Introduction and validation of the open symptom framework: a public domain modular framework for patient-reported measurement of symptoms related to cancer and its treatment.

PURPOSE: We provide an initial description and validation of some public domain patient-reported outcome (PRO) items to assess cancer symptom burden to address immediate barriers to symptom assessment use in clinical practice and facilitate future research. METHODS: We created the Open Symptom Framework (OSF), a flexible tool for clinical cancer-related symptom assessment. The items comprise six components: recall period, concept, symptom, qualifier(s), a definition, and a 5-point Likert-type response. We recruited patients receiving cancer therapy in the United States and United Kingdom. We assessed external construct validity by comparing OSF scores to the PRO-CTCAE measure and assessed reliability, scalability, dimensionality, and item ordering within a non-parametric item response theory framework. We tested differential item functioning for country, age, gender, and level of education. RESULTS: We developed a framework alongside clinical and psychometric experts and debrieifed with 10 patients. For validation, we recruited 331patients. All items correlated with the PRO-CTCAE equivalents (r = 0.55-0.96, all p < 0.01). Mokken analysis confirmed the scalability and unidimensionality of all symptom scales with multiple items at the scale (Ho = 0.61-0.75) and item level (Hi = 0.60-0.76). Items are interpreted consistently between demographic groups (Crit = 0 for all groups). CONCLUSION: The public domain OSF has excellent psychometric properties including face, content, and criterion validity and can facilitate the development of flexible, robust measurements to fulfil stakeholder need. The OSF was designed specifically to support clinical assessment but will function well for research. Further work is planned to increase the number of symptoms and number of questions per symptom within the framework.

Crystalline phases found in rapidly quenched Ni-Nb-Zr alloys.

The properties of metallic alloys can be significantly improved by developing non-equilibrium phases in the microstructures through rapid solidification techniques, thus the characterisation of these unusual structures is extremely important. In this research, the microstructures of three rapidly quenched alloys, namely Ni65.2 Nb33.8 Zr1.0 , Ni54.8 Nb31.1 Zr14.1 and Ni54.8 Nb21.6 Zr23.6 (at. %) were investigated in greater detail in order to determine the structures and compositions of their crystalline phases. These crystalline phases were characterised using a combination of scanning electron microscopy, energy dispersive x-ray spectroscopy, x-ray diffraction and transmission electron microscopy techniques. The phases were compared to the crystalline structures reported in the literature. Our results indicate some agreement with the Ni-Nb phase diagram and an isothermal section of the Ni-Nb-Zr phase diagram; however, it is detected zirconium solubility in the Ni3 Nb phase, as well as, the absence of expected crystalline phases.

Laboratory tests to identify patients at risk of early major adverse events: a prospective pilot study.

BACKGROUND/AIMS: To test whether commonly measured laboratory variables can identify surgical patients at risk of major adverse events (death, unplanned intensive care unit (ICU) admission or rapid response team (RRT) activation). METHODS: We conducted a prospective observational study in a surgical ward of a university-affiliated hospital in a cohort of 834 surgical patients admitted for >24 h. We applied a previously validated multivariable model-derived risk assessment to each combined set of common laboratory tests to identify patients at risk. We compared the clinical course of such patients with that of control patients from the same ward who had blood tests but were identified as low risk. RESULTS: We studied 7955 batches and 73,428 individual tests in 834 patients (males 55%; average age 65.8 ± 17.6 years). Among these patients, 66 (7.9%) were identified as 'high risk'. High-risk patients were older (75.9 vs 61.8 years of age; P < 0.0001), had much greater early (48 h) mortality (6/66 (9%) vs 4/768 (0.5%); P < 0.0001) and greater overall hospital mortality (11/66 (16.7%) vs 9/768 (1.2%); P < 0.0001). They also had more early (8/66 (12.1%) vs 14/768 (1.8%); P = 0.0001) and overall in-hospital unplanned ICU admissions (12/66 (18.2%) vs 18/768 (2.3%); P < 0.0001) and more early (26/66 (39.3%) vs 50/768 (6.5%); P < 0.0001) and overall in-hospital RRT calls (26/66 (39.4%) vs 55/768 (7.2%); P < 0.0001). CONCLUSIONS: Commonly performed laboratory tests identify surgical ward patients at risk of early major adverse events. Further studies are needed to assess whether such identification system can be used to trigger interventions that help improve patient outcomes.

Weight change associated with corticosteroid therapy in adolescents with systemic lupus erythematosus.

UNLABELLED: Physical appearance is very important to adolescents and weight gain secondary to corticosteroid (CS) treatment may have a direct impact on adolescent development. Understanding weight gain in adolescents with SLE who are being treated with CS will help clinicians develop strategies for prevention of nonadherence, obesity and eating disorders in this population. METHODS: Patients aged 11-18 years old with newly diagnosed SLE between January,1995 and December, 2006 were identified through the Rheumatology database at the Sickkids hospital, Canada. All charts were reviewed. Patients were categorized based on final BMI status as normal, overweight and obese. Risk factors for being obese were examined by logistic regression model analysis. RESULTS: Of 236 patients, 78% fulfilled the criteria. 85% were female with mean age at onset of diagnosis was 14 ± 1.7 years. Mean duration of CS treatment was 50 ± 31 months and mean cumulative CS dosage was 34.11 ± 32.7 g of prednisone. At baseline, 10% had BMI >25 kg/m(2) while at the end of the study, 20% were overweight and 10.4% were obese. In addition, 61% gained <10 kg while 15% gained ≥20 kg. Initial BMI was a significant predictors for final BMI (OR = 27.59, 95%CI = 6.04-126.09, p < .001) while male (OR = 8.50, 95%CI = 2.95-24.5, p < 0.000) and cumulative CS dosage (OR = 1.53, 95%CI = 1.05-2.23, p < .05) were the significant predictors for weight gain >10 kg. Duration of CS treatment did not correlate with obesity. CONCLUSION: Although a significant number of patients became overweight or obese after being treated with CS, most gained <10 kg. Obesity secondary to CS treatment in SLE patients was significantly correlated with baseline BMI, gender and cumulative CS dosage.

Postoperative hypothermia and patient outcomes after major elective non-cardiac surgery.

Using a multicentre adult patient database from Australia and New Zealand, we obtained the lowest and highest temperature in the first 24 h after admission to the intensive care unit after elective non-cardiac surgery. Hypothermia was defined as core temperature < 36 °C; transient hypothermia as a temperature < 36 °C that was corrected within 24 h, and persistent hypothermia as hypothermia not corrected within 24 h. We studied 50,689 patients. Hypothermia occurred in 23,165 (46%) patients, was transient in 22,810 (45%), and was persistent in 608 (1.2%) patients. On multivariate analysis, neither transient (OR = 1.07, 95% CI 0.96-1.20) nor persistent (OR = 1.50. 95% CI 0.96-2.33) hypothermia was independently associated with increased hospital mortality.

Reduced transcriptional regulatory competence of the androgen receptor in X-linked spinal and bulbar muscular atrophy.

Expansion of the long (CAG; glutamine)n repeat in the first exon of the X-linked human androgen receptor gene (hAR) causes spinal and bulbar muscular atrophy, frequently in association with mild androgen insensitivity. The relevant normal motor neurons are preferentially stimulated by androgen, however no motor neuron disorder occurs with any other known AR mutation, including those that cause complete androgen insensitivity. We have found that a polyglutamine (Gln) expanded AR transactivates an androgen-responsive reporter gene subnormally. Other groups have reported that a poly Gln-deleted AR transactivates normally. A parsimonious interpretation of all these facts is that poly Gln expansion causes the AR to lose a function that is necessary for full androgen sensitivity and to gain a function that is selectively motor neuronotoxic.

Comparison of convergent beam electron diffraction and geometric phase analysis for strain measurement in a strained silicon device.

Convergent beam electron diffraction and geometric phase analysis were used to measure strain in the gate channel of a p-type strained silicon metal-oxide-semiconductor field-effect transistor. These measurements were made on exactly the same transmission electron microscopy specimen allowing for direct comparison of the relative advantages of each technique. The trends in the strain values show good agreement in both the [110] and [001] directions, but the absolute strain values are offset from each other. This difference in the absolute strain measured using the two techniques is attributed to the way the reference strain is defined for each.

ERK1/2 signaling pathway in mast cell activation-induced sensitization of esophageal nodose C-fiber neurons.

Sensitization of esophageal nociceptive afferents by inflammatory mediators plays an important role in esophageal inflammatory nociception. Our previous studies demonstrated that esophageal mast cell activation increases the excitability of esophageal nodose C-fibers. But the intracellular mechanism of this sensitization process is still less clear. We hypothesize that extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling pathway plays an important role in mast cell activation-induced sensitization of esophageal nodose C-fiber neurons. Mast cell activation and in vivo esophageal distension-induced phosphorylations of ERK1/2 were studied by immuno-staining and Western blot in esophageal nodose neurons. Extracellular recordings were performed from nodose neurons using ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. Nerve excitabilities were compared by action potentials evoked by esophageal distensions before and after mast cell activations with/without pretreatment of mitogen-activated protein kinases (MAPK)/ERK kinase inhibitor U0126. The expressions of phospho-ERK1/2 (p-ERK1/2) in the same nodose ganglia were then studied by Western blot. Mast cell activation enhances in vivo esophageal distension-induced phosphorylation of ERK1/2 in nodose neurons. This can be prevented by pretreatment with mast cell stabilizer cromolyn. In ex vivo esophageal-vagal preparations, both mast cell activation and proteinase-activated receptor 2 (PAR2)-activating peptide perfusion increases esophageal distension-induced mechano-excitability of esophageal nodose C-fibers and phosphorylation of ERK1/2 in nodose neurons. Pretreatment with MAPK/ERK kinase inhibitor U0126 prevents these potentiation effects. Collectively, our data demonstrated that mast cell activation enhances esophageal distension-induced mechano-excitability and phosphorylation of ERK1/2 in esophageal nodose C-fiber neurons. This reveals a new intracellular pathway of esophageal peripheral sensitization and inflammatory nociception.

Using a <670> zone axis for convergent beam electron diffraction measurements of lattice strain in strained silicon.

Convergent beam electron diffraction patterns of silicon from the gate channel region of a complementary metal-oxide-semiconductor transistor with recessed Si(.82)Ge(.18) stressors were analysed using three zone axes: <230>, <340> and <670>. Values measured using these axes were compared with each other with regards to strain along the [110] and the [001] directions. It was demonstrated that strain measurements made using all three axes showed reasonable agreement with each other: an increase in the [110] compressive strain and a switch from compressive to tensile strain in the [001] with decreasing distance below the gate. It was also observed that the strain calculations using the <230> axis had the lowest uncertainty whereas the <670> axis allowed for measurements closest to the gate due to the improved lateral resolution at that tilt angle.

Video. Chopstick surgery: a novel technique enables use of the Da Vinci Robot to perform single-incision laparoscopic surgery.

INTRODUCTION: Single-incision laparoscopic surgery (SILS) is limited by the coaxial arrangement of the instruments. A surgical robot with "wristed" instruments could overcome this limitation but the "arms" collide when working coaxially. This video demonstrates a new technique of "chopstick surgery," which enables use of the robotic arms through a single incision without collision. METHODS: Experiments were conducted utilizing the da Vinci S® robot (Sunnyvale, CA) in a porcine model with three laparoscopic ports (12 mm, 2-5 mm) introduced through a single "incision." Pilot work conducted while performing Fundamentals of Laparoscopic Surgery (FLS) tasks determined the optimal setup for SILS to be a triangular port arrangement with 2-cm trocar distance and remote center at the abdominal wall. Using this setup, an experienced robotic surgeon performed a cholecystectomy and nephrectomy in a porcine model utilizing the "chopstick" technique. The chopstick arrangement crosses the instruments at the abdominal wall so that the right instrument is on the left side of the target and the left instrument on the right. This arrangement prevents collision of the external robotic arms. To correct for the change in handedness, the robotic console is instructed to drive the "left" instrument with the right hand effector and the "right" instrument with the left. RESULTS: Both procedures were satisfactorily completed with no external collision of the robotic arms, in acceptable times and with no technical complications. This is consistent with results obtained in the box trainer where the chopstick configuration enabled significantly improved times in all tasks and decreased number of errors and eliminated instrument collisions. CONCLUSION: Chopstick surgery significantly enhances the functionality of the surgical robot when working through a small single incision. This technique will enable surgeons to utilize the robot for SILS and possibly for intraluminal or transluminal surgery.

Senescent leaf exudate increases mosquito survival and microbial activity.

We conducted experiments to evaluate the effects of soluble components in senescent leaf material on the growth and development of the eastern tree hole mosquito, Aedes triseriatus (Say). Oak leaves that were either leached for three days to remove the labile nutrient fraction, or were not leached, served as basal nutrient inputs in each experiment.Mosquito performance in microcosms containing leachate only was significantly worse compared with microcosms containing leaf material in combination with either leachate or water, indicating the importance of leaf substrates to mosquito production.Adult mosquito biomass, emergence, and development time were significantly higher in microcosms containing unleached leaves compared with leached leaf material. Additions of leachate to leached leaf treatments enhanced adult production, but not to the level observed in unleached leaf treatments.Filtered and unfiltered leachate added substantial nitrogen and phosphorus to microcosms and significantly affected mosquito growth responses. Bacterial productivity and abundance were also significantly affected by leachate additions and filtering.Taken together, these results suggest that while leaves decline with respect to nutritional value during decomposition, they remain important components of the habitat as substrates for microbial growth and mosquito feeding, particularly when nutrients (here, leachate) enter the system. Our results also illustrate the importance of soluble leaf material, which enhances mosquito production through effects on microbial community dynamics.

An acute trophic cascade among microorganisms in the tree hole ecosystem following removal of omnivorous mosquito larvae.

Results of two field experiments showed that selective removal of omnivorous mosquito larvae (Aedes triseriatus (Say)) functioning as top predators in the food web of a temperate, tree hole ecosystem resulted rapidly in increased abundance of flagellate and then ciliate populations. Flagellate density increased from <1 per ml to >103 per ml within 4 days of omnivore removal, followed shortly thereafter by an increase in ciliate density from <1 per ml to >102 per ml, after which flagellate density declined, and flagellate and ciliate densities stabilized. Rod-shaped bacteria increased slightly in density after removal of larval mosquitoes, then declined as protist density increased. Cocciform bacteria did not vary in density with these changes, thus the trophic cascade dampened at the remotest trophic level. Concomitant with the increase in protist densities, some bacteria formed elongated filaments >10 µm in length, likely an anti-predation, morphological response stimulated by suddenly intensified grazing as protozoan density rose. Results suggest that feeding by omnivorous mosquito larvae exhibited strong top-down effects on flagellate and ciliate populations, depressing them to below their equilibrium densities and nearly to extinction in tree hole ecosystems.

Perceptions of transitional care needs and experiences in pediatric heart transplant recipients.

Survival following pediatric heart transplantation (HTx) continues to improve. The transition from pediatric to adult care is becoming a pivotal stage in the ongoing medical management of this population. Published data support enhanced outcomes for adolescent patients with increased attention to transitional care. The purpose of this study was to explore the 'transition experience' of adolescent HTx recipients and families. All teens (12-18 years) and parents at a single-center HTx program were invited to participate in semistructured interviews. Qualitative, phenomenological methodology was used to build theoretical knowledge and guided the data collection and analysis. The study population included 14 patients (7 males) with a mean age of 15.7 +/- 1.8 years (11.7-17.8 years) and at a mean of 4.1 +/- 3.3 years post-HTx (0.3-9.2 years) at the time of study participation. Major themes identified included: (i) adolescent disinterest and apathy regarding transition to adult care versus parental anxiety about their child's eventual departure from the pediatric transplant center, (ii) perceived differences in pediatric versus adult care and (iii) identification of strategies described as helpful in facilitating the transition. Understanding the experiences and perceptions of adolescent HTx recipients and their parents is crucial to planning effective transitional care and necessary for evidenced-based practice.

Uranium disequilibrium in groundwater: an isotope dilution approach in hydrologic investigations.

The distribution and environmental disequilibrium patterns of naturally occurring uranium isotopes (U(234) and U(238)) in waters of the Floridan aquifer suggest that variations in the ratios of isotopic activity and concentrations can be used quantitatively to evaluate mixing proportions of waters from differing sources. Uranium is probably unique in its potential for this approach, which seems to have general usefulness in hydrologic investigations.

Use of a non-ICU specialty ward for immediate post-operative management of head and neck free flaps; a randomized controlled trial.

OBJECTIVES: Compare length of stay, flap failure rate, medical and surgical complications and cost when patients undergoing head and neck free flap reconstruction are monitored in an intensive care unit (ICU) versus a specialty ward unit postoperatively. MATERIALS AND METHODS: A prospective, non-inferiority, randomized controlled trial was conducted from 7/22/2016 to 9/12/2018 at a single institution. Patients were randomized to the ICU or specialty ward unit. Flap check protocols were identical between the groups. Perioperative and postoperative outcome variables were assessed and compared. RESULTS: 131 patients were enrolled in the study and 118 ultimately underwent head and neck free flap reconstruction. 57 were randomized to the ICU and 61 to the specialty ward unit. There were no significant differences between the ICU and specialty ward unit groups with regard to demographic variables including age, gender, co-morbidities, tobacco or alcohol use, prior chemotherapy or radiation therapy treatment. There were no significant differences in perioperative variables including need for transfusion, tracheostomy, ischemia time, blood loss, fluid administration or post-operative antibiotic use. There was no significant difference in the primary outcome variable, length of stay. There were no significant differences in the number of the medical or surgical complications, flap failure rate, or hospital costs. CONCLUSION: In this prospective, randomized controlled trial, head and neck free-flap patients cared for on a specialty ward in the immediate post-operative period had equivalent outcomes to those cared for in the ICU.

Influence of palliative surgical resection on overall survival in patients with advanced colorectal cancer: a retrospective single institutional study.

BACKGROUND: The role of palliative surgical resection in patients presenting with locally advanced or metastatic colorectal cancer (CRC) is unclear. Resection is often limited to symptomatic management of bleeding, obstruction, perforation or for relief of pain, in patients with an adequate performance status and an expected life span of over several weeks. An exploratory analysis to evaluate the influence of a palliative surgical resection on survival outcome in patients with advanced CRC is reported. METHOD: A retrospective review of medical records of all patients diagnosed with advanced CRC at our institution between the years 1998 and 2003 was undertaken. Tumour registry data were reviewed to identify age, gender, modalities of therapy [i.e. surgery (S), chemotherapy (C), radiation] and overall survival. IRB approval was obtained for this study. RESULTS: One hundred and eighty-five patients were identified. Median age was 67 years (range 30-99). M:F ratio was 1:1. Sixty-two per cent of patients (115/185) underwent a palliative surgical intervention. Median survival of patients who underwent S and those that did not undergo S was 22 and 3 months respectively (P < 0.0001). Forty-eight per cent of patients (79/184) underwent systemic C. Median survival of patients who received C + S, and patients who received C alone was 30 and 15 months respectively (P < 0.0004). Fifty-one per cent of patients who underwent S, received C; 30% of patients who did not undergo S, received C. Chemotherapy data were available on 46 of 79 patients. Patients treated with S + C, and C without S, received a median of 9 and 6 months of therapy respectively. The median number of regimens used were similar in both. CONCLUSION: These exploratory data suggest a positive influence of a palliative resection performed during the disease course of patients with advanced CRC. The increased frequency of utilization and the more prolonged duration of C in the surgically treated patients may in part contribute to this improved survival. This may also be reflective of performance status at the time of diagnosis. Future trials enrolling patients with advanced CRC should prospectively stratify for surgical intervention to further clarify the influence of this modality on the outcome of systemic therapy in this disease.

Bacterial community structure in tree hole habitats of Ochlerotatus triseriatus: influences of larval feeding.

We investigated the bacterial community composition of tree holes in relation to the presence and absence of larvae of the mosquito Ochlerotatus triseriatus. Larvae were eliminated from a subset of natural tree holes with Bacillus thuringiensis serovar israelensis, and total bacterial numbers, slow- and fast-growing colony-forming units on minimal media, and 16S rRNA gene sequence data from water column and leaf material were obtained. Total bacterial counts did not change significantly with treatment; however, the number of slow-growing cultivable bacteria significantly increased in the absence of larvae. Sequence classifications and comparisons of sequence libraries using LIBSHUFF indicated that the elimination of larvae significantly altered bacterial community composition. Major groups apparently affected by larvae were Flavobacteriaceae, Rhodobacteraceae, Comamonadaceae, and Sphingomonadaceae. A clear dominance of Flavobacteriaceae in the water column after larval removal suggests members of this group are a major bacterial food source.

Characterization of the Mercury pulsed power x-ray source spectrum using multichannel density aerogel Cherenkov detectors.

The Aerogel Cherenkov Detector for Cygnus (ACD/C) is a time-dependent, x-ray spectral detector that uses SiO2 aerogels spanning an index of refraction (n = 1.02-1.07) corresponding to a 1.1-2.3 MeV x-ray energy threshold. The ACD/C was developed for pulsed power x-ray sources like Cygnus located at the Nevada National Site and Mercury located at the Naval Research Laboratory (NRL). Aerogels sit between the measurement capabilities of gas (>2 MeV) and solids such as fused silica (>0.3 MeV). The detector uses an aluminum converter to Compton scatter incoming x-rays and create relativistic electrons, which produce Cherenkov light in an aerogel or a fused silica medium. The ACD/C was fielded at the NRL when Mercury was tuned to produce up to 4.8 MeV endpoint bremsstrahlung. Despite a high radiation and electromagnetic interference background, the ACD/C was able to achieve high signal over noise across five aerogel densities and fused silica, including a signal to noise for a 1.1 MeV aerogel threshold. Previous experiments at Cygnus observed a signal that was comparable to the noise (1×) at the same threshold. The ACD/C observed time-resolved rise and fall times for different energy thresholds of the photon spectrum. Monte Carlo simulations of the ACD/C's aerogel response curves were folded with a simulation of Mercury's photon energy spectrum and agree within the error to the observed result.

High-frequency developmental abnormalities in p53-deficient mice.

BACKGROUND: Several strains of mice carrying null mutations of the tumour suppressor gene p53 have been developed. It has been reported that homozygous mice from all of these strains develop normally to birth, but then succumb rapidly to neoplasia. RESULTS: Here, we report that a significant proportion of female p53-/- mice die during embryogenesis or in the period between birth and weaning, being subject to a spectrum of abnormalities. In a significant proportion (23%) of p53-/- female embryos, the normal process of neural tube closure failed, leading to exencephaly and subsequent anencephaly. Although this phenomenon was predominantly associated with females, we observed one affected male embryo. In addition to a spectrum of neural tube defects, many of these embryos exhibited a range of craniofacial malformations, including ocular abnormalities and defects in upper incisor tooth formation. We observed a significant reduction in the number of p53-/- female progeny of p53+/- x p53+/- matings, and also in an in utero analysis of the p53+/- female progeny of p53-/- x p53+/+ matings. When male mice were exposed to irradiation prior to mating, a significant increase in the rate of abnormality was seen in the progeny, which was specifically associated with p53 deficiency. CONCLUSIONS: We have identified a high rate of developmental abnormalities associated with p53 deficiency. This manifests itself as a spectrum of lesions, predominantly female-associated defects in neural tube closure. These defects may arise either because p53 plays a physiological role at the time of neural tube closure, or because of an abnormally high frequency of mutation within the haploid gametes of p53-null parents.