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Aim: Xen2174 is a synthetic 13-amino acid peptide that binds specifically to the norepinephrine transporter, which results in inhibition of norepinephrine uptake. It is being developed as a possible treatment for moderate to severe pain and is delivered intrathecally. The current study was performed to assess the pharmacodynamics (PD) and the cerebrospinal fluid (CSF) pharmacokinetics (PK) of Xen2174 in healthy subjects., Methods: This was a randomized, blinded, placebo-controlled study in healthy subjects. The study was divided into three treatment arms. Each group consisted of eight subjects on active treatment and two or three subjects on placebo. The CSF was sampled for 32 h using an intrathecal catheter. PD assessments were performed using a battery of nociceptive tasks (electrical pain, pressure pain and cold pressor tasks)., Results: Twenty-five subjects were administered Xen2174. CSF PK analysis showed a higher area under the CSF concentration-time curve of Xen2174 in the highest dose group than allowed by the predefined safety margin based on nonclinical data. The most common adverse event was post-lumbar puncture syndrome, with no difference in incidence between treatment groups. Although no statistically significant differences were observed in the PD assessments between the different dosages of Xen2174 and placebo, pain tolerability in the highest dose group was higher than in the placebo group [contrast least squares mean pressure pain tolerance threshold of Xen2174 2.5 mg-placebo (95% confidence interval), 22.2% (-5.0%, 57.1%); P = 0.1131]., Conclusions: At the Xen2174 dose level of 2.5 mg, CSF concentrations exceeded the prespecified exposure limit based on the nonclinical safety margin. No statistically significant effects on evoked pain tests were observed., (© 2016 The British Pharmacological Society.)

Aim: Head and neck (H&N) cancer patients can undergo anatomical change throughout radiotherapy treatment. Adaptive radiotherapy (ART) is effective in addressing the impact of this change on the planned dose distribution. The aim of this study was to identify pretreatment factors that influence the need for and timing of replanning for patients receiving chemoradiotherapy for node-positive nasopharyngeal (NPC) and oropharyngeal carcinoma (OPC)., Methods: Of 110 patients enrolled in a prospective H&N ART study, 21 (19%) underwent a second planning scan (re-CT) and were included in this review. Univariate and multivariate analysis was used to compare those patients who were replanned with those that were not. Factors influencing the timing of replanning were assessed including patient and tumor characteristics and structure volume details., Results: Of the five replanned patients, three were diagnosed with NPC (P = 0.06) and had significantly larger initial nodal volumes (median volume 140.3 cc vs. 39.1 cc, P = 0.019). Overall the median time of re-CT was significantly different between replanned and non-replanned patients, with replanned patients having an earlier re-CT: median fraction 18 versus fraction 23 (P = 0.01). Specifically, NPC patients who were replanned had a re-CT performed earlier than OPC patients (median fraction 11 vs. 20)., Conclusion: For H&N patients with large nodes receiving definitive chemoradiotherapy, replanning may be considered at the commencement of week 3 for NPC patients and in week 4 of treatment for OPC patients. This information may facilitate a forward planning approach to H&N ART that enables allocation of departmental resources prior to treatment commencement., (© 2016 John Wiley & Sons Australia, Ltd.)

Intermetatarsal neuroma or Morton's neuroma is a painful condition of the foot resulting from an entrapment of the common digital nerve typically in the third intermetatarsal space. The pain can be severe and especially problematic with walking. Treatment options are limited and surgery may lead to permanent numbness in the toes. Capsaicin, the pungent ingredient of hot peppers, produces analgesia by inducing retraction of nociceptive afferents from the area of innervation and is effective in treating certain neuropathic pain disorders. A randomized double-blind placebo-controlled study was conducted to test the efficacy, tolerability, and safety of a single 0.1 mg dose of capsaicin vs placebo injected into the region of the neuroma. A total of 58 subjects diagnosed with Morton's neuroma with foot pain ≥4 (0-10 numerical pain rating scale) were injected with 2 mL of lidocaine into the intermetatarsal space proximal to the neuroma to provide local anesthesia. After 5 minutes, 0.1 mg capsaicin or placebo was injected into the intermetatarsal space containing the painful neuroma. Average foot pain was rated for 2 weeks before through 4 weeks after injection. At weeks 1 and 4, the decrease in pain was significantly greater in the subjects treated with capsaicin (P = 0.021 and P = 0.019, respectively). A trend toward significance was noted at weeks 2 and 3. Improvements in functional interference scores and reductions in oral analgesic use were also seen in the capsaicin-treated group. These findings suggest that injection of capsaicin is an efficacious treatment option for patients with painful intermetatarsal neuroma.

Background and Purpose: Adaptive radiotherapy (ART) can account for the dosimetric impact of anatomical change in head and neck cancer patients; however it can be resource intensive. Consequently, it is imperative that patients likely to require ART are identified. The purpose of this study was to find predictive factors that identify oropharyngeal squamous cell carcinoma (OPC) and nasopharyngeal carcinoma (NPC) patients more likely to need ART., Materials and Methods: One hundred and ten patients with OPC or NPC were analysed. Patient demographics and tumour characteristics were compared between patients who were replanned and those that were not. Factors found to be significant were included in logistic regression models. Risk profiles were developed from these models. A dosimetric analysis was performed., Results: Nodal disease stage, pre-treatment largest involved node size, diagnosis and initial weight (categorised in 2 groups) were identified as significant for inclusion in the model. Two models were found to be significant (p=0.001), correctly classifying 98.2% and 96.1% of patients respectively. Three ART risk profiles were developed., Conclusion: Predictive factors identifying OPC or NPC patients more likely to require ART were reported. A risk profile approach could facilitate the effective implementation of ART into radiotherapy departments through forward planning and appropriate resource allocation., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: To determine percentages of domestic cats and dogs vaccinated against rabies, identify barriers to vaccination, and assess knowledge about rabies in a semirural New Mexico community after a skunk rabies outbreak., Design: Cross-sectional, door-to-door, bilingual, community-based participatory survey., Sample: 366 residential properties in Eddy County, NM., Procedures: The New Mexico Department of Health and CDC administered surveys and analyzed data., Results: Individuals at 247 of the 366 residential properties participated in the survey. One hundred eighty of the 247 (73%) households owned a dog (n = 292) or cat (163). Cats were more likely than dogs to not have an up-to-date rabies vaccination status (prevalence ratio, 3.2; 95% confidence interval, 2.3 to 4.4). Cost and time or scheduling were the most frequently identified barriers to vaccination. One hundred sixty (65%) respondents did not know livestock can transmit rabies, 78 (32%) did not know rabies is fatal, and 89 (36%) did not know a bat scratching a person can be an exposure. Only 187 (76%) respondents indicated they would contact animal control if they saw a sick skunk, and only 166 (67%) indicated they would contact animal control if bitten by a dog they did not own., Conclusions and Clinical Relevance: Findings indicated that rabies vaccination prevalence among pet dogs and cats was low, despite the fact that the region had experienced a skunk rabies outbreak during the previous 2 years. In addition, substantial percentages of respondents did not have correct knowledge of rabies or rabies exposure.

The authors performed an open-label, rater-blinded, add-on study of sodium oxybate in 20 patients with ethanol-responsive myoclonus or essential tremor. Blinded ratings of videotaped examinations showed improvements in myoclonus at rest, stimulus-sensitive myoclonus, action myoclonus, functional performance, and postural and kinetic tremor. Tolerability was acceptable, and more than half of the patients chose to continue treatment after the trial. Double-blind placebo-controlled studies in these disorders are warranted.

ABSTRACT A previously uncharacterized virus was isolated from fall-planted sweet corn (Zea mays L., Syngenta GSS 0966) leaves showing fine chlorotic streaks. Symptomatic plants were negative in enzyme-linked immunosorbent assay against many maize viruses, but reacted weakly with antisera to Sorghum stunt mosaic virus suggesting a distant relationship between the viruses. The virus was readily transmitted by vascular puncture inoculation (VPI), but not by leaf-rub inoculation. Symptoms on maize included dwarfing and fine chlorotic streaks along intermediate and small veins that developed 12 to 17 days post-VPI. The isolated virus was bacilliform (231 +/- 5 nm long and 71 +/- 2 nm wide), with a knobby surface, and obvious helical structure typical of rhabdovirus morphology. Nucleorhabdovirus virions were observed by transmission electron microscopy of infected maize leaf tissue sections. Proteins unique to infected plants were observed in extracts of infected leaves, and the isolated virion contained three proteins with molecular masses 82 +/- 2, 50 +/- 3, and 32 +/- 2 kDa. Preliminary sequence analysis indicated the virus had similarity to members of the family Rhabdoviridae. The virus was transmitted by Graminella nigrifrons under persistent conditions. The data indicate the virus, provisionally designated Maize fine streak virus, is a new species in the genus Nucleorhabdovirus.

For the past 15 years, the Rp1-D gene has controlled common rust on sweet corn in North America. In August and September 1999, isolates of Puccinia sorghi were collected from Rp1-D sweet corn hybrids in Illinois, Wisconsin, Minnesota, Michigan, and New York. This was the first widespread occurrence in the continental United States of P. sorghi virulent on the Rp1-D gene (1). Isolates of P. sorghi collected from Los Mochis, Mexico, in March 2000 had a pattern of virulence similar to the pattern for the isolates collected in the Midwest in 1999 (2). In April and May 2000, small uredinia were observed on Rp1-D sweet corn in Florida and Texas. In Florida, isolates were collected from six different locations within a 13-km radius near Belle Glade. Three isolates were collected each from Rp1-D and non-Rp sweet corn hybrids. Isolates also were collected from two Rp1-D sweet corn hybrids and a non-Rp sweet corn hybrid near Hondo, TX. Inocula of isolates were increased through one uredinial generation in the greenhouse. Several 1-cm 2 pieces of leaf tissue with sporulating uredinia were placed in 15 ml of a solution of water and Tween 20. This inoculum was placed in whorls of five two-leaved seedlings of a susceptible hybrid, 'Primetime.' Urediniospores from newly formed uredinia were collected 10 days later and used as inocula to assay each isolate. Two isolates from Florida (one each from an Rp1-D and a non-Rp hybrid) were assayed on a non-Rp susceptible check, 20 different single Rp genes, and nine compound Rp genes. Other isolates were assayed on two replicates of a non-Rp susceptible check, a source of Rp1-D, and five single Rp genes that were effective against the isolates collected from the Midwest in 1999 and from Mexico in 2000. Each experimental unit consisted of five plants grown in 10-cm-diameter pots. Plants at the two-leaf stage were inoculated three times within 5 days by filling whorls with a urediniospore suspension. Rust reactions were rated 10 days after the final inoculation. Isolates collected in Florida from non-Rp hybrids were avirulent on Rp1-D but those collected in Texas from non-Rp hybrids were virulent on Rp1-D. Isolates collected in Florida and Texas from Rp1-D hybrids had a similar pattern of virulence as isolates collected from the Midwest in 1999 and from Mexico in March 2000; that is, effective single Rp genes included Rp1-E, Rp-G, Rp1-I, and Rp1-K. A source that we previously believed was Rp1-L now appears to be Rp-G. These are the first reports from Florida and Texas of P. sorghi virulent on Rp1-D, and they are the first occurrences of virulence against Rp1-D in the continental U.S. in 2000. Apparently, P. sorghi with virulence against Rp1-D has become established in an area where common rust inocula for North America overwinters. References: (1) J. K. Pataky and W. F. Tracy. Plant Dis. 83:1177, 1999. (2) J. K. Pataky et al. Plant Dis. 84:810, 2000.

The purposes of this investigation were to quantify the noise component of child breath-by-breath data, investigate the major determinants of the breath-to-breath noise, and to characterise the noise statistically. Twenty-four healthy children (12 males and 12 females) of mean (SD) age 13.1 (0.3) years completed 25 min of steady-state cycle ergometry at an exercise intensity of 50 W. Ventilatory and gas exchange variables were computed breath-by-breath. The mean (SD) oxygen consumption (VO2) ranged from 0.72 (0.16) to 0.92 (0.26) l x min(-1); mean (SD) carbon dioxide production (VCO2) ranged from 0.67 (0.20) l x min(-1) to 0.85 (0.16) l x min(-1); and mean (SD) minute ventilation ranged from 17.81 (3.54) l x min(-1) to 24.97 (5.63) l x min(-1). The majority of the breath-to-breath noise distributions differed significantly from Gaussian distributions with equivalent mean and SD parameters. The values of the normalised autocorrelation functions indicated a negligible breath-to-breath correlation. Tidal volume accounted for the majority of the VO2 (43%) and VCO2 (49%) variance. The breath-to-breath noise can be explained in terms of variations in the breathing pattern, although the large noise magnitude, together with the relatively small attainable response amplitudes in children reduces the certainty with which ventilatory and gas exchange kinetics can be measured.

Teaching wilderness medicine to medical students comes alive when nontraditional methods are used. In our wilderness medicine elective at the University of Massachusetts Medical School, the teaching is primarily experientially based. The following anecdote illustrates the magic that can happen when teaching is done via the scenario-debriefing method.

The relation of reflectance to backscatter and absorption parameters is investigated for waters more turbid than those of previous investigations. Experimental data are examined for river waters in which beam attenuation values range from 8.9 to 18.9 m(_1) at 550 nm. Attenuation, absorption, backscatter, and irradiance reflectance spectral properties are presented for wavelengths between 450 and 800 nm. Comparisons of reflectance with backscatter to absorption ratio and backscatter with absorption plus backscatter ratio indicate that data for turbid waters do not fit linear or polynomial models which are presently available in the literature.

An instrument has been developed that directly measures the multispectral absorption coefficient of turbid natural water. The design incorporates methods for compensation of variation in the internal light source intensity, correction of the spectrally dependent nature of the optical elements, and correction for variation in background light level. When used in conjunction with a spectrally matched total attenuation instrument, the spectrally dependent scattering coefficient can also be derived. Systematic errors associated with multiple scattering have been estimated using Monte Carlo techniques.

The theoretical concepts underlying remote sensing of estuarine parameters using laser excitation are examined. The concepts are extended to include Mie scattering as a measure of the total suspended solids and to develop the water Raman signal as an internal standard. Experimental validation of the theory was performed using backscattered laser light from a laboratory tank to simulate a remote-sensing geometry. Artificially prepared sediments and biological cultures were employed to check specific aspects of the theory under controlled conditions. Natural samples gathered from a variety of water types were also analyzed in the tank to further enhance the simulation. The results indicate that it should be possible to remotely quantify total suspended solids, dissolved organics, attenuation coefficient, chlorophyll a, and phycoerythrin in estuarine water using laser excitation.

A spectroscopic technique has been developed and experimentally verified for measuring OH concentrations behind shock waves. A water-cooled, rf-powered lamp was used to generate OH background lines sufficiently narrow to allow the peak absorption technique to be used to compute concentration from the measured absorption. Measurements of absorption by known OH concentrations in incident shock waves over a temperature range from about 1000 K to 2400 K and a pressure range from about 100 Torr to 600 Torr were used to verify the technique. Experimental runs were made with a spectral width containing four lines and another containing eight lines. A quantitative relationship between absorbance and OH concentration was obtained by using a rotationless oscillator strength, f(00) of 8.45 x 10 (-4), and a = 250 (P/T) as the damping constant expression.