Early evidence for mounted horseback riding in northwest China.

Horseback riding was a transformative force in the ancient world, prompting radical shifts in human mobility, warfare, trade, and interaction. In China, domestic horses laid the foundation for trade, communication, and state infrastructure along the ancient Silk Road, while also stimulating key military, social, and political changes in Chinese society. Nonetheless, the emergence and adoption of mounted horseback riding in China is still poorly understood, particularly due to a lack of direct archaeological data. Here we present a detailed osteological study of eight horse skeletons dated to ca. 350 BCE from the sites of Shirenzigou and Xigou in Xinjiang, northwest China, prior to the formalization of Silk Road trade across this key region. Our analyses reveal characteristic osteological changes associated with equestrian practices on all specimens. Alongside other relevant archaeological evidence, these data provide direct evidence for mounted horseback riding, horse equipment, and mounted archery in northwest China by the late first millennium BCE. Most importantly, our results suggest that this region may have played a crucial role in the spread of equestrian technologies from the Eurasian interior to the settled civilizations of early China, where horses facilitated the rise of the first united Chinese empires and the emergence of transcontinental trade networks.

The lipid phosphatase-like protein PLPPR1 associates with RhoGDI1 to modulate RhoA activation in response to axon growth inhibitory molecules.

Phospholipid Phosphatase-Related Protein Type 1 (PLPPR1) is a member of a family of lipid phosphatase related proteins, integral membrane proteins characterized by six transmembrane domains. This family of proteins is enriched in the brain and recent data indicate potential pleiotropic functions in several different contexts. An inherent ability of this family of proteins is to induce morphological changes, and we have previously reported that members of this family interact with each other and may function co-operatively. However, the function of PLPPR1 is not yet understood. Here we show that the expression of PLPPR1 reduces the inhibition of neurite outgrowth of cultured mouse hippocampal neurons by chondroitin sulfate proteoglycans and the retraction of neurites of Neuro-2a cells by lysophosphatidic acid (LPA). Further, we show that PLPPR1 reduces the activation of Ras homolog family member A (RhoA) by LPA in Neuro-2a cells, and that this is because of an association of PLPPR1with the Rho-specific guanine nucleotide dissociation inhibitor (RhoGDI1). These results establish a novel signaling pathway for the PLPPR1 protein.

Imidazolinium N-Heterocyclic Carbene Ligands for Enhanced Stability on Gold Surfaces.

N-heterocyclic carbenes (NHCs) have emerged as versatile and robust ligands for noble metal surface modifications due to their ability to form compact, self-assembled monolayers. Despite a growing body of research, previous NHC surface modification schemes have employed just two structural motifs: the benzimidazolium NHC and the imidazolium NHC. However, different NHC moieties, including saturated NHCs, are often more effective in homogenous catalysis chemistry than these aforementioned motifs and may impart numerous advantages to NHC surfaces, such as increased stability and access to chiral groups. This work explores the preparation and stability of NHC-coated gold surfaces using imidazolium and imidazolinium NHC ligands. X-ray photoelectron spectroscopy and surface-enhanced Raman spectroscopy demonstrate the attachment of NHC ligands to the gold surface and show enhanced stability of imidazolinium compared to the traditional imidazolium under harsh acidic conditions.

Three-dimensional imaging of localized surface plasmon resonances of metal nanoparticles.

The remarkable optical properties of metal nanoparticles are governed by the excitation of localized surface plasmon resonances (LSPRs). The sensitivity of each LSPR mode, whose spatial distribution and resonant energy depend on the nanoparticle structure, composition and environment, has given rise to many potential photonic, optoelectronic, catalytic, photovoltaic, and gas- and bio-sensing applications. However, the precise interplay between the three-dimensional (3D) nanoparticle structure and the LSPRs is not always fully understood and a spectrally sensitive 3D imaging technique is needed to visualize the excitation on the nanometre scale. Here we show that 3D images related to LSPRs of an individual silver nanocube can be reconstructed through the application of electron energy-loss spectrum imaging, mapping the excitation across a range of orientations, with a novel combination of non-negative matrix factorization, compressed sensing and electron tomography. Our results extend the idea of substrate-mediated hybridization of dipolar and quadrupolar modes predicted by theory, simulations, and electron and optical spectroscopy, and provide experimental evidence of higher-energy mode hybridization. This work represents an advance both in the understanding of the optical response of noble-metal nanoparticles and in the probing, analysis and visualization of LSPRs.

The organisation of critical care for burn patients in the UK: epidemiology and comparison of mortality prediction models.

In the UK, a network of specialist centres has been set up to provide critical care for burn patients. However, some burn patients are admitted to general intensive care units. Little is known about the casemix of these patients and how it compares with patients in specialist burn centres. It is not known whether burn-specific or generic risk prediction models perform better when applied to patients managed in intensive care units. We examined admissions for burns in the Case Mix Programme Database from April 2010 to March 2016. The casemix, activity and outcome in general and specialist burn intensive care units were compared and the fit of two burn-specific risk prediction models (revised Baux and Belgian Outcome in Burn Injury models) and one generic model (Intensive Care National Audit and Research Centre model) were compared. Patients in burn intensive care units had more extensive injuries compared with patients in general intensive care units (median (IQR [range]) burn surface area 16 (7-32 [0-98])% vs. 8 (1-18 [0-100])%, respectively) but in-hospital mortality was similar (22.8% vs. 19.0%, respectively). The discrimination and calibration of the generic Intensive Care National Audit and Research Centre model was superior to the revised Baux and Belgian Outcome in Burn Injury burn-specific models for patients managed on both specialist burn and general intensive care units.

Epidemiology of sepsis and septic shock in critical care units: comparison between sepsis-2 and sepsis-3 populations using a national critical care database.

BACKGROUND: New sepsis and septic shock definitions could change the epidemiology of sepsis because of differences in criteria. We therefore compared the sepsis populations identified by the old and new definitions. METHODS: We used a high-quality, national, intensive care unit (ICU) database of 654 918 consecutive admissions to 189 adult ICUs in England, from January 2011 to December 2015. Primary outcome was acute hospital mortality. We compared old (Sepsis-2) and new (Sepsis-3) incidence, outcomes, trends in outcomes, and predictive validity of sepsis and septic shock populations. RESULTS: From among 197 724 Sepsis-2 severe sepsis and 197 142 Sepsis-3 sepsis cases, we identified 153 257 Sepsis-2 septic shock and 39 262 Sepsis-3 septic shock cases. The extrapolated population incidence of Sepsis-3 sepsis and Sepsis-3 septic shock was 101.8 and 19.3 per 100 000 person-years, respectively, in 2015. Sepsis-2 severe sepsis and Sepsis-3 sepsis had similar incidence, similar mortality and showed significant risk-adjusted improvements in mortality over time. Sepsis-3 septic shock had a much higher Acute Physiology And Chronic Health Evaluation II (APACHE II) score, greater mortality and no risk-adjusted trends in mortality improvement compared with Sepsis-2 septic shock. ICU admissions identified either as Sepsis-3 sepsis or septic shock and as Sepsis-2 severe sepsis or septic shock had significantly greater risk-adjusted odds of death compared with non-sepsis admissions (P<0.001). The predictive validity was greatest for Sepsis-3 septic shock. CONCLUSIONS: In an ICU database, compared with Sepsis-2, Sepsis-3 identifies a similar sepsis population with 92% overlap and much smaller septic shock population with improved predictive validity.

The Assessment of Risk in Cardiothoracic Intensive Care (ARCtIC): prediction of hospital mortality after admission to cardiothoracic critical care.

The models used to predict outcome after adult general critical care may not be applicable to cardiothoracic critical care. Therefore, we analysed data from the Case Mix Programme to identify variables associated with hospital mortality after admission to cardiothoracic critical care units and to develop a risk-prediction model. We derived predictive models for hospital mortality from variables measured in 17,002 patients within 24 h of admission to five cardiothoracic critical care units. The final model included 10 variables: creatinine; white blood count; mean arterial blood pressure; functional dependency; platelet count; arterial pH; age; Glasgow Coma Score; arterial lactate; and route of admission. We included additional interaction terms between creatinine, lactate, platelet count and cardiac surgery as the admitting diagnosis. We validated this model against 10,238 other admissions, for which the c index (95% CI) was 0.904 (0.89-0.92) and the Brier score was 0.055, while the slope and intercept of the calibration plot were 0.961 and -0.183, respectively. The discrimination and calibration of our model suggest that it might be used to predict hospital mortality after admission to cardiothoracic critical care units.

An evaluation of the clinical and cost-effectiveness of alternative care locations for critically ill adult patients with acute traumatic brain injury.

BACKGROUND: For critically ill adult patients with acute traumatic brain injury (TBI), we assessed the clinical and cost-effectiveness of: (a) Management in dedicated neurocritical care units versus combined neuro/general critical care units within neuroscience centres. (b) 'Early' transfer to a neuroscience centre versus 'no or late' transfer for those who present at a non-neuroscience centre. METHODS: The Risk Adjustment In Neurocritical care (RAIN) Study included prospective admissions following acute TBI to 67 UK adult critical care units during 2009-11. Data were collected on baseline case-mix, mortality, resource use, and at six months, Glasgow Outcome Scale Extended (GOSE), and quality of life (QOL) (EuroQol 5D-3L). We report incremental effectiveness, costs and cost per Quality-Adjusted Life Year (QALY) of the alternative care locations, adjusting for baseline differences with validated risk prediction models. We tested the robustness of results in sensitivity analyses. FINDINGS: Dedicated neurocritical care unit patients (N = 1324) had similar six-month mortality, higher QOL (mean gain 0.048, 95% CI -0.002 to 0.099) and increased average costs compared with those managed in combined neuro/general units (N = 1341), with a lifetime cost per QALY gained of £14,000. 'Early' transfer to a neuroscience centre (N = 584) was associated with lower mortality (odds ratio 0.52, 0.34-0.80), higher QOL for survivors (mean gain 0.13, 0.032-0.225), but positive incremental costs (£15,001, £11,123 to £18,880) compared with 'late or no transfer' (N = 263). The lifetime cost per QALY gained for 'early' transfer was £11,000. CONCLUSIONS: For critically ill adult patients with acute TBI, within neuroscience centres management in dedicated neurocritical care units versus combined neuro/general units led to improved QoL and higher costs, on average, but these differences were not statistically significant. This study finds that 'early' transfer to a neuroscience centre is associated with reduced mortality, improvement in QOL and is cost-effective.

The impact of dissociation on perceptual priming and intrusions after listening to auditory narratives.

This study investigates the causal role of dissociation in intrusive memory development and possible underlying aberrant memory processes (e.g., increased perceptual priming). Using an audio-only adaption of the trauma film paradigm, we divided 60 participants into 3 conditions and presented them with different visual tasks-mirror staring, dot staring, or neutral images. The former 2 conditions were hypothesized to induce dissociation. Postaudio, a number of factors were assessed, including state dissociation, perceptual priming and conceptual priming, as well as intrusions over 3 days. Participants in the dissociation conditions displayed an increase in perceptual priming compared to those in the control condition and reported more distressing intrusions. No differences were found in conceptual priming and the overall number of intrusions between conditions. Findings contribute to the growing knowledge on the impact of dissociation and cognitive processing in the etiology of posttraumatic stress disorder intrusions.

The Dark Side of EDX Tomography: Modeling Detector Shadowing to Aid 3D Elemental Signal Analysis.

A simple model is proposed to account for the loss of collected X-ray signal by the shadowing of X-ray detectors in the scanning transmission electron microscope. The model is intended to aid the analysis of three-dimensional elemental data sets acquired using energy-dispersive X-ray tomography methods where shadow-free specimen holders are unsuitable or unavailable. The model also provides a useful measure of the detection system geometry.

Survival after postoperative morbidity: a longitudinal observational cohort study.

BACKGROUND: Previous studies have suggested that there may be long-term harm associated with postoperative complications. Uncertainty exists however, because of the need for risk adjustment and inconsistent definitions of postoperative morbidity. METHODS: We did a longitudinal observational cohort study of patients undergoing major surgery. Case-mix adjustment was applied and morbidity was recorded using a validated outcome measure. Cox proportional hazards modelling using time-dependent covariates was used to measure the independent relationship between prolonged postoperative morbidity and longer term survival. RESULTS: Data were analysed for 1362 patients. The median length of stay was 9 days and the median follow-up time was 6.5 yr. Independent of perioperative risk, postoperative neurological morbidity (prevalence 2.9%) was associated with a relative hazard for long-term mortality of 2.00 [P=0.001; 95% confidence interval (CI) 1.32-3.04]. Prolonged postoperative morbidity (prevalence 15.6%) conferred a relative hazard for death in the first 12 months after surgery of 3.51 (P<0.001; 95% CI 2.28-5.42) and for the next 2 yr of 2.44 (P<0.001; 95% CI 1.62-3.65), returning to baseline thereafter. CONCLUSIONS: Prolonged morbidity after surgery is associated with a risk of premature death for a longer duration than perhaps is commonly thought; however, this risk falls with time. We suggest that prolonged postoperative morbidity measured in this way may be a valid indicator of the quality of surgical healthcare. Our findings reinforce the importance of research and quality improvement initiatives aimed at reducing the duration and severity of postoperative complications.

Observational study of current use of selective decontamination of the digestive tract in UK critical care units.

BACKGROUND: Evidence supporting selective decontamination of the digestive tract (SDD) is reasonably strong. We set out to determine use in UK critical care units and to compare patient outcomes between units that do and those that do not use SDD. METHODS: A total of 250 UK general critical care units were surveyed. Case mix, outcomes, and lengths of stay for admissions to SDD units (with and without an i.v. component) and non-SDD units were compared using data from the Intensive Care National Audit & Research Centre Case Mix Programme database. RESULTS: A response was received from all the 250 critical care units surveyed. Of these, 13 (5.2%) reported using SDD on some or all admissions, and of these, 3 reported using an i.v. component. Data on 284,690 admissions (April 2008-March 2011) from units reporting to the ICNARC Case Mix Programme (CMP) were included in the analyses. Admissions to SDD (n=196) and non-SDD (n=9) units were a similar case mix with similar infection rates and average lengths of stay in the unit and hospital. There was no difference in risk-adjusted unit or hospital mortality. The rate of unit-acquired infections in blood was significantly lower in SDD units using an i.v. component. CONCLUSIONS: Use of SDD in UK critical care is very low. The rate of unit-acquired infections in blood was significantly lower in SDD units using an i.v. component, but did not translate into a difference in acute hospital mortality or length of stay. There is a need to better understand the barriers to adoption of SDD into clinical practice and such work is underway.

A monoclinic polymorph of chloro-thia-zide.

A new polymorph of the diuretic chloro-thia-zide, 6-chloro-1,1-dioxo-2H-1,2,4-benzo-thia-zine-7-sulfonamide, C7H6ClN3O4S2, is described. Crystallized from basic aqueous solution, this monoclinic polymorph is found to be less thermodynamically favoured than the known triclinic polymorph and to feature only N-H⋯O type inter-molecular hydrogen bonds as opposed to the N-H⋯O and N-H⋯N type hydrogen bonds found in the P1 form.

DNA metabarcoding analysis of the bare-nosed wombat (Vombatus ursinus) diet.

Wombats are native herbivorous grazers that have adapted to Australia's low-quality forage. Studies on diet selection by bare-nosed wombats (Vombatus ursinus) are limited and are either observational or based on microhistological studies. The current study determined the diet of wombats through DNA metabarcoding across five study sites in New South Wales over a one-year period. Metabarcoding was chosen as it is non-invasive, less time consuming and more specific than traditional techniques. The list of 209 plant species identified as eaten by wombats in this study is much higher than previously reported, with grasses being the most common plant group identified in all samples. Most dietary items identified were introduced plant species. Seasonal differences in plants eaten occurred at four of the five study sites and may reflect dietary abundance and floristic composition at different times of year. Further studies are required to determine if the dietary items differ markedly across the entire range of wombats, and if nutrition influences dietary preferences.

Exploring Pseudomonas syringae pv. tomato biofilm-like aggregate formation in susceptible and PTI-responding Arabidopsis thaliana.

Bacterial biofilm-like aggregates have been observed in plants, but their role in pathogenicity is underinvestigated. In the present study, we observed that extracellular DNA and polysaccharides colocalized with green fluorescent protein (GFP)-expressing Pseudomonas syringae pv. tomato (Pst) aggregates in Arabidopsis leaves, suggesting that Pst aggregates are biofilms. GFP-expressing Pst, Pst ΔalgU ΔmucAB (Pst algU mutant), and Pst ΔalgD ΔalgU ΔmucAB (Pst algU algD mutant) were examined to explore the roles of (1) alginate, a potential biofilm component; (2) Pst AlgU, thought to regulate alginate biosynthesis and some type III secretion system effector genes; and (3) intercellular salicylic acid (SA) accumulation during pathogen-associated molecular pattern-triggered immunity (PTI). Pst formed extensive aggregates in susceptible plants, whereas aggregate numbers and size were reduced in Pst algU and Pst algD algU mutants, and both multiplied poorly in planta, suggesting that aggregate formation contributes to Pst success in planta. However, in SA-deficient sid2-2 plants, Pst algD algU mutant multiplication and aggregate formation were partially restored, suggesting plant-produced SA contributes to suppression of Pst aggregate formation. Pst algD algU mutants formed fewer and smaller aggregates than Pst algU mutants, suggesting both AlgU and AlgD contribute to Pst aggregate formation. Col-0 plants accumulated low levels of SA in response to Pst and both mutants (Pst algU and Pst algD algU), suggesting the regulatory functions of AlgU are not involved in suppressing SA-mediated plant defence. Plant PTI was associated with highly reduced Pst aggregate formation and accumulation of intercellular SA in flg22-induced PTI-responding wild-type Col-0, but not in PTI-incompetent fls2, suggesting intercellular SA accumulation by Arabidopsis contributes to suppression of Pst biofilm-like aggregate formation during PTI.

Killer whale acoustic patterns respond to prey abundance and environmental variability around the Prince Edward Islands, Southern Ocean.

Killer whales are apex predators with temporally and spatially varying distributions throughout the world's oceans. Their ecology and behaviour are poorly understood in most regions due to limited research, often because of logistical challenges. Here, we used a passive acoustic monitoring device to investigate the seasonal acoustic occurrence and diel vocalizing behaviour of killer whales around the remote sub-Antarctic Prince Edward Islands (PEIs), Southern Ocean. Killer whales showed diel vocalizing patterns that varied seasonally in relation to their prey abundance and social activities. Killer whale calls were intermittently detected year-round with a high number of hours containing calls in October to December, and a secondary peak in February to May, corresponding to seal prey abundance. Random forest modelling identified wind speed as the primary predictor of the occurrence of killer whale calls (with a negative correlation) while sea surface height, chlorophyll-a and sea surface temperature were moderately important. We provide the first acoustic evidence that killer whale occurrence around the PEIs might coincide with variability in environmental conditions and prey abundance. Our results provide the first indication of diel vocalizing pattern of killer whales in the Southern Ocean. This knowledge is important for understanding killer whale ecology and adaptation to the changing oceans.

An integrated approach to evaluating alternative risk prediction strategies: a case study comparing alternative approaches for preventing invasive fungal disease.

OBJECTIVES: This article proposes an integrated approach to the development, validation, and evaluation of new risk prediction models illustrated with the Fungal Infection Risk Evaluation study, which developed risk models to identify non-neutropenic, critically ill adult patients at high risk of invasive fungal disease (IFD). METHODS: Our decision-analytical model compared alternative strategies for preventing IFD at up to three clinical decision time points (critical care admission, after 24 hours, and end of day 3), followed with antifungal prophylaxis for those judged "high" risk versus "no formal risk assessment." We developed prognostic models to predict the risk of IFD before critical care unit discharge, with data from 35,455 admissions to 70 UK adult, critical care units, and validated the models externally. The decision model was populated with positive predictive values and negative predictive values from the best-fitting risk models. We projected lifetime cost-effectiveness and expected value of partial perfect information for groups of parameters. RESULTS: The risk prediction models performed well in internal and external validation. Risk assessment and prophylaxis at the end of day 3 was the most cost-effective strategy at the 2% and 1% risk threshold. Risk assessment at each time point was the most cost-effective strategy at a 0.5% risk threshold. Expected values of partial perfect information were high for positive predictive values or negative predictive values (£11 million-£13 million) and quality-adjusted life-years (£11 million). CONCLUSIONS: It is cost-effective to formally assess the risk of IFD for non-neutropenic, critically ill adult patients. This integrated approach to developing and evaluating risk models is useful for informing clinical practice and future research investment.

Perioperative increase in global blood flow to explicit defined goals and outcomes after surgery: a Cochrane Systematic Review.

This systematic review and meta-analysis summarizes the clinical effects of increasing perioperative blood flow using fluids with or without inotropes/vasoactive drugs to explicit defined goals in adults. We included randomized controlled trials of adult patients (aged 16 years or older) undergoing surgery. We included 31 studies of 5292 participants. There was no difference in mortality at the longest follow-up: 282/2615 (10.8%) died in the control group and 238/2677 (8.9%) in the treatment group, RR of 0.89 (95% CI: 0.76-1.05; P=0.18). However, the results were sensitive to analytical methods and withdrawal of studies with methodological limitations. The intervention reduced the rate of three morbidities (renal failure, respiratory failure, and wound infections) but not the rates of arrhythmia, myocardial infarction, congestive cardiac failure, venous thrombosis, and other types of infections. The number of patients with complications was also reduced by the intervention. Hospital length of stay was reduced in the treatment group by 1.16 days. There was no difference in critical care length of stay. The primary analysis of this review showed no difference between groups but this result was sensitive to the method of analysis, withdrawal of studies with methodological limitations, and was dominated by a single large study. Patients receiving this intervention stayed in hospital 1 day less with fewer complications. It is unlikely that the intervention causes harm. The balance of current evidence does not support widespread implementation of this approach to reduce mortality but does suggest that complications and duration of hospital stay are reduced.

The effect of prey abundance and fisheries on the survival, reproduction, and social structure of killer whales (Orcinus orca) at subantarctic Marion Island.

Most marine apex predators are keystone species that fundamentally influence their ecosystems through cascading top-down processes. Reductions in worldwide predator abundances, attributed to environmental- and anthropogenic-induced changes to prey availability and negative interactions with fisheries, can have far-reaching ecosystem impacts. We tested whether the survival of killer whales (Orcinus orca) observed at Marion Island in the Southern Indian Ocean correlated with social structure and prey variables (direct measures of prey abundance, Patagonian toothfish fishery effort, and environmental proxies) using multistate models of capture-recapture data spanning 12 years (2006-2018). We also tested the effect of these same variables on killer whale social structure and reproduction measured over the same period. Indices of social structure had the strongest correlation with survival, with higher sociality associated with increased survival probability. Survival was also positively correlated with Patagonian toothfish fishing effort during the previous year, suggesting that fishery-linked resource availability is an important determinant of survival. No correlation between survival and environmental proxies of prey abundance was found. At-island prey availability influenced the social structure of Marion Island killer whales, but none of the variables explained variability in reproduction. Future increases in legal fishing activity may benefit this population of killer whales through the artificial provisioning of resources they provide.