The vaporization of a superheated droplet emulsion into gas bubbles using ultrasound-termed acoustic droplet vaporization (ADV)-has potential therapeutic applications in embolotherapy and drug ...delivery. The optimization of ADV for therapeutic applications can be enhanced by understanding the physical mechanisms underlying ADV, which are currently not clearly elucidated. Acoustic cavitation is one possible mechanism. This paper investigates the relationship between ADV and inertial cavitation (IC) thresholds (measured as peak rarefactional pressures) by studying parameters that are known to influence the IC threshold. These parameters include bulk fluid properties such as gas saturation, temperature, viscosity, and surface tension; droplet parameters such as degree of superheat, surfactant type, and size; and acoustic properties such as pulse repetition frequency and pulse width. In all cases the ADV threshold occurred at a lower rarefactional pressure than the IC threshold, indicating that the phase transition occurs before IC events. The viscosity and temperature of the bulk fluid are shown to influence both thresholds directly and inversely, respectively. An inverse trend is observed between threshold and diameter for droplets in the 1 to 2.5 mum range. Based on a choice of experimental parameters, it is possible to achieve ADV with or without IC.
In non-inferiority trials, there is a concern that intention-to-treat (ITT) analysis, by including participants who did not receive the planned interventions, may bias towards making the treatment ...and control arms look similar and lead to mistaken claims of non-inferiority. In contrast, per protocol (PP) analysis is viewed as less likely to make this mistake and therefore preferable in non-inferiority trials. In a systematic review of antibiotic non-inferiority trials, we compared ITT and PP analyses to determine which analysis was more conservative.
In a secondary analysis of a systematic review, we included non-inferiority trials that compared different antibiotic regimens, used absolute risk reduction (ARR) as the main outcome and reported both ITT and PP analyses. All estimates and confidence intervals (CIs) were oriented so that a negative ARR favored the control arm, and a positive ARR favored the treatment arm. We compared ITT to PP analyses results. The more conservative analysis between ITT and PP analyses was defined as the one having a more negative lower CI limit.
The analysis included 164 comparisons from 154 studies. In terms of the ARR, ITT analysis yielded the more conservative point estimate and lower CI limit in 83 (50.6%) and 92 (56.1%) comparisons respectively. The lower CI limits in ITT analysis favored the control arm more than in PP analysis (median of - 7.5% vs. -6.9%, p = 0.0402). CIs were slightly wider in ITT analyses than in PP analyses (median of 13.3% vs. 12.4%, p < 0.0001). The median success rate was 89% (interquartile range IQR 82 to 93%) in the PP population and 44% (IQR 23 to 60%) in the patients who were included in the ITT population but excluded from the PP population (p < 0.0001).
Contrary to common belief, ITT analysis was more conservative than PP analysis in the majority of antibiotic non-inferiority trials. The lower treatment success rate in the ITT analysis led to a larger variance and wider CI, resulting in a more conservative lower CI limit. ITT analysis should be mandatory and considered as either the primary or co-primary analysis for non-inferiority trials.
PROSPERO registration number CRD42020165040 .
The use of race-specific seedling genes for resistance is the primary means of controlling crown rust of oat (Puccinia coronata f. sp. avenae) in the United States. To better utilize those resistance ...genes, knowledge of the occurrence and frequency of corresponding virulence in the population of P. coronata f. sp. avenae in the United States is essential. In total, 571 single-pustule isolates of oat crown rust were collected from cultivated and wild oat (Avena sativa and A. fatua, respectively) in the major oat production areas of the United States from 2006 through 2009. They were tested for virulence on seedlings of 31 differential oat lines in the greenhouse. In all, 201 races were found among the 357 isolates from the spring oat region of the north-central United States, and 140 races were found among 214 isolates from the southern winter oat region. The crown rust populations from the winter and spring oat regions were clearly differentiated from one another, differing in the frequency of virulence for 24 of the 31 differentials. Some virulence associations previously reported in the U.S. oat crown rust population were also found in both regions in this survey, even when the dataset was clone corrected. Associations between virulence to the Pc genes were predominately positive in both regions but both positive and negative associations occurred more frequently in the winter oat region, where sexual reproduction does not occur. Some of the virulence diversity in the oat crown rust population in the United States can be related to the deployment of resistance genes in commercial oat cultivars and virulence associations existing in the oat crown rust population. When data from a previous report covering 2001 through 2005 is combined with data reported in this article, the mean virulence of the U.S. populations of crown rust continued to increase from 2001 to 2009. Virulence to Pc38, Pc39, Pc45, Pc48, Pc52, Pc55, Pc56, Pc57, Pc59, Pc62, Pc63, Pc64, Pc68, and Pc96 significantly increased in one or both regions during this time period. No significant declines in virulence frequency were found in either region. Genes for crown rust resistance derived from A. sterilis appear to be as rapidly defeated as has happened to Pc genes from A. sativa. There is an urgent need to find additional sources of effective resistance to P. coronata f. sp. avenae and introgress it into adapted oat cultivars.
Thallium chemistry is experiencing unprecedented importance. Therefore, it is valuable to characterize some of the simplest thallium compounds. Stationary points along the singlet and triplet Tl 2H 2 ...potential energy surface have been characterized. Stationary point geometries were optimized with the CCSD(T)/aug‐cc‐pwCVQZ‐PP method. Harmonic vibrational frequencies were computed at the same level of theory while anharmonic vibrational frequencies were computed at the CCSD(T)/aug‐cc‐pwCVTZ‐PP level of theory. Final energetics were obtained with the CCSDT(Q) method. Basis sets up to augmented quintuple‐zeta cardinality (aug‐cc‐pwCV5Z‐PP) were employed to obtain energetics in order to extrapolate to the complete basis set limits using the focal point approach. Zero‐point vibrational energy corrections were appended to the extrapolated energies in order to determine relative energies at 0 K. It was found that the planar dibridged isomer lies lowest in energy while the linear structure lies highest in energy. The results were compared to other group 13 M 2H 2 (M = B, Al, Ga, In, and Tl) theoretical studies and some interesting variations are found. With respect to experiment, incompatibilities exist.
•The proposed method segments ultrasound images into major tissue components.•Our method eliminates differences and inconsistencies in ultrasound interpretation.•Comparison between our method and ...manual segmentation demonstrated good consistency.
Segmentation of an ultrasound image into functional tissues is of great importance to clinical diagnosis of breast cancer. However, many studies are found to segment only the mass of interest and not all major tissues. Differences and inconsistencies in ultrasound interpretation call for an automated segmentation method to make results operator-independent. Furthermore, manual segmentation of entire three-dimensional (3D) ultrasound volumes is time-consuming, resource-intensive, and clinically impractical. Here, we propose an automated algorithm to segment 3D ultrasound volumes into three major tissue types: cyst/mass, fatty tissue, and fibro-glandular tissue. To test its efficacy and consistency, the proposed automated method was employed on a database of 21 cases of whole breast ultrasound. Experimental results show that our proposed method not only distinguishes fat and non-fat tissues correctly, but performs well in classifying cyst/mass. Comparison of density assessment between the automated method and manual segmentation demonstrates good consistency with an accuracy of 85.7%. Quantitative comparison of corresponding tissue volumes, which uses overlap ratio, gives an average similarity of 74.54%, consistent with values seen in MRI brain segmentations. Thus, our proposed method exhibits great potential as an automated approach to segment 3D whole breast ultrasound volumes into functionally distinct tissues that may help to correct ultrasound speed of sound aberrations and assist in density based prognosis of breast cancer.
We present a two-dimensional (2D) snapshot multispectral imager that utilizes the optical transmission characteristics of nanohole arrays (NHAs) in a gold film to resolve a mixture of input colors ...into multiple spectral bands. The multispectral device consists of blocks of NHAs, wherein each NHA has a unique periodicity that results in transmission resonances and minima in the visible and near-infrared regions. The multispectral device was illuminated over a wide spectral range, and the transmission was spectrally unmixed using a least-squares estimation algorithm. A NHA-based multispectral imaging system was built and tested in both reflection and transmission modes. The NHA-based multispectral imager was capable of extracting 2D multispectral images representative of four independent bands within the spectral range of 662 nm to 832 nm for a variety of targets. The multispectral device can potentially be integrated into a variety of imaging sensor systems.
Performance of the LHCb RICH detector at the LHC Adinolfi, M.; Aglieri Rinella, G.; Albrecht, E. ...
The European physical journal. C, Particles and fields,
05/2013, Letnik:
73, Številka:
5
Journal Article
Recenzirano
Odprti dostop
The LHCb experiment has been taking data at the Large Hadron Collider (LHC) at CERN since the end of 2009. One of its key detector components is the Ring-Imaging Cherenkov (RICH) system. This ...provides charged particle identification over a wide momentum range, from 2–100 GeV/
c
. The operation and control, software, and online monitoring of the RICH system are described. The particle identification performance is presented, as measured using data from the LHC. Excellent separation of hadronic particle types (
π
, K, p) is achieved.
Type 1 Diabetes Mellitus (T1DM) is a disease characterized by the destruction of insulin‐secreting pancreatic beta cells and results in hyperglycemia, muscle wasting, and vascular dysfunction. ...Patients afflicted with T1DM suffer from increased morbidity and early mortality, largely driven by an inability to appropriately maintain glucose homeostasis. Skeletal muscle is the body’s largest metabolic reservoir, absorbing significant amounts of glucose from the bloodstream. The myokine myostatin is a potent negative regulator of muscle growth and is upregulated in T1DM patients but downregulated following regular exercise. Physical exercise is also known to improve cardiovascular health and increase insulin sensitivity of muscle, but many T1DM patients are unable to exercise at a level that conveys benefit due to muscle atrophy. Thus, directly targeting skeletal muscle, independent of exercise, may prove beneficial for T1DM therapy. Our hypothesis is that genetic deletion of myostatin will preserve glucose homeostasis, maintain muscle function, and protect against vascular dysfunction and cardiometabolic effects in a mouse model of T1DM.
T1DM was induced via streptozotocin (STZ) in adult male mice with (WT) and without myostatin (MyoKO). Multiple variables were assessed including glucose homeostasis (plasma glucose, HbA1c, IGTT), fluid dynamics, muscle function (in vivo plantarflexion), and vascular function (ex vivo pressure myography of gracilis arteriole).
Myostatin deletion inhibited STZ‐induced increases in plasma glucose, preserved fluid dynamics, and prevented decreases in muscle function, independent of insulin. Further, endothelial function was protected with myostatin deletion. Taken together, this data suggests that myostatin inhibition may be a target for effective treatment and management of the cardiometabolic and skeletal muscle dysfunction that occurs with T1DM.
In 2013, afatinib was approved for non-small-cell lung cancer with subsequent indication expansion. We investigated published afatinib clinical trials to assess risk and benefit profiles for the drug ...in its approved indication of non-small-cell lung cancer as well as in off-label uses. Previous literature demonstrates excessive patient burden and limited benefit as afatinib has spread into more indications. A trial analysis is needed to establish efficacy and risk.
In this investigation, we screened literature databases and clinical trial registries for trials of afatinib as monotherapy or in combination interventions for cancer treatment. We extracted participant demographics, adverse event characteristics, as well as clinical and surrogate endpoints for each trial. Studies were deemed positive, negative, or indeterminate based on their achieving of primary endpoints as well as their safety.
Our search yielded 2444 articles; we excluded 2352 articles for a final inclusion of 92 trials of 8859 patients. Our sample had 49 (53%) positive trials, 27 (29%) negative trials, and 16 (17%) indeterminate trials. The most common off-label indications for afatinib were breast cancer and squamous cell carcinoma of head and neck. The median OS for all trials was 8.4 months, median PFS 3.4 months, and the total ORR was 29.6%. Our study found that trials performed in disease states beyond the initial indications were largely negative with little patient benefit. The adverse events within our trial sample appear to be in line with expectations for toxicity.
These results are consistent with other studies that present similar findings, such as in Carlisle et al which indicate limited efficacy in nonapproved indications. Future trials should keep this potential evidence and patient burden in mind before initiation of those trials. This study contributes to the understanding of afatinib's risk-benefit profile across many clinical applications.
Several studies suggest that nasal nitric oxide (nNO) measurement could be a test for primary ciliary dyskinesia (PCD), but the procedure and interpretation have not been standardized.
To use a ...standard protocol for measuring nNO to establish a disease-specific cutoff value at one site, and then validate at six other sites.
At the lead site, nNO was prospectively measured in individuals later confirmed to have PCD by ciliary ultrastructural defects (n = 143) or DNAH11 mutations (n = 6); and in 78 healthy and 146 disease control subjects, including individuals with asthma (n = 37), cystic fibrosis (n = 77), and chronic obstructive pulmonary disease (n = 32). A disease-specific cutoff value was determined, using generalized estimating equations (GEEs). Six other sites prospectively measured nNO in 155 consecutive individuals enrolled for evaluation for possible PCD.
At the lead site, nNO values in PCD (mean ± standard deviation, 20.7 ± 24.1 nl/min; range, 1.5-207.3 nl/min) only rarely overlapped with the nNO values of healthy control subjects (304.6 ± 118.8; 125.5-867.0 nl/min), asthma (267.8 ± 103.2; 125.0-589.7 nl/min), or chronic obstructive pulmonary disease (223.7 ± 87.1; 109.7-449.1 nl/min); however, there was overlap with cystic fibrosis (134.0 ± 73.5; 15.6-386.1 nl/min). The disease-specific nNO cutoff value was defined at 77 nl/minute (sensitivity, 0.98; specificity, >0.999). At six other sites, this cutoff identified 70 of the 71 (98.6%) participants with confirmed PCD.
Using a standardized protocol in multicenter studies, nNO measurement accurately identifies individuals with PCD, and supports its usefulness as a test to support the clinical diagnosis of PCD.
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