Frequency of theta rhythm is controlled by acceleration, but not speed, in running rats

The theta rhythm organizes neural activity across hippocampus and entorhinal cortex. A role for theta oscillations in spatial navigation is supported by half a century of research reporting that theta frequency encodes running speed linearly so that displacement can be estimated through theta frequency integration. We show that this relationship is an artifact caused by the fact that the speed of freely moving animals could not be systematically disentangled from acceleration. Using an experimental procedure that clamps running speed at pre-set values, we find that the theta frequency of local field potentials and spike activity is linearly related to positive acceleration, but not negative acceleration or speed. The modulation by positive-only acceleration makes rhythmic activity at theta frequency unfit as a code to compute displacement or any other kinematic variable. Temporally precise variations in theta frequency may instead serve as a mechanism for speeding up entorhinal-hippocampal computations during accelerated movement.Fil: Kropff, Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina. Norwegian University of Science and Technology; NoruegaFil: Carmichael, James E.. Norwegian University of Science and Technology; NoruegaFil: Moser, Edvard I.. Norwegian University of Science and Technology; NoruegaFil: Moser, May Britt. Norwegian University of Science and Technology; Norueg

DSMM XI study: dose definition for intravenous cyclophosphamide in combination with bortezomib/dexamethasone for remission induction in patients with newly diagnosed myeloma

A clinical trial was initiated to evaluate the recommended dose of cyclophosphamide in combination with bortezomib and dexamethasone as induction treatment before stem cell transplantation for younger patients with newly diagnosed multiple myeloma (MM). Thirty patients were treated with three 21-day cycles of bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 plus dexamethasone 40 mg on the day of bortezomib injection and the day after plus cyclophosphamide at 900, 1,200, or 1,500 mg/m2 on day 1. The maximum tolerated dose of cyclophosphamide was defined as 900 mg/m2. At this dose level, 92% of patients achieved at least a partial response. The overall response rate [complete response (CR) plus partial response (PR)] across all dose levels was 77%, with a 10% CR rate. No patient experienced progressive disease. The most frequent adverse events were hematological and gastrointestinal toxicities as well as neuropathy. The results suggest that bortezomib in combination with cyclophosphamide at 900 mg/m2 and dexamethasone is an effective induction treatment for patients with newly diagnosed MM that warrants further investigation

Practical Indicators for Risk of Airborne Transmission in Shared Indoor Environments and Their Application to COVID-19 Outbreaks

Some infectious diseases, including COVID-19, can undergo airborne transmission. This may happen at close proximity, but as time indoors increases, infections can occur in shared room air despite distancing. We propose two indicators of infection risk for this situation, that is, relative risk parameter (Hr) and risk parameter (H). They combine the key factors that control airborne disease transmission indoors: viruscontaining aerosol generation rate, breathing flow rate, masking and its quality, ventilation and aerosol-removal rates, number of occupants, and duration of exposure. COVID-19 outbreaks show a clear trend that is consistent with airborne infection and enable recommendations to minimize transmission risk. Transmission in typical prepandemic indoor spaces is highly sensitive to mitigation efforts. Previous outbreaks of measles, influenza, and tuberculosis were also assessed. Measles outbreaks occur at much lower risk parameter values than COVID-19, while tuberculosis outbreaks are observed at higher risk parameter values. Because both diseases are accepted as airborne, the fact that COVID-19 is less contagious than measles does not rule out airborne transmission. It is important that future outbreak reports include information on masking, ventilation and aerosol-removal rates, number of occupants, and duration of exposure, to investigate airborne transmission

CGIAR modeling approaches for resource-constrained scenarios: I. Accelerating crop breeding for a changing climate.

Crop improvement efforts aiming at increasing crop production (quantity, quality) and adapting to climate change have been subject of active research over the past years. But, the question remains 'to what extent can breeding gains be achieved under a changing climate, at a pace sufficient to usefully contribute to climate adaptation, mitigation and food security?'. Here, we address this question by critically reviewing how model-based approaches can be used to assist breeding activities, with particular focus on all CGIAR (formerly the Consultative Group on International Agricultural Research but now known simply as CGIAR) breeding programs. Crop modeling can underpin breeding efforts in many different ways, including assessing genotypic adaptability and stability, characterizing and identifying target breeding environments, identifying tradeoffs among traits for such environments, and making predictions of the likely breeding value of the genotypes. Crop modeling science within the CGIAR has contributed to all of these. However, much progress remains to be done if modeling is to effectively contribute to more targeted and impactful breeding programs under changing climates. In a period in which CGIAR breeding programs are undergoing a major modernization process, crop modelers will need to be part of crop improvement teams, with a common understanding of breeding pipelines and model capabilities and limitations, and common data standards and protocols, to ensure they follow and deliver according to clearly defined breeding products. This will, in turn, enable more rapid and better-targeted crop modeling activities, thus directly contributing to accelerated and more impactful breeding efforts.Online Version of Record before inclusion in an issue

Modeling perennial groundcover effects on annual maize grain crop growth with the Agricultural Production Systems sIMulator

The inclusion of perennial groundcover (PGC) in maize production offers a tenable solution to natural resources-related concerns associated with conventional maize; however, insight into system management and key information gaps is needed to guide future research. We therefore extended the Agricultural Production Systems sIMulator (APSIM) to an annual and perennial intercrop by integrating annual and perennial APSIM modules. These were parameterized for Kentucky bluegrass (KB) (Poa pratensis L.) or creeping red fescue (CF) (Festuca rubra L.) as PGC using a three-year dataset. Our objectives for this intercropping modeling study were to: i) simultaneously model a PGC and annual cash crop using APSIM software; ii) utilize APSIM to understand interactive processes in the maize-PGC system; and iii) utilize the calibrated model to explore both production and environmental benefits via scenario modeling. For objective I, the integrated model successfully predicted maize total aboveground biomass (TAB) (relative root mean square error, RRMSE of 13- 27%) and PGC above- and belowground tissue N concentration (RRMSE of 11-18%). The calibrated model effectively captured observed trends in PGC biomass accumulation and soil nitrate (NO3). For objective II, model analysis showed that competition for light was the primary maize yield penalty factor from PGC, while water and N impacted maize yield later in the maize growing season. In objective III, we concluded that effective PGC suppression produces minimal maize yield loss and significant environmental benefits; conversely, poor groundcover suppression may produce unfavorable environmental consequences and decrease maize grain yield. Effective PGC suppression is key for long-term system success