William Edwards Ladd, M.D. (1880-1967): the description of his bands.

In the early 20th century, an established surgical specialty catering to pediatric surgery did not exist, and pediatric surgical ailments were operated on by general surgeons. With his devotion to childhood diseases and his unique thinking in surgical development, William E. Ladd would become a leading figure in America by pioneering the field of pediatric surgery

Overt Mycobacterium avium subsp. paratuberculosis Infection: An Infrequent Occurrence in Archived Tissue from False TB Reactor Cattle in Michigan, USA

The objective of this study was to retrospectively determine whether or not cattle from the state of Michigan which were classified as bovine tuberculosis reactors, based on currently approved field and laboratory testing methods, were overtly infected with Mycobacterium avium subsp. paratuberculosis (MAP). Included in this study were 384 adult cattle submitted to the Diagnostic Center for Population and Animal Health over a seven-year period. Cattle were tested utilizing standard methods to confirm that all cattle were lesion and culture negative for infection with Mycobacterium bovis at postmortem examination. Retrospective analysis of formalin-fixed, paraffin-embedded sections of ileum and ileocecal lymph node were evaluated by histopathology, acid-fast staining, and PCR assays to detect MAP. Overall, only 1.04 percent of cattle showed overt infection with MAP on visual examination of sections of ileum and/or ileo-cecal lymph node. This increased slightly to 2.1 percent of cattle likely infected with MAP after additional testing using a PCR assay. Based on these results, we found no evidence that overt infection with MAP plays a major role in the false tuberculosis reactor test results for cattle examined in this study

Guidance for the evaluation and treatment of hereditary and acquired thrombophilia

Thrombophilias are hereditary and/or acquired conditions that predispose patients to thrombosis. Testing for thrombophilia is commonly performed in patients with venous thrombosis and their relatives; however such testing usually does not provide information that impacts management and may result in harm. This manuscript, initiated by the Anticoagulation Forum, provides clinical guidance for thrombophilia testing in five clinical situations: following 1) provoked venous thromboembolism, 2) unprovoked venous thromboembolism; 3) in relatives of patients with thrombosis, 4) in female relatives of patients with thrombosis considering estrogen use; and 5) in female relatives of patients with thrombosis who are considering pregnancy. Additionally, guidance is provided regarding the timing of thrombophilia testing. The role of thrombophilia testing in arterial thrombosis and for evaluation of recurrent pregnancy loss is not addressed. Statements are based on existing guidelines and consensus expert opinion where guidelines are lacking. We recommend that thrombophilia testing not be performed in most situations. When performed, it should be used in a highly selective manner, and only in circumstances where the information obtained will influence a decision important to the patient, and outweigh the potential risks of testing. Testing should not be performed during acute thrombosis or during the initial (3-month) period of anticoagulation

Intensity modulated radiation therapy dose painting for localized prostate cancer using(11)C-choline positron emission tomography scans

PURPOSE: To demonstrate the technical feasibility of intensity modulated radiation therapy (IMRT) dose painting using¹¹C-choline positron emission tomography PET scans in patients with localized prostate cancer. METHODS AND MATERIALS: This was an RT planning study of 8 patients with prostate cancer who had ¹¹C-choline PET scans prior to radical prostatectomy. Two contours were semiautomatically generated on the basis of the PET scans for each patient: 60% and 70% of the maximum standardized uptake values (SUV(60%) and SUV(70%)). Three IMRT plans were generated for each patient: PLAN(78), which consisted of whole-prostate radiation therapy to 78 Gy; PLAN(78-90), which consisted of whole-prostate RT to 78 Gy, a boost to the SUV(60%) to 84 Gy, and a further boost to the SUV(70%) to 90 Gy; and PLAN(72-90), which consisted of whole-prostate RT to 72 Gy, a boost to the SUV(60%) to 84 Gy, and a further boost to the SUV(70%) to 90 Gy. The feasibility of these plans was judged by their ability to reach prescription doses while adhering to published dose constraints. Tumor control probabilities based on PET scan-defined volumes (TCP(PET)) and on prostatectomy-defined volumes (TCP(path)), and rectal normal tissue complication probabilities (NTCP) were compared between the plans. RESULTS: All plans for all patients reached prescription doses while adhering to dose constraints. TCP(PET) values for PLAN(78), PLAN(78-90), and PLAN(72-90) were 65%, 97%, and 96%, respectively. TCP(path) values were 71%, 97%, and 89%, respectively. Both PLAN(78-90) and PLAN(72-90) had significantly higher TCP(PET) (P=.002 and .001) and TCP(path) (P<.001 and .014) values than PLAN(78). PLAN(78-90) and PLAN(72-90) were not significantly different in terms of TCP(PET) or TCP(path). There were no significant differences in rectal NTCPs between the 3 plans. CONCLUSIONS: IMRT dose painting for localized prostate cancer using (11)C-choline PET scans is technically feasible. Dose painting results in higher TCPs without higher NTCPs.Joe H. Chang, Daryl Lim Joon, Sze Ting Lee, Sylvia J. Gong, Nigel J. Anderson, Andrew M. Scott, Ian D. Davis, David Clouston, Damien Bolton, Christopher S. Hamilton, Vincent Kho

Correcting the extended-source calibration for the <i>Herschel</i>-SPIRE Fourier-transform spectrometer

We describe an update to the Herschel-Spectral and Photometric Imaging Receiver (SPIRE) Fourier-transform spectrometer (FTS) calibration for extended sources, which incorporates a correction for the frequency-dependent far-field feedhorn efficiency, ηff. This significant correction affects all FTS extended-source calibrated spectra in sparse or mapping mode, regardless of the spectral resolution. Line fluxes and continuum levels are underestimated by factors of 1.3–2 in thespectrometer long wavelength band (447–1018 GHz; 671–294 μm) and 1.4–1.5 in the spectrometer short wavelength band (944–1568 GHz; 318–191 μm). The correction was implemented in the FTS pipeline version 14.1 and has also been described in the SPIRE Handbook since 2017 February. Studies based on extended-source calibrated spectra produced prior to this pipeline version should be critically reconsidered using the current products available in the Herschel Science Archive. Once the extended-source calibrated spectra are corrected for ηff, the synthetic photometry and the broad-band intensities from SPIRE photometer maps agree within 2–4 per cent – similar levels to the comparison of point-source calibrated spectra and photometry from point-source calibrated maps. The two calibration schemes for the FTS are now self-consistent: the conversion between the corrected extended-source and point-source calibrated spectra can be achieved with the beam solid angle and a gain correction that accounts for the diffraction loss

Comparison of [(11)C]choline positron emission tomography with T2- and diffusion-weighted magnetic resonance imaging for delineating malignant intraprostatic lesions

Purpose: To compare the accuracy of ¹¹C-choline (CHOL) positron emission tomography (PET) with the combination of T2-weighted (T2W) and diffusion-weighted (DW) magnetic resonance imaging (MRI) for delineating malignant intraprostatic lesions (IPLs) for guiding focal therapies and to investigate factors predicting the accuracy of CHOL-PET. Methods and Materials: This study included 21 patients who underwent CHOL-PET and T2W-/DW-MRI prior to radical prostatectomy. Two observers manually delineated IPL contours for each scan, and automatic IPL contours were generated on CHOL-PET based on varying proportions of the maximum standardized uptake value (SUV). IPLs identified on prostatectomy specimens defined the reference standard contours. The imaging-based contours were compared with the reference standard contours using Dice similarity coefficient (DSC), sensitivity and specificity. Factors that could potentially predict the DSC of the best contouring method were analyzed using linear models. Results: The best automatic contouring method, SUV60, had similar correlations (DSC 0.59) with the manual PET contours (DSC 0.52, P=0.127) and significantly better correlations than the manual MRI contours (DSC 0.37, P<0.001). The sensitivity and specificity values were 72% and 71% for SUV60; 53% and 86% for PET manual contouring; and 28% and 92% for MRI manual contouring. The tumor volume and transition zone pattern could independently predict the accuracy of CHOL-PET. Conclusions: CHOL-PET is superior to the combination of T2W- and DW-MRI for delineating IPLs. The accuracy of CHOL-PET is insufficient for gland-sparing focal therapies, 3 however may be accurate enough for focal boost therapies. The transition zone pattern is a new classification that may predict for how well CHOL-PET delineates IPLs.Joe H. Chang, Daryl Lim Joon, Ian D. Davis, Sze Ting Lee, Chee-Yan Hiew, Stephen Esler, Sylvia J. Gong, Morikatsu Wada, David Clouston, Richard O'Sullivan, Yin P. Goh, Damien Bolton, Andrew M. Scott, Vincent Kho

ASELL : the advancing science by enhancing learning in the laboratory project

Most science educators and researchers will agree that the laboratory experience ranks as a major factor that influences students&rsquo; attitudes to their science courses. Consequently, good laboratory programs should play a major role in influencing student learning and performance. The laboratory program can be pivotal in defining a student\u27s experience in the sciences, and if done poorly, can be a major contributing factor in causing disengagement from the subject area. The challenge remains to provide students with laboratory activities that are relevant, engaging and offer effective learning opportunities

Diffusion-weighted MRI, (11)C-choline PET and (18)F-fluorodeoxyglucose PET for predicting the Gleason score in prostate carcinoma

Objectives To evaluate the accuracy of transrectal ultrasoundguided (TRUS) biopsy, diffusion-weighted (DW) magnetic resonance imaging (MRI), ¹¹C-choline (CHOL) positron emission tomography (PET), and 18F-fluorodeoxyglucose (FDG) PET in predicting the prostatectomy Gleason risk (GR). Methods The study included 21 patients who underwent TRUS biopsy and multi-technique imaging before radical prostatectomy. Values from five different tests (TRUS biopsy, DW MRI, CHOL PET, FDG PET, and combined DW MRI/ CHOL PET) were correlated with the prostatectomy GR using Spearman’s ρ. Tests that were found to have significant correlations were used to classify patients into GR groups. Results The following tests had significant correlations with prostatectomy GR: TRUS biopsy (ρ=0.617, P =0.003), DW MRI (ρ=–0.601, P =0.004), and combined DW MRI/CHOL PET (ρ=–0.623, P =0.003). CHOL PET alone and FDG PET only had weak correlations. The correct GR classification rates were 67 % with TRUS biopsy, 67 % with DW MRI, and 76 % with combined DW MRI/CHOL PET. Conclusions DW MRI and combined DW MRI/CHOL PET have significant correlations and high rates of correct classification of the prostatectomy GR, the strength and accuracy of which are comparable with TRUS biopsy. Key Points • Accurate determination of the Gleason score is essential for prostate cancer management. • DW MRI ± CHOL PET correlated significantly with prostatectomy Gleason score. • These correlations are similar to that between TRUS biopsy and prostatectomyJoe H. Chang, Daryl Lim Joon, Sze Ting Lee, Chee-Yan Hiew, Stephen Esler, Sylvia J. Gong, Morikatsu Wada, David Clouston, Richard O, Sullivan, Yin P. Goh, Henri Tochon-Danguy, J. Gordon Chan, Damien Bolton, Andrew M. Scott, Vincent Khoo, Ian D. Davi

Crystal Structure of Monoclonal 6B5 Fab Complexed with Phencyclidine

The crystal structure of monoclonal antibody (mAb) 6B5 Fab fragment complexed with 1-(1-phenylcyclohexyl)piperidine (PCP or phencyclidine) was determined at 2.2-A resolution. 6B5 was originally produced from a mouse immunized with a phencyclidine analogue hapten 5-[N-(1'phenylcyclohexyl)amino]pentanoic acid conjugated to bovine serum albumin. This mAb was selected for further study because of its high affinity (Kd = 2 x 10(-9) M/liter) for PCP and usefulness in reversing PCP-induced central nervous system toxicity in laboratory animals. The dominant feature of the 6B5 Fab.PCP complex is the deep binding site and hydrophobic nature of the interaction. The ligand binding pocket of 6B5 Fab has numerous aromatic side chains, as compared with other known Fab structures. The most notable feature of the binding site is a Trp at position 97H (H-chain), and the side chain of this residue appears to act as a hydrophobic umbrella on the ligand in the antigen binding pocket. There are only two other known Fabs found with a Trp at the 97H position in complementarity determining region (CDR) H3, but they do not play a major role in the interaction with their respective antigens; in both Fab TE33 and R6.5 the Trp 97H side chain is positioned away from the bound antigen. Comparison of the CDR residues of 6B5 with other Fab structures with similar CDR sizes and amino acid compositions reveals a number of important patterns of residue substitutions that appear to be critical for specific PCP ligand interactions