Modeling and prediction of surgical procedure times

Accurate prediction of medical operation times is of crucial importance for cost efficient operation room planning in hospitals. This paper investigates the possible dependence of procedure times on surgeon factors like age, experience, gender, and team composition. The effect of these factors is estimated for over 30 different types of medical operations in two hospitals, by means of ANOVA models for logarithmic case durations. The estimation data set contains about 30,000 observations from 2005 till 2008. The relevance of surgeon factors depends on the type of operation. The factors found most often to be significant are team composition, experience, and daytime. Contrary to widespread opinions among surgeons, gender has nearly never a significant effect. By incorporating surgeon factors, the accuracy of out-of-sample prediction of case durations of about 1,250 surgical operations in 2009 is improved by up to more than 15 percent as compared to current planning procedures

Morph-dependent fitness and directional change of morph frequencies over time in a Dutch population of Common buzzards <i>Buteo buteo</i>

How genetic polymorphisms are maintained in a population is a key question in evolutionary ecology. Previous work on a plumage colour polymorphism in the common buzzard Buteo buteo suggested heterozygote advantage as the mechanism maintaining the co-existence of three morphs (light, intermediate and dark). We took advantage of 20 years of life history data collected in a Dutch population to replicate earlier studies on the relationship between colour morph and fitness in this species. We examined differences between morphs in adult apparent survival, breeding success, annual number of fledglings produced and cumulative reproductive success. We found that cumulative reproductive success differed among morphs, with the intermediate morph having highest fitness. We also found assortative mating for colour morph, whereby assortative pairs were more likely to produce offspring and had longer-lasting pair bonds than disassortative pairs. Over the 20-year study period, the proportion of individuals with an intermediate morph increased. This apparent evolutionary change did not just arise from selection on individual phenotypes, but also from fitness benefits of assortative mating. The increased frequency of intermediates might also be due to immigration or drift. We hypothesize that genetic variation is maintained through spatial variation in selection pressures. Further studies should investigate morph-dependent dispersal behaviour and habitat choice

Inheritance patterns of plumage coloration in common buzzards <i>Buteo buteo</i> do not support a one-locus two-allele model

Balancing selection is a major mechanism to maintain colour polymorphisms over evolutionary time. In common buzzards, variation in plumage colour was reportedly maintained by a heterozygote advantage: heterozygote intermediates had higher fitness than homozygote light and dark morphs. Here, we challenge one of the basic premises of the heterozygote advantage hypothesis, by testing whether plumage colour variation in common buzzards follows a one-locus two-allele inheritance model. Using a long-term population study with 202 families, we show that colour variation in buzzards is highly heritable. However, we find no support for a simple Mendelian one-locus two-allele model of inheritance. Our results rather suggest that buzzard plumage colour should be considered a quantitative polygenic trait. As a consequence, it is unlikely that the proposed heterozygote advantage is the mechanism that maintains this genetic variation. We hypothesize that plumage colour effects on fitness might depend on the environment, but this remains to be tested

Renal function is a major determinant of ICU-acquired hypernatremia:A balance study on sodium handling

Background and Objectives: The development of ICU-acquired hypernatremia (IAH) is almost exclusively attributed to `too much salt and too little water'. However, intrinsic mechanisms also have been suggested to play a role. To identify the determinants of IAH, we designed a prospective controlled study. Methods: Patients with an anticipated length of stay ICU > 48 hours were included. Patients with hypernatremia on admission and/or on renal replacement therapy were excluded. Patients without IAH were compared with patients with borderline hypernatremia (>= 143 mmol/L, IAH 143) and more severe hypernatremia (> 145 mmol/L, IAH 145). Results: We included 89 patients, of which 51% developed IAH 143 and 29% IAH 145. Sodium intake was high in all patients. Fluid balances were slightly positive and comparable between the groups. Patients with IAH 145 were more severely ill on admission, and during admission, their sodium intake, cumulative sodium balances, serum creatinine and copeptin levels were higher. According to the free water clearance, all the patients conserved water. On multivariate analysis, the baseline serum creatinine was an independent risk factor for the development of IAH 143 and IAH 145. Also, the copeptin levels remained significant for IAH 143 and IAH 145. Sodium intake remained only significant for patients with IAH 145. Conclusions: Our data support the hypothesis that IAH is due to the combination of higher sodium intake and a urinary concentration deficit, as a manifestation of the renal impairment elicited by severe illness

An altered gp100 peptide ligand with decreased binding by TCR and CD8α dissects T cell cytotoxicity from production of cytokines and activation of NFAT

Altered peptide ligands (APLs) provide useful tools to study T cell activation and potentially direct immune responses to improve treatment of cancer patients. To better understand and exploit APLs, we studied the relationship between APLs and T cell function in more detail. Here, we tested a broad panel of gp100280-288 APLs with respect to T cell cytotoxicity, production of cytokines, and activation of Nuclear Factor of Activated T cells (NFAT) by human T cells gene-engineered with a gp100-HLA-A2-specific TCRαβ. We demonstrated that gp100-specific cytotoxicity, production of cytokines, and activation of NFAT were not affected by APLs with single amino acid substitutions, except for an APL with an amino acid substitution at position 3 (APL A3), which did not elicit any T cell response. A gp100 peptide with a double amino acid mutation (APL S4S6) elicited T cell cytotoxicity and production of IFNγ, and to a lesser extent TNFα, IL-4, and IL-5, but not production of IL-2 and IL-10, or activation of NFAT. Notably, T cell receptor (TCR)-mediated functions showed decreases in sensitivities for S4S6 versus gp100 wild-type (wt) peptide, which were minor for cytotoxicity but at least a 1000-fold more prominent for the production of cytokines. TCR-engineered T cells did not bind A3-HLA-A2, but did bind S4S6-HLA-A2 although to a lowered extent compared to wt peptide-HLA-A2. Moreover, S4S6-induced T cell function demonstrated an enhanced dependency on CD8α. Taken together, most gp100 APLs functioned as agonists, but A3 and S4S6 peptides acted as a null ligand and partial agonist, respectively. Our results further suggest that TCR-mediated cytotoxicity can be dissected from production of cytokines and activation of NFAT, and that the agonist potential of peptide mutants relates to the extent of binding by TCR and CD8α. These findings may facilitate the design of APLs to advance the study of T cell activation and their use for therapeutic applications

Hormonal control during infancy and testicular adrenal rest tumor development in males with congenital adrenal hyperplasia: a retrospective multicenter cohort study

IMPORTANCE Testicular adrenal rest tumors (TARTs), often found in male patients with congenital adrenal hyperplasia (CAH), are benign lesions causing testicular damage and infertility. We hypothesize that chronically elevated adrenocorticotropic hormone exposure during early life may promote TART development. OBJECTIVE This study aimed to examine the association between commencing adequate glucocorticoid treatment early after birth and TART development. DESIGN AND PARTICIPANTS This retrospective multicenter (n = 22) open cohort study collected longitudinal clinical and biochemical data of the first 4 years of life using the I-CAH registry and included 188 male patients (median age 13 years; interquartile range: 10-17) with 21-hydroxylase deficiency (n = 181) or 11-hydroxylase deficiency (n = 7). All patients underwent at least 1 testicular ultrasound. RESULTS TART was detected in 72 (38%) of the patients. Prevalence varied between centers. When adjusted for CAH phenotype, a delayed CAH diagnosis of >1 year, compared with a diagnosis within 1 month of life, was associated with a 2.6 times higher risk of TART diagnosis. TART onset was not predicted by biochemical disease control or bone age advancement in the first 4 years of life, but increased height standard deviation scores at the end of the 4-year study period were associated with a 27% higher risk of TART diagnosis. CONCLUSIONS AND RELEVANCE A delayed CAH diagnosis of >1 year vs CAH diagnosis within 1 month after birth was associated with a higher risk of TART development, which may be attributed to poor disease control in early life

Fibrodysplasia Ossificans Progressiva: what have we achieved and where are we now? follow-up to the 2015 Lorentz Workshop

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare progressive genetic disease effecting one in a million individuals. During their life, patients with FOP progressively develop bone in the soft tissues resulting in increasing immobility and early death. A mutation in the ACVR1 gene was identified as the causative mutation of FOP in 2006. After this, the pathophysiology of FOP has been further elucidated through the efforts of research groups worldwide. In 2015, a workshop was held to gather these groups and discuss the new challenges in FOP research. Here we present an overview and update on these topics

Robotically driven construction of buildings: Exploring on-demand building components production

Robotically Driven Construction of Buildings (RDCB) is an exploration into design to production solutions for robotically driven construction of buildings initiated by the faculties of Civil Engineering and Architecture, TU Delft and Architecture, TU Eindhoven and implemented 2014 within the 3TU Lighthouse framework. The aim of was to involve the disciplines of architecture, robotics, materials science, and structural design in order to integrate knowledge from the individual disciplines and develop new numerically controlled manufacturing techniques and building-design optimisation methods for adding creative value to buildings in a cost-effective and sustainable way.RDCB builds up on expertise developed at Hyperbody with respect to applications of robotics in architecture and this paper presents the contribution of the Robotic Building team from Hyperbody, Faculty of Architecture, TU Delft to the RDCB project. The contribution is in line with Europe’s aim to improve material and energy efficiency of buildings and efficiency of construction processes. Robotically driven construction and customised building materials have the potential to realise this in a cost-effective way and at the same time reduce accidents and health hazards for workers in the building sector. In order to achieve this RDCB is distributing materials as needed and where needed. This requires exploration of a variety of techniques and implies working with customised materials and techniques while finding the best methods of applying materials in the logic of specific force flows or thermal dissipation patterns.RDCB advances multi- and trans-disciplinary knowledge in robotically driven construction by designing and engineering new building systems for the on-demand production of customisable building components (Bier, 2014). The main consideration is that in architecture and building construction the factory of the future employs building materials and components that can be on site robotically processed and assembled

Discovertebral (Andersson) lesions in severe ankylosing spondylitis: a study using MRI and conventional radiography

The objective of this study is to investigate the prevalence of Andersson lesions (AL) in ankylosing spondylitis (AS) patients who will start anti-tumor necrosis factor (TNF) treatment. Radiographs and magnetic resonance imaging (MRI) of the spine were performed before therapy with anti-TNF. ALs were defined as discovertebral endplate destructions on MRI, associated with bone marrow edema and fat replacement or sclerosis, a decreased signal on T1, enhancement after contrast administration (gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA)), and increased signal on T2 and short tau inversion recovery (STIR). Additionally, conventional radiography showed a fracture line, irregular endplates, and increased sclerosis of adjacent vertebral bodies. Fifty-six AS patients were included, 68% males, mean age of 43 years, and mean disease duration of 11 years. The mean bath ankylosing spondylitis disease activity index was 6.4, and 24% of all patients had ankylosis. Only one patient showed a discovertebral abnormality with bone marrow edema of more than 50% of the vertebral bodies adjacent to the intervertebral disk of T7/T8 and T9/T10, a hypodense signal area on T1, and a high signal on STIR. Irregular endplates were depicted, and T1 after Gd-DTPA demonstrated high signal intensity around the disk margins. However, no fracture line was visible on conventional radiology, and therefore, this case was not considered to be an AL. No AL was detected in our AS patients, who were candidates for anti-TNF treatment. One patient showed a discovertebral abnormality on MRI, without a fracture line on conventional radiology. The relative small proportion of patients with a long-established disease might explain this finding for, particularly, an ankylosed spine is prone to develop an AL