Insights into the Influence of Priors in Posterior Mapping of Discrete Morphological Characters: A Case Study in Annonaceae

Background - Posterior mapping is an increasingly popular hierarchical Bayesian based method used to infer character histories and reconstruct ancestral states at nodes of molecular phylogenies, notably of morphological characters. As for all Bayesian analyses specification of prior values is an integrative and important part of the analysis. He we provide an example of how alternative prior choices can seriously influence results and mislead interpretations. Methods/Principal Findings - For two contrasting discrete morphological characters, namely a slow and a fast evolving character found in the plant family Annonaceae, we specified a total of eight different prior distributions per character. We investigated how these prior settings affected important summary statistics. Our analyses showed that the different prior distributions had marked effects on the results in terms of average number of character state changes. These differences arise because priors play a crucial role in determining which areas of parameter space the values of the simulation will be drawn from, independent of the data at hand. However, priors seemed to fit the data better if they would result in a more even sampling of parameter space (normal posterior distribution), in which case alternative standard deviation values had little effect on the results. The most probable character history for each character was affected differently by the prior. For the slower evolving character, the same character history always had the highest posterior probability independent of the priors used. In contrast, the faster evolving character showed different most probable character histories depending on the prior. These differences could be related to the level of homoplasy exhibited by each character. Conclusions - Although our analyses were restricted to two morphological characters within a single family, our results underline the importance of carefully choosing prior values for posterior mapping. Prior specification will be of crucial importance when interpreting the results in a meaningful way. It is hard to suggest a statistically sound method for prior specification without more detailed studies. Meanwhile, we propose that the data could be used to estimate the prior value of the gamma distribution placed on the transformation rate in posterior mappin

Phase I trial of the combination of the Akt inhibitor nelfinavir and chemoradiation for locally advanced rectal cancer

PURPOSE: To investigate the toxicity of nelfinavir, administered during preoperative chemoradiotherapy (CRT) in patients with locally advanced cancer. MATERIAL AND METHODS: Twelve patients were treated with to 50.4Gy combined with capecitabine 825mg/m2 BID. Three dose levels nelfinavir were tested: 750mg BID (DL1), 1250mg BID (DL2) and an level of 1000mg BID (DL3). Surgery was performed between 8 and 10weeks completion of CRT. Primary endpoint was dose-limiting toxicity (DLT), any grade 3 or higher non-hematological or grade 4 or higher toxicity. RESULTS: Eleven patients could be analyzed: 5 were treated in DL2 and 3 in DL3. The first 3 patients in DL1 did not develop a DLT. In patient developed gr 3 diarrhea, 1 patient had gr 3 transaminase patient had a gr 3 cholangitis with unknown cause. An intermediate dose tested in DL3. In this group 2 patients developed gr 3 diarrhea and 1 3 transaminase elevation and gr 4 post-operative wound complication. patients achieved a pathological complete response (pCR). CONCLUSIONS: 750mg BID was defined as the recommended phase II dose in combination capecitabine and 50.4Gy pre-operative radiotherapy in rectal cancer. response evaluations are promising, but a further phase II study is more information about efficacy of this treatment regimen

Lymph node response to chemoradiotherapy in oesophageal cancer patients: relationship with radiotherapy fields

Background The presence of lymph node metastasis (LNmets) is a poor prognostic factor in oesophageal cancer (OeC) patients treated with neoadjuvant chemoradiotherapy (nCRT) followed by surgery. Tumour regression grade (TRG) in LNmets has been suggested as a predictor for survival. The aim of this study was to investigate whether TRG in LNmets is related to their location within the radiotherapy (RT) field. Methods Histopathological TRG was retrospectively classified in 2565 lymph nodes (LNs) from 117 OeC patients treated with nCRT and surgery as: (A) no tumour, no signs of regression; (B) tumour without regression; (C) viable tumour and regression; and (D) complete response. Multivariate survival analysis was used to investigate the relationship between LN location within the RT field, pathological TRG of the LN and TRG of the primary tumour. Results In 63 (54%) patients, viable tumour cells or signs of regression were seen in 264 (10.2%) LNs which were classified as TRG-B (n = 56), C (n = 104) or D (n = 104) LNs. 73% of B, C and D LNs were located within the RT field. There was a trend towards a relationship between LN response and anatomical LN location with respect to the RT field (p = 0.052). Multivariate analysis showed that only the presence of LNmets within the RT field with TRG-B is related to poor overall survival. Conclusion Patients have the best survival if all LNmets show tumour regression, even if LNmets are located outside the RT field. Response in LNmets to nCRT is heterogeneous which warrants further studies to better understand underlying mechanisms

A comparison between real-time intraoperative voice dictation and the operative report in laparoscopic cholecystectomy:a multicenter prospective observational study

Purpose: The current operative report often inadequately reflects events occurring during laparoscopic cholecystectomy (LC). The addition of intraoperative video recording to the operative report has already proven to add important information. It was hypothesized that real-time intraoperative voice dictation (RIVD) can provide an equal or more complete overview of the operative procedure compared to the narrative operative report (NR) produced postoperatively. Methods: SONAR is a multicenter prospective observational trial, conducted at four surgical centers in the Netherlands. Elective LCs of patients aged 18 years and older were included. Participating surgeons were requested to dictate the essential steps of LC during surgery. RIVDs and NRs were reviewed according to the stepwise LC guideline of the Dutch Society for Surgery. The cumulative adequacy rates for RIVDs were compared with those of the postoperatively written NR. Results: 79 of 90 cases were eligible for inclusion and available for further analysis. RIVD resulted in a significantly higher adequacy rate compared to NR for the circumferential dissection of the cystic duct and artery (NR 32.5% vs. RIVD 61.0%, P = 0.016). NR had higher adequacy rates in reporting the transection of the cystic duct (NR 100% vs. RIVD 77.9%, P = &lt; 0.001) and the removal of the gallbladder from the liver bed (NR 98.7% vs. RIVD 68.8%, P &lt; 0.001). The total adequacy was not significantly different between the two reporting methods (NR 78.0% vs. RIVD 76.4%, P = 1.00). Conclusion: Overall, the adequacy of RIVD is comparable to the postoperatively written NR in reporting surgical steps in LC. However, the most essential surgical step, the circumferential dissection of the cystic duct and artery, was reported more adequately in RIVD.</p

Effect of iso-energetic exchange of dietary fat and starch on growth performance and body composition of broilers : Experiment 1

Dietary factors such as the concentrations of protein/amino acids, fat, and starch + sugar and their ratio, may affect the post-absorptive metabolism of energy and protein and energy deposition in the body. In a 2x2 factorial design, the effects of two dietary crude protein (high protein (HP) vs. low protein (LP) concentrations; 200/190 vs. 170/160 g/kg in grower and finisher phase) and two dietary fat/starch concentrations; (high fat (HF); fat and starch 105 and 340 g/kg, respectively) and (low fat (LF); fat and starch 65 and 420 g/kg, respectively) on growth performance and body composition of Ross 308 broilers were studied (9 to 35 d). From this experiment it can be concluded that dietary energy source and protein level in iso-energetic diets, balanced for first limiting essential amino acids, influence growth performance and body composition of broilers

The Amsterdam wrist rules: The multicenter prospective derivation and external validation of a clinical decision rule for the use of radiography in acute wrist trauma

Background: Although only 39 % of patients with wrist trauma have sustained a fracture, the majority of patients is routinely referred for radiography. The purpose of this study was to derive and externally validate a clinical decision rule that selects patients with acute wrist trauma in the Emergency Department (ED) for radiography. Methods: This multicenter prospective study consisted of three components: (1) derivation of a clinical prediction model for detecting wrist fractures in patients following wrist trauma; (2) external validation of this model; and (3) design of a clinical decision rule. The study was conducted in the EDs of five Dutch hospitals: one academic hospital (derivation cohort) and four regional hospitals (external validation cohort). We included all adult patients with acute wrist trauma. The main outcome was fracture of the wrist (distal radius, distal ulna or carpal bones) diagnosed on conventional X-rays. Results: A total of 882 patients were analyzed; 487 in the derivation cohort and 395 in the validation cohort. We derived a clinical prediction model with eight variables: age; sex, swelling of the wrist; swelling of the anatomical snuffbox, visible deformation; distal radius tender to palpation; pain on radial deviation and painful axial compression of the thumb. The Area Under the Curve at external validation of this model was 0.81 (95 % CI: 0.77-0.85). The sensitivity and specificity of the Amsterdam Wrist Rules (AWR) in the external validation cohort were 98 % (95 % CI: 95-99 %) and 21 % (95 % CI: 15 %-28). The negative predictive value was 90 % (95 % CI: 81-99 %). Conclusions: The Amsterdam Wrist Rules is a clinical prediction rule with a high sensitivity and negative predictive value for fractures of the wrist. Although external validation showed low specificity and 100 % sensitivity could not be achieved, the Amsterdam Wrist Rules can provide physicians in the Emergency Department with a useful screening tool to select patients with acute wrist trauma for radiography. The upcoming implementation study will further reveal the impact of the Amsterdam Wrist Rules on the anticipated reduction of X-rays requested, missed fractures, Emergency Department waiting times and health care costs. Trial registration: This study was registered in the Dutch Trial Registry, reference number NTR2544 on October 1st, 2010

A clinical decision rule for the use of plain radiography in children after acute wrist injury: development and external validation of the Amsterdam Pediatric Wrist Rules

Background: In most hospitals, children with acute wrist trauma are routinely referred for radiography. Objective: To develop and validate a clinical decision rule to decide whether radiography in children with wrist trauma is required. Materials and methods: We prospectively developed and validated a clinical decision rule in two study populations. All children who presented in the emergency department of four hospitals with pain following wrist trauma were included and evaluated for 18 clinical variables. The outcome was a wrist fracture diagnosed by plain radiography. Results: Included in the study were 787 children. The prediction model consisted of six variables: age, swelling of the distal radius, visible deformation, distal radius tender to palpation, anatomical snuffbox tender to palpation, and painful or abnormal supination. The model showed an area under the receiver operator characteristics curve of 0.79 (95% CI: 0.76-0.83). The sensitivity and specificity were 95.9% and 37.3%, respectively. The use of this model would have resulted in a 22% absolute reduction of radiographic examinations. In a validation study, 7/170 fractures (4.1%, 95% CI: 1.7-8.3%) would have been missed using the decision model. Conclusion: The decision model may be a valuable tool to decide whether radiography in children after wrist trauma is required

ConR: An R package to assist large-scale multispecies preliminary conservation assessments using distribution data

Published online: 16 Dec 2017The Red List Categories and the accompanying five criteria developed by the International Union for Conservation of Nature (IUCN) provide an authoritative and comprehensive methodology to assess the conservation status of organisms. Red List criterion B, which principally uses distribution data, is the most widely used to assess conservation status, particularly of plant species. No software package has previously been available to perform large-scale multispecies calculations of the three main criterion B parameters [extent of occurrence (EOO), area of occupancy (AOO) and an estimate of the number of locations] and provide preliminary conservation assessments using an automated batch process. We developed ConR, a dedicated R package, as a rapid and efficient tool to conduct large numbers of preliminary assessments, thereby facilitating complete Red List assessment. ConR (1) calculates key geographic range parameters (AOO and EOO) and estimates the number of locations sensu IUCN needed for an assessment under criterion B; (2) uses this information in a batch process to generate preliminary assessments of multiple species; (3) summarize the parameters and preliminary assessments in a spreadsheet; and (4) provides a visualization of the results by generating maps suitable for the submission of full assessments to the IUCN Red List. ConR can be used for any living organism for which reliable georeferenced distribution data are available. As distributional data for taxa become increasingly available via large open access datasets, ConR provides a novel, timely tool to guide and accelerate the work of the conservation and taxonomic communities by enabling practitioners to conduct preliminary assessments simultaneously for hundreds or even thousands of species in an efficient and time-saving way

Routine versus on demand removal of the syndesmotic screw; a protocol for an international randomised controlled trial (RODEO-trial)

Background: Syndesmotic injuries are common and their incidence is rising. In case of surgical fixation of the syndesmosis a metal syndesmotic screw is used most often. It is however unclear whether this screw needs to be removed routinely after the syndesmosis has healed. Traditionally the screw is removed after six to 12 weeks as it is thought to hamper ankle functional and to be a source of pain. Some studies however suggest this is only the case in a minority of patients. We therefore aim to investigate the effect of retaining the syndesmotic screw on functional outcome. Design: This is a pragmatic international multicentre randomised controlled trial in patients with an acute syndesmotic injury for which a metallic syndesmotic screw was placed. Patients will be randomised to either routine removal of the syndesmotic screw or removal on demand. Primary outcome is functional recovery at 12 months measured with the Olerud-Molander Score. Secondary outcomes are quality of life, pain and costs. In total 194 patients will be needed to demonstrate non-inferiority between the two interventions at 80% power and a significance level of 0.025 including 15% loss to follow-up. Discussion: If removal on demand of the syndesmotic screw is non-inferior to routine removal in terms of functional outcome, this will offer a strong argument to adopt this as standard practice of care. This means that patients will not have to undergo a secondary procedure, leading to less complications and subsequent lower costs.Peer reviewe

Routine versus on demand removal of the syndesmotic screw; a protocol for an international randomised controlled trial (RODEO-trial) (vol 19, 35, 2018)

Peer reviewe