The list of the chromosome races of the common shrew Sorex araneus (updated 2002)

In 1996 the International Sorex araneus Cytogenetics Committee (ISACC) published a comprehensive list of 50 chromosome races of the common shrew Sorex araneus (lima et al. 1996). Since that time twenty one new races have been described and three races have been removed from the list. The present list summarises the data about races described since the 1996 publication. The rules introduced by Searle et al. (1991) and Hausser et al. (1994) were followed in the compilation of the list. It can be considered a reference for further studies of evolutionary relationships between the chromosome races of Sorex araneus. A summary table of all the 68 known races, arranged alphabetically according to their names, is given.

Treatment and outcomes of acute basilar artery occlusion in the Basilar Artery International Cooperation Study (BASICS): a prospective registry study.

BACKGROUND: Treatment strategies for acute basilar artery occlusion (BAO) are based on case series and data that have been extrapolated from stroke intervention trials in other cerebrovascular territories, and information on the efficacy of different treatments in unselected patients with BAO is scarce. We therefore assessed outcomes and differences in treatment response after BAO. METHODS: The Basilar Artery International Cooperation Study (BASICS) is a prospective, observational registry of consecutive patients who presented with an acute symptomatic and radiologically confirmed BAO between November 1, 2002, and October 1, 2007. Stroke severity at time of treatment was dichotomised as severe (coma, locked-in state, or tetraplegia) or mild to moderate (any deficit that was less than severe). Outcome was assessed at 1 month. Poor outcome was defined as a modified Rankin scale score of 4 or 5, or death. Patients were divided into three groups according to the treatment they received: antithrombotic treatment only (AT), which comprised antiplatelet drugs or systemic anticoagulation; primary intravenous thrombolysis (IVT), including subsequent intra-arterial thrombolysis; or intra-arterial therapy (IAT), which comprised thrombolysis, mechanical thrombectomy, stenting, or a combination of these approaches. Risk ratios (RR) for treatment effects were adjusted for age, the severity of neurological deficits at the time of treatment, time to treatment, prodromal minor stroke, location of the occlusion, and diabetes. FINDINGS: 619 patients were entered in the registry. 27 patients were excluded from the analyses because they did not receive AT, IVT, or IAT, and all had a poor outcome. Of the 592 patients who were analysed, 183 were treated with only AT, 121 with IVT, and 288 with IAT. Overall, 402 (68%) of the analysed patients had a poor outcome. No statistically significant superiority was found for any treatment strategy. Compared with outcome after AT, patients with a mild-to-moderate deficit (n=245) had about the same risk of poor outcome after IVT (adjusted RR 0.94, 95% CI 0.60-1.45) or after IAT (adjusted RR 1.29, 0.97-1.72) but had a worse outcome after IAT compared with IVT (adjusted RR 1.49, 1.00-2.23). Compared with AT, patients with a severe deficit (n=347) had a lower risk of poor outcome after IVT (adjusted RR 0.88, 0.76-1.01) or IAT (adjusted RR 0.94, 0.86-1.02), whereas outcomes were similar after treatment with IAT or IVT (adjusted RR 1.06, 0.91-1.22). INTERPRETATION: Most patients in the BASICS registry received IAT. Our results do not support unequivocal superiority of IAT over IVT, and the efficacy of IAT versus IVT in patients with an acute BAO needs to be assessed in a randomised controlled trial. FUNDING: Department of Neurology, University Medical Center Utrecht.

Anastomotic longitudinal stress due to modification of arterial longitudinal properties after anastomosis.

BACKGROUND: In our hands, in vivo segmental vessel length changes up to 5% because of blood pressure: increasing in arterial pressure is associated to decrease in segmental vessel length. METHODS AND MATERIAL: Using two piezoelectric crystals sutured on vessel wall and a high fidelity pressure probe, we recorded artery length variations as function of blood pressure, before and after an end-to-end anastomosis on four pigs carotid arteries. RESULTS: Mean arterial pressure before anastomosis = 73 mmHg (+/- 12); mean arterial pressure after anastomosis = 91 mmHg (+/- 14); mean crystals displacement before anastomosis during systole = -0.21 mm; mean crystals displacement after anastomosis during systole = +0.24 mm; mean distance between crystals before anastomosis = 12.3 mm (+/- 0.8) and after anastomosis = 11.2 mm (+/- 0.5). CONCLUSIONS: In the acute phase following an end-to-end anastomosis, an increase in blood pressure causes increasing in vessel length, with an exponential correlation. The anastomosis is constantly subjected to a longitudinal traction whose magnitude depends on blood pressure.

Structural alterations of the coronary arterial wall are associated with myocardial flow heterogeneity in type 2 diabetes mellitus.

PURPOSE: To determine the relationship between carotid intima-media thickness (IMT), coronary artery calcification (CAC), and myocardial blood flow (MBF) at rest and during vasomotor stress in type 2 diabetes mellitus (DM). METHODS: In 68 individuals, carotid IMT was measured using high-resolution vascular ultrasound, while the presence of CAC was determined with electron beam tomography (EBT). Global and regional MBF was determined in milliliters per gram per minute with (13)N-ammonia and positron emission tomography (PET) at rest, during cold pressor testing (CPT), and during adenosine (ADO) stimulation. RESULTS: There was neither a relationship between carotid IMT and CAC (r = 0.10, p = 0.32) nor between carotid IMT and coronary circulatory function in response to CPT and during ADO (r = -0.18, p = 0.25 and r = 0.10, p = 0.54, respectively). In 33 individuals, EBT detected CAC with a mean Agatston-derived calcium score of 44 +/- 18. There was a significant difference in regional MBFs between territories with and without CAC at rest and during ADO-stimulated hyperemia (0.69 +/- 0.24 vs. 0.74 +/- 0.23 and 1.82 +/- 0.50 vs. 1.95 +/- 0.51 ml/g/min; p < or = 0.05, respectively) and also during CPT in DM but less pronounced (0.81 +/- 0.24 vs. 0.83 +/- 0.23 ml/g/min; p = ns). The increase in CAC was paralleled with a progressive regional decrease in resting as well as in CPT- and ADO-related MBFs (r = -0.36, p < or = 0.014; r = -0.46, p < or = 0.007; and r = -0.33, p < or = 0.041, respectively). CONCLUSIONS: The absence of any correlation between carotid IMT and coronary circulatory function in type 2 DM suggests different features and stages of early atherosclerosis in the peripheral and coronary circulation. PET-measured MBF heterogeneity at rest and during vasomotor stress may reflect downstream fluid dynamic effects of coronary artery disease (CAD)-related early structural alterations of the arterial wall.

Exome sequencing identifies DYNC2H1 mutations as a common cause of asphyxiating thoracic dystrophy (Jeune syndrome) without major polydactyly, renal or retinal involvement.

BACKGROUND: Jeune asphyxiating thoracic dystrophy (JATD) is a rare, often lethal, recessively inherited chondrodysplasia characterised by shortened ribs and long bones, sometimes accompanied by polydactyly, and renal, liver and retinal disease. Mutations in intraflagellar transport (IFT) genes cause JATD, including the IFT dynein-2 motor subunit gene DYNC2H1. Genetic heterogeneity and the large DYNC2H1 gene size have hindered JATD genetic diagnosis. AIMS AND METHODS: To determine the contribution to JATD we screened DYNC2H1 in 71 JATD patients JATD patients combining SNP mapping, Sanger sequencing and exome sequencing. RESULTS AND CONCLUSIONS: We detected 34 DYNC2H1 mutations in 29/71 (41%) patients from 19/57 families (33%), showing it as a major cause of JATD especially in Northern European patients. This included 13 early protein termination mutations (nonsense/frameshift, deletion, splice site) but no patients carried these in combination, suggesting the human phenotype is at least partly hypomorphic. In addition, 21 missense mutations were distributed across DYNC2H1 and these showed some clustering to functional domains, especially the ATP motor domain. DYNC2H1 patients largely lacked significant extra-skeletal involvement, demonstrating an important genotype-phenotype correlation in JATD. Significant variability exists in the course and severity of the thoracic phenotype, both between affected siblings with identical DYNC2H1 alleles and among individuals with different alleles, which suggests the DYNC2H1 phenotype might be subject to modifier alleles, non-genetic or epigenetic factors. Assessment of fibroblasts from patients showed accumulation of anterograde IFT proteins in the ciliary tips, confirming defects similar to patients with other retrograde IFT machinery mutations, which may be of undervalued potential for diagnostic purposes.

Association Study of Common Genetic Variants and HIV-1 Acquisition in 6,300 Infected Cases and 7,200 Controls.

Multiple genome-wide association studies (GWAS) have been performed in HIV-1 infected individuals, identifying common genetic influences on viral control and disease course. Similarly, common genetic correlates of acquisition of HIV-1 after exposure have been interrogated using GWAS, although in generally small samples. Under the auspices of the International Collaboration for the Genomics of HIV, we have combined the genome-wide single nucleotide polymorphism (SNP) data collected by 25 cohorts, studies, or institutions on HIV-1 infected individuals and compared them to carefully matched population-level data sets (a list of all collaborators appears in Note S1 in Text S1). After imputation using the 1,000 Genomes Project reference panel, we tested approximately 8 million common DNA variants (SNPs and indels) for association with HIV-1 acquisition in 6,334 infected patients and 7,247 population samples of European ancestry. Initial association testing identified the SNP rs4418214, the C allele of which is known to tag the HLA-B*57:01 and B*27:05 alleles, as genome-wide significant (p = 3.6×10(-11)). However, restricting analysis to individuals with a known date of seroconversion suggested that this association was due to the frailty bias in studies of lethal diseases. Further analyses including testing recessive genetic models, testing for bulk effects of non-genome-wide significant variants, stratifying by sexual or parenteral transmission risk and testing previously reported associations showed no evidence for genetic influence on HIV-1 acquisition (with the exception of CCR5Δ32 homozygosity). Thus, these data suggest that genetic influences on HIV acquisition are either rare or have smaller effects than can be detected by this sample size.

Expression of neuroectodermal antigens common to melanomas, gliomas, and neuroblastomas. I. Identification by monoclonal anti-melanoma and anti-glioma antibodies.

The reactivity spectrum of five different monoclonal anti-melanoma antibodies cross-reacting with gliomas and neuroblastomas and one monoclonal anti-glioma antibody cross-reacting with melanomas and neuroblastomas was investigated. Comparison of the binding activity of these monoclonal antibodies for 11 melanoma, seven glioma, and three neuroblastoma cell lines showed that each of these clones had a different pattern of cross-reactivity. The results indicated that the antigenic determinants detected by these antibodies were not associated with the same antigen and thus suggested the existence of at least six different antigens common to melanomas, gliomas, and neuroblastomas. Since all these tumors are known to derive from cells originating embryologically from the neural crest, it can be assumed that the antigens recognized by our monoclonal antibodies are neuroectodermal differentiation antigens. However, absorption with fetal brain homogenates abolished only the binding of monoclonal anti-glioma antibody, but did not modify the binding of monoclonal anti-melanoma antibodies.

Carotid Dose Spring in Definitive Irradiation of T1N0 Squamous Cell Laryngeal Carcinoma Using Helical Tomotherapy

Purpose/Objective(s): To implement a carotid dose sparing protocol using helical Tomotherapy in T1N0 squamous cell laryngeal carcinoma.Materials/Methods: Between July and August 2010, 7 men with stage T1N0 laryngeal carcinoma were included in this study. Age ranged from 47 - 74 years. Staging included endoscopic examination, CT-scan and MRI when indicated. Planned irradiation dose was 70 Gy in 35 fractions over 7 weeks. A simple treatment planning algorithm for carotid sparing was used: maximum point dose to the carotids 35 Gy, to the spinal cord 30 Gy, and 100% PTV volume to be covered with 95% of the prescribed dose. Carotid volume of interest extended to 1 cm above and below of the PTV. Doses to the carotid arteries, to the critical organs, and to the planned target volume (PTV) with our standard laryngeal irradiation protocol was compared. Daily megavoltage scans were obtained before each fraction. When necessary, the Planned Adaptive software (TomoTherapy Inc., Madison, WI) was used to evaluatethe need for a re-planning, which has never been indicated. Dose data were extracted using the VelocityAI software (Atlanta, GA), and data normalization and dose-volume histogram (DVH) interpolation were realized using the Igor Pro software (Portland, OR).Results:A significant (p\0.05) carotid dose sparing compared to our standard protocol with an average maximum point dose of 38.3 Gy (standard deviation [SD] 4.05 Gy), average mean dose of 18.59 Gy (SD 0.83 Gy) was achieved. In all patients, 95% of the carotid volume received less than 28.4 Gy (SD 0.98 Gy). The average maximum point dose to the spinal cord was 25.8 Gy (SD 3.24 Gy). PTV was fully covered with more than 95% of the prescribed dose for all patients with an average maximum point dose of 74.1 Gy and the absolute maximum dose in a single patient of 75.2 Gy. To date, the clinical outcomes have been excellent. Three patients (42%) developed stage 1 mucositis that was conservatively managed, and all the patients presented a mild to moderate dysphonia. All adverse effects resolved spontaneously in the month following the end of treatment. Early local control rate is 100% considering a 4 - 5 months post treatment follow-up.Conclusions: Helical Tomotherapy allows a clinically significant decrease of carotid irradiation dose compared to standard irradiation protocols with an acceptable spinal cord dose tradeoff. Moreover, this technique allows the PTV to be homogenously covered with a curative irradiation dose. Daily control imaging brings added security margins especially when working with high dose gradients. Further investigations and follow-up are underway to better evaluate the late clinical outcomes especially the local control rate, late laryngeal and vascular toxicity, and expected potential impact on cerebrovascular events.

Neuropeptide Y infusion decreases plasma renin activity in postmyocardial infarction rats.

We wished to determine if chronic neuropeptide Y (NPY) infusion (1 ng/min for 1 week by Alzet minipump) could decrease plasma renin activity (PRA) and norepinephrine (NE) in a rat myocardial infarction (MI) model of moderate compensated congestive heart failure (CHF). CHF was produced by prior (6-8 weeks) ligation of the left coronary artery; control rats were sham-operated. Carotid arterial blood was drawn for PRA and NE in conscious unrestrained rats that had been instrumented 24 h earlier. MI rats had increased PRA as compared with sham-operated rats [8.73 +/- 1.27 vs. 5.10 +/- 0.91 ng angiotensin (AI) I/ml.h, mean +/- SE]. During chronic NPY infusion, PRA was reduced to normal in the MI group (4.78 +/- 0.91) but was not affected in the sham group (5.65 +/- 0.51). Plasma NE was altered similarly, but the changes did not reach statistical significance. These data suggest that NPY has the capacity to restrain renin release in moderate compensated CHF.

Iterative image reconstruction techniques: cardiothoracic computed tomography applications.

Iterative image reconstruction algorithms provide significant improvements over traditional filtered back projection in computed tomography (CT). Clinically available through recent advances in modern CT technology, iterative reconstruction enhances image quality through cyclical image calculation, suppressing image noise and artifacts, particularly blooming artifacts. The advantages of iterative reconstruction are apparent in traditionally challenging cases-for example, in obese patients, those with significant artery calcification, or those with coronary artery stents. In addition, as clinical use of CT has grown, so have concerns over ionizing radiation associated with CT examinations. Through noise reduction, iterative reconstruction has been shown to permit radiation dose reduction while preserving diagnostic image quality. This approach is becoming increasingly attractive as the routine use of CT for pediatric and repeated follow-up evaluation grows ever more common. Cardiovascular CT in particular, with its focus on detailed structural and functional analyses, stands to benefit greatly from the promising iterative solutions that are readily available.

Testing the use of two types of nest box by the common dormouse Muscardinus avellanarius

British mammalogists have used two different systems for surveying the common dormouse Muscardinus avellanarius: a modified bird nest box with the entrance facing the tree trunk, and a smaller, cheaper model called a "nest tube". However, only few data comparing different nest box systems are currently available. To determine which system is more efficient, we compared the use of the large (GB-type) and small nest boxes (DE-type, a commercial wooden mouse trap without a door) in three Swiss forest. The presence of Muscardinus, potential competitors, and any evidence of occupation were examined in 60 pairs of nest boxes based on 2,280 nest box checks conducted over 5 years. Mean annual occupation and cumulative numbers of Muscardinus present were both significantly higher for the DE than for the GB boxes (64.6% versus 32.1%, and 149 versus 67 dormice, respectively). In contrast, the annual occupation by competitors including Glis glis, Apodemus spp. and hole-nesting birds was significantly higher in the GB than in the DE boxes in all forest (19-68% versus 0-16%, depending on the species and forest). These results suggest that smaller nest boxes are preferred by the common dormouse and are rarely occupied by competitors. These boxes hence appear to be preferable for studying Muscardinus populations.

Mophological analysis of the human vasculature from medical imaging. Application to cerebral and coranary arteries

In this project, we have investigated new ways of modelling and analysis of human vasculature from Medical images. The research was divided in two main areas: cerebral vasculature analysis and coronary arteries modeling. Regarding cerebral vasculature analysis, we have studed cerebral aneurysms, internal carotid and the Circle of Willis (CoW). Aneurysms are abnormal vessel enlargements that can rupture causing important cerebral damages or death. The understanding of this pathology, together with its virtual treatment, and image diagnosis and prognosis, includes identification and detailed measurement of the aneurysms. In this context, we have proposed two automatic aneurysm isolation method, to separate the abnormal part of the vessel from the healthy part, to homogenize and speed-up the processing pipeline usually employed to study this pathology, [Cardenes2011TMI, arrabide2011MedPhys]. The results obtained from both methods have been also compared and validatied in [Cardenes2012MBEC]. A second important task here the analysis of the internal carotid [Bogunovic2011Media] and the automatic labelling of the CoW, Bogunovic2011MICCAI, Bogunovic2012TMI]. The second area of research covers the study of coronary arteries, specially coronary bifurcations because there is where the formation of atherosclerotic plaque is more common, and where the intervention is more challenging. Therefore, we proposed a novel modelling method from Computed Tomography Angiography (CTA) images, combined with Conventional Coronary Angiography (CCA), to obtain realistic vascular models of coronary bifurcations, presented in [Cardenes2011MICCAI], and fully validated including phantom experiments in [Cardene2013MedPhys]. The realistic models obtained from this method are being used to simulate stenting procedures, and to investigate the hemodynamic variables in coronary bifurcations in the works submitted in [Morlachi2012, Chiastra2012]. Additionally, another preliminary work has been done to reconstruct the coronary tree from rotational angiography, and published in [Cardenes2012ISBI].

Comparativecost-effectivenessanalyses of cardiacmagneticresonanceimaging versus invasive coronary angiography combined with fractional flow reserve testing to diagnose ischemia in coronary artery disease

Introduction: According to guidelines, patients with coronary artery disease (CAD) should undergo revascularization if myocardial ischemia is present. While coronary angiography (CXA) allows the morphological assessment of CAD, the fractional flow reserve (FFR) has proved to be a complementary invasive test to assess the functional significance of CAD, i.e. to detect ischemia. Perfusion Cardiac Magnetic Resonance (CMR) has turned out to be a robust non-invasive technique to assess myocardial ischemia. The objective: is to compare the cost-effectiveness ratio - defined as the costs per patient correctly diagnosed - of two algorithms used to diagnose hemodynamically significant CAD in relation to the pretest likelihood of CAD: 1) aCMRto assess ischemia before referring positive patients to CXA (CMR + CXA), 2) a CXA in all patients combined with a FFR test in patients with angiographically positive stenoses (CXA + FFR). Methods: The costs, evaluated from the health care system perspective in the Swiss, German, the United Kingdom (UK) and the United States (US) contexts, included public prices of the different tests considered as outpatient procedures, complications' costs and costs induced by diagnosis errors (false negative). The effectiveness criterion wasthe ability to accurately identify apatient with significantCAD.Test performancesused in the model were based on the clinical literature. Using a mathematical model, we compared the cost-effectiveness ratio for both algorithms for hypothetical patient cohorts with different pretest likelihood of CAD. Results: The cost-effectiveness ratio decreased hyperbolically with increasing pretest likelihood of CAD for both strategies. CMR + CXA and CXA + FFR were equally costeffective at a pretest likelihood of CAD of 62% in Switzerland, 67% in Germany, 83% in the UK and 84% in the US with costs of CHF 5'794, Euros 1'472, £ 2'685 and $ 2'126 per patient correctly diagnosed. Below these thresholds, CMR + CXA showed lower costs per patient correctly diagnosed than CXA + FFR. Implications for the health care system/professionals/patients/society These results facilitate decision making for the clinical use of new generations of imaging procedures to detect ischemia. They show to what extent the cost-effectiveness to diagnose CAD depends on the prevalence of the disease.