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Many genes that drive normal cellular development also contribute to oncogenesis. Medulloblastoma (MB) tumors likely arise from neuronal progenitors in the cerebellum, and we hypothesized that the heterogeneity observed in MBs with sonic hedgehog (SHH) activation could be due to differences in developmental pathways. To investigate this question, here we perform single-nucleus RNA sequencing on highly differentiated SHH MBs with extensively nodular histology and observed malignant cells resembling each stage of canonical granule neuron development. Through innovative computational approaches, we connect these results to published datasets and find that some established molecular subtypes of SHH MB appear arrested at different developmental stages. Additionally, using multiplexed proteomic imaging and MALDI imaging mass spectrometry, we identify distinct histological and metabolic profiles for highly differentiated tumors. Our approaches are applicable to understanding the interplay between heterogeneity and differentiation in other cancers and can provide important insights for the design of targeted therapies., (© 2024. The Author(s).)

Background: Pediatric laryngotracheal stenosis often requires open airway reconstruction. While these surgeries establish an airway for adequate ventilation, many patients develop subsequent dysphonia. Numerous studies have reported outcomes related to voice., Objective: This study aims to evaluate dysphonia in pediatric patients following open airway reconstruction, focusing on acoustic parameters, perceptual voice quality, and voice-related quality of life., Methods: A comprehensive search using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines across 6 databases identified articles involving pediatric patients who underwent open airway reconstruction and reported postoperative vocal acoustic parameters, perceptual voice quality, voice-related quality of life, or vocal mechanics. Articles were assessed for bias risk, and common outcomes were synthesized qualitatively and quantitatively using meta-analyses., Results: Among 4089 articles, 21 were included, involving 497 pediatric patients. Laryngotracheoplasty was the most common procedure followed by cricotracheal resection. The Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) scale was frequently used to assess voice quality, with a mean score of 55.6 [95% confidence intervals (CIs): 47.9-63.3]. Voice-related quality of life was measured using the pediatric Voice Handicap Index (pVHI) and Pediatric Voice-Related Quality of Life Survey, with mean scores of 35.6 (95% CI: 21.4-49.7) and 83.7 (95% CI: 74.1-93.2), respectively. The fundamental frequency was 210.5 (95% CI: 174.6-246.3). Other common findings included supraglottic phonation, anterior commissure blunting, posterior glottic diastasis, and abnormal vocal cord mobility., Conclusion: Pediatric patients experiencing dysphonia after open airway reconstruction exhibited moderately decreased voice quality and reduced voice-related quality of life. However, there was inconsistency in study protocols and outcome measures used. Preserving voice quality during airway reconstruction is crucial to avoid negative impacts on quality of life., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Image-guided procedures play a critical role in the clinical practice of radiologists. Training radiology residents in these procedures, with early teaching of basic but fundamental skills, is therefore crucial to develop competence before they become autonomous and start their practice. It has been proposed in the literature that low-fidelity phantoms are appropriate to teach novice trainees. The authors propose a series of phantoms to teach the core skills necessary to perform procedures early in resident training. The phantoms described can be used to train skills necessary for performing US-guided biopsy, US-guided vascular puncture, cone-beam CT drainage, and fluoroscopy-guided lumbar puncture, as well as using the parallax effect to determine relative position at fluoroscopy. Phantoms are a valuable training tool, although it is important to consider the teaching audience when choosing or creating a model. For novices, a range of inexpensive low-fidelity gelatin-based phantoms can be used to train core skills in image-guided procedures. The online slide presentation from the RSNA Annual Meeting is available for this article. © RSNA, 2021.

Objective: The first pediatric tracheostomy tube change often occurs within 7 days after placement; however, the optimal timing is not known. The primary objective was to determine the rate of adverse events of an early tube change. Secondary objectives compared rates of significant peristomal wounds, sedation requirements, and expedited intensive care discharges., Study Design: Prospective randomized controlled trial., Setting: Tertiary children's hospital between October 2018 and April 2020., Methods: A randomized controlled trial enrolled children under 24 months to early (day 4) or late (day 7) first tracheostomy tube changes., Results: Sixteen children were enrolled with 10 randomized to an early change. Median age was 5.9 months (interquartile range, 5.4-8.3), and 86.7% required tracheostomy for respiratory failure. All tracheostomy tube changes were performed without adverse events. There were no accidental decannulations. Significant wounds developed in 10% of children with early tracheostomy tube changes and 83.3% of children with late tracheostomy tube changes (odds ratio [OR], 45.0; 95% CI, 2.3-885.6; P = .01). This significant reduction in wound complications justified concluding trial enrollment. Hours of dexmedetomidine sedation ( P = .11) and boluses of midazolam during the first 7 days ( P = .08) were no different between groups. After the first change, 90% of the early group were discharged from intensive care within 5 weeks compared to 33.3% of patients in the late group (OR, 18.0; 95% CI, 1.2-260.9; P = .03)., Conclusion: The first tracheostomy tube change in children can occur without adverse events on day 4, resulting in fewer significant peristomal wounds and earlier intensive care discharge.

Objective: Emergent medical crises, such as acute airway obstruction, are often managed by interdisciplinary teams. However, resident training in crisis resource management traditionally occurs in silos. Our objective was to compare the current state of interdisciplinary crisis resource management (IDCRM) training of otolaryngology residents with other disciplines., Methods: A survey study examining (1) the frequency with which residents are involved in interdisciplinary crises, (2) the current state of interdisciplinary training, and (3) the desired training was conducted targeting Canadian residents in the following disciplines: otolaryngology, anesthesiology, emergency medicine, general surgery, obstetrics and gynecology, internal medicine, pediatric emergency medicine, and pediatric/neonatal intensive care., Results: A total of 474 surveys were completed (response rate, 12%). On average, residents were involved in 13 interdisciplinary crises per year. Only 8% of otolaryngology residents had access to IDCRM training, as opposed to 66% of anesthesiology residents. Otolaryngology residents reported receiving an average of 0.3 hours per year of interdisciplinary training, as compared with 5.4 hours per year for pediatric emergency medicine residents. Ninety-six percent of residents desired more IDCRM training, with 95% reporting a preference for simulation-based training., Discussion: Residents reported participating in crises managed by interdisciplinary teams. There is strong interest in IDCRM and crisis resource management training; however, it is not uniformly available across Canadian residency programs. Despite their pivotal role in managing critical emergencies such as acute airway obstruction, otolaryngology residents received the least training., Implication: IDCRM should be explicitly taught since it reflects reality and may positively affect patient outcomes., Competing Interests: Competing interests: None.

In this work, the dependence of the morphology and stability of the extended solid of carbon monoxide (CO) is correlated to the rate of transformation from the molecular CO to extended solid of CO using optical imaging, photoluminescence, Raman spectroscopy, and X-ray diffraction. The analyses show the rate and pressure of the transformation to be strongly controlled by catalytic effects, both chemical and optical. In a larger volume per reaction area, the transformation was found to require either a longer time at an elevated pressure or a higher pressure compared to a sample synthesized in a smaller volume per reaction area, leading to the conclusion that the transformation rate is slower for a sample in a larger volume per reaction area. A faster rate of transformation was also noted when the reaction area of a CO sample was catalyzed with H 2 SO 4 . Through variation of the volume per reaction area, pressure or the addition of catalysts, it was possible to control the rate of the phase transition and therefore the morphology. In general, the extended solid of CO synthesized with a faster rate showed a more ordered structure and increased metastability relative to the material formed with a slower compression rate.

Background: Chronic suppurative otitis media can be recalcitrant and difficult to treat, particularly with the increasing occurrence of antibiotic resistance. Lactobacillus plantarum is a probiotic that has been shown to decrease S. aureus and P. aeruginosa growth in wounds, making it a good candidate for the treatment of chronic suppurative otitis media. However, before it can be applied in the ear, its ototoxicity potential must be evaluated., Methods: A prospective controlled trial was conducted in a chinchilla animal model at the Animal care research facilities of the Montreal Children's Hospital Research Institute to determine whether Lactobacillus plantarum is ototoxic when applied transtympanically. Ten chinchillas each had one ear randomly assigned to receive 10 9  CFU/mL of Lactobacillus plantarum solution, while the contralateral ear received saline. Auditory brainstem responses were measured bilaterally at 8, 20, 25 kHz before, at 7-10 days after application, and at 28 days after application of probiotic or saline. Facial nerve and vestibular function were assessed clinically., Results: There were no statistically significant differences in hearing thresholds between control and experimental ears at 28 days after application. A difference of 11 dB was noted in the 25 kHz range at day 7-10, but resolved by day 28. No animals receiving probiotics developed vestibular nerve dysfunction. There was no histologic evidence of auditory hair cell damaged evidenced by scanning electron microscopy., Conclusion: Our study suggests that a single application of Lactobacillus plantarum at 10 9  CFU/mL does not cause ototoxicity in a chinchilla animal model. These preliminary safety evaluations and the pathogen inhibitory effects of L. plantarum demonstrated by previous studies present this probiotic as a candidate of interest for further investigation.

Current approaches for topical vaginal administration of nanoparticles result in poor retention and extensive leakage. To overcome these challenges, we developed a nanoparticle-releasing nanofiber delivery platform and evaluated its ability to improve nanoparticle retention in a murine model. We individually tailored two components of this drug delivery system for optimal interaction with mucus, designing (1) mucoadhesive fibers for better retention in the vaginal tract, and (2) PEGylated nanoparticles that diffuse quickly through mucus. We hypothesized that this novel dual-functioning (mucoadhesive/mucus-penetrating) composite material would provide enhanced retention of nanoparticles in the vaginal mucosa. Equivalent doses of fluorescent nanoparticles were vaginally administered to mice in either water (aqueous suspension) or fiber composites, and fluorescent content was quantified in cervicovaginal mucus and vaginal tissue at time points from 24 h to 7d. We also fabricated composite fibers containing etravirine-loaded nanoparticles and evaluated the pharmacokinetics over 7d. We found that our composite materials provided approximately 30-fold greater retention of nanoparticles in the reproductive tract at 24 h compared to aqueous suspensions. Compared to nanoparticles in aqueous suspension, the nanoparticles in fiber composites exhibited sustained and higher etravirine concentrations after 24 h and up to 7d, demonstrating the capabilities of this new delivery platform to sustain nanoparticle release out to 3d and drug retention out to one week after a single administration. This is the first report of nanoparticle-releasing fibers for vaginal drug delivery, as well as the first study of a single delivery system that combines two components uniquely engineered for complementary interactions with mucus., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Otolaryngology-head and neck surgery (OTL-HNS) residents face a variety of difficult, high-stress situations, which may occur early in their training. Since these events occur infrequently, simulation-based learning has become an important part of residents' training and is already well established in fields such as anesthesia and emergency medicine. In the domain of OTL-HNS, it is gradually gaining in popularity. Crisis Resource Management (CRM), a program adapted from the aviation industry, aims to improve outcomes of crisis situations by attempting to mitigate human errors. Some examples of CRM principles include cultivating situational awareness; promoting proper use of available resources; and improving rapid decision making, particularly in high-acuity, low-frequency clinical situations. Our pilot project sought to integrate CRM principles into an airway simulation course for OTL-HNS residents, but most important, it evaluated whether learning objectives were met, through use of a novel error identification model.

Background: In otologic surgery good visualization is paramount, and patients with bleeding diatheses or who need to be anti-coagulated can present a significant challenge. Here, we determine whether Floseal™, a hemostatic matrix, is ototoxic in a validated animal model., Methods: Nine chinchillas housed in the animal care facilities of the Montreal Children's Hospital Research Institute were used for the study. After a myringotomy incision was made in each tympanic membrane, baseline auditory brainstem response measurements were performed at 8, 20, and 25 kHz. In each animal one ear was randomized to receive Floseal™ to the middle ear cavity, whereas the other ear served as the control and received 0.9% sodium chloride. Outcome measures included early (day 7) and late (day 30) auditory brainstem response, clinical evidence of facial nerve or vestibular disturbance and histological evidence of ototoxity., Results: There was no significant hearing threshold shift on auditory brainstem response across all tested frequencies for both experimental and control ear. No animals receiving Floseal™ developed facial or vestibular nerve dysfunction and there was no histological evidence of ototoxicity., Conclusion: Based on the preliminary ototoxicity assessment on nine chinchillas, transtympanic Floseal™ does not appear to be ototoxic. More studies are warranted to assess the safety and applicability of the product in humans.

Objective: Hypocalcemia following thyroidectomy often prolongs hospital stay and is potentially life-threatening. The objective of this study is to determine whether the season when thyroidectomy is performed is associated with postoperative hypocalcemia., Study Design: Retrospective case series of patients undergoing thyroid surgery from 2009 to 2015., Setting: Tertiary care academic institution in Montreal, Canada., Subjects and Methods: A consecutive sample of 823 patients undergoing thyroidectomy by a single high-volume otolaryngologist for a suspected or confirmed thyroid malignancy. Patient demographics, procedure type, calcium and vitamin D supplementation, and seasonal rate of hypocalcemia postthyroidectomy were calculated and compared., Results: Average seasonal rates of postthyroidectomy hypocalcemia in the winter, spring, summer, and autumn were, respectively, 8.3% (8 of 216), 7.3% (12 of 165), 1.5% (3 of 201), and 3.5% (8 of 228; P < .005). Patients operated in the winter were 5.6 times more likely to develop hypocalcemia as compared with those in the summer (P < .01; 95% confidence interval: 1.7-18.7). In a multiple regression analysis factoring in season when surgery was performed, procedure type, and preoperative vitamin D/calcium supplementation, surgery occurring in the winter predicted a hypocalcemia event (correlation coefficient [SE]: 0.72 [0.024], P = .026; 0.006 [0.025], P = .81; 0.004 [0.019], P = .82, respectively)., Conclusion: In this study, patients undergoing thyroidectomy in the winter months were more likely to develop postoperative hypocalcemia when compared with those operated in the summer. Further studies are needed to understand the role of vitamin D in the observed seasonal difference in hypocalcemia rates., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.)

Background & Objectives: Preterm infants are at highest risk for severe rotavirus gastroenteritis. While rotavirus vaccination is recommended for age-eligible, clinically stable preterm infants, controversy exists regarding vaccination of these infants during hospitalization. The objectives of this study were to examine tolerance of pentavalent rotavirus vaccination (RV5) among hospitalized infants and nosocomial rotavirus transmission in the neonatal intensive care units (NICU) at two urban hospitals., Methods: A retrospective, medical chart review of patients receiving RV5 vaccine was conducted to examine clinical histories of vaccine recipients. Average risk differences of gastrointestinal complications were estimated between the three days prior and up to four weeks following RV5 vaccination. A generalized linear regression model was used to examine the association between days since RV5 administration and daily feeding totals, using fixed effects to account for individual-level clustering. Rates of nosocomial rotavirus from active surveillance were compared between pre- and post-NICU-based vaccination periods., Results: From July 1, 2011 to March 30, 2013, RV5 vaccination was initiated for 102 NICU patients. No changes in the average risk of gastrointestinal complications or daily feeding among participants overall were detected following RV5 administration. Rates of nosocomial rotavirus were similar during the periods before and after NICU-based vaccination., Conclusions: On average, RV5 appeared to be well tolerated among vaccine recipients, with no increase in nosocomial rotavirus transmission observed following NICU-based rotavirus vaccination. While the benefits of a RV5 NICU-based vaccination program for otherwise eligible preterm infants seem to outweigh the possible risk of vaccine virus transmission, further studies are needed., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: The aim of this project was to develop a set of quality indicators to assess surgical decision making in the care of patients with non-small cell lung cancer (NSCLC)., Methods: A multidisciplinary Expert Panel of 16 physicians used a modified Delphi process to identify quality indicators that evaluated the processes of care in patients with NSCLC. A systematic review identified potential indicators, which were rated on actionability, validity, usefulness, discriminability, and feasibility in two rounds of questionnaires. The first questionnaire was completed by the Expert Panel and by the larger thoracic surgical community of practice; the second questionnaire was sent to only the Expert Panel. Expert Panel members attended an in-person meeting to review the results of the two questionnaires and to compile the final list of indicators by consensus., Results: From the literature review, 41 potential indicators were identified. An additional 16 indicators were suggested by the Expert Panel: 13 indicators in the two rounds of questionnaires and three after the discussion at the in-person meeting. One further indicator was identified after the in-person meeting. In the end, 17 indicators were chosen from seven domains: preoperative assessment, staging, surgical procedures, pathology, adjuvant therapy, surgical outcomes, and miscellaneous, Conclusions: By use of a modified Delphi process, 17 indicators to assess the quality of processes of surgical care for patients with NSCLC were developed., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Squalene, an intermediate in the biosynthesis of cholesterol, has a 24-carbon backbone with six methyl groups and six isolated double bonds. Capillary flow techniques have been used to determine its translational diffusion constant, D, at room temperature in squalane, n-C16, and three n-C8-squalane mixtures. The D values have a weaker dependence on viscosity, η, than predicted by the Stokes-Einstein relation, D = kBT/(6πηr). A fit to the modified relation, D/T = ASE/η(p), gives p = 0.820 ± 0.028; p = 1 for the Stokes-Einstein limit. The translational motion of squalene appears to be much like that of n-alkane solutes with comparable chain lengths; their D values show similar deviations from the Stokes-Einstein model. The n-alkane with the same carbon chain length as squalene, n-C24, has a near-equal p value of 0.844 ± 0.018 in n-alkane solvents. The values of the hydrodynamic radius, r, for n-C24, squalene, and other n-alkane solutes decrease as the viscosity increases and have a common dependence on the van der Waals volumes of the solute and solvent. The possibility of studying squalene in lipid droplets and membranes is discussed.

Laser shock Hugoniot data were obtained using ultrafast dynamic ellipsometry (UDE) for both nonideal (ethanol/water solutions with mole percent χ(ethanol) = 0%, 3.4%, 5.4%, 7.5%, 9.7%, 11%, 18%, 33%, 56%, 100%) and ideal liquid mixtures (toluene/fluorobenzene solutions with mole percent χ(toluene) = 0%, 26.0%, 49.1%, 74.9%, 100%). The shock and particle velocities obtained from the UDE data were compared to the universal liquid Hugoniot (ULH) and to literature shock (plate impact) data where available. It was found that the water UDE data fit to a ULH-form equation suggests an intercept of 1.32 km/s, lower than the literature ambient sound speed in water of 1.495 km/s (Mijakovic et al. J. Mol. Liq. 2011, 164, 66-73). Similarly, the ethanol UDE data fit to a ULH-form equation suggests an intercept of 1.45 km/s, which lies above the literature ambient sound speed in ethanol of 1.14 km/s. Both the literature plate impact and UDE Hugoniot data lie below the ULH for water. Likewise, the literature plate impact and UDE Hugoniot data lie above the ULH for ethanol. The UDE Hugoniot data for the mixtures of water and ethanol cross the predictions of the ULH near the same concentration where the sound speed reaches a maximum. In contrast, the UDE data from the ideal liquids and their mixtures are well behaved and agree with ULH predictions across the concentration range. The deviations of the nonideal ethanol/water data from the ULH suggest that complex hydrogen bonding networks in ethanol/water mixtures alter the compressibility of the mixture.

Questions: Should surgery be considered for colorectal cancer (crc) patients who have liver metastases plus (a) pulmonary metastases, (b) portal nodal disease, or (c) other extrahepatic metastases (ehms)?What is the role of chemotherapy in the surgical management of crc with liver metastases in (a) patients with resectable disease in the liver, or (b) patients with initially unresectable disease in the liver that is downsized with chemotherapy ("conversion")?What is the role of liver resection when one or more crc liver metastases have radiographic complete response (rcr) after chemotherapy?, Perspectives: Advances in chemotherapy have improved survival in crc patients with liver metastases. The 5-year survival with chemotherapy alone is typically less than 1%, although two recent studies with folfox or folfoxiri (or both) reported rates of 5%-10%. However, liver resection is the treatment that is most effective in achieving long-term survival and offering the possibility of a cure in stage iv crc patients with liver metastases. This guideline deals with the role of chemotherapy with surgery, and the role of surgery when there are liver metastases plus ehms. Because only a proportion of patients with crc metastatic disease are considered for liver resection, and because management of this patient population is complex, multidisciplinary management is required., Methodology: Recommendations in the present guideline were formulated based on a prepublication version of a recent systematic review on this topic. The draft methodology experts, and external review by clinical practitioners. Feedback was incorporated into the final version of the guideline., Practice Guideline: These recommendations apply to patients with liver metastases from crc who have had or will have a complete (R0) resection of the primary cancer and who are being considered for resection of the liver, or liver plus specific and limited ehms, with curative intent. 1(a). Patients with liver and lung metastases should be seen in consultation with a thoracic surgeon. Combined or staged metastasectomy is recommended when, taking into account anatomic and physiologic considerations, the assessment is that all pulmonary metastases can also be completely removed. Furthermore, liver resection may be indicated in patients who have had a prior lung resection, and vice versa.1(b). Routine liver resection is not recommended in patients with portal nodal disease. This group includes patients with radiologically suspicious portal nodes or malignant portal nodes found preoperatively or intraoperatively. Liver plus nodal resection, together with perioperative systemic therapy, may be an option-after a full discussion with the patient-in cases with limited nodal involvement and with metastases that can be completely resected.1(c). Routine liver resection is not recommended in patients with nonpulmonary ehms. Liver plus extrahepatic resection, together with perioperative systemic therapy, may be an option-after a full discussion with the patient-for metastases that can be completely resected.2(a). Perioperative chemotherapy, either before and after resection, or after resection, is recommended in patients with resectable liver metastatic disease. This recommendation extends to patients with ehms that can be completely resected (R0). Risks and potential benefits of perioperative chemotherapy should be discussed for patients with resectable liver metastases. The data on whether patients with previous oxaliplatin-based chemotherapy or a short interval from completion of adjuvant therapy for primary crc might benefit from perioperative chemotherapy are limited.2(b). Liver resection is recommended in patients with initially unresectable metastatic liver disease who have a sufficient downstaging response to conversion chemotherapy. If complete resection has been achieved, postoperative chemotherapy should be considered.3. Surgical resection of all lesions, including lesions with rcr, is recommended when technically feasible and when adequate functional liver can be left as a remnant. When a lesion with rcr is present in a portion of the liver that cannot be resected, surgery may still be a reasonable therapeutic strategy if all other visible disease can be resected. Postoperative chemotherapy might be considered in those patients. Close follow-up of the lesion with rcr is warranted to allow localized treatment or further resection for an in situ recurrence.

Objective: To determine whether patients with vitamin D deficiency (VDD) are at increased risk for hypocalcemia following total thyroidectomy., Methods: A retrospective study of 246 consecutive patients undergoing thyroidectomy at a McGill University teaching hospital was conducted. Patients who had subtotal thyroidectomy or concomitant parathyroidectomy or whose laboratory tests were incomplete for analysis were excluded, as were pediatric patients. The remaining 139 patients had preoperative 25-hydroxyvitamin D [25(OH)D], corrected calcium, and parathyroid hormone (PTH) measured. Postoperatively, PTH and serum calcium were measured to assess for hypocalcemia. Low vitamin D (LVD) was defined as 25(OH)D ≤ 70 nmol/L (≤ 28 ng/mL), which includes vitamin D insufficiency, 25(OH)D > 35 nmol/L (> 14 ng/mL) but ≤ 70 nmol/L (≤ 28 ng/mL), and VDD, 25(OH)D ≤ 35 nmol/L (≤ 14 ng/mL). Adequate vitamin D (AVD) corresponded to levels > 35 nmol/L (> 14 ng/mL), whereas optimal vitamin D (OVD) levels corresponded to levels > 70 nmol/L (> 28 ng/mL)., Results: The rate of postthyroidectomy hypocalcemia in OVD patients was 10.4% (8 of 77) compared to 3.2% (2 of 62) in LVD patients (odds ratio  =  0.29, p  =  .10). There was no hypocalcemia in the 9 VDD patients, meaning that all hypocalcemic episodes occurred in patients with AVD (7.7%; 10 of 130). The mean preoperative PTH levels for LVD patients was 4.65 pmol/L (43 ng/L) compared to 4.18 pmol/L (38.9 ng/L) for OVD patients (p  =  .073)., Conclusions: In this series, preoperative LVD did not predict early postthyroidectomy hypocalcemia. On the contrary, it showed a trend toward protective effect. Adaptive changes in the parathyroid glands, such as hypertrophy, hyperplasia, or the ability to secrete more hormone secondary to prolonged VDD, may contribute to this phenomenon. A large prospective study is needed to better understand the relationship between preoperative vitamin D levels and postoperative hypocalcemia.

Background: To determine the role of liver resection in patients with liver and extrahepatic colorectal cancer metastases and the role of chemotherapy in patients in conjunction with liver resection., Methods: MEDLINE and EMBASE databases were searched for articles published between 1995 and 2010, along with hand searching., Results: A total of 4875 articles were identified, and 83 were retained for inclusion. Meta-analysis was not performed because of heterogeneity and poor quality of the evidence. Outcomes in patients who had liver and lung metastases, liver and portal node metastases, and liver and other extrahepatic disease were reported in 14, 10, and 14 studies, respectively. The role of perioperative chemotherapy was assessed in 30 studies, including 1 randomized controlled trial and 1 pooled analysis. Ten studies assessed the role of chemotherapy in patients with initially unresectable disease, and 5 studies assessed the need for operation after a radiologic complete response., Conclusion: The review suggests that: (1) select patients with pulmonary and hepatic CRC metastases may benefit from resection; (2) perioperative chemotherapy may improve outcome in patients undergoing a liver resection; (3) patients whose CRC liver metastases are initially unresectable may benefit from chemotherapy to identify a subgroup who may benefit later from resection; (4) after radiographic complete response (RCR), lesions should be resected if possible., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Objectives: Advances in surgical techniques and chemotherapeutic options have expanded indications for surgery in patients with metastatic colorectal cancer. This study aimed to examine how hepatopancreatobiliary (HPB) surgeons approach the management of patients with hepatic colorectal cancer metastases (HCCM)., Methods: A web-based survey utilizing 10 clinical scenarios was distributed by e-mail to 37 HPB surgeons in Ontario, Canada. The study region has a population of approximately 13 million people and a universal, single-payer health care system. Descriptive analyses were used to tabulate results., Results: Twenty-two (59%) surgeons responded to the survey. The majority (19/22, 86%) of respondents favoured neoadjuvant chemotherapy for patients with multiple synchronous and unilobar metastases; only nine of 22 (41%) respondents favoured neoadjuvant chemotherapy for patients with a single synchronous metastasis. In the setting of residual resectable disease following downstaging chemotherapy, 77% (17/22) of surgeons advocated hepatic resection with either radiofrequency ablation (RFA) or wedge resection of the 'ghost' lesions. Over 80% of surgeons would perform a liver and pulmonary resection in a patient with hepatic and multiple unilobar lung metastases. None would offer liver resection to patients with multiple retroperitoneal node involvement, although 55% (12/22) would do so if a single retroperitoneal node was involved. Preoperative portal vein embolization was favoured over RFA in patients with a small metastasis and inadequate functional hepatic volume., Conclusions: Notable heterogeneity was observed among Ontario's HPB surgeons in approaches to HCCM., (© 2012 International Hepato-Pancreato-Biliary Association.)

Background: In Quebec, the influenza A (H1N1) pandemic was managed using a top-down style that left many involved players with critical views and frustrations. We aimed to describe physicians' perceptions--infectious diseases specialists/medical microbiologists (IDMM) and public health/preventive medicine specialists (PHPMS)--in regards to issues encountered with the pandemics management at the physician level and highlight suggested improvements for future healthcare emergencies., Methods: In April 2010, Quebec IDMM and PHPMS physicians were invited to anonymously complete a web-based learning needs assessment. The survey included both open-ended and multiple-choice questions. Descriptive statistics were used to report on the frequency distribution of multiple choice responses whereas thematic content analysis was used to analyse qualitative data generated from the survey and help understand respondents' experience and perceptions with the pandemics., Results: Of the 102 respondents, 85.3% reported difficulties or frustrations in their practice during the pandemic. The thematic analysis revealed two core themes describing the problems experienced in the pandemic management: coordination and resource-related difficulties. Coordination issues included communication, clinical practice guidelines, decision-making, roles and responsibilities, epidemiological investigation, and public health expert advisory committees. Resources issues included laboratory resources, patient management, and vaccination process., Conclusion: Together, the quantitative and qualitative data suggest a need for improved coordination, a better definition of roles and responsibilities, increased use of information technologies, merged communications, and transparency in the decisional process. Increased flexibility and less contradiction in clinical practice guidelines from different sources and increased laboratory/clinical capacity were felt critical to the proper management of infectious disease emergencies.

Using hole-burning spectroscopy, we show that excitation energy transfer (EET) time in ethynyl-linked chlorophyll trefoil (ChlT1) monomer is very fast (∼2.5 ps) at liquid helium temperature. This is consistent with data obtained by femtosecond transient spectroscopy experiments performed at room temperature, in which an EET time of 1.8 ps was observed (Kelley, R. F. et al. Angew. Chem. Int. Ed. 2006, 45, 7979). This finding further supports the importance of through-bond electronic coupling at low temperature. In addition, we show that ChlT1 (even at very low concentrations) in methyl tetrahydrofuran-ethanol glass (1:200 v/v; T ∼ 5 K) forms different types of aggregates. It is demonstrated that the relative distribution of various types of aggregates (whose possible structures are briefly discussed) depends on the cooling rate and matrix composition. For example, the EET time in two types of ChlT1-based aggregates is slower by a factor of ∼5-7 with respect to that observed for ChlT1 monomer. This indicates that ChlT1 aggregates can retain ultrafast energy transfer properties similar to those observed in natural photosynthetic antennas. It is anticipated that such building blocks could be utilized in future photovoltaic devices.

Plate impact experiments on the (210), (100), and (111) planes were performed to examine the role of crystalline anisotropy on the shock-induced decomposition of cyclotrimethylenetrinitramine (RDX) crystals. Time-resolved emission spectroscopy was used to probe the decomposition of single crystals shocked to peak stresses ranging between 7 and 20 GPa. Emission produced by decomposition intermediates was analyzed in terms of induction time to emission, emission intensity, and the emission spectra shapes as a function of stress and time. Utilizing these features, we found that the shock-induced decomposition of RDX crystals exhibits considerable anisotropy. Crystals shocked on the (210) and (100) planes were more sensitive to decomposition than crystals shocked on the (111) plane. The possible sources of the observed anisotropy are discussed with regard to the inelastic deformation mechanisms of shocked RDX. Our results suggest that, despite the anisotropy observed for shock initiation, decomposition pathways for all three orientations are similar.

We report low temperature (T) optical spectra of the isolated CP47 antenna complex from Photosystem II (PSII) with a low-T fluorescence emission maximum near 695 nm and not, as previously reported, at 690-693 nm. The latter emission is suggested to result from three distinct bands: a lowest-state emission band near 695 nm (labeled F1) originating from the lowest-energy excitonic state A1 of intact complexes (located near 693 nm and characterized by very weak oscillator strength) as well as emission peaks near 691 nm (FT1) and 685 nm (FT2) originating from subpopulations of partly destabilized complexes. The observation of the F1 emission is in excellent agreement with the 695 nm emission observed in intact PSII cores and thylakoid membranes. We argue that the band near 684 nm previously observed in singlet-minus-triplet spectra originates from a subpopulation of partially destabilized complexes with lowest-energy traps located near 684 nm in absorption (referred to as AT2) giving rise to FT2 emission. It is demonstrated that varying contributions from the F1, FT1, and FT2 emission bands led to different maxima of fluorescence spectra reported in the literature. The fluorescence spectra are consistent with the zero-phonon hole action spectra obtained in absorption mode, the profiles of the nonresonantly burned holes as a function of fluence, as well as the fluorescence line-narrowed spectra obtained for the Q(y) band. The lowest Q(y) state in absorption band (A1) is characterized by an electron-phonon coupling with the Huang-Rhys factor S of approximately 1 and an inhomogeneous width of approximately 180 cm(-1). The mean phonon frequency of the A1 band is 20 cm(-1). In contrast to previous observations, intact isolated CP47 reveals negligible contribution from the triplet-bottleneck hole, i.e., the AT2 trap. It has been shown that Chls in intact CP47 are connected via efficient excitation energy transfer to the A1 trap near 693 nm and that the position of the fluorescence maximum depends on the burn fluence. That is, the 695 nm fluorescence maximum shifts blue with increasing fluence, in agreement with nonresonant hole burned spectra. The above findings provide important constraints and parameters for future excitonic calculations, which in turn should offer new insight into the excitonic structure and composition of low-energy absorption traps.

Objective: The objective of the current study was to describe the burden of back-over collisions within the context of other child pedestrian collisions as identified through a pediatric emergency room injury surveillance database., Methods: Injury data for child pedestrian motor vehicle collisions from 1994 to 2003 were obtained from the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP). Back-over collisions involving children under the age of 14 were identified and classified by written narratives. Characteristics of children involved in back-over collisions were described, and for those admitted to hospital, the nature of injury was compared with other types of child pedestrian collisions., Results: There were 4295 child pedestrian motor vehicle collisions reported to CHIRPP during the study time period. Of the 4295 children, 148 (3.4%) were injured in a back-over collision, with 49 (33.1%) of these collisions involving a vehicle backing out of a driveway. Children involved in back-over collisions were significantly younger than those in forward-moving/other collisions; however, almost 50 percent of back-over collisions involved children older than age 4. Children involved in back-over collisions on driveways were significantly younger than those involved in collisions occurring at other locations. Of those admitted to hospital, children in back-over collisions were more likely to sustain injuries to internal organs. Children in back-over collisions were less likely to sustain severe/mild head injuries and hip/leg fractures., Conclusions: Although back-over collisions represent a small proportion of pedestrian motor vehicle collisions, they tend to involve more severe injuries, as indicated by their admission to hospital. It was found that older children are also at risk of back-over collisions and back-over collisions occur in areas other than driveways. In order to lessen the burden of back-over collisions, interventions must address children of different ages and a variety of locations.

It is still unclear whether hyperquenched water (i.e., amorphous glassy water) heated to about 140-150 K remains glassy until it crystallizes near 154 K or whether instead it turns into a supercooled and very viscous liquid. It has been proposed that the glass transition temperature (T(g)) for water is 165 K and not, as previously thought, 136 K [V. Velikov et al., Science, 294, 2335 (2001)]. Support for both interpretations exists in the literature, since the T(g) of water is difficult to measure due to the formation of metastable cubic ice (I(c)) near 154 K. To address the nature of water in the 110-160 K temperature range, a confocal microscopy approach is used to study whether single-probe molecules (i.e., Rhodamine 700, Rh-700) embedded in hyperquenched glassy water (HGW) rotate in the temperature range of 110-160 K. If T(g) is 136 K and the liquid above this temperature is fragile (or strong with the fragility index m > 7), then rotation of the Rh-700 molecules should be observed several degrees above T(g). It is shown that no anticorrelated fluorescence intensity changes of single molecules in HGW (when excited at orthogonal polarizations) were observed up to temperatures of 160 K, although such changes were detected in control experiments performed for hyperquenched glassy ethanol (fragile liquid) at 99 K, that is, at T(g) + 2 K. The viscosity at which single Rh-700 molecules rotate in ethanol at 99 K is estimated to be about 10(12) poise. Since single-molecule spectroscopy did not reveal any rotation of probe molecules in HGW above 136 K, we conclude that water above 136 K is most likely a solid (i.e., glass), supporting the assignment that water remains glassy until it crystallizes near T = 154 K. It cannot be excluded, of course, that the value of m for water is smaller than 7 (i.e., water above 136 K could be an extremely strong liquid), but this possibility is considered unlikely as this would make water the strongest liquid ever known.

The CP43 core antenna complex of photosystem II is known to possess two quasi-degenerate "red"-trap states (Jankowiak, R. et al. J. Phys. Chem. B 2000, 104, 11805). It has been suggested recently (Zazubovich, V.; Jankowiak, R. J. Lumin. 2007, 127, 245) that the site distribution functions of the red states (A and B) are uncorrelated and that narrow holes are burned in the subpopulations of chlorophylls (Chls) from states A and B that are the lowest-energy Chl in their complex and previously thought not to transfer energy. This model of uncorrelated excitation energy transfer (EET) between the quasidegenerate bands is expanded by taking into account both electron-phonon and vibrational coupling. The model is applied to fit simultaneously absorption, emission, zero-phonon action, and transient hole burned (HB) spectra obtained for the CP43 complex with minimized contribution from aggregation. It is demonstrated that the above listed spectra can be well-fitted using the uncorrelated EET model, providing strong evidence for the existence of efficient energy transfer between the two lowest energy states, A and B (either from A to B or from B to A), in CP43. Possible candidate Chls for the low-energy A and B states are discussed, providing a link between CP43 structure and spectroscopy. Finally, we propose that persistent holes originate from regular NPHB accompanied by the redistribution of oscillator strength due to excitonic interactions, rather than photoconversion involving Chl-protein hydrogen bonding, as suggested before ( Hughes J. L. et al. Biochemistry 2006, 45, 12345 ). In the accompanying paper (Reppert, M.; Zazubovich, V.; Dang, N. C.; Seibert, M.; Jankowiak, R. J. Phys. Chem. B 2008, 9934), it is demonstrated that the model discussed in this manuscript is consistent with excitonic calculations, which also provide very good fits to both transient and persistent HB spectra obtained under non-line-narrowing conditions.

The CP43 protein complex of the core antenna of higher plant photosystem II (PSII) has two quasidegenerate "red" absorption states. It has been shown in the accompanying paper I (Dang, N. C., et al. J. Phys. Chem. B 2008, 112, 9921.) that the site distribution functions (SDFs) of red-states A and B are uncorrelated and the narrow holes are burned in subpopulations of chlorophylls (Chls) from states A and B that are the lowest-energy pigments in their particular CP43 complexes and cannot further transfer energy downhill. In this work, we present the results of a series of Monte Carlo simulations using the 3.0-A structure of the PSII core complex from cyanobacteria (Loll, B., et al. Nature 2005, 303, 1040.) to model absorption, emission, persistent, and transient hole burned (HB) spectra. At the current structural resolution, we found calculated site energies (obtained from INDO/S calculations) to be only suggestive because their values are different for the two monomers of CP43 in the PS II dimer. As a result, to probe the excitonic structure, a simple fitting procedure was employed to optimize Chl site energies from various starting values corresponding to different A/B pigment combinations to provide simultaneously good fits to several types of optical spectra. It is demonstrated that the shape of the calculated absorption, emission, and transient/persistent hole-burned spectra is consistent with experimental data and our model for excitation energy transfer between two quasi-degenerate lowest-E states (A and B) with uncorrelated SDFs discussed in paper I. Calculations revealed that absorption changes observed near 670 nm in the non-line-narrowed persistent HB spectra (assigned to photoconversion involving Chl-protein hydrogen-bonding by Hughes (Biochemistry 2006, 45, 12345.) are most likely the result of nonphotochemical hole-burning (NPHB) accompanied by the redistribution of oscillator strength due to modified excitonic interactions. We argue that a unique redistribution of oscillator strength during the NPHB process helps to assign Chls contributing to the low-energy states. It is demonstrated that the 4.2 K asymmetric triplet-bottleneck (transient) hole is mostly contributed to by both A and B states, with the hole profile described by a subensemble of pigments, which are the lowest-energy pigments (B s- and A s-type) in their complexes. The same lowest-energy Chls contribute to the observed fluorescence spectra. On the basis of our excitonic calculations, the best Chl candidates that contribute to the low-energy A and B states are Chl 44 and Chl 37, respectively.

Antibody cross-reactivity makes separation and differentiation of enantiomeric analytes one of the most challenging problems in immunoanalytical research, particularly for the analysis of structurally related biological molecules [such as benzo( a)pyrene (BP) metabolites and BP-derived DNA adducts]. It has recently been shown that the interaction of enantiomers of BP tetrols (BPT) with a promiscuous anti-polycyclic aromatic hydrocarbon ( anti-PAH) monoclonal antibody (mAb) allowed for separation of all four enantiomeric isomers using immunoaffinity capillary electrophoresis [ Grubor, N. M. , Armstrong, D. W. , and Jankowiak, R. ( 2006) Electrophoresis 27, 1078 ] and unambiguous spectral resolution using fluorescence line narrowing spectroscopy (FLNS) [ Grubor, N. M. , Liu, Y. , Han, X. , Armstrong, D.W. , and Jankowiak, R. ( 2006) J. Am.Chem. Soc. 128, 6409 ]. Here, we expand the use of the above two methodologies to the group of biologically important molecules that are products of BP diol epoxide (BPDE)-induced DNA damage. Four diastereomeric anti-BPDE-derived deoxyguanosine (dG) adducts, that is, (+)- and (-)- anti-trans-BPDE- N (2)-dG and (+)- and (-)- anti-cis-BPDE- N (2)-dG, were electrophoretically separated and spectroscopically differentiated using 8E11 mAb raised against BP-DNA conjugates. In fluorescence line narrowing spectroscopy (FLNS) experiments, complexes of BPDE-dG adducts with mAb revealed differences in fluorescence origin band positions, bandwidths, and vibrational patterns for all four BPDE- N (2)-dG adducts. Narrow fluorescence origin bands observed for (-)- trans-BPDE-dG (70 cm (-1)) and (+)- trans-BPDE- N (2)-dG (80 cm (-1)) suggest spatial constraint within the mAb binding pocket. Broader origin bands observed for cis type adducts ( approximately 120 cm (-1)) in 8E11 mAb suggest different binding geometries and/or conformational changes, as also indicated by changes in vibrational frequencies observed for the (+)- anti-cis and (-)- anti-cis adducts complexed with mAb. FLNS revealed that binding conformations and interactions within the mAb binding pocket are different for each adduct, enabling unambiguous positive identification. The methodologies described in this manuscript could also be used for analysis of DNA adducts following enzymatic hydrolysis of BPDE-adducted DNA to free nucleosides.

Recently, we have identified proinsulin (P-Ins)(73-90) as an immunodominant T cell epitope of HLA-DRB1*0401 (DR4) subjects with beta-islet cell autoimmunity and of HLA-DR4/CD4 double-transgenic mice immunized with human P-Ins. We have compared the fine specificities of one human CD4 T cell clone and two mouse T cell hybridoma clones recognizing this epitope, and, although these three clones all recognized the same core region (LALEGSLQK), there were major differences in how they interacted with the peptide (p)/HLA complex, reflecting the fact that human P-Ins is a foreign antigen in the mouse and an autoantigen in the type 1 diabetes patient. The human T cell clone was forkhead transcription factor 3 (Foxp3)-positive, a marker for regulatory T cell lineages, and secreted predominantly IL-5, IL-10, and low levels of IFNgamma in response to P-Ins(73-90). This finding is compatible with the previously detected regulatory cytokine pattern in subjects with beta-cell autoimmunity. However, added N- or C-terminal amino acids drastically changed HLA and tetramer binding capacity as well as T cell reactivity and the cytokine phenotype of the P-Ins(73-90)-specific human CD4 T cell clone, suggesting a potential for this P-Ins epitope as a target for therapeutic intervention in HLA-DR4-positive humans with beta-islet cell autoimmunity or recent-onset type 1 diabetes.