Early quick acuity score provides more complete data on emergency department walkouts.

INTRODUCTION: Many prior studies have compared the acuity of Emergency Department (ED) patients who have Left Without Being Seen (LWBS) against non-LWBS patients. A weakness in these studies is that patients may walk out prior to the assignment of a triage score, biasing comparisons. We report an operational change whereby acuity was assessed immediately upon patient arrival. We hypothesized more patients would receive acuity scores with EQAS. We also sought to compare LWBS and non-LWBS patient characteristics with reduced bias. SETTING: urban, academic medical center. Retrospective cohort study, electronic chart review, collecting data on all ED patients presenting between 4/1/2010 and 10/31/2011 ( Traditional Acuity Score period, TAS) and from 11/1/2011 to 3/31/2012 ( Early Quick Acuity Score period, EQAS). We recorded disposition (LWBS versus non-LWBS), acuity and demographics. For each subject during the EQAS period, we calculated how many prior ED visits and how many prior walkouts the subject had had during the TAS period. RESULTS: Acuity was recorded in 92,275 of 94,526 patients (97.6%) for TAS period, and 25,577 of 25,760 patients (99.3%) for EQAS period, a difference of 1.7% (1.5%, 1.8%). LWBS patients had acuity scores recorded in 5,180 of 7,040 cases (73.6%) during TAS period, compared with 897 of 1,010 cases (88.8%) during the EQAS period, a difference of 15.2% (14.8%, 15.7%). LWBS were more likely than non-LWBS to be male, were younger and had lower acuity scores. LWBS averaged 5.3 prior ED visits compared with 2.8 by non-LWBS, a difference of 2.5 (1.5, 3.5). LWBS averaged 1.3 prior ED walkouts compared with 0.2 among non-LWBS, a difference of 1.1 (0.8, 1.3). CONCLUSIONS: EQAS resulted in a higher proportion of patients receiving acuity scores, particularly among LWBS. This offers more complete data when comparing LWBS and non-LWBS patient characteristics. The comparison reinforced findings from prior studies

Catastrophic Spontaneous Uterine and Bladder Rupture in an Unscarred Uterus

Introduction: Uterine rupture during pregnancy is a rare event which can be life-threatening for both the patient and the fetus. This case report describes a rare complication of uterine rupture which ultimately required a hysterectomy and extensive urologic reconstruction. Case Description: A 36-year-old patient presented to the hospital after term pre-labor rupture of membranes. The patient underwent induction of labor which ultimately resulted in a uterine rupture in an unscarred uterus. The rupture extended into the posterior bladder wall, right ureter, urethra, and anterior vaginal wall, resulting in a vesicovaginal fistula. The patient required a cesarean hysterectomy due to the uterine damage. Cystorrhaphy with right percutaneous nephrostomy tube and suprapubic catheter placement were performed due to the extensive urologic sequelae. Months later, the patient underwent ureteroneocystostomy for definitive urologic management. Discussion: Bladder rupture is a rare complication of uterine rupture and can occur in an unscarred uterus. Intrapartum bladder rupture should be considered in patients who develop gross hematuria or anterior vaginal wall laceration in the setting of uterine rupture. Maternal morbidity and mortality due to uterine rupture is decreased when care is provided at a tertiary referral or trauma center. This should be taken into consideration when planning deliveries with an increased risk of uterine rupture. Furthermore, providers performing vaginal deliveries should be aware of this rare complication to optimize maternal and neonatal outcomes

Concepts of GPCR-controlled navigation in the immune system

G-protein-coupled receptor (GPCR) signaling is essential for the spatiotemporal control of leukocyte dynamics during immune responses. For efficient navigation through mammalian tissues, most leukocyte types express more than one GPCR on their surface and sense a wide range of chemokines and chemoattractants, leading to basic forms of leukocyte movement (chemokinesis, haptokinesis, chemotaxis, haptotaxis, and chemorepulsion). How leukocytes integrate multiple GPCR signals and make directional decisions in lymphoid and inflamed tissues is still subject of intense research. Many of our concepts on GPCR-controlled leukocyte navigation in the presence of multiple GPCR signals derive from in vitro chemotaxis studies and lower vertebrates. In this review, we refer to these concepts and critically contemplate their relevance for the directional movement of several leukocyte subsets (neutrophils, T cells, and dendritic cells) in the complexity of mouse tissues. We discuss how leukocyte navigation can be regulated at the level of only a single GPCR (surface expression, competitive antagonism, oligomerization, homologous desensitization, and receptor internalization) or multiple GPCRs (synergy, hierarchical and non-hierarchical competition, sequential signaling, heterologous desensitization, and agonist scavenging). In particular, we will highlight recent advances in understanding GPCR-controlled leukocyte navigation by intravital microscopy of immune cells in mice

CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis

Macrophages abundantly found in the tumor microenvironment enhance malignancy(1). At metastatic sites a distinct population of metastasis associated macrophages (MAMs) promote tumor cell extravasation, seeding and persistent growth(2). Our study has defined the origin of these macrophages by showing Gr1+ inflammatory monocytes (IMs) are preferentially recruited to pulmonary metastases but not primary mammary tumors, a process also found for human IMs in pulmonary metastases of human breast cancer cells. The recruitment of these CCR2 (receptor for chemokine CCL2) expressing IMs and subsequently MAMs and their interaction with metastasizing tumor cells is dependent on tumor and stromal synthesized CCL2 (FigS1). Inhibition of CCL2/CCR2 signaling using anti-CCL2 antibodies blocks IM recruitment and inhibits metastasis in vivo and prolongs the survival of tumor-bearing mice. Depletion of tumor cell-derived CCL2 also inhibits metastatic seeding. IMs promote tumor cell extravasation in a process that requires monocyte-derived VEGF. CCL2 expression and macrophage infiltration are correlated with poor prognosis and metastatic disease in human breast cancer (Fig S2)(3-6). Our data provides the mechanistic link between these two clinical associations and indicates new therapeutic targets for treating metastatic breast disease

The Quark Beam Function at NNLL

In hard collisions at a hadron collider the most appropriate description of the initial state depends on what is measured in the final state. Parton distribution functions (PDFs) evolved to the hard collision scale Q are appropriate for inclusive observables, but not for measurements with a specific number of hard jets, leptons, and photons. Here the incoming protons are probed and lose their identity to an incoming jet at a scale \mu_B << Q, and the initial state is described by universal beam functions. We discuss the field-theoretic treatment of beam functions, and show that the beam function has the same RG evolution as the jet function to all orders in perturbation theory. In contrast to PDF evolution, the beam function evolution does not mix quarks and gluons and changes the virtuality of the colliding parton at fixed momentum fraction. At \mu_B, the incoming jet can be described perturbatively, and we give a detailed derivation of the one-loop matching of the quark beam function onto quark and gluon PDFs. We compute the associated NLO Wilson coefficients and explicitly verify the cancellation of IR singularities. As an application, we give an expression for the next-to-next-to-leading logarithmic order (NNLL) resummed Drell-Yan beam thrust cross section.Comment: 54 pages, 9 figures; v2: notation simplified in a few places, typos fixed; v3: journal versio

The proline-rich domain of tau plays a role in interactions with actin

<p>Abstract</p> <p>Background</p> <p>The microtubule-associated protein tau is able to interact with actin and serves as a cross-linker between the microtubule and actin networks. The microtubule-binding domain of tau is known to be involved in its interaction with actin. Here, we address the question of whether the other domains of tau also interact with actin.</p> <p>Results</p> <p>Several tau truncation and deletion mutants were constructed, namely N-terminal region (tauN), proline-rich domain (tauPRD), microtubule binding domain (tauMTBD) and C-terminal region (tauC) truncation mutants, and microtubule binding domain (tauΔMTBD) and proline-rich domain/microtubule binding domain (tauΔPRD&MTBD) deletion mutants. The proline-rich domain truncation mutant (tauPRD) and the microtubule binding domain deletion mutant (tauΔMTBD) promoted the formation of actin filaments. However, actin assembly was not observed in the presence of the N-terminal and C-terminal truncation mutants. These results indicate that the proline-rich domain is involved in the association of tau with G-actin. Furthermore, results from co-sedimentation, solid phase assays and electron microscopy showed that the proline-rich domain is also capable of binding to F-actin and inducing F-actin bundles. Using solid phase assays to analyze apparent dissociation constants for the binding of tau and its mutants to F-actin resulted in a sequence of affinity for F-actin: tau >> microtubule binding domain > proline-rich domain. Moreover, we observed that the proline-rich domain was able to associate with and bundle F-actin at physiological ionic strength.</p> <p>Conclusion</p> <p>The proline-rich domain is a functional structure playing a role in the association of tau with actin. This suggests that the proline-rich domain and the microtubule-binding domain of tau are both involved in binding to and bundling F-actin.</p

Cumulative Exposure to Lead in Relation to Cognitive Function in Older Women

Background: Recent data indicate that chronic low-level exposure to lead is associated with accelerated declines in cognition in older age, but this has not been examined in women. Objective: We examined biomarkers of lead exposure in relation to performance on a battery of cognitive tests among older women. Methods: Patella and tibia bone lead—measures of cumulative exposure over many years—and blood lead, a measure of recent exposure, were assessed in 587 women 47–74 years of age. We assessed their cognitive function 5 years later using validated telephone interviews. Results: Mean ± SD lead levels in tibia, patella, and blood were 10.5 ± 9.7 μg/g bone, 12.6 ± 11.6 μg/g bone, and 2.9 ± 1.9 μg/dL, respectively, consistent with community-level exposures. In multivariable-adjusted analyses of all cognitive tests combined, levels of all three lead biomarkers were associated with worse cognitive performance. The association between bone lead and letter fluency score differed dramatically from the other bone lead-cognitive score associations, and exclusion of this particular score from the combined analyses strengthened the associations between bone lead and cognitive performance. Results were statistically significant only for tibia lead: one SD increase in tibia lead corresponded to a 0.051-unit lower standardized summary cognitive score (95% confidence interval: −0.099 to −0.003; p = 0.04), similar to the difference in cognitive scores we observed between women who were 3 years apart in age. Conclusions: These findings suggest that cumulative exposure to lead, even at low levels experienced in community settings, may have adverse consequences for women’s cognition in older age

Two-Loop Soft Corrections and Resummation of the Thrust Distribution in the Dijet Region

The thrust distribution in electron-positron annihilation is a classical precision QCD observable. Using renormalization group (RG) evolution in Laplace space, we perform the resummation of logarithmically enhanced corrections in the dijet limit, $T\to 1$ to next-to-next-to-leading logarithmic (NNLL) accuracy. We independently derive the two-loop soft function for the thrust distribution and extract an analytical expression for the NNLL resummation coefficient $g_3$. To combine the resummed expressions with the fixed-order results, we derive the $\log(R)$-matching and $R$-matching of the NNLL approximation to the fixed-order NNLO distribution.Comment: 50 pages, 12 figures, 1 table. Few minor changes. Version accepted for publication in JHE

Core components for effective infection prevention and control programmes: new WHO evidence-based recommendations

Abstract Health care-associated infections (HAI) are a major public health problem with a significant impact on morbidity, mortality and quality of life. They represent also an important economic burden to health systems worldwide. However, a large proportion of HAI are preventable through effective infection prevention and control (IPC) measures. Improvements in IPC at the national and facility level are critical for the successful containment of antimicrobial resistance and the prevention of HAI, including outbreaks of highly transmissible diseases through high quality care within the context of universal health coverage. Given the limited availability of IPC evidence-based guidance and standards, the World Health Organization (WHO) decided to prioritize the development of global recommendations on the core components of effective IPC programmes both at the national and acute health care facility level, based on systematic literature reviews and expert consensus. The aim of the guideline development process was to identify the evidence and evaluate its quality, consider patient values and preferences, resource implications, and the feasibility and acceptability of the recommendations. As a result, 11 recommendations and three good practice statements are presented here, including a summary of the supporting evidence, and form the substance of a new WHO IPC guideline

Mitochondrial complex I and cell death: a semi-automatic shotgun model

Mitochondrial dysfunction often leads to cell death and disease. We can now draw correlations between the dysfunction of one of the most important mitochondrial enzymes, NADH:ubiquinone reductase or complex I, and its structural organization thanks to the recent advances in the X-ray structure of its bacterial homologs. The new structural information on bacterial complex I provide essential clues to finally understand how complex I may work. However, the same information remains difficult to interpret for many scientists working on mitochondrial complex I from different angles, especially in the field of cell death. Here, we present a novel way of interpreting the bacterial structural information in accessible terms. On the basis of the analogy to semi-automatic shotguns, we propose a novel functional model that incorporates recent structural information with previous evidence derived from studies on mitochondrial diseases, as well as functional bioenergetics