Analysis of the Structure of Heavy Ion Irradiated LaFeO3 Using Grazing Angle X-ray Absorption Spectroscopy.

Crystalline ceramics are candidate materials for the immobilization of radionuclides, particularly transuranics (such as U, Pu, and Am), arising from the nuclear fuel cycle. Due to the α-decay of transuranics and the associated recoil of the parent nucleus, crystalline materials may eventually be rendered amorphous through changes to the crystal lattice caused by these recoil events. Previous work has shown irradiation of titanate-based ceramics to change the local cation environment significantly, particularly in the case of Ti which was shown to change from 6- to 5-fold coordination. Here, this work expands the Ti-based study to investigate the behavior in Fe-based materials, using LaFeO3 as an example material. Irradiation was simulated by heavy ion implantation of the bulk LaFeO3 ceramic, with the resulting amorphous layer characterized with grazing angle X-ray absorption spectroscopy (GA-XAS). Insights into the Fe speciation changes exhibited by the amorphized surface layer were provided through quantitative analysis, including pre-edge analysis, and modeling of the extended X-ray absorption fine structure (EXAFS), of the GA-XAS data.

Impact of stereochemistry on rheology and nanostructure of PLA-PEO-PLA triblocks: stiff gels at intermediate l/d-lactide ratios.

We report rheology and structural studies of poly(lactide)-poly(ethylene oxide)-poly(lactide) (PLA-PEO-PLA) triblock copolymer gels with various ratios of l-lactide and d-lactide in the PLA blocks. These materials form associative micellar gels in water, and previous work has shown that stereoregular triblocks with a l/d ratio of 100/0 form much stiffer gels than triblocks with a 50/50 l/d ratio. Our systems display an unexpected maximum in the storage modulus, G', of the hydrogels at intermediate l/d ratio. The impact of stereochemistry on the rheology is very striking; gels with an l/d ratio of 85/15 have storage moduli that are ∼1-2 orders of magnitude higher than hydrogels with l/d ratios of 100/0. No stereocomplexation is observed in the gels, although PLLA crystals are found for gels with l/d ratios of 95/5 and 90/10, and SANS results show a decrease in the intermicellar spacing for intermediate l/d ratios. We expect the dominant contribution to the elasticity of the gels to be intermicellar bridging chains and attribute the rheology to a competition between an increase in the time for PLA endblocks to pull out of micelles as the l/d ratio is increased and PLLA crystallization occurs, and a decrease in the number of bridging chains for micelles with crystalline PLA domains, as formation of bridges may be hindered by crowded crystalline PLA domains. These results provide a new strategy for controlling the rheology of PLA-based hydrogels for potential applications in biomaterials, as well as fundamental insights into how intermicellar interactions can be tuned via stereochemistry.

Reproductive effort and success of males in scramble-competition polygyny: Evidence for trade-offs between foraging and mate search.

Patterns of male reproductive allocation provide insight into life-history characteristics. The trade-offs associated with resource and female group defence are well-defined. However, less is understood about trade-offs in species that practise scramble-competition polygyny, where successful strategies may favour competitive mate-searching rather than contest competition and fighting. White-tailed deer (Odocoileus virginianus) practise scramble-competition polygyny where solitary males search for and assess receptivity of females scattered across the landscape. Physically mature males are expected to do most of the breeding because of the high energetic costs of reproduction and high social status. However, young males may collectively sire one-third of offspring. To gain a better understanding of trade-offs associated with scramble-competition polygyny, we quantified metrics associated with reproductive effort and success. We quantified changes in body mass of harvested males, energetic costs of locomotion based on movements of GPS radiocollared males and timing of reproduction via temporal genetic parentage assignments. Young males (1.5 and 2.5 years old) sired offspring, but their mating success was mainly limited to peak rut, when most females were in oestrus. Furthermore, multiple paternity was common, indicating opportunistic reproduction. Reproductive effort, indexed by body mass loss, was highest in prime-age males (5.5-6.5 years old). Surprisingly, young and postprime males also exhibited significant body mass loss, indicative of investment in reproductive effort. Movement rates increased twofold to fourfold during rut as a function of mate search activities, but cost of locomotion would cause only about one-third of observed body mass loss. Because males are capital breeders, we infer most of body mass loss is due to reduced foraging. In scramble-competition polygyny, the repeated location of potential mates and assessment of their oestrous status appear to be important constituents of male mating strategies. Therefore, mating success may be influenced by time management and spatial memory, and not based solely on social dominance. Thus, reproductive effort should be greater for individuals capable of reducing time foraging. For those that cannot, opportunistic mating opportunities may arise when operative adult sex ratios are low. Our analyses reveal valuable insight into the trade-offs associated with scramble-competition polygyny.

Growing Canopy on a College Campus: Understanding Urban Forest Change through Archival Records and Aerial Photography.

Many municipalities are setting ambitious tree canopy cover goals to increase the extent of their urban forests. A historical perspective on urban forest development can help cities strategize how to establish and achieve appropriate tree cover targets. To understand how long-term urban forest change occurs, we examined the history of trees on an urban college campus: the University of Pennsylvania in Philadelphia, PA. Using a mixed methods approach, including qualitative assessments of archival records (1870-2017), complemented by quantitative analysis of tree cover from aerial imagery (1970-2012), our analysis revealed drastic canopy cover increase in the late 20th and early 21st centuries along with the principle mechanisms of that change. We organized the historical narrative into periods reflecting campus planting actions and management approaches; these periods are also connected to broader urban greening and city planning movements, such as City Beautiful and urban sustainability. University faculty in botany, landscape architecture, and urban design contributed to the design of campus green spaces, developed comprehensive landscape plans, and advocated for campus trees. A 1977 Landscape Development Plan was particularly influential, setting forth design principles and planting recommendations that enabled the dramatic canopy cover gains we observed, and continue to guide landscape management today. Our results indicate that increasing urban tree cover requires generational time scales and systematic management coupled with a clear urban design vision and long-term commitments. With the campus as a microcosm of broader trends in urban forest development, we conclude with a discussion of implications for municipal tree cover planning.

Physiological carry-over effects of variable precipitation are mediated by reproductive status in a long-lived ungulate.

In the age of global climate change, extreme climatic events are expected to increase in frequency and severity. Animals will be forced to cope with these novel stressors in their environment. Glucocorticoids (i.e. 'stress' hormones) facilitate an animal's ability to cope with their environment. To date, most studies involving glucocorticoids focus on the immediate physiological effects of an environmental stressor on an individual, few studies have investigated the long-term physiological impacts of such stressors. Here, we tested the hypothesis that previous exposure to an environmental stressor will impart lasting consequences to an individual's glucocorticoid levels. In semi-arid environments, variable rainfall drives forage availability for herbivores. Reduced seasonal precipitation can present an extreme environmental stressor potentially imparting long-term impacts on an individual's glucocorticoid levels. We examined the effects of rainfall and environmental characteristics (i.e. soil and vegetation attributes) during fawn-rearing (i.e. summer) on subsequent glucocorticoid levels of female white-tailed deer (Odocoileus virginianus) in autumn. We captured 124 adult (≥2.5-year-old) female deer via aerial net-gunning during autumn of 2015, 2016 and 2021 across four populations spanning a gradient of environmental characteristics and rainfall in the semi-arid environment of South Texas, USA. We found for every 1 cm decrease in summer rainfall, faecal glucocorticoid levels in autumn increased 6.9%, but only in lactating females. Glucocorticoid levels in non-lactating, female deer were relatively insensitive to environmental conditions. Our study demonstrates the long-lasting effects of environmental stressors on an individual's glucocorticoid levels. A better understanding of the long-term effects stressors impart on an individual's glucocorticoid levels will help to evaluate the totality of the cost of a stressor to an individual's welfare and predict the consequences of future climate scenarios.

Long-term open-label safety study of rizatriptan acute treatment in pediatric migraineurs.

OBJECTIVE: To evaluate the safety/tolerability of rizatriptan in the long-term acute treatment of migraine in pediatric patients. BACKGROUND: Acute migraine treatment options for children are limited. A recent single-attack trial demonstrated that rizatriptan is effective in eliminating migraine headache pain in this population. We evaluated the long-term safety and efficacy of rizatriptan when used for intermittent acute treatment. METHODS: Open-label study in pediatric migraineurs ages 12-17 years. Patients weighing <40 kg received rizatriptan (orally disintegrating tablet) 5 mg, and those weighing ≥40 kg received 10 mg. Patients could treat up to 8 mild/moderate/severe migraine attacks per month for up to 12 months. One dose of study medication was allowed in a 24-hour period. RESULTS: A total of 674 patients were enrolled, and 606 patients were treated with study medication (N = 583 for 10 mg, N = 23 for 5 mg). The mean duration in the study was 292 days, and the mean number of doses of study medication taken was 20. Over the course of the study within 14 days post-any-dose, 66.0% (400) of the 606 treated patients had any adverse event, 2.3% (14) discontinued due to an adverse event, 2.6% (16) had a serious adverse event, and 23.4% (142) had a triptan-related adverse event. Of the 16 patients with serious adverse events within 14 days post-any-dose, the adverse events in 3 were considered drug-related; all 3 patient's adverse events were classified as serious only because they were associated with an overdose (use of >1 dose of study medication in a 24-hour period). The mean percentage of patient's attacks with pain freedom at 2-hours post-dose was 46.3%; this was relatively consistent over time (Months 1-3 = 43.7%, Months 4-6 = 51.9%, Months 7-9 = 49.9%, Months 10-12 = 49.5%). CONCLUSION: Rizatriptan was generally safe and well tolerated in the long-term acute treatment of migraine in pediatric patients aged 12-17 years and demonstrated a consistent treatment effect over time.

Predicting response to pregabalin from pretreatment pain quality: clinical applications of the pain quality assessment scale.

OBJECTIVE: The aim of this study is to assess the Pain Quality Assessment Scale (PQAS) in predicting pregabalin in peripheral neuropathic pain (NP). STUDY DESIGN: Post hoc analysis of a double-blind, placebo-controlled, enriched enrollment, randomized withdrawal trial evaluating pregabalin in 99 patients with NP who completed the PQAS, which comprises 20 questions regarding individual pain domains and qualities that are scored into three scales: paroxysmal, deep, and surface. METHODS: Patients rated the average pain intensity and pain quality using the PQAS at baseline; average pain intensity was assessed again after 40 days of treatment with pregabalin. Associations between pretreatment PQAS scores and treatment response were estimated using Pearson's r. Logistic regression was used to identify pretitration PQAS scores contributing unique variance to predicting treatment response. RESULTS: Fifty participants provided baseline PQAS scores and received pregabalin for the entire length of the study. Nine of 23 PQAS baseline scales and items were significantly associated with treatment response to pregabalin: the paroxysmal and deep scales, and the items assessing the following pain domains and qualities: intensity, electric, tingling, cramping, radiating, throbbing, and deep (P values range, 0.002-0.045; rs range, 0.28-0.43). The PQAS items assessing sharp, hot, and unpleasant pain items demonstrated nonsignificant trends (P < 0.10) to be associated with treatment response. In the logistic regression analysis, pretitration PQAS scores had 77% sensitivity and 83% specificity to correctly identify pregabalin responders. Significantly correlated PQAS items had a sensitivity of 85% and specificity of 76%. CONCLUSION: Pretitration PQAS scores reliably predicted pregabalin responders in patients with NP.

Functional and phylogenetic implications of septal pore ultrastructure in the ascoma of Neolecta vitellina.

Neolecta represents the earliest derived extant ascomycete lineage (Taphrinomycotina) to produce ascomata. For this reason the genus has been of interest with regard to ascoma evolution in ascomycetes. However, the evidence is equivocal regarding whether the Neolecta ascoma is homologous or analogous to ascomata produced in the later derived ascomycete lineages (Pezizomycotina). We investigated phylogenetically informative septal pore ultrastructure of Neolecta vitellina to compare with Pezizomycotina. We found that crystalline bodies that block nonascogenous septal pores in Neolecta differ from Woronin bodies, a synapomorphy for the Pezizomycotina, in three ways: (i) vacuolar origin, (ii) associated material and (iii) being loosely membrane bound. We also observed a unique type of membranous material within the septal pore, as well as distant from the septal pore, that appears to be associated with the endoplasmic reticulum. The vacuolar crystals and membranous material might have a function analagous to septal pore structures (e.g. Woronin bodies, lamellate structures) in the Pezizomycotina. Morphological evidence from our study supports an independently derived septal pore-occluding structure in the Neolecta lineage.

Relationships between plant species richness and grazing intensity in a semiarid ecosystem.

Plant species richness is an important property of ecosystems that is altered by grazing. In a semiarid environment, we tested the hypotheses that (1) small-scale herbaceous plant species richness declines linearly with increasing grazing intensity by large ungulates, (2) precipitation and percent sand interact with grazing intensity, and (3) response of herbaceous plant species richness to increasing intensity of ungulate grazing varies with patch productivity. During January-March 2012, we randomly allocated 50, 1.5-m × 1.5-m grazing exclosures within each of six 2500 ha study sites across South Texas, USA. We counted the number of herbaceous plant species and harvested vegetation in 0.25-m2 plots within exclosures (ungrazed control plots) and in the grazed area outside the exclosures (grazed treatment plots) during October-November 2012-2019. We estimated percent use (grazing intensity) based on the difference in herbaceous plant standing crop between control plots and treatment plots. We selected the negative binomial regression model that best explained the relationship between grazing intensity and herbaceous plant species richness using the Schwarz-Bayesian information criterion. After accounting for the positive effect of precipitation and percent sand on herbaceous plant species richness, species richness/0.25 m2 increased slightly from 0% to 30% grazing intensity and then declined with increasing grazing intensity. Linear and quadratic responses of herbaceous plant species richness to increasing grazing intensity were greater for the least productive patches (<15.7 g/0.25 m2) than for productive patches (≥15.7 g/0.25 m2). Our results followed the pattern predicted by the intermediate disturbance hypothesis model for the effect of grazing intensity on small-scale herbaceous plant species richness.

The Clinical Frailty Scale for mortality prediction of old acutely admitted intensive care patients: a meta-analysis of individual patient-level data.

BACKGROUND: This large-scale analysis pools individual data about the Clinical Frailty Scale (CFS) to predict outcome in the intensive care unit (ICU). METHODS: A systematic search identified all clinical trials that used the CFS in the ICU (PubMed searched until 24th June 2020). All patients who were electively admitted were excluded. The primary outcome was ICU mortality. Regression models were estimated on the complete data set, and for missing data, multiple imputations were utilised. Cox models were adjusted for age, sex, and illness acuity score (SOFA, SAPS II or APACHE II). RESULTS: 12 studies from 30 countries with anonymised individualised patient data were included (n = 23,989 patients). In the univariate analysis for all patients, being frail (CFS ≥ 5) was associated with an increased risk of ICU mortality, but not after adjustment. In older patients (≥ 65 years) there was an independent association with ICU mortality both in the complete case analysis (HR 1.34 (95% CI 1.25-1.44), p < 0.0001) and in the multiple imputation analysis (HR 1.35 (95% CI 1.26-1.45), p < 0.0001, adjusted for SOFA). In older patients, being vulnerable (CFS 4) alone did not significantly differ from being frail. After adjustment, a CFS of 4-5, 6, and ≥ 7 was associated with a significantly worse outcome compared to CFS of 1-3. CONCLUSIONS: Being frail is associated with a significantly increased risk for ICU mortality in older patients, while being vulnerable alone did not significantly differ. New Frailty categories might reflect its "continuum" better and predict ICU outcome more accurately. TRIAL REGISTRATION: Open Science Framework (OSF: https://osf.io/8buwk/ ).

Efficacy and tolerability of rizatriptan in pediatric migraineurs: results from a randomized, double-blind, placebo-controlled trial using a novel adaptive enrichment design.

BACKGROUND: Treatment options for children and adolescents with migraine are limited. This study evaluated rizatriptan for the acute treatment of migraine in children and adolescents. METHODS: Randomized, double-blind, placebo-controlled, parallel-group trial in migraineurs 6-17 years old with unsatisfactory response to nonsteroidal anti-inflammatory drugs or acetaminophen/paracetamol. The trial included a double-blind run-in with weight-based rizatriptan dosing (5 mg for < 40 kg, 10 mg for ≥ 40 kg). In the Stage 1 run-in, patients were randomized in a ratio of 20:1 placebo:rizatriptan and were instructed to treat within 30 minutes of a moderate/severe migraine. Patients with mild/no pain after 15 minutes of treatment (responders) took no further study medication, whereas patients with moderate/severe pain (non-responders) proceeded to take study medication in Stage 2. Non-responders who received placebo in Stage 1 were randomized 1:1 to rizatriptan:placebo, whereas non-responders who received rizatriptan in Stage 1 were allocated to placebo in Stage 2. The primary efficacy endpoint was pain freedom at 2 hours after Stage 2 dose in 12-17-year-olds. RESULTS: A higher proportion of 12-17-year-olds on rizatriptan had pain freedom at 2 hours compared with those on placebo: 87/284 (30.6%) versus 63/286 (22.0%), odds ratio = 1.55 [95% CI: 1.06 to 2.26], p = 0.025. Adverse events within 14 days of dose in 12-17-year-olds were similar for rizatriptan and placebo. The pattern of findings was similar in 6-17-year-olds. CONCLUSION: Rizatriptan demonstrated a statistically significant improvement over placebo in eliminating pain and was generally well tolerated in migraineurs aged 12-17 and 6-17 years. TRIAL REGISTRATION: ClinicalTrials.gov NCT01001234.

Reconstructing the early evolution of Fungi using a six-gene phylogeny.

The ancestors of fungi are believed to be simple aquatic forms with flagellated spores, similar to members of the extant phylum Chytridiomycota (chytrids). Current classifications assume that chytrids form an early-diverging clade within the kingdom Fungi and imply a single loss of the spore flagellum, leading to the diversification of terrestrial fungi. Here we develop phylogenetic hypotheses for Fungi using data from six gene regions and nearly 200 species. Our results indicate that there may have been at least four independent losses of the flagellum in the kingdom Fungi. These losses of swimming spores coincided with the evolution of new mechanisms of spore dispersal, such as aerial dispersal in mycelial groups and polar tube eversion in the microsporidia (unicellular forms that lack mitochondria). The enigmatic microsporidia seem to be derived from an endoparasitic chytrid ancestor similar to Rozella allomycis, on the earliest diverging branch of the fungal phylogenetic tree.

The FRAIL-FIT 30 Study - Factors influencing 30-day mortality in frail patients admitted to ICU: A retrospective observational cohort study.

Background: Frailty is a multi-dimensional syndrome of reduced reserve, resulting from overlapping physiological decrements across multiple systems. The contributing factors, temporality and magnitude of frailty's effect on mortality after ICU admission are unclear. This study assessed frailty's impact on mortality and life sustaining therapy (LST) use, following ICU admission. Methods: This single-centre retrospective observational cohort study analysed data collected prospectively in Glasgow Royal Infirmary ICU. Of 684 eligible patients, 171 were frail and 513 were non-frail. Frailty was quantified using the Rockwood Clinical Frailty Scale (CFS). All patients were followed up 1-year after ICU admission. The primary outcome was all-cause mortality at 30-days post-ICU admission. Key secondary outcomes included mortality at 1-year and LST use. Results: Frail patients were significantly less likely to survive 30-days post-ICU admission (61.4% vs 81.1%, p < 0.001). This continued to 1-year (48.5% vs 68.2%, p < 0.001). Frailty significantly increased mortality hazards in covariate-adjusted analyses at 30-days (HR 1.56; 95%CI 1.14-2.15; p = 0.006), and 1-year (HR 1.35; 95%CI 1.03-1.76; p = 0.028). Single-point CFS increases were associated with a 30-day mortality hazard of 1.23 (95%CI 1.13-1.34; p < 0.001) in unadjusted analyses, and 1.11 (95%CI 1.01-1.22; p = 0.026) after covariate adjustment. Frail patients received significantly more days of LST (median[IQR]: 5[3,11] vs 4[2,9], p = 0.008). Conclusion: Frailty was significantly associated with greater mortality at all time points studied, but most notably in the first 30-days post-ICU admission. This was despite greater LST use. The accrual effect of frailty increased adverse outcomes. Point-by-point use of frailty scoring could allow for more informed decision making in ICU.

Animal use of fence crossings in southwestern rangelands.

Net-wire fencing built to confine livestock is common on rangelands in the Southwestern USA, yet the impacts of livestock fencing on wildlife are largely unknown. Many wildlife species cross beneath fences at defined crossing locations because they prefer to crawl underneath rather than jump over fences. Animals occasionally become entangled jumping or climbing over fences, leading to injury or death. More commonly, repeated crossings under net-wire fencing by large animals lead to fence damage, though the damage is often tolerated by landowners until the openings affect the ability to enclose livestock. The usage, placement, characteristics, and passage rates of fence crossings beneath net-wire fencing are poorly understood. We monitored 20 randomly selected fence crossings on net-wire livestock fencing across two study sites on rangelands in South Texas, USA, from April 2018 to March 2019. We assessed the characteristics of fence-crossing locations (openings beneath the fence created by animals to aid in crossing) and quantified crossing rates and the probability of crossing by all species of animals via trail cameras. We documented 10,889 attempted crossing events, with 58% (n = 6271) successful. Overall, 15 species of medium- and large-size mammals and turkey (Meleagris gallopavo) contributed to crossing events. Crossing locations received 3-4 crossing attempts per day on average, but the number of attempts and probability of successful crossing varied by location and fence condition. The probability of crossing attempts was most consistently influenced by the opening size of the crossing and season; as crossing size (opening) increased, the probability of successful crossing significantly increased for all species. Peaks in crossing activity corresponded with species' daily and seasonal movements and activity. The density and size of fence-crossing locations were dependent on fence maintenance and not associated with vegetation communities or habitat variables. However, crossing locations were often re-established in the same locations after fence repairs. This is one of the few studies to monitor how all animal species present interacted with net-wire livestock fencing in rangelands. Our results will help land managers understand the impact of net-wire livestock fencing on animal movement.

Randomized controlled trial of the CGRP receptor antagonist MK-3207 in the acute treatment of migraine.

BACKGROUND: This study evaluated the CGRP receptor antagonist MK-3207 for acute treatment of migraine. METHODS: Multicenter, double-blind, randomized, placebo-controlled, parallel-group, two-stage adaptive study with two interim efficacy analyses to facilitate optimal dose selection. Migraine patients were initially randomized to MK-3207 2.5, 5, 10, 20, 50 and 100 mg or placebo to treat a moderate/severe migraine. One or more doses were to be discontinued based on the first interim analysis and a lower or higher dose could be added based on the second interim analysis. The primary endpoint was two-hour pain freedom. RESULTS: A total of 547 patients took study medication. After the first interim analysis, the two lowest MK-3207 doses (2.5, 5 mg) were identified as showing insufficient efficacy. Per the pre-specified adaptive design decision rule, only the 2.5-mg group was discontinued and the five highest doses (5, 10, 20, 50, 100 mg) were continued into the second stage. After the second interim efficacy analysis, a 200 mg dose was added due to insufficient efficacy at the top three (20, 50, 100 mg) doses. A positive dose-response trend was demonstrated when data were combined across all MK-3207 doses for two-hour pain freedom (p < .001). The pairwise difference versus placebo for two-hour pain freedom was significant for 200 mg (p < .001) and nominally significant for 100 mg and 10 mg (p < .05). The incidence of adverse events appeared comparable between active treatment groups and placebo, and did not appear to increase with increasing dose. CONCLUSIONS: MK-3207 was effective and generally well tolerated in the acute treatment of migraine.

Efficacy and tolerability of rizatriptan for the treatment of acute migraine in sumatriptan non-responders.

OBJECTIVE: The study was carried out to assess the efficacy and tolerability of rizatriptan orally disintegrating tablet (ODT) for treating acute migraine in patients who are non-responders to sumatriptan. BACKGROUND: Many migraineurs report dissatisfaction with sumatriptan efficacy. It is unclear whether sumatriptan 100 mg non-responders will respond to other triptans. METHODS: This was a randomized, placebo-controlled, double-blind study in adults with >1-year history of ICHD-II (International Classification of Headache Disorders, second edition) migraine who reported that they generally do not respond to sumatriptan (≥50% unsatisfactory response). In the baseline phase, participants treated a single moderate/severe migraine attack with open-label generic sumatriptan 100 mg. Those who continued to experience moderate/severe pain at two hours post-dose were eligible to enter the double-blind treatment phase, during which participants treated three migraine attacks in crossover fashion (two with rizatriptan 10-mg ODT, one with placebo) after being randomly assigned to one of three treatment sequences (1 : 1 : 1 ratio). The primary endpoint was two-hour pain relief. RESULTS: A total of 102 (94%) participants treated at least one study migraine. Pain relief at two hours was significantly greater with rizatriptan compared with placebo (51% vs. 20%, p < .001). Response rates also favored rizatriptan on two-hour pain freedom (22% vs. 12%, p = .013) as well as 24-hour sustained pain relief (38% vs. 14%, p < .001) and sustained pain freedom (20% vs. 11%, p = .036). Treatment was generally well tolerated. CONCLUSION: Rizatriptan 10-mg ODT was superior to placebo at providing two-hour pain relief and two-hour pain freedom in the treatment of acute migraine in those who do not respond to sumatriptan 100 mg. Rizatriptan was generally well tolerated in this population.

Randomized controlled study of telcagepant plus ibuprofen or acetaminophen in migraine.

OBJECTIVE: To evaluate the efficacy and tolerability of telcagepant when co-administered with ibuprofen or acetaminophen for the acute treatment of migraine. BACKGROUND: Telcagepant is an oral calcitonin gene-related peptide receptor antagonist which is being evaluated for the acute treatment of migraine. Combining telcagepant with analgesics that have a different mechanism of action could produce greater efficacy. METHODS: Randomized, double-blind, placebo-controlled study. Patients were randomized to treat a moderate or severe migraine headache with either telcagepant 280 mg + ibuprofen 400 mg (N = 171), telcagepant 280 mg + acetaminophen 1000 mg (N = 171), telcagepant 280 mg (N =170), or placebo (N = 171). The primary efficacy endpoint was 2-hour pain freedom. The study had approximately 88% power to detect an additive effect of at least 15 percentage points (telcagepant combination vs telcagepant monotherapy) and 48% power to detect an additive effect of at least 10 percentage points. Safety and tolerability were assessed by adverse events and laboratory tests. RESULTS: The percentages of patients with 2-hour pain freedom were greater in each active treatment group compared to placebo (P < .001): telcagepant + ibuprofen = 35.2%, telcagepant + acetaminophen = 38.3%, telcagepant = 31.2%, placebo = 10.9%. No significant differences were seen for either of the combination groups vs telcagepant monotherapy, but both were numerically larger than telcagepant monotherapy. All the active treatments were generally well tolerated. The percentage of patients reporting any adverse event within 48 hours was higher in the active treatment groups than placebo: telcagepant + ibuprofen = 30.3%, telcagepant + acetaminophen = 31.6%, telcagepant = 24.8%, placebo = 18.2%. The most common adverse events reported by ≥ 4 patients in one or more of the treatment groups that included telcagepant were fatigue, nausea, dizziness, somnolence, dry mouth, and tremor. CONCLUSIONS: The combination of telcagepant 280 mg with either ibuprofen 400 mg or acetaminophen 1000 mg did not show a statistically significant difference from telcagepant alone. Numerically greater treatment effects in the combination treatment groups over the telcagepant 280 mg monotherapy suggest that telcagepant combination treatments may merit further evaluation in studies powered to detect smaller additive benefits. (Clinicaltrials.gov; NCT00758836).

Can Reactive Airways Dysfunction Syndrome (RADS) be iatrogenic?

Reactive airways dysfunction syndrome (RADS) is an asthma-like illness that develops after a single high-level exposure to a pulmonary irritant. Two different cases are reviewed, in which the exposure circumstances were not sufficient to result in adverse health effects yet resulted in persistent respiratory symptoms and a clinical diagnosis of RADS. Potential explanations for an erroneous diagnosis of RADS included an incomplete exposure assessment, medication adverse effects that can contribute to respiratory symptoms, and alternative explanations for respiratory symptoms or test findings. In particular, the empirical use of bronchodilator medications without a clear indication appeared to contribute to continued respiratory symptoms. Without a clear understanding of the patient's exposure, a RADS diagnosis should be carefully considered. The possibility of an iatrogenic sequence of events in which medication adverse effects facilitate respiratory symptoms and a mistaken RADS diagnosis should be considered, particularly in patients who have a poorly defined exposure history.

The value of HAZWOPER medical surveillance.

Medical surveillance is mandated for workers with potential exposure to hazardous materials. However, little guidance is provided regarding the components of a medical surveillance testing program for these individuals. This article describes the medical surveillance program for a group of 72 employees who respond to hazardous material releases throughout the United States. Conditions related to chemical exposures were not identified in this group. However, several non-occupational health conditions were identified, including a relatively high prevalence of one or more signs of metabolic syndrome. Medical surveillance may provide valuable information regarding an individual's underlying health status and non-occupational health conditions to be addressed at an early stage.

Amine-Catalyzed Chain Polymerization of Ethyl Glyoxylate from Alcohol and Thiol Initiators.

Polyacetals have significant potential as degradable polymers, but aldehyde polymerizations are generally difficult to control. Here we show that polymerization of ethyl glyoxylate can be initiated from alcohols or thiols by activation with triethylamine to afford poly(ethyl glyoxylate) with controllable molecular weights and relatively low dispersities (D = 1.3-1.4), as evidenced by MALDI-TOF mass spectrometry. Stabilization against depolymerization by chain-capping with benzyl chloroformate was found to proceed without side reactions observed from chain-capping with tolyl isocyanate. The use of the stronger base DBU leads to competing side reactions that limit polymer molecular weight.