155 research outputs found
Ultrasonic NDE of Adhesive Bonds: The Inverse Problem
Over the past quarter century, a wide variety of ultrasonic techniques have been developed to determine the phase velocity and thickness of elastic plates. Techniques to measure the phase velocity include toneburst [1–4], separable pulse methods [5–7], and spectroscopy [8–11]. These classical methods require that the specimen be thick enough such that two successive echoes from the front and the back faces of the specimen, respectively, be separable in the time domain. Kinra and Dayal [12], developed a through transmission technique which removes this particular limitation of the classical methods. This technique works satisfactorily for the measurement of the phase velocity for specimens whose thickness is greater than one-half of the wavelength; for thinner specimens, however, their numerical algorithm runs into convergence problems. Moreover, their numerical algorithm cannot be used to determine thickness at any wavelength. The reasons for their convergence problems are discussed in detail by Iyer, Hanneman and Kinra [13]. They demonstrated that a detailed sensitivity analysis is a necessary pre-requisite for the development of a robust inversion algorithm. Accordingly, a new inversion scheme based on the method of least squares was developed by Iyer and Kinra to determine thickness from the measurements of phase, magnitude and complex spectrum, respectively, [14–17]. In all of the above ultrasonic methods only one parameter can be determined i.e., an accurate knowledge of thickness is required to determine the wavespeed and vice versa. This defines the central objective of the present work: In this paper we present a technique for determining, simultaneously, the thickness and wavespeed of a thin layer
Predicting Short-term MCI-to-AD Progression Using Imaging, CSF, Genetic Factors, Cognitive Resilience, and Demographics.
In the Alzheimer’s disease (AD) continuum, the prodromal state of mild cognitive impairment (MCI)
precedes AD dementia and identifying MCI individuals at risk of progression is important for clinical
management. Our goal was to develop generalizable multivariate models that integrate highdimensional data (multimodal neuroimaging and cerebrospinal fuid biomarkers, genetic factors,
and measures of cognitive resilience) for identifcation of MCI individuals who progress to AD within
3 years. Our main fndings were i) we were able to build generalizable models with clinically relevant
accuracy (~93%) for identifying MCI individuals who progress to AD within 3 years; ii) markers of AD
pathophysiology (amyloid, tau, neuronal injury) accounted for large shares of the variance in predicting
progression; iii) our methodology allowed us to discover that expression of CR1 (complement receptor
1), an AD susceptibility gene involved in immune pathways, uniquely added independent predictive
value. This work highlights the value of optimized machine learning approaches for analyzing
multimodal patient information for making predictive assessments
Holographic c-theorems in arbitrary dimensions
We re-examine holographic versions of the c-theorem and entanglement entropy
in the context of higher curvature gravity and the AdS/CFT correspondence. We
select the gravity theories by tuning the gravitational couplings to eliminate
non-unitary operators in the boundary theory and demonstrate that all of these
theories obey a holographic c-theorem. In cases where the dual CFT is
even-dimensional, we show that the quantity that flows is the central charge
associated with the A-type trace anomaly. Here, unlike in conventional
holographic constructions with Einstein gravity, we are able to distinguish
this quantity from other central charges or the leading coefficient in the
entropy density of a thermal bath. In general, we are also able to identify
this quantity with the coefficient of a universal contribution to the
entanglement entropy in a particular construction. Our results suggest that
these coefficients appearing in entanglement entropy play the role of central
charges in odd-dimensional CFT's. We conjecture a new c-theorem on the space of
odd-dimensional field theories, which extends Cardy's proposal for even
dimensions. Beyond holography, we were able to show that for any
even-dimensional CFT, the universal coefficient appearing the entanglement
entropy which we calculate is precisely the A-type central charge.Comment: 62 pages, 4 figures, few typo's correcte
Free Cysteine Modulates the Conformation of Human C/EBP Homologous Protein
The C/EBP Homologous Protein (CHOP) is a nuclear protein that is integral to the unfolded protein response culminating from endoplasmic reticulum stress. Previously, CHOP was shown to comprise extensive disordered regions and to self-associate in solution. In the current study, the intrinsically disordered nature of this protein was characterized further by comprehensive in silico analyses. Using circular dichroism, differential scanning calorimetry and nuclear magnetic resonance, we investigated the global conformation and secondary structure of CHOP and demonstrated, for the first time, that conformational changes in this protein can be induced by the free amino acid l-cysteine. Addition of l-cysteine caused a significant dose-dependent decrease in the protein helicity – dropping from 69.1% to 23.8% in the presence of 1 mM of l-cysteine – and a sequential transition to a more disordered state, unlike that caused by thermal denaturation. Furthermore, the presence of small amounts of free amino acid (80 µM, an 8∶1 cysteine∶CHOP ratio) during CHOP thermal denaturation altered the molecular mechanism of its melting process, leading to a complex, multi-step transition. On the other hand, high levels (4 mM) of free l-cysteine seemed to cause a complete loss of rigid cooperatively melting structure. These results suggested a potential regulatory function of l-cysteine which may lead to changes in global conformation of CHOP in response to the cellular redox state and/or endoplasmic reticulum stress
Mitochondrial respiratory states and rate
As the knowledge base and importance of mitochondrial physiology to human health expands, the necessity for harmonizing the terminologyconcerning mitochondrial respiratory states and rates has become increasingly apparent. Thechemiosmotic theoryestablishes the mechanism of energy transformationandcoupling in oxidative phosphorylation. Theunifying concept of the protonmotive force providestheframeworkfordeveloping a consistent theoretical foundation ofmitochondrial physiology and bioenergetics.We followguidelines of the International Union of Pure and Applied Chemistry(IUPAC)onterminology inphysical chemistry, extended by considerationsofopen systems and thermodynamicsof irreversible processes.Theconcept-driven constructive terminology incorporates the meaning of each quantity and alignsconcepts and symbols withthe nomenclature of classicalbioenergetics. We endeavour to provide a balanced view ofmitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes.Uniform standards for evaluation of respiratory states and rates will ultimatelycontribute to reproducibility between laboratories and thussupport the development of databases of mitochondrial respiratory function in species, tissues, and cells.Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery
Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.
BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112
Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy
Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe
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