Life Science Industry Regional Clusters: Spatial Concentrations in Denver/Boulder, Colorado and Triad/Triangle, North Carolina

This research examines the importance of proximity and the role of distance within the life science sector of the economy for the interacting metropolitan regions of Denver and Boulder, Colorado and Triad and Triangle, North Carolina. This sector is characterized by high technology employment, research and development, and knowledge spillovers. The thesis of this research is that synergies among sectors within the life science industry exist between proximate places to build a regional economic growth engine. Denver/Boulder, CO and Triad/Triangle, NC are complementary regions which share benefits of interactions within the growing life science sector of the economy because of proximity, strong commuting ties, a solid university system, and adequate research funding. Statistics and data regarding labor sources and employment, commuting patterns, and funding come from the Bureau of Labor Statistics, ReferenceUSA Employment database, Census Transportation Planning Package, and the National Institute of Health. Employment figures are classified by selected life science sectors within the North American Industry Classification System (NAICS). Analysis of these statistics will demonstrate the clustering of life science employment, ease of mobility within the regions, and strength of research and development within the study areas. Conclusions demonstrate that proximate places in Colorado and North Carolina possess the attributes necessary to maintain a successful economic environment for the life science industry to develop

Southern hemisphere plants show more delays than advances in flowering phenology

Shifts in flowering phenology have been studied in detail in the northern hemisphere and are a key plant response to climate change. However, there are relatively fewer data on species' phenological shifts in the southern hemisphere. We combined historic field data, data from herbarium specimens dating back to 1842 and modern field data for 37 Australian species to determine whether species were flowering earlier in the year than they had in the past. We also combined our results with data compiled in the southern and northern hemispheres, respectively, to determine whether southern hemisphere species are showing fewer advances in flowering phenology through time. Across our study species, we found that 12 species had undergone significant shifts in flowering time, with four species advancing their flowering and eight species delaying their flowering. The remaining 25 species showed no significant shifts in their flowering phenology. These findings are important because delays or lack of shifts in flowering phenology can lead to mismatches in trophic interactions between plants and pollinators or seed dispersers, which can have substantial impacts on ecosystem functioning and primary productivity. Combining our field results with data compiled from the literature showed that only 58.5% of southern hemisphere species were advancing their flowering time, compared with 81.6% of species that were advancing their flowering time in the northern hemisphere. Our study provides further evidence that it is not adequate for ecologists to assume that southern hemisphere ecosystems will respond to future climate change in the same way as ecosystems north of the Equator. Synthesis. Field data and data from the literature indicate that southern hemisphere species are showing fewer advances in their flowering phenology through time, especially in comparison to northern hemisphere species

Pain and analgesic use associated with skeletal-related events in patients with advanced cancer and bone metastases

PURPOSE: Bone metastases secondary to solid tumors increase the risk of skeletal-related events (SREs), including the occurrence of pathological fracture (PF), radiation to bone (RB), surgery to bone (SB), and spinal cord compression (SCC). The aim of this study was to evaluate the impact of SREs on patients' pain, analgesic use, and pain interference with daily functioning. METHODS: Data were combined from patients with solid tumors and bone metastases who received denosumab or zoledronic acid across three identically designed phase 3 trials (N = 5543). Pain severity (worst pain) and pain interference were assessed using the Brief Pain Inventory at baseline and each monthly visit. Analgesic use was quantified using the Analgesic Quantification Algorithm. RESULTS: The proportion of patients with moderate/severe pain and strong opioid use generally increased in the 6 months preceding an SRE and remained elevated, while they remained relatively consistent over time in patients without an SRE. Regression analysis indicated that all SRE types were significantly associated with an increased risk of progression to moderate/severe pain and strong opioid use. PF, RB, and SCC were associated with significantly greater risk of pain interference overall. Results were similar for pain interference with emotional well-being. All SRE types were associated with significantly greater risk of pain interference with physical function. CONCLUSIONS: SREs are associated with increased pain and analgesic use in patients with bone metastases. Treatments that prevent SREs may decrease pain and the need for opioid analgesics and reduce the impact of pain on daily functioning

Pain and analgesic use associated with skeletal-related events in patients with advanced cancer and bone metastases

PURPOSE: Bone metastases secondary to solid tumors increase the risk of skeletal-related events (SREs), including the occurrence of pathological fracture (PF), radiation to bone (RB), surgery to bone (SB), and spinal cord compression (SCC). The aim of this study was to evaluate the impact of SREs on patients' pain, analgesic use, and pain interference with daily functioning. METHODS: Data were combined from patients with solid tumors and bone metastases who received denosumab or zoledronic acid across three identically designed phase 3 trials (N = 5543). Pain severity (worst pain) and pain interference were assessed using the Brief Pain Inventory at baseline and each monthly visit. Analgesic use was quantified using the Analgesic Quantification Algorithm. RESULTS: The proportion of patients with moderate/severe pain and strong opioid use generally increased in the 6 months preceding an SRE and remained elevated, while they remained relatively consistent over time in patients without an SRE. Regression analysis indicated that all SRE types were significantly associated with an increased risk of progression to moderate/severe pain and strong opioid use. PF, RB, and SCC were associated with significantly greater risk of pain interference overall. Results were similar for pain interference with emotional well-being. All SRE types were associated with significantly greater risk of pain interference with physical function. CONCLUSIONS: SREs are associated with increased pain and analgesic use in patients with bone metastases. Treatments that prevent SREs may decrease pain and the need for opioid analgesics and reduce the impact of pain on daily functioning

Pain outcomes in patients with bone metastases from advanced cancer: assessment and management with bone-targeting agents

Bone metastases in advanced cancer frequently cause painful complications that impair patient physical activity and negatively affect quality of life. Pain is often underreported and poorly managed in these patients. The most commonly used pain assessment instruments are visual analogue scales, a single-item measure, and the Brief Pain Inventory Questionnaire-Short Form. The World Health Organization analgesic ladder and the Analgesic Quantification Algorithm are used to evaluate analgesic use. Bone-targeting agents, such as denosumab or bisphosphonates, prevent skeletal complications (i.e., radiation to bone, pathologic fractures, surgery to bone, and spinal cord compression) and can also improve pain outcomes in patients with metastatic bone disease. We have reviewed pain outcomes and analgesic use and reported pain data from an integrated analysis of randomized controlled studies of denosumab versus the bisphosphonate zoledronic acid (ZA) in patients with bone metastases from advanced solid tumors. Intravenous bisphosphonates improved pain outcomes in patients with bone metastases from solid tumors. Compared with ZA, denosumab further prevented pain worsening and delayed the need for treatment with strong opioids. In patients with no or mild pain at baseline, denosumab reduced the risk of increasing pain severity and delayed pain worsening along with the time to increased pain interference compared with ZA, suggesting that use of denosumab (with appropriate calcium and vitamin D supplementation) before patients develop bone pain may improve outcomes. These data also support the use of validated pain assessments to optimize treatment and reduce the burden of pain associated with metastatic bone disease

Cell-Cycle Dependence of Transcription Dominates Noise in Gene Expression

The large variability in mRNA and protein levels found from both static and dynamic measurements in single cells has been largely attributed to random periods of transcription, often occurring in bursts. The cell cycle has a pronounced global role in affecting transcriptional and translational output, but how this influences transcriptional statistics from noisy promoters is unknown and generally ignored by current stochastic models. Here we show that variable transcription from the synthetic tetO promoter in S. cerevisiae is dominated by its dependence on the cell cycle. Real-time measurements of fluorescent protein at high expression levels indicate tetO promoters increase transcription rate ~2-fold in S/G2/M similar to constitutive genes. At low expression levels, where tetO promoters are thought to generate infrequent bursts of transcription, we observe random pulses of expression restricted to S/G2/M, which are correlated between homologous promoters present in the same cell. The analysis of static, single-cell mRNA measurements at different points along the cell cycle corroborates these findings. Our results demonstrate that highly variable mRNA distributions in yeast are not solely the result of randomly switching between periods of active and inactive gene expression, but instead largely driven by differences in transcriptional activity between G1 and S/G2/M.GM095733BBBE 103316MIT Startup Fun

Poor Thermal Care Practices among Home Births in Nepal: Further Analysis of Nepal Demographic and Health Survey 2011

Introduction - Hypothermia is a major factor associated with neonatal mortality in low and middle income countries. Thermal care protection of newborn through a series of measures taken at birth and during the initial days of life is recommended to reduce the hypothermia and associated neonatal mortality. This study aimed to identify the prevalence of and the factors associated with receiving ‘optimum thermal care’ among home born newborns of Nepal. Methods - Data from the Nepal Demographic and Health Surveys (NDHS) 2011 were used for this study. Women who reported a home birth for their most recent childbirth was included in the study. Factors associated with optimum thermal care were examined using Chi-square test followed by logistic regression. Results - A total of 2464 newborns were included in the study. A total of 57.6 % were dried before the placenta was delivered; 60.3% were wrapped; 24.5% had not bathing during the first 24 hours, and 63.9% were breastfed within one hour of birth. Overall, only 248 (10.7%; 95% CI (8.8 %, 12.9%)) newborns received optimum thermal care. Newborns whose mothers had achieved higher education (OR 2.810; 95% CI (1.132, 6.976)), attended four or more antenatal care visits (OR 2.563; 95% CI (1.309, 5.017)), and those whose birth were attended by skilled attendants (OR 2.178; 95% CI (1.428, 3.323)) were likely to receive optimum thermal care. Conclusion - The current study showed that only one in ten newborns in Nepal received optimum thermal care. Future newborn survival programs should focus on those mothers who are uneducated; who do not attend the recommended four or more attend antenatal care visits; and those who deliver without the assistance of skilled birth attendants to reduce the risk of neonatal hypothermia in Nepal

Dendritic Morphology Predicts Pattern Recognition Performance in Multi-compartmental Model Neurons with and without Active Conductances

This is an Open Access article published under the Creative Commons Attribution license CC BY 4.0 which allows users to read, copy, distribute and make derivative works, as long as the author of the original work is citedIn this paper we examine how a neuron’s dendritic morphology can affect its pattern recognition performance. We use two different algorithms to systematically explore the space of dendritic morphologies: an algorithm that generates all possible dendritic trees with 22 terminal points, and one that creates representative samples of trees with 128 terminal points. Based on these trees, we construct multi-compartmental models. To assess the performance of the resulting neuronal models, we quantify their ability to discriminate learnt and novel input patterns. We find that the dendritic morphology does have a considerable effect on pattern recognition performance and that the neuronal performance is inversely correlated with the mean depth of the dendritic tree. The results also reveal that the asymmetry index of the dendritic tree does not correlate with the performance for the full range of tree morphologies. The performance of neurons with dendritic tapering is best predicted by the mean and variance of the electrotonic distance of their synapses to the soma. All relationships found for passive neuron models also hold, even in more accentuated form, for neurons with active membranesPeer reviewedFinal Published versio