Next-generation sequencing (NGS) technology has expanded in the last decades with significant improvements in the reliability, sequencing chemistry, pipeline analyses, data interpretation and costs. ...Such advances make the use of NGS feasible in clinical practice today. This review describes the recent technological developments in NGS applied to the field of oncology. A number of clinical applications are reviewed, i.e., mutation detection in inherited cancer syndromes based on DNA-sequencing, detection of spliceogenic variants based on RNA-sequencing, DNA-sequencing to identify risk modifiers and application for pre-implantation genetic diagnosis, cancer somatic mutation analysis, pharmacogenetics and liquid biopsy. Conclusive remarks, clinical limitations, implications and ethical considerations that relate to the different applications are provided.
Purpose Antimuscarinic drug treatment is known to have side effects and, consequently, poor adherence in therapeutic regimens. In this systematic review we study the long-term (greater than 6 months) ...adherence to antimuscarinic drugs in daily clinical practice, and identify factors contributing to poor adherence and persistence. Materials and Methods This systematic review was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A literature search was performed using PubMed® and Embase™ using synonyms for incontinence, overactive bladder and antimuscarinics combined with synonyms for medication adherence. We chose to include only pharmaceutical database studies (using prescription/insurance claim data) and patient self-report studies, using established pharmacoepidemiological parameters such as persistence rate and medication possession rate. Results A total of 1,245 titles were screened, of which 102 abstracts were assessed. Fourteen studies were ultimately included, comprising 190,279 unique patients (mean age 69.5 years). Regardless of which specific antimuscarinic drug is studied, persistence rates are usually poor. Considering all drugs together, median persistence rates were 12.0% to 39.4% (with an outlier of 75.5%) at 12 months, 8.0% to 15.0% at 18 months and 6.0% to 12.0% at 24 months. At 36 months persistence rates ranged from 0.0% (darifenacin) to 16.0% (trospium). Mean reported medication possession rates were also low, with a mean of 0.37 at 12 months. Risk factors for discontinuation were identified, with the most important being younger age group, use of oxybutynin and use of immediate release formulations. Conclusions Improvement in adherence and persistence with antimuscarinic medication should be an important goal in the development of new drugs for overactive bladder and urinary incontinence.
•Irradiance and PV production data from a PV plant are used to estimate cloud speed.•A new method to derive cloud speed from three sensors at arbitrary positions is demonstrated.•A second method is ...used for validation with an overall annual RMSE of 20.9%
Clouds are the dominant source of PV power output variability and their velocity is a principal input to most short-term forecast models. A new method for deriving cloud speed from data collected at a triplet of sensors at arbitrary positions is presented; cloud speed and the angle of the cloud front are determined from the time delays in two cloud front arrivals at the sensors. Five reference cells at the 48MW PV plant at Henderson (NV), were used to provide two different triplets of sensors. Over a year of operation cloud speeds from 3 to 35ms−1 were obtained. Cloud speeds are validated using cross-correlation of power output from 96 inverters at the plant. Overall bias errors were less than 1% and the overall annual RMSE was 20.9%, but results varied with season.
Abstract Context The introduction of magnetic resonance imaging-guided biopsies (MRI-GB) has changed the paradigm concerning prostate biopsies. Three techniques of MRI-GB are available: (1) in-bore ...MRI target biopsy (MRI-TB), (2) MRI-transrectal ultrasound fusion (FUS-TB), and (3) cognitive registration (COG-TB). Objective To evaluate whether MRI-GB has increased detection rates of (clinically significant) prostate cancer (PCa) compared with transrectal ultrasound-guided biopsy (TRUS-GB) in patients at risk for PCa, and which technique of MRI-GB has the highest detection rate of (clinically significant) PCa. Evidence acquisition We performed a literature search in PubMed, Embase, and CENTRAL databases. Studies were evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 checklist and START recommendations. The initial search identified 2562 studies and 43 were included in the meta-analysis. Evidence synthesis Among the included studies 11 used MRI-TB, 17 used FUS-TB, 11 used COG-TB, and four used a combination of techniques. In 34 studies concurrent TRUS-GB was performed. There was no significant difference between MRI-GB (all techniques combined) and TRUS-GB for overall PCa detection (relative risk RR 0.97 0.90–1.07). MRI-GB had higher detection rates of clinically significant PCa (csPCa) compared with TRUS-GB (RR 1.16 1.02–1.32), and a lower yield of insignificant PCa (RR 0.47 0.35–0.63). There was a significant advantage ( p = 0.02) of MRI-TB compared with COG-TB for overall PCa detection. For overall PCa detection there was no significant advantage of MRI-TB compared with FUS-TB ( p = 0.13), and neither for FUS-TB compared with COG-TB ( p = 0.11). For csPCa detection there was no significant advantage of any one technique of MRI-GB. The impact of lesion characteristics such as size and localisation could not be assessed. Conclusions MRI-GB had similar overall PCa detection rates compared with TRUS-GB, increased rates of csPCa, and decreased rates of insignificant PCa. MRI-TB has a superior overall PCa detection compared with COG-TB. FUS-TB and MRI-TB appear to have similar detection rates. Head-to-head comparisons of MRI-GB techniques are limited and are needed to confirm our findings. Patient summary Our review shows that magnetic resonance imaging-guided biopsy detects more clinically significant prostate cancer (PCa) and less insignificant PCa compared with systematic biopsy in men at risk for PCa.
Guidelines advise multiparametric magnetic resonance imaging (mpMRI) before repeat biopsy in patients with negative systematic biopsy (SB) and a suspicion of prostate cancer (PCa), enabling MRI ...targeted biopsy (TB). No consensus exists regarding which of the three available techniques of TB should be preferred.
To compare detection rates of overall PCa and clinically significant PCa (csPCa) for the three MRI-based TB techniques.
Multicenter randomised controlled trial, including 665 men with prior negative SB and a persistent suspicion of PCa, conducted between 2014 and 2017 in two nonacademic teaching hospitals and an academic hospital.
All patients underwent 3-T mpMRI evaluated with Prostate Imaging Reporting and Data System (PIRADS) version 2. If imaging demonstrated PIRADS ≥3 lesions, patients were randomised 1:1:1 for one TB technique: MRI-transrectal ultrasound (TRUS) fusion TB (FUS-TB), cognitive registration TRUS TB (COG-TB), or in-bore MRI TB (MRI-TB).
Primary (overall PCa detection) and secondary (csPCa detection Gleason score ≥3+4) outcomes were compared using Pearson chi-square test.
On mpMRI, 234/665 (35%) patients had PIRADS ≥3 lesions and underwent TB. There were no significant differences in the detection rates of overall PCa (FUS-TB 49%, COG-TB 44%, MRI-TB 55%, p=0.4). PCa detection rate differences were −5% between FUS-TB and MRI-TB (p=0.5, 95% confidence interval CI −21% to 11%), 6% between FUS-TB and COG-TB (p=0.5, 95% CI −10% to 21%), and −11% between COG-TB and MRI-TB (p=0.17, 95% CI −26% to 5%). There were no significant differences in the detection rates of csPCa (FUS-TB 34%, COG-TB 33%, MRI-TB 33%, p>0.9). Differences in csPCa detection rates were 2% between FUS-TB and MRI-TB (p=0.8, 95% CI −13% to 16%), 1% between FUS-TB and COG-TB (p>0.9, 95% CI −14% to 16%), and 1% between COG-TB and MRI-TB (p>0.9, 95% CI −14% to 16%). The main study limitation was a low rate of PIRADS ≥3 lesions on mpMRI, causing underpowering for primary outcome.
We found no significant differences in the detection rates of (cs)PCa among the three MRI-based TB techniques.
In this study, we compared the detection rates of (aggressive) prostate cancer among men with prior negative biopsies and a persistent suspicion of cancer using three different techniques of targeted biopsy based on magnetic resonance imaging. We found no significant differences in the detection rates of (aggressive) prostate cancer among the three techniques.
In a repeat biopsy setting, multiparametric magnetic resonance imaging (mpMRI)-based targeted biopsy has a high detection rate of (clinically significant) prostate cancer. There were no significant differences in the detection rates of (clinically significant) prostate cancer among three techniques of mpMRI-based targeted biopsy.
Techniques to treat urethral stricture and hypospadias are restricted, as substitution of the unhealthy urethra with tissue from other origins (skin, bladder or buccal mucosa) has some limitations. ...Therefore, alternative sources of tissue for use in urethral reconstructions are considered, such as ex vivo engineered constructs.
To review recent literature on tissue engineering for human urethral reconstruction.
A search was made in the PubMed and Embase databases restricted to the last 25 years and the English language.
A total of 45 articles were selected describing the use of tissue engineering in urethral reconstruction. The results are discussed in four groups: autologous cell cultures, matrices/scaffolds, cell-seeded scaffolds, and clinical results of urethral reconstructions using these materials. Different progenitor cells were used, isolated from either urine or adipose tissue, but slightly better results were obtained with in vitro expansion of urothelial cells from bladder washings, tissue biopsies from the bladder (urothelium) or the oral cavity (buccal mucosa). Compared with a synthetic scaffold, a biological scaffold has the advantage of bioactive extracellular matrix proteins on its surface. When applied clinically, a non-seeded matrix only seems suited for use as an onlay graft. When a tubularized substitution is the aim, a cell-seeded construct seems more beneficial.
Considerable experience is available with tissue engineering of urethral tissue in vitro, produced with cells of different origin. Clinical and in vivo experiments show promising results.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study explores the rheological and tribological behavior of water-based lubricants (WBLs) as potential alternatives for electric vehicle (EV) applications. As the transportation sector ...increasingly shifts towards EVs to reduce carbon emissions, the demand for efficient lubricants becomes critical. WBLs here are defined as fluids containing a minimum of 50 wt% water mixed with glycerol, ethylene glycol (MEG), polyethylene glycol (PEG), or one of two polyalkylene glycols (PAGs). Rheological properties were investigated and compared with traditional lubricating oils. Results demonstrate distinctive rheological characteristics in WBLs, with viscosity–temperature responses resembling traditional oils with lowered pressure–viscosity coefficients. Nevertheless, WBLs exhibit promising film-forming capabilities in highly loaded contacts. Additionally, in sliding contacts, WBLs generally display lower friction coefficients compared to traditional oils, with PEG exhibiting the lowest value near 0.1. These findings suggest that WBLs may offer advantages in reducing friction and energy loss in EV applications. Furthermore, sliding wear tests indicate low wear rates in WBLs such as PEG, PAG, and glycerol, supporting their potential as viable lubrication options. The study highlights the importance of high-pressure rheology and tribochemistry in wear mechanisms among the different lubricants.
Recent research on management innovation, i.e. new managerial processes, practices, or structures that change the nature of managerial work, suggests it can be an important source of competitive ...advantage. In this study, we focus on management innovation at the organization level and investigate the role of leadership behaviour as a key antecedent. Due to its prominent role within organizations, top management has the ability to greatly influence management innovation. In particular, we focus on leadership behaviour and examine transformational and transactional leadership. Additionally, as contextual variables like organizational size may influence the impact of leadership, we investigate its moderating role. Findings show that both leadership behaviours contribute to management innovation. Interestingly, our study indicates that smaller, less complex, organizations benefit more from transactional leadership in realizing management innovation. On the other hand, larger organizations need to draw on transformational leaders to compensate for their complexity and allow management innovation to flourish.
Previous research focuses on firm and business unit level ambidexterity. Therefore, conceptual and empirically validated understanding about ambidexterity at the individual level of analysis is very ...scarce. This paper addresses this gap in the literature by investigating managers' ambidexterity, delivering three contributions to theory and empirical research on ambidexterity: first, by proposing three related characteristics of ambidextrous managers; second, by developing a model and associated hypotheses on both the direct and interaction effects of formal structural and personal coordination mechanisms on managers' ambidexterity; and third, by testing the hypotheses based on a sample of 716 business unit level and operational level managers.
Findings regarding the formal structural mechanisms indicate that a manager's decision-making authority positively relates to this manager's ambidexterity, whereas formalization of a manager's tasks has no significant relationship with this manager's ambidexterity. Regarding the personal coordination mechanisms, findings indicate that both the participation of a manager in cross-functional interfaces and the connectedness of a manager to other organization members positively relate to this manager's ambidexterity. Furthermore, results show positive interaction effects between the formal structural and personal coordination mechanisms on managers' ambidexterity. The paper's theoretical contributions and empirical results increase our understanding about managers' ambidexterity and about how different types and combinations of coordination mechanisms relate to variation in managers' ambidexterity.
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