Multiplexing of frequency-modulation spectroscopy by spread-spectrum codes, demonstrated in continuous-wave LIDAR.

Frequency-modulation spectroscopy (FMS) is generally suited to code-division multiplexing, and we demonstrate that capacity in a form of continuous-wave LIDAR, utilizing a sharp CO2 absorption transition at 1.6 µm in simple ranging setups. The approach retains the advantages of FMS, including coherent detection and good rejection of broad absorption backgrounds. Extensions of this multiplexed approach to the continuous, simultaneous detection of several transitions would come by transmitting an encoded combination of frequency-modulated carriers, each tuned to detect a unique absorption transition. Signal analysis at the receiver involves a simple process of de-multiplexing that, in a general application, reveals targets at various distances and the absorption-related FMS signals in between.

A prospective comparison of MRI-US fused targeted biopsy versus systematic ultrasound-guided biopsy for detecting clinically significant prostate cancer in patients on active surveillance.

BACKGROUND: In active surveillance (AS) patients: (i) To compare the ability of a multiparametric MRI (mpMRI)-ultrasound biopsy system to detect clinically significant (CS) prostate cancer with systematic 12-core biopsy (R-TRUSBx), and (ii) To assess the predictive value of mpMRI with biopsy as the reference standard. METHODS: Seventy-two men on AS prospectively underwent 3T mpMRI . MRI-ultrasound fusion biopsy (UroNavBx) and R-TRUSBx was performed. CS cancer was defined using two thresholds: 1) GS ≥ 7 (CS7) and 2) GS = 6 with >50% involvement (GS6). CS cancer detection rates and predictive values were determined. RESULTS: CS7 cancers were found in 19/72 (26%), 7 (37%) identified by UroNavBx alone, 2 (11%) by R-TRUSBx alone (P = 0.182). UroNav targeted biopsy was 6.3× more likely to yield a core positive for CS7 cancer compared with R-TRUSBx (25% of 141 versus 4% of 874, P < 0.001). Upgrading of GS occurred in 15/72 patients (21%), 13 (87%) detected by UroNavBx and 10 (67%) by R-TRUSBx. The NPV of mpMRI for CS7 cancer was 100%. MRI suspicion level significantly predicted CS cancer on multivariate analysis (OR 3.6, P < 0.001). CONCLUSION: UroNavBx detected CS cancer with far fewer cores compared with R-TRUSBx, and mpMRI had a perfect negative predictive value in this population.

Effect of Bronsted Acids and Bases, and Lewis Acid (Sn(2+)) on the Regiochemistry of the Reaction of Amines with Trifluoromethyl-ß-diketones: Reaction of 3-Aminopyrrole to Selectively Produce Regioisomeric 1H-Pyrrolo[3,2-b]pyridines.

Reaction of 3-aminopyrrole (as its salt) with trifluoromethyl-ß-diketones gave γ-1H-pyrrolo[3,2-b]pyridines via reaction at the less reactive carbonyl group. The trifluoromethyl group increased the electrophilicity of the adjacent carbonyl group and decreased the basicity of the hydroxyl group of the CF3 amino alcohol formed. This amino alcohol was formed faster, but its subsequent dehydration to the ß-enaminone was slow resulting in the preferential formation of the γ-regioisomer. Reaction of 4,4,4-trifluoro-1-phenyl-1,3-butadione with 3-aminopyrrole was carried out using a series of 6 amine buffers. Yields of the α-1H-pyrrolo[3,2-b]pyridine increased as the pKa of the amine buffer decreased. Surprisingly the yield went down at higher pKas. There was a change in mechanism as the reaction mixture became more basic. With strong amines trifluoromethyl-ß-diketones were present mainly or completely as the enolate. Under reductive conditions (3-nitropyrrole/Sn/AcOH/trifluoromethyl-ß-diketone) the α-1H-pyrrolo[3,2-b]pyridine was the major product as a result of Lewis acid catalysis by Sn(2+). Similar α-regiochemistry was observed when the reaction of the 3-aminopyrrole salt with trifluoromethyl-ß-diketones was carried out in the presence of base and tin(II) acetate.

Computational expressions for signals in frequency-modulation spectroscopy.

General expressions for the signals in frequency-modulation spectroscopy (FMS) appear in the literature but are often reduced to simple analytical equations following the assumption of a weak modulation index. This is little help to the experimentalist who wants to predict signals for modulation depths of the order of unity or greater, where strong FMS signals reside. Here, we develop general formulas for FMS signals in the case of an absorber with a Voigt line shape and then link these expressions to an example and existing numerical code for the line shape. The resulting computational recipe is easy to implement and exercised here to show where the larger FMS signals are found over the coordinates of modulation index and modulation frequency. One can also estimate from provided curves the in-phase FMS signal over a wide range of modulation parameters at either the Lorentzian-broadening or Doppler-broadening limit, or anywhere in between by interpolation.

Prostate imaging: evaluation of a reusable two-channel endorectal receiver coil for MR imaging at 1.5 T.

PURPOSE: To prospectively compare image quality with use of a two-channel solid reusable phased-array endorectal receiver coil (SPAC) with that of the single-channel inflatable endorectal balloon coil currently in widespread use for 1.5-T magnetic resonance (MR) imaging of the prostate. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Multiparametric prostate MR imaging at 1.5 T was performed in patients who were suspected of having cancer. Thirty consecutive patients were included (mean age, 66.1 years; range, 49-76 years). The first 15 patients were imaged by using a balloon coil and an eight-channel external array, and the remaining 15 were imaged with a SPAC alone. One patient was imaged with both techniques. Axial T2-weighted images acquired at both standard and high spatial resolution were used to compare image quality between coils. Qualitative assessments of image quality were made separately by three radiologists. Signal-to-noise ratio (SNR) profiles were determined on a pixel-by-pixel basis in a 1-cm central band in the prostate by using T1-weighted axial images at the apex, midgland, and base. Interrater reliability was determined by using a two-way intraclass correlation coefficient, qualitative scores were compared by using the Student t test for independent samples, and SNR profiles were plotted by using a Biot-Savart curve approximation. RESULTS: SNR of the SPAC was significantly better compared with that of the balloon coil at distances up to 3.0 cm at the apex and 3.5 cm at the base and midgland (P < .001). There was a 7% improvement in SNR at the mean maximal anteroposterior prostate dimension in this cohort and a 96% improvement at half this distance. At both standard and high spatial resolution, significant improvements in overall image quality (P = .015 and P < .001, respectively), visibility of the anterior gland (P = .009 and P < .001, respectively), and noise (P < .001 and P < .001, respectively) were seen when the SPAC was used. Interrater reliability was 0.536 (95% confidence interval: 0.461, 0.603). CONCLUSION: Both SNR and image quality were significantly improved with use of the SPAC at 1.5 T compared with use of the single-channel inflatable endorectal balloon coil.

Incorporating endorectal MR elastography into multi-parametric MRI for prostate cancer imaging: Initial feasibility in volunteers.

PURPOSE: To investigate the tolerability and technical feasibility of performing endorectal MR elastography (eMRE) in human volunteers within the representative age group commonly affected by prostate cancer. MATERIALS AND METHODS: Endorectal MRE was conducted on seven volunteers in a 1.5 Tesla (T) MR imager using a rigid endorectal coil. Another five volunteers were imaged on a 3T MR imager using an inflatable balloon type endorectal coil. Tolerability was accessed for vibration amplitudes of ±1-50 µm and for frequencies of 100-300 Hz. RESULTS: All 12 volunteers tolerated the displacements necessary to successfully perform eMRE. Shear waves with frequencies up to 300 Hz could propagate across the entire prostate using both coil designs. CONCLUSION: The results of this study motivate further investigation of eMRE in prostate cancer patients to help determine if there is an added value of integrating eMRE into existing multi-parametric prostate MRI exams.

Aromaticity and aminopyrroles: desmotropy and solution tautomerism of 1H-pyrrol-3-aminium and 1H-pyrrol-3(2H)-iminium cation: a stable σ-complex.

Protonation of 3-aminopyrrole at C-2 gave the σ-complex 1H-pyrrol-3(2H)-iminium cation, whereas protonation at the exoamino group gave its 1H-pyrrol-3-aminium tautomer. Both tautomers were isolated as their respective tetrakis(pentafluorophenyl)borate salt, an example of desmotropy. In solution, the NH(3)-tautomer was favored in hydrogen-bonding solvents and the CH(2)-tautomer in CH(2)Cl(2). A combination of effects on the aromaticity of the aminopyrrole ring increased the relative stability of the σ-complexes (conjugate acids) such that they can be readily observed or isolated.

Chlorotropy of 1-chlorobenzimidazole.

The chlorotropy observed by NMR in this study occurred by the rapid intermolecular transfer of a chloro group between 1-chlorobenzimidazole and benzimidazole in CCl4/CH3OH/K2CO3 solution.

Four mechanisms in the reactions of 3-aminopyrrole with 1,3,5-triazines: inverse electron demand Diels-Alder cycloadditions vs S(N)Ar reactions via uncatalyzed and acid-catalyzed pathways.

Reaction of 3-aminopyrrole with seven 1,3,5-triazines was studied in a one-step reaction (in situ formation of 3-aminopyrrole) and a two-step reaction (using the tetraphenylborate salt and an amine base). An inverse-electron demand Diels-Alder reaction (IEDDA) was observed with R1 = CF3, CO2Et, and H with the formation of 5H-pyrrolo[3,2-d]pyrimidine derivatives. S(N)Ar was observed when 2,4,6-trifluoro- or 2,4,6-trichloro-1,3,5-triazine were used--1,3,5-triazines that had leaving groups. If excess 1,3,5-triazine was present the initial S(N)Ar product reacted further, in the presence of acid and water, with another equivalent of 1,3,5-triazine to give compounds containing three linked heterocyclic rings. No reaction was observed with R1 = C6H5 and OCH3. Four mechanisms are proposed to explain the experimental results: uncatalyzed and acid catalyzed inverse electron demand Diels-Alder cascades leading to cycloaddition, and uncatalyzed and acid-catalyzed S(N)Ar reactions leading, respectively, to single and double substitution products. Acid catalysis was a factor when there was reduced reactivity in either reactant.

Electronic and steric effects on the mechanism of the inverse electron demand Diels-Alder reaction of 2-aminopyrroles with 1,3,5-triazines: identification of five intermediates by 1H, 13C, 15N, and 19F NMR spectroscopy.

The inverse electron demand Diels-Alder (IEDDA) reaction of 1-tert-butyl-2-aminopyrrole with 2,4,6-tris(trifluoromethyl)-1,3,5-triazine in THF-d(8) to give a pyrrolo[2,3-d]pyrimidine was studied by (1)H, (13)C, (15)N, and (19)F NMR spectroscopy, and five intermediates were identified. A zwitterion was the first intermediate detected, and it cyclized to a tricyclic adduct and its conjugate acid. It also gave a neutral imine via a proton switch. The tricyclic adduct underwent a retro-Diels-Alder reaction, but the expected CF(3)CN was not detected. NMR indicated that the amino group of the 2-aminopyrrole was bonded to the CF(3)CN to form a trifluoroacetoamidinium ion. The products of the retro-Diels-Alder reaction reacted rapidly with each other to give the final intermediate observed. Acid-catalyzed loss of an amidine gave the final aromatic product. This is the first study in which direct experimental evidence for the order of the steps in the IEDDA cascade reaction of 1,3,5-triazines with amino-containing dienophiles has been obtained. This study and analogous 1,3-dipolar cycloaddition reactions, in which zwitterions have been detected or proposed, have two factors in common: electronic effects that stabilize the zwitterions and steric effects that inhibit their cyclization.

Cardiac interstitial tetraploid cells can escape replicative senescence in rodents but not large mammals.

Cardiomyocyte ploidy has been described but remains obscure in cardiac interstitial cells. Ploidy of c-kit+ cardiac interstitial cells was assessed using confocal, karyotypic, and flow cytometric technique. Notable differences were found between rodent (rat, mouse) c-kit+ cardiac interstitial cells possessing mononuclear tetraploid (4n) content, compared to large mammals (human, swine) with mononuclear diploid (2n) content. In-situ analysis, confirmed with fresh isolates, revealed diploid content in human c-kit+ cardiac interstitial cells and a mixture of diploid and tetraploid content in mouse. Downregulation of the p53 signaling pathway provides evidence why rodent, but not human, c-kit+ cardiac interstitial cells escape replicative senescence. Single cell transcriptional profiling reveals distinctions between diploid versus tetraploid populations in mouse c-kit+ cardiac interstitial cells, alluding to functional divergences. Collectively, these data reveal notable species-specific biological differences in c-kit+ cardiac interstitial cells, which could account for challenges in extrapolation of myocardial from preclinical studies to clinical trials.

Phase-locked scanning interferometer for frequency stabilization of multiple lasers.

We report a simple scheme for stabilizing and tuning the length of a conventional piezo-driven optical cavity against the resonant transmission of a master laser. In contrast with other schemes, we drive the piezo at its mechanical resonance of 5 kHz over an amplitude equivalent to one free spectral range and use a feedback circuit that incorporates phase-sensitive detection of the master-laser transmission. The bandwidth of our cavity-lock circuit is limited only by the resonance frequency of the cavity piezo and is 1.4 kHz. The stabilized mean cavity length reaches in 30 s a minimum Allan deviation of approximately 10 kHz (a length stability of 20 parts per trillion) equaling that of the polarization-stabilized He-Ne we use as our master laser. Here, we investigate the mechanical characteristics of the cavity, describe the lock circuit and its measured performance, and provide simple analytical relations between the phase-sensitive signal and cavity displacement. Our setup economizes the cost and amount of equipment necessary for stabilizing multiple continuous-wave lasers operating at different wavelengths.

Pharmacokinetic analysis of prostate cancer using independent component analysis.

Dynamic contrast enhanced (DCE)-MRI combined with pharmacokinetic (PK) modeling of a tumor provides information about its perfusion and vascular permeability. Most PK models require the time course of contrast agent concentration in blood plasma as an input, which cannot be measured directly at the tissue of interest, and is approximated with an arterial input function (AIF). Variability in methods used in estimating the AIF and inter-observer variability in region of interest selection are major sources of discrepancy between different studies. This study had two aims. The first was to determine whether a local vascular input function (VIF) estimated using an adaptive complex independent component analysis (AC-ICA) algorithm could be used to estimate PK parameters from clinical dynamic contrast enhanced (DCE)-MRI studies. The second aim was to determine whether normalizing the input function using its area under the curve would improve the results of PK analysis. AC-ICA was applied to DCE-MRI of 27 prostate cancer patients and the intravascular signal was estimated. This signal was converted into contrast agent concentration to give a local vascular input function (VIF) which was used as the input function for PK analysis. We compared K(trans) values for normal peripheral zone (PZ) and tumor tissues using the local VIF with those calculated using a conventional AIF obtained from the femoral artery. We also compared the K(trans) values obtained from the un-normalized input functions with the KN(trans) values obtained after normalizing the AIF and local VIF. Normalization of the input function resulted in smaller variation in PK parameters (KN(trans) vs. K(trans) for normal PZ tissue was 0.20±0.04mM.min(-1) vs. 0.87±0.54min(-1) for local VIF and 0.21±0.07mM.min(-1) vs. 0.25±0.29min(-1) for AIF) and better separation of the normal and tumor tissues (effect-size of this separation using KN(trans) vs. K(trans) was 0.89 vs. 0.75 for local VIF and 0.94 vs. 0.41 for AIF). The AC-ICA and AIF-based analyses provided similar (KN(trans)) values in normal PZ tissue of prostate across patients. Normalizing the input function before PK analysis significantly improved the reproducibility of the PK parameters and increased the separation between normal and tumor tissues. Using AC-ICA allows a local VIF to be estimated and the resulting PK parameters are similar to those obtained using a more conventional AIF; this may be valuable in studies where an artery is not available in the field of view.

Evaluation of the prevalence of urinary tract infection in rural Panamanian women.

OBJECTIVE: Urinary tract infection (UTI) is the most common non-intestinal infection worldwide. In the developed world, incidence and prevalence of UTI would be similar owing to the relatively short duration of illness experienced by women with ready access to healthcare services. We hypothesize that, in the developing world, factors limiting access to care and those which may increase the likelihood of developing UTI, result in increased morbidity. This difference is reflected in an increased prevalence of UTI in regions where women suffer the effects of UTI for extended periods of time. METHODS: This study represents a cross sectional analysis of UTI prevalence in rural western Panama conducted over the course of a 3-day medical mission. All women 18-45 years of age reporting to the medical brigade clinic were tested for UTI by dipstick urinalysis and a brief history regardless of whether they themselves were presenting with a complaint. RESULTS: UTI was diagnosed clinically by providers in 29.8% of the women tested although only 21.15% of these same women met the evidence-based study criteria. This prevalence of 21.15% is seven times greater than reported by the Panamanian Ministry of Health. When comparing the effectiveness of clinical diagnosis relative to urinalysis by dipstick, a Kappa coefficient revealed only low moderate agreement (0.42; SE 0.0955). CONCLUSIONS: The prevalence of UTI in rural western Panama is greater than would be expected based on prevalence data from either the US or Panamanian Ministry of Health and may represent an opportunity for targeted interventions, including educational programming about UTI prevention.

Implantable cardioverter-defibrillator implantation as a bridge to cardiac transplantation.

Implantable cardioverter-defibrillators (ICDs) have been shown to reduce sudden cardiac death in select patients with impaired left ventricular function. However, consensus guidelines on ICD use have not historically addressed patients waiting for heart transplantation, and further evidence is needed to broaden and strengthen current recommendations. The objective of the present study was to review all patients listed for heart transplantation at a single institution and evaluate the impact of ICD implantation while waiting. All consecutive patients listed for heart transplantation at the Queen Elizabeth II Health Sciences Center, Halifax, Nova Scotia, from 1995 to July 2006, were included in the study (n = 124). We observed 12 deaths while waiting among patients listed for transplantation (10%), with all deaths occurring in the non-ICD patients. In patients who did have an ICD prior to transplantation, 17% received appropriate defibrillation therapy while awaiting transplantation, and 3 of 12 patients in the non-ICD population who died while waiting died suddenly, suggesting that ICDs could be used as a "bridge to transplantation" in patients with refractory heart failure who are to be listed for heart transplantation.