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Raman micro-spectroscopy is becoming very popular in the field of radiobiology and radiation oncology for its ability to assess the cellular damage at the molecular level. It can be used to monitor the minimum doses required to lethally damage tumor cells, as well as to reduce the risk of excess dose being delivered to healthy surrounding cells. These results can be achieved also thanks to the development of specific data analysis methods enabling the extraction of information embedded in the Raman spectra of complex samples, such as human cells. Among different data analysis procedures, multivariate analysis has been proven to be particularly effective. The principal component analysis (PCA) method has been largely used for analyzing Raman spectra from cells and tissues. In some cases, the PCA can be performed on selected wavenumber ranges of Raman spectra to get information embedded in those specific ranges (interval-PCA). In the present work, the application of these methods to the analysis of Raman spectra from single SH-SY5Y neuroblastoma cells following the exposure to graded doses of X-rays is reported and specific details from X-ray effects on nucleus and cytoplasm regions are obtained. In addition, the biochemical changes occurring in these cells are also discussed by using an alternative approach, namely the analysis of difference spectra, obtained by subtracting the cytoplasm-related spectrum from the corresponding one detected at the nucleus. It's worth to note that multivariate analysis has allowed us to unravel the subtle modifications, due to X-ray irradiation, of Raman features related to specific components. These results pave the way to develop proper data analysis methods allowing to manage, on one hand, the complexity of the Raman spectra of cells and tissues and, on the other hand, the high number of spectra needed to consider the intrinsic variability of biological samples.

XDCP0044.0-2033 is the most massive galaxy cluster known at z>1.5 and its core shows a high density of galaxies which are experiencing mergers and hosting nuclear activity. We present a multi-wavelength study of a region located 157 kpc from the center of this galaxy cluster, for which we have photometric and spectroscopic multi-wavelength observations (high resolution HST images in F105W, F140W and F160W bands, NIR KMOS data in H and YJ bands and Chandra ACIS-S X-ray data). Our main goal is to investigate the environmental effects acting on the galaxies inhabiting this high density region. We find that the analyzed region hosts at least nine different sources, six of them confirmed to be cluster members within a narrow redshift range 1.5728

Aims: We present the X-ray imaging and spectral analysis of the diffuse emission around the radio galaxy J1140-2629 (the Spiderweb galaxy) at z = 2.16 and of its nuclear emission, based on a deep (700 ks) Chandra observation. Methods: We obtained a robust characterization of the unresolved nuclear emission, and carefully computed the contamination in the surrounding regions due to the wings of the instrument point spread function. Then, we quantified the extended emission within a radius of 12 arcsec. We used the Jansky Very Large Array radio image to identify the regions overlapping the jets, and performed X-ray spectral analysis separately in the jet regions and in the complementary area. Results: We find that the Spiderweb galaxy hosts a mildly absorbed quasar, showing a modest yet significant spectral and flux variability on a timescale of ∼1 year (observed frame). We find that the emission in the jet regions is well described by a power law with a spectral index of Γ ∼ 2 − 2.5, and it is consistent with inverse-Compton upscattering of the cosmic microwave background photons by the relativistic electrons. We also find a roughly symmetric, diffuse emission within a radius of ∼100 kpc centered on the Spiderweb galaxy. This emission, which is not associated with the jets, is significantly softer and consistent with thermal bremsstrahlung from a hot intracluster medium (ICM) with a temperature of kT = 2.0−0.4+0.7 keV, and a metallicity of Z < 1.6 Z⊙ at 1σ c.l. The average electron density within 100 kpc is ne = (1.51 ± 0.24 ± 0.14) × 10−2 cm−3, corresponding to an upper limit for the total ICM mass of ≤(1.76 ± 0.30 ± 0.17) × 1012 M⊙ (where error bars are 1σ statistical and systematic, respectively). The rest-frame luminosity L0.5 − 10 keV = (2.0 ± 0.5) × 1044 erg s−1 is about a factor of 2 higher than the extrapolated L − T relation for massive clusters, but still consistent within the scatter. If we apply hydrostatic equilibrium to the ICM, we measure a total gravitational mass M(

The mechanism of T cell antigen receptor (TCR-CD3) signaling remains elusive. Here, we identify mutations in the transmembrane region of TCRβ or CD3ζ that augment peptide T cell antigen receptor (pMHC)-induced signaling not explicable by enhanced ligand binding, lateral diffusion, clustering, or co-receptor function. Using a biochemical assay and molecular dynamics simulation, we demonstrate that the gain-of-function mutations loosen the interaction between TCRαβ and CD3ζ. Similar to the activating mutations, pMHC binding reduces TCRαβ cohesion with CD3ζ. This event occurs prior to CD3ζ phosphorylation and at 0°C. Moreover, we demonstrate that soluble monovalent pMHC alone induces signaling and reduces TCRαβ cohesion with CD3ζ in membrane-bound or solubilised TCR-CD3. Our data provide compelling evidence that pMHC binding suffices to activate allosteric changes propagating from TCRαβ to the CD3 subunits, reconfiguring interchain transmembrane region interactions. These dynamic modifications could change the arrangement of TCR-CD3 boundary lipids to license CD3ζ phosphorylation and initiate signal propagation.

Immergersi in un'opera pittorica, da spettatore a protagonista della scena rappresentata, è stato da sempre, da parte di chi ama l'arte, un sogno ricorrente, ancor più suggestivo se la scena è la rappresentazione di Gesù con gli Apostoli nei suoi ultimi momenti. Il caso di studio è la splendida "Ultima Cena" dell'artista fiammingo "Gaspar Hovic". La tela, dipinta ad olio (tardo XV sec. d. C.) e custodita nella Chiesa Matrice S. M. Veterana di Triggiano (BA), è stata riprodotta e sceneggiata in un contesto architettonico dall'aspetto suggestivo, con l'uso e l'integrazione di innovative tecnologie: la fotogrammetria digitale, la modellazione solida, la fotografia immersiva. Dopo uno studio storico-artistico dell'opera e l'approfondimento dei concetti della geometria descrittiva, sono stati realizzati virtualmente il luogo, la raffigurazione di oggetti ed i protagonisti, materializzando in 3D l'intera scena. Il paradigma informatico della Realtà Virtuale (Virtual Reality - VR) proietta lo spettatore in modo immersivo nel contesto tridimensionale, attraverso l'uso di visori VR, consentendogli di "entrare" nella tela ed osservare l'opera da inesplorati punti di vista, che in una rappresentazione 2D sono celati. L'opera è così arricchita da nuovi tratti ed elementi pittorici e valorizzata dalla visione fruibile del messaggio artistico dell'autore, tra le incongruenze architettoniche degli elementi dipinti o il gioco di prospettive che mettono in risalto le situazioni sceneggiate.

At the Max Planck Institute for plasma physics in Greifswald, Germany, the world's largest nuclear fusion experiment of modular stellarator type Wendelstein 7-X has started plasma operation. The hot hydrogen plasma is confined in a plasma vessel by an electromagnetic field generated by 50 non-planar and 20 planar superconducting coils. The superconducting coils are encased in cast stainless steel housings. The coils are bolted onto a central support ring and welded together by so called lateral support elements (LSEs). In this paper, a procedure, based on a global–local finite element method (FEM)–dual boundary element method (DBEM) approach, is developed to simulate the propagation of multiple cracks detected in LSEs and undergoing a fatigue load spectrum. The global stress analysis on the superconducting coils is performed by FEM whereas the sub-modelling approach is adopted to solve the crack propagation in the DBEM environment. The boundary conditions applied on the DBEM submodel are the displacements calculated by the FEM global analysis, in correspondence of the cut surfaces (there are no body forces nor external loads applied on the submodel volume). Two cracks are simultaneously introduced, and a linear elastic fracture mechanics analysis is performed. Results in terms of cracks growth rates and evolving crack shapes are provided, and the residual life of the component is forecast.

LDL cholesterol(LDL-C) has been the cornerstone measurement for assessing cardiovascular risk for nearly 10 years.Recent data demonstrate that apolipoprotein B (Apo-B) is a better measure of circulating LDL and the concentration is a more reliable indicator of risk than LDL-C.In this report,we review the studies of a apo B and LDL-C reported to date,discuss potential advantages of their measurement over that of LDL-C and the present information related to standardization. In line with recently guidelines,the addition of apo B represents a next most important step. Thus,it appears to consider using apo B along with LDL-C to asses LDL related risk for an period until the superiority of apo B is generally recognized. Recent genome-mitochondrial DNA association studies have pinpointed many loci associated with neurovegetative disease's. We have studied the association between genetic mutation factors on a whole mtDNA in longitudinal study design has enabled the investigation of genetic variation influencing trait values over time.

Background The optimal therapeutic regimen for managing childhood idiopathic nephrotic syndrome (INS) is still under debate. We have evaluated the choice of steroid regimen and of symptomatic treatment adopted by pediatricians and pediatric nephrologists in a large number of centers as the first step towards establishing a shared protocol Methods This was a multicenter, retrospective study. A total of 231 children (132 admitted to pediatric units) aged 6 months to

Residential care settings (RCSs) are community-based housing and supportive services providers. Many RCSs predominantly serve older adults and younger people with physical disabilities. Medicaid beneficiaries’ access to these RCSs is of concern to policymakers and other stakeholders because providing community-based—rather than institutional—services is potentially less expensive and preferred by most people. To better understand Medicaid beneficiaries’ access to RCSs that focus on older adults and young people with physical disabilities, we examined Medicaid policies in 50 states and the District of Columbia, interviewed subject matter experts (n=7), and conducted four state case studies informed by reviews of policies and interviews with stakeholders (n=27). Interviewees identified numerous factors influencing Medicaid beneficiaries’ access to these RCSs, including the supply of Medicaid-certified RCSs relative to the older adult population, Medicaid reimbursement rates, initiatives that affect room and board costs for Medicaid beneficiaries, and policies that may incentivize RCSs to serve Medicaid beneficiaries. These factors can affect Medicaid beneficiaries’ access to RCSs by limiting the number of RCSs that participate in Medicaid, restricting the number of beds that RCSs allot to Medicaid beneficiaries, and by determining whether room and board rates will be affordable for Medicaid beneficiaries. The implications of these findings vis-à-vis implementation of federal Medicaid home and community-based services rules and continued implementation of managed long-term services and supports programs are discussed.

Context: Variants on the nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP-1) gene have been associated with obesity and insulin resistance. Because insulin resistance is a pivotal factor in the development of metabolic syndrome (MS) and impaired glucose tolerance (IGT), we aimed to test the association between the K121Q and rs997509 ENPP-1 variants with obesity, MS and IGT in obese children and adolescents. Methods: We screened 809 children, 409 obese and 400 lean controls. Obese subjects underwent a standard oral glucose tolerance test, whole body insulin sensitivity index (WBISI) and homeostasis model assessment (HOMA) were calculated. Results: No difference in prevalence for K121Q and rs997509 polymorphisms between obese and controls (P > 0.05) were observed. Obese children carrying the rs997509 rare allele showed higher insulin (P = 0.001), HOMA (P < .001) and lower WBISI values (P = 0.04) compared with common allele homozygous. A similar observation was done for K121Q variant, with 121Q allele carriers showing higher insulin (P = 0.03) and HOMA(P = 0.04) values than 121K homozygotes. Moreover, subjects carrying the rs997509 rare allele had higher risk of MS (odds ratio 2.4, 95% confidence interval: 1.3– 4.3) and IGT (odds ratio 4.7, 95% confidence interval: 1.9 –11.4) than common allele homozygotes. Evaluating combined effects of both polymorphisms, which are in strong linkage disequilibrium, we showed that the effect on insulin sensitivity was due to the rs997509 T variant. Conclusion:We conclude that the ENPP1 rs997509T allele can predispose obese children to MS and IGT and that this variant might drive the association between the ENPP1 121Q allele and insulin resistance.

L’articolo fa un confronto tra le differenti forme urbane delle città del Nord Africa, in particolare quelle della Tunisia (Tunisi, Kairouan, Tozeur, Nefta). Tali città, distribuite tra il Nord ed il Sud del paese, esprimono, nelle loro medine, l’identità della forma urbana e ne dichiarano la modernità lungo i loro bordi. Tunisi, posta tra due laghi, costruisce la sua modernità con la città coloniale che, anche se con linguaggi diversi, evidenzia i temi del Mediterraneo. La città di Kairouan mantiene la sua identità nella grande moschea, luogo centrale di organizzazione urbana. Le città d’oasi, come Tozeur e Nefta, esprimono il loro rapporto col paesaggio ed evidenziano con le loro architetture i materiali usati.

OBJECTIVE: To evaluate the thyroidal lymphoid infiltrate (TLI) in thyroidal functional status (TFS) for differences among patients with Hashimoto's thyroiditis (HT). STUDY DESIGN: Flow-cytometry (FC) was applied to thyroidal fine-needle cytology samples in 57 patients. TLI was analyzed using a fluorescence-activated cell sorter (FACS) scan and fluorescence antibodies CD3, CD4, CD5, CD8, CD10, and CD19 and kappa and lambda light chains. TFS was determined by serum thyroid-stimulating hormone (TSH), FT3 and FT4 immunoassays, in specific clinical settings, to classify the cases as hyperthyroid, euthyroid and hypothyroid. FC assessment was then compared with the corresponding TFS. RESULTS: B-lymphocytes were present in 44 cases (77%). T-lymphocytes were present in all the cases; CD4/CD8 = 2:1 ratio was observed in 16 euthyroid, 1 hyperthyroid and 3 hypothyroid; CD4/CD8 > or = 3:1 ratio in 22 euthyroid, 2 hyperthyroid and 2 hypothyroid cases; CD4/CD8 < or = 1:1 ratio in 1 euthyroid, 3 hyperthyroid and in 7 hypothyroid cases. Grouping hyperthyroid and hypothyroid cases, a significant association was observed with the CD4/CD8 < or = 1:1 ratio (p < 0.01). CONCLUSION: Intrathyroidal CD4/CD8 < 1:1 ratio might be the expression of intense apoptosis in the early phases of HT, generally followed by the restoration of CD4/CD8 balance; persistence of increased intrathyroidal CD8 might be related to intense thyroidal damage and thus an increasing risk of hypothyroidism.

Morphometrical evaluation of thyroidal follicular cells is influenced by several factors including suppressive therapy. Morphometry may be useful in the follow-up of NHG to evaluate the effects of L-thyroxine and that this therapy reduces the size of thyreocytes; the same therapy, however, seems to have little or no effect on Hürthle cells.

Desmoplastic small round cell tumor (DSRCT) is a rare but well-defined neoplasm generally forming in the abdominal or pelvic cavity of young males and has distinct clinical, immunohistochemical and molecular features. Cytologic features of DSRCT have been described on fine needle aspiration of primary tumors. An occult lymph node metastasis of DSRCT diagnosed through the cytologic features, a basic immunocytochemical panel and DNA ploidy evaluation on cytospins obtained by fine needle aspiration is reported. CASE: Aspiration cytology was performed on an inguinal lymph node from a 20-year-old male. A Diff-Quik-stained smear showed mature lymphocytes and groups of undifferentiated, small cells with scanty cytoplasm, dense and coarse chromatin, and small nucleoli. Basic immunocytochemical stains showed negativity for leukocyte-common antigen and neuron-specific enolase and positivity for cytokeratin cocktail (Cam 5.2), vimentin and desmin, the last with characteristic paranuclear dotlike positivity. DNA ploidy evaluation showed an aneuploid histogram with a low 5c exceeding rate. CONCLUSION: Cytologic and immunocytochemical features suggest the diagnosis of DSRCT on fine needle aspiration cytology samples even in cases of a metastatic, unknown primary tumor. Because of the tumor's aggressiveness, a rapid and accurate diagnosis is required.

The characterization of an economic and ease-to-use carbon paste acetylcholinesterase (AChE) based biosensor to determine the concentration of pesticides Paraoxon and Dichlorvos is discussed. AChE hydrolyses acetylthiocholine (ATCh) in thiocoline (TC) and acetic acid (AA). When AChE is immobilized into a paste carbon working electrode kept at +410 mV vs. Ag/AgCl electrode, the enzyme reaction rate using acetylthiocholine chloride (ATCl) as substrate is monitored as a current intensity. Because Paraoxon and Dichlorvos inhibit the AChE reaction, the decrease of the current intensity, at fixed ATCl concentration, is a measure of their concentration. Linear calibration curves for Paraoxon and Dichlorvos determination have been obtained. The detection limits resulted to be 0.86 ppb and 4.2 ppb for Paraoxon and Dichlorvos, respectively, while the extension of the linear range was up 23 ppb for the former pesticide and up to 33 ppb for the latter. Because the inhibited enzyme can be reactivated when immediately treated with an oxime, the biosensor reactivation has been studied when 1,1'-trimethylene bis 4-formylpyridinium bromide dioxime (TMB-4) and pyridine 2-aldoxime methiodide (2-PAM) were used. TMB-4 resulted more effective. The comparison with the behavior of similar AChE based biosensors is also presented.

Micro-Raman spectroscopy is a very promising tool for medical applications, thanks to its sensitivity to subtle changes in the chemical and structural characteristics of biological specimens. To fully exploit these promises, building a method of data analysis properly suited for the case under study is crucial. Here, a linear or univariate approach using a R 2 determination coefficient is proposed for discriminating Raman spectra even with small differences. The validity of the proposed approach has been tested using Raman spectra of high purity glucose solutions collected in the 600 to 1,600 cm -1 region and also from solutions with two known solutes at different concentrations. After this validation step, the proposed analysis has been applied to Raman spectra from oral human tissues affected by Pemphigus Vulgaris (PV), a rare life-threatening autoimmune disease, for monitoring disease follow-up. Raman spectra have been obtained in the wavenumber regions from 1,050 to 1,700 cm -1 and 2,700 to 3,200 cm -1 from tissues of patients at different stages of pathology (active PV, under therapy and PV in remission stage) as confirmed by histopathological and immunofluorescence analysis. Differences in the spectra depending on tissue illness stage have been detected at 1,150-1,250 cm -1 (amide III) and 1,420-1,450 cm -1 (CH 3 deformation) regions and around 1,650 cm -1 (amide I) and 2,930 cm -1 (CH 3 symmetric stretch). The analysis of tissue Raman spectra by the proposed univariate method has allowed us to effectively differentiate tissues at different stages of pathology.

La tasa de crecimiento es uno de los parámetros básicos que describe la dinámica poblacional. Numerosos métodos han sido utilizados para determinarla, siendo comúnmente muy difícil detectar incrementos en el micro-crecimiento de las valvas a escala menor que la décima de micrón. Estudios previos sobre crecimiento de Mesodesma mactroides en distintos puntos de su distribución se basaron en el desplazamiento de la talla de cohortes a través del tiempo y en marcas de crecimiento. Éste trabajo pretende determinar la tasa de crecimiento in situ del bivalvo M. mactroides que habita la playa arenosa intermareal de Santa Teresita (S36°32, W56°41), Provincia de Buenos Aires (Argentina). A tal fin, se recolectaron 551 individuos en Febrero de 2007. Entre ellos, 416 fueron sumergidos tres horas en solución de calceina (50 mg/L). El resto, fue asignado al grupo control. Todos los animales fueron mantenidos in situ en jaulas experimentales internamente recubiertas con una red de 1 mm de trama. Tres jaulas contenían animales tratados con calceina y una jaula, al grupo control. El experimento duró 63 días, con muestreos semanales. Las valvas de los animales sacrificados en cada muestreo se cortaron transversalmente a lo largo del eje de mayor crecimiento, siendo luego examinadas y fotografíadas en microscopio de fluorescencia. Se determinó el crecimiento con un micrómetro, midiendo la distancia entre la marca de tinción por calceina y el borde de la valva. Un individuo que midió 50.15 mm luego de 35 días de experimento, registró por ejemplo, un crecimiento de 220 µm correspondiente a una tasa absoluta de crecimiento de 6.29 µm/día calculada como: (SL2-SL1)/(t2-t1)=ΔSL/Δt donde, SL1 es la longitud de la valva antes de la tinción (t1) y SL2 la longitud de la valva al final del período de crecimiento (t2). La calceina probó ser un marcador de crecimiento útil para M. mactroides. La delgada banda fluorescente, constituyo un distinguible punto de partida para el intervalo de tiempo estudiado, siendo una referencia medible con mucha precisión (escala µm). La marcación con calceina no afecto la supervivencia de M. mactroides, pudiéndose considerar como un marcador no letal útil para experimentos in situ con bivalvos.

En los últimos 30 años el partido de la costa ha sufrido un crecimiento demográfico importante. Las poblaciones de bivalvos fueron las más afectadas debido a que sus hábitats naturales fueron modificados. Las extracciones ilegales y el impacto de la actividad turística masiva son probablemente los dos factores principales que influyen negativamente sobre la recuperación de estas comunidades. Por este motivo es de suma importancia conocer el estado actual de estas poblaciones y como son afectadas por los cambios del entorno. Para ello es muy importante estudiar la dinámica poblacional y la biología reproductiva. Se determinó el crecimiento con un micrómetro, midiendo la distancia entre la marca de tinción por calceina y el borde de la valva. Un individuo que midió 50.15 mm luego de 35 días de experimento, registró por ejemplo, un crecimiento de 220 µm correspondiente a una tasa absoluta de crecimiento de 6.29 µm/día calculada como: (SL2-SL1)/(t2-t1)=ΔSL/Δt donde, SL1 es la longitud de la valva antes de la tinción (t1) y SL2 la longitud de la valva al final del período de crecimiento (t2). La calceina probó ser un marcador de crecimiento útil para M. mactroides. La delgada banda fluorescente, constituyo un distinguible punto de partida para el intervalo de tiempo estudiado, siendo una referencia medible con mucha precisión (escala µm). La marcación con calceina no afecto la supervivencia de M. mactroides, pudiéndose considerar como un marcador no letal útil para experimentos in situ con bivalvos. Para el estudio de los otros parámetros se midió el largo total (Lt) en 3000 ejemplares. Muestras, de todas las tallas, tomadas al azar en estas localidades, fueron empleadas para estudiar el ciclo reproductivo y la talla de primera madurez sexual las muestras fueron fijadas en solución de Bouin, para su posterior estudio histológico. En la distribución de tallas descripta para cada mes seobserva una cohorte con tallas mínimas de 2.17 mm en febrero y abril máximas de 64 mm en septiembre y noviembre (2004/5) La densidad de individuos x m2 es de 543 encontrándose solo individuos en Santa Tersita. La almeja amarilla alcanza su madurez sexual a una talla de 16.36 mm. Todos estos resultados, colocan a estas poblaciones en un estado muy vulnerable ante cualquier cambio inesperado sobre el ambiente.

Cavities in human teeth were fabricated by means of Er:YAG laser and compared with samples processed by using conventional drill. The cavities of lased and unlased samples were cured with two different composite resins (Bis-GMA vs PEX) to investigate differences in their adhesion properties. Morphological characterization of the sample surfaces by SEM analysis was performed. The same samples were then examined by micro-Raman spectroscopy by using He-Ne laser visible light excitation, in order to characterize the dentin/resin interfaces. The Raman spectra exhibited typical peaks of dentine. Resin contributions to the Raman spectra were also detected and have been used to monitor the interface properties of the boundary region. The dependence of the Raman spectrum on spatial position has been monitored. In both lased and unlased samples the PEX diffusion in dentine is limited in a region of order of 10 micrometer depth. A larger interdiffusion region is observed at the boundary of dentine and Bis-GMA resin.

An analitical approach is developed that allows for computing the time resolved transmittance signal through a slab of turbid material in presence of spatially varying Gaussian absorptive inhomogeneity included in thescattering slab.The perturbed time-resolved signal is calculated in the framework of the diffusion approximation up to the first order correction in the relative degree of the absrptive perturbation parameter. Numerical FEM simulations arecompared with the prediction of the perturbation-based approach for different values of the optical coefficients of the inhomogeneity and of the host medium and for different size of the inclusion

To evaluate whether commonly used cytologic criteria for the diagnosis of endometriosis are sufficiently specific, to assess the possible role of special methods in the differential diagnosis and to assess the clinical meaning and drawbacks of a cytopathologic diagnosis of endometriosis by fine needle aspiration. STUDY DESIGN: We retrieved 10 cases of endometriosis from our files that had been diagnosed primarily by fine needle cytology (FNC) with subsequent tissue study. In some cases additional cytospin preparations and/or smears had been used for cytochemistry (periodic acid-Schiff stain, mucicarmine) or immunocytochemistry (pan-cytokeratin, cytokeratin 7, vimentin, CD10) using a 3-step streptavidin-biotin-immunoperoxidase reaction. RESULTS: The cell pattern and immunocytochemical profile of the cases suggested a diagnosis of endometriosis. All cases were histologically confirmed. CONCLUSION: With optimal preparations a confident cytologic diagnosis of endometriosis may be made with ease, permitting correct treatment of the disease and, in selected cases, planning of preoperative pharmacologic therapy.