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.

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.

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.

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.

Aerogel Cherenkov detector for characterizing the intense flash x-ray source, Cygnus, spectrum.

An aerogel Cherenkov detector is proposed to measure the X-ray energy spectrum from the Cygnus-intense flash X-ray source operated at the Nevada National Security Site. An array of aerogels set at a variety of thresholds between 1 and 3 MeV will be adequate to map out the bremsstrahlung X-ray production of the Cygnus, where the maximum energy of the spectrum is normally around 2.5 MeV. In addition to the Cherenkov radiation from aerogels, one possible competing light-production mechanism is optical transition radiation (OTR), which may be significant in aerogels due to the large number of transitions from SiO2 clusters to vacuum voids. To examine whether OTR is a problem, four aerogel samples were tested using a mono-energetic electron beam (varied in the range of 1-3 MeV) at NSTec Los Alamos Operations. It was demonstrated that aerogels can be used as a Cherenkov medium, where the rate of the light production is about two orders magnitude higher when the electron beam energy is above threshold.

Predictive cytokine biomarkers of clinical response to glatiramer acetate therapy in multiple sclerosis.

A prospective study of 62 patients with relapsing-remitting multiple sclerosis (RRMS) treated with Glatiramer acetate (GA) was conducted to evaluate the value of baseline and treatment-modulated cytokines in predicting the clinical response to the drug after 2years of therapy. There were 32 responders and 30 non-responders. GA upregulated Th2/regulatory cytokines and inhibited Th1 cytokines in sera or PBMC supernatants 3 and 6months into treatment. We found two prognostic models with clinical utility. A model based on IL-18 at baseline, the change in TNFa from baseline to 3months, the change in IL-4 from baseline to 6months, and the change in the log of the ratio of TNFa/IL-4 from baseline to 6months had an area under the curve (AUC) of 0.80. A high IL-18 level at baseline and a reduction of TNF-alpha over time are associated with a response to GA. Although the study identified predictive biomarkers of clinical response to GA, the results will need to be validated in other data sets.

Phase transition and surface sublimation of a mobile Potts model.

We study in this paper the phase transition in a mobile Potts model by the use of Monte Carlo simulation. The mobile Potts model is related to a diluted Potts model, which is also studied here by a mean-field approximation. We consider a lattice where each site is either vacant or occupied by a q-state Potts spin. The Potts spin can move from one site to a nearby vacant site. In order to study the surface sublimation, we consider a system of Potts spins contained in a recipient with a concentration c defined as the ratio of the number of Potts spins N(s) to the total number of lattice sites N(L)=N(x)×N(y)×N(z). Taking into account the attractive interaction between the nearest-neighboring Potts spins, we study the phase transitions as functions of various physical parameters such as the temperature, the shape of the recipient, and the spin concentration. We show that as the temperature increases, surface spins are detached from the solid phase to form a gas in the empty space. Surface order parameters indicate different behaviors depending on the distance to the surface. At high temperatures, if the concentration is high enough, the interior spins undergo a first-order phase transition to an orientationally disordered phase. The mean-field results are shown as functions of temperature, pressure, and chemical potential, which confirm in particular the first-order character of the transition.

Sir John Struthers (1823-1899), Professor of Anatomy in the University of Aberdeen (1863-1889), President of the Royal College of Surgeons of Edinburgh (1895-1897).

Between 1841 and 1845 John Struthers attended both the University of Edinburgh and some of the various Extra-mural Schools of Medicine associated with Surgeons' Hall. While a medical student he became a Member of the Hunterian Medical Society of Edinburgh and later was elected one of their Annual Presidents. He graduated with the MD Edin and obtained both the LRCS Edin and the FRCS Edin diplomas in 1845. Shortly afterwards he was invited to teach Anatomy in Dr Handyside's Extra-mural School in Edinburgh. The College of Surgeons certified him to teach Anatomy in October 1847. He had two brothers, and all three read Medicine in Edinburgh. His younger brother, Alexander, died of cholera in the Crimea in 1855 while his older brother James, who had been a bachelor all his life, practised as a Consultant Physician in Leith Hospital, Edinburgh, until his death.When associated with Dr Handyside's Extra-mural School in Edinburgh, John taught Anatomy there until he was elected to the Chair of Anatomy in Aberdeen in 1863. Much of his time was spent in Aberdeen teaching Anatomy and in upgrading the administrative facilities there. He resigned from this Chair in 1889 and subsequently was elected President of Leith Hospital from 1891 to 1897. This was in succession to his older brother, James, who had died in 1891. Later, he was elected President of the Royal College of Surgeons of Edinburgh from 1895 to 1897 and acted as its Vice-President from 1897 until his death in 1899. In 1898, Queen Victoria knighted him. His youngest son, John William Struthers, was the only one of his clinically qualified sons to survive him and subsequently was elected President of the Edinburgh College of Surgeons from 1941 to 1943.

Effective inhibition of c-MET-mediated signaling, growth and migration of ovarian cancer cells is influenced by the ovarian tissue microenvironment.

The signaling mediated by c-MET and its ligand, hepatocyte growth factor (HGF), has been implicated in malignant progression of cancer involving stimulation of proliferation, invasion and metastasis. We studied the c-MET/HGF axis as a mediator of tumor-stromal interaction in ovarian cancer and the value of targeting c-MET for the treatment of ovarian cancer. To assess c-MET signaling, we established in vitro models of the microenvironment using primary and immortalized human fibroblasts from normal ovary and tumor samples and epithelial ovarian cancer cell lines. We found that fibroblast from normal ovaries secreted high levels of HGF (1500-3800 pg/ml) as compared with tumor-derived fibroblasts (undetectable level) and could elicit cellular biological responses on c-MET-expressing ovarian cancer cells including increase of cell proliferation and migration (2- to 140-fold increase). HGF secreted by fibroblasts was also found sequestered within extracellular matrices (ECMs) and when degraded this ECM-derived HGF stimulated cancer cell migration (1.5- to 24-fold). In cells containing constitutive c-MET phosphorylation, recombinant HGF and fibroblast-derived HGF negligibly affect c-MET phosphorylation on Tyr(1234) and Tyr(1003). However, both sources of HGF increased the phosphorylation of c-MET on Tyr(1349), the multi-substrate docking site, by more than sixfold and led to activation of downstream signaling transducers. DCC-2701 (Deciphera Pharmaceuticals, LLC), a novel c-MET/TIE-2/VEGFR inhibitor was able to effectively reduce tumor burden in vivo and block c-MET pTyr(1349)-mediated signaling, cell growth and migration as compared with a HGF antagonist in vitro. Importantly, DCC-2701's anti-proliferative activity was dependent on c-MET activation induced by stromal human fibroblasts and to a lesser extent exogenous HGF. Our data suggest for the first time that DCC-2701 may be superior to HGF antagonists that are in clinical trials and that pTyr(1349) levels might be a good indicator of c-MET activation and likely response to targeted therapy as a result of signals from the microenvironment.

Role of prostaglandins in spinal transmission of the exercise pressor reflex in decerebrated rats.

Previous studies found that prostaglandins in skeletal muscle play a role in evoking the exercise pressor reflex; however the role played by prostaglandins in the spinal transmission of the reflex is not known. We determined, therefore, whether or not spinal blockade of cyclooxygenase (COX) activity and/or spinal blockade of endoperoxide (EP) 2 or 4 receptors attenuated the exercise pressor reflex in decerebrated rats. We first established that intrathecal doses of a non-specific COX inhibitor Ketorolac (100 µg in 10 µl), a COX-2-specific inhibitor Celecoxib (100 µg in 10 µl), an EP2 antagonist PF-04418948 (10 µg in 10 µl), and an EP4 antagonist L-161,982 (4 µg in 10 µl) effectively attenuated the pressor responses to intrathecal injections of arachidonic acid (100 µg in 10 µl), EP2 agonist Butaprost (4 ng in 10 µl), and EP4 agonist TCS 2510 (6.25 µg in 2.5 µl), respectively. Once effective doses were established, we statically contracted the hind limb before and after intrathecal injections of Ketorolac, Celecoxib, the EP2 antagonist and the EP4 antagonist. We found that Ketorolac significantly attenuated the pressor response to static contraction (before Ketorolac: 23 ± 5 mmHg, after Ketorolac 14 ± 5 mmHg; p<0.05) whereas Celecoxib had no effect. We also found that 8 µg of L-161,982, but not 4 µg of L-161,982, significantly attenuated the pressor response to static contraction (before L-161,982: 21 ± 4 mmHg, after L-161,982 12 ± 3 mmHg; p<0.05), whereas PF-04418948 (10 µg) had no effect. We conclude that spinal COX-1, but not COX-2, plays a role in evoking the exercise pressor reflex, and that the spinal prostaglandins produced by this enzyme are most likely activating spinal EP4 receptors, but not EP2 receptors.

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.

Temporal association of ambient temperature and relative humidity with Spirocerca lupi infection of Onthophagus sellatus: a 14-year longitudinal study.

The parasitic nematode Spirocerca lupi causes major morbidity and mortality in dogs. The scarab beetle Onthophagus sellatus is its major intermediate host in Israel. We investigated the prevalence of beetle infection by S. lupi in different years between 1994 and 2008. The average monthly maximum and minimum relative humidity (RH) and ambient temperature (AT) throughout the study period were calculated based on daily meteorological data. The infection prevalence decreased over the study period, possibly due to a chronological change resulting from increased preventive treatment of dogs against S. lupi, or climate change. Multivariate analysis was performed for these two hypotheses. Under the first hypothesis, chronological change was forced into the model, and environmental variables were inserted stepwise. The final model included beetle-collection date, minimum RH (RH min) during the month preceding beetle collection, its interaction with maximal AT (AT max) during that same month, and the interaction of maximal RH (RH max) and AT max, during the month of beetle collection. Under the second hypothesis, chronological change was not forced. The final model included RH max during the month of beetle collection, average RH (RHave) during the month preceding beetle collection, and its interaction with AT max during the latter month. The results suggest that under both hypotheses, RH and AT during the month preceding beetle collection influence S. lupi's ability to develop and survive in O. sellatus, and may be used to predict the risk to dogs of S. lupi infection.

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.

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.

Mach-Zehnder recording systems for pulsed power diagnostics.

Fiber-optic transmission and recording systems, based on Mach-Zehnder modulators, have been developed and installed at the National Ignition Facility (NIF), and are being developed for other pulsed-power facilities such as the Z accelerator at Sandia, with different requirements. We present the design and performance characteristics for the mature analog links, based on the system developed for the Gamma Reaction History diagnostic at the OMEGA laser and at NIF. For a single detector channel, two Mach-Zehnders are used to provide high dynamic range at the full recording bandwidth with no gaps in the coverage. We present laboratory and shot data to estimate upper limits on the radiation effects as they impact recorded data quality. Finally, we will assess the technology readiness level for mature and developing implementations of Mach-Zehnder links for these environments.

Three Licentiates of the Royal College of Surgeons of Edinburgh who were decorated with the Victoria Cross.

Since the Victoria Cross was introduced in January 1856 by Queen Victoria to reward acts of valour in the face of the enemy, initially during the Crimean War, over 1350 medals have been awarded. Of these, three were awarded to medical officers who had previously gained the Licentiate Diploma of the Royal College of Surgeons of Edinburgh (LRCS Edin) - Valentine Munbee McMaster on 25 September 1857, Henry Thomas Sylvester on 20 November 1857 (although the acts of valour for which he was awarded his VC occurred on two occasions in September 1855) and Campbell Mellis (or Millis) Douglas on 7 May 1867.

The sexual abuse of young people with a disability or chronic health condition.

For several reasons, children and youth with a disability or chronic health condition are at an increased risk of sexual abuse. Health care providers, along with parents and caregivers, need to maintain a high level of suspicion concerning possible sexual abuse of this population. Physicians especially need to advocate for policies to prevent or detect abuse in hospitals, schools and other institutional settings. Such policies include the thorough screening and monitoring of employees and volunteers; chaperoning physical examinations and treatment procedures; supervising outings; and ensuring an institutional culture that promotes patient privacy. In addition, physicians should promote patient self-awareness and empowerment, and provide early anticipatory guidance concerning sexuality, personal empowerment and abuse risks. The present document replaces the previous Canadian Paediatric Society position statement published in 1997.

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.

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.