Metabolic basis to Sherpa altitude adaptation.

The Himalayan Sherpas, a human population of Tibetan descent, are highly adapted to life in the hypobaric hypoxia of high altitude. Mechanisms involving enhanced tissue oxygen delivery in comparison to Lowlander populations have been postulated to play a role in such adaptation. Whether differences in tissue oxygen utilization (i.e., metabolic adaptation) underpin this adaptation is not known, however. We sought to address this issue, applying parallel molecular, biochemical, physiological, and genetic approaches to the study of Sherpas and native Lowlanders, studied before and during exposure to hypobaric hypoxia on a gradual ascent to Mount Everest Base Camp (5,300 m). Compared with Lowlanders, Sherpas demonstrated a lower capacity for fatty acid oxidation in skeletal muscle biopsies, along with enhanced efficiency of oxygen utilization, improved muscle energetics, and protection against oxidative stress. This adaptation appeared to be related, in part, to a putatively advantageous allele for the peroxisome proliferator-activated receptor A (PPARA) gene, which was enriched in the Sherpas compared with the Lowlanders. Our findings suggest that metabolic adaptations underpin human evolution to life at high altitude, and could have an impact upon our understanding of human diseases in which hypoxia is a feature.

Tablet Computing in Clinical Training of Pediatric Residents.

BACKGROUND: Medical residents receive both medical education and clinical skills training. New technologies and pedagogies are being developed to address each of these phases. Our research focuses on the efficacy of an iPad(®) (Apple, Cupertino, CA) for clinical skills training. MATERIALS AND METHODS: For a period of 3 years, the University of South Florida provided incoming pediatric residents (n=94) with an iPad. At the end of the 3-year program, we surveyed the residents, measuring perceptions and satisfaction of iPad use in clinical training. RESULTS: Sixty percent of the residents responded to the survey. Ninety-three percent reported at least some iPad usage per day on clinical activities. We classified 13 facets of clinical training into three conceptual areas and provided figures detailing iPad use for each facet relative to other facets in the same cluster. The obtaining, management, and display of information are primary uses of iPad applications in clinical training. Finally, we provide information relative to perceived obstacles in clinical training, with weight of the device being the most frequently cited. CONCLUSIONS: The role of graduate medical education is changing with the introduction of new technologies. These technologies can differentially impact the various aspects of residency education and training. Residents reported using an iPad extensively in their clinical training. We argue that in addition to impacting traditional educational strategies, iPads can successfully facilitate aspects of clinical training in medical education.

Starting fresh: a mixed method study of follower job satisfaction, trust, and views of their leader's behavior.

Introduction: The leadership literature has been dominated by the study of broad styles rather than the identification of specific key behaviors. To address this deficiency, a mixed method approach was utilized to explore how follower behavioral descriptions of their leaders would relate to potential outcomes of trust in that leader and job satisfaction. Methods: Data were collected from 273 hospital direct reports of 44 managers. They were asked to first describe the leadership approach of their managers in their own words, and then complete quantitative measures of the two potential outcomes. Results: The qualitative responses were coded into nine leadership behavior themes listed here in order from most to least often mentioned: Kindness, Supportive, Open to Input, Allow Autonomy, Engage with Team, Transparency, Fairness, Professionalism, Hold Accountable. All behavior themes related significantly to trust of the leader, with three themes relating significantly to job satisfaction (Transparency, Fairness, and Professionalism). Discussion: These results provide a more specific view of leader behavior than does the typical style approach.

Organizational science and cybersecurity: abundant opportunities for research at the interface.

Cybersecurity is an ever-present problem for organizations, but organizational science has barely begun to enter the arena of cybersecurity research. As a result, the "human factor" in cybersecurity research is much less studied than its technological counterpart. The current manuscript serves as an introduction and invitation to cybersecurity research by organizational scientists. We define cybersecurity, provide definitions of key cybersecurity constructs relevant to employee behavior, illuminate the unique opportunities available to organizational scientists in the cybersecurity arena (e.g., publication venues that reach new audiences, novel sources of external funding), and provide overall conceptual frameworks of the antecedents of employees' cybersecurity behavior. In so doing, we emphasize both end-users of cybersecurity in organizations and employees focused specifically on cybersecurity work. We provide an expansive agenda for future organizational science research on cybersecurity-and we describe the benefits such research can provide not only to cybersecurity but also to basic research in organizational science itself. We end by providing a list of potential objections to the proposed research along with our responses to these objections. It is our hope that the current manuscript will catalyze research at the interface of organizational science and cybersecurity.

Outcome of endoscopic treatment of adult postintubation tracheal stenosis.

OBJECTIVES/HYPOTHESIS: To assess the results of primary endoscopic treatment of adult postintubation tracheal stenosis, to identify predictors of a successful outcome, and better define the scope and limitations of minimally-invasive surgery for this condition. METHODS: Sixty-two consecutive patients treated between April 2003 and 2006 with initial endoscopic surgery were prospectively studied. Patient and lesion characteristics, treatment details, complications, decannulation, and open surgery rates were recorded. Actuarial analysis and Cox regression were used to identify predictors of decannulation and freedom from external surgery. RESULTS: There were 34 male patients and the average age was 45 +/- 16 years. The average stenosis height was 18 mm (range: 5-55 mm), and 82% of lesions were Myer-Cotton grades III or IV. Lesion height and intubation-to-treatment latency independently predicted success of endoscopic surgery. Ninety-six percent of patients with lesions <30 mm in height were treated endoscopically, but the success rate fell to 20% for lesions longer than 30 mm. Patients with recalcitrant lesions underwent airway augmentation (n = 11) or resection (n = 3), with a 79% success rate. All patients were decannulated, but some, predominantly morbidly obese patients, required long-term stents for dynamic airway compromise. Ninety-eight percent of re-interventions occurred within 6 months. CONCLUSIONS: Minimally invasive treatment is effective in postintubation airway stenosis and obviates the need for open cervicomediastinal surgery in most patients. Patients with old and long lesions are less likely to be cured endoscopically. For most patients in this subgroup, endoscopic surgery makes airway augmentation a viable, less invasive alternative to resection. Patients were unlikely to require further therapy after 6 months of symptom-free follow-up.

Quantifying the physiology of laryngotracheal stenosis: changes in pulmonary dynamics in response to graded extrathoracic resistive loading.

OBJECTIVES/HYPOTHESIS: A model of airway obstruction was developed to study the impact of changes in airway resistance on ventilatory mechanics. This was used to derive quantitative indices of airway obstruction to aid in the objective diagnosis and physiological monitoring of adult patients with laryngotracheal stenosis (LTS). METHODS: Six airway resistors, the characteristics of which mirrored the selective impediment to inspiratory airflow that occurs in patients with LTS, were created and calibrated. Maximum-effort flow-volume loops were obtained from 15 volunteers with resistors placed in series with the spirometer. Diagnostic and monitoring performances of various flow-volume indices were assessed with receiver-operating characteristics (ROC) and analysis of variance (ANOVA), respectively. Promising indices were further evaluated in patients with LTS. RESULTS: Experimentally, the ratio of expiratory and inspiratory flows at midvital capacity (MEF50/MIF50) and peak expiratory to inspiratory flow ratio (PEF/PIF) had diagnostic sensitivities of 87% and 89%, respectively. The best index, both experimentally and clinically, was the ratio of area under the expiratory and inspiratory curves (ratio of integrals), with experimental and clinical sensitivities of 97% and 100%, respectively. A clinical specificity of 95%, and area under the curve of 0.965 were achieved for this index. Both PEF/PIF and the ratio of integrals could identify step changes in airway resistance greater than 10 cmH2O . sec . L (P < .05; ANOVA). CONCLUSIONS: Flow-volume testing is simple and noninvasive and can be used to quantify the diagnosis and physiological monitoring of patients with LTS. The ratio of areas under the expiratory and inspiratory curves appears to be the optimal index for this purpose.

Early endoscopic treatment of acute inflammatory airway lesions improves the outcome of postintubation airway stenosis.

OBJECTIVES/HYPOTHESIS: The objective of this study was to compare the results of treating acute postintubation stenotic airway lesions with the results of treating mature lesions and to assess whether early intervention improves the outcome. METHODS: Patients without previous surgery, treated for postintubation airway stenosis, were reviewed. Those with airway lesions presenting within weeks of intubation (n = 11) were treated with intralesional steroids, laser reduction, and balloon dilatation. Patients with mature airway lesions (n = 20) were initially treated with laser, balloon dilatation, and topical mitomycin C. Preoperative patient and lesion characteristics, details of the treatment, and intervention-free intervals were recorded. Data were compared with unpaired Student t test or chi test as appropriate, and intervention-free intervals were compared with log-rank statistics. Cox regression was used to identify independent predictors of intervention-free interval. RESULTS: There were 18 males and 13 females. The average age at presentation was 47 +/- 2.7 years. The two groups were statistically comparable for demographic and lesion characteristics. Patients treated for acute injury required significantly fewer interventions (P < .03), the majority being treated with a single treatment. They had a significantly longer intervention-free interval (P < .02; log-rank analysis) and did not require external laryngotracheal reconstruction (P < .001) compared with patients treated for mature fibrotic scars leading to airway stenosis. CONCLUSIONS: Early treatment of acute fibroinflammatory airway lesions has the potential to favorably modify the natural history of postintubation tracheal injury, raising the tantalizing possibility of an early cure. These findings have significant implications for early identification, referral, and treatment of postintubation tracheal stenosis and need to be confirmed with further studies.

Bacterial colonization of airway stents: a promoter of granulation tissue formation following laryngotracheal reconstruction.

OBJECTIVE: To investigate whether airway granulation, a common occurrence during laryngotracheal reconstructive surgery and a common cause of delays in definitive treatment and treatment failure, is associated with a microbial etiology. DESIGN: Prospective case-control study. SETTING: Tertiary referral airway reconstruction unit. PATIENTS: Patients who had an airway stent as part of their treatment for laryngotracheal stenosis. INTERVENTIONS: All airway stents were sent for microbiological analysis. Information about patient demographics, lesion characteristics, and presence of airway granulation tissue at different times during treatment were obtained and correlated against the microbiological findings from airway stents. MAIN OUTCOME MEASURES: A chi2 test was used to correlate airway colonization with specific pathogens and occurrence of airway granulation. Logistic regression analysis was used to identify independent microbiological predictors of airway granulation. RESULTS: Thirty-one airway stents were removed from 26 patients. The mean (SD) age at presentation was 42 (18) years, and postintubation tracheal stenosis was the most common etiology. There were highly significant associations between stent colonization with Staphylococcus aureus and Pseudomonas aeruginosa and the occurrence of airway granulation (P<.02), and these microorganisms were independently associated with the risk of developing airway granulation. Furthermore, S aureus was associated with persistence of airway granulation on average 4 months following removal of the stent. CONCLUSIONS: Airway granulation seems to be associated not with polymicrobial airway colonization but with infection with specific pathogenic microorganisms. All patients undergoing laryngotracheoplasty should receive antibiotic prophylaxis to cover these microorganisms, and the development and use of antibiotic-impregnated airway stents should be explored.

Database for the collection and analysis of clinical data and images of neoplasms of the sinonasal tract.

The Neoplasms of the Sinonasal Tract software package (NSNT v 1.0) implements a complete visual database for patients with sinonasal neoplasia, facilitating standardization of data and statistical analysis. The software, which is compatible with the Macintosh and Windows platforms, provides multiuser application with a dedicated server (on Windows NT or 2000 or Macintosh OS 9 or X and a network of clients) together with web access, if required. The system hardware consists of an Apple Power Macintosh G4500 MHz computer with PCI bus, 256 Mb of RAM plus 60 Gb hard disk, or any IBM-compatible computer with a Pentium 2 processor. Image acquisition may be performed with different frame-grabber cards for analog or digital video input of different standards (PAL, SECAM, or NTSC) and levels of quality (VHS, S-VHS, Betacam, Mini DV, DV). The visual database is based on 4th Dimension by 4D Inc, and video compression is made in real-time MPEG format. Six sections have been developed: demographics, symptoms, extent of disease, radiology, treatment, and follow-up. Acquisition of data includes computed tomography and magnetic resonance imaging, histology, and endoscopy images, allowing sequential comparison. Statistical analysis integral to the program provides Kaplan-Meier survival curves. The development of a dedicated, user-friendly database for sinonasal neoplasia facilitates a multicenter network and has obvious clinical and research benefits.

Evaluation of ricinine, a ricin biomarker, from a non-lethal castor bean ingestion.

A case is presented of the attempted suicide of a 58-year-old man using castor beans. The patient came to the emergency room complaining of nausea, vomiting and diarrhea for nine hours following the ingestion of six castor beans. Urine samples were taken throughout the hospital stay and submitted to the Centers for Disease Control and Prevention for analysis of ricinine, a castor bean component. The samples were found to be positive for ricinine, with a maximum concentration of 674 µg/g-creatinine excreted approximately 23 h post-exposure. Subsequent samples demonstrated lower ricinine concentrations, with the final sample taken at 62 h post-exposure at a concentration of 135 µg/g-creatinine of ricinine. The estimated urinary excretion half-life was approximately 15 h and the recovery of ricinine in the urine over the three days was estimated to be less than 10%. The patient fully recovered with supportive care and was discharged from the hospital six days after admission.

Fenofibrate administration does not affect muscle triglyceride concentration or insulin sensitivity in humans.

Animal data suggest that males, in particular, rely on peroxisome proliferator activated receptor-α activity to maintain normal muscle triglyceride metabolism. We sought to examine whether this was also true in men vs women and its relationship to insulin sensitivity (Si). Normolipidemic obese men (n = 9) and women (n = 9) underwent an assessment of Si (intravenous glucose tolerance test) and intramuscular triglyceride (IMTG) metabolism (gas chromatography/mass spectrometry and gas chromatography-combustion isotope ratio mass spectrometry from plasma and muscle biopsies taken after infusion of [U-(13)C]palmitate) before and after 12 weeks of fenofibrate treatment. Women were more insulin sensitive (Si: 5.2 ± 0.7 vs 2.4 ± 0.4 ×10(-4)/ µU/mL, W vs M, P < .01) at baseline despite similar IMTG concentration (41.9 ± 15.5 vs 30.8 ± 5.1 µg/mg dry weight, W vs M, P = .43) and IMTG fractional synthesis rate (FSR) (0.27%/h ± 0.07%/h vs 0.35%/h ± 0.06%/h, W vs M, P = .41) as men. Fenofibrate enhanced FSR in men (0.35 ± 0.06 to 0.54 ± 0.06, P = .05), with no such change seen in women (0.27 ± 0.07 to 0.32 ± 0.13, P = .73) and no change in IMTG concentration in either group (23.0 ± 3.9 in M, P = .26 vs baseline; 36.3 ± 12.0 in W, P = .79 vs baseline). Insulin sensitivity was unaffected by fenofibrate (P ≥ .68). Lower percentage saturation of IMTG in women vs men before (29.1% ± 2.3% vs 35.2% ± 1.7%, P = .06) and after (27.3% ± 2.8% vs 35.1% ± 1.9%, P = .04) fenofibrate most closely related to their greater Si (R(2) = 0.34, P = .10) and was largely unchanged by the drug. Peroxisome proliferator activated receptor-α agonist therapy had little effect on IMTG metabolism in men or women. Intramuscular triglyceride saturation, rather than IMTG concentration or FSR, most closely (but not significantly) related to Si and was unchanged by fenofibrate administration.

Occult squamous cell carcinoma of the uvula detected by F-18 FDG PET/CT in a case of carcinoma of unknown primary in the head and neck.

Incidence of unknown primary head/neck tumors with metastatic cervical lymphadenopathy at time of diagnosis is approximately 2% to 9%. Detecting site of original disease is challenging. We present a 75-year-old woman with bulky unilateral level 2 and 3 lymphadenopathy. Clinical examination and computed tomography (CT) did not reveal detectable abnormalities except neck-node metastases; biopsy indicated metastatic squamous cell carcinoma (SCC). F-18 FDG PET/CT imaging was performed to detect the primary tumor site, which revealed a small metabolically-avid lesion in uvula, biopsy demonstrated SCC, the origin of metastatic disease. F-18 FDG PET/CT imaging of unknown primary head/neck tumors can have positive impact in identifying small occult primary tumor foci.

Should we treat lung metastases from adenoid cystic carcinoma of the head and neck in asymptomatic patients?

Adenoid cystic carcinoma is a rare malignant tumor that is well known for its deceptively encouraging 5-year survival rate and its dismal survival rate at longer intervals. Controversy exists as to the benefit of regularly following asymptomatic patients to look for distant metastases because even if one is found, the options for further management are limited. When a metastasis is limited to the lung in an asymptomatic patient with no locoregional recurrence, metastasectomy might provide some long-term benefit, although we cannot know for certain. We encountered such a case, and we opted for surgical resection rather than a conservative approach. There is a need for multicenter trials so that the management of such patients, be it active or conservative, can be evidence-based.

Penicillium species as a rare isolate in tracheal granulation tissue: a case series.

INTRODUCTION: Granulation tissue formation is a major problem complicating the treatment of upper airway stenosis. We present two cases of recurrent tracheal granulation tissue colonisation by Penicillium species in patients undergoing laryngotracheal reconstructive surgery for post-intubation tracheal stenosis. We believe that although most Penicillium species do not cause invasive disease they can be a contributory factor to the occurrence of upper airway stenosis. CASE PRESENTATION: A microbiological and mycological study of tracheal granulation tissue in two patients with recurrent laryngotracheal stenosis was carried out. Penicillium species was seen microscopically and cultured from tracheal granulation tissue. Neither patient grew any bacteria known to be associated with airway granulation tissue formation. Amphotericin B, itraconazole, flucytosine voriconazole and caspofungin were highly active against both isolates. CONCLUSION: A search for a fungal cause should form part of the investigation for recurrent tracheal granulation tissue during laryngotracheal reconstruction.

Endoscopic resection of malignant tumors of the nose and sinuses.

BACKGROUND: Since the introduction of endoscopic surgery, its role has been gradually extended to encompass a range of pathologies, including sinonasal tumors, facilitated by the ability to repair significant skull-base defects. However, the rarity and long natural history of malignant tumors make it difficult to accrue cohorts comparable with the established gold standard of craniofacial resection. METHODS: In this prospective cohort study, after histological confirmation and a staging imaging protocol, patients deemed suitable were offered the option of an entirely endoscopic resection as an alternative to craniofacial resection. The procedure was performed under frozen section control. The long-term follow-up protocol included both MRI and examination under anesthesia at 3- to 4-month intervals in the first 2 years and 6-month intervals thereafter. RESULTS: There were 49 patients, 26 men and 23 women, aged 34-88 years (mean, 60 years). Follow-up ranged from 6 to 126 months (mean, 36 months). Thirty-seven cases underwent radiotherapy and 14 cases underwent adjuvant chemotherapy. A wide range of pathologies included 15 cases of adenocarcinoma, 11 malignant melanomas, and 11 olfactory neuroblastomas. Hospital stay was a mean of 5 days, with no significant postoperative complications. Thirty-six patients are alive and well, 7 patients have residual disease, 4 patients are dead of disease, and 2 patients have died of intercurrent disease. Three patients have been subsequently converted to craniofacial resection. Overall survival was 88% at 5 years. CONCLUSION: These initial results suggest that endoscopic resection may provide an alternative to craniofacial resection in selected cases of sinonasal malignancy.

Craniofacial resection for tumors of the nasal cavity and paranasal sinuses: a 25-year experience.

BACKGROUND: Craniofacial resection is the established "gold standard" for surgical treatment of tumors affecting the anterior skull base. METHODS: This study analyzed 308 patients (220 males, 88 females) who had undergone craniofacial resection for sinonasal neoplasia with up to 25-year follow-up. RESULTS: An overall actuarial survival of 65% at 5 years and 47% at 10 years was found for the cohort as a whole. For patients with malignant tumors, the 5-year actuarial survival was 59%, falling to 40% at 10 years. For patients with benign pathology, the actuarial survival was 92% at 5 years falling to 82% at 10 years. Statistical analysis again identified brain involvement, type of malignancy, and orbital involvement as the 3 most significant prognostic factors. CONCLUSION: Analysis of one of the largest single institution cohorts over a 25-year period provides a baseline against which other approaches such as an entirely endoscopic skull base resection must be judged.