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Previously, a specific dietary supplement, selected vegetables (SV), was found to be associated with prolonged survival of stage III and IV non-small cell lung cancer (NSCLC) patients. In this study, several anticancer components in SV were measured; the anticancer activity of SV was assessed using a lung tumor model, line 1 in BALB/c mice. SV was also used in conjunction with conventional therapies by stage IIIB and IV NSCLC patients whose survival and clinical responses were evaluated. A daily portion (283 g) of SV was found to contain 63 mg of inositol hexaphosphate, 4.4 mg of daidzein, 2.6 mg of genistein, and 16 mg of coumestrol. Mouse food containing 5% SV (wt/wt) was associated with a 53-74% inhibition of tumor growth rate. Fourteen of the 18 patients who ingested SV daily for 2-46 months were included in the analyses; none showed evidence of toxicity. The first Lawrence Erlbaum Associatesd case remained tumor free for >133 months; the second case showed complete regression of multiple brain lesions after using SV and radiotherapy. The median survival time of the remaining 12 patients was 33.5 months, and one-year survival was >70%. The median survival time of the 16 'intent-to-treat' patients (including ineligible patients) was 20 months, and one-year survival was 55%. The Karnofsky performance status of eligible patients was 55 ± 13 at entry but improved to 92 ± 9 after use of SV for five months or longer (p < 0.01). Five patients had stable lesions for 30, 30, 20, 12, and 2 months; two of them, whose primary tumor was resected, used SV alone and demonstrated an objective response of their metastatic tumors. In addition to the two Lawrence Erlbaum Associatesd cases, eight patients had no new metastases after using SV. Three patients had complete regression of brain metastases after using radiotherapy and SV. In this study, daily ingestion of SV was associated with objective responses, prolonged survival, and attenuation of the normal pattern of progression of stage IIIB and IV NSCLC. A large randomized phase III clinical trial is needed to confirm the results observed in this pilot study. [ABSTRACT FROM AUTHOR]

Objective: Venous thromboembolism (VTE) chemoprophylaxis in pediatric patients with traumatic brain injury (TBI) requires balancing the risk of progression of intracranial bleeding versus the risk of VTE. The identification of VTE risk factors requires analysis of a very large data set. This case-control study aimed to identify VTE risk factors in pediatric patients with TBI in order to develop a TBI-specific association model that can be used for VTE risk stratification in this population., Methods: The study included patients (aged 1-17 years) from the 2013-2019 US National Trauma Data Bank who were admitted for TBI in order to identify risk factors for VTE. Stepwise logistic regression was used to develop an association model., Results: Of 44,128 study participants, 257 (0.58%) developed VTE. Risk factors associated with VTE included age (OR 1.045, 95% CI 1.010-1.080), body mass index (OR 1.034, 95% CI 1.013-1.055), Injury Severity Score (OR 1.049, 95% CI 1.039-1.059), blood product administration (OR 1.436, 95% CI 1.008-2.046), presence of a central venous catheter (OR 3.333, 95% CI 2.431-4.571), and development of ventilator-associated pneumonia (OR 3.650, 95% CI 2.469-5.396). Based on this model, the predicted VTE risk in pediatric patients with TBI ranged from 0% to 16.8%., Conclusions: A model that includes age, body mass index, Injury Severity Score, blood transfusion, use of a central venous catheter, and ventilator-associated pneumonia can help to risk stratify pediatric patients with TBI from the standpoint of implementation of VTE chemoprophylaxis.

The lifecycle of black carbon (BC)-containing particles from biomass burns is examined using aircraft and surface observations of the BC mixing state for plume ages from ∼15 min to 10 days. Because BC is nonvolatile and chemically inert, changes in the mixing state of BC-containing particles are driven solely by changes in particle coating, which is mainly secondary organic aerosol (SOA). The coating mass initially increases rapidly ( k growth = 0.84 h -1 ), then remains relatively constant for 1-2 days as plume dilution no longer supports further growth, and then decreases slowly until only ∼30% of the maximum coating mass remains after 10 days ( k loss = 0.011 h -1 ). The mass ratio of coating-to-core for a BC-containing particle with a 100 nm mass-equivalent diameter BC core reaches a maximum of ∼20 after a few hours and drops to ∼5 after 10 days of aging. The initial increase in coating mass can be used to determine SOA formation rates. The slow loss of coating material, not captured in global models, comprises the dominant fraction of the lifecycle of these particles. Coating-to-core mass ratios of BC particles in the stratosphere are much greater than those in the free troposphere indicating a different lifecycle.

The esterification of carotenoids has been associated with high-level accumulation, greater stability and potentially improved dietary bioavailability. Engineering the formation of ketocarotenoids into tomato fruit has resulted in the esterification of these non-endogenous metabolites. A genotype of tomato was created that contains; (i) the mutant pale yellow petal (pyp)1-1 allele, which is responsible for the absence of carotenoid esters in tomato flowers and (ii) the heterologous enzymes for ketocarotenoid formation. Analysis of the resulting progeny showed altered quantitative and qualitative differences in esterified carotenoids. For example, in ripe fruit tissues, in the presence of the pyp mutant allele, non-endogenous ketocarotenoid esters were absent while their free forms accumulated. These data demonstrate the involvement of the PYP gene product in the esterification of diverse xanthophylls., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: During the coronavirus disease 2019 pandemic, New York instituted a statewide stay-at-home mandate to lower viral transmission. While public health guidelines advised continued provision of timely care for patients, disruption of safety-net health care and public fear have been proposed to be related to indirect deaths because of delays in presentation. We hypothesized that admissions for emergency general surgery (EGS) diagnoses would decrease during the pandemic and that mortality for these patients would increase., Methods: A multicenter observational study comparing EGS admissions from January to May 2020 to 2018 and 2019 across 11 NYC hospitals in the largest public health care system in the United States was performed. Emergency general surgery diagnoses were defined using International Classification Diseases, Tenth Revision, codes and grouped into seven common diagnosis categories: appendicitis, cholecystitis, small/large bowel, peptic ulcer disease, groin hernia, ventral hernia, and necrotizing soft tissue infection. Baseline demographics were compared including age, race/ethnicity, and payor status. Outcomes included coronavirus disease (COVID) status and mortality., Results: A total of 1,376 patients were admitted for EGS diagnoses from January to May 2020, a decrease compared with both 2018 (1,789) and 2019 (1,668) (p < 0.0001). This drop was most notable after the stay-at-home mandate (March 22, 2020; week 12). From March to May 2020, 3.3%, 19.2%, and 6.0% of EGS admissions were incidentally COVID positive, respectively. Mortality increased in March to May 2020 compared with 2019 (2.2% vs. 0.7%); this difference was statistically significant between April 2020 and April 2019 (4.1% vs. 0.9%, p = 0.045)., Conclusion: Supporting our hypothesis, the coronavirus disease 2019 pandemic and subsequent stay-at-home mandate resulted in decreased EGS admissions between March and May 2020 compared with prior years. During this time, there was also a statistically significant increase in mortality, which peaked at the height of COVID infection rates in our population., Level of Evidence: Epidemiological, level IV., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Wildfire is a major source of biomass burning aerosols, which greatly impact Earth climate. Tree species in North America (NA) boreal forests can support high-intensity crown fires, resulting in elevated injection height and longer lifetime (on the order of months) of the wildfire aerosols. Given the long lifetime, the properties of aged NA wildfire aerosols are required to understand and quantify their effects on radiation and climate. Here we present comprehensive characterization of climatically relevant properties, including optical properties and cloud condensation nuclei (CCN) activities of aged NA wildfire aerosols, emitted from the record-breaking Canadian wildfires in August 2017. Despite the extreme injection height of ~12 km, some of the wildfire plumes descended into the marine boundary layer in the eastern North Atlantic over a period of ~2 weeks, owing to the dry intrusions behind mid-latitude cyclones. The aged wildfire aerosols have high single scattering albedos at 529 nm (ω 529 ; 0.92-0.95) while low absorption Ångström exponents (Å abs ) at 464 nm/648 nm (0.7-0.9). In comparison, Å abs of fresh/slightly aged ones are typically 1.4-3.5. This low Å abs indicates a nearly complete loss of brown carbon, likely due to bleaching and/or evaporation, during the long-range transport. The nearly complete loss suggests that on global average, direct radiative forcing of BrC may be minor. Combining Mie calculations and the measured aerosol hygroscopicity, volatility and size distributions, we show that the high ω 529 and low Å abs values are best explained by an external mixture of non-absorbing organic particles and absorbing particles of large BC cores (>~110 nm diameter) with thick non-absorbing coatings. The accelerated descent of the wildfire plume also led to strong increase of CCN concentration at the supersaturation levels representative of marine low clouds. The hygroscopicity parameter, κ CCN , of the aged wildfire aerosols varies from 0.2 to 0.4, substantially lower than that of background marine boundary layer aerosols. However, the high fraction of particles with large diameter (i.e., within accumulation size ranges, ~100-250 nm) compensates for the low values of κ, and as a result, the aged NA wildfire aerosols contribute more efficiently to CCN population. These results provide direct evidence that the long-range transported NA wildfires can strongly influence CCN concentration in remote marine boundary layer, therefore the radiative properties of marine low clouds. Given the expected increases of NA wildfire intensity and frequency and regular occurrence of dry intrusion following mid-latitude cyclones, the influence of NA wildfire aerosols on CCN and clouds in remote marine environment need to be further examined., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Thoracic endovascular techniques for aneurysm repair offer less invasive alternatives to open strategies. Both approaches, however, are associated with the risk for neurological complications. Despite adjuncts to maintain spinal cord perfusion, ischaemia and paraplegia continue to occur during thoracoabdominal aortic aneurysm (TAAA) repair. Staging of such extensive procedures has been proven to decrease the risk for spinal cord injury. Archived biopsy specimens may offer insight into the molecular signature of the reorganization and expansion of the spinal collateral network during staged endovascular interventions in the setting of TAAA., Methods: Biological replicates of total RNA were isolated from existing paraspinous muscle samples from 22 Yorkshire pigs randomized to 1 of 3 simulated TAAA repair strategies as part of a previous study employing coil embolization of spinal segmental arteries within the thoracic and lumbar spine. Gene expression profiling was performed using the Affymetrix GeneChip Porcine array., Results: Microarray analysis identified 649 differentially expressed porcine genes (≥1.3-fold change, P ≤ 0.05) when comparing paralysed and non-paralysed subjects. Of these, 355 were available for further analysis. When mapped to the human genome, 169 Homo sapiens orthologues were identified. Integrated interpretation of gene expression profiles indicated the significant regulation of transcriptional regulators (such as nuclear factor кB), cytokine (including CXCL12) elements contributing to hypoxia signalling in the cardiovascular system (vascular endothelial growth factor and UBE2) and cytoskeletal elements (like dystrophin (DMD) and matrix metallopeptidase (MMP))., Conclusions: This study demonstrates the ability of microarray-based platforms to detect the differential expression of genes in paraspinous muscle during staged TAAA repair. Pathway enrichment analysis detected subcellular actors accompanying the neuroprotective effects of staged endovascular coiling. These observations provide new insight into the potential prognostic and therapeutic value of gene expression profiling in monitoring and modulating the arteriolar remodelling in the collateral network., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

The Gram-negative proteobacteria genus Burkholderia encompasses multiple bacterial species that are pathogenic to humans and other vertebrates. Two pathogenic species of interest within this genus are Burkholderia pseudomallei (Bpm) and the B. cepacia complex (Bcc); the former is the causative agent of melioidosis in humans and other mammals, and the latter is associated with pneumonia in immunocompromised patients. One understudied and shared characteristic of these two pathogenic groups is their ability to persist and establish chronic infection within the host. In this review, we will explore the depth of knowledge about chronic infections caused by persistent Bpm and Bcc. We examine the host risk factors and immune responses associated with more severe chronic infections. We also discuss host adaptation and phenotypes associated with persistent Burkholderia species. Lastly, we survey how other intracellular bacteria associated with chronic infections are combatted and explore possible future applications to target Burkholderia Our goal is to highlight understudied areas that should be addressed for a more thorough understanding of chronic Burkholderia infections and how to combat them., (© FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Ice nucleating particles (INPs) are vital for ice initiation in, and precipitation from, mixed-phase clouds. A source of INPs from oceans within sea spray aerosol (SSA) emissions has been suggested in previous studies but remained unconfirmed. Here, we show that INPs are emitted using real wave breaking in a laboratory flume to produce SSA. The number concentrations of INPs from laboratory-generated SSA, when normalized to typical total aerosol number concentrations in the marine boundary layer, agree well with measurements from diverse regions over the oceans. Data in the present study are also in accord with previously published INP measurements made over remote ocean regions. INP number concentrations active within liquid water droplets increase exponentially in number with a decrease in temperature below 0 °C, averaging an order of magnitude increase per 5 °C interval. The plausibility of a strong increase in SSA INP emissions in association with phytoplankton blooms is also shown in laboratory simulations. Nevertheless, INP number concentrations, or active site densities approximated using "dry" geometric SSA surface areas, are a few orders of magnitude lower than corresponding concentrations or site densities in the surface boundary layer over continental regions. These findings have important implications for cloud radiative forcing and precipitation within low-level and midlevel marine clouds unaffected by continental INP sources, such as may occur over the Southern Ocean.

Borrelia hermsii, a spirochete and cause of relapsing fever, is notable for its immune evasion by multiphasic antigenic variation within its vertebrate host. This is based on a diverse repertoire of surface antigen genes, only one of which is expressed at a time. Another major surface protein, the Variable Tick Protein (Vtp), is expressed in the tick vector and is invariable at its genetic locus. Given the limited immune systems of ticks, the finding of considerable diversity among the Vtp proteins of different strains of B. hermsii was unexpected. We investigated one explanation for this diversity of Vtp proteins, namely expression of the protein in mammals and a consequent elicitation of a specific immune response. Mice were infected with B. hermsii of either the HS1 or CC1 strain, which have antigenically distinctive Vtp proteins but otherwise have similar repertoires of the variable surface antigens. Subsequently collected sera were examined for antibody reactivities against Vtp and other antigens using Western blot analysis, dot blot, and protein microarray. Week-6 sera of infected mice contained antibodies that were largely specific for the Vtp of the infecting strain and were not attributable to antibody cross-reactivities. The antibody responses of the mice infected with different strains were otherwise similar. Further evidence of in vivo expression of the vtp gene was from enumeration of cDNA sequence reads that mapped to a set of selected B. hermsii genes. This measure of transcription of the infecting strain's vtp gene was ~10% of that for the abundantly-expressed, serotype-defining variable antigen gene but similar to that of genes known for in vivo expression. The findings of Vtp expression in a vertebrate host and elicitation of a specific anti-Vtp antibody response support the view that balancing selection by host adaptive immunity accounts in part for the observed diversity of Vtp proteins.

Coccidioidomycosis, or valley fever, is a growing health concern endemic to the southwestern United States. Safer, more effective, and more easily administered drugs are needed especially for severe, chronic, or unresponsive infections. The novel fungal CYP51 inhibitor VT-1161 demonstrated in vitro antifungal activity, with MIC50 and MIC90 values of 1 and 2 μg/ml, respectively, against 52 Coccidioides clinical isolates. In the initial animal study, oral doses of 10 and 50 mg/kg VT-1161 significantly reduced fungal burdens and increased survival time in a lethal respiratory model in comparison with treatment with a placebo (P < 0.001). Oral doses of 25 and 50 mg/kg VT-1161 were similarly efficacious in the murine central nervous system (CNS) model compared to placebo treatment (P < 0.001). All comparisons with the positive-control drug, fluconazole at 50 mg/kg per day, demonstrated either statistical equivalence or superiority of VT-1161. VT-1161 treatment also prevented dissemination of infection from the original inoculation site to a greater extent than fluconazole. Many of these in vivo results can be explained by the long half-life of VT-1161 leading to sustained high plasma levels. Thus, the efficacy and pharmacokinetics of VT-1161 are attractive characteristics for long-term treatment of this serious fungal infection., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

Coccidioides immitis and Coccidioides posadasii are soil-dwelling fungi and the causative agents of coccidioidomycosis, a mycosis endemic to certain semiarid regions in the Americas. The most common route of infection is by inhalation of airborne Coccidioides arthroconidia. Once a susceptible host inhales the conidia, a transition to mature endosporulated spherules can occur within the first 5 days of infection. For this study, we examined the host response in a murine model of coccidioidomycosis during a time period of infection that has not been well characterized. We collected lung tissue and bronchoalveolar lavage fluid (BALF) from BALB/c mice that were infected with a C. immitis pure strain, a C. immitis hybrid strain, or a C. posadasii strain as well as uninfected mice. We compared the host responses to the Coccidioides strains used in this study by assessing the level of transcription of selected cytokine genes in lung tissues and characterized host and fungal proteins present in BALF. Host response varied depending on the Coccidioides strain that was used and did not appear to be overly robust. This study provides a foundation to begin to dissect the host immune response early in infection, to detect abundant Coccidioides proteins, and to develop diagnostics that target these early time points of infection., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

To identify and characterize surface proteins expressed by the relapsing fever (RF) agent Borrelia hermsii in the blood of infected mice, we used a cell-free filtrate of their blood to immunize congenic naive mice. The resultant antiserum was used for Western blotting of cell lysates, and gel slices corresponding to reactive bands were subjected to liquid chromatography-tandem mass spectrometry, followed by a search of the proteome database with the peptides. One of the immunogens was identified as the BHA007 protein, which is encoded by a 174-kb linear plasmid. BHA007 had sequence features of lipoproteins, was surface exposed by the criteria of in situ protease susceptibility and agglutination of Vtp(-) cells by anti-BHA007 antibodies, and was not essential for in vitro growth. BHA007 elicited antibodies during experimental infection of mice, but immunization with recombinant protein did not confer protection against needle-delivered infection. Open reading frames (ORFs) orthologous to BHA007 were found on large plasmids of other RF species, including the coding sequences for the CihC proteins of Borrelia duttonii and B. recurrentis, but not in Lyme disease Borrelia species. Recombinant BHA007 bound both human and bovine fibronectin with Kd (dissociation constant) values of 22 and 33 nM, respectively, and bound to C4-binding protein with less affinity. The distant homology of BHA007 and its orthologs to BBK32 proteins of Lyme disease species, as well as to previously described BBK32-like proteins in relapsing fever species, indicates that BHA007 is a member of a large family of multifunctional proteins in Borrelia species that bind to fibronectin as well as other host proteins.

Glutamine serves as an important source of energy and building blocks for many tumor cells. The first step in glutamine utilization is its conversion to glutamate by the mitochondrial enzyme glutaminase. CB-839 is a potent, selective, and orally bioavailable inhibitor of both splice variants of glutaminase (KGA and GAC). CB-839 had antiproliferative activity in a triple-negative breast cancer (TNBC) cell line, HCC-1806, that was associated with a marked decrease in glutamine consumption, glutamate production, oxygen consumption, and the steady-state levels of glutathione and several tricarboxylic acid cycle intermediates. In contrast, no antiproliferative activity was observed in an estrogen receptor-positive cell line, T47D, and only modest effects on glutamine consumption and downstream metabolites were observed. Across a panel of breast cancer cell lines, GAC protein expression and glutaminase activity were elevated in the majority of TNBC cell lines relative to receptor positive cells. Furthermore, the TNBC subtype displayed the greatest sensitivity to CB-839 treatment and this sensitivity was correlated with (i) dependence on extracellular glutamine for growth, (ii) intracellular glutamate and glutamine levels, and (iii) GAC (but not KGA) expression, a potential biomarker for sensitivity. CB-839 displayed significant antitumor activity in two xenograft models: as a single agent in a patient-derived TNBC model and in a basal like HER2(+) cell line model, JIMT-1, both as a single agent and in combination with paclitaxel. Together, these data provide a strong rationale for the clinical investigation of CB-839 as a targeted therapeutic in patients with TNBC and other glutamine-dependent tumors.

Firearm trauma is the second most common cause of serious injury among adolescents in the Republic of Djibouti. The aim of this study was to explore the sociodemographic correlates of serious injury and non-fatal gunshot trauma among adolescents in Djibouti. Using multinomial logistic regression, we compared a sample of adolescents (N = 1,711) who self-reported a non-firearm-related serious injury (n = 587) and those who reported a firearm-related injury (n = 101) with non-injured participants (n = 1,023) during a 12-month recall period. Analyses targeted demographic, behavioral, social, mental health, and family factors. After adjusting for covariates, participants reporting a non-firearm-related serious injury were more likely to report having been involved in physical fights (relative risk ratio [RRR] = 145; confidence interval [CI] = [1.04, 2.02), being bullied (RRR = 2.83; CI = [2.24, 3.56]), feeling lonely (RRR = 1.48; CI = [1.11, 1.96]), having signs of depression (RRR = 1.27; CI = [1.02, 1.58]), and be truant from school (RRR = 1.68; CI = [1.25, 2.28]). Those who reported a gunshot injury recorded being bullied (RRR = 2.83; CI = [1.77, 4.53]) and physically attacked at higher rates (RRR = 1.78; CI = [1.09, 2.89]). Serious injuries, whether firearm related or not, are important threats to adolescent health in Djibouti with potentially serious health-related correlates. More research, particularly multilevel designs, are needed to explain context-relevant factors associated with serious trauma in Djibouti.

Blood is the specimen of choice for most laboratory tests for diagnosis and disease monitoring. Sampling exhaled breath is a noninvasive alternative to phlebotomy and has the potential for real-time monitoring at the bedside. Improved instrumentation has advanced breath analysis for several gaseous compounds from humans. However, application to small animal models of diseases and physiology has been limited. To extend breath analysis to mice, we crafted a means for collecting nose-only breath samples from groups and individual animals who were awake. Samples were subjected to gas chromatography and mass spectrometry procedures developed for highly sensitive analysis of trace volatile organic compounds (VOCs) in the atmosphere. We evaluated the system with experimental systemic infections of severe combined immunodeficiency Mus musculus with the bacterium Borrelia hermsii. Infected mice developed bacterial densities of ∼10(7) per ml of blood by day 4 or 5 and in comparison to uninfected controls had hepatosplenomegaly and elevations of both inflammatory and anti-inflammatory cytokines. While 12 samples from individual infected mice on days 4 and 5 and 6 samples from uninfected mice did not significantly differ for 72 different VOCs, carbon monoxide (CO) was elevated in samples from infected mice, with a mean (95% confidence limits) effect size of 4.2 (2.8-5.6), when differences in CO2 in the breath were taken into account. Normalized CO values declined to the uninfected range after one day of treatment with the antibiotic ceftriaxone. Strongly correlated with CO in the breath were levels of heme oxygenase-1 protein in serum and HMOX1 transcripts in whole blood. These results (i) provide further evidence of the informativeness of CO concentration in the exhaled breath during systemic infection and inflammation, and (ii) encourage evaluation of this noninvasive analytic approach in other various other rodent models of infection and for utility in clinical management.

Objectives: To offer a systematic review of the body of literature in the emerging field of telemedicine in the management of acute-phase injuries., Materials and Methods: We conducted a literature review., Results: Telemedicine has only recently been applied to the specialties of trauma, emergency care, and surgery. The potential benefits of telemedicine include a decrease in travel expenses, enhanced continuity of care, and increased access to specialized consultants in medically underserved and rural areas., Conclusions: There still exist barriers to the use of teletechnologies in medicine that limit their wider adoption. Poor infrastructure, limited equipment availability, and insufficient access to training and education for medical personnel have prevented wider use.

In domain wall (DW) excitation experiments, nonlinearity (NL) intrinsic to the DW dynamics is often hard to distinguish from perturbation due to the confining potential or DW distortion. Here we numerically investigate the dynamic oscillations of magnetostatically coupled DWs: a system well understood in the quasistatic limit. NL is observed, even for a harmonic potential, due to the intrinsic DW motion. This behavior is principally dependent on terms normally associated with the DW canonical momentum and is in contrast with a NL restoring potential. This NL is not observable in quasistatic measurements, relatively insensitive to the confining potential, and may be tuned by the nanowire parameters. The shown NLs are present in any DW restoring potential and must be accounted for when probing DW potential landscapes.

The objective of this study was to identify the incidence of burn injuries among children in a sub-Saharan urban area and describe contributing factors in the home environment. A cross-sectional household survey was conducted in Dar es Salaam, Tanzania between 8 and 22 July 2009. Demographic characteristics of participants were reported using descriptive statistics. Bivariate analyses using Pearson's chi-square tests for categorical variables were used to explore possible associations. Burns represented 16.3% of reported injuries. The one-month incidence was calculated to be 1.73%. The most common contributor to burn injury was open flame 36.9%, followed by hot liquids 33.8%. Most burns occurred in urban areas with 88% occurring in the home. A significant association with burn injury was found in the 0-4 age category. There exists a continued need for research examining the mechanisms of safety provision in the home in low resource settings, especially concerning burn injury.

Domain wall (DW) pinning in ferromagnetic nanowires is in general a complex process. Distortions of the DW shape make quantitative agreement between modeling and experiment difficult. Here we demonstrate pinning using nanometer scale localized stray fields. This type of interaction gives well-characterized, tailorable potential landscapes that do not appreciably distort the DW. Our experimental results are in excellent quantitative agreement with an Arrhenius-Néel model of depinning--a result only possible when the modeled potential profile agrees fully with that experienced by the DW., (© 2011 American Physical Society)

The behavior of NaCl nanoparticles as a function of relative humidity (RH) has been characterized using non-contact environmental atomic force microscopy (e-AFM) to measure the heights of particles deposited on a prepared hydrophobic surface. Cubic NaCl nanoparticles with sides of 35 and 80 nm were found to take up water reversibly with increasing RH well below the bulk deliquescence relative humidity (DRH) of 75% at 23(∘)C, and to form a liquid-like surface layer of thickness 2 to 5 nm, with measurable uptake (>2 nm increase in particle height) beginning at 70% RH. The maximum thickness of the layer increased with increasing RH and increasing particle size over the range studied. The liquid-like behavior of the layer was indicated by a reversible rounding at the upper surface of the particles, fit to a parabolic cross-section, where the ratio of particle height to maximum radius of curvature increases from zero (flat top) at 68% RH to 0.7 ± 0.3 at 74% RH. These observations, which are consistent with a reorganization of mass on the solid NaCl nanocrystal at RH below the DRH, suggest that the deliquescence of NaCl nanoparticles is more complex than an abrupt first-order phase transition. The height measurements are consistent with a phenomenological model that assumes favorable contributions to the free energy of formation of a liquid layer on solid NaCl due both to van der Waals interactions, which depend partly upon the Hamaker constant, A(film), of the interaction between the thin liquid film and the solid NaCl, and to a longer-range electrostatic interaction over a characteristic length of persistence, ξ; the best fit to the data corresponded to A(film)= 1 kT and ξ = 2.33 nm.

We begin with premises about natural science, its fundamental protocols and its limitations. With those in mind, we construct alternative descriptive models of consciousness, each comprising a synthesis of recent literature in cognitive science. Presuming that consciousness arose through natural selection, we eliminate the subset of alternatives that lack selectable physical phenotypes, leaving the subset with limited free will (mostly in the form of free won't). We argue that membership in this subset implies a two-way exchange of energy between the conscious mental realm and the physical realm of the brain. We propose an analogy between the mental and physical phases of energy and the phases (e.g., gas/liquid) of matter, and a possible realization in the form of a generic resonator. As candidate undergirdings of such a system, we propose astroglial-pyramidal cell and electromagnetic-field models. Finally, we consider the problem of identification of the presence of consciousness in other beings or in machines.

We systematically study individual micro- and nanometric polycrystalline cobalt wires grown by focused-electron-beam-induced-deposition. The deposits were grown in a range of aspect ratios varying from 1 up to 26. The minimum lateral dimension of the nanowires was 150 nm, for a thickness of 40 nm. Atomic force microscopy images show beam-current-dependent profiles, associated with different regimes of deposition. The magnetization reversal of individual nanowires is studied by means of the spatially resolved magneto-optical Kerr effect. Abrupt switching is observed, with a systematic dependence on the wire's dimensions. This dependence of the coercive field is understood in magnetostatic terms, and agrees well with previous results on cobalt wires grown with different techniques. The influence of compositional gradients along the structural profile on the magnetic reversal is studied by using micromagnetic simulations. This work demonstrates the feasibility of using this technique to fabricate highly pure magnetic nanostructures, and highlights the advantages and disadvantages of the technique with respect to more conventional ones.

We examine size-dependent deliquescence/efflorescence phase transformation for particles down to several nanometers in size. Thermodynamic properties of inorganic salt particles, coated with aqueous solution layers of varying thickness and surrounded by vapor, are analyzed. A thin layer criterion (TLC) is introduced to define a limiting deliquescence relative humidity (RH(D)) for small particles. This requires: (1) equality of chemical potentials between salt in an undissolved core, and thin adsorbed solution layer, and (2) equality of chemical potentials between water in the thin layer and vapor phase. The usual bulk deliquescence conditions are recovered in the limit of large dry particle size. Nanosize particles are found to deliquesce at relative humidity just below the RH(D) on crossing a nucleation barrier, located at a critical solution layer thickness. This barrier vanishes precisely at the RH(D) defined by the TLC. Concepts and methods from nucleation theory including the kinetic potential, self-consistent nucleation theory, nucleation theorems, and the Gibbs dividing surface provide theoretical foundation and point to unifying features of small particle deliquescence/efflorescence processes. These include common thermodynamic area constructions, useful for interpretation of small particle water uptake measurements, and a common free-energy surface, with constant RH cross sections describing deliquescence and efflorescence related through the nucleation theorem.

The magnetostatic interaction between two oppositely charged transverse domain walls (TDWs) in adjacent Permalloy nanowires is experimentally demonstrated. The dependence of the pinning strength on wire separation is investigated for distances between 13 and 125 nm. The results can be described fully by considering the distribution of magnetic charge within rigid, isolated TDWs. Alternative DW internal structure cannot reproduce this observed dependence. Modeling suggests the TDW internal structure is not appreciably disturbed, and remains rigid although the pinning strength is significant.

Proteasome inhibition has been validated as a therapeutic modality in the treatment of multiple myeloma and non-Hodgkin's lymphoma. Carfilzomib, an epoxyketone currently undergoing clinical trials in malignant diseases, is a highly selective inhibitor of the chymotrypsin-like (CT-L) activity of the proteasome. A chemistry effort was initiated to discover orally bioavailable analogues of carfilzomib, which would have potential for improved dosing flexibility and patient convenience over intravenously administered agents. The lead compound, 2-Me-5-thiazole-Ser(OMe)-Ser(OMe)-Phe-ketoepoxide (58) (PR-047), selectively inhibited CT-L activity of both the constitutive proteasome (beta5) and immunoproteasome (LMP7) and demonstrated an absolute bioavailability of up to 39% in rodents and dogs. It was well tolerated with repeated oral administration at doses resulting in >80% proteasome inhibition in most tissues and elicited an antitumor response equivalent to intravenously administered carfilzomib in multiple human tumor xenograft and mouse syngeneic models. The favorable pharmacologic profile supports its further development for the treatment of malignant diseases.

The motion of transverse domain walls (DWs) in thin Permalloy nanowires has been studied by locally detecting the chirality of the moving DW, using a cross-shaped trap acting as a chirality filter. We find that structural changes of the DW occur over a characteristic minimum distance: the "DW fidelity length." The measured field dependence of the fidelity length is in good qualitative agreement with a 1D analytical model and with published results of numerical simulations and experiments. We also demonstrate extension of the fidelity length to meter length scales using a series of filters.

Clinical studies with bortezomib have validated the proteasome as a therapeutic target for the treatment of multiple myeloma and non-Hodgkin's lymphoma. However, significant toxicities have restricted the intensity of bortezomib dosing. Here we describe the antitumor activity of PR-171, a novel epoxyketone-based irreversible proteasome inhibitor that is currently in clinical development. In comparison to bortezomib, PR-171 exhibits equal potency but greater selectivity for the chymotrypsin-like activity of the proteasome. In cell culture, PR-171 is more cytotoxic than bortezomib following brief treatments that mimic the in vivo pharmacokinetics of both molecules. Hematologic tumor cells exhibit the greatest sensitivity to brief exposure, whereas solid tumor cells and nontransformed cell types are less sensitive to such treatments. Cellular consequences of PR-171 treatment include the accumulation of proteasome substrates and induction of cell cycle arrest and/or apoptosis. Administration of PR-171 to animals results in the dose-dependent inhibition of the chymotrypsin-like proteasome activity in all tissues examined with the exception of the brain. PR-171 is well tolerated when administered for either 2 or 5 consecutive days at doses resulting in >80% proteasome inhibition in blood and most tissues. In human tumor xenograft models, PR-171 mediates an antitumor response that is both dose and schedule dependent. The antitumor efficacy of PR-171 delivered on 2 consecutive days is stronger than that of bortezomib administered on its clinical dosing schedule. These studies show the tolerability, efficacy, and dosing flexibility of PR-171 and provide validation for the clinical testing of PR-171 in the treatment of hematologic malignancies using dose-intensive schedules.

Second-order reverse correlation (second-order Wiener-kernel analysis) was carried out between spike responses in single afferent units from the basilar papilla of the red-eared turtle and band limited white noise auditory stimuli. For units with best excitatory frequencies (BEFs) below approximately 500 Hz, the analysis revealed suppression similar to that observed previously in anuran amphibians. For units with higher BEFs, the analysis revealed dc response with narrow-band tuning centered about the BEF, combined with broad-band ac response at lower frequencies. For all units, the analysis revealed the relative timing and tuning of excitation and various forms of inhibitory or suppressive effects.

Adenosine is a purine nucleoside that regulates cell function through G protein-coupled receptors that activate or inhibit adenylyl cyclase. Based on the understanding that cAMP regulates alveolar epithelial active Na(+) transport, we hypothesized that adenosine and its receptors have the potential to regulate alveolar ion transport and airspace fluid content. Herein, we report that type 1 (A(1)R), 2a (A(2a)R), 2b (A(2b)R), and 3 (A(3)R) adenosine receptors are present in rat and mouse lungs and alveolar type 1 and 2 epithelial cells (AT1 and AT2). Rat AT2 cells generated and produced cAMP in response to adenosine, and micromolar concentrations of adenosine were measured in bronchoalveolar lavage fluid from mice. Ussing chamber studies of rat AT2 cells indicated that adenosine affects ion transport through engagement of A(1)R, A(2a)R, and/or A(3)R through a mechanism that increases CFTR and amiloride-sensitive channel function. Intratracheal instillation of low concentrations of adenosine (< or =10(-8)M) or either A(2a)R- or A(3)R-specific agonists increased alveolar fluid clearance (AFC), whereas physiologic concentrations of adenosine (> or =10(-6)M) reduced AFC in mice and rats via an A(1)R-dependent pathway. Instillation of a CFTR inhibitor (CFTR(inh-172)) attenuated adenosine-mediated down-regulation of AFC, suggesting that adenosine causes Cl(-) efflux by means of CFTR. These studies report a role for adenosine in regulation of alveolar ion transport and fluid clearance. These findings suggest that physiologic concentrations of adenosine allow the alveolar epithelium to counterbalance active Na(+) absorption with Cl(-) efflux through engagement of the A(1)R and raise the possibility that adenosine receptor ligands can be used to treat pulmonary edema.

This paper presents rational, theoretical, and empirical grounds for doubting the principle of determinism in nature and in the brain, and discusses implications of this for free will and the chaos model of the brain. Small number particle systems are practically indeterministic and may be intrinsically indeterministic. Determinism in nature has often been taken to preclude free will. Strict determinism is a concept frequently applied to systems theory, establishing, e.g., the uniqueness of state-space trajectories. In order to consider determinism as a law of nature, however, one must be able to subject it to empirical tests. Presently, one is not able to and whether this can be shown to enable free will or not is not clear. It does remove, at least for the present, determinism itself as a rationale for precluding free will. The work partially supports the chaos model, but weakens the computational computer metaphor of brain function.

Insect prey of the Namib golden mole congregate beneath clumps of grass scattered among the sand dunes of the Namib Desert. In the presence of the light winds that typically blow over the Namib Desert, these grass clumps emit low-amplitude vibrations that are transmitted through the sand. While foraging in the sand-swimming mode (a few centimeters below the surface of the sand), some moles apparently were attracted toward manmade sources emitting vibrations matching those recorded from the grass clumps. This is the first direct evidence that these desert mammals use seismic cues for navigation.

Beta-adrenergic receptors (betaAR) regulate active Na+ transport in the alveolar epithelium and accelerate clearance of excess airspace fluid. Accumulating data indicates that the cystic fibrosis transmembrane conductance regulator (CFTR) is important for upregulation of the active ion transport that is needed to maintain alveolar fluid homeostasis during pulmonary edema. We hypothesized that betaAR regulation of alveolar active transport may be mediated via a CFTR dependent pathway. To test this hypothesis we used a recombinant adenovirus that expresses a human CFTR cDNA (adCFTR) to increase CFTR function in the alveolar epithelium of normal rats and mice. Alveolar fluid clearance (AFC), an index of alveolar active Na+ transport, was 92% greater in CFTR overexpressing lungs than controls. Addition of the Cl- channel blockers NPPB, glibenclamide, or bumetanide and experiments using Cl- free alveolar instillate solutions indicate that the accelerated AFC in this model is due to increased Cl- channel function. Conversely, CFTR overexpression in mice with no beta1- or beta2-adrenergic receptors had no effect on AFC. Overexpression of a human beta2AR in the alveolar epithelium significantly increased AFC in normal mice but had no effect in mice with a non-functional human CFTR gene (Deltaphi508 mutation). These studies indicate that upregulation of alveolar CFTR function speeds clearance of excess fluid from the airspace and that CFTRs effect on active Na+ transport requires the betaAR. These studies reveal a previously undetected interdependency between CFTR and betaAR that is essential for upregulation of active Na+ transport and fluid clearance in the alveolus.

Aldose reductase (AR), a member of the aldo-keto reductase family, has been implicated in the development of vascular and neurological complications of diabetes. Recently, we demonstrated that aldose reductase is a component of myocardial ischemic injury and that inhibitors of this enzyme protect rat hearts from ischemia-reperfusion injury. To rigorously test the effect of aldose reductase on myocardial ischemia-reperfusion injury, we used transgenic mice broadly overexpressing human aldose reductase (ARTg) driven by the major histocompatibility complex I promoter. Hearts from these ARTg or littermate mice (WT) (n=6 in each group) were isolated, perfused under normoxic conditions, then subjected to 50 min of severe low flow ischemia followed by 60 min of reperfusion. Creatine kinase (CK) release (a marker of ischemic injury) was measured during reperfusion; left ventricular developed pressure (LVDP), end diastolic pressure (EDP), and ATP were measured throughout the protocol. CK release was significantly greater in ARTg mice compared with the WT mice. LVDP recovery was significantly reduced in ARTg mice compared with the WT mice. Furthermore, ATP content was higher in WT mice compared with ARTg mice during ischemia and reperfusion. Infarct size measured by staining techniques and myocardial damage evaluated histologically were also significantly worse in ARTg mice hearts than in controls. Pharmacological inhibition of aldose reductase significantly reduced ischemic injury and improved functional recovery in ARTg mice. These data strongly support key roles for AR in ischemic injury and impairment of functional and metabolic recovery after ischemia. We propose that interventions targeting AR may provide a novel adjunctive approach to protect ischemic myocardium.

The spectro-temporal receptive field [Hear. Res 5 (1981) 147; IEEE Trans BME 15 (1993) 177] provides an explicit image of the spectral and temporal aspects of the responsiveness of a primary auditory afferent axon. It exhibits the net effects of the competition between excitatory and inhibitory (or suppressive) phenomena. In this paper, we introduce a method for derivation of the spectro-temporal receptive field directly from a second-order Wiener kernel (produced by second-order reverse correlation between spike responses and broad-band white-noise stimulus); and we expand the concept of the spectro-temporal receptive field by applying the new method not only to the second-order kernel itself, but also to its excitatory and inhibitory subkernels. This produces separate spectro-temporal images of the excitatory and inhibitory phenomena putatively underlying the competition. Applied, in simulations, to models with known underlying excitatory and suppressive tuning and timing properties, the method successfully extracted a faithful image of those properties for excitation and one for inhibition. Applied to three auditory axons from the frog, it produced images consistent with previously published physiology.

The spectro-temporal receptive field [Hear. Res 5 (1981) 147; IEEE Trans BME 15 (1993) 177] provides an explicit image of the spectral and temporal aspects of the responsiveness of a primary auditory afferent axon. It exhibits the net effects of the competition between excitatory and inhibitory (or suppressive) phenomena. In this paper, we introduce a method for derivation of the spectro-temporal receptive field directly from a second-order Wiener kernel (produced by second-order reverse correlation between spike responses and broad-band white-noise stimulus); and we expand the concept of the spectro-temporal receptive field by applying the new method not only to the second-order kernel itself, but also to its excitatory and inhibitory subkernels. This produces separate spectro-temporal images of the excitatory and inhibitory phenomena putatively underlying the competition. Applied, in simulations, to models with known underlying excitatory and suppressive tuning and timing properties, the method successfully extracted a faithful image of those properties for excitation and one for inhibition. Applied to three auditory axons from the frog, it produced images consistent with previously published physiology.

Information about the tuning and timing of excitation in cochlear axons with low-characteristic frequency (CF) is embodied in the first-order Wiener kernel, or reverse correlation function. For high-CF axons, the highest-ranking eigenvector (or singular vector) of the second-order Wiener kernel often can serve as a surrogate for the first-order kernel, providing the same information. For mid-CF axons, the two functions are essentially identical. In this paper we apply these tools to gerbil cochlear-nerve axons with CFs ranging from 700 Hz to 14 kHz. Eigen or singular-value decomposition of the second-order Wiener kernel allows us to separate excitatory and suppressive effects, and to determine precisely the timing of the latter.