Flexible modelling of spatial variation in agricultural field trials with the R package INLA

The objective of this paper was to fit different established spatial models for analysing agricultural field trials using the open-source R package INLA. Spatial variation is common in field trials, and accounting for it increases the accuracy of estimated genetic effects. However, this is still hindered by the lack of available software implementations. We compare some established spatial models and show possibilities for flexible modelling with respect to field trial design and joint modelling over multiple years and locations. We use a Bayesian framework and for statistical inference the integrated nested Laplace approximations (INLA) implemented in the R package INLA. The spatial models we use are the well-known independent row and column effects, separable first-order autoregressive ( AR1⊗AR1 ) models and a Gaussian random field (Matérn) model that is approximated via the stochastic partial differential equation approach. The Matérn model can accommodate flexible field trial designs and yields interpretable parameters. We test the models in a simulation study imitating a wheat breeding programme with different levels of spatial variation, with and without genome-wide markers and with combining data over two locations, modelling spatial and genetic effects jointly. The results show comparable predictive performance for both the AR1⊗AR1 and the Matérn models. We also present an example of fitting the models to a real wheat breeding data and simulated tree breeding data with the Nelder wheel design to show the flexibility of the Matérn model and the R package INLA

DNA Sequence Profiles of the Colorectal Cancer Critical Gene Set KRAS-BRAF-PIK3CA-PTEN-TP53 Related to Age at Disease Onset

The incidence of colorectal cancer (CRC) increases with age and early onset indicates an increased likelihood for genetic predisposition for this disease. The somatic genetics of tumor development in relation to patient age remains mostly unknown. We have examined the mutation status of five known cancer critical genes in relation to age at diagnosis, and compared the genomic complexity of tumors from young patients without known CRC syndromes with those from elderly patients. Among 181 CRC patients, stratified by microsatellite instability status, DNA sequence changes were identified in KRAS (32%), BRAF (16%), PIK3CA (4%), PTEN (14%) and TP53 (51%). In patients younger than 50 years (n = 45), PIK3CA mutations were not observed and TP53 mutations were more frequent than in the older age groups. The total gene mutation index was lowest in tumors from the youngest patients. In contrast, the genome complexity, assessed as copy number aberrations, was highest in tumors from the youngest patients. A comparable number of tumors from young (<50 years) and old patients (>70 years) was quadruple negative for the four predictive gene markers (KRAS-BRAF-PIK3CA-PTEN); however, 16% of young versus only 1% of the old patients had tumor mutations in PTEN/PIK3CA exclusively. This implies that mutation testing for prediction of EGFR treatment response may be restricted to KRAS and BRAF in elderly (>70 years) patients. Distinct genetic differences found in tumors from young and elderly patients, whom are comparable for known clinical and pathological variables, indicate that young patients have a different genetic risk profile for CRC development than older patients

Differential distribution of B7.1 (CD80) and B7.2 (CD86) costimulatory molecules on mucosal macrophage subsets in human inflammatory bowel disease (IBD)

The molecules B7.1 and B7.2 deliver costimulatory signals of critical importance to naive T cells, and may thus be involved in abrogation of oral tolerance in IBD. Functional disparity apparently exists among antigen-presenting cells in vivo. We wanted to examine if differential B7 expression occurs on mucosal macrophage subsets. Cryosections of bowel specimens from patients with IBD and normal controls were subjected to immunofluorescence and immunoperoxidase staining. In normal mucosa, selective subepithelial accumulation of B7.2+ cells was found. In inflamed IBD mucosa, however, subsets appeared consisting of both B7.2hi and B7.1hi cells as well as CD14hi macrophages. Notably, outside lymphoid aggregates the prominent fraction of recently recruited CD14hi macrophages comprised most (≈ 80%) of the B7.1hi cells, whereas most (≈ 70%) B7.2hi cells were identified as resident mucosal macrophages (CD14lo or CD14−). Differential expression of B7.1 and B7.2 on two functionally different subsets of intestinal macrophages implies separate immunoregulatory roles for the two molecules. This finding is in keeping with recent experimental data demonstrating that monocyte-derived cells are crucial for immune responses at mucosal surfaces. Preferential B7.1 up-regulation might be critical in breaking the immunological tolerance to luminal antigens in IBD, but it cannot be excluded that it is a secondary pathogenic event

CT and operative images for evaluation of right colectomy with extended D3 mesenterectomy anterior and posterior to the mesenteric vessels

Background Surgical techniques like complete mesocolic excision (CME) and D3 mesenterectomy, D3 refering to the N3 lymph node groups central in the mesentery removed at surgery, were introduced without proper evaluation of the lymphadenectomy. The aim of this study was to measure the vascular stumps and evaluate the extent and quality of lymphadenectomy after right colectomy with extended D3 mesenterectomy anterior/posterior to the mesenteric vessels. We also compared the investigation methods. Methods Residual vascular stumps were measured using three-dimensional (3D) reconstructed anatomy from follow-up computed tomography (CT) datasets and images taken during surgery. The quality of central lymphadenectomy was evaluated on the images. Results In total, 31 patients (15 females), median age 67 years (50–78), with stage I (n=7), stage II (n= 13), and stage III (n= 11) disease, were operated. Tumor locations were: 14 (45%) in the cecum, ten (32%) in the ascending colon, three (10%) in the hepatic flexure, and four (13%) in the transverse colon. The middle colic artery (MCA) was divided at its origin (13 patients) or its right branch (18 patients). Median lengths (range) of residual vascular stumps measured on 3D reconstructed CT and photographic images taken during surgery were: right colic artery: 0.0 mm (0.0–1.8)/0.0 mm (0.0–1.1), ileocolic artery: 0.0 mm (0.0–7.2)/0.0 mm (0.0–3.0), ileocolic vein: 0.0 mm (0.0–7.5)/0.0 mm (0.0–0.0), MCA: 0.0 mm (0.0–18.1)/1.0 mm (0.0–8.0), and right branch of the MCA: 0.0 mm (0.0–1.8)/0.0 mm (0.0–2.0). There was no significant difference between average lengths measured with the two techniques. The extent of lymphadenectomy was deemed acceptable in all patients. No differences in stump lengths were found in patients with different vascular crossing patterns in the central mesentery and presumably different degree of difficulty at surgery. Conclusion The results demonstrate very short residual vascular stumps and together with operative photographs provide objective evidence for superior lymphadenectomy in right colectomy with extended D3 mesenterectomy

Dealing with physical barriers in bottlenose dolphin (Tursiops truncatus) distribution

Worldwide, cetacean species have started to be protected, but they are still very vulnerable to accidental damage from an expanding range of human activities at sea. To properly manage these potential threats we need a detailed understanding of the seasonal distributions of these highly mobile populations. To achieve this goal, a growing effort has been underway to develop species distribution models (SDMs) that correctly describe and predict preferred species areas. However, accuracy is not always easy to achieve when physical barriers, such as islands, are present. Indeed, SDMs assume, if only implicitly, that the spatial effect is stationary, and that correlation is only dependent on the distance between observations and not on the direction or a spatial coordinates. The application of stationary SDMs in these cases could lead to incorrect predictions and, consequently, to uninformed decision making. In this study, we identify vulnerable habitats for the bottlenose dolphin in the Archipelago de La Maddalena, Northern Sardinia (Italy) using Bayesian hierarchical SDMs that account for the physical barriers issue and provide a full specification of the associated uncertainty. The approach we propose constitutes a major step forward in the understanding of cetacean species in many ecosystems where physical, geographical and topographical barriers are present

Navigating the mesentery: part II. Vascular abnormalities and a review of the literature

Aim Vascular abnormalities present advantages and/or disadvantages for the patient undergoing surgery. The aims of this study were to define, classify and demonstrate the courses, and to assess the clinical value, of arterial and venous abnormalities in the central mesentery. Method We conducted a review of the anatomy of 340 patients planned for enrolment in the ‘Safe Radical D3 Right Hemicolectomy for Cancer through Preoperative Biphasic MDCT Angiography' trial, 312 of whom were submitted to surgery. Vascular abnormalities were analysed in context with surgical notes and images. A metaanalysis of the literature was performed. Results Arterial Abnormalities were found in 28 (8.2%) of the 340 patients and were classified into the following three groups based on anticipated surgical difficulty: group 1, accessory or replaced arteries to solid organs [14 (4.1%)]; group 2, arterial shunts [11 (3.2%)] between the coeliac trunk and the superior mesenteric artery, which resulted in bleeding in three patients; and group 3, common stem abnormalities [3 (0.9%)]. Two groups of superior mesenteric vein abnormalities were noted. The first included morphological abnormalities in a single vein [4 (1.2%)]: aneurysm [1 (0.3%)]; and ring variants of principal tributaries [3 (0.9%)]. The second included double superior mesenteric vein trunks [31 (9.1%)]: genuine bifid [10 (2.9%)]; and pseudo bifid [21 (6.2%)]. The meta-analysis revealed 26 articles, including 10 series of anatomical dissections or angiographies [1970 cases with 205 (10.4%) arterial abnormalities] and 16 case reports, none of which described a clinical or surgical setting. Conclusion Vascular abnormalities occur frequently. Arterial abnormalities are a hazard when inadvertent injury occurs during surgery. Preoperative knowledge of a bifid superior mesenteric vein is useful

Navigating the mesentery: a comparative pre- and per-operative visualization of the vascular anatomy

Awareness of anatomy is critical for performing safe surgery within the root of the mesentery. Our aim was to investigate the anatomical relationship between the superior mesenteric artery (SMA) and vein (SMV) and their branches within a predefined D3 area of the right colon and to compare preoperatively established three-dimensional (3D) mesenteric vessel anatomy from CT with that found at surgery