Substantial Dose-response Relationship with Clinical Outcome for Lung Stereotactic Body Radiotherapy (SBRT) Delivered via Online Image Guidance

Purpose: To examine potential tumor dose-response relationships with various non-small cell lung cancer (NSCLC) SBRT fractionation regimens delivered with online CT-based image guidance. American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, C

Centerscope

Centerscope, formerly Scope, was published by the Boston University Medical Center "to communicate the concern of the Medical Center for the development and maintenance of improved health care in contemporary society.

Hypercapnic ventilatory response in mice lacking the 65 kDa isoform of Glutamic Acid Decarboxylase (GAD65)

BACKGROUND: Recent reports have shown that there are developmental changes in the ventilatory response to hypercapnia in the rat. These are characterized by an initial large response to carbon dioxide immediately after birth followed by a decline with a trough at one week of age, followed by a return in sensitivity. A second abnormality is seen at postnatal day 5 (P5) rats in that they cannot maintain the increase in frequency for 5 min of hypercapnia. In mice lacking GAD65 the release of GABA during sustained synaptic activation is reduced. We hypothesized that this developmental pattern would be present in the mouse which is also less mature at birth and that GABA mediates this relative respiratory depression. METHODS: In awake C57BL/6J and GAD65-/- mice the ventilatory response to 5% carbon dioxide (CO2) was examined at P2, P4, P6, P7, P12.5, P14.5 and P21.5, using body plethysmography. RESULTS: Minute ventilation (VE) relative to baseline during hypercapnia from P2 through P7 was generally less than from P12.5 onwards, but there was no trough as in the rat. Breaking VE down into its two components showed that tidal volume remained elevated for the 5 min of exposure to 5% CO2. At P6, but not at other ages, respiratory frequency declined with time and at 5 min was less that at 2 and 3 min. GAD65-/- animals at P6 showed a sustained increase in respiratory rate for the five mins exposure to CO2. CONCLUSION: These results show, that in contrast to the rat, mice do not show a decline in minute ventilatory response to CO2 at one week of age. Similiar to the rat at P5, mice at P6 are unable to sustain an increase in CO2 induced respiratory frequency and GAD65 contributes to this fall off

Genotypic determinants of fluoroquinolone and macrolide resistance in Neisseria gonorrhoeae.

Background:High rates of antimicrobial resistance (AMR) in Neisseria gonorrhoeae hinder effective treatment, but molecular AMR diagnostics may help address the challenge. This study aimed to appraise the literature for resistance-associated genotypic markers linked to fluoroquinolones and macrolides, to identify and review their use in diagnostics. Methods: Medline and EMBASE databases were searched and data pooled to evaluate associations between genotype and phenotypic resistance. The minimum inhibitory concentration (MIC) cut-offs were ≤ 0.06 mg L-1 for non-resistance to ciprofloxacin and ≤ 0.5 mg L-1 for non-resistance to azithromycin. Results: Diagnostic accuracy estimates were limited by data availability and reporting. It was found that: 1) S91 and D95 mutations in the GyrA protein independently predicted ciprofloxacin resistance and, used together, gave 98.6% (95% confidence interval (CI) 98.0-99.0%) sensitivity and 91.4% (95%CI 88.6-93.7%) specificity; 2) the number of 23S rRNA gene alleles with C2611T or A2059G mutations was highly correlated with azithromycin resistance, with mutation in any allele giving a sensitivity and specificity of 66.1% (95%CI 62.1-70.0%) and 98.9% (95%CI 97.5-99.5%) respectively. Estimated negative (NPV) and positive predictive values (PPV) for a 23S rRNA diagnostic were 98.6% (95%CI 96.8-99.4%) and 71.5% (95%CI 68.0-74.8%) respectively; 3) mutation at amino acid position G45 in the MtrR protein independently predicted azithromycin resistance; however, when combined with 23S rRNA, did not improve the PPV or NPV. Conclusions: Viable candidates for markers of resistance detection for incorporation into diagnostics were demonstrated. Such tests may enhance antibiotic stewardship and treatment options

Heat and moisture exchangers (HMEs) and heated humidifiers (HHs) in adult critically ill patients: a systematic review, meta-analysis and meta-regression of randomized controlled trials

The aims of this systematic review and meta-analysis of randomized controlled trials are to evaluate the effects of active heated humidifiers (HHs) and moisture exchangers (HMEs) in preventing artificial airway occlusion and pneumonia, and on mortality in adult critically ill patients. In addition, we planned to perform a meta-regression analysis to evaluate the relationship between the incidence of artificial airway occlusion, pneumonia and mortality and clinical features of adult critically ill patients

Characterizing the heterogeneity of disruptions in the resolution of trauma among women exposed to childhood maltreatment

Abstract The previously observed heterogeneity in developmental and intergenerational trajectories of childhood trauma may root from interindividual differences in the way trauma-exposed individuals have resolved these experiences. The current study explored whether distinctive patterns of impaired mentalization in relation to trauma could be identified in a sample of 825 pregnant women who experienced childhood maltreatment and whether these heterogeneous patterns were marked by significant differences in internalized and externalized problems during pregnancy, intimate partner violence, personality dysfunctions, and antenatal attachment. A latent profile analysis applied to the seven subscales of the Failure to Mentalize Trauma Questionnaire unraveled interindividual variability in mentalizing impairments among pregnant women exposed to childhood maltreatment by identifying five distinctive types of psychological responses to trauma, each being associated in cross-sectional analyses with a specific set of symptoms and dysfunctions. Overall, the study highlights the need for tailored interventions based on the individuals’ specific impairments in mentalizing trauma and calls for future developmental research exploring the longitudinal correlates of the five documented profiles of trauma processing

Optimizing the specificity window of biomolecular receptors using structure-switching and allostery

To ensure maximum specificity (i.e., minimize cross -reactivity with structurally similar analogues of the desired target), most bioassays invoke "stringency", the careful tuning of the conditions employed (e.g., pH, ionic strength, or temperature). Willingness to control assay conditions will fall, however, as quantitative, single-step biosensors begin to replace multistep analytical processes. This is especially true for sensors deployed in vivo, where the tuning of such parameters is not just inconvenient but impossible. In response, we describe here the rational adaptation of two strategies employed by nature to tune the affinity of biomolecular receptors so as to optimize the placement of their specificity "windows" without the need to alter measurement conditions: structure-switching and allosteric control. We quantitatively validate these approaches using two distinct, DNA-based receptors: a simple, linear-chain DNA suitable for detecting a complementary DNA strand and a structurally complex DNA aptamer used for the detection of a small-molecuIe drug. Using these models, we show that, without altering assay conditions, structure -switching and allostery can tune the concentration range over which a receptor achieves optimal specificity over orders of magnitude, thus optimally matching the specificity window with the range of target concentrations expected to be seen in a given application

Detection of target DNA using fluorescent cationic polymer and peptide nucleic acid probes on solid support

BACKGROUND: Nucleic acids detection using microarrays requires labelling of target nucleic acids with fluorophores or other reporter molecules prior to hybridization. RESULTS: Using surface-bound peptide nucleic acids (PNA) probes and soluble fluorescent cationic polythiophenes, we show a simple and sensitive electrostatic approach to detect and identify unlabelled target nucleic acid on microarray. CONCLUSION: This simple methodology opens exciting possibilities for applied genetic analysis for the diagnosis of infections, identification of genetic mutations, and forensic inquiries. This electrostatic strategy could also be used with other nucleic acid detection methods such as electrochemistry, silver staining, metallization, quantum dots, or electrochemical dyes

Steel waste valorisation Steel Slag Waste Effect on Concrete Shrinkage

The concept of sustainability is becoming widespread every day in society, enterprises and institutions. Defining something as sustainable means that the relationship that it establishes with the environment does not represent an aggression or a threat to the latter neither when it is being utilized nor when it stops performing the function for which was designed. To make this happen we need a system in which the main priority is recycling. Everything mentioned above is related to what is called the “Circular Economy”. Concrete is one of the most widely used construction materials in the world. However, the production of portland cement, an essential constituent of concrete, leads to the release of significant amounts of CO22. The global production of concrete represents more than 5% of the anthropogenic emissions of carbon dioxide every year, mainly from the production of cement. The replacement of cement by fly ash and other industrial waste, such as steel slags, is a good example of how resource conservation can be improved and contamination can be reduced. On the other hand, future trends are predicted to increase demand for steel worldwide. Mainly due to the expected improvement in the living standards and demands of underdeveloped populations. The steelmaking process produces a by-product called slag ranging from 10 to 15% per tonne of steel, where reuse is still reduced and much of it is deposited in a landfill. This study presents laboratory test results on the total and autogenous shrinkage of medium strength concrete with partial replacement of cement by slags. Two different slags were tested, namely ladle furnaces slags (LFS) and ground granulated blast furnace slags (GGBFS). The results show the concrete shrinkage behavior when 25% of substitution are used. These data are important to predict future behavior and show that for the substitution dosages used there are no significant divergences for the shrinkage.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech