Background
For many patients with lung disease the only proven intervention to improve survival and quality of life is lung transplantation (LTx). Esophageal dysmotility and gastroesophageal reflux ...(GER) are common in patients with respiratory disease, and often associate with worse prognosis following LTx. Which, if any patients, should be excluded from LTx based on esophageal concerns remains unclear. Our aim was to understand the effect of LTx on esophageal motility diagnosis and examine how this and the other physiological and mechanical factors relate to GER and clearance of boluses swallowed.
Methods
We prospectively recruited 62 patients with restrictive (RLD) and obstructive (OLD) lung disease (aged 33–75 years; 42 men) who underwent high resolution impedance manometry and 24‐h pH‐impedance before and after LTx.
Key Results
RLD patients with normal motility were more likely to remain normal (p = 0.02), or if having abnormal motility to change to normal (p = 0.07) post‐LTx than OLD patients. Esophageal length (EL) was greater in OLD than RLD patients' pre‐LTx (p < 0.001), reducing only in OLD patients' post‐LTx (p = 0.02). Reduced EL post‐LTx associated with greater contractile reserve (r = 0.735; p = 0.01) and increased likelihood of motility normalization (p = 0.10). Clearance of reflux improved (p = 0.01) and associated with increased mean nocturnal baseline impedance (p < 0.001) in RLD but not OLD. Peristaltic breaks and thoraco‐abdominal pressure gradient impact both esophageal clearance of reflux and boluses swallowed (p < 0.05).
Conclusions and Inferences
RLD patients are more likely to show improvement in esophageal motility than OLD patients post‐LTx. However, the effect on GER is more difficult to predict and requires other GI, anatomical and pulmonary factors to be taken into consideration.
Patients with restrictive lung disease are more likely to show improvement in esophageal motility than patients with obstructive disease following lung transplantation. Effects on gastroesophageal reflux are more complex and difficult to predict because of contributory factors, such as motility, anatomical differences (e.g., esophageal length), and lung mechanics (e.g., TAPG).
The study was designed to assess the possibility of using circulating miRNAs (serum miRNAs) as diagnostic biomarkers in colorectal cancer (CRC) and to identify their possibility as candidates for ...targeted therapy.
The study involved two sample sets: 1- a training set which included 90 patients with colorectal related disease (30 with CRC, 18 with inflammatory bowel disease (IBD), 18 with colonic polyps (CP) and 24 with different colonic symptoms but without any colonoscopic abnormality who were enrolled as control group) and 2- a validation set which included 100 CRC patients. Serum miRNAs were extracted from all subjects to assess the expression profiles for the following miRNAs (miR-17, miR-18a, miR-19a, miR-19b, miR-20a, miR-21, miR-146a, miR-223, miR-24, miR-454, miR-183, miR-135a, miR- 135b and miR- 92a) using the custom miScript miRNA PCR-based sybergreen array. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic performance of the studied miRNAs for colorectal cancer diagnosis.
Data analysis of miRNA from the training set showed that; compared to control group, only miR-19b was significantly up-regulated in patients with IBD group (fold change = 5.24, p = 0.016), whereas in patients with colonic polyps, miR-18a was significantly up-regulated (fold change = 3.49, p-value = 0.018). On the other hand, miR-17, miR-19a, miR-20a and miR-223 were significantly up-regulated (fold change = 2.35, 3.07, 2.38 and 10.35; respectively and p-value = 0.02, 0.015, 0.017 and 0.016; respectively in CRC patients. However, the validation set showed that only miR-223 was significantly up-regulated in CRC patients (fold change = 4.06, p-value = 0.04).
Aberrant miRNA expressions are highly involved in the cascade of colorectal carcinogenesis. We have found that (miR-17, miR-19a, miR-20a and miR-223) could be used as diagnostic biomarkers for CRC. On the other hand, miR-19b and miR-18a could be used as diagnostic biomarkers for CP and IBD respectively.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Physiologically based pharmacokinetic (PBPK) modeling and simulation is a tool that can help predict the pharmacokinetics of drugs in humans and evaluate the effects of intrinsic (e.g., organ ...dysfunction, age, genetics) and extrinsic (e.g., drug–drug interactions) factors, alone or in combinations, on drug exposure. The use of this tool is increasing at all stages of the drug development process. This report reviews recent instances of the use of PBPK in decision‐making during regulatory review. The examples are based on Center for Drug Evaluation and Research reviews of several submissions for investigational new drugs (INDs) and new drug applications (NDAs) received between July 2008 and June 2010. The use of PBPK modeling and simulation facilitated the following types of decisions: the need to conduct specific clinical pharmacology studies, specific study designs, and appropriate labeling language. The report also discusses the challenges encountered when PBPK modeling and simulation were used in these cases and recommends approaches to facilitating full utilization of this tool.
Clinical Pharmacology & Therapeutics (2011) 89 2, 259–267. doi:10.1038/clpt.2010.298
•The COVID-19 pandemic can no longer be mitigated by a nationwide approach of individual nations alone.•Considering an ‘all hands-on deck’ concept, we present a comprehensive list of tools and ...entities responsible for and enabling them, as well a conceptual framework to achieve the maximum impact.•Included are the roles of individuals, communities, government and other sectors such as school systems, health, institutions, and business.•We call on all countries to act synergistically to minimize everyone's risk, to maximize collaboration, and to commit to shared progress.
The COVID-19 pandemic can no longer be mitigated by a nationwide approach of individual nations alone. Given its scale and accelerating expansion, COVID-19 requires a coordinated and simultaneous Whole- of-World approach that galvanizes clear global leadership and solidarity from all governments of the world. Considering an ‘all hands-on deck’ concept, we present a comprehensive list of tools and entities responsible for enabling them, as well a conceptual framework to achieve the maximum impact. The list is drawn from pandemic mitigation tools developed in response to past outbreaks including influenza, coronaviruses, and Ebola, and includes tools to minimize transmission in various settings including person-to-person, crowd, funerals, travel, workplace, and events and gatherings including business, social and religious venues. Included are the roles of individuals, communities, government and other sectors such as school systems, health, institutions, and business. While individuals and communities have significant responsibilities to prevent person-to-person transmission, other entities can play a significant role to enable individuals and communities to make use of the tools. Historic and current data indicate the role of political will, whole-of-government approach, and the role of early introduction of mitigation measures. There is also an urgent need to further elucidate the immunologic mechanisms underlying the epidemiological characteristics such as the low disease burden among women, and the role of COVID-19 in inducing Kawasaki-like syndromes in children. Understanding the role of and development of anti-inflammatory strategies based on our understanding of pro-inflammatory cytokines (IL1, IL-6) is also critical. Similarly, the role of oxygen therapy as an anti-inflammatory strategy is evident and access to oxygen therapy should be prioritized to avoid the aggravation of COVID-19 infection. We highlight the need for global solidarity to share both mitigation commodities and infrastructure between countries. Given the global reach of COVID-19 and potential for repeat waves of outbreaks, we call on all countries and communities to act synergistically and emphasize the need for synchronized pan-global mitigation efforts to minimize everyone's risk, to maximize collaboration, and to commit to shared progress.
ABSTRACT
We present the new code NADA-FLD to solve multidimensional neutrino-hydrodynamics in full general relativity (GR) in spherical polar coordinates. The energy-dependent neutrino transport ...assumes the flux-limited diffusion approximation and evolves the neutrino energy densities measured in the frame comoving with the fluid. Operator splitting is used to avoid multidimensional coupling of grid cells in implicit integration steps involving matrix inversions. Terms describing lateral diffusion and advection are integrated explicitly using the Allen–Cheng or the Runge–Kutta–Legendre method, which remain stable even in the optically thin regime. We discuss several toy-model problems in one and two dimensions to test the basic functionality and individual components of the transport scheme. We also perform fully dynamic core-collapse supernova (CCSN) simulations in spherical symmetry. For a Newtonian model, we find good agreement with the M1 code ALCAR, and for a GR model, we reproduce the main effects of GR in CCSNe already found by previous works.
Textual databases are useful sources of information and knowledge and if these are well utilised then issues related to future project management and product or service quality improvement may be ...resolved. A large part of corporate information, approximately 80%, is available in textual data formats. Text Classification techniques are well known for managing on-line sources of digital documents. The identification of key issues discussed within textual data and their classification into two different classes could help decision makers or knowledge workers to manage their future activities better. This research is relevant for most text based documents and is demonstrated on Post Project Reviews (PPRs) which are valuable source of information and knowledge. The application of textual data mining techniques for discovering useful knowledge and classifying textual data into different classes is a relatively new area of research. The research work presented in this paper is focused on the use of hybrid applications of text mining or textual data mining techniques to classify textual data into two different classes. The research applies clustering techniques at the first stage and Apriori Association Rule Mining at the second stage. The Apriori Association Rule of Mining is applied to generate
Multiple Key Term Phrasal Knowledge Sequences (MKTPKS) which are later used for classification. Additionally, studies were made to improve the classification accuracies of the classifiers i.e. C4.5,
K-NN, Naïve Bayes and Support Vector Machines (SVMs). The classification accuracies were measured and the results compared with those of a single term based classification model. The methodology proposed could be used to analyse any free formatted textual data and in the current research it has been demonstrated on an industrial dataset consisting of Post Project Reviews (PPRs) collected from the construction industry. The data or information available in these reviews is codified in multiple different formats but in the current research scenario only free formatted text documents are examined. Experiments showed that the performance of classifiers improved through adopting the proposed methodology.
Malignant pleural effusion (MPE) is a common clinical problem with described investigation pathways. While thoracic ultrasound (TUS) has been shown to be accurate in pleural fluid detection, its use ...in the diagnosis of malignant pleural disease has not been assessed. A study was undertaken to assess the diagnostic accuracy of TUS in differentiating malignant and benign pleural disease.
52 consecutive patients with suspected MPE underwent TUS and contrast-enhanced CT (CECT). TUS was used to assess pleural surfaces using previously published CT imaging criteria for malignancy, diaphragmatic thickness/nodularity, effusion size/nature and presence of hepatic metastasis (in right-sided effusions). A TUS diagnosis of malignant or benign disease was made blind to clinical data/other investigations by a second blinded operator using anonymised TUS video clips. The TUS diagnosis was compared with the definitive clinical diagnosis and in addition to the diagnosis found at CECT.
A definitive malignant diagnosis was based on histocytology (30/33; 91%) and clinical/CT follow-up (3/33; 9%). Benign diagnoses were based on negative histocytology and follow-up over 12 months in 19/19 patients. TUS correctly diagnosed malignancy in 26/33 patients (sensitivity 73%, specificity 100%, positive predictive value 100%, negative predictive value 79%) and benign disease in 19/19. Pleural thickening >1 cm, pleural nodularity and diaphragmatic thickening >7 mm were highly suggestive of malignant disease.
TUS is useful in differentiating malignant from benign pleural disease in patients presenting with suspected MPE and may become an important adjunct in the diagnostic pathway.
ABSTRACT
We investigate the final collapse of rotating and non-rotating pulsational pair-instability supernova progenitors with zero-age-main-sequence masses of 60, 80, and 115 M⊙ and iron cores ...between 2.37 and 2.72 M⊙ by 2D hydrodynamics simulations. Using the general relativistic NADA-FLD code with energy-dependent three-flavour neutrino transport by flux-limited diffusion allows us to follow the evolution beyond the moment when the transiently forming neutron star (NS) collapses to a black hole (BH), which happens within 350–580 ms after bounce in all cases. Because of high neutrino luminosities and mean energies, neutrino heating leads to shock revival within ≲ 250 ms post bounce in all cases except the rapidly rotating 60 M⊙ model. In the latter case, centrifugal effects support a 10 per cent higher NS mass but reduce the radiated neutrino luminosities and mean energies by ∼20 per cent and ∼10 per cent, respectively, and the neutrino-heating rate by roughly a factor of two compared to the non-rotating counterpart. After BH formation, the neutrino luminosities drop steeply but continue on a 1–2 orders of magnitude lower level for several 100 ms because of aspherical accretion of neutrino and shock-heated matter, before the ultimately spherical collapse of the outer progenitor shells suppresses the neutrino emission to negligible values. In all shock-reviving models BH accretion swallows the entire neutrino-heated matter and the explosion energies decrease from maxima around 1.5 × 1051 erg to zero within a few seconds latest. Nevertheless, the shock or a sonic pulse moves outward and may trigger mass-loss, which we estimate by long-time simulations with the prometheus code. We also provide gravitational-wave signals.
Patients of African ancestry have the poorest outcome and the shortest survival rates from cancer globally. This could be attributed to many variables including racial, biological, socioeconomic and ...sociocultural factors (either single, multiple or combined), which may be responsible for this major health problem. We sought to assess the most common types of cancer that endanger the health of the African people, and tried to investigate the real differences between African and other Non-African patients regarding incidence, prevalence and mortality rates of different cancers. Therefore, identifying the underlying aetiological causes responsible for the increased incidence and mortality rates of African patients will allow for changing the current plans, to make optimized modalities for proper screening, diagnosis and treatment for those African patients, in order to improve their survival and outcomes.
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