Molecular Diagnostics in the Evaluation of Thyroid Nodules: Current Use and Prospective Opportunities

Thyroid cancer is the most common endocrine malignancy with an estimated 43,800 new cases to be diagnosed in 2022 and representing the 7th most common cancer in women. While thyroid nodules are very common, being identified in over 60% of randomly selected adults, only 5-15% of thyroid nodules harbor thyroid malignancy. Therefore, it is incumbent upon physicians to detect and treat thyroid malignancies as is clinically appropriate and avoid unnecessary invasive procedures in patients with benign asymptomatic lesions. Over the last 15-20 years, rapid advances have been made in cytomolecular testing to aid in thyroid nodule management. Initially, indeterminate thyroid nodules, those with Bethesda III or IV cytology and approximately a 10-40% risk of malignancy, were studied to assess benignity or malignancy. More recently, next generation sequencing and micro-RNA technology platforms have refined the diagnostic capacity of thyroid nodule molecular testing and have introduced opportunities to glean prognostic information from both cytologically indeterminate and malignant thyroid nodules. Therefore, clinicians can move beyond determination of malignancy, and utilize contemporary molecular information to aid in decisions such as extent of surgery and post-therapy monitoring plans. Future opportunities include molecularly derived information about tumor behavior, neo-adjuvant treatment opportunities and response to thyroid cancer therapies

Fractional Generalization of Gradient Systems

We consider a fractional generalization of gradient systems. We use differential forms and exterior derivatives of fractional orders. Examples of fractional gradient systems are considered. We describe the stationary states of these systems.Comment: 11 pages, LaTe

Adverse Impact of a History of Violence for Women with Breast, Cervical, Endometrial, or Overian Cancer

The experience of physical and sexual violence (victimization) is common among U.S. women and is associated with adverse health consequences. The study objectives were to estimate the prevalence of victimization in women with cancer and to examine associations with demographics, cancer screening, and cancer stage. METHODS: From 2004 to 2005, 101 women with breast, cervical, endometrial, or ovarian cancer were interviewed to collect demographics, cancer screening history, health care access/use, and violence history. Chisquare and Fisher exact tests were used test risk-factor associations. A multinomial logistic regression model was used for multivariable analysis. RESULTS: The prevalence of a history of violence was 48.5% (49/101 women), and within that group, 46.9% (23/49) had a positive childhood violence screen, 75.5% (37/49) had a positive adult screen, and 55% (27/49) reported sexual violence at any age. Women with a positive violence screen differed significantly from women with a negative screen in that they were younger (P .031), more often divorced (P.012), more likely to smoke (P.010), more often lacked commercial insurance (P.036), and had more advanced stage of disease (P.013), but they did not differ with regard to race, cancer type, education level, alcohol or drug use, or cancer screening compliance. Multivariable analysis revealed that only stage remained significant; women with a history of violence had a 2.6-fold increased chance of diagnosis in later stages (odds ratio 2.61, 95% confidence interval 1.03– 6.59). CONCLUSION: A history of violence in breast, ovarian, endometrial, and ovarian cancer patients was extremely common and correlated with advanced stage at diagnosis

Fractional Variations for Dynamical Systems: Hamilton and Lagrange Approaches

Fractional generalization of an exterior derivative for calculus of variations is defined. The Hamilton and Lagrange approaches are considered. Fractional Hamilton and Euler-Lagrange equations are derived. Fractional equations of motion are obtained by fractional variation of Lagrangian and Hamiltonian that have only integer derivatives.Comment: 21 pages, LaTe

Wave Energy

Part of the immense solar energy input to the earth is converted by natural processes into energy associated with ocean waves. The geographical location of the United Kingdom renders it one of the world ' s most favoured countries with respect to the potential availability of wave energy. In principle. the waves reaching our coastal waters from the North Atlantic might satisfy a considerable fraction of our electricity demand provided that reasonably high overall conversion efficiencies can be achieved . Inventors have recognised the power of the sea for many decades. and there has been no lack of ideas on how it might be tapped . But none of the ideas was developed on a substantial scale. since ample and relatively cheap supplies of other resources were always available . In recent years. however. there has been a growing recognition that--on a world scale-the presently used forms of energy may become too expensive,. too scarce or otherwise unavailable to meet our energy needs by themselves . The Government's responsibility is to ensure that as wide a range as possible of energy supply options are available when they may be needed . Research and development can provide the necessary technical and econom i c data on which the ultimate choices can be made . Within this context. the Government announced in 197 6 the start of an R and D programme on wave energy for which the first phase was to be a feasibility study lasting for two years. The funding level has been increased twice since that time to maintain the momentum of the programme in the light of technical progress . The programme has had three main components: -exploratory deve lopment of several different engineering concepts of wave energy converter; -supporting research in relevant engineering and scientific areas : • the collection and analysis of wave data. • analysis of the structural response to wave-induced motions. • mooring. • energy conversion and transm issi on. • environmental aspects ; -working up preliminary reference designs of full scale stations for tech nical and economic appraisal. The purpose of this paper is to review the present state of knowledge of wave energy in the light of the achievements of the first two-year phase of the programme . Development of the converters Four potential designs of converter were adopted for initial study. since the sparse data available were insufficient to enable a single concept to be chosen with confidence. Proposals for alternative concepts are received on a continuing basis and are assessed against a number of criteria: two of them have so far been added to the programme in order to explore new principles Apart from the basic technical differences the six designs differ from each other in their degree of complexity and their state of development. as described in Chapter 3 . Work on two of the designs has been advanced from laboratory wave tanks to the testing of 1 / 1 0th scale models in natural open water at Loch Ness and in the Solent. For all the designs . a combination of theoretical studies. laboratory work and engineering appraisal has clarified the factors which will prove to be the most crucial in determining which of them could be chosen for more extensive development. The programme has progressed from establishing the scientific feasibility of wave energy converters to confirming the engineering feasibility of designing and building some of the designs . In very broad terms: -the early part of the programme placed considerable emphasis on optimising the efficiency of extraction of the wave energy and proving the scientific feasibility ; -the present stage is concerned with the technical viability and is identifying the main cost centres in the designs . which can then be tackled by further R and D; -the immediate future must also place emphasis not only on the problems of construction . operation and maintenance. and on ways in which unit costs may be reduced . but also on the ability to survive in the most severe wave conditions . Whilst the technical feasibility of some types of converter has been established, we are far from the stage of recommending that a full scale generating station should be built . Of the four original concepts. no single design has yet emerged which is outstandingly better than the other designs when all factors are taken into account . The designs have changed considerably in the course of the feasibility study. and a continuing process of evol ution can be expected as in the early stages of any technical development programme. The optimum design may emerge from further changes in one of the original concepts. from a synthesis of ideas or from an alternative concept . The wave energy is distributed over a wide frequency and energy bandwidth and no des ign has yet been optimised to operate at or near peak efficiency over the whole spectrum. However, one of the new concepts introduced into the programme recently may offer significant advantages in this respect. Supporting research The extent of the available data on waves in the sea areas of primary interest is inadequate as yet for the full assessment of the resource . A start has been made in collecting and analysing new data. which will take several years to reach a satisfactory level. The results so far confirm the general point that the locations around the United Kingdom with the most abundant wave energy lie to the west of the Outer Hebrides, where several hundred km of searoom are available with average annual power levels in the range 35-60 kW / m of wavefront. The majority of the designs un der consideration are free-floating and the converters would operate on or near the water surface-- one of the most hostile environments for engineering structures . The ult imate feasibility. technical and economic . of all designs of floating converter will depend upon extensive further work on mooring and anchoring . Whilst over-designed mooring systems based on present knowledge have allowed the open water trials to proceed with the objective of gaining experience . the existing knowledge is not adequate to design cost-effective mooring systems which will ensure survival at full scale under storm conditions . Considerable progress has been made in assessing and under3tanding suitable energy conversion and transmission systems for the various designs of converter , but much more remains to be done to arrive at the most cost-effective solutions . The general engineering difficulties are quite basic and are related to the properties of the natural wave spectrum : -the conversion system must be able to handle large short-term variations in the instantaneous power level ; -the peak power level in the sea (of the order of 10,OOO kW /m) can be many times greater than the average power level (a few tens of kW / m) ; -the primary output is not in a form which can be handled conventionally (it is . of course . variable with time in a complex way). Moreover. apart from the randomness. other general problems arise from the low energy density of the input and the relatively low speeds and frequency of movement induced by the waves . Engineering devices to transmit large amounts of energy under such conditions must themselves be large. heavy and expensive . The efficient generation of electricity requires machinery operating at relatively high and preferably constant speed . The transition from the one regime to the other appears to be more straightforward for systems involving air turbines than for those which do not: some designs of converter may prove to be intractable in this respect. Many possible forms of energy transmission to the mainland have been reviewed . as summarised in Chapter 6 . Whilst it has been recommended that several options should be kept open in the continuing studies it is likely that most attention will be given to electricity. The overall flow of energy from the waves to a final user connected to the electricity grid involves many separate steps . each of which can involve loss of some of the energy . This can have a considerable influence on the system economics and further work in this area will need to concentrate on both reducing the number of steps and increasing the efficiency (including the directional efficiency of t he converters themselves ) of those which must remain . Unless this can be achieved the usable resource will be only a small proportion of our needs : some pointers to substantial improvements are beginning to emerge. Environmental studies have not revealed any major detrimental effects of the converters provided they are well offshore. More information is needed on the behaviour of salmon and herring off the Outer Hebrides to confirm that the fisheries would not be affected significantly by the widespread installation of converters. Concluding remarks: The costing studies of the reference designs which have been evolved so far indicate that wave-produced electricity is likely to be expensive compared with either nuclear or fossil fuels unless some major breakthrough in the engineering can be achieved . However . this does not imply that the possibility of wave energy should be abandoned at this stage . It must be emphasised that the subject is still at a very ear ly state of development and many unknown factors remain to be resolved . Under these circumstances, wave energy is best regarded at present as a possible insurance technology- the consequences of failure of one of our existing major energy supplies are so severe that it is worth paying an insurance premium to explore fully the alternatives . Nevertheless. the evidence from the feasibility study so far does not allow a recommendation for a full-scale development programme to be made at this time . Much more can be achieved to explore and then to narrow the design choices by continuing work at about the 1 / 1 0th scale coupled with . on the one hand . limited trials of some critical components at larger scale and . on the other hand . f urther creative engineering on the drawing board and laboratory work in a new generation of wave tanks (of which the forerunner has been successfully commissioned at Edinburgh University). The programme has generated a broad basis of knowledge of all aspects of wave energy which did not exist before. so that we can now identify clearly the critical problems to be tackled by further work

Fractional Vector Calculus and Fractional Maxwell's Equations

The theory of derivatives and integrals of non-integer order goes back to Leibniz, Liouville, Grunwald, Letnikov and Riemann. The history of fractional vector calculus (FVC) has only 10 years. The main approaches to formulate a FVC, which are used in the physics during the past few years, will be briefly described in this paper. We solve some problems of consistent formulations of FVC by using a fractional generalization of the Fundamental Theorem of Calculus. We define the differential and integral vector operations. The fractional Green's, Stokes' and Gauss's theorems are formulated. The proofs of these theorems are realized for simplest regions. A fractional generalization of exterior differential calculus of differential forms is discussed. Fractional nonlocal Maxwell's equations and the corresponding fractional wave equations are considered.Comment: 42 pages, LaTe

Skunk River Review Fall 2000, Vol 12

https://openspace.dmacc.edu/skunkriver/1020/thumbnail.jp

Variation in Antibiotic Susceptibility of Uropathogens by Age among Ambulatory Pediatric Patients

We compared uropathogen antibiotic susceptibility across age groups of ambulatory pediatric patients. For Escherichia coli (n=5,099) and other Gram-negative rods (n=626), significant differences (p<0.05) existed across age groups for ampicillin, cefazolin, and trimethoprim/sulfamethoxazole susceptibility. In E. coli, differences in trimethoprim/sulfamethoxazole susceptibility varied from 79% in children under 2 to 88% in ages 16-18 (p<0.001) while ampicillin susceptibility varied from 30% in children under 2 to 53% in ages 2-5 (p=0.015). Uropathogen susceptibility to common urinary anti-infectives may be lower in the youngest children. Further investigation into these differences is needed to facilitate appropriate and prudent treatment of urinary tract infections.This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier and can be found at: http://www.sciencedirect.com/science/journal/08825963

Incidental durotomy: predictive risk model and external validation of natural language process identification algorithm

OBJECTIVE Incidental durotomy is a common complication of elective lumbar spine surgery seen in up to 11% of cases. Prior studies have suggested patient age and body habitus along with a history of prior surgery as being associated with an increased risk of dural tear. To date, no calculator has been developed for quantifying risk. Here, the authors' aim was to identify independent predictors of incidental durotomy, present a novel predictive calculator, and externally validate a novel method to identify incidental durotomies using natural language processing (NLP).METHODS The authors retrospectively reviewed all patients who underwent elective lumbar spine procedures at a tertiary academic hospital for degenerative pathologies between July 2016 and November 2018. Data were collected regarding surgical details, patient demographic information, and patient medical comorbidities. The primary outcome was incidental durotomy, which was identified both through manual extraction and the NLP algorithm. Multivariable logistic regression was used to identify independent predictors of incidental durotomy. Bootstrapping was then employed to estimate optimism in the model, which was corrected for; this model was converted to a calculator and deployed online.RESULTS Of the 1279 elective lumbar surgery patients included in this study, incidental durotomy occurred in 108 (8.4%). Risk factors for incidental durotomy on multivariable logistic regression were increased surgical duration, older age, revision versus index surgery, and case starts after 4 PM. This model had an area under curve (AUC) of 0.73 in predicting incidental durotomies. The previously established NLP method was used to identify cases of incidental durotomy, of which it demonstrated excellent discrimination (AUC 0.97).CONCLUSIONS Using multivariable analysis, the authors found that increased surgical duration, older patient age, cases started after 4 PM, and a history of prior spine surgery are all independent positive predictors of incidental durotomy in patients undergoing elective lumbar surgery. Additionally, the authors put forth the first version of a clinical calculator for durotomy risk that could be used prospectively by spine surgeons when counseling patients about their surgical risk. Lastly, the authors presented an external validation of an NLP algorithm used to identify incidental durotomies through the review of free-text operative notes. The authors believe that these tools can aid clinicians and researchers in their efforts to prevent this costly complication in spine surgery

The landscape model: a model for exploring trade-offs between agricultural production and the environment

We describe a model framework that simulates spatial and temporal interactions in agricultural landscapes and that can be used to explore trade-offs between production and environment so helping to determine solutions to the problems of sustainable food production. Here we focus on models of agricultural production, water movement and nutrient flow in a landscape. We validate these models against data from two long-term experiments, (the first a continuous wheat experiment and the other a permanent grass-land experiment) and an experiment where water and nutrient flow are measured from isolated catchments. The model simulated wheat yield (RMSE 20.3–28.6%), grain N (RMSE 21.3–42.5%) and P (RMSE 20.2–29% excluding the nil N plots), and total soil organic carbon particularly well (RMSE 3.1 − 13.8 %), the simulations of water flow were also reasonable (RMSE 180.36 and 226.02%). We illustrate the use of our model framework to explore trade-offs between production and nutrient losses