Guidelines for the use of cell lines in biomedical research

Cell-line misidentification and contamination with microorganisms, such as mycoplasma, together with instability, both genetic and phenotypic, are among the problems that continue to affect cell culture. Many of these problems are avoidable with the necessary foresight, and these Guidelines have been prepared to provide those new to the field and others engaged in teaching and instruction with the information necessary to increase their awareness of the problems and to enable them to deal with them effectively. The Guidelines cover areas such as development, acquisition, authentication, cryopreservation, transfer of cell lines between laboratories, microbial contamination, characterisation, instability and misidentification. Advice is also given on complying with current legal and ethical requirements when deriving cell lines from human and animal tissues, the selection and maintenance of equipment and how to deal with problems that may arise

HabEx polarization ray trace and aberration analysis

The flux difference between a terrestrial exoplanet and a much brighter nearby star creates an enormous optical design challenge for space-based imaging systems. Coronagraphs are designed to block the star’s flux and obtain a high-dynamic-range image of the exoplanet. The contrast of an optical system is calculated using the point spread function (PSF). Contrast quantifies starlight suppression of an imaging system at a given separation of the two objects. Contrast requirements can be as small as 10^(−10) for earth-like planets. This work reports an analysis of the September 2017 Habitable Exoplanet Imaging Mission (HabEx) end-to-end optical system prescription for geometric and polarization aberrations across the 450 to 550 nm channel. The Lyot coronagraph was modeled with a vector vortex charge 6 mask but without adaptive optics (AO) to correct the phase of the Jones pupil. The detector plane irradiance was calculated for three states of the telescope/coronagraph system: (1) free of geometric and polarization aberrations; (2) isotropic mirror coatings throughout the end-toend system; and (3) isotropic mirrors with form birefringence on the primary mirror. For each of these three states the system response both with and without a coronagraph mask was calculated. Two merit functions were defined to quantify the system’s ability to attenuate starlight: (1) normalized polychromatic irradiance (NPI), and (2) starlight suppression factor (SSF). Both of these are dimensionless and their values are functions of position across the focal plane. The NPI is defined as the irradiance point-by-point across the detector plane with a coronagraph mask divided by the value of the on-axis irradiance without a coronagraph mask. The SSF is the irradiance point-by-point across the detector plane with a coronagraph mask divided by the pointby-point value of the irradiance across the detector plane without a coronagraph mask. Both the NPI and the SSF provide insights into coronagraph performance. Deviations from the aberration-free case are calculated and summarized in table 2. The conclusions are: (1) the HabEx optical system is well-balanced for both geometric and polarization aberrations; (2) the spatially dependent polarization reflectivity for the HabEx primary mirror should be specified to ensure the coating is isotropic; (3) AO to correct the two orthogonal polarization-dependent wavefront errors is essential

HabEx polarization ray trace and aberration analysis

The flux difference between a terrestrial exoplanet and a much brighter nearby star creates an enormous optical design challenge for space-based imaging systems. Coronagraphs are designed to block the star’s flux and obtain a high-dynamic-range image of the exoplanet. The contrast of an optical system is calculated using the point spread function (PSF). Contrast quantifies starlight suppression of an imaging system at a given separation of the two objects. Contrast requirements can be as small as 10^(−10) for earth-like planets. This work reports an analysis of the September 2017 Habitable Exoplanet Imaging Mission (HabEx) end-to-end optical system prescription for geometric and polarization aberrations across the 450 to 550 nm channel. The Lyot coronagraph was modeled with a vector vortex charge 6 mask but without adaptive optics (AO) to correct the phase of the Jones pupil. The detector plane irradiance was calculated for three states of the telescope/coronagraph system: (1) free of geometric and polarization aberrations; (2) isotropic mirror coatings throughout the end-toend system; and (3) isotropic mirrors with form birefringence on the primary mirror. For each of these three states the system response both with and without a coronagraph mask was calculated. Two merit functions were defined to quantify the system’s ability to attenuate starlight: (1) normalized polychromatic irradiance (NPI), and (2) starlight suppression factor (SSF). Both of these are dimensionless and their values are functions of position across the focal plane. The NPI is defined as the irradiance point-by-point across the detector plane with a coronagraph mask divided by the value of the on-axis irradiance without a coronagraph mask. The SSF is the irradiance point-by-point across the detector plane with a coronagraph mask divided by the pointby-point value of the irradiance across the detector plane without a coronagraph mask. Both the NPI and the SSF provide insights into coronagraph performance. Deviations from the aberration-free case are calculated and summarized in table 2. The conclusions are: (1) the HabEx optical system is well-balanced for both geometric and polarization aberrations; (2) the spatially dependent polarization reflectivity for the HabEx primary mirror should be specified to ensure the coating is isotropic; (3) AO to correct the two orthogonal polarization-dependent wavefront errors is essential

The effect of ageing on fMRI: Correction for the confounding effects of vascular reactivity evaluated by joint fMRI and MEG in 335 adults.

In functional magnetic resonance imaging (fMRI) research one is typically interested in neural activity. However, the blood-oxygenation level-dependent (BOLD) signal is a composite of both neural and vascular activity. As factors such as age or medication may alter vascular function, it is essential to account for changes in neurovascular coupling when investigating neurocognitive functioning with fMRI. The resting-state fluctuation amplitude (RSFA) in the fMRI signal (rsfMRI) has been proposed as an index of vascular reactivity. The RSFA compares favourably with other techniques such as breath-hold and hypercapnia, but the latter are more difficult to perform in some populations, such as older adults. The RSFA is therefore a candidate for use in adjusting for age-related changes in vascular reactivity in fMRI studies. The use of RSFA is predicated on its sensitivity to vascular rather than neural factors; however, the extent to which each of these factors contributes to RSFA remains to be characterized. The present work addressed these issues by comparing RSFA (i.e., rsfMRI variability) to proxy measures of (i) cardiovascular function in terms of heart rate (HR) and heart rate variability (HRV) and (ii) neural activity in terms of resting state magnetoencephalography (rsMEG). We derived summary scores of RSFA, a sensorimotor task BOLD activation, cardiovascular function and rsMEG variability for 335 healthy older adults in the population-based Cambridge Centre for Ageing and Neuroscience cohort (Cam-CAN; www.cam-can.com). Mediation analysis revealed that the effects of ageing on RSFA were significantly mediated by vascular factors, but importantly not by the variability in neuronal activity. Furthermore, the converse effects of ageing on the rsMEG variability were not mediated by vascular factors. We then examined the effect of RSFA scaling of task-based BOLD in the sensorimotor task. The scaling analysis revealed that much of the effects of age on task-based activation studies with fMRI do not survive correction for changes in vascular reactivity, and are likely to have been overestimated in previous fMRI studies of ageing. The results from the mediation analysis demonstrate that RSFA is modulated by measures of vascular function and is not driven solely by changes in the variance of neural activity. Based on these findings we propose that the RSFA scaling method is articularly useful in large scale and longitudinal neuroimaging studies of ageing, or with frail participants, where alternative measures of vascular reactivity are impractical.The Cambridge Centre for Ageing and Neuroscience (Cam-CAN) research was supported by the Biotechnology and Biological Sciences Research Council (grant number BB/H008217/1). We are grateful to the Cam-CAN respondents and their primary care teams in Cambridge for their participation in this study. We also thank col- leagues at the MRC Cognition and Brain Sciences Unit MEG and MRI facilities for their assistance.This is the final version of the article. It first appeared at http://onlinelibrary.wiley.com/doi/10.1002/hbm.22768/ful

Recruitment and reach in a school-based pediatric obesity intervention trial in rural areas

Introduction: The purpose of this study is to evaluate two recruitment strategies on schools and participant participation rates and representativeness (reach) within a pediatric obesity treatment trial tailored for families who live in rural areas. Methods: Recruitment of schools was evaluated based on their progress toward enrolling participants. Recruitment and reach of participants were evaluated using (1) participation rates and (2) representativeness of demographics and weight status of participants compared to eligible participants (who did not consent and enroll) and all students (regardless of eligibility). School recruitment, as well as participant recruitment and reach, were evaluated across recruitment methods comparing opt-in (i.e., caregivers agreed to allow their child to be screened for eligibility) vs. screen-first (i.e., all children screened for eligibility). Results: Of the 395 schools contacted, 34 schools (8.6%) expressed initial interest; of these, 27 (79%) proceeded to recruit participants, and 18 (53%) ultimately participated in the program. Of schools who initiated recruitment, 75% of schools using the opt-in method and 60% of schools using the screen-first method continued participation and were able to recruit a sufficient number of participants. The average participation rate (number of enrolled individuals divided by those who were eligible) from all 18 schools was 21.6%. This percentage was higher in schools using the screen-first method (average of 29.7%) compared to schools using the opt-in method (13.5%). Study participants were representative of the student population based on sex (female), race (White), and eligibility for free and reduced-price lunch. Study participants had higher body mass index (BMI) metrics (BMI, BMIz, and BMI%) than eligible non-participants. Conclusions: Schools using the opt-in recruitment were more likely to enroll at least 5 families and administer the intervention. However, the participation rate was higher in screen-first schools. The overall study sample was representative of the school demographics

The Politics of Commerce : The Congress of Chambers of Commerce of the Empire, 1886-1914

Peer reviewedPublisher PD

Transnational agricultural land acquisitions threaten biodiversity in the Global South

Agricultural large-scale land acquisitions have been linked with enhanced deforestation and land use change. Yet the extent to which transnational agricultural large-scale land acquisitions (TALSLAs) contribute to—or merely correlate with—deforestation, and the expected biodiversity impacts of the intended land use changes across ecosystems, remains unclear. We examine 178 georeferenced TALSLA locations in 40 countries to address this gap. While forest cover within TALSLAs decreased by 17% between 2000 and 2018 and became more fragmented, the spatio-temporal patterns of deforestation varied substantially across regions. While deforestation rates within initially forested TALSLAs were 1.5 (Asia) to 2 times (Africa) higher than immediately surrounding areas, we detected no such difference in Europe and Latin America. Our findings suggest that, whereas TALSLAs may have accelerated forest loss in Asia, a different mechanism might emerge in Africa where TALSLAs target areas already experiencing elevated deforestation. Regarding biodiversity (here focused on vertebrate species), we find that nearly all (91%) studied deals will likely experience substantial losses in relative species richness (−14.1% on average within each deal)—with mixed outcomes for relative abundance—due to the intended land use transitions. We also find that 39% of TALSLAs fall at least partially within biodiversity hotspots, placing these areas at heightened risk of biodiversity loss. Taken together, these findings suggest distinct regional differences in the nature of the association between TALSLAs and forest loss and provide new evidence of TALSLAs as an emerging threat to biodiversity in the Global South

Empirical Constraints on Turbulence in Protoplanetary Accretion Disks

We present arcsecond-scale Submillimeter Array observations of the CO(3-2) line emission from the disks around the young stars HD 163296 and TW Hya at a spectral resolution of 44 m/s. These observations probe below the ~100 m/s turbulent linewidth inferred from lower-resolution observations, and allow us to place constraints on the turbulent linewidth in the disk atmospheres. We reproduce the observed CO(3-2) emission using two physical models of disk structure: (1) a power-law temperature distribution with a tapered density distribution following a simple functional form for an evolving accretion disk, and (2) the radiative transfer models developed by D'Alessio et al. that can reproduce the dust emission probed by the spectral energy distribution. Both types of models yield a low upper limit on the turbulent linewidth (Doppler b-parameter) in the TW Hya system (<40 m/s), and a tentative (3-sigma) detection of a ~300 m/s turbulent linewidth in the upper layers of the HD 163296 disk. These correspond to roughly <10% and 40% of the sound speed at size scales commensurate with the resolution of the data. The derived linewidths imply a turbulent viscosity coefficient, alpha, of order 0.01 and provide observational support for theoretical predictions of subsonic turbulence in protoplanetary accretion disks.Comment: 18 pages, 9 figures, accepted for publication in Ap

Decimal Dilemmas: Interpreting and Addressing Misconceptions

In this article, a student's misconception of multiplication and division of decials is analyzed and findings are presented from preservice teachers’ interpretation of that misconception. The authors then highlight common decimal misconceptions, outline two strategies for addressing such misconceptions in the classroom, and include final remarks connecting the professional noticing framework with addressing misconceptions in mathematics

Growth hormone deficiency in megalencephaly-capillary malformation syndrome: An association with activating mutations in PIK3CA

Megalencephaly-capillary malformation syndrome (MCAP) is a brain overgrowth disorder characterized by cortical malformations (specifically polymicrogyria), vascular anomalies, and segmental overgrowth secondary to somatic activating mutations in the PI3K-AKT-MTOR pathway (PIK3CA). Cases of growth failure and hypoglycemia have been reported in patients with MCAP, raising the suspicion for unappreciated growth hormone (GH) deficiency. Here we report an observational multicenter study of children with MCAP and GH deficiency. Eleven participants were confirmed to have GH deficiency, all with very low or undetectable circulating concentrations of insulin-like growth factor-1 and insulin-like growth factor binding protein-3. Seven underwent GH stimulation testing and all had insufficient responses with a median GH peak of 3.7 ng/ml (range 1.1-8.6). Growth patterns revealed a drastic decline in length z-scores within the first year of life but then stabilized afterward. Five were treated with GH; one discontinued due to inconsolability. The other four participants continued on GH with improvement in linear growth velocity. Other endocrinopathies were identified in 7 of the 11 participants in this cohort. This study indicates that GH deficiency is associated with MCAP and that children with MCAP and hypoglycemia and/or postnatal growth failure should be evaluated for GH deficiency and other endocrinopathies