Effect of build angle and layer height on the accuracy of 3-dimensional printed dental models.

INTRODUCTION: Three-dimensional (3D) printing technologies are profoundly changing the landscape of orthodontics. To optimize treatment-oriented applications, dimensional fidelity is required for 3D-printed orthodontic models. This study aimed to evaluate the effect of build angle and layer height on the accuracy of 3D-printed dental models and if each of their influences on print accuracy was conditional on the other. METHODS: A maxillary cast was scanned using an intraoral scanner. One hundred thirty-two study models were printed at various combinations of build angle (0°, 30°, 60°, 90°) and layer height (20 µm, 50 µm, 100 µm) with a digital light processing printer (n = 11 per group). The models were digitally scanned, and deviation analyzed using a 3D best-fit algorithm in metrology software. RESULTS: A statistically significant interaction was consistently found between build angle and layer height for each positive deviation, negative deviation, and proportion out of bounds. Average deviations of all study models were within clinically acceptable ranges, but the least accurate models were printed at 0°/20 µm. Although there was a tendency for an oblique build angle of 30° or 60° with a smaller layer height of 20 µm or 50 µm to print the most accurate models, 95 % confidence intervals overlapped with all other angles and heights except for 0°/20 µm. CONCLUSIONS: Build angle and layer height have statistically significant interactive effects on the accuracy of 3D-printed dental models. Overall, digital light processing printers produced models within clinically acceptable bounds, but the choice of build angle and layer height should be considered in conjunction with the clinical application, desired print time, and preferred efficiency of each print job.

Active pollination drives selection for reduced pollen-ovule ratios.

PREMISE: Variation in pollen-ovule ratios is thought to reflect the degree of pollen transfer efficiency-the more efficient the process, the fewer pollen grains needed. Few studies have directly examined the relationship between pollen-ovule ratio and pollen transfer efficiency. For active pollination in the pollination brood mutualisms of yuccas and yucca moths, figs and fig wasps, senita and senita moths, and leafflowers and leafflower moths, pollinators purposefully collect pollen and place it directly on the stigmatic surface of conspecific flowers. The tight coupling of insect reproductive interests with pollination of the flowers in which larvae develop ensures that pollination is highly efficient. METHODS: We used the multiple evolutionary transitions between passive pollination and more efficient active pollination to test if increased pollen transfer efficiency leads to reduced pollen-ovule ratios. We collected pollen and ovule data from a suite of plant species from each of the pollination brood mutualisms and used phylogenetically controlled tests and sister-group comparisons to examine whether the shift to active pollination resulted in reduced pollen-ovule ratios. RESULTS: Across all transitions between passive and active pollination in plants, actively pollinated plants had significantly lower pollen-ovule ratios than closely related passively pollinated taxa. Phylogenetically corrected comparisons demonstrated that actively pollinated plant species had an average 76% reduction in the pollen-ovule ratio. CONCLUSIONS: The results for active pollination systems support the general utility of pollen-ovule ratios as indicators of pollination efficiency and the central importance of pollen transfer efficiency in the evolution of pollen-ovule ratio.

A national survey of out-of-hours working and fatigue in consultants in anaesthesia and paediatric intensive care in the UK and Ireland.

The tragic death of an anaesthetic trainee driving home after a series of night shifts prompted a national survey of fatigue in trainee anaesthetists. This indicated that fatigue was widespread, with significant impact on trainees' health and well-being. Consultants deliver an increasing proportion of patient care resulting in long periods of continuous daytime duty and overnight on-call work, so we wished to investigate their experience of out-of-hours working and the causes and impact of work-related fatigue. We conducted a national survey of consultant anaesthetists and paediatric intensivists in the UK and Ireland between 25 June and 6 August 2018. The response rate was 46% (94% of hospitals were represented): 84% of respondents (95%CI 83.1-84.9%) contribute to a night on-call rota with 32% (30.9-33.1%) working 1:8 or more frequently. Sleep disturbance on-call is common: 47% (45.6-48.4%) typically receive two to three phone calls overnight, and 48% (46.6-49.4%) take 30 min or more to fall back to sleep. Only 15% (14.0-16.0%) reported always achieving 11 h of rest between their on-call and their next clinical duty, as stipulated by the European Working Time Directive. Moreover, 24% (22.8-25.2%) stated that there is no departmental arrangement for covering scheduled clinical duties following a night on-call if they have been in the hospital overnight. Overall, 91% (90.3-91.7%) reported work-related fatigue with over half reporting a moderate or significantly negative impact on health, well-being and home life. We discuss potential explanations for these results and ways to mitigate the effects of fatigue among consultants.

Increased symptoms of stiffness 1 year after total knee arthroplasty are associated with a worse functional outcome and lower rate of patient satisfaction.

PURPOSE: Symptoms of stiffness after total knee arthroplasty (TKA) cause significant morbidity, but there is limited data to facilitate identification of those most at risk after surgery. Stratifying risk can aid earlier directed treatment options. METHODS: A retrospective cohort consisting of 2589 patients undergoing a primary TKA was identified from an established arthroplasty database. Patient demographics, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and short form (SF) 12 scores were collected pre-operatively and 1 year post-operatively. In addition, patient satisfaction was assessed for 1 year. Patients with a worse WOMAC stiffness score in 1 year were defined as the "increased" stiffness group and the other cohort as the non-stiffness group. RESULTS: At 1 year after surgery 129 (5%) patients had a significant increase in their stiffness symptoms (20%, 95% confidence interval (CI) 17.9-22.0, p < 0.001), and had significantly (all p < 0.001) less of an improvement in their pain, function and total WOMAC scores, and SF-12 scores compared to the non-stiffness group (n = 2460). Patient satisfaction was significantly lower (odds ratio (OR) 0.178, CI 0.121 to 0.262, p < 0.001) for the increased stiffness group. Logistic regression analysis identified male gender (OR 1.66, p = 0.02), lung disease (OR 2.06, p = 0.002), diabetes (OR 1.82, p = 0.02), back pain (OR 1.81, p = 0.005), and a pre-operative stiffness score of 44 or more (OR 5.79, p < 0.001) were significantly predictive of increased stiffness. CONCLUSION: Patients with increased symptoms of stiffness after TKA have a worse functional outcome and a lower rate of patient satisfaction, and patients at risk of being in this group should be informed pre-operatively. LEVEL OF EVIDENCE: Retrospective prognostic study, Level III.

Effect of print layer height on the assessment of 3D-printed models.

INTRODUCTION: Many variables can affect the accuracy of 3D-printed orthodontic models, and the effects of different printing parameters on the clinical utility of the printed models are just beginning to be understood. The objective of this study was to investigate the effect of print layer height on the assessment of 3D-printed orthodontic models with the use of the American Board of Orthodontics Cast-Radiograph Evaluation grading system. METHODS: Twelve cases were scanned using a desktop model scanner and 3D-printed using a stereolithography-based printer at three different layer heights (25, 50, and 100-µm; n = 12 per group). All models were scored by eleven graders using the Cast-Radiograph Evaluation grading system. All models were scored a second time, at least two weeks later. RESULTS: No statistically significant effects of print layer height were found on the scoring of the models for any of the grading metrics or total score. 3D-printed models of each layer height were highly positively correlated with stone models for the total score, with the strongest correlation found with models printed at 100-µm. CONCLUSIONS: 100-µm layer height 3D-printed models are potentially clinically acceptable for the purposes of evaluation of treatment outcomes, diagnosis and treatment planning, and residency training.

Yield responses of arable crops to liming - An evaluation of relationships between yields and soil pH from a long-term liming experiment.

The management of optimal soil pH is fundamental to sustainable crop production. Understanding the lime requirement for arable crops has developed gradually over the last several decades. The aim of this study was to examine the yield-pH relationship for a range of arable crops to understand their response to liming, based on the Long-Term Liming experiments established in 1962 at Rothamsted Research, UK. The main treatments of four different rates of lime and, therefore, four distinctly different soil pH levels were maintained for 35 years at two sites (Rothamsted and Woburn). The pH ranged from 4.4 to 8.0. The lime response was tested on the following crops: spring barley, spring oats, spring beans, spring lupins, winter lupins, potatoes, linseed, winter oilseed rape, winter triticale and winter wheat. Relative yield (RY) was used for non-linear regression analysis to detect site, year and phosphorus (P) fertiliser effects on the relationship with pH. Liming had a highly significant positive effect on soil pH, but overall there was no consistent increase or decrease in soil extractable P (Olsen) or exchangeable K. There were significant site effects detected for RY for most crops which reflect differences in the two soil types. Spring oats and potatoes had very weak responses to lime within the pH range tested. For spring barley, winter triticale, winter wheat and winter oilseed rape significant effects of P fertiliser on the yield-pH relationship were found, although the nature of effects differed between crops and sites. Findings from the Long-Term Liming experiment are invaluable in improving the fundamental understanding on the yield-pH relationship for important arable crops and this has significant implications on selecting crops for rotations. The pH at 90% RY was calculated for selected crops and the beneficial effect of fertiliser P was detected in significantly reducing the critical pH value.

Genetically predicted complement component 4A expression: effects on memory function and middle temporal lobe activation.

BACKGROUND: The longstanding association between the major histocompatibility complex (MHC) locus and schizophrenia (SZ) risk has recently been accounted for, partially, by structural variation at the complement component 4 (C4) gene. This structural variation generates varying levels of C4 RNA expression, and genetic information from the MHC region can now be used to predict C4 RNA expression in the brain. Increased predicted C4A RNA expression is associated with the risk of SZ, and C4 is reported to influence synaptic pruning in animal models. METHODS: Based on our previous studies associating MHC SZ risk variants with poorer memory performance, we tested whether increased predicted C4A RNA expression was associated with reduced memory function in a large (n = 1238) dataset of psychosis cases and healthy participants, and with altered task-dependent cortical activation in a subset of these samples. RESULTS: We observed that increased predicted C4A RNA expression predicted poorer performance on measures of memory recall (p = 0.016, corrected). Furthermore, in healthy participants, we found that increased predicted C4A RNA expression was associated with a pattern of reduced cortical activity in middle temporal cortex during a measure of visual processing (p < 0.05, corrected). CONCLUSIONS: These data suggest that the effects of C4 on cognition were observable at both a cortical and behavioural level, and may represent one mechanism by which illness risk is mediated. As such, deficits in learning and memory may represent a therapeutic target for new molecular developments aimed at altering C4's developmental role.

The anatomy of forearm free flap phalloplasty for transgender surgery.

Transgender surgeries are becoming more frequent and visual interpretation of anatomy is essential for both surgeons and patients. Since the forearm free flap phalloplasty was introduced in 1984, it has been known to provide reliable cosmetic and functional results for transitioning men compared with phalloplasty by different flaps. Surgical text descriptions were enhanced by the creation of new anatomic illustrations. The forearm free flap consists of the anterior forearm skin, subcutaneous tissue, fascia containing the radial artery as the perforator and its venae comitantes, cephalic and basilic veins, and lateral and medial antebrachial cutaneous nerves are demonstrated in relation to the surgically derived flap. Song's forearm free flap phalloplasty requires two surgical stages with a three-month interval between the stages: prelamination of a neourethra and construction of a neophallus. The neophallus created by forearm flap phalloplasty is reported to achieve acceptable aesthetical and psychological satisfaction, appropriate size and shape, and satisfying sexual intercourse. Despite increasing experiences in gender confirming surgery with modifications made by many authors, urethral complications including fistula and/or stricture formation are the leading causes of reoperation. The poor esthetic outcome of the forearm donor site and a decrease in rigidity of the neophallus are the main limitations. Illustrations of anatomy help inform surgical choice and understanding of risks and benefits by patients. The anatomy of the free forearm flap phalloplasty supports creation of a neophallus for transsexual anatomy revision. Clin. Anat. 31:145-151, 2018. © 2017 Wiley Periodicals, Inc.

Patient age of less than 55 years is not an independent predictor of functional improvement or satisfaction after total knee arthroplasty.

INTRODUCTION: Management of the young patient with end-stage osteoarthritis of the knee is difficult, with surgical options of osteotomy, partial or total knee arthroplasty (TKA). The primary aim of this study was to assess whether age of less than 55 years was an independent predictor of functional outcome and satisfaction after total knee arthroplasty (TKA). The secondary aims were to identify pre-operative differences in patient demographics, comorbidity and function between patients less than 55 years old compared to those 55 years old and over. MATERIALS AND METHODS: A retrospective cohort consisting of 2589 patients undergoing a primary TKA was identified from an established arthroplasty database. Patient demographics, comorbidity, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Short Form (SF) 12 scores were collected pre-operatively and 1 year post-operatively. In addition, patient satisfaction was assessed at 1 year. Regression analysis was used to identify independent pre-operative predictors of change in the WOMAC and SF-12 scores, and patient satisfaction. RESULTS: Patients less than 55 years old were significantly less likely to be satisfied with the overall outcome of their TKA (OR 0.4, p = 0.001). After adjusting for confounding variables age group was not an independent predictor of overall satisfaction with overall outcome (OR 0.71, p = 0.16). Independent predictors of an increased risk of dissatisfaction with the overall outcome at 1 year were depression (OR 0.58, p = 0.008) and worse pre-operative SF-12 MCS (p = 0.04). CONCLUSION: Age of less than 55 years is not an independent predictor of functional outcome or rate of patient satisfaction after TKA. However, depression and poor mental health are significantly more prevalent in patients less than 55 years old and were independently associated with a lower satisfaction rate.

Enhancing genomic prediction with genome-wide association studies in multiparental maize populations.

Genome-wide association mapping using dense marker sets has identified some nucleotide variants affecting complex traits that have been validated with fine-mapping and functional analysis. However, many sequence variants associated with complex traits in maize have small effects and low repeatability. In contrast to genome-wide association study (GWAS), genomic prediction (GP) is typically based on models incorporating information from all available markers, rather than modeling effects of individual loci. We considered methods to integrate results of GWASs into GP models in the context of multiple interconnected families. We compared association tests based on a biallelic additive model constraining the effect of a single-nucleotide polymorphism (SNP) to be equal across all families in which it segregates to a model in which the effect of a SNP can vary across families. Association SNPs were then included as fixed effects into a GP model that also included the random effects of the whole genome background. Simulation studies revealed that the effectiveness of this joint approach depends on the extent of polygenicity of the traits. Congruent with this finding, cross-validation studies indicated that GP including the fixed effects of the most significantly associated SNPs along with the polygenic background was more accurate than the polygenic background model alone for moderately complex but not highly polygenic traits measured in the maize nested association mapping population. Individual SNPs with strong and robust association signals can effectively improve GP. Our approach provides a new integrative modeling approach for both reliable gene discovery and robust GP.

A national survey of the effects of fatigue on trainees in anaesthesia in the UK.

Long daytime and overnight shifts remain a major feature of working life for trainees in anaesthesia. Over the past 10 years, there has been an increase in awareness and understanding of the potential effects of fatigue on both the doctor and the patient. The Working Time Regulations (1998) implemented the European Working Time Directive into UK law, and in August 2009 it was applied to junior doctors, reducing the maximum hours worked from an average of 56 per week to 48. Despite this, there is evidence that problems with inadequate rest and fatigue persist. There is no official guidance regarding provision of a minimum standard of rest facilities for doctors in the National Health Service, and the way in which rest is achieved by trainee anaesthetists during their on-call shift depends on rota staffing and workload. We conducted a national survey to assess the incidence and effects of fatigue among the 3772 anaesthetists in training within the UK. We achieved a response rate of 59% (2231/3772 responses), with data from 100% of NHS trusts. Fatigue remains prevalent among junior anaesthetists, with reports that it has effects on physical health (73.6% [95%CI 71.8-75.5]), psychological wellbeing (71.2% [69.2-73.1]) and personal relationships (67.9% [65.9-70.0]). The most problematic factor remains night shift work, with many respondents commenting on the absence of breaks, inadequate rest facilities and 57.0% (55.0-59.1) stating they had experienced an accident or near-miss when travelling home from night shifts. We discuss potential explanations for the results, and present a plan to address the issues raised by this survey, aiming to change the culture around fatigue for the better.

Landscape genetics of a pollinator longhorn beetle [Typocerus v. velutinus (Olivier)] on a continuous habitat surface.

Landscape connectivity, the degree to which the landscape structure facilitates or impedes organismal movement and gene flow, is increasingly important to conservationists and land managers. Metrics for describing the undulating shape of continuous habitat surfaces can expand the usefulness of continuous gradient surfaces that describe habitat and predict the flow of organisms and genes. We adopted a landscape gradient model of habitat and used surface metrics of connectivity to model the genetic continuity between populations of the banded longhorn beetle [Typocerus v. velutinus (Olivier)] collected at 17 sites across a fragmentation gradient in Indiana, USA. We tested the hypothesis that greater habitat connectivity facilitates gene flow between beetle populations against a null model of isolation by distance (IBD). We used next-generation sequencing to develop 10 polymorphic microsatellite loci and genotype the individual beetles to assess the population genetic structure. Isolation by distance did not explain the population genetic structure. The surface metrics model of habitat connectivity explained the variance in genetic dissimilarities 30 times better than the IBD model. We conclude that surface metrology of habitat maps is a powerful extension of landscape genetics in heterogeneous landscapes.

Significant understaging is seen in clinically staged T2N0 esophageal cancer patients undergoing esophagectomy.

This study aimed to determine the impact of preoperative staging on the treatment of clinical T2N0 (cT2N0) esophageal cancer patients undergoing esophagectomy. We reviewed a retrospective cohort of 27 patients treated at a single institution between 1999 and 2011. Clinical staging was performed with computed tomography, positron emission tomography, and endoscopic ultrasound. Patients were separated into two groups: neoadjuvant therapy followed by surgery (NEOSURG) and surgery alone (SURG). There were 11 patients (41%) in the NEOSURG group and 16 patients (59%) in the SURG group. In the NEOSURG group, three of 11 patients (27%) had a pathological complete response and eight (73%) were partial or nonresponders after neoadjuvant therapy. In the SURG group, nine of 16 patients (56%) were understaged, 6 (38%) were overstaged, and 1 (6%) was correctly staged. In the entire cohort, despite being clinically node negative, 14 of 27 patients (52%) had node-positive disease (5/11 [45%] in the NEOSURG group, and 9/16 [56%] in the SURG group). Overall survival rate was not statistically significant between the two groups (P = 0.96). Many cT2N0 patients are clinically understaged and show no preoperative evidence of node-positive disease. Consequently, neoadjuvant therapy may have a beneficial role in treatment.

Preoperative carboplatin and paclitaxel-based chemoradiotherapy for esophageal carcinoma: results of a modified CROSS regimen utilizing radiation doses greater than 41.4 Gy.

Trimodality therapy for resectable esophageal and gastroesophageal junction cancers utilizing preoperative radiotherapy with concurrent carboplatin and paclitaxel-based chemotherapy is being increasingly utilized secondary to the results of the phase III CROSS trial. However, there is a paucity of reports of this regimen as a component of chemoradiotherapy in North America. We aim to report on our clinical experience using a modified CROSS regimen with higher radiotherapy doses. Patients with advanced (cT2-cT4 or node positive) esophageal or gastroesophageal junction carcinoma who received preoperative carboplatin/paclitaxel-based chemoradiotherapy with radiation doses of greater than 41.4 Gray (Gy) followed by esophagectomy were identified from an institutional database. Patient, imaging, treatment, and tumor response characteristics were analyzed. Twenty-four patients were analyzed. All but one tumor had adenocarcinoma histology. The median radiation dose was 50.4 Gy. Pathologic complete response was achieved in 29% of patients, with all receiving 50.4 Gy. Three early postoperative deaths were seen, due in part to acute respiratory distress syndrome and all three patients received 50-50.4 Gy. With a median follow-up of 9.4 months (23 days-2 years), median survival was 24 months. Trimodality therapy utilizing concurrent carboplatin/paclitaxel with North American radiotherapy doses appeared to have similar pathologic complete response rates compared with the CROSS trial, but may be associated with higher toxicity. Although the sample size is small and further follow-up is necessary, radiation doses greater than 41.4 Gy may not be warranted secondary to a potentially increased risk of severe radiation-induced acute lung injury.

Joint-multiple family linkage analysis predicts within-family variation better than single-family analysis of the maize nested association mapping population.

Quantitative trait locus (QTL) mapping has been used to dissect the genetic architecture of complex traits and predict phenotypes for marker-assisted selection. Many QTL mapping studies in plants have been limited to one biparental family population. Joint analysis of multiple biparental families offers an alternative approach to QTL mapping with a wider scope of inference. Joint-multiple population analysis should have higher power to detect QTL shared among multiple families, but may have lower power to detect rare QTL. We compared prediction ability of single-family and joint-family QTL analysis methods with fivefold cross-validation for 6 diverse traits using the maize nested association mapping population, which comprises 25 biparental recombinant inbred families. Joint-family QTL analysis had higher mean prediction abilities than single-family QTL analysis for all traits at most significance thresholds, and was always better at more stringent significance thresholds. Most robust QTL (detected in >50% of data samples) were restricted to one family and were often not detected at high frequency by joint-family analysis, implying substantial genetic heterogeneity among families for complex traits in maize. The superior predictive ability of joint-family QTL models despite important genetic differences among families suggests that joint-family models capture sufficient smaller effect QTL that are shared across families to compensate for missing some rare large-effect QTL.

Hallauer's Tusón: a decade of selection for tropical-to-temperate phenological adaptation in maize.

Crop species exhibit an astounding capacity for environmental adaptation, but genetic bottlenecks resulting from intense selection for adaptation and productivity can lead to a genetically vulnerable crop. Improving the genetic resiliency of temperate maize depends upon the use of tropical germplasm, which harbors a rich source of natural allelic diversity. Here, the adaptation process was studied in a tropical maize population subjected to 10 recurrent generations of directional selection for early flowering in a single temperate environment in Iowa, USA. We evaluated the response to this selection across a geographical range spanning from 43.05° (WI) to 18.00° (PR) latitude. The capacity for an all-tropical maize population to become adapted to a temperate environment was revealed in a marked fashion: on average, families from generation 10 flowered 20 days earlier than families in generation 0, with a nine-day separation between the latest generation 10 family and the earliest generation 0 family. Results suggest that adaptation was primarily due to selection on genetic main effects tailored to temperature-dependent plasticity in flowering time. Genotype-by-environment interactions represented a relatively small component of the phenotypic variation in flowering time, but were sufficient to produce a signature of localized adaptation that radiated latitudinally, in partial association with daylength and temperature, from the original location of selection. Furthermore, the original population exhibited a maladaptive syndrome including excessive ear and plant heights along with later flowering; this was reduced in frequency by selection for flowering time.

A comparison of techniques for assessing farmland bumblebee populations.

Agri-environment schemes have been implemented across the European Union in order to reverse declines in farmland biodiversity. To assess the impact of these schemes for bumblebees, accurate measures of their populations are required. Here, we compared bumblebee population estimates on 16 farms using three commonly used techniques: standardised line transects, coloured pan traps and molecular estimates of nest abundance. There was no significant correlation between the estimates obtained by the three techniques, suggesting that each technique captured a different aspect of local bumblebee population size and distribution in the landscape. Bumblebee abundance as observed on the transects was positively influenced by the number of flowers present on the transect. The number of bumblebees caught in pan traps was positively influenced by the density of flowers surrounding the trapping location and negatively influenced by wider landscape heterogeneity. Molecular estimates of the number of nests of Bombus terrestris and B. hortorum were positively associated with the proportion of the landscape covered in oilseed rape and field beans. Both direct survey techniques are strongly affected by floral abundance immediately around the survey site, potentially leading to misleading results if attempting to infer overall abundance in an area or on a farm. In contrast, whilst the molecular method suffers from an inability to detect sister pairs at low sample sizes, it appears to be unaffected by the abundance of forage and thus is the preferred survey technique.

A phase I study of cabozantinib (XL184) in patients with renal cell cancer.

BACKGROUND: Cabozantinib targets tyrosine kinases including the hepatocyte growth factor receptor (MET) and vascular endothelial growth factor (VEGF) receptor 2, which are important drug targets in renal cell carcinoma (RCC). PATIENTS AND METHODS: This single-arm open-label phase I trial evaluated the safety and tolerability of cabozantinib in heavily pretreated patients with metastatic clear cell RCC. RESULTS: The study enrolled 25 RCC patients for whom standard therapy had failed. Patients received a median of two prior systemic agents, and most patients had previously received at least one VEGF pathway inhibiting therapy (22 patients [88%]). Common adverse events included fatigue, diarrhea, nausea, proteinuria, appetite decreased, palmar-plantar erythrodysesthesia, and vomiting. Partial response was reported in seven patients (28%). Median progression-free survival was 12.9 months, and median overall survival was 15.0 months. CONCLUSION: Cabozantinib demonstrates preliminary anti-tumor activity and a safety profile similar to that seen with other multitargeted VEGFR tyrosine kinase inhibitors in advanced RCC patients. Further evaluation of cabozantinib in RCC is warranted. ClinicalTrials.gov identifier: NCT01100619.

Identification and characterisation of TLR18-21 genes in Atlantic salmon (Salmo salar).

Teleost fish possess many types of toll-like receptor (TLR) some of which exist in other vertebrate groups and some that do not (ie so-called "fish-specific" TLRs). In this study, we identified in Atlantic salmon (Salmo salar) whole-genome shotgun (WGS) contigs seven TLRs that are not found in mammals, including six types of fish-specific TLRs (one TLR18, one TLR19, and four TLR20 members (two of which are putative soluble forms (s)) and one TLR21. Phylogenetic analysis revealed that teleost TLR19-21 are closely related with murine TLR11-TLR13, whilst teleost TLR18 groups with mammalian TLR1, 2, 6 and 10. A typical TLR protein domain structure was found in all these TLRs with the exception of TLR20b(s) and TLR20c(s). TLR-GFP expression plasmids transfected into SHK-1 cells showed that salmon TLR19, TLR20a and TLR20d were preferentially localised to the intracellular compartment. Real time PCR analysis suggested that salmon TLR19-TLR21 are mainly expressed in immune related organs, such as spleen, head kidney and gills, while TLR18 transcripts are more abundant in muscle. In vitro stimulation of primary head kidney cells with type I IFN, IFNγ and IL-1ß had no impact on TLR expression. Infectious salmon anaemia virus (ISAV) infection, in vivo, down-regulated TLR20a, TLR20b(s), TLR20d and TLR21 in infected salmon kidney tissue. In contrast, up-regulation of TLR19 and TLR20a expression was found in posterior kidney in rainbow trout with clinical proliferative kidney disease (PKD).

Intracranial hypertension in subarachnoid hamorrhage: outcome after decompressive craniectomy.

Intracranial hypertension can occur following aneurysmal subarachnoid haemorrhage (SAH). It can be treated with decompressive craniectomy (DC) with the aim of reducing intracranial pressure, increasing cerebral perfusion and reducing further morbidity and mortality. We studied the outcome of patients undergoing DC following SAH at our institution, to ascertain whether the use of this treatment can be rationalized.