic classification is a direct extension of the classical Markov theorem that classifies links in $S^3$ up to isotopy, and potentially leads to powerful new link invariants, which have been explored in special cases by the first author. It also provides a controlled range of isotopy moves, useful for studying skein modules of three-manifolds.

Oxygen consumption by carnivorous reptiles increases enormously after they have eaten a large meal in order to meet metabolic demands, and this places an extra load on the cardiovascular system. Here we show that there is an extraordinarily rapid 40% increase in ventricular muscle mass in Burmese pythons (Python molurus) a mere 48 hours after feeding, which results from increased gene expression of muscle-contractile proteins. As this fully reversible hypertrophy occurs naturally, it could provide a useful model for investigating the mechanisms that lead to cardiac growth in other animals.

The magnetic field-induced changes in the conductivity of metals are the subject of intense interest, both for revealing new phenomena and as a valuable tool for determining their Fermi surface. Here we report a hitherto unobserved magnetoresistive effect in ultra-clean layered metals, namely a negative longitudinal magnetoresistance that is capable of overcoming their very pronounced orbital one. This effect is correlated with the interlayer coupling disappearing for fields applied along the so-called Yamaji angles where the interlayer coupling vanishes. Therefore, it is intrinsically associated with the Fermi points in the field-induced quasi-one-dimensional electronic dispersion, implying that it results from the axial anomaly among these Fermi points. In its original formulation, the anomaly is predicted to violate separate number conservation laws for left- and right-handed chiral (for example, Weyl) fermions. Its observation in PdCoO 2 , PtCoO 2 and Sr 2 RuO 4 suggests that the anomaly affects the transport of clean conductors, in particular near the quantum limit. In Weyl semimetals, unusual electronic transport phenomena are predicted to occur, such as an axial anomaly which violates the conservation of chiral fermions. Here, the authors evidence such behaviour via the occurrence of negative magnetoresistance in layered high-purity non-magnetic metals.

During hibernation, ground squirrels (Spermophilus lateralis) show unusually altered expression of skeletal muscle myosin heavy-chains. Some muscle groups show transitions from fast to slower myosin isoforms despite atrophy, which are not predicted from other mammalian studies of inactivity. We measure myosin protein and mRNA expression, and the mRNA expression of genes important in atrophy and metabolism in a time-course of muscle plasticity prior to, and during extended hibernation. We also investigate the role of strictly low-temperature processes by comparing torpid individuals at 20 and 4°C. Shifts in myosin isoform expression happen at both temperatures, before the onset of torpor, or within the first month of torpor, in all muscles demonstrating isoform remodeling. Skeletal muscle atrophy is greatly attenuated in this hibernating species, and even may be absent in some muscles. When present, atrophy develops early in hibernation, and does not progress in the final 3 months of torpor. Myostatin mRNA is down-regulated 50-75% in the soleus and diaphragm, two important muscles that are spared of atrophy. The transcription factor FOXO1, which spurs proteolytic degradation of contractile proteins through regulation of the ubiquitin ligase MAFbx, is also generally down-regulated, and may contribute to reduced atrophy. Hypoxia-inducible factor (HIF-1α) mRNA expression was reduced 50% in some muscles, while elevated more than 300% in others. Our collective findings most strongly support early, seasonal, phenotype changes in skeletal muscles which are not uniquely confined to, or prompted by, torpor at 4°C. Such seasonal control of myosin would be a novel mechanism in mammalian skeletal muscle, which otherwise is most susceptible to mechanical loading and limb-activity patterns.

The collation of an updated European core curriculum in public health is more important than ever in the context of previous and emerging public health emergencies. threats and challenges which pose risk to world populations. It is timely to update and rethink current public health curricula to ensure adequate representation of emergency preparedness as a core element and to assist future workforces to be equipped with knowledge and skills to address these threats and challenges. As part of the development of the ASPHER Core Curriculum for Public Health, a scoping exercise of subject areas delivered in academic public health programmes was conducted through a survey of member Schools and Institutes of Public Health in Europe. Respondents were invited to share indicative content of their curricula in areas of expertise. From a total of 58 replies, 15 (26%) noted expertise in aspects of Emergency Preparedness. Based on the received curriculum a subject specific survey to assess content and education delivery level was completed. Based upon the expert advisory group input, a curriculum with 5 curricular themes and over 45 curricular elements has been developed for multiple levels of education. Preparedness regardless for what public health emergency comes in all its domains is inextricably linked with positive outcomes. It is an increasingly vital component of public health education. Recognising that not all schools may be in a position to offer teaching in emergency preparedness, consideration could be given to collating existing training materials and tools and sharing information and expertise through online platforms so that preparedness education can be integrated into all public health curricula. Key messages • An updated European public health curriculum must prioritize emergency preparedness to equip future professionals for emerging threats and global health challenges. • Emergency preparedness is vital for positive public health outcomes; shared tools and resources can help integrate it into all public health education programmes.

Quantum critical behaviour has been observed in many metallic systems that do not behave conventionally as Fermi liquids. High-magnetic-field experiments now reveal clear evidence for quantum criticality in an iron-based high-temperature superconductor. The physics of quantum critical phase transitions connects to some of the most difficult problems in condensed matter physics, including metal–insulator transitions, frustrated magnetism and high-temperature superconductivity. Near a quantum critical point, a new kind of metal emerges, the thermodynamic and transport properties of which do not fit into the unified phenomenology for conventional metals—the Landau Fermi-liquid theory—characterized by a low-temperature limiting T -linear specific heat and a T 2 resistivity 1 . Studying the evolution of the temperature dependence of these observables as a function of a control parameter leads to the identification of both the presence and the nature of the quantum phase transition in candidate systems. In this study we measure the transport properties of BaFe 2 (As 1− x P x ) 2 below the critical temperature T c by suppressing superconductivity with high magnetic fields. At sufficiently low temperatures, the resistivity of all compositions ( ) crosses over from a linear to a quadratic temperature dependence, consistent with a low-temperature Fermi-liquid ground state. As compositions with optimal T c are approached from the overdoped side, this crossover becomes steeper, consistent with models of quantum criticality where the effective Fermi temperature T F goes to zero.