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The opportunities offered by utilizing time-independent Hamiltonian structure as controls are explored for manipulating quantum dynamics. Two scenarios are investigated using different manifestations of Hamiltonian structure to illustrate the generality of the concept. In scenario I, optimally shaped electrostatic potentials are generated to flexibly control electron scattering in a two-dimensional subsurface plane of a semiconductor. A simulation is performed showing the utility of optimally setting the individual voltages applied to a multi-pixel surface gate array in order to produce a spatially inhomogeneous potential within the subsurface scattering plane. The coherent constructive and destructive electron wave interferences are manipulated by optimally adjusting the potential shapes to alter the scattering patterns. In scenario II, molecular vibrational wave packets are controlled by means of optimally selecting the Hamiltonian structure in cooperation with an applied field. As an illustration of the concept, a collection (i.e., a level set) of dipole functions is identified where each member serves with the same applied electric field to produce the desired final transition probability. The level set algorithm additionally found Hamiltonian structure controls exhibiting desirable physical properties. The prospects of utilizing the applied field and Hamiltonian structure simultaneously as controls is also explored. The control scenarios I and II indicate the gains offered by algorithmically guided molecular or material discovery for manipulating quantum dynamics phenomenon.
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Melanoma is often initially evaluated by the dermatologist. A methodical evaluation requires complete history and detailed clinical physical examination and appropriate decisions regarding biopsies. Accurate diagnosis and staging require clinicopathologic correlation and an excellent relationship with the dermatopathologist. Subsequent definitive treatment may be managed entirely by the dermatologist or might require a multidisciplinary team of specialists.
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Neoplasias de Cabeza y Cuello , Melanoma , Dermatólogos , Cabeza , Neoplasias de Cabeza y Cuello/diagnóstico , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Melanoma/diagnóstico , Melanoma/cirugía , CuelloRESUMEN
Identifying optimal conditions for chemical and material synthesis as well as optimizing the properties of the products is often much easier than simple reasoning would predict. The potential search space is infinite in principle and enormous in practice, yet optimal molecules, materials, and synthesis conditions for many objectives can often be found by performing a reasonable number of distinct experiments. Considering the goal of chemical synthesis or property identification as optimal control problems provides insight into this good fortune. Both of these goals may be described by a fitness function J that depends on a suitable set of variables (e.g., reactant concentrations, components of a material, processing conditions, etc.). The relationship between J and the variables specifies the fitness landscape for the target objective. Upon making simple physical assumptions, this work demonstrates that the fitness landscape for chemical optimization contains no local sub-optimal maxima that may hinder attainment of the absolute best value of J. This feature provides a basis to explain the many reported efficient optimizations of synthesis conditions and molecular or material properties. We refer to this development as OptiChem theory. The predicted characteristics of chemical fitness landscapes are assessed through a broad examination of the recent literature, which shows ample evidence of trap-free landscapes for many objectives. The fundamental and practical implications of OptiChem theory for chemistry are discussed.
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Persistent quantum control (PQC) aims to maintain an observable objective value over a period of time following the action of an applied field. This paper assesses the feasibility of achieving PQC for arbitrary finite-level systems and observables. The analysis is carried out independent of the particular method used for state preparation. The PQC behavior is optimized over the set of physically accessible prepared states for both open and closed systems. The quality of observable value persistence in the postcontrol period was found to vary with the required duration of persistence, the system temperature, the chosen observable operator, and the energy levels of the system. The alignment of a rigid diatomic rotor is studied as a model system. The theoretical estimates of PQC behavior are encouraging and suggest feasible exploration in the laboratory using currently available technology.
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A controlled quantum system possesses a search landscape defined by the target physical objective as a function of the controls. This paper focuses on the landscape for the transition probability P(i â f) between the states of a finite level quantum system. Traditionally, the controls are applied fields; here, we extend the notion of control to also include the Hamiltonian structure, in the form of time independent matrix elements. Level sets of controls that produce the same transition probability value are shown to exist at the bottom P(i â f)=0.0 and top P(i â f)=1.0 of the landscape with the field and/or Hamiltonian structure as controls. We present an algorithm to continuously explore these level sets starting from an initial point residing at either extreme value of P(i â f). The technique can also identify control solutions that exhibit the desirable properties of (a) robustness at the top and (b) the ability to rapidly rise towards an optimal control from the bottom. Numerical simulations are presented to illustrate the varied control behavior at the top and bottom of the landscape for several simple model systems.
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This paper demonstrates the existence of multiple solutions at each time point in tracking control of quantum systems. These solutions are shown to arise from the nonlinear dependence of the short-time propagators U(t + delta t,t) on the control field. The multiplicity of solutions depends on the parameters of the controlled system and the nature of the imposed track. Multiple solutions necessitate that a choice be made at each time point, resulting in an exponentially expanding space of distinct control fields that maintain the prescribed track. This behavior is illustrated by application to a small model system. The presence of multiple tracking control fields is consistent with behavior observed from quantum control landscape theory.
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Optimal dynamic discrimination (ODD) uses closed-loop learning control techniques to discriminate between similar quantum systems. ODD achieves discrimination by employing a shaped control (laser) pulse to simultaneously exploit the unique quantum dynamics particular to each system, even when they are quite similar. In this work, ODD is viewed in the context of multiobjective optimization, where the competing objectives are the degree of similarity of the quantum systems and the level of controlled discrimination that can be achieved. To facilitate this study, the D-MORPH gradient algorithm is extended to handle multiple quantum systems and multiple objectives. This work explores the trade-off between laser resources (e.g., the length of the pulse, fluence, etc.) and ODD's ability to discriminate between similar systems. A mechanism analysis is performed to identify the dominant pathways utilized to achieve discrimination between similar systems.
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Scleromyxedema and lichen myxedematosus (LM) are rare disorders that fall along the spectrum of primary cutaneous mucinoses. Scleromyxedema is a systemic form that classically presents with generalized waxy papules, sclerodermoid eruption, and monoclonal gammopathy; LM is a localized form limited to the skin that classically presents with white, firm, waxy papules and lacks monoclonal gammopathy. According to diagnostic criteria established in 2001, the diagnosis of both conditions requires absence of thyroid disease. However, atypical cases that lack monoclonal gammopathy and that present with hypothyroidism have been reported, suggesting that these criteria may require revision. First, we report a case of a 58-year-old female with a history of Hashimoto thyroiditis and biopsy-proven scleromyxedema responsive to intravenous immunoglobulin therapy with delayed presentation of monoclonal gammopathy. Next, we report a case of a 54-year-old female with a history of hypothyroidism, Hodgkin's lymphoma in remission after radiation and chemotherapy, and concurrent rheumatoid arthritis, with biopsy-proven LM temporarily responsive to systemic steroids. Our cases demonstrate that patients with papular mucinoses can have a multitude of concurrent and prior rheumatologic and endocrine conditions, including thyroid disease, which should not preclude a diagnosis of scleromyxedema and LM.
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This article reviews the dermatologic and allergic conditions of the eyelid. Topics include various eyelid dermatitis, inflammatory lesions, infections, benign and malignant tumor, urticaria, vascular lesions, and others. Treatment considerations for these conditions of the eyelid are also discussed.
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Blefaritis/inmunología , Párpados/inmunología , Hipersensibilidad , Enfermedades de la Piel/inmunología , Dermatitis Seborreica/inmunología , Humanos , Vitíligo/inmunologíaRESUMEN
Lentigo maligna (LM) is an in situ variant of melanoma. Although LM has the potential for invasion, it often has a greatly protracted radial growth phase and may remain indolent for years. The current standard of care is surgical excision, but this often results in substantial morbidity; thus, nonsurgical approaches continue to be investigated. Imiquimod cream 5% is an immunomodulatory agent that previously has been reported to successfully eradicate LM. We evaluated the treatment course of topical imiquimod in 12 patients with LM. Data from patients with biopsy-proven LM were collected retrospectively, reviewed, and summarized. Patients ranged in age from 54 to 83 years. Most patients chose imiquimod cream as their initial form of treatment; however, other patients had a history of LM recurrence after excision or had positive histologic margins at the time of excision. Initial application regimens varied from 2 to 7 times weekly. The average duration of treatment was 15.7 weeks but ranged from 7 to 44 weeks. Results of posttreatment biopsies of the most clinically suspicious areas in 6 patients showed histologic clearance; 2 patients demonstrated single atypical melanocytes and 4 patients demonstrated clinical clearance without histologic confirmation. These findings suggest that imiquimod cream 5% may be an effective alternative treatment for LM.
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Adyuvantes Inmunológicos/administración & dosificación , Aminoquinolinas/administración & dosificación , Antineoplásicos/administración & dosificación , Neoplasias Faciales/tratamiento farmacológico , Peca Melanótica de Hutchinson/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Administración Tópica , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Imiquimod , Masculino , Persona de Mediana Edad , Pomadas , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: To date, patients with pre-existing autoimmune conditions have been excluded from immunotherapy trials out of concern for severe autoimmune exacerbations. CASE PRESENTATION: We describe the first case of a patient with metastatic cKIT mutated acral melanoma, brain metastasis, and pre-existing severe autoimmune bullous pemphigoid (BP) with stable and asymptomatic disease 10 months after treatment with pembrolizumab. The patient experienced severe BP exacerbation after therapy with ipilimumab requiring systemic immune suppression, but nonetheless pembrolizumab was administered on further disease progression. CONCLUSIONS: This case suggests that pembrolizumab may confer more benefit than risk even in patients with known severe autoimmune conditions who require intermittent systemic immunosuppression.
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PURPOSE OF REVIEW: The importance of consistency and accuracy of medical terminology must be recognized by all health care providers and researchers. Yet, recent publications by recognized authorities regarding atopic dermatitis seem to defy that basic tenet. I (an allergist/dermatologist) have (objectively) reviewed and (subjectively) interpreted the currently (peer reviewed) published designations etymologically, and some of their concepts scientifically. RECENT FINDINGS: Interdisciplinary, regional and international meetings have been discussing, assessing, and deliberating the newest data and observations, consistently realizing little consensus. The concluding trivial agreement denotes their individual bias. Given the same information, allergists, dermatologists, and generalists do not conceptualize, and yet dogmatically manage patients with atopic dermatitis. SUMMARY: Etymologically, and scientifically, atopic dermatitis can only be distinctively designated as the dermatologic syndrome, which heralds the atopic diathesis. Concomitantly, atopic dermatitis without atopy would be an oxymoron. Definitions based on anachronistic criteria demand updating. IgE, like eosinophilia, must be appreciated as epiphenomena of the transient Th1/Th2 cell reversal, which clearly differentiates 'atopic eczema' from all the 'other' eczemas. Failure to recognize the isomorphic feature of the eczema of atopic dermatitis denies patients with an essential therapeutic modality, namely 'Do not scratch, nor rub'. Education regarding the 'triggers' of itch would yield greater success (from recurrences), than prescribing immunomodulation.
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Dermatitis Atópica , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/etiología , Dermatitis Atópica/terapia , Humanos , Prurito/etiología , Prurito/terapia , Terminología como AsuntoRESUMEN
The dermatologic anachronistic adage, "If wet--dry it, if dry--wet it!" has bee perhaps justifiably replaced by "Call the dermatologist to prescribe a steroid!" To say this without knowledge of the contents of this article and more importantly, to accept such cliches, is a disservice to the patient and a litigious liability to the prescriber. Recognizing the risk/benefit ratio of the most commonly used anti-inflammatory agents is essential. All therapies are most effective when used for their specific diagnosis. This article attempts to provide an update on the geometrically progressing knowledge regarding the uses and misuses of GCSs for the eye and skin.
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Antiinflamatorios/farmacología , Ojo/efectos de los fármacos , Glucocorticoides/farmacología , Piel/efectos de los fármacos , Administración Tópica , Antiinflamatorios/administración & dosificación , Antiinflamatorios/efectos adversos , Oftalmopatías/tratamiento farmacológico , Glucocorticoides/administración & dosificación , Glucocorticoides/efectos adversos , Humanos , Enfermedades de la Piel/tratamiento farmacológico , Síndrome de Abstinencia a SustanciasRESUMEN
This review begins with a brief survey of the neurophysiology and neuroanatomy of pruritus, and goes on to describe the etiology of the major allergic and nonallergic pruritic disorders. The etiology of pruritus often suggests the appropriate treatment. For example, urticaria, which is primarily mediated by histamine, is amenable to treatment with H1 antihistamines. Second-generation, nonsedating antihistamines appear to be more effective than sedating antihistamines, perhaps because of better compliance. Other systemic pharmacologic options may be useful in nonhistamine-mediated disorders, for example, immunomodulators for inflammation-induced pruritus or opiate antagonists for atopic dermatitis. Nonpharmacologic measures, such as proper skin care, and physical modalities, such as phototherapy or acupuncture, may also be helpful.
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Prurito/etiología , Prurito/terapia , Enfermedades de la Piel/etiología , Enfermedades de la Piel/terapia , Humanos , Prurito/fisiopatología , Enfermedades de la Piel/fisiopatologíaRESUMEN
PURPOSE OF REVIEW: All terms referring to job-related (occupational) rashes are clearly defined. Ranking as the second most common occupational disorder, the importance of occupational dermatoses is illustrated. RECENT FINDINGS: 90-95% of occupational dermatoses result from a contact-type dermatitis. Until recently, 4/5 cases were believed to be of the irritant, rather than allergic type of contact dermatitis, however, with more extensive patch testing, more than half the cases were found to be allergic. SUMMARY: The direct causes of occupational dermatoses: chemical, mechanical, physical, and biological in nature are presented. The implications of assigning the degree and type of occupational dermatoses are explained. Workmans compensation is based on a no-fault arrangement, stating that unrestricted treatment and compensation is allowable only when negligence on the part of the employer is proven. Employee benefits are then determined by the duration and degree of disability sustained - all of which becomes litigational. Predisposing host factors, i.e. intellectual ability, anatomic site, atopy, skin pigmentation, age of skin, and immunosuppression (by disease or medication) are usually ignored. Environmental factors at the workplace must be considered conducive to occupational diseases. The full spectrum of irritant contact dermatitis is discussed with examples of each described. Allergic contact dermatitis and patch testing - the gold standard for identification of putative allergens is extensively discussed. Differentiating irritant contact dermatitis from allergic contact dermatitis is elucidated. The other non-contact type skin reactions are briefly mentioned.
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Dermatitis Profesional/epidemiología , Dermatitis Profesional/etiología , Dermatitis Profesional/clasificación , Humanos , Incidencia , Exposición Profesional/efectos adversos , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
Acknowledging urticaria as a symptom of mast cell degranulation is stressed. The biology of the mast cell, and the recognized immunologic and non-immunologic mast cell secretagogues are individually discussed along with mechanisms of activation and mediators released. The major, preformed mediator histamine in the skin produces a prototypic, short-lived urticaria, however, the clinical spectrum and pattern of "hives" indicate that other mediators contribute to the polymorphism and variable behavior of this symptom. The clinical assessment is almost exclusively restricted to the history and physical examination. Features to review and examine are presented. The cause of "acute" urticaria is identifiable (by history) in the majority of patients, and except for hives that accompany an anaphylactic reaction, these patients rarely present to the physician for care. The persistent, or "chronic" hiver whose history cannot elicit a cause, is rarely triggered by an individual trigger, despite extensive professional evaluation. Evidence to support changing the chronological, "acute" and "chronic" classification of urticaria to "identifiable" and "non-identifiable" triggered urticaria is discussed, as is the futility of extensive, costly laboratory work-ups. The natural history of urticaria reveals that management should be directed toward allowing the patient to maintain an acceptable quality of life (with or without some urticaria), until the episode resolves.
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Urticaria/inmunología , Urticaria/fisiopatología , Enfermedad Crónica , Liberación de Histamina , Humanos , Mastocitos/inmunología , Urticaria/diagnóstico , Urticaria/dietoterapiaRESUMEN
Atopic dermatitis, the dermatologic manifestation of the atopic diathesis, has a variety of clinical presentations. This disease probably should be considered a syndrome--a group of signs and symptoms that frequently occur together in an identifiable pattern. The following update describes the spectrum of atopic dermatitis and summarizes current thinking about the etiology of the disease.
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Dermatitis Atópica , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/epidemiología , Dermatitis Atópica/etiología , Dermatitis Atópica/fisiopatología , Diagnóstico Diferencial , Eccema/diagnóstico , HumanosRESUMEN
The general objective of quantum control is the manipulation of atomic scale physical and chemical phenomena through the application of external control fields. These tailored fields, or photonic reagents, exhibit systematic properties analogous to those of ordinary laboratory reagents. This analogous behavior is explored further here by considering the controlled response of a family of homologous quantum systems to a single common photonic reagent. A level set of dynamically homologous quantum systems is defined as the family that produces the same value(s) for a target physical observable(s) when controlled by a common photonic reagent. This paper investigates the scope of homologous quantum system control using the level set exploration technique (L-SET). L-SET enables the identification of continuous families of dynamically homologous quantum systems. Each quantum system is specified by a point in a hypercube whose edges are labeled by Hamiltonian matrix elements. Numerical examples are presented with simple finite level systems to illustrate the L-SET concepts. Both connected and disconnected families of dynamically homologous systems are shown to exist.