Comparison of Cannabinoid CB1 Receptor Binding in Adolescent and Adult Rats: A Positron Emission Tomography Study Using [18F]MK-9470

Despite the important role of cannabinoid CB1 receptors (CB1R) in brain development, little is known about their status during adolescence, a critical period for both the development of psychosis and for initiation to substance abuse. In the present study, we assessed the ontogeny of CB1R in adolescent and adult rats in vivo using positron emission tomography with [18F]MK-9470. Analysis of covariance (ANCOVA) to control for body weight that would potentially influence [18F]MK-9470 values between the two groups revealed a main effect of age (F(1,109)=5.0, P = 0.02) on [18F]MK-9470 absolute binding (calculated as percentage of injected dose) with adult estimated marginal means being higher compared to adolescents amongst 11 brain regions. This finding was confirmed using in vitro autoradiography with [3H]CP55,940 (F(10,99)=140.1, P < 0.0001). This ontogenetic pattern, suggesting increase of CB1R during the transition from adolescence to adulthood, is the opposite of most other neuroreceptor systems undergoing pruning during this period

A non-rigid registration method for mouse whole body skeleton registration

Micro-CT/PET imaging scanner provides a powerful tool to study tumor in small rodents in response to therapy. Accurate image registration is a necessary step to quantify the characteristics of images acquired in longitudinal studies. Small animal registration is challenging because of the very deformable body of the animal often resulting in different postures despite physical restraints. In this paper, we propose a non-rigid registration approach for the automatic registration of mouse whole body skeletons, which is based on our improved 3D shape context non-rigid registration method. The whole body skeleton registration approach has been tested on 21 pairs of mouse CT images with variations of individuals and time-instances. The experimental results demonstrated the stability and accuracy of the proposed method for automatic mouse whole body skeleton registration

An improved 3D shape context registration method for non-rigid surface registration

3D shape context is a method to define matching points between similar shapes as a pre-processing step to non-rigid registration. The main limitation of the approach is point mismatching, which includes long geodesic distance mismatch and neighbors crossing mismatch. In this paper, we propose a topological structure verification method to correct the long geodesic distance mismatch and a correspondence field smoothing method to correct the neighbors crossing mismatch. A robust 3D shape context model is proposed and further combined with thin-plate spline model for non-rigid surface registration. The method was tested on phantoms and rat hind limb skeletons from micro CT images. The results from experiments on mouse hind limb skeletons indicate that the approach is robust

Opportunistic dose amplification for proton and carbon ion therapy via capture of internally generated thermal neutrons

This paper presents Neutron Capture Enhanced Particle Therapy (NCEPT), a method for enhancing the radiation dose delivered to a tumour relative to surrounding healthy tissues during proton and carbon ion therapy by capturing thermal neutrons produced inside the treatment volume during irradiation. NCEPT utilises extant and in-development boron-10 and gadolinium-157-based drugs from the related field of neutron capture therapy. Using Monte Carlo simulations, we demonstrate that a typical proton or carbon ion therapy treatment plan generates an approximately uniform thermal neutron field within the target volume, centred around the beam path. The tissue concentrations of neutron capture agents required to obtain an arbitrary 10% increase in biological effective dose are estimated for realistic treatment plans, and compared to concentrations previously reported in the literature. We conclude that the proposed method is theoretically feasible, and can provide a worthwhile improvement in the dose delivered to the tumour relative to healthy tissue with readily achievable concentrations of neutron capture enhancement drugs

The Boston criteria version 2.0 for cerebral amyloid angiopathy:a multicentre, retrospective, MRI–neuropathology diagnostic accuracy study

BACKGROUND: Cerebral amyloid angiopathy (CAA) is an age-related small vessel disease, characterised pathologically by progressive deposition of amyloid β in the cerebrovascular wall. The Boston criteria are used worldwide for the in-vivo diagnosis of CAA but have not been updated since 2010, before the emergence of additional MRI markers. We report an international collaborative study aiming to update and externally validate the Boston diagnostic criteria across the full spectrum of clinical CAA presentations. METHODS: In this multicentre, hospital-based, retrospective, MRI and neuropathology diagnostic accuracy study, we did a retrospective analysis of clinical, radiological, and histopathological data available to sites participating in the International CAA Association to formulate updated Boston criteria and establish their diagnostic accuracy across different populations and clinical presentations. Ten North American and European academic medical centres identified patients aged 50 years and older with potential CAA-related clinical presentations (ie, spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes), available brain MRI, and histopathological assessment for CAA diagnosis. MRI scans were centrally rated at Massachusetts General Hospital (Boston, MA, USA) for haemorrhagic and non-haemorrhagic CAA markers, and brain tissue samples were rated by neuropathologists at the contributing sites. We derived the Boston criteria version 2.0 (v2.0) by selecting MRI features to optimise diagnostic specificity and sensitivity in a prespecified derivation cohort (Boston cases 1994-2012, n=159), then externally validated the criteria in a prespecified temporal validation cohort (Boston cases 2012-18, n=59) and a geographical validation cohort (non-Boston cases 2004-18; n=123), comparing accuracy of the new criteria to the currently used modified Boston criteria with histopathological assessment of CAA as the diagnostic standard. We also assessed performance of the v2.0 criteria in patients across all cohorts who had the diagnostic gold standard of brain autopsy. FINDINGS: The study protocol was finalised on Jan 15, 2017, patient identification was completed on Dec 31, 2018, and imaging analyses were completed on Sept 30, 2019. Of 401 potentially eligible patients presenting to Massachusetts General Hospital, 218 were eligible to be included in the analysis; of 160 patient datasets from other centres, 123 were included. Using the derivation cohort, we derived provisional criteria for probable CAA requiring the presence of at least two strictly lobar haemorrhagic lesions (ie, intracerebral haemorrhages, cerebral microbleeds, or foci of cortical superficial siderosis) or at least one strictly lobar haemorrhagic lesion and at least one white matter characteristic (ie, severe visible perivascular spaces in centrum semiovale or white matter hyperintensities in a multispot pattern). The sensitivity and specificity of these criteria were 74·8% (95% CI 65·4-82·7) and 84·6% (71·9-93·1) in the derivation cohort, 92·5% (79·6-98·4) and 89·5% (66·9-98·7) in the temporal validation cohort, 80·2% (70·8-87·6) and 81·5% (61·9-93·7) in the geographical validation cohort, and 74·5% (65·4-82·4) and 95·0% (83·1-99·4) in all patients who had autopsy as the diagnostic standard. The area under the receiver operating characteristic curve (AUC) was 0·797 (0·732-0·861) in the derivation cohort, 0·910 (0·828-0·992) in the temporal validation cohort, 0·808 (0·724-0·893) in the geographical validation cohort, and 0·848 (0·794-0·901) in patients who had autopsy as the diagnostic standard. The v2.0 Boston criteria for probable CAA had superior accuracy to the current Boston criteria (sensitivity 64·5% [54·9-73·4]; specificity 95·0% [83·1-99·4]; AUC 0·798 [0·741-0854]; p=0·0005 for comparison of AUC) across all individuals who had autopsy as the diagnostic standard. INTERPRETATION: The Boston criteria v2.0 incorporate emerging MRI markers of CAA to enhance sensitivity without compromising their specificity in our cohorts of patients aged 50 years and older presenting with spontaneous intracerebral haemorrhage, cognitive impairment, or transient focal neurological episodes. Future studies will be needed to determine generalisability of the v.2.0 criteria across the full range of patients and clinical presentations. FUNDING: US National Institutes of Health (R01 AG26484)

Variation in clutch size in relation to nest size in birds

Peer reviewe

The SIB Swiss Institute of Bioinformatics' resources: focus on curated databases

The SIB Swiss Institute of Bioinformatics (www.isb-sib.ch) provides world-class bioinformatics databases, software tools, services and training to the international life science community in academia and industry. These solutions allow life scientists to turn the exponentially growing amount of data into knowledge. Here, we provide an overview of SIB's resources and competence areas, with a strong focus on curated databases and SIB's most popular and widely used resources. In particular, SIB's Bioinformatics resource portal ExPASy features over 150 resources, including UniProtKB/Swiss-Prot, ENZYME, PROSITE, neXtProt, STRING, UniCarbKB, SugarBindDB, SwissRegulon, EPD, arrayMap, Bgee, SWISS-MODEL Repository, OMA, OrthoDB and other databases, which are briefly described in this article

Reconstrucition d'images cardiaques dynamiques synchronisees a l'ECG par maximum de vraisemblance sur les signaux obtenus a faible taux de comptage avec une gamma-camera

INIST T 71632 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEFRFranc

The vaginal radical trachelectomy: an update of a series of 125 cases and 106 pregnancies. Gynecol Oncol 2008;111: S105–10

Objective. To review our first consecutive 125 vaginal radical trachelectomies (VRT) to assess the oncologic, fertility and obstetrical outcomes. Methods. Data from our prospective database was used to identify all VRT planned between October 1991 to March 2010 in patients with early-stage cervical cancer (stages IA, IB and IIA). Chi-square test, Fisher&apos;s exact test and Student t-test were used to compare baseline characteristics and Kaplan-Meier survival curves were constructed and compared with the use of the log-rank test. Results. During the study period, 140 VRT were planned and 125 were performed. The median age of the patients was 31 and 75% were nulliparous. The majority of the lesions were stage IA2 (21%) or IB1 (69%) and 41% were grade 1. In terms of histology, 56% were squamous and 37% were adenocarcinomas. Vascular space invasion was present in 29% of cases, and 88.5% of the lesions measured ≤ 2 cm. The mean follow-up was 93 months (range: 4-225 months). There were 6 recurrences (4.8%) and 2 deaths (1.6%) following VRT. The actuarial 5-year recurrence-free survival was 95.8% [95% CI: 0.90-0.98], whereas it was 79% [95% CI: 0.49-0.93] in the group where the VRT was abandoned (p = 0.001). Higher tumor grade, LVSI and size N 2 cm appeared to be predictive of the risk of abandoning VRT (p = 0.001, p = 0.025 and p = 0.03 respectively). Tumor size N2 cm was statistically significantly associated with a higher risk of recurrence (p = 0.001). In terms of obstetrical outcome, 58 women conceived a total of 106 pregnancies. The first and second trimester miscarriage rates were 20% and 3% respectively, and 77 (73%) of the pregnancies reached the third trimester, of which 58 (75%) delivered at term. Overall, 15 (13.5%) patients experienced fertility problems, 40% of which were due to cervical factor. Twelve (80%) were able to conceive, the majority with assisted reproductive technologies. Conclusion. VRT is an oncologically safe procedure in well-selected patients with early-stage disease. Lesion size N 2 cm appears to be associated with a higher risk of recurrence and a higher risk of abandoning the planned VRT. Fertility and obstetrical outcomes post VRT are excellent

From intuition to professionalization:a qualitative study about the development of teacher identity in internal medicine senior residents

Objectives: Professional identity can be defined as a developmental process. Literature suggests that residents aiming to practice in a teaching institution should receive support for the development of teaching competencies as much as they do for medical competencies, but there is limited data on how to recognize teacher identity development in residents. Our study focused on the manifestations of teacher identity development in a group of senior residents in a four-week optional pedagogy rotation. In particular, we were interested in seeing teacher identity development towards the end of the residency program, at a time when clinician identity begins to consolidate.Methods: A qualitative and exploratory approach guided our study design. Participants were internal medicine residents, (from Yr4 to Yr6) at University of Montréal, who intended working in a university setting and were interested in developing a teaching project. Focus groups were held at three separate moments: 1) before rotation, 2) after rotation and, 3) six months after rotation. Direct content analysis was chosen to analyze our findings. Results: We observed the emergence and the evolution of teacher identity and furthermore, we identified six development pathways, which underpin the development of teacher professional identity: 1) From awkward and stereotyped usage to mastery of concepts and teaching techniques, 2) From the reproduction of implicit norms of the clinical setting to the establishment of pedagogical norms 3) From the feeling of powerlessness in teaching to a feeling of mastery and taking initiatives 4)From teaching intuitively to reasoning pedagogically 5) From a teacher based paradigm to the discovery of the learner-centered paradigm and 6) From an emerging identity as a clinician to the simultaneous construction of twin identities:clinician and teacher. Six development indicators providing operational cues to help recognize different facets of teacher identity development were then identified. Conclusion: The identity development pathways allowed us to gain deeper insights about how teacher identity develops in internal medicine residents toward the end of a pedagogical rotation. It is our hope that these findings will help educators recognize and support the development of teacher identity in their residents