Mesoscale analysis by numerical modeling coupled with satellite-based sounding

November 1988.Principal investigators: Thomas H. Vonder Haar, James F.W. Purdom.Includes bibliographical references.This dissertation deals with the development of a system for time-continuous mesoscale analysis and its use in studying the mesoscale distribution of summertime convective cloud development in the Northeastern Colorado region. There were two basic components of the system — a version of the CSU Regional Atmospheric Modeling System (RAMS) and an algorithm for retrieving temperatures and water vapor concentrations from VISSR Atmospheric Sounder (VAS) data. The system was designed to avoid some of the problems that researchers have encountered when satellite-retrieved parameters have been input to models. The primary distinguishing feature of the new method is that there is an intimate coupling of the retrieval and modeling processes. Water vapor concentrations and ground surface temperatures were the foci of the analyses. In preparation for analysis experiments we tested the sensitivity of a two-dimensional version of the model to various controls on the behavior of water vapor concentrations and surface temperatures. For water vapor mixing ratios, variations that might be caused by analysis errors had very little impact on the dynamics of circulations in the pre-convective stage. In contrast, ground surface temperature variations were shown to have a large impact on circulations, so analysis errors are very relevant to pre-convective dynamics. The first comparisons of the coupled analysis method with other, related, methods was by means of two-dimensional simulations. Analyses in which surface temperatures were derived from satellite-retrievals were compared with the alternative of relying on energy balance computations. The energy balance computations were so sensitive to soil characteristics, which were simulated as unknown, that the satellite retrieval method gave better results even with cloud contamination. In water vapor analysis comparisons no single method was superior in every respect, but the coupled method performed relatively well. Vertical gradients and horizontal gradients were well represented, and the method was relatively insensitive to a common problem in pre-convective analysis — contamination of satellite data by increasing amounts of small convective clouds. Analysis methods were further compared in a three-dimensional case study for 21 August 1983. The horizontal and time variations of satellite-retrieved surface temperatures closely corresponded to the conventional shelter temperature observations, but had much greater detail. In contrast, the energy balance-based temperatures tended to increase too quickly during the morning and lacked some of the observed gradients. According to the retrievals, there can be very large mesoscale gradients in temperatures at the ground surface even on the relatively flat plains. In the case study water vapor analyses there were substantial differences among the results of the several methods that were intercompared. The study demonstrated that, when the first set of satellite data is less reliable than the later sets, some of the contamination lingers throughout the time-continuous coupled analysis results. However, the coupled method generally appeared to be the most valuable of the methods considered in this study because it exploited the major strengths of the numerical model and the satellite data while making it relatively easy to recognize any impacts of their weaknesses. The results of this dissertation support the hypothesis that both ground surface temperatures and terrain variations can play important roles in pre-convective water vapor kinematics through their influences on vertical and horizontal winds. The development of convective clouds corresponded largely, but not exclusively, with convergence and deepening of low-level water vapor. The analysis system proved to be valuable for forecasting through the close correspondence between derived stability indices and later convective development. The new method is a step in the expanding capability of meteorologists to combine tools and sources of data for understanding and forecasting mesoscale phenomena.Research supported by National Oceanic and Atmospheric Administration Grant NA-85-RAH-05045 (53-1209) and in part by Army Research Office Center for Geosciences, Grant DALL-03-86-K-9175

Approximate Query Service on Autonomous IoT Cameras

Elf is a runtime for an energy-constrained camera to continuously summarize video scenes as approximate object counts. Elf's novelty centers on planning the camera's count actions under energy constraint. (1) Elf explores the rich action space spanned by the number of sample image frames and the choice of per-frame object counters; it unifies errors from both sources into one single bounded error. (2) To decide count actions at run time, Elf employs a learning-based planner, jointly optimizing for past and future videos without delaying result materialization. Tested with more than 1,000 hours of videos and under realistic energy constraints, Elf continuously generates object counts within only 11% of the true counts on average. Alongside the counts, Elf presents narrow errors shown to be bounded and up to 3.4x smaller than competitive baselines. At a higher level, Elf makes a case for advancing the geographic frontier of video analytics

Guidelines of the International Headache Society for controlled trials of pharmacological preventive treatment for persistent post-traumatic headache attributed to mild traumatic brain injury

Background: Persistent headache attributed to traumatic injury to the head is divided into two subtypes, one attributed to moderate or severe traumatic injury and another attributed to mild traumatic injury (i.e., concussion). The latter is much more prevalent, in part because more than 90% of cases with traumatic brain injury are classified as mild. The pathophysiology of persistent post-traumatic headache is poorly understood and the underlying mechanisms are likely multifactorial. There is currently no approved treatment specifically for persistent post-traumatic headache, and management strategies rely on medications used for migraine or tension-type headache. Therefore, high-quality trials are urgently needed to support clinical decision-making and optimize management strategies. International guidelines can facilitate appropriate trial design and ensure the acquisition of high-quality data evaluating the efficacy, tolerability, and safety of available and novel pharmacological therapies for the preventive treatment of persistent post-traumatic headache. Methods: The development of this guideline was based on a literature review of available studies in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, along with a review of previously published guidelines for controlled trials of preventive treatment for episodic and chronic migraine. The identified literature was critically appraised, and due to the scarcity of scientific evidence, recommendations were primarily based on the consensus of experts in the field. Objective: To provide guidelines for designing state-of-the-art controlled clinical trials aimed at evaluating the effectiveness of preventive treatments for persistent post-traumatic headache attributed to mild traumatic brain injury

Estimating the clinical effectiveness and value-based price range of erenumab for the prevention of migraine in patients with prior treatment failures: a US societal perspective

BACKGROUND: Frequent migraine with four or more headache days per month is a common, disabling neurovascular disease. From a US societal perspective, this analysis models the clinical efficacy and estimates the value-based price (VBP) for erenumab, a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor. METHODS: A Markov health state transition model was developed to estimate the incremental costs, quality-adjusted life-years (QALYs), and value-based price range for erenumab in migraine prevention. The model comprises "on preventive treatment", "off preventive treatment", and "death" health states across a 10-year time horizon. The evaluation compared erenumab to no preventive treatment in episodic and chronic migraine patients that have failed at least one preventive therapy. Therapeutic benefits are based on estimated changes in monthly migraine days (MMD) from erenumab pivotal clinical trials and a network meta-analysis of migraine studies. Utilities were estimated using previously published mapping algorithms. A VBP analysis was performed to identify maximum erenumab annual prices at willingness-to-pay (WTP) thresholds of $100,000-$200,000 per QALY. Estimates of VBP under different scenarios such as choice of different comparators, assumptions around inclusion of placebo effect, and exclusion of work productivity losses were also generated. RESULTS: Erenumab resulted in incremental QALYs of 0.185 vs supportive care (SC) and estimated cost offsets due to reduced MMD of $8,482 over 10 years, with an average duration of treatment of 2.01 years. The estimated VBP at WTP thresholds of$100,000-$200,000 for erenumab compared to SC ranged from$14,238-$23,998. VBP estimates including the placebo effect and excluding work productivity ranged from$7,445-$13,809; increasing to$12,151-$18,589 with onabotulinumtoxinA as a comparator in chronic migraine. CONCLUSION: Erenumab is predicted to reduce migraine-related direct and indirect costs, and increase QALYs compared to SC

Evaluation of single-footprint AIRS CH4 profile retrieval uncertainties using aircraft profile measurements

We evaluate the uncertainties of methane optimal estimation retrievals from single-footprint thermal infrared observations from the Atmospheric Infrared Sounder (AIRS). These retrievals are primarily sensitive to atmospheric methane in the mid-troposphere through the lower stratosphere (&sim;2 to &sim;17&thinsp;km). We compare them to in situ observations made from aircraft during the HIAPER Pole to Pole Observations (HIPPO) and Atmospheric Tomography Mission (ATom) campaigns, and from the NOAA GML aircraft network, between the surface and 5&ndash;13&thinsp;km, across a range of years, latitudes between 60∘&thinsp;S to 80∘&thinsp;N, and over land and ocean. After a global, pressure-dependent bias correction, we find that the land and ocean have similar biases and that the reported observation error (combined measurement and interference errors) of &sim;27&thinsp;ppb is consistent with the SD between aircraft and individual AIRS observations. A single observation has measurement (noise related) uncertainty of &sim;17&thinsp;ppb, a &sim;20&thinsp;ppb uncertainty from radiative interferences (e.g., from water or temperature), and &sim;30&thinsp;ppb due to &ldquo;smoothing error&rdquo;, which is partially removed when making comparisons to in situ measurements or models in a way that accounts for this regularization. We estimate a 10&thinsp;ppb validation uncertainty because the aircraft typically did not measure methane at altitudes where the AIRS measurements have some sensitivity, e.g., the stratosphere, and there is uncertainty in the truth that we validate against. Daily averaging only partly reduces the difference between aircraft and satellite observation, likely because of correlated errors introduced into the retrieval from temperature and water vapor. For example, averaging nine observations only reduces the aircraft&ndash;model difference to &sim;17&thinsp;ppb vs. the expected &sim;10&thinsp;ppb. Seasonal averages can reduce this &sim;17&thinsp;ppb uncertainty further to &sim;10&thinsp;ppb, as determined through comparison with NOAA aircraft, likely because uncertainties related to radiative effects of temperature and water vapor are reduced when averaged over a season. &nbsp;</p

Brief review on systematic hypothermia for the protection of central nervous system during aortic arch surgery: a double-sword tool?

Antegrade selective cerebral perfusion in conjunction with hypothermia attenuate postoperative neurological injury, which in turn still remains the main cause of mortality and morbidity following aortic arch surgery. Hypothermic circulatory arrest however could be a useful tool during arch surgery, surgery for chronic thromboembolic disease, air on the arterial line during CPB, during cavotomy for extraction of renal cell carcinoma with level IV extension, or when dealing with difficult trauma to the SVC or IVC. Cerebral protective effects with hypothermic procedures including inhibition of neuron excitation, and discharge of excitable amino acids, and thereby, prevention of an increase in intercellular calcium ions, hyperoxidation of lipids in cell membranes, and free radical production

Monitoring quality of care in hepatocellular carcinoma: A modified delphi consensus

Although there are several established international guidelines on the management of hepatocellular carcinoma (HCC), there is limited information detailing specific indicators of good quality care. The aim of this study was to develop a core set of quality indicators (QIs) to underpin the management of HCC. We undertook a modified, two-round, Delphi consensus study comprising a working group and experts involved in the management of HCC as well as consumer representatives. QIs were derived from an extensive review of the literature. The role of the participants was to identify the most important and measurable QIs for inclusion in an HCC clinical quality registry. From an initial 94 QIs, 40 were proposed to the participants. Of these, 23 QIs ultimately met the inclusion criteria and were included in the final set. This included (a) nine related to the initial diagnosis and staging, including timing to diagnosis, required baseline clinical and laboratory assessments, prior surveillance for HCC, diagnostic imaging and pathology, tumor staging, and multidisciplinary care; (b) thirteen related to treatment and management, including role of antiviral therapy, timing to treatment, localized ablation and locoregional therapy, surgery, transplantation, systemic therapy, method of response assessment, and supportive care; and (c) one outcome assessment related to surgical mortality. Conclusion: We identified a core set of nationally agreed measurable QIs for the diagnosis, staging, and management of HCC. The adherence to these best practice QIs may lead to system-level improvement in quality of care and, ultimately, improvement in patient outcomes, including survival

Altered translation of GATA1 in Diamond-Blackfan anemia

Ribosomal protein haploinsufficiency occurs in diverse human diseases including Diamond-Blackfan anemia (DBA)[superscript 1, 2], congenital asplenia[superscript 3] and T cell leukemia[superscript 4]. Yet, how mutations in genes encoding ubiquitously expressed proteins such as these result in cell-type– and tissue-specific defects remains unknown[superscript 5]. Here, we identify mutations in GATA1, encoding the critical hematopoietic transcription factor GATA-binding protein-1, that reduce levels of full-length GATA1 protein and cause DBA in rare instances. We show that ribosomal protein haploinsufficiency, the more common cause of DBA, can lead to decreased GATA1 mRNA translation, possibly resulting from a higher threshold for initiation of translation of this mRNA in comparison with other mRNAs. In primary hematopoietic cells from patients with mutations in RPS19, encoding ribosomal protein S19, the amplitude of a transcriptional signature of GATA1 target genes was globally and specifically reduced, indicating that the activity, but not the mRNA level, of GATA1 is decreased in patients with DBA associated with mutations affecting ribosomal proteins. Moreover, the defective hematopoiesis observed in patients with DBA associated with ribosomal protein haploinsufficiency could be partially overcome by increasing GATA1 protein levels. Our results provide a paradigm by which selective defects in translation due to mutations affecting ubiquitous ribosomal proteins can result in human disease.National Institutes of Health (U.S.) (Grant P01 HL32262)National Institutes of Health (U.S.) (Grant U54 HG003067-09

Targeting Angiogenesis-Dependent Calcified Neoplasms Using Combined Polymer Therapeutics

There is an immense clinical need for novel therapeutics for the treatment of angiogenesis-dependent calcified neoplasms such as osteosarcomas and bone metastases. We developed a new therapeutic strategy to target bone metastases and calcified neoplasms using combined polymer-bound angiogenesis inhibitors. Using an advanced "living polymerization" technique, the reversible addition-fragmentation chain transfer (RAFT), we conjugated the aminobisphosphonate alendronate (ALN), and the potent anti-angiogenic agent TNP-470 with N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer through a Glycine-Glycine-Proline-Norleucine linker, cleaved by cathepsin K, a cysteine protease overexpressed at resorption sites in bone tissues. In this approach, dual targeting is achieved. Passive accumulation is possible due to the increase in molecular weight following polymer conjugation of the drugs, thus extravasating from the tumor leaky vessels and not from normal healthy vessels. Active targeting to the calcified tissues is achieved by ALN's affinity to bone mineral.The anti-angiogenic and antitumor potency of HPMA copolymer-ALN-TNP-470 conjugate was evaluated both in vitro and in vivo. We show that free and conjugated ALN-TNP-470 have synergistic anti-angiogenic and antitumor activity by inhibiting proliferation, migration and capillary-like tube formation of endothelial and human osteosarcoma cells in vitro. Evaluation of anti-angiogenic, antitumor activity and body distribution of HPMA copolymer-ALN-TNP-470 conjugate was performed on severe combined immunodeficiency (SCID) male mice inoculated with mCherry-labeled MG-63-Ras human osteosarcoma and by modified Miles permeability assay. Our targeted bi-specific conjugate reduced VEGF-induced vascular hyperpermeability by 92% and remarkably inhibited osteosarcoma growth in mice by 96%.This is the first report to describe a new concept of a narrowly-dispersed combined polymer therapeutic designed to target both tumor and endothelial compartments of bone metastases and calcified neoplasms at a single administration. This new approach of co-delivery of two synergistic drugs may have clinical utility as a potential therapy for angiogenesis-dependent cancers such as osteosarcoma and bone metastases