A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page

Технологические решения для строительства разведочной вертикальной скважины глубиной 2680 метров на газовом месторождении (ХМАО)

Технологические решения для строительства разведочной вертикальной скважины глубиной 2680 метров на газовом месторождении (ХМАО).Technological solutions for the construction of an exploration vertical well with a depth of 2680 meters at the gas field (KHMAO)

Data from: Looking up: a dozen years of evolution of neurology clerkships in the United States

Objective: To report a 2017 survey of all US medical school neurology clerkship directors (CDs) and to compare the results to similar surveys conducted in 2005 and 2012. Methods: An American Academy of Neurology (AAN) Consortium of Neurology Clerkship Directors (CNCD) workgroup developed the survey that was sent to all neurology CDs listed in the AAN CNCD database. Comparisons were made to similar 2005 and 2012 surveys. Results: The response rate was 92 of 146 programs (63%). Among the responding institutions, neurology is required in 94% of schools and is 4 weeks in length in 75%. From 2005 to 2017, clerkships shifted out of a fourth-year-only rotation (p = 0.035) to earlier curricular time points. CD protected time averages 0.24 full-time equivalent (FTE), with 31% of CDs reporting 0.26 to 0.50 FTE support, a >4-fold increase from prior surveys (p 12 years increased from 9% in 2005 to 23% in 2017. Twenty-seven percent also serve as division chief/director, and 22% direct a preclinical neuroscience course. Forty-nine percent of CDs are very satisfied in their role, increased from 34% in 2012 (p = 0.046). The majority of CDs identify as white and male, with none identifying as black/African American. Conclusion: Changes since 2005 and 2012 include shifting of the neurology clerkship to earlier in the medical school curriculum and an increase in CD salary support. CDs are more satisfied than reflected in previous surveys and stay in the role longer. There is a lack of racial diversity among neurology CDs

Phase 1/2 Dose-Escalation Study of the Use of Intensity Modulated Radiation Therapy to Treat the Prostate and Pelvic Nodes in Patients With Prostate Cancer

Purpose: To investigate the feasibility of dose escalation and hypofractionation of pelvic lymph node intensity modulated radiation therapy (PLN-IMRT) in prostate cancer (PCa). Methods and Materials: In a phase 1/2 study, patients with advanced localized PCa were sequentially treated with 70 to 74 Gy to the prostate and dose-escalating PLN-IMRT at doses of 50 Gy (cohort 1), 55 Gy (cohort 2), and 60 Gy (cohort 3) in 35 to 37 fractions. Two hypofractionated cohorts received 60 Gy to the prostate and 47 Gy to PLN in 20 fractions over 4 weeks (cohort 4) and 5 weeks (cohort 5). All patients received long-course androgen deprivation therapy. Primary outcome was late Radiation Therapy Oncology Group toxicity at 2 years after radiation therapy for all cohorts. Secondary outcomes were acute and late toxicity using other clinician/patient-reported instruments and treatment efficacy. Results: Between August 9, 2000, and June 9, 2010, 447 patients were enrolled. Median follow-up was 90 months. The 2-year rates of grade 2+ bowel/bladder toxicity were as follows: cohort 1, 8.3%/4.2% (95% confidence interval 2.2%-29.4%/0.6%-26.1%); cohort 2, 8.9%/5.9% (4.1%-18.7%/2.3%-15.0%); cohort 3, 13.2%/2.9% (8.6%-20.2%/1.1%-7.7%); cohort 4, 16.4%/4.8% (9.2%-28.4%/1.6%-14.3%); cohort 5, 12.2%/7.3% (7.6%-19.5%/3.9%-13.6%). Prevalence of bowel and bladder toxicity seemed to be stable over time. Other scales mirrored these results. The biochemical/clinical failureefree rate was 71% (66%-75%) at 5 years for the whole group, with pelvic lymph node control in 94% of patients. Conclusion s: This study shows the safety and tolerability of PLN-IMRT. Ongoing and planned phase 3 studies will need to demonstrate an increase in efficacy using PLN-IMRT to offset the small increase in bowel side effects compared with prostate-only IMRT. (C) 2017 The Authors. Published by Elsevier Inc