| 141. |
- Kocherlakota, Prashant, et al.
(author)
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Constraints on black-hole charges with the 2017 EHT observations of M87∗
- 2021
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In: Physical Review D. - 2470-0010 .- 2470-0029. ; 103:10
-
Journal article (peer-reviewed)abstract
- Our understanding of strong gravity near supermassive compact objects has recently improved thanks to the measurements made by the Event Horizon Telescope (EHT). We use here the M87∗ shadow size to infer constraints on the physical charges of a large variety of nonrotating or rotating black holes. For example, we show that the quality of the measurements is already sufficient to rule out that M87∗ is a highly charged dilaton black hole. Similarly, when considering black holes with two physical and independent charges, we are able to exclude considerable regions of the space of parameters for the doubly-charged dilaton and the Sen black holes.
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| 142. |
- Kowdley, Kris V, et al.
(author)
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A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis.
- 2018
-
In: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3350 .- 0270-9139. ; 67:5, s. 1890-1902
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Journal article (peer-reviewed)abstract
- Obeticholic acid (OCA), a potent farnesoid X receptor agonist, was studied as monotherapy in an international, randomized, double-blind, placebo-controlled phase 2 study in patients with primary biliary cholangitis who were then followed for up to 6 years. The goals of the study were to assess the benefit of OCA in the absence of ursodeoxycholic acid, which is relevant for patients who are intolerant of ursodeoxycholic acid and at higher risk of disease progression. Patients were randomized and dosed with placebo (n = 23), OCA 10 mg (n = 20), or OCA 50 mg (n = 16) given as monotherapy once daily for 3 months (1 randomized patient withdrew prior to dosing). The primary endpoint was the percent change in alkaline phosphatase from baseline to the end of the double-blind phase of the study. Secondary and exploratory endpoints included change from baseline to month 3/early termination in markers of cholestasis, hepatocellular injury, and farnesoid X receptor activation. Efficacy and safety continue to be monitored through an ongoing 6-year open-label extension (N = 28). Alkaline phosphatase was reduced in both OCA groups (median% [Q1, Q3], OCA 10 mg -53.9% [-62.5, -29.3], OCA 50 mg -37.2% [-54.8, -24.6]) compared to placebo (-0.8% [-6.4, 8.7]; P < 0.0001) at the end of the study, with similar reductions observed through 6 years of open-label extension treatment. OCA improved many secondary and exploratory endpoints (including γ-glutamyl transpeptidase, alanine aminotransferase, conjugated bilirubin, and immunoglobulin M). Pruritus was the most common adverse event; 15% (OCA 10 mg) and 38% (OCA 50 mg) discontinued due to pruritus.OCA monotherapy significantly improved alkaline phosphatase and other biochemical markers predictive of improved long-term clinical outcomes. Pruritus increased dose-dependently with OCA treatment. Biochemical improvements were observed through 6 years of open-label extension treatment. (Hepatology 2017).
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| 143. |
- Laffey, John G, et al.
(author)
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Potentially modifiable factors contributing to outcome from acute respiratory distress syndrome : the LUNG SAFE study
- 2016
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In: Intensive Care Medicine. - : Springer. - 0342-4642 .- 1432-1238. ; 42:12, s. 1865-1876
-
Journal article (peer-reviewed)abstract
- Purpose: To improve the outcome of the acute respiratory distress syndrome (ARDS), one needs to identify potentially modifiable factors associated with mortality.Methods: The large observational study to understand the global impact of severe acute respiratory failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients with severe respiratory failure, conducted in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across five continents. A pre-specified secondary aim was to examine the factors associated with outcome. Analyses were restricted to patients (93.1 %) fulfilling ARDS criteria on day 1-2 who received invasive mechanical ventilation.Result: 2377 patients were included in the analysis. Potentially modifiable factors associated with increased hospital mortality in multivariable analyses include lower PEEP, higher peak inspiratory, plateau, and driving pressures, and increased respiratory rate. The impact of tidal volume on outcome was unclear. Having fewer ICU beds was also associated with higher hospital mortality. Non-modifiable factors associated with worsened outcome from ARDS included older age, active neoplasm, hematologic neoplasm, and chronic liver failure. Severity of illness indices including lower pH, lower PaO2/FiO2 ratio, and higher non-pulmonary SOFA score were associated with poorer outcome. Of the 578 (24.3 %) patients with a limitation of life-sustaining therapies or measures decision, 498 (86.0 %) died in hospital. Factors associated with increased likelihood of limitation of life-sustaining therapies or measures decision included older age, immunosuppression, neoplasia, lower pH and increased non-pulmonary SOFA scores.Conclusions: Higher PEEP, lower peak, plateau, and driving pressures, and lower respiratory rate are associated with improved survival from ARDS.
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| 144. |
- Luciano, Alison, et al.
(author)
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Predictors of Incarceration Among Urban Adults With Co-Occurring Severe Mental Illness and a Substance Use Disorder
- 2014
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In: Psychiatric Services. - : American Psychiatric Publishing. - 1075-2730 .- 1557-9700. ; 65:11, s. 1325-1331
-
Journal article (peer-reviewed)abstract
- Objective: People with severe mental illness and a co-occurring substance use disorder (co-occurring disorders) who live in urban areas experience high rates of incarceration. This study examined sociodemographic, clinical, economic, and community integration factors as predictors of incarceration among people with co-occurring disorders. Methods: This secondary analysis used data from a randomized controlled trial of assertive community treatment versus standard case management. In the parent study, researchers interviewed 198 people with co-occurring disorders from two urban mental health centers in Connecticut at baseline and every six months for three years. Researchers tracked incarceration, clinical engagement and status, employment, living situation, social relationships, and substance use. The study reported here used bivariate analyses and logistic regression analyses to compare individuals who were incarcerated during the study period with those who were not. Results: The overall incarceration rate was 38% during the study period. In multivariate analyses, prior incarceration predicted incarceration during the study period (odds ratio [OR]=3.26). Two factors were associated with a reduced likelihood of incarceration: friendships with individuals who did not use substances (OR=.19) and substance use treatment engagement (OR=.60) Conclusions: Positive social relationships and engagement in substance use treatment are promising service and policy targets to prevent incarceration in this high-risk population.
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| 145. |
- Luciano, Juan V., et al.
(author)
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The Contribution of the Psychologist in the Assessment and Treatment of Fibromyalgia
- 2023
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In: CURRENT TREATMENT OPTIONS IN RHEUMATOLOGY. - : Springer Nature. - 2198-6002. ; 9:2, s. 11-31
-
Journal article (peer-reviewed)abstract
- Purpose of reviewThis review focuses on the role of psychologists in the assessment and treatment of fibromyalgia syndrome (FMS), a highly prevalent condition characterized by chronic widespread pain, fatigue, cognitive problems, distress, and disability.Recent findingsA large body of work supports the effectiveness and cost-utility of psychological therapies for the improvement of a wide range of symptoms associated with FMS. However, patients with FMS are best assessed and treated by a multidisciplinary team, in which psychologists have an important role. Multidisciplinary treatment, in which each healthcare professional offers his or her own expertise to the patient, has been shown to produce more ubiquitous treatment effects for this complex syndrome than single discipline treatments. Considering the empirical evidence and documented experience of patients, people with FMS can benefit from integrated care, combining education, exercise, and psychotherapeutic approaches, including cognitive-behavioral therapy.There has been a call for more health economics research to demonstrate the cost-effectiveness of psychological therapies. In this paper, we highlight the added value of psychologists as members of multidisciplinary treatment teams, who can assess and treat the maladaptive cognitive, emotional, and behavioral symptoms that are commonly seen in individuals with FMS.
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| 146. |
- Luciano, Mark G., et al.
(author)
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Epidural Oscillating Cardiac-Gated Intracranial Implant Modulates Cerebral Blood Flow
- 2020
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In: Neurosurgery. - : Oxford University Press. - 0148-396X .- 1524-4040. ; 87:6, s. 1299-1310
-
Journal article (peer-reviewed)abstract
- Background: We have previously reported a method and device capable of manipulating ICP pulsatility while minimally effecting mean ICP.Objective: To test the hypothesis that different modulations of the intracranial pressure (ICP) pulse waveform will have a differential effect on cerebral blood flow (CBF).Methods: Using an epidural balloon catheter attached to a cardiac-gated oscillating pump, 13 canine subjects underwent ICP waveform manipulation comparing different sequences of oscillation in successive animals. The epidural balloon was implanted unilaterally superior to the Sylvian sulcus. Subjects underwent ICP pulse augmentation, reduction and inversion protocols, directly comparing time segments of system activation and deactivation. ICP and CBF were measured bilaterally along with systemic pressure and heart rate. CBF was measured using both thermal diffusion, and laser doppler probes.Results: The activation of the cardiac-gate balloon implant resulted in an ipsilateral/contralateral ICP pulse amplitude increase with augmentation (217%/202% respectively, P < .0005) and inversion (139%/120%, P < .0005). The observed changes associated with the ICP mean values were smaller, increasing with augmentation (23%/31%, P < .0001) while decreasing with inversion (7%/11%, P = .006/.0003) and reduction (4%/5%, P < .0005). CBF increase was observed for both inversion and reduction protocols (28%/7.4%, P < .0001/P = .006 and 2.4%/1.3%, P < .0001/P = .003), but not the augmentation protocol. The change in CBF was correlated with ICP pulse amplitude and systolic peak changes and not with change in mean ICP or systemic variables (heart rate, arterial blood pressure).Conclusion: Cardiac-gated manipulation of ICP pulsatility allows the study of intracranial pulsatile dynamics and provides a potential means of altering CBF.
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| 147. |
- Luciano, Mark G., et al.
(author)
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Novel method for dynamic control of intracranial pressure
- 2017
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In: Journal of Neurosurgery. - 0022-3085 .- 1933-0693. ; 126:5, s. 1629-1640
-
Journal article (peer-reviewed)abstract
- OBJECT Intracranial pressure (ICP) pulsations are generally considered a passive result of the pulsatility of blood flow. Active experimental modification of ICP pulsations would allow investigation of potential active effects on blood and CSF flow and potentially create a new platform for the treatment of acute and chronic low blood flow states as well as a method of CSF substance clearance and delivery. This study presents a novel method and device for altering the ICP waveform via cardiac-gated volume changes.METHODS The novel device used in this experiment (named Cadence) consists of a small air-filled inelastic balloon (approximately 1.0 ml) implanted into the intracranial space and connected to an external programmable pump, triggered by an R-wave detector. Balloons were implanted into the epidural space above 1 of the hemispheres of 19 canines for up to 10 hours. When activated, the balloons were programed to cyclically inflate with the cardiac cycle with variable delay, phase, and volume. The ICP response was measured in both hemispheres. Additionally, cerebral blood flow (heat diffusion and laser Doppler) was studied in 16 canines.RESULTS This system, depending on the inflation pattern of the balloon, allowed a flattening of the ICP waveform, increase in the ICP waveform amplitude, or phase shift of the wave. This occurred with small mean ICP changes, typically around ± 2 mm Hg (15%). Bilateral ICP effects were observed with activation of the device: balloon inflation at each systole increased the systolic ICP pulse (up to 16 mm Hg, 1200%) and deflation at systole decreased or even inverted the systolic ICP pulse (-0.5 to -19 mm Hg, -5% to -1600%) in a dose-(balloon volume) dependent fashion. No aphysiological or deleterious effects on systemic pressure (≤ ±10 mm Hg; 13% change in mean pressure) or cardiac rate (≤ ± 17 beats per minute; 16% change) were observed during up to 4 hours of balloon activity.CONCLUSIONS The results of these initial studies using an intracranially implanted, cardiac-gated, volume-oscillating balloon suggest the Cadence device can be used to modify ICP pulsations, without physiologically deleterious effects on mean ICP, systemic vascular effects, or brain injury. This device and technique may be used to study the role of ICP pulsatility in intracranial hemo- and hydrodynamic processes and introduces the creation of a potential platform of a cardiac-gated system for treatment of acute and chronic low blood flow states, and diseases requiring augmentation of CSF substance clearance or delivery.
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| 148. |
- Maddali, Manoj V., et al.
(author)
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Validation and utility of ARDS subphenotypes identified by machine-learning models using clinical data : an observational, multicohort, retrospective analysis
- 2022
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In: The Lancet Respiratory Medicine. - 2213-2600. ; 10:4, s. 367-377
-
Journal article (peer-reviewed)abstract
- Background: Two acute respiratory distress syndrome (ARDS) subphenotypes (hyperinflammatory and hypoinflammatory) with distinct clinical and biological features and differential treatment responses have been identified using latent class analysis (LCA) in seven individual cohorts. To facilitate bedside identification of subphenotypes, clinical classifier models using readily available clinical variables have been described in four randomised controlled trials. We aimed to assess the performance of these models in observational cohorts of ARDS. Methods: In this observational, multicohort, retrospective study, we validated two machine-learning clinical classifier models for assigning ARDS subphenotypes in two observational cohorts of patients with ARDS: Early Assessment of Renal and Lung Injury (EARLI; n=335) and Validating Acute Lung Injury Markers for Diagnosis (VALID; n=452), with LCA-derived subphenotypes as the gold standard. The primary model comprised only vital signs and laboratory variables, and the secondary model comprised all predictors in the primary model, with the addition of ventilatory variables and demographics. Model performance was assessed by calculating the area under the receiver operating characteristic curve (AUC) and calibration plots, and assigning subphenotypes using a probability cutoff value of 0·5 to determine sensitivity, specificity, and accuracy of the assignments. We also assessed the performance of the primary model in EARLI using data automatically extracted from an electronic health record (EHR; EHR-derived EARLI cohort). In Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE; n=2813), a multinational, observational ARDS cohort, we applied a custom classifier model (with fewer variables than the primary model) to determine the prognostic value of the subphenotypes and tested their interaction with the positive end-expiratory pressure (PEEP) strategy, with 90-day mortality as the dependent variable. Findings: The primary clinical classifier model had an area under receiver operating characteristic curve (AUC) of 0·92 (95% CI 0·90–0·95) in EARLI and 0·88 (0·84–0·91) in VALID. Performance of the primary model was similar when using exclusively EHR-derived predictors compared with manually curated predictors (AUC=0·88 [95% CI 0·81–0·94] vs 0·92 [0·88–0·97]). In LUNG SAFE, 90-day mortality was higher in patients assigned the hyperinflammatory subphenotype than in those with the hypoinflammatory phenotype (414 [57%] of 725 vs 694 [33%] of 2088; p<0·0001). There was a significant treatment interaction with PEEP strategy and ARDS subphenotype (p=0·041), with lower 90-day mortality in the high PEEP group of patients with the hyperinflammatory subphenotype (hyperinflammatory subphenotype: 169 [54%] of 313 patients in the high PEEP group vs 127 [62%] of 205 patients in the low PEEP group; hypoinflammatory subphenotype: 231 [34%] of 675 patients in the high PEEP group vs 233 [32%] of 734 patients in the low PEEP group). Interpretation: Classifier models using clinical variables alone can accurately assign ARDS subphenotypes in observational cohorts. Application of these models can provide valuable prognostic information and could inform management strategies for personalised treatment, including application of PEEP, once prospectively validated. Funding: US National Institutes of Health and European Society of Intensive Care Medicine.
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| 149. |
- Matos, Marina N., et al.
(author)
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Metagenomics unveils the attributes of the alginolytic guilds of sediments from four distant cold coastal environments
- 2016
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In: Environmental Microbiology. - : Wiley. - 1462-2912 .- 1462-2920. ; 18:12, s. 4471-4484
-
Journal article (peer-reviewed)abstract
- Alginates are abundant polysaccharides in brown algae that constitute an important energy source for marine heterotrophic bacteria. Despite the key role of alginate degradation processes in the marine carbon cycle, little information is available on the bacterial populations involved in these processes. The aim of this work was to gain a better understanding of alginate utilization capabilities in cold coastal environments. Sediment metagenomes from four high-latitude regions of both Hemispheres were interrogated for alginate lyase gene homologue sequences and their genomic context. Sediments contained highly abundant and diverse bacterial assemblages with alginolytic potential, including members of Bacteroidetes and Proteobacteria, as well as several poorly characterized taxa. The microbial communities in Arctic and Antarctic sediments exhibited the most similar alginolytic profiles, whereas brackish sediments showed distinct structures with a higher proportion of novel genes. Examination of the gene neighbourhood of the alginate lyase homologues revealed distinct patterns depending on the potential lineage of the scaffolds, with evidence of evolutionary relationships among alginolytic gene clusters from Bacteroidetes and Proteobacteria. This information is relevant for understanding carbon fluxes in cold coastal environments and provides valuable information for the development of biotechnological applications from brown algae biomass.
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| 150. |
- Nawaz, Muhammad, et al.
(author)
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The emerging role of extracellular vesicles as biomarkers for urogenital cancers.
- 2014
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In: Nature reviews. Urology. - : Springer Science and Business Media LLC. - 1759-4820 .- 1759-4812. ; 11, s. 688-701
-
Journal article (peer-reviewed)abstract
- The knowledge gained from comprehensive profiling projects that aim to define the complex genomic alterations present within cancers will undoubtedly improve our ability to detect and treat those diseases, but the influence of these resources on our understanding of basic cancer biology is still to be demonstrated. Extracellular vesicles have gained considerable attention in past years, both as mediators of intercellular signalling and as potential sources for the discovery of novel cancer biomarkers. In general, research on extracellular vesicles investigates either the basic mechanism of vesicle formation and cargo incorporation, or the isolation of vesicles from available body fluids for biomarker discovery. A deeper understanding of the cargo molecules present in extracellular vesicles obtained from patients with urogenital cancers, through high-throughput proteomics or genomics approaches, will aid in the identification of novel diagnostic and prognostic biomarkers, and can potentially lead to the discovery of new therapeutic targets.
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