Tip of the iceberg: extracardiac CT findings in infective endocarditis.

Infective endocarditis (IE) is a disease with high morbidity and mortality rate, but diagnosis is confounded by diverse clinical presentations, which mimic other pathologies. A history of illicit intravenous drug use, previous cardiac valve surgery, and indwelling intracardiac devices increases the risk for developing infective endocarditis. The modified Duke criteria serve as the standard diagnostic tool, though its accuracy is reduced in certain cases. Radiologists in the Emergency Room setting reading body CT may be the first to identify the secondary extra-cardiac complications and facilitate expeditious management by considering otherwise unsuspected infective endocarditis. This review highlights common extracardiac complications of IE and their corresponding CT findings in the chest, abdomen, pelvis, and brain. If IE is suspected radiologists should suggest further investigation with echocardiography.

Conservation genomics of an endangered montane amphibian reveals low population structure, low genomic diversity and selection pressure from disease.

Wildlife diseases are a major global threat to biodiversity. Boreal toads (Anaxyrus [Bufo] boreas) are a state-endangered species in the southern Rocky Mountains of Colorado and New Mexico, and a species of concern in Wyoming, largely due to lethal skin infections caused by the amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd). We performed conservation and landscape genomic analyses using single nucleotide polymorphisms from double-digest, restriction site-associated DNA sequencing in combination with the development of the first boreal toad (and first North American toad) reference genome to investigate population structure, genomic diversity, landscape connectivity and adaptive divergence. Genomic diversity (π = 0.00034-0.00040) and effective population sizes (Ne = 8.9-38.4) were low, likely due to post-Pleistocene founder effects and Bd-related population crashes over the last three decades. Population structure was also low, likely due to formerly high connectivity among a higher density of geographically proximate populations. Boreal toad gene flow was facilitated by low precipitation, cold minimum temperatures, less tree canopy, low heat load and less urbanization. We found >8X more putatively adaptive loci related to Bd intensity than to all other environmental factors combined, and evidence for genes under selection related to immune response, heart development and regulation and skin function. These data suggest boreal toads in habitats with Bd have experienced stronger selection pressure from disease than from other, broad-scale environmental variations. These findings can be used by managers to conserve and recover the species through actions including reintroduction and supplementation of populations that have declined due to Bd.

A multicenter prospective evaluation of owner medication adherence for feline cardiovascular disease in the referral setting.

OBJECTIVE: The aim of this paper is to evaluate owners' chronic medication adherence for management of feline cardiovascular disease in the small animal referral setting. ANIMALS, MATERIALS AND METHODS: A questionnaire-based study of owners at five multispecialty, small animal referral centers was conducted. Owners completed a written survey evaluating demographics, degree of medication adherence, and difficulties encountered for medication adherence. Owners were free to decline participation in the study. RESULTS: Fifty-four questionnaires were available for review. The most common diagnosis was hypertrophic cardiomyopathy (n = 31, 57.4%). Clopidogrel was the most cited medication that was difficult to administer consistently (n = 13, 24.0%) although twenty owners (37.0%) reported no difficulty consistently administering medications. "Taste of medication" (n = 14, 25.9%) was the most reported reason for difficulty medicating their cat, and most owners (n = 36, 66.7%) stated twice daily was the highest frequency of heart medications they feel they can consistently administer. Fifty owners (92.6%) met the criteria for medication adherence. CONCLUSIONS: Chronic medication adherence in this study population was high. Clopidogrel was the most difficult medication to consistently administer, and twice a day dosing was the highest frequency of medication administration most owners could achieve. Cardiologists should be aware of these factors when determining optimal treatment protocols for the management of cardiovascular disease in cats.

Impact of Increased Enoxaparin Dosing on Anti-Xa Levels for Venous Thromboembolism Prophylaxis in Trauma Patients.

INTRODUCTION: Venous thromboembolism (VTE) contributes to significant morbidity in trauma patients while increasing hospital costs and length of stay. Standard trauma prophylaxis dosing with enoxaparin 30 mg twice daily may be inadequate to prevent VTEs. The objective of this study was to compare standard dosing of enoxaparin to an increased dose of enoxaparin 40 mg twice daily for trauma patients. We hypothesized that increasing thromboprophylaxis dosing leads to an increase in therapeutic anti-Xa levels and reduced VTE rates. METHODS: A retrospective study was performed from January 2020 to June 2021 at a Level I trauma center, following implementation of an increased enoxaparin dosing strategy. Patients with increased enoxaparin dosing were compared with those who received standard dosing. The primary outcome evaluated was the incidence of subtherapeutic anti-Xa levels. Secondary outcomes evaluated VTE rates and clinically significant bleed. RESULTS: A total of 204 trauma patients were identified. Ninety-one patients received an increased enoxaparin dose compared to 113 who received standard dosing. The baseline demographics of both groups were similar (P > .05). Subtherapeutic levels were higher with standard dosing compared to the increased dose (50 vs 22%, P = .003). Higher VTE rates were observed with standard dosing compared to higher dosing (6.2 vs 3.3%) but with a lower incidence of major bleed (1.8 vs 4.4%). Overall annual VTE rates decreased from 1.6 to 1.3% after implementation of the increased dosing regimen. CONCLUSIONS: This study demonstrated that an increased dosing strategy decreased rates of subtherapeutic anti-Xa levels and trended toward lower overall VTE rates in trauma.

Stab Wound to the Right Ventricle With Creation of Ventricular Septal Defect Managed With an Endovascular Occlusive Patch.

Penetrating trauma to the cardiac box is associated with high rates of cardiac injury, structural complications, morbidity, and mortality. Early identification and intervention of these injuries is paramount to obtaining good patient outcomes. In this paper, we report a 55-year-old male who sustained a single stab wound to left chest which perforated the right ventricle. The patient also sustained a muscular ventricular septal defect (VSD) which led to a prolonged intensive care unit (ICU) course complicated by late pericardial tamponade. We present successful management of this patient's initial injury along with his ICU course culminating in successful endovascular occlusive patch VSD repair.

Prognostic value of strain by feature-tracking cardiac magnetic resonance in arrhythmogenic right ventricular cardiomyopathy.

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by ventricular dysfunction and ventricular arrhythmias (VA). Adequate arrhythmic risk assessment is important to prevent sudden cardiac death. We aimed to study the incremental value of strain by feature-tracking cardiac magnetic resonance imaging (FT-CMR) in predicting sustained VA in ARVC patients. METHODS AND RESULTS: CMR images of 132 ARVC patients (43% male, 40.6 ± 16.0 years) without prior VA were analysed for global and regional right and left ventricular (RV, LV) strain. Primary outcome was sustained VA during follow-up. We performed multivariable regression assessing strain, in combination with (i) RV ejection fraction (EF); (ii) LVEF; and (iii) the ARVC risk calculator. False discovery rate adjusted P-values were given to correct for multiple comparisons and c-statistics were calculated for each model. During 4.3 (2.0-7.9) years of follow-up, 19% of patients experienced sustained VA. Compared to patients without VA, those with VA had significantly reduced RV longitudinal (P ≤ 0.03) and LV circumferential (P ≤ 0.04) strain. In addition, patients with VA had significantly reduced biventricular EF (P ≤ 0.02). After correcting for RVEF, LVEF, and the ARVC risk calculator separately in multivariable analysis, both RV and LV strain lost their significance [hazard ratio 1.03-1.18, P > 0.05]. Likewise, while strain improved the c-statistic in combination with RVEF, LVEF, and the ARVC risk calculator separately, this did not reach statistical significance (P ≥ 0.18). CONCLUSION: Both RV longitudinal and LV circumferential strain are reduced in ARVC patients with sustained VA during follow-up. However, strain does not have incremental value over RVEF, LVEF, and the ARVC VA risk calculator.

The Impact of FASTPASS: A Collaboration With Emergency Department to Improve Management of Patients With Gallbladder Disease and Acute Appendicitis.

BACKGROUND: Efficient Emergency Department (ED) throughput depends on several factors, including collaboration and consultation with surgical services. The acute care surgery service (ACS) collaborated with ED to implement a new process termed "FASTPASS" (FP), which might improve patient-care for those with acute appendicitis and gallbladder disease. The aim of this study was to evaluate the 1-year outcome of FP. METHODS: FASTPASS is a joint collaboration between ACS and ED. ED physicians were provided with a simple check-list for diagnosing young males (<50-year old) with acute appendicitis (AA) and young males or females (<50-year old) with gallbladder disease (GBD). Once ED deemed patients fit our FP check-list, patients were directly admitted (FASTPASSed) to the observation unit. The ACS then came to evaluate the patients for possible surgical intervention. We performed outcome analysis before and after the institution of the FP. Outcomes of interest were ED length of stay (LOS), time from ED to the operating room (OR) (door-to-knife), hospital LOS (HLOS), and cost. RESULTS: During our 1-year study period, for those patients who underwent GBD/AA surgery, 56 (26%) GBD and 27 (26%) AA patients met FP criteria. Compared to the non-FP patients during FP period, FP halved ED LOS for GBD (7.4 ± 3.0 versus 3.5 ± 1.7 h, P < 0.001) and AA (6.7 ± 3.3 versus. 1.8 ± 1.6 h, P < 0.001). Similar outcome benefits were observed for door-to-knife time, HLOS, and costs. CONCLUSIONS: In this study, the FP process improved ED throughput in a single, highly-trained ER leading to an overall improved patient care process. A future study involving multiple EDs and different disease processes may help decrease ED overcrowding and improve healthcare system efficiency.

Enhanced design considerations on the buckling and dynamics of Gannet-inspired systems during water entry.

To provide a more complete analysis of Gannet birds and Gannet-inspired drones during diving, this work considers an improved beam model to describe the static and dynamic characteristics of Gannet and Gannet-like drones at impact. The beam model consists of two different geometric and material property beams under continuity conditions to better understand the geometrical and material parameters' influence on the structural statics and dynamics of these kinds of systems. Using Hamilton's principle, the equations of motion, continuity, and boundary conditions considering Euler-Bernoulli and Timoshenko theories are derived. Then, applying the continuity and boundary conditions, the static and dynamic analyses are conducted to examine the impact buckling speeds, the buckled shapes, the natural frequencies at different impact velocities for bioinspired drone design, and the post-buckled mode shapes. The buckled configurations suggest that the body of the Gannet most likely has a different bending and torsional stiffness than the neck. The results indicate that the amount of softening in the joints contributes significantly to not only the speed at which the bird will buckle, but also the buckling profile of the bird. To obtain a physical buckling profile of the Gannet, a stiffer boundary condition at the end of the bird body model is needed due to the increased bending stiffness properties of the body compared to the neck as well as the position of the wings and feet surpassing the end of the body. The results also demonstrate that to build a bioinspired diving drone that falls within a smaller air-vehicle range, the amount of error between theories in predicting the static and dynamic buckling behavior of the system becomes significantly more evident. The dynamic characteristics and mode shapes of the Gannet-like systems are provided for further drone design insight on the impact speeds the drone can achieve without responding to an external excitation frequency from a propeller or actuator.

Investigations on the buckling and dynamics of diving-inspired systems when entering water.

This work provides comparative modeling approaches to determine the velocities and natural frequencies of plunge-diving bird and bioinspired drone systems when entering water. These systems are chosen to further explain the survival of diving birds as they impact water and to provide insight into the design geometry and material choice of bioinspired diving drones. A nonlinear reduced-order model is developed and utilized to analyze the dive at impact considering both Timoshenko and Euler-Bernoulli beam theories. Using Hamilton's principle, the equations of motion are first derived. Then, static and dynamic buckling analyses are conducted. For this study, a geometrically simplified cone-beam system is considered, where the cone represents the head and the beam represents both the neck and body of the plunge-diving systems. The first study is to analyze the effects different diving drone materials and cone dimensions play on the sensitivity of the system. The second study applies geometric parameters to the cone-beam system representative of a plunge-diving bird (Northern gannet) and a surface-diving bird (Double-crested cormorant). The results show that choosing a material with a higher Young's modulus and a cone with a smaller half angle increase the velocity at which buckling occurs. The buckling velocities of the predicted Northern gannet model appear to be much greater than the average recorded diving speeds, suggesting that the bird is capable of plunge-diving at more extreme conditions. The natural frequencies are found for the aforementioned plunge-diving systems to predict failure if any external frequencies are known to act on the system while on a mission, such as conditions dependent on the climate or environment. It is shown in all buckling studies that the Euler-Bernoulli beam theory consistently overestimates the responses when compared with the Timoshenko beam theory. In the dynamic responses, Euler-Bernoulli beam theory overestimates for the pre-buckling region, then underestimates at the start of the post-buckling region until a point where the two theories cross paths. The amount of error with Euler-Bernoulli beam theory depends heavily on the slenderness ratio of the beam due to the theory being a simplification of the Timoshenko beam theory. It is noted that as the development of a more realistic bird model improves, the thickness will become significant and the use of Euler-Bernoulli beam theory at the point of impact will no longer be a valid assumption.

Nonlinear modeling and experimental verification of Gannet-inspired beam systems during diving.

A nonlinear model is proposed to answer at which diving speeds and beak angles will cause injury to Gannet-inspired beam systems during plunge-diving. In doing so, the critical velocities at which buckling occurs with various types of boundary conditions are first obtained for vertical dives and the resulting forces at the point of impact are determined. The Gannet-inspired system is modeled as an Euler-Bernoulli beam to represent the neck and body of the Gannet, while the head of the Gannet is modeled as a cone with varying half-angles. The experimental investigations of Gannet-like diving systems are first introduced to present the varying parameters and assumptions of the simplified model. Next, the resulting forces during impact are investigated and a study is conducted to compare various approximations of the drag coefficient for the cone-shaped head. Considering the mid-plane stretching nonlinearity, the equations of motion for the structural system under various types of boundary conditions are derived using the Hamilton's principle. The characteristic equations, buckled configurations, and critical velocities are determined for each set of boundary conditions. The results show that the system with the smallest half-beak angle and thus the lowest drag force and beam length delays the critical velocity and is most representative of a Gannet during diving. The obtained results demonstrate great agreement with the conducted experiments. For clamped-clamped boundary conditions, the critical velocity is found to be the greatest because of the increased stability at both ends of the beam. It is also noted that a nonlinear approximation for the coefficient of drag offers the best fit with the provided experimental values when compared to a hyperbolic tangent approximation, which predicts the coefficient of drag to be less than that obtained in experiments, and thus predicts that the systems will buckle at higher velocities.

Engineering and Application of LOV2-Based Photoswitches.

Cellular optogenetic switches, a novel class of biological tools, have improved our understanding of biological phenomena that were previously intractable. While the design and engineering of these proteins has historically varied, they are all based on borrowed elements from plant and bacterial photoreceptors. In general terms, each of the optogenetic switches designed to date exploits the endogenous light-induced change in photoreceptor conformation while repurposing its effect to target a different biological phenomenon. We focus on the well-characterized light-oxygen-voltage 2 (LOV2) domain from Avena sativa phototropin 1 as our cornerstone for design. While the function of the LOV2 domain in the context of the phototropin protein is not fully elucidated, its thorough biophysical characterization as an isolated domain has created a strong foundation for engineering of photoswitches. In this chapter, we examine the biophysical characteristics of the LOV2 domain that may be exploited to produce an optogenetic switch and summarize previous design efforts to provide guidelines for an effective design. Furthermore, we provide protocols for assays including fluorescence polarization, phage display, and microscopy that are optimized for validating, improving, and using newly designed photoswitches.

Use of short-term breath measures to estimate daily methane production by cattle.

Methods to measure enteric methane (CH4) emissions from individual ruminants in their production environment are required to validate emission inventories and verify mitigation claims. Estimates of daily methane production (DMP) based on consolidated short-term emission measurements are developing, but method verification is required. Two cattle experiments were undertaken to test the hypothesis that DMP estimated by averaging multiple short-term breath measures of methane emission rate did not differ from DMP measured in respiration chambers (RC). Short-term emission rates were obtained from a GreenFeed Emissions Monitoring (GEM) unit, which measured emission rate while cattle consumed a dispensed supplement. In experiment 1 (Expt. 1), four non-lactating cattle (LW=518 kg) were adapted for 18 days then measured for six consecutive periods. Each period consisted of 2 days of ad libitum intake and GEM emission measurement followed by 1 day in the RC. A prototype GEM unit releasing water as an attractant (GEM water) was also evaluated in Expt. 1. Experiment 2 (Expt. 2) was a larger study based on similar design with 10 cattle (LW=365 kg), adapted for 21 days and GEM measurement was extended to 3 days in each of the six periods. In Expt. 1, there was no difference in DMP estimated by the GEM unit relative to the RC (209.7 v. 215.1 g CH(4)/day) and no difference between these methods in methane yield (MY, 22.7 v. 23.7 g CH(4)/kg of dry matter intake, DMI). In Expt. 2, the correlation between GEM and RC measures of DMP and MY were assessed using 95% confidence intervals, with no difference in DMP or MY between methods and high correlations between GEM and RC measures for DMP (r=0.85; 215 v. 198 g CH(4)/day SEM=3.0) and for MY (r=0.60; 23.8 v. 22.1 g CH(4)/kg DMI SEM=0.42). When data from both experiments was combined neither DMP nor MY differed between GEM- and RC-based measures (P>0.05). GEM water-based estimates of DMP and MY were lower than RC and GEM (P<0.05). Cattle accessed the GEM water unit with similar frequency to the GEM unit (2.8 v. 3.5 times/day, respectively) but eructation frequency was reduced from 1.31 times/min (GEM) to once every 2.6 min (GEM water). These studies confirm the hypothesis that DMP estimated by averaging multiple short-term breath measures of methane emission rate using GEM does not differ from measures of DMP obtained from RCs. Further, combining many short-term measures of methane production rate during supplement consumption provides an estimate of DMP, which can be usefully applied in estimating MY.

Effect of home-based light treatment on persons with dementia and their caregivers.

Sleep disorders are problematic for persons with dementia and their family caregivers. This randomized controlled trial with crossover evaluated the effects of an innovative blue-white light therapy on 17 pairs of home-dwelling persons with dementia and their caregivers. Subjects with dementia received blue-white light and control ('red-yellow' light) for six weeks separated by a four-week washout. Neither actigraphic nor most self-reported sleep measures significantly differed for subjects with dementia. For caregivers, both sleep and role strain improved. No evidence of retinal light toxicity was observed. Six weeks of modest doses of blue-white light appear to improve sleep in caregivers but not in persons with dementia. Greater or prolonged circadian stimulation may be needed to determine if light is an effective treatment for persons with dementia.

Comparison of methods to determine methane emissions from dairy cows in farm conditions.

Nutritional and animal-selection strategies to mitigate enteric methane (CH4) depend on accurate, cost-effective methods to determine emissions from a large number of animals. The objective of the present study was to compare 2 spot-sampling methods to determine CH4 emissions from dairy cows, using gas quantification equipment installed in concentrate feeders or automatic milking stalls. In the first method (sniffer method), CH4 and carbon dioxide (CO2) concentrations were measured in close proximity to the muzzle of the animal, and average CH4 concentrations or CH4/CO2 ratio was calculated. In the second method (flux method), measurement of CH4 and CO2 concentration was combined with an active airflow inside the feed troughs for capture of emitted gas and measurements of CH4 and CO2 fluxes. A muzzle sensor was used allowing data to be filtered when the muzzle was not near the sampling inlet. In a laboratory study, a model cow head was built that emitted CO2 at a constant rate. It was found that CO2 concentrations using the sniffer method decreased up to 39% when the distance of the muzzle from the sampling inlet increased to 30cm, but no muzzle-position effects were observed for the flux method. The methods were compared in 2 on-farm studies conducted using 32 (experiment 1) or 59 (experiment 2) cows in a switch-back design of 5 (experiment 1) or 4 (experiment 2) periods for replicated comparisons between methods. Between-cow coefficient of variation (CV) in CH4 was smaller for the flux than the sniffer method (experiment 1, CV=11.0 vs. 17.5%, and experiment 2, 17.6 vs. 28.0%). Repeatability of the measurements from both methods were high (0.72-0.88), but the relationship between the sniffer and flux methods was weak (R(2)=0.09 in both experiments). With the flux method CH4 was found to be correlated to dry matter intake or body weight, but this was not the case with the sniffer method. The CH4/CO2 ratio was more highly correlated between the flux and sniffer methods (R(2)=0.30), and CV was similar (6.4-8.8%). In experiment 2, cow muzzle position was highly repeatable (0.82) and influenced sniffer and flux method results when not filtered for muzzle position. It was concluded that the flux method provides more reliable estimates of CH4 emissions than the sniffer method. The sniffer method appears to be affected by variable air-mixing conditions created by geometry of feed trough, muzzle movement, and muzzle position.

Further Evidence of Contrasting Phenotypes Caused by Reciprocal Deletions and Duplications: Duplication of NSD1 Causes Growth Retardation and Microcephaly.

Microduplications of the Sotos syndrome region containing NSD1 on 5q35 have recently been proposed to cause a syndrome of microcephaly, short stature and developmental delay. To further characterize this emerging syndrome, we report the clinical details of 12 individuals from 8 families found to have interstitial duplications involving NSD1, ranging in size from 370 kb to 3.7 Mb. All individuals are microcephalic, and height and childhood weight range from below average to severely restricted. Mild-to-moderate learning disabilities and/or developmental delay are present in all individuals, including carrier family members of probands; dysmorphic features and digital anomalies are present in a majority. Craniosynostosis is present in the individual with the largest duplication, though the duplication does not include MSX2, mutations of which can cause craniosynostosis, on 5q35.2. A comparison of the smallest duplication in our cohort that includes the entire NSD1 gene to the individual with the largest duplication that only partially overlaps NSD1 suggests that whole-gene duplication of NSD1 in and of itself may be sufficient to cause the abnormal growth parameters seen in these patients. NSD1 duplications may therefore be added to a growing list of copy number variations for which deletion and duplication of specific genes have contrasting effects on body development.

Ubiquitin-activating enzyme (UBA1) is required for sperm capacitation, acrosomal exocytosis and sperm-egg coat penetration during porcine fertilization.

Protein ubiquitination is a stable, covalent post-translational modification that alters protein activity and/or targets proteins for proteolysis by the 26S proteasome. The E1-type ubiquitin-activating enzyme (UBA1) is responsible for ubiquitin activation, the initial step of ubiquitin-protein ligation. Proteasomal proteolysis of ubiquitinated spermatozoa and oocyte proteins occurs during mammalian fertilization, particularly at the site of sperm acrosome contact with oocyte zona pellucida. However, it is not clear whether the substrates are solely proteins ubiquitinated during gametogenesis or if de novo ubiquitination also occurs during fertilization supported by ubiquitin-activating and -conjugating enzymes present in the sperm acrosome. Along this line of inquiry, UBA1 was detected in boar sperm-acrosomal extracts by Western blotting (WB). Immunofluorescence revealed accumulation of UBA1 in the nuclei of spermatogonia, spermatocytes and spermatids, and in the acrosomal caps of round and elongating spermatids. Thiol ester assays utilizing biotinylated ubiquitin and isolated sperm acrosomes confirmed the enzymatic activity of the resident UBA1. A specific UBA1 inhibitor, PYR-41, altered the remodelling of the outer acrosomal membrane (OAM) during sperm capacitation, monitored using flow cytometry of fluorescein isothiocyanate-conjugated peanut agglutinin (FITC-PNA). Although viable and motile, the spermatozoa capacitated in the presence of PYR-41, showed significantly reduced fertilization rates during in vitro fertilization (IVF; p < 0.05). Similarly, the fertilization rate was lowered by the addition of PYR-41 directly into fertilization medium during IVF. In WB, high Mr bands, suggestive of protein ubiquitination, were detected in non-capacitated spermatozoa by antibodies against ubiquitin; WB with anti-phosphotyrosine antibodies and antibodies against acrosomal proteins SPINK2 (acrosin inhibitor) and AQN1 (spermadhesin) revealed that the capacitation-induced modification of those proteins was altered by PYR-41. In summary, it appears that de novo protein ubiquitination involving UBA1 contributes to sperm capacitation and acrosomal function during fertilization.

Establishing the detection threshold for Bacillus subtilis in a complex matrix using an inorganic fingerprint approach.

Methods for the detection and characterization of airborne biological warfare agents, such as bacteria, using their DNA or organic composition are fairly well developed. This approach is useful for identifying the type of bacterial strain once the organism has been isolated from the matrix sampled (e.g., dust particles) and can identify genetically related organisms, which might be helpful during a forensic investigation. However, this genetic signature will not reveal information related to the methods used to grow and weaponize the organism. Bacteria will take on an inorganic signature that is related to their growth and processing history. Therefore, the ability to characterize the inorganic fingerprint of a biological particle has the potential to detect the presence of a bio-agent and expand the forensic tools available to those investigating the origin of biological weapons. This investigation builds on previous work documenting the usefulness of the inorganic fingerprint and evaluates the limits of detection in the presence of background dust. Based on ICP-MS measurements and mixing models of digested mixtures of laboratory cultured Bacillus subtilis (anthrax stimulant) and NIST Standard Reference Material 2709 (dust stimulant), the inorganic fingerprint method is capable of detecting toxicologically relevant levels of a bio-warfare agent in the presence of a complex background matrix.

Interaction of 5-HT2A and 5-HT2C receptors in R(-)-2,5-dimethoxy-4-iodoamphetamine-elicited head twitch behavior in mice.

Drug-elicited head-twitch behavior is a useful model for studying hallucinogen activity at 5-HT(2A) receptors in the mouse. Chemically diverse compounds active in this assay yield biphasic dose-effect curves, but there is no compelling explanation for the "descending" portion of these functions. A set of experiments was designed to test the hypothesis that the induction of head-twitch behavior is mediated by agonist actions at 5-HT(2A) receptors, whereas the inhibition of head-twitch behavior observed at higher doses results from competing agonist activity at 5-HT(2C) receptors. The effects of the phenethylamine hallucinogen R(-)-2,5-dimethoxy-4-iodoamphetamine (DOI) on head-twitch behavior were studied over a range of doses in the mouse, generating a characteristic biphasic dose-response curve. Pretreatment with the selective 5-HT(2A) antagonist (+)-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine-methanol (M100907) shifted only the ascending limb of the DOI dose-effect function, whereas pretreatment with the nonselective 5-HT(2A/2C) antagonist 3-{2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl}quinazoline-2,4(1H,3H)-dione (ketanserin) produced a parallel shift to the right in the DOI dose-response curve. Administration of the 5-HT(2C) agonist S-2-(chloro-5-fluoro-indol-l-yl)-1-methylethylamine (Ro 60-0175) noncompetitively inhibited DOI-elicited head-twitch behavior across the entire dose-effect function. Finally, pretreatment with the selective 5-HT(2C) antagonists 6-chloro-5-methyl-1-[(2-[2-methylpyrid-3-yloxy]pyrid-5yl)carbamoyl]indoline (SB242084) or 8-[5-(2,4-dimethoxy-5-(4-trifluoromethylphenylsulfonamido)phenyl-5-oxopentyl]-1,3,8-triazaspiro[4,5]decane-2,4-dione hydrochloride (RS 102221) did not alter DOI-elicited head-twitch behavior on the ascending limb of the dose-response curve but shifted the descending limb of the DOI dose-response function to the right. The results of these experiments provide strong evidence that DOI-elicited head-twitch behavior is a 5-HT(2A) agonist-mediated effect, with subsequent inhibition of head-twitch behavior being driven by competing 5-HT(2C) agonist activity.

Fabrication of guided-mode resonance elements by nanoimprint lithography.

This paper addresses utilization of nanoimprint lithography for fabrication of nanopatterned resonant photonic elements. These compact periodic films resonate sharply when illuminated with light. The attendant spectral and angular signatures are useful in design of photonic devices for various applications. It is of interest to design and optimize resonant leaky-mode elements with prescribed filtering, polarization, and security attributes. Applying nanoimprint lithography techniques, we fabricate prototype devices using polymer materials produced by Dymax Corporation. The initial prototypes are designed for use in the near-IR and telecommunications spectral regions. We apply holographic surface-relief gratings as master templates. With these templates, we have formed submasters in PDMS (polydimethylsiloxane) to function as imprint stamps for the soft lithography steps. Using these submasters, we fabricate periodic surfaces in UV-curable polymers with resonant films deposited on the surface by sputtering. Several example devices possessing resonance efficiencies exceeding 90% are presented along with their spectral and angular characteristics.