关键词： competing risks   hazard ratio   hypothesis testing   restricted mean time lost   sample size   survival analysis  

摘要： In clinical and epidemiologic studies, hazard ratios are often applied to compare treatment effects between 2 groups for survival data. For competing-risks data, the corresponding quantities of interest are cause-specific hazard ratios and subdistribution hazard ratios. However, they both have some limitations related to model assumptions and clinical interpretation. Therefore, we recommend restricted mean time lost (RMTL) as an alternative measure that is easy to interpret in a competing-risks framework. Based on the difference in RMTL (RMTLd), we propose a new estimator, hypothetical test, and sample-size formula. Simulation results show that estimation of the RMTLd is accurate and that the RMTLd test has robust statistical performance (both type I error and statistical power). The results of 3 example analyses also verify the performance of the RMTLd test. From the perspectives of clinical interpretation, application conditions, and statistical performance, we recommend that the RMTLd be reported along with the hazard ratio in analyses of competing-risks data and that the RMTLd even be regarded as the primary outcome when the proportional hazards assumption fails.

关键词： Hemopatch   Laparoscopic partial nephrectomy   Veriset   Hemostasis   Complication  

摘要： Background Improvements in laparoscopic partial nephrectomy (LPN) in order to minimize perioperative warm ischemia time (WIT), complications, and consequently patient outcome are desirable. Veriset (TM) is a ready-to-use hemostatic patch of absorbable oxidized cellulose and hydrogel components that has earlier been implemented in vascular and hepatic surgery. We report our experience using this device in LPN. Methods Patients with a solitary malignant renal mass suspicious for renal cancer underwent LPN with either the use of Veriset (TM) hemostatic patch (n = 40) or conventional suture technique (n = 40). Patient characteristics, operation time and WIT, postoperative course and complications were recorded retrospectively. Tumor complexity was calculated according to the R.E.N.A.L. score. Outcome was determined according to the "trifecta" criteria (negative surgical margin, WIT < 25 min, no complications within 30 days). Results No significant differences with regard to clinical parameters and median R.E.N.A.L. score (6) were observed between both groups. Operation time (mean 127.1 min vs. 162. 8 min;p = 0.001) and WIT were both lower in the Veriset (TM) group (14.6 min vs. 20.6 min;p = 0.01). No differences in surgical margins (p = 0.602) and overall complication rates at 30 (p = 0.599) and 90 days (p = 0.611) postoperatively were noticed. The surgical outcome according to "trifecta" was achieved in 65% of patients using Veriset (TM) and in 57.5% of patients by suture closure, respectively. Conclusion The hemostatic Veriset (TM) patch can successfully be implemented in LPN. Handling and application appear favorable, thereby reducing operation time and WIT. The present results suggest that the device may represent an alternative to parenchyma suturing in LPN.

关键词： maternal health services   quality improvement   length of stay   patient satisfaction  

摘要： Background Patients in remote communities who risk premature delivery require transfer to a tertiary care centre for obstetric and neonatal care. Following stabilisation, many patients are candidates for outpatient management but cannot be discharged to their home communities due to lack of neonatal intensive care unit (ICU) support. Problem Without outpatient accommodation proximal to neonatal ICU, these patients face prolonged hospitalisation-an expensive option with medical, social and psychological consequences. Therefore, we sought to establish an alternative accommodation for out-of-town stable antepartum patients. Methods Quality Improvement approaches were used to identify process strengths and opportunities for improvement on the antepartum ward in a tertiary care centre. Physician and patient surveys informed outpatient accommodation programme development by a multidisciplinary team. The intervention was implemented using a plan-do-study-act cycle. Barriers to patient discharge and enrolment in the programme were analysed by completing thematic and strengths-weaknesses-opportunities-threats (SWOT) analysis. Results Physicians broadly supported safe outpatient management, whereas patients were hesitant to leave the hospital even when physicians assured safety. Our alternative accommodation was pre-existing and cost-effective, however, we encountered significant barriers. The physical space limited family visits and social interaction, lacked desired amenities,and the programme proved inconvenient to patients. The thematic and SWOT analysis identified aspects of the intervention which can be optimised to develop future actionable strategies. Conclusion The utilisation of acute care beds is costly for the healthcare system and must be allocated judiciously. Patient needs, experience and health system barriers need to be considered when establishing alternative outpatient accommodations and strategies for stable antepartum patients.

关键词： food protein-induced enterocolitis syndrome (FPIES)   fish   bony fish   cartilaginous fish  

摘要： In the Mediterranean region, fish is a common cause of food protein-induced enterocolitis syndrome (FPIES) in children. No laboratory tests specific to FPIES are available, and oral food challenge (OFC) is the gold standard for its diagnosis and testing for achievement of tolerance. Children with FPIES to fish are usually advised to avoid all fish, regardless of the species. Fish are typically classified into bony and cartilaginous, which are phylogenetically distant species and therefore contain less cross-reacting allergens. The protein beta-parvalbumin, considered a pan-allergenic, is found in bony fish, while the non-allergenic alpha-parvalbumin is commonly found in cartilaginous fish. Based on this difference, as a first step in the therapeutic process of children with FPIES caused by a certain fish in the bony fish category (i.e., hake, cod, perch, sardine, gilthead sea bream, red mullet, sole, megrim, sea bass, anchovy, tuna, swordfish, trout, etc.), an OFC to an alternative from the category of cartilaginous fish is suggested (i.e., blue shark, tope shark, dogfish, monkfish, skate, and ray) and vice versa. Regarding the increased mercury content in some sharks and other large species, the maximum limit imposed by the European Food Safety Authority (EFSA) for weekly mercury intake must be considered. An algorithm for the management of fish-FPIES, including alternative fish species, is proposed.

关键词： Microalgae   Electrocoagulation optimization   Harvesting   Biomass valorisation   Metal recovery  

摘要： Electrocoagulation is a promising technology to harvest microalgal biomass. However, the commonly used aluminum electrodes release undesired salts that decrease biomass value. In this study, alternative iron, zinc, and magnesium electrodes and operational parameters pH, time and current density were studied to harvest Nannochloropsis oceanica. For recovery efficiency and concentration factor the initial pH was most important using iron electrodes, while time and current density were more relevant using zinc and magnesium electrodes. Optimal parameters resulted in biomass recovery efficiencies > 95%, biomass was concentrated 2.8-7.2 times and contained 15.7-29.1% ashes. Elemental analysis revealed metal salts in harvested biomass resulting from electrode corrosion. Finally, ash contents could be reduced by 65% using EDTA as a chelating agent. The electrocoagulation harvested microalgal biomass enriched in essential metals may be a promising bioresource for agricultural growth inducers, or functional ingredients for feed.

关键词： human-computer interface   human movement analysis   cerebral palsy   hidden Markov model   assistive technology  

摘要： The use of assistive technologies can mitigate or reduce the challenges faced by individuals with motor disabilities to use computer systems. However, those who feature severe involuntary movements often have fewer options at hand. This work describes an application that can recognize the user's head using a conventional webcam, track its motion, model the desired functional movement, and recognize it to enable the use of a virtual keyboard. The proposed classifier features a flexible structure and may be personalized for different user need. Experimental results obtained with participants with no neurological disorders have shown that classifiers based on Hidden Markov Models provided similar or better performance than a classifier based on position threshold. However, motion segmentation and interpretation modules were sensitive to involuntary movements featured by participants with cerebral palsy that took part in the study.

关键词： Computer-assisted diagnosis   Early detection of cancer   Pulmonary nodules   Artificial intelligence   Computed tomography  

摘要： Objective: To evaluate the performance of a deep learning-based computer-aided detection (DL-CAD) system in a Chinese low-dose CT (LDCT) lung cancer screening program. Materials and methods: One-hundred-and-eighty individuals with a lung nodule on their baseline LDCT lung cancer screening scan were randomly mixed with screenees without nodules in a 1:1 ratio (total: 360 individuals). All scans were assessed by double reading and subsequently processed by an academic DL-CAD system. The findings of double reading and the DL-CAD system were then evaluated by two senior radiologists to derive the reference standard. The detection performance was evaluated by the Free Response Operating Characteristic curve, sensitivity and false-positive (FP) rate. The senior radiologists categorized nodules according to nodule diameter, type (solid, part-solid, non-solid) and Lung-RADS. Results: The reference standard consisted of 262 nodules >= 4 mm in 196 individuals;359 findings were considered false positives. The DL-CAD system achieved a sensitivity of 90.1% with 1.0 FP/scan for detection of lung nodules regardless of size or type, whereas double reading had a sensitivity of 76.0% with 0.04 FP/scan (P = 0.001). The sensitivity for detection of nodules >= 4 - <= 6 mm was significantly higher with DL-CAD than with double reading (86.3% vs. 58.9% respectively;P = 0.001). Sixty-three nodules were only identified by the DL-CAD system, and 27 nodules only found by double reading. The DL-CAD system reached similar performance compared to double reading in Lung-RADS 3 (94.3% vs. 90.0%, P = 0.549) and Lung-RADS 4 nodules (100.0% vs. 97.0%, P = 1.000), but showed a higher sensitivity in Lung-RADS 2 (86.2% vs. 65.4%, P < 0.001). Conclusions: The DL-CAD system can accurately detect pulmonary nodules on LDCT, with an acceptable false-positive rate of 1 nodule per scan and has higher detection performance than double reading. This DL-CAD system may assist radiologists in nodule detection in LDC

摘要： BACKGROUND: Chronic arsenic exposure via drinking water is associated with an increased risk of developing cancer and noncancer chronic diseases. Pre-mRNAs are often subject to alternative splicing, generating mRNA isoforms encoding functionally distinct protein isoforms. The resulting imbalance in isoform species can result in pathogenic changes in critical signaling pathways. Alternative splicing as a mechanism of arsenic-induced toxicity and carcinogenicity is understudied. OBJECTIVE: This study aimed to accurately profile differential alternative splicing events in human keratinocytes induced by chronic arsenic exposure that might play a role in carcinogenesis. METHODS: Independent quadruplicate cultures of immortalized human keratinocytes (HaCaT) were maintained continuously for 28 wk with 0 or 100 nM sodium arsenite. RNA-sequencing (RNA-Seq) was performed with poly(A) RNA isolated from cells harvested at 7, 19, and 28 wk with subsequent replicate multivariate analysis of transcript splicing (rMATS) analysis to detect and quantify differential alternative splicing events. Reverse transcriptase-polymerase chain reaction (RT-PCR) for selected alternative splicing events was performed to validate RNA-Seq predictions. Functional enrichment was performed by gene ontology (GO) analysis of the differential alternative splicing event data set at each time point. RESULTS: At least 600 differential alternative splicing events were detected at each time point tested, comprising all the five main types of alternative splicing and occurring in both open reading frames (ORFs) and untranslated regions (UTRs). Based on functional relevance ELK4, SHC1, and XRRA1 were selected for validation of predicted alternative splicing events at 7 wk by RT-PCR. Densitometric analysis of RT-PCR data corroborated the rMATS predicted alternative splicing for all three events. Protein expression validation of the selected alternative splicing events was challenging given that very few isoform-

关键词： Human Genetics   Molecular Medicine   Gene Function   Metabolic Diseases  

摘要： The discovery of introns over four decades ago revealed a new vision of genes and their interrupted arrangement. Throughout the years, it has appeared that introns play essential roles in the regulation of gene expression. Unique processing of excised introns through the formation of lariats suggests a widespread role for these molecules in the structure and function of cells. In addition to rapid destruction, these lariats may linger on in the nucleus or may even be exported to the cytoplasm, where they remain stable circular RNAs (circRNAs). Alternative splicing (AS) is a source of diversity in mature transcripts harboring retained introns (RI-mRNAs). Such RNAs may contain one or more entire retained intron(s) (RIs), but they may also have intron fragments resulting from sequential excision of smaller subfragments via recursive splicing (RS), which is characteristic of long introns. There are many potential fates of RI-mRNAs, including their downregulation via nuclear and cytoplasmic surveillance systems and the generation of new protein isoforms with potentially different functions. Various reports have linked the presence of such unprocessed transcripts in mammals to important roles in normal development and in disease-related conditions. In certain human neurological-neuromuscular disorders, including myotonic dystrophy type 2 (DM2), frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS) and Duchenne muscular dystrophy (DMD), peculiar processing of long introns has been identified and is associated with their pathogenic effects. In this review, we discuss different mechanisms involved in the processing of introns during AS and the functions of these large sections of the genome in our biology.