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Incisional hernia is a frequent long-term complication after abdominal surgery, with a prevalence greater than 30% in high-risk groups. The aim of the PRIMA trial was to evaluate the effectiveness of mesh reinforcement in high-risk patients, to prevent incisional hernia. We did a multicentre, double-blind, randomised controlled trial at 11 hospitals in Austria, Germany, and the Netherlands. We included patients aged 18 years or older who were undergoing elective midline laparotomy and had either an abdominal aortic aneurysm or a body-mass index (BMI) of 27 kg/m2 or higher. We randomly assigned participants using a computer-generated randomisation sequence to one of three treatment groups: primary suture; onlay mesh reinforcement; or sublay mesh reinforcement. The primary endpoint was incidence of incisional hernia during 2 years of follow-up, analysed by intention to treat. Adjusted odds ratios (ORs) were estimated by logistic regression. This trial is registered at ClinicalTrials.gov, number NCT00761475. Between March, 2009, and December, 2012, 498 patients were enrolled to the study, of whom 18 were excluded before randomisation. Therefore, we included 480 patients in the primary analysis: 107 were assigned primary suture only, 188 were allocated onlay mesh reinforcement, and 185 were assigned sublay mesh reinforcement. 92 patients were identified with an incisional hernia, 33 (30%) who were allocated primary suture only, 25 (13%) who were assigned onlay mesh reinforcement, and 34 (18%) who were assigned sublay mesh reinforcement (onlay mesh reinforcement vs primary suture, OR 0·37, 95% CI 0·20–0·69; p=0·0016; sublay mesh reinforcement vs primary suture, 0·55, 0·30–1·00; p=0·05). Seromas were more frequent in patients allocated onlay mesh reinforcement (34 of 188) than in those assigned primary suture (five of 107; p=0·002) or sublay mesh reinforcement (13 of 185; p=0·002). The incidence of wound infection did not differ between treatment groups (14 of 107 primary suture; 25 of 188 onlay mesh reinforcement; and 19 of 185 sublay mesh reinforcement). A significant reduction in incidence of incisional hernia was achieved with onlay mesh reinforcement compared with sublay mesh reinforcement and primary suture only. Onlay mesh reinforcement has the potential to become the standard treatment for high-risk patients undergoing midline laparotomy. Baxter; B Braun Surgical SA.

Previously, we proposed a likelihood ratio system for pairwise source comparison of gunshot residue (GSR) samples based on elemental composition. Only pairs of GSR samples from the same location type (e.g., hand-hand) were considered, as the data originates from casework and ground truth is not available for samples from different location types (e.g., hand-cartridge case). This lack of sample pairs taken from different locations is a limitation, as casework will usually require such sample pairs to be evaluated. In this study, we test the impact of this sampling location limitation by evaluating the model with an experimental dataset for which ground truth was available for same-location as well as different-location pairs. We find a sharp decline in the performance of the model, with Cllr deteriorating from 0.35 to 0.98. Additional exploration of various system extensions does not lead to significant improvements. We discuss the potential causes for this decline and conclude the system is not currently ready for application in forensic casework. •We validate an LR system for forensic source comparison of gunshot residue samples.•We find that performance drops to near random for different-location comparisons.•We conclude that the LR system is not currently ready for application in casework.

Endovascular repair of abdominal aortic aneurysms avoids much of the risk associated with conventional surgical repair. In two randomized trials, this technique has been shown to be associated with lower rates of perioperative morbidity and mortality. Longer-term follow-up data from one of these trials (the Dutch Randomized Endovascular Aneurysm Management [DREAM] trial) show that the survival advantage of endovascular repair is not sustained after the first postoperative year. Endovascular repair of abdominal aortic aneurysms has been shown to be associated with lower rates of perioperative morbidity and mortality. Longer-term follow-up data show that the survival advantage of endovascular repair is not sustained after the first postoperative year. Two randomized trials have demonstrated better outcomes with elective endovascular repair of abdominal aortic aneurysms than with conventional open repair in the first month after the procedure. 1 , 2 The reported in-hospital mortality rates in these two trials were 4.6 percent and 6.0 percent for open repair and 1.6 percent and 1.2 percent for endovascular repair, respectively. Although the relevance of a reduction in perioperative risk should not be underestimated from the patient's perspective, the improvement in early survival with the use of a less invasive technique is not surprising. 3 Consequently, both reports stressed the need for longer-term data before a . . .

Abnormal (deviating from the target) variations in the plasma vertical position Z and current Ip (such as vertical displacements, transient Ip ‘spikes’ and quenches) constitute common elements of a disruption, a phenomenon that is to be mitigated, or ultimately avoided in future reactor-relevant tokamaks. While these abnormalities are generally recognized cross-shot and cross-device, details in terms of appearance (or not) and order of these abnormalities in disruption event chains (DEC) are bound to the plasma state at the time of the chain initiation. Detection of these abnormalities is thus indicative not only of the onset of the plasma collapse itself but also of the disruption driving cause that is promoted at a particular plasma state. Here, the occurrence of disruptions, explored via the detection of an Ip quench, and the analysis of DEC constituted by Ip and Z abnormalities is reported for in total seven full device-year pairs of operation of three machines (4, 2 and 1 years of KSTAR, MAST-U and NSTX-U operation, respectively) using the DECAF code expanded tools and capabilities. It is shown that the disruption occurrence depends not only on the details of the plasma state but also on (device-dependent) technical elements of the shot exit scenario. Year-to-year changes in the main disruption causes and a reduction in the disruptivity rate, bound by device and operation upgrades, are reported. Particular trigger instances of DEC (and the full chains when applicable) are shown to occupy different parts of the operation space diagrams, in accordance with prior expectations. Plasma elongation is identified as an important factor influencing details of the chains and its role will be further explored.

Various environmental signals integrate into a network of floral regulatory genes leading to the final decision on when to flower. Although a wealth of qualitative knowledge is available on how flowering time genes regulate each other, only a few studies incorporated this knowledge into predictive models. Such models are invaluable as they enable to investigate how various types of inputs are combined to give a quantitative readout. To investigate the effect of gene expression disturbances on flowering time, we developed a dynamic model for the regulation of flowering time in Arabidopsis thaliana. Model parameters were estimated based on expression time-courses for relevant genes, and a consistent set of flowering times for plants of various genetic backgrounds. Validation was performed by predicting changes in expression level in mutant backgrounds and comparing these predictions with independent expression data, and by comparison of predicted and experimental flowering times for several double mutants. Remarkably, the model predicts that a disturbance in a particular gene has not necessarily the largest impact on directly connected genes. For example, the model predicts that SUPPRESSOR OF OVEREXPRESSION OF CONSTANS (SOC1) mutation has a larger impact on APETALA1 (AP1), which is not directly regulated by SOC1, compared to its effect on LEAFY (LFY) which is under direct control of SOC1. This was confirmed by expression data. Another model prediction involves the importance of cooperativity in the regulation of APETALA1 (AP1) by LFY, a prediction supported by experimental evidence. Concluding, our model for flowering time gene regulation enables to address how different quantitative inputs are combined into one quantitative output, flowering time.

Inference of protein functions is one of the most important aims of modern biology. To fully exploit the large volumes of genomic data typically produced in modern-day genomic experiments, automated computational methods for protein function prediction are urgently needed. Established methods use sequence or structure similarity to infer functions but those types of data do not suffice to determine the biological context in which proteins act. Current high-throughput biological experiments produce large amounts of data on the interactions between proteins. Such data can be used to infer interaction networks and to predict the biological process that the protein is involved in. Here, we develop a probabilistic approach for protein function prediction using network data, such as protein-protein interaction measurements. We take a Bayesian approach to an existing Markov Random Field method by performing simultaneous estimation of the model parameters and prediction of protein functions. We use an adaptive Markov Chain Monte Carlo algorithm that leads to more accurate parameter estimates and consequently to improved prediction performance compared to the standard Markov Random Fields method. We tested our method using a high quality S. cereviciae validation network with 1622 proteins against 90 Gene Ontology terms of different levels of abstraction. Compared to three other protein function prediction methods, our approach shows very good prediction performance. Our method can be directly applied to protein-protein interaction or coexpression networks, but also can be extended to use multiple data sources. We apply our method to physical protein interaction data from S. cerevisiae and provide novel predictions, using 340 Gene Ontology terms, for 1170 unannotated proteins and we evaluate the predictions using the available literature.

Background Laparoscopic surgery has become popular during the last decade, mainly because it is associated with fewer postoperative complications than the conventional open approach. It remains unclear, however, if this benefit is observed after laparoscopic correction of perforated peptic ulcer (PPU). The goal of the present study was to evaluate whether laparoscopic closure of a PPU is as safe as conventional open correction. Methods The study was based on a randomized controlled trial in which nine medical centers from the Netherlands participated. A total of 109 patients with symptoms of PPU and evidence of air under the diaphragm were scheduled to receive a PPU repair. After exclusion of 8 patients during the operation, outcomes were analyzed for laparotomy ( n  = 49) and for the laparoscopic procedure ( n  = 52). Results Operating time in the laparoscopy group was significantly longer than in the open group (75 min versus 50 min). Differences regarding postoperative dosage of opiates and the visual analog scale (VAS) for pain scoring system were in favor of the laparoscopic procedure. The VAS score on postoperative days 1, 3, and 7 was significant lower ( P  < 0.05) in the laparoscopic group. Complications were equally distributed. Hospital stay was also comparable: 6.5 days in the laparoscopic group versus 8.0 days in the open group ( P  = 0.235). Conclusions Laparoscopic repair of PPU is a safe procedure compared with open repair. The results considering postoperative pain favor the laparoscopic procedure.

Saccharomyces cerevisiae CEN.PK 113-7D is widely used for metabolic engineering and systems biology research in industry and academia. We sequenced, assembled, annotated and analyzed its genome. Single-nucleotide variations (SNV), insertions/deletions (indels) and differences in genome organization compared to the reference strain S. cerevisiae S288C were analyzed. In addition to a few large deletions and duplications, nearly 3000 indels were identified in the CEN.PK113-7D genome relative to S288C. These differences were overrepresented in genes whose functions are related to transcriptional regulation and chromatin remodelling. Some of these variations were caused by unstable tandem repeats, suggesting an innate evolvability of the corresponding genes. Besides a previously characterized mutation in adenylate cyclase, the CEN.PK113-7D genome sequence revealed a significant enrichment of non-synonymous mutations in genes encoding for components of the cAMP signalling pathway. Some phenotypic characteristics of the CEN.PK113-7D strains were explained by the presence of additional specific metabolic genes relative to S288C. In particular, the presence of the BIO1 and BIO6 genes correlated with a biotin prototrophy of CEN.PK113-7D. Furthermore, the copy number, chromosomal location and sequences of the MAL loci were resolved. The assembled sequence reveals that CEN.PK113-7D has a mosaic genome that combines characteristics of laboratory strains and wild-industrial strains.

Several genome-wide studies demonstrated that alternative splicing (AS) significantly increases the transcriptome complexity in plants. However, the impact of AS on the functional diversity of proteins is difficult to assess using genome-wide approaches. The availability of detailed sequence annotations for specific genes and gene families allows for a more detailed assessment of the potential effect of AS on their function. One example is the plant MADS-domain transcription factor family, members of which interact to form protein complexes that function in transcription regulation. Here, we perform an in silico analysis of the potential impact of AS on the protein-protein interaction capabilities of MIKC-type MADS-domain proteins. We first confirmed the expression of transcript isoforms resulting from predicted AS events. Expressed transcript isoforms were considered functional if they were likely to be translated and if their corresponding AS events either had an effect on predicted dimerisation motifs or occurred in regions known to be involved in multimeric complex formation, or otherwise, if their effect was conserved in different species. Nine out of twelve MIKC MADS-box genes predicted to produce multiple protein isoforms harbored putative functional AS events according to those criteria. AS events with conserved effects were only found at the borders of or within the K-box domain. We illustrate how AS can contribute to the evolution of interaction networks through an example of selective inclusion of a recently evolved interaction motif in the MADS AFFECTING FLOWERING1-3 (MAF1-3) subclade. Furthermore, we demonstrate the potential effect of an AS event in SHORT VEGETATIVE PHASE (SVP), resulting in the deletion of a short sequence stretch including a predicted interaction motif, by overexpression of the fully spliced and the alternatively spliced SVP transcripts. For most of the AS events we were able to formulate hypotheses about the potential impact on the interaction capabilities of the encoded MIKC proteins.

Key summary points Aim Development of a new frailty assessment that can be administered by outpatient care nurses, the nurse directed frailty assessment (NDFA). Findings The NDFA identifies patients at risk for hospitalisation, emergency department visits, and mortality within 12 months equally well as the comprehensive geriatric assessment (CGA)-based frailty index. Message The NDFA can help with selection of patients that might benefit from a referral to a Geriatrician, and future research is necessary to determine the effectiveness of the NDFA in other settings than the geriatric medicine outpatient population. Methods This is a validation study of a new frailty assessment that can be administered by outpatient care nurses. The nurse directed frailty assessment (NDFA) encompasses the medical, psychological, social, and functional domain, based on standard care, and can be performed without any specialised equipment. Performance of the NDFA is compared to a comprehensive geriatric assessment (CGA)-based frailty index (FI), with generalised linear model with reporting of hazard ratios (HR) and 95% confidence intervals (95% CI). The best cutoff value for the NDFA was assessed by Youden index and the area under the receiver operator curve (ROC). Results Within 1 year, 15 patients (5%) died, 57 (18%) had an unplanned hospital admission, and 83 (26%) visited the emergency department (ED). Based on the Youden index and ROC curve, the best cutoff value for the NDFA was 4 points. With a binary logistic regression model, an HR of 3.59 (95% CI 1.16–11.15, p  < 0.001) was found for mortality. In the general mixed model with Poisson logistic regression, an HR of 1.78 (95% CI 1.06–2.97, p 0.028) was found for unplanned hospital and an HR of 1.87 (95% CI 1.25–2.78, p 0.002) was found for ED visits. The HR and 95% CI of the FI were similar for all three outcome measures. Conclusions The NDFA identifies patients at risk for hospitalisation, emergency department visits, and mortality within 12 months equally well as the FI. Further research is necessary to determine the effectiveness of the NDFA in other settings than the geriatric medicine outpatient population.