Endothelial Cell Calcium Influx Mediates Trauma-induced Endothelial Permeability.

OBJECTIVE: We aimed to investigate if ex vivo plasma from injured patients causes endothelial calcium (Ca2+) influx as a mechanism of trauma-induced endothelial permeability. SUMMARY BACKGROUND DATA: Endothelial permeability after trauma contributes to post-injury organ dysfunction. While the mechanisms remain unclear, emerging evidence suggests intracellular Ca2+ signaling may play a role. METHODS: Ex vivo plasma from injured patients with "Low Injury/Low Shock" (injury severity score [ISS]<15, base excess [BE])≥-6mEq/L) and "High Injury/High Shock" (ISS≥15, BE<-6mEq/L) were used to treat endothelial cells. Experimental conditions included Ca2+ removal from the extracellular buffer, cyclopiazonic acid pre-treatment to deplete intracellular Ca2+ stores, and GSK2193874 pre-treatment to block the TRPV4 Ca2+ channel. Live cell fluorescence microscopy and ECIS were used to assess cytosolic Ca2+ increases and permeability, respectively. Western blot and live cell actin staining were used to assess myosin light chain (MLC) phosphorylation and actomyosin contraction. RESULTS: Compared to Low Injury/Low Shock plasma, High Injury/High Shock induced greater cytosolic Ca2+ increase. Cytosolic Ca2+ increase, MLC phosphorylation, and actin cytoskeletal contraction were lower without extracellular Ca2+ present. High Injury/High Shock plasma did not induce endothelial permeability without extracellular Ca2+ present. TRPV4 inhibition lowered trauma plasma-induced endothelial Ca2+ influx and permeability. CONCLUSIONS: This study illuminates a novel mechanism of post-injury endotheliopathy involving Ca2+ influx via the TRPV4 channel. TRPV4 inhibition mitigates trauma-induced endothelial permeability. Moreover, widespread endothelial Ca2+ influx may contribute to trauma-induced hypocalcemia. This study provides the mechanistic basis for the development of Ca2+-targeted therapies and interventions in the care of severely injured patients.

Randomized controlled trial of mechanical thrombectomy vs catheter-directed thrombolysis for acute hemodynamically stable pulmonary embolism: Rationale and design of the PEERLESS study.

BACKGROUND: The identification of hemodynamically stable pulmonary embolism (PE) patients who may benefit from advanced treatment beyond anticoagulation is unclear. However, when intervention is deemed necessary by the PE patient's care team, data to select the most advantageous interventional treatment option are lacking. Limiting factors include major bleeding risks with systemic and locally delivered thrombolytics and the overall lack of randomized controlled trial (RCT) data for interventional treatment strategies. Considering the expansion of the pulmonary embolism response team (PERT) model, corresponding rise in interventional treatment, and number of thrombolytic and nonthrombolytic catheter-directed devices coming to market, robust evidence is needed to identify the safest and most effective interventional option for patients. METHODS: The PEERLESS study (ClinicalTrials.gov identifier: NCT05111613) is a currently enrolling multinational RCT comparing large-bore mechanical thrombectomy (MT) with the FlowTriever System (Inari Medical, Irvine, CA) vs catheter-directed thrombolysis (CDT). A total of 550 hemodynamically stable PE patients with right ventricular (RV) dysfunction and additional clinical risk factors will undergo 1:1 randomization. Up to 150 additional patients with absolute thrombolytic contraindications may be enrolled into a nonrandomized MT cohort for separate analysis. The primary end point will be assessed at hospital discharge or 7 days post procedure, whichever is sooner, and is a composite of the following clinical outcomes constructed as a hierarchal win ratio: (1) all-cause mortality, (2) intracranial hemorrhage, (3) major bleeding, (4) clinical deterioration and/or escalation to bailout, and (5) intensive care unit admission and length of stay. The first 4 components of the win ratio will be adjudicated by a Clinical Events Committee, and all components will be assessed individually as secondary end points. Other key secondary end points include all-cause mortality and readmission within 30 days of procedure and device- and drug-related serious adverse events through the 30-day visit. IMPLICATIONS: PEERLESS is the first RCT to compare 2 different interventional treatment strategies for hemodynamically stable PE and results will inform strategy selection after the physician or PERT determines advanced therapy is warranted.

Altered regulation of DPF3, a member of the SWI/SNF complexes, underlies the 14q24 renal cancer susceptibility locus.

Our study investigated the underlying mechanism for the 14q24 renal cell carcinoma (RCC) susceptibility risk locus identified by a genome-wide association study (GWAS). The sentinel single-nucleotide polymorphism (SNP), rs4903064, at 14q24 confers an allele-specific effect on expression of the double PHD fingers 3 (DPF3) of the BAF SWI/SNF complex as assessed by massively parallel reporter assay, confirmatory luciferase assays, and eQTL analyses. Overexpression of DPF3 in renal cell lines increases growth rates and alters chromatin accessibility and gene expression, leading to inhibition of apoptosis and activation of oncogenic pathways. siRNA interference of multiple DPF3-deregulated genes reduces growth. Our results indicate that germline variation in DPF3, a component of the BAF complex, part of the SWI/SNF complexes, can lead to reduced apoptosis and activation of the STAT3 pathway, both critical in RCC carcinogenesis. In addition, we show that altered DPF3 expression in the 14q24 RCC locus could influence the effectiveness of immunotherapy treatment for RCC by regulating tumor cytokine secretion and immune cell activation.

Whole Blood Thrombin Generation in Severely Injured Patients Requiring Massive Transfusion.

BACKGROUND: Despite the prevalence of hypocoagulability after injury, the majority of trauma patients paradoxically present with elevated thrombin generation (TG). Although several studies have examined plasma TG post injury, this has not been assessed in whole blood. We hypothesize that whole blood TG is lower in hypocoagulopathy, and TG effectively predicts massive transfusion (MT). STUDY DESIGN: Blood was collected from trauma activation patients at an urban Level I trauma center. Whole blood TG was performed with a prototype point-of-care device. Whole blood TG values in healthy volunteers were compared with trauma patients, and TG values were examined in trauma patients with shock and MT requirement. RESULTS: Overall, 118 patients were included. Compared with healthy volunteers, trauma patients overall presented with more robust TG; however, those arriving in shock (n = 23) had a depressed TG, with significantly lower peak thrombin (88.3 vs 133.0 nM; p = 0.01) and slower maximum rate of TG (27.4 vs 48.3 nM/min; p = 0.04). Patients who required MT (n = 26) had significantly decreased TG, with a longer lag time (median 4.8 vs 3.9 minutes, p = 0.04), decreased peak thrombin (median 71.4 vs 124.2 nM; p = 0.0003), and lower maximum rate of TG (median 15.8 vs 39.4 nM/min; p = 0.01). Area under the receiver operating characteristics (AUROC) analysis revealed lag time (AUROC 0.6), peak thrombin (AUROC 0.7), and maximum rate of TG (AUROC 0.7) predict early MT. CONCLUSIONS: These data challenge the prevailing bias that all trauma patients present with elevated TG and highlight that deficient thrombin contributes to the hypocoagulopathic phenotype of trauma-induced coagulopathy. In addition, whole blood TG predicts MT, suggesting point-of-care whole blood TG can be a useful tool for diagnostic and therapeutic strategies in trauma.

The Cuban Human Brain Mapping Project, a young and middle age population-based EEG, MRI, and cognition dataset.

The Cuban Human Brain Mapping Project (CHBMP) repository is an open multimodal neuroimaging and cognitive dataset from 282 young and middle age healthy participants (31.9 ± 9.3 years, age range 18-68 years). This dataset was acquired from 2004 to 2008 as a subset of a larger stratified random sample of 2,019 participants from La Lisa municipality in La Habana, Cuba. The exclusion criteria included the presence of disease or brain dysfunctions. Participant data that is being shared comprises i) high-density (64-120 channels) resting-state electroencephalograms (EEG), ii) magnetic resonance images (MRI), iii) psychological tests (MMSE, WAIS-III, computerized go-no go reaction time), as well as iv,) demographic information (age, gender, education, ethnicity, handedness, and weight). The EEG data contains recordings with at least 30 minutes in duration including the following conditions: eyes closed, eyes open, hyperventilation, and subsequent recovery. The MRI consists of anatomical T1 as well as diffusion-weighted (DWI) images acquired on a 1.5 Tesla system. The dataset presented here is hosted by Synapse.org and available at https://chbmp-open.loris.ca .

Examining the Effect of Hypertonic Saline Administered for Reduction of Intracranial Hypertension on Coagulation.

BACKGROUND: Hypertonic saline (23.4%, HTS) bolus administration is common practice for refractory intracranial hypertension, but its effects on coagulation are unknown. We hypothesize that 23.4% HTS in whole blood results in progressive impairment of coagulation in vitro and in vivo in a murine model of traumatic brain injury (TBI). STUDY DESIGN: For the in vitro study, whole blood was collected from 10 healthy volunteers, and citrated native thrombelastography was performed with normal saline (0.9%, NS) and 23.4% HTS in serial dilutions (2.5%, 5%, and 10%). For the in vivo experiment, we assessed the effects of 23.4% HTS bolus vs NS on serial thrombelastography and tail-bleeding times in a TBI murine model (n = 10 rats with TBI and 10 controls). RESULTS: For the in vitro work, clinically relevant concentrations of HTS (2.5% dilution) shortened time to clot formation and increased clot strength (maximum amplitude) compared with control and NS. With higher HTS dosing (5% and 10% blood dilution), there was progressive prolongation of time to clot formation, decreased angle, and decreased maximum amplitude. In the in vivo study, there was no significant difference in thrombelastography measurements or tail-bleeding times after bolus administration of 23.4% HTS compared with NS at 2.5% blood volume. CONCLUSIONS: At clinically relevant dilutions of HTS, there is a paradoxical shortening of time to clot formation and increase in clot strength in vitro and no significant effects in a murine TBI model. However, with excess dilution, caution should be exercised when using serial HTS boluses in TBI patients at risk for trauma-induced coagulopathy.

Systematic integration of GATA transcription factors and epigenomes via IDEAS paints the regulatory landscape of hematopoietic cells.

Members of the GATA family of transcription factors play key roles in the differentiation of specific cell lineages by regulating the expression of target genes. Three GATA factors play distinct roles in hematopoietic differentiation. In order to better understand how these GATA factors function to regulate genes throughout the genome, we are studying the epigenomic and transcriptional landscapes of hematopoietic cells in a model-driven, integrative fashion. We have formed the collaborative multi-lab VISION project to conduct ValIdated Systematic IntegratiON of epigenomic data in mouse and human hematopoiesis. The epigenomic data included nuclease accessibility in chromatin, CTCF occupancy, and histone H3 modifications for 20 cell types covering hematopoietic stem cells, multilineage progenitor cells, and mature cells across the blood cell lineages of mouse. The analysis used the Integrative and Discriminative Epigenome Annotation System (IDEAS), which learns all common combinations of features (epigenetic states) simultaneously in two dimensions-along chromosomes and across cell types. The result is a segmentation that effectively paints the regulatory landscape in readily interpretable views, revealing constitutively active or silent loci as well as the loci specifically induced or repressed in each stage and lineage. Nuclease accessible DNA segments in active chromatin states were designated candidate cis-regulatory elements in each cell type, providing one of the most comprehensive registries of candidate hematopoietic regulatory elements to date. Applications of VISION resources are illustrated for the regulation of genes encoding GATA1, GATA2, GATA3, and Ikaros. VISION resources are freely available from our website http://usevision.org.

Final Two-Year Outcomes for the Sentry Bioconvertible Inferior Vena Cava Filter in Patients Requiring Temporary Protection from Pulmonary Embolism.

PURPOSE: To report final 2-year outcomes with the Sentry bioconvertible inferior vena cava (IVC) filter in patients requiring temporary protection against pulmonary embolism (PE). MATERIALS AND METHODS: In a prospective multicenter trial, the Sentry filter was implanted in 129 patients with documented deep vein thrombosis (DVT) and/or PE (67.5%) or who were at temporary risk of developing DVT/PE (32.6%). Patients were monitored and bioconversion status ascertained by radiography, computed tomography (CT), and CT venography through 2 years. RESULTS: The composite primary 6-month endpoint of clinical success was achieved in 97.4% (111/114) of patients. The rate of new symptomatic PE was 0% (n = 126) through 1 year and 2.4% (n = 85) through the second year of follow-up, with 2 new nonfatal cases at 581 and 624 days that were adjudicated as not related to the procedure or device. Two patients (1.6%) developed symptomatic caval thrombosis during the first month and underwent successful interventions without recurrence. No other filter-related symptomatic complications occurred through 2 years. There was no filter tilting, migration, embolization, fracture, or caval perforation and no filter-related deaths through 2 years. Filter bioconversion was successful for 95.7% (110/115) of patients at 6 months, 96.4% (106/110) of patients at 12 months, and 96.5% (82/85) of patients at 24 months. Through 24 months of follow-up, there was no evidence of late-stage IVC obstruction or thrombosis after filter bioconversion or of thrombogenicity associated with retracted filter arms. CONCLUSIONS: The Sentry IVC filter provided safe and effective protection against PE, with a high rate of intended bioconversion and a low rate of device-related complications, through 2 years of follow-up.

Climate change and cultural resilience in late pre-Columbian Amazonia.

The long-term response of ancient societies to climate change has been a matter of global debate. Until recently, the lack of integrative studies using archaeological, palaeoecological and palaeoclimatological data prevented an evaluation of the relationship between climate change, distinct subsistence strategies and cultural transformations across the largest rainforest of the world, Amazonia. Here we review the most relevant cultural changes seen in the archaeological record of six different regions within Greater Amazonia during late pre-Columbian times. We compare the chronology of those cultural transitions with high-resolution regional palaeoclimate proxies, showing that, while some societies faced major reorganization during periods of climate change, others were unaffected and even flourished. We propose that societies with intensive, specialized land-use systems were vulnerable to transient climate change. In contrast, land-use systems that relied primarily on polyculture agroforestry, resulting in the formation of enriched forests and fertile Amazonian dark earth in the long term, were more resilient to climate change.

Trauma Resuscitation Consideration: Sex Matters.

BACKGROUND: Sex dimorphisms in coagulation have been recognized, but whole blood assessment of these dimorphisms and their relationship to outcomes in trauma have not been investigated. This study characterizes the viscoelastic hemostatic profile of severely injured patients by sex, and examines how sex-specific coagulation differences affect clinical outcomes, specifically, massive transfusion (MT) and death. We hypothesized that severely injured females are more hypercoagulable and therefore, have lower rates of MT and mortality. STUDY DESIGN: Hemostatic profiles and clinical outcomes from all trauma activation patients from 2 level I trauma centers were examined, with sex as an experimental variable. As part of a prospective study, whole blood was collected and thrombelastography (TEG) was performed. Coagulation profiles were compared between sexes, and association with MT and mortality were examined. Poisson regression with robust standard errors was performed. RESULTS: Overall, 464 patients (23% female) were included. By TEG, females had a more hypercoagulable profile, with a higher angle (clot propagation) and maximum amplitude (MA, clot strength). Females were less likely to present with hyperfibrinolysis or prolonged activating clotting time than males. In the setting of depressed clot strength (abnormal MA), female sex conferred a survival benefit, and hyperfibrinolysis was associated with higher case-fatality rate in males. CONCLUSIONS: Severely injured females have a more hypercoagulable profile than males. This hypercoagulable status conferred a protective effect against mortality in the setting of diminished clot strength. The mechanism behind these dimorphisms needs to be elucidated and may have treatment implications for sex-specific trauma resuscitation.

Severe traumatic brain injury is associated with a unique coagulopathy phenotype.

BACKGROUND: Traumatic brain injury (TBI) patients present on a spectrum from hypocoagulability to hypercoagulability, depending on the injury complexity, severity, and time since injury. Prior studies have found a unique coagulopathy associated with TBI using conventional coagulation assays such as INR; however, few studies have assessed the association of TBI and coagulopathy using viscoelastic assays that comprehensively evaluate the coagulation in whole blood. This study aims to reevaluate the TBI-specific trauma-induced coagulopathy using arrival thrombelastography. Because brain tissue is high in key procoagulant molecules, we hypothesize that isolated TBI is associated with procoagulant and hypofibrinolytic profiles compared with injuries of the torso, extremities, and polytrauma, including TBI. METHODS: Data are from the prospective Trauma Activation Protocol study. Activated clotting time (ACT), angle, maximum amplitude (MA), 30-minute percent lysis after MA (LY30), and functional fibrinogen levels (FFLEV) were recorded. Patients were categorized into isolated severe TBI (I-TBI), severe TBI with torso and extremity injuries (TBI + TORSO/EXTREMITIES), and isolated torso and extremity injuries (I-TORSO/EXTREMITIES). Poisson regression was used to adjust for multiple confounders. RESULTS: Overall, 572 patients (48 I-TBI, 45 TBI + TORSO/EXTREMITIES, 479 I-TORSO/EXTREMITIES) were included in this analysis. The groups differed in INR, ACT, angle, MA, and FFLEV but not in 30-minute percent lysis. When compared with I-Torso/Extremities, after adjustment for confounders, severe I-TBI was independently associated with ACT less than 128 seconds (relative risk [RR], 1.5; 95% confidence interval [CI], 1.1-2.2), angle less than 65 degrees (RR, 2.2; 95% CI, 1.4-3.6), FFLEV less than 356 (RR, 1.7; 95% CI, 1.2-2.4) but not MA less than 55 mm, hyperfibrinolysis, fibrinolysis shutdown, or partial thromboplastin time (PTT) greater than 30. CONCLUSION: Severe I-TBI was independently associated with a distinct coagulopathy with delayed clot formation but did not appear to be associated with fibrinolysis abnormalities. Low fibrinogen and longer ACT values associated with I-TBI suggest that early coagulation factor replacement may be indicated in I-TBI patients over empiric antifibrinolytic therapy. Mechanisms triggering coagulopathy in TBI are unique and warrant further investigation. LEVEL OF EVIDENCE: Retrospective cohort study, prognostic, level III.

One-Year Analysis of the Prospective Multicenter SENTRY Clinical Trial: Safety and Effectiveness of the Novate Sentry Bioconvertible Inferior Vena Cava Filter.

PURPOSE: To prospectively assess the Sentry bioconvertible inferior vena cava (IVC) filter in patients requiring temporary protection against pulmonary embolism (PE). MATERIALS AND METHODS: At 23 sites, 129 patients with documented deep vein thrombosis (DVT) or PE, or at temporary risk of developing DVT or PE, unable to use anticoagulation were enrolled. The primary end point was clinical success, including successful filter deployment, freedom from new symptomatic PE through 60 days before filter bioconversion, and 6-month freedom from filter-related complications. Patients were monitored by means of radiography, computerized tomography (CT), and CT venography to assess filtering configuration through 60 days, filter bioconversion, and incidence of PE and filter-related complications through 12 months. RESULTS: Clinical success was achieved in 111 of 114 evaluable patients (97.4%, 95% confidence interval [CI] 92.5%-99.1%). The rate of freedom from new symptomatic PE through 60 days was 100% (n = 129, 95% CI 97.1%-100.0%), and there were no cases of PE through 12 months for either therapeutic or prophylactic indications. Two patients (1.6%) developed symptomatic caval thrombosis during the first month; neither experienced recurrence after successful interventions. There was no filter tilting, migration, embolization, fracture, or caval perforation by the filter, and no filter-related death through 12 months. Filter bioconversion was successful for 95.7% (110/115) at 6 months and for 96.4% (106/110) at 12 months. CONCLUSIONS: The Sentry IVC filter provided safe and effective protection against PE, with a high rate of intended bioconversion and a low rate of device-related complications, through 12 months of imaging-intense follow-up.

Platelet dense granules begin to selectively accumulate mepacrine during proplatelet formation.

Platelet dense granules (DGs) are storage organelles for calcium ions, small organic molecules such as ADP and serotonin, and larger polyphosphates that are secreted upon platelet stimulation to enhance platelet activation, adhesion, and stabilization at sites of vascular damage. DGs are thought to fully mature within megakaryocytes (MKs) prior to platelet formation. Here we challenge this notion by exploiting vital fluorescent dyes to distinguish mildly acidic DGs from highly acidic compartments by microscopy in platelets and MKs. In isolated primary mouse platelets, compartments labeled by mepacrine - a fluorescent weak base that accumulates in DGs - are readily distinguishable from highly acidic compartments, likely lysosomes, that are labeled by the acidic pH indicator, LysoTracker, and from endolysosomes and alpha granules labeled by internalized and partially digested DQ™ BSA. By contrast, in murine fetal liver- and human CD34+ cell-derived MKs and the megakaryocytoid cell lines, MEG-01 and differentiated G1ME2, labeling by mepacrine overlapped nearly completely with labeling by LysoTracker and partially with labeling by DQ™ BSA. Mepacrine labeling in G1ME2-derived MKs was fully sensitive to proton ATPase inhibitors, but was only partially sensitive in platelets. These data indicate that mepacrine in MKs accumulates as a weak base in endolysosomes but is likely pumped into or retained in separate DGs in platelets. Fluorescent puncta that labeled uniquely for mepacrine were first evident in G1ME2-derived proplatelets, suggesting that DGs undergo a maturation step that initiates in the final stages of MK differentiation.

Key tumor suppressor genes inactivated by "greater promoter" methylation and somatic mutations in head and neck cancer.

Tumor suppressor genes (TSGs) are commonly inactivated by somatic mutation and/or promoter methylation; yet, recent high-throughput genomic studies have not identified key TSGs inactivated by both mechanisms. We pursued an integrated molecular analysis based on methylation binding domain sequencing (MBD-seq), 450K Methylation arrays, whole exome sequencing, and whole genome gene expression arrays in primary head and neck squamous cell carcinoma (HNSCC) tumors and matched uvulopalatopharyngoplasty tissue samples (UPPPs). We uncovered 186 downregulated genes harboring cancer specific promoter methylation including PAX1 and PAX5 and we identified 10 key tumor suppressor genes (GABRB3, HOXC12, PARP15, SLCO4C1, CDKN2A, PAX1, PIK3AP1, HOXC6, PLCB1, and ZIC4) inactivated by both promoter methylation and/or somatic mutation. Among the novel tumor suppressor genes discovered with dual mechanisms of inactivation, we found a high frequency of genomic and epigenomic alterations in the PAX gene family of transcription factors, which selectively impact canonical NOTCH and TP53 pathways to determine cell fate, cell survival, and genome maintenance. Our results highlight the importance of assessing TSGs at the genomic and epigenomic level to identify key pathways in HNSCC, deregulated by simultaneous promoter methylation and somatic mutations.

Incidence of injury among male Brazilian jiujitsu fighters at the World Jiu-Jitsu No-Gi Championship 2009.

CONTEXT: Brazilian jiujitsu is a modern combat martial art that uses joint locks to submit an opponent and achieve victory. This form of martial art is a relatively young but rapidly growing combat sport worldwide. OBJECTIVE: To determine the cumulative injury incidence and risk of injury by belt rank and body region at an international-level Brazilian jiujitsu tournament. DESIGN: Descriptive epidemiology study. SETTING: World Jiu-Jitsu No-Gi Championship 2009 in Long Beach, California. PATIENTS OR OTHER PARTICIPANTS: We monitored 951 athletes (age range, 18-50 years) enrolled to compete in the World Jiu-Jitsu No-Gi Championship 2009. INTERVENTION(S): Fighters were categorized by belt level for group comparisons (belt experience). Incidence rates per 1000 athlete-exposures (AEs) and incidence rate ratios were compared by belt rank. MAIN OUTCOME MEASURE(S): Incidence rates and incidence rate ratios. RESULTS: During the tournament, 1606 AEs and 62 total injuries were reported. Of these injuries, 40 affected the joints, for an overall incidence rate of 24.9 per 1000 AEs. The joint incidence rate by belt rank was 21.5 per 1000 AEs for blue, 21.3 per 1000 AEs for purple, 25.2 per 1000 AEs for brown, and 35.1 per 1000 AEs for black. We found no differences for incidence rate ratios of joint injury among individual belt groups (P > .05). More experienced (brown belt and black belt) competitors had a higher injury risk than the less experienced (blue belt and purple belt) competitors; however, the difference was not significant (incidence rate ratio = 1.65, 95% confidence interval = 0.9, 2.9; P = .06). The incidence of joint injury was highest at the knee (7.5 per 1000 AEs) and elbow (7.5 per 1000 AEs). CONCLUSIONS: The data from this international Brazilian jiujitsu tournament indicated that the risk of joint injury was similar among belt ranks or experience during this Brazilian jiujitsu competition. The knee and elbow were the joints most susceptible to injury. Future investigation of injury mechanism is warranted to develop strategies to reduce potential risk factors attributed to injury.

Attentional selection of levels within hierarchically organized figures is mediated by object-files.

Objects frequently have a hierarchical organization (tree-branch-leaf). How do we select the level to be attended? This has been explored with compound letters: a global letter built from local letters. One explanation, backed by much empirical support, is that attentional competition is biased toward certain spatial frequency (SF) bands across all locations and objects (a SF filter). This view assumes that the global and local letters are carried respectively by low and high SF bands, and that the bias can persist over time. Here we advocate a complementary view in which perception of hierarchical level is determined by how we represent letters in object-files. Although many properties bound to an object-file (i.e., position, color, even shape) can mutate without affecting its persistence over time, we posit that same object-file cannot be used to store information from different hierarchical levels. Thus, selection of level would be independent from locations but not from the way objects are represented at each moment. These views were contrasted via an attentional blink paradigm that presented letters within compound figures, but only one level at a time. Attending to two letters in rapid succession was easier if they were at the same-compared to different-levels, as predicted by both accounts. However, only the object-file account was able to explain why it was easier to report two targets on the same moving object compared to the same targets on distinct objects. The interference of different masks on target recognition was also easier to predict by the object-file account than by an SF filter. The methods introduced here allowed us to investigate attention to hierarchical levels and to object-files within the same empirical framework. The data suggests that SF information is used to structure the internal organization of object representations, a process understood best by integrating object-file theory with previous models of hierarchical perception.

Asynchronous presentation of global and local information reveals effects of attention on brain electrical activity specific to each level.

The neural basis of selective attention within hierarchically organized Navon figures has been extensively studied with event related potentials (ERPs), by contrasting responses obtained when attending the global and the local echelons. The findings are inherently ambiguous because both levels are always presented together. Thus, only a mixture of the brain responses to two levels can be observed. Here, we use a method that allows unveiling of global and local letters at distinct times, enabling estimation of separate ERPs related to each level. Two interspersed oddball streams were presented, each using letters from one level and comprised of frequent distracters and rare targets. Previous work and our Experiment 1 show that it is difficult to divide attention between two such streams of stimuli. ERP recording in Experiment 2 evinced an early selection negativity (SN, with latencies to the 50% area of about 266 ms for global distracters and 276 ms for local distracters) that was larger for attended relative to unattended distracters. The SN was larger over right posterior occipito-temporal derivations for global stimuli and over left posterior occipito-temporal derivations for local stimuli (although the latter was less strongly lateralized). A discrimination negativity (DN, accompanied by a P3b) was larger for attended targets relative to attended distracters, with latencies to the 50% area of about 316 ms for global stimuli and 301 ms for local stimuli, which presented a similar distribution for both levels over left temporo-parietal electrodes. The two negativities apparently index successive stages in the processing of a selected level within a compound figure. By resolving the ambiguity of traditional designs, our method allowed us to observe the effects of attention for each hierarchical level on its own.

Infection control in field hospitals after a natural disaster: lessons learned after the 2010 earthquake in Haiti.

After the January 12, 2010, earthquake in Haiti, Project Medishare and the University of Miami organized, built, and staffed a 200-bed field hospital (the University of Miami Hospital in Haiti [UMHH]) on the outskirts of Port-au-Prince. We describe the operational challenges of providing a safe environment at the UMHH. Furthermore, we compared how these issues were addressed at this ad hoc hospital with how they were addressed at the field hospital of the Israel Defense Force, a fully deployable hospital with an organization fine-tuned as a result of prior disaster situations, also in Haiti.