Additive- and Metal-Free, Predictably 1,2- and 1,3-Regioselective, Photoinduced Dual C-H/C-X Borylation of Haloarenes.

We report herein a simple, additive- and metal-free, photoinduced, dual C-H/C-X borylation of chloro-, bromo-, and iodoarenes. The reaction produces 1,2- and 1,3-diborylarenes on gram scales under batch and continuous flow conditions. The regioselectivity of the dual C-H/C-X borylation is determined by the solvent and the substituents in the parent haloarenes.

Scalable, Metal- and Additive-Free, Photoinduced Borylation of Haloarenes and Quaternary Arylammonium Salts.

We report herein a simple, metal- and additive-free, photoinduced borylation of haloarenes, including electron-rich fluoroarenes, as well as arylammonium salts directly to boronic acids. This borylation method has a broad scope and functional group tolerance. We show that it can be further extended to boronic esters and carried out on gram scale as well as under flow conditions.

The clinical relevance of pre-formed anti-HLA and anti-MICA antibodies after cord blood transplantation in children.

Preformed anti-HLA antibodies (AHA) are known to be associated with delayed engraftment and reduced overall survival after adult hematopoietic stem cell transplantation. However, limited data is available in pediatric patients. In this study, we explored the role of AHA on clinical outcomes in 70 pediatric patients who received a single unit of HLA mismatch cord blood for hematologic malignancies, immunodeficiencies or metabolic diseases. The presence of AHA was detected in 44% (31/70) of the patients. Preformed class I AHA was associated with an increased occurrence of grade 1-4 acute graft-versus host disease (p<0.05). The presence of anti- major-histocompatibility-complex class I-related chain A antigens (MICA) antibodies was significantly associated with a reduced platelet recovery after transplantation (p<0.05). AHA of class II with the strength of antibody titer measured as the mean fluorescence intensity above 2000 was associated with reduced event-free survival (p<0.05). A reduction of high titer of AHA and anti-MICA antibodies might have to be considered before cord blood transplantation in pediatric patients for better outcomes.

Detection and identification of first and second heart sounds using empirical mode decomposition.

We present a novel, low complexity method for the detection of the first and second of heart sounds (S1 and S2, respectively) and the periods of systole and diastole without using an electrocardiogram reference. The algorithm uses a technique called empirical mode decomposition to produce intensity envelopes of the main heart sounds in the time domain. The performance of the algorithm was evaluated using 14,000 cardiac periods from 100 normal and abnormal digital phonocardiographic recordings. The sensitivity of the detection method was 88.3% for both S1 and S2, and the precision (positive predictive value) was 95.8% for both S1 and S2.

Prediction of area under the cyclosporine concentration versus time curve in children undergoing hematopoietic stem cell transplantation.

This prospective study aimed to validate a previously developed first-dose limited sampling strategy (LSS) to predict the area under the cyclosporine concentration-versus-time curve (AUC) and to develop and then validate an LSS to predict cyclosporine AUC at steady state. This two-center Canadian study included children (ages .4 to 17.2 years) undergoing myeloablative allogeneic hematopoietic stem cell transplantation receiving cyclosporine for acute graft-versus-host disease prophylaxis. There were three cohorts, each incorporating 24 AUC determinations: first-dose LSS validation, steady-state LSS development, and steady-state LSS validation. Patients contributing data to either of the development cohorts were excluded from the corresponding validation group. Cyclosporine was given every 12 hours as a 2-hour infusion. Cyclosporine AUC was determined after administration of the first cyclosporine dose (8 samples) and then once weekly (9 samples) until engraftment. Steady-state LSSs were developed using stepwise multiple linear regression. An LSS was considered to provide an acceptable estimate of AUC if the lower limit of the 95% confidence limit (CL) of the intraclass coefficient was .8 or higher and both bias and precision were 15% or less. Fifty-three children age .4 to 18 years participated. Cyclosporine concentrations drawn up to 4 hours from the start of the infusion correlated most strongly with AUC. The previously developed first-dose LSSs and three steady-state LSSs met criteria for acceptability. The intraclass coefficients of the three-point first-dose LSS validation cohort, three-point steady-state LSS development cohort, and three-point steady-state LSS validation cohort were .974 (95% CL: .941 to .988), .984 (95% CL: .965 to .993), and .993 (95% CL: .984 to .997), respectively. The three-point first-dose (2, 6, and 8 hours) and steady-state (2, 2.5, and 8 hours) LSSs are valid measures of cyclosporine AUC after intravenous administration over 2 hours. Their use in a prospective evaluation of the relationship between cyclosporine AUC and hematopoietic stem cell transplantation clinical outcomes in children is suggested.

Digital Subtraction Phonocardiography (DSP) applied to the detection and characterization of heart murmurs.

BACKGROUND: During the cardiac cycle, the heart normally produces repeatable physiological sounds. However, under pathologic conditions, such as with heart valve stenosis or a ventricular septal defect, blood flow turbulence leads to the production of additional sounds, called murmurs. Murmurs are random in nature, while the underlying heart sounds are not (being deterministic). INNOVATION: We show that a new analytical technique, which we call Digital Subtraction Phonocardiography (DSP), can be used to separate the random murmur component of the phonocardiogram from the underlying deterministic heart sounds. METHODS: We digitally recorded the phonocardiogram from the anterior chest wall in 60 infants and adults using a high-speed USB interface and the program Gold Wave http://www.goldwave.com. The recordings included individuals with cardiac structural disease as well as recordings from normal individuals and from individuals with innocent heart murmurs. Digital Subtraction Analysis of the signal was performed using a custom computer program called Murmurgram. In essence, this program subtracts the recorded sound from two adjacent cardiac cycles to produce a difference signal, herein called a "murmurgram". Other software used included Spectrogram (Version 16), GoldWave (Version 5.55) as well as custom MATLAB code. RESULTS: Our preliminary data is presented as a series of eight cases. These cases show how advanced signal processing techniques can be used to separate heart sounds from murmurs. Note that these results are preliminary in that normal ranges for obtained test results have not yet been established. CONCLUSIONS: Cardiac murmurs can be separated from underlying deterministic heart sounds using DSP. DSP has the potential to become a reliable and economical new diagnostic approach to screening for structural heart disease. However, DSP must be further evaluated in a large series of patients with well-characterized pathology to determine its clinical potential.

A color spectrographic phonocardiography (CSP) applied to the detection and characterization of heart murmurs: preliminary results.

BACKGROUND: Although cardiac auscultation remains important to detect abnormal sounds and murmurs indicative of cardiac pathology, the application of electronic methods remains seldom used in everyday clinical practice. In this report we provide preliminary data showing how the phonocardiogram can be analyzed using color spectrographic techniques and discuss how such information may be of future value for noninvasive cardiac monitoring. METHODS: We digitally recorded the phonocardiogram using a high-speed USB interface and the program Gold Wave http://www.goldwave.com in 55 infants and adults with cardiac structural disease as well as from normal individuals and individuals with innocent murmurs. Color spectrographic analysis of the signal was performed using Spectrogram (Version 16) as a well as custom MATLAB code. RESULTS: Our preliminary data is presented as a series of seven cases. CONCLUSIONS: We expect the application of spectrographic techniques to phonocardiography to grow substantially as ongoing research demonstrates its utility in various clinical settings. Our evaluation of a simple, low-cost phonocardiographic recording and analysis system to assist in determining the characteristic features of heart murmurs shows promise in helping distinguish innocent systolic murmurs from pathological murmurs in children and is expected to useful in other clinical settings as well.