Three-dimensional tomographic reconstruction using Voronoi weighting.

Three-dimensional tomographic reconstruction requires careful selection of the illumination angles, often under certain measurement constraints. When the angular distribution must be nonuniform, appropriate selection of the reconstruction weights is necessary. We show that Voronoi weighting can significantly improve the fidelity of optical diffraction tomography.

Post-traumatic stress disorder prevalence and sleep quality in fire victims and rescue workers in southern Brazil: a cross-sectional study.

OBJECTIVES: This survey was conducted to evaluate the prevalence of post-traumatic stress disorder (PTSD) and the sleep quality in victims and rescue team of the third deadliest nightclub fire in the world. STUDY DESIGN: A cross-sectional study. METHODS: Participants were victims and rescue workers exposed to a fire at a nightclub, which occurred in January 2013 in Southern Brazil. The Pittsburgh Sleep Quality Index (PSQI), composed of seven subjective sleep variables (including daytime dysfunction), and PTSD Checklist - Civilian version (PCL-C) were applied to all people who sought medical attention at the local reference center in the first year after the event. Comprehensive information was obtained concerning sociodemographic factors, health status, and sleep complaints. RESULTS: A total of 370 individuals, 190 victims and 180 rescue workers, were included. Participants were 70% male, with an average age of 29 years. The prevalence of PTSD was 31.9%, ranging from 24.4% for rescue workers to 38.9% for victims. The prevalence of poor sleep quality was 65.9%, ranging from 56.1% for rescue workers to 75.3% for victims. Most of the participants with PTSD (91.5%) had PSQI scores >5 (poor sleepers), against 54.0% of the non-PTSD individuals. All seven PSQI subscores showed significant differences between PTSD and non-PTSD individuals, especially daytime dysfunction. Sex, shift work, previous psychiatric disease, and sleep quality remained associated with PTSD in adjusted models, with a prevalence ratio (95% CI) of 1.76 (1.28-2.43) in females, 1.73 (1.17-2.55) in shift workers, 1.36 (1.03-1.80) in individuals with psychiatric disease history, and 5.42 (2.55-11.52) in poor sleepers. CONCLUSIONS: The presence of daytime dysfunction increased by at least tenfold the prevalence of PTSD in this sample. Considering that daytime dysfunction was shown to be strongly associated with PTSD, sleep-related issues should be addressed in the assessment of individuals exposed to traumatic events, both victims and rescuers. Factors like shift work and female sex were also associated with PTSD, especially among victims.

Design of a 3000-Pixel Transition-Edge Sensor X-Ray Spectrometer for Microcircuit Tomography.

Feature sizes in integrated circuits have decreased substantially over time, and it has become increasingly difficult to three-dimensionally image these complex circuits after fabrication. This can be important for process development, defect analysis, and detection of unexpected structures in externally sourced chips, among other applications. Here, we report on a non-destructive, tabletop approach that addresses this imaging problem through x-ray tomography, which we uniquely realize with an instrument that combines a scanning electron microscope (SEM) with a transition-edge sensor (TES) x-ray spectrometer. Our approach uses the highly focused SEM electron beam to generate a small x-ray generation region in a carefully designed target layer that is placed over the sample being tested. With the high collection efficiency and resolving power of a TES spectrometer, we can isolate x-rays generated in the target from background and trace their paths through regions of interest in the sample layers, providing information about the various materials along the x-ray paths through their attenuation functions. We have recently demonstrated our approach using a 240 Mo/Cu bilayer TES prototype instrument on a simplified test sample containing features with sizes of ∼ 1 µm. Currently, we are designing and building a 3000 Mo/Au bilayer TES spectrometer upgrade, which is expected to improve the imaging speed by factor of up to 60 through a combination of increased detector number and detector speed.

Use of Transition Models to Design High Performance TESs for the LCLS-II Soft X-Ray Spectrometer.

We are designing an array of transition-edge sensor (TES) microcalorimeters for a soft X-ray spectrometer at the Linac Coherent Light Source at SLAC National Accelerator Laboratory to coincide with upgrades to the free electron laser facility. The complete spectrometer will have 1000 TES pixels with energy resolution of 0.5 eV full-width at half-maximum (FWHM) for incident energies below 1 keV while maintaining pulse decay-time constants shorter than 100 µs. Historically, TES pixels have often been designed for a particular scientific application via a combination of simple scaling relations and trial-and-error experimentation with device geometry. We have improved upon this process by using our understanding of transition physics to guide TES design. Using the two-fluid approximation of the phase-slip line model for TES resistance, we determine how the geometry and critical temperature of a TES will affect the shape of the transition. We have used these techniques to design sensors with a critical temperature of 55 mK. The best sensors achieve an energy resolution of 0.75 eV FWHM at 1.25 keV. Building upon this result, we show how the next generation of sensors can be designed to reach our goal of 0.5 eV resolution.

Structure Elucidation of Coxsackievirus A16 in Complex with GPP3 Informs a Systematic Review of Highly Potent Capsid Binders to Enteroviruses.

The replication of enterovirus 71 (EV71) and coxsackievirus A16 (CVA16), which are the major cause of hand, foot and mouth disease (HFMD) in children, can be inhibited by the capsid binder GPP3. Here, we present the crystal structure of CVA16 in complex with GPP3, which clarifies the role of the key residues involved in interactions with the inhibitor. Based on this model, in silico docking was performed to investigate the interactions with the two next-generation capsid binders NLD and ALD, which we show to be potent inhibitors of a panel of enteroviruses with potentially interesting pharmacological properties. A meta-analysis was performed using the available structural information to obtain a deeper insight into those structural features required for capsid binders to interact effectively and also those that confer broad-spectrum anti-enterovirus activity.

Prototype phantoms for characterization of ultralow field magnetic resonance imaging.

PURPOSE: Prototype phantoms were designed, constructed, and characterized for the purpose of calibrating ultralow field magnetic resonance imaging (ULF MRI) systems. The phantoms were designed to measure spatial resolution and to quantify sensitivity to systematic variation of proton density and relaxation time, T1 . METHODS: The phantoms were characterized first with conventional magnetic resonance scanners at 1.5 and 3 T, and subsequently with a prototype ULF MRI scanner between 107 and 128 µT . RESULTS: The ULF system demonstrated a 2-mm spatial resolution and, using T1 measurements, distinguished aqueous solutions of MnCl2 differing by 20 µM [Mn(2+) ]. CONCLUSION: The prototype phantoms proved well-matched to ULF MRI applications, and allowed direct comparison of the performance of ULF and clinical systems.

SLAC microresonator RF (SMuRF) electronics: A tone-tracking readout system for superconducting microwave resonator arrays.

We describe the newest generation of the SLAC Microresonator RF (SMuRF) electronics, a warm digital control and readout system for microwave-frequency resonator-based cryogenic detector and multiplexer systems, such as microwave superconducting quantum interference device multiplexers (µmux) or microwave kinetic inductance detectors. Ultra-sensitive measurements in particle physics and astronomy increasingly rely on large arrays of cryogenic sensors, which in turn necessitate highly multiplexed readout and accompanying room-temperature electronics. Microwave-frequency resonators are a popular tool for cryogenic multiplexing, with the potential to multiplex thousands of detector channels on one readout line. The SMuRF system provides the capability for reading out up to 3328 channels across a 4-8 GHz bandwidth. Notably, the SMuRF system is unique in its implementation of a closed-loop tone-tracking algorithm that minimizes RF power transmitted to the cold amplifier, substantially relaxing system linearity requirements and effective noise from intermodulation products. Here, we present a description of the hardware, firmware, and software systems of the SMuRF electronics, comparing achieved performance with science-driven design requirements. In particular, we focus on the case of large-channel-count, low-bandwidth applications, but the system has been easily reconfigured for high-bandwidth applications. The system described here has been successfully deployed in lab settings and field sites around the world and is baselined for use on upcoming large-scale observatories.

A model for excess Johnson noise in superconducting transition-edge sensors.

Transition-edge sensors (TESs) are two-dimensional superconducting films utilized as highly sensitive detectors of energy or power. These detectors are voltage biased in the superconducting-normal transition where the film resistance is both finite and a strong function of temperature. Unfortunately, the amount of electrical noise observed in TESs exceeds the predictions of existing noise theories. We describe a possible mechanism for the unexplained excess noise, which we term "mixed-down noise." The source is Johnson noise, which is mixed down to low frequencies by Josephson oscillations in devices with a nonlinear current-voltage relationship. We derive an expression for the power spectral density of this noise and show that its predictions agree with measured data.

Configurable error correction of code-division multiplexed TES detectors with a cryotron switch.

The development of a superconducting analog to the transistor with extremely low power dissipation will accelerate the proliferation of low-temperature circuitry operating in the milliKelvin regime. The thin-film, magnetically actuated cryotron switch is a candidate building block for more complicated and flexible milliKelvin circuitry. We demonstrate its utility for implementing reconfigurable circuitry by integrating a cryotron switch into flux-summed code-division SQUID multiplexed readout for large arrays of transition-edge-sensor (TES) microcalorimeters. Code-division multiplexing eliminates the noise penalty of time-division multiplexing while being drop-in compatible with the latter's control electronics. However, code-division multiplexing is susceptible to single-point failure mechanisms which can result in an unconstrained demodulation matrix and the loss of information from many sensing elements. In the event of a failure, the integrated cryotron switch provides a zero-signal output from a single TES, enabling the demodulation matrix used to compute TES signals from SQUID signals to be constrained and data recovered from the remaining sensors. This demonstration of configurable error correction provides both a realworld application of the cryotron switch and a foundation for more complex circuitry at milliKelvin temperatures.

Effect of mouse strain and gender on LD(50) of yessotoxin.

The aim of the present study was to determine whether the intraperitoneal LD(50) for yessotoxin (YTX) in mice varies with strain or gender. Thirty-six male and 36 female mice, of body weight 16-20 g, from each of the strains ICR (CD-1), Swiss (CFW-1) and NMRI were employed. They were not fasted before YTX treatment. At each dose, nine mice were injected with YTX solutions at 1.0 mL/20 g body weight, and observed for 24h. Symptoms and time to death were recorded. Within each mouse strain and gender arm, the study was performed as a basic four level Response Surface Pathway designed trial with nine mice at each dose level. YTX was isolated from a culture of Protoceratium reticulatum. The LD(50) values for female and male mice, respectively, were estimated as 380 and 462 microg/kg for the ICR, 269 and 328 microg/kg for the Swiss, and 314 and 412 microg/kg for the NMRI strains. The increases in LD(50) from female to male mice were found to be 22% for ICR, 22% for Swiss and 31% for NMRI. The largest difference in LD(50) among mouse strains was detected between the ICR and Swiss strains, where the deviation was 41% in both females and males. The difference between mouse strains was found significant (p = 0.03). For all three strains, females were more susceptible than males, with a difference in LD(50) of 1.2-1.3-fold. The largest difference between the least- and most-susceptible strain was 1.4-fold for both females and males. The largest difference in LD(50), 1.7-fold, was observed between female Swiss and male ICR mice. The difference between genders was not significant (p = 0.12). These results indicate that other factors, like handling of the animals, and the source and handling of the toxin, may significantly influence the outcome of studies on acute toxicity since the reported differences in LD(50) vary by a factor of about seven.

Relative toxicity of dinophysistoxin-2 (DTX-2) compared with okadaic acid, based on acute intraperitoneal toxicity in mice.

When substituting the mouse bioassay for lipophilic marine algal toxins in shellfish with analytical methods, science based factors of relative toxicity for all analogues that contribute to health risk to consumers are necessary. The aim of this paper is to establish the relative intraperitoneal toxicity of dinophysistoxin-2 (DTX-2) compared with okadaic acid (OA). The study was performed as an open, randomised parallel group trial with a four level response surface design within each of the two parallels. In accordance with the response surface design model, the LD50 for DTX-2 and OA was 338 and 206 microg/kg, respectively. By use of common regression analysis, the LD50 of DTX-2 and OA were estimated to 352 microg/kg and 204 microg/kg, respectively. The deviations between the LD50 estimates by the two methods was 4% for DTX-2 and less than 1% for OA. Taken together, these results indicate that the relative toxicity of DTX-2 is about 0.6, compared to OA. Results from the PP2A assay correspond very well with the results obtained by the mouse bioassay. The IC50 concentrations for DTX-2 and OA were 5.94 and 2.81 ng/mL, respectively. This indicates that OA is about twice as toxic as DTX-2. Since inhibition of PP2A is acknowledged as the main mechanism of toxicity of the OA group toxins, this supports the establishment of a relative toxicity factor of DTX-2 of 0.6 compared with OA.

A Thin-Film Cryotron Suitable For Use as an Ultra-Low-Temperature Switch.

Low-temperature superconducting circuits have become important for many scientific applications. However, there are presently no high current-capacity switches (~1 mA) with low power dissipation for sub-Kelvin operation. One candidate for a sub-Kelvin switch is the cryotron, a device in which the superconductivity of a wire is suppressed with a magnetic field. Here, we demonstrate a cryotron switch suitable for sub-Kelvin temperatures. In the closed state, the maximum device current is about 900 µA. The device is switched to its open state with 2 mA of control current and has a leakage of approximately 500 nA. The transition between the closed and open states of the device is faster than 200 ns, where the measurement is limited by the speed of our measurement apparatus. We also discuss low-temperature applications for our cryotron such as a single-pole, double-throw switch.

Comparison of ELISA and LC-MS analyses for yessotoxins in blue mussels (Mytilus edulis).

Blue mussels (Mytilus edulis) collected from Flødevigen Bay, Norway, in 2001 and 2002 were analysed for yessotoxins (YTXs) by ELISA and yessotoxin (YTX), 45-hydroxyYTX, and carboxyYTX by LC-MS. Results from the two methods were compared to evaluate the ELISA. The response in the ELISA was 3-13 times higher than LC-MS, probably due to the antibodies binding to other YTX analogues not included in the LC-MS analysis. Nevertheless, the correlation between ELISA and LC-MS was good, with r2 values> or =0.8. The results indicate that the ELISA is a reliable method for estimating the total level of YTXs in mussels, and are consistent with extensive metabolism of algal YTXs in mussels. YTX was a minor component in the blue mussels at all times compared to 45-hydroxyYTX and especially carboxyYTX, except when the P. reticulatum bloom occurred. The results also indicate the presence of significant amounts of YTX analogues in addition to those measured by LC-MS. All samples below 4 mg/kg by ELISA were below the current EU regulatory limit of 1 mg/kg by LC-MS. Therefore, we propose using ELISA as a screening tool with a cut-off limit at 4 mg/kg for negative samples, whereas samples above this limit would be reanalyzed by LC-MS.

Obstructive sleep apnea syndrome in obese Singapore children.

We set out to determine the prevalence of obstructive sleep apnea syndrome (OSAS) among obese Singapore school children and identify risk factors for OSAS. This study was designed as a prospective study in three phases. Parents completed a questionnaire with regards to sleep and daytime symptoms in Phase 1. Children suspected to have OSAS based on the questionnaire and all with a percent ideal body weight (IBW) >/=180 were called for clinic visits in Phase 2. All whose percent IBW >/=180 and those in whom the physicians strongly suspected OSAS were subjected to a polysomnogram in phase 3. The children were recruited from the School Health Nutritional Clinic for obese children. The investigations were carried out at Tan Tock Seng Hospital. In all, 3,671 children were screened with the questionnaire. Of these, 146 were selected to undergo polysomnography. Twenty-six had abnormal sleep studies with apnea/hypoxia indices (AHIs) >5/hr. The significant clinical feature which correlated with OSAS was sleep sitting up (P = 0.005). The risk is higher in morbidly obese (IBW >/=180), with a prevalence of 13.3% (8/60), than in less obese children (IBW <180). One in eight (12.5%) of these children was asymptomatic and would have been missed based on the questionnaire. Presence of adenotonsillar hypertrophy led to increased risk of OSAS. The prevalence of OSAS was 0.7% (26/3,671) among the obese schoolchildren in Singapore, which is similar to the prevalence reported by others. Using discriminant analysis, the estimated prevalence increased to 5.7%. In the morbidly obese (IBW >/=180), the prevalence rate is higher at 13.3%.

Flexible endoscopic tracheo-oesophageal puncture under local anaesthetic.

Blom-Singer valve prosthesis is an increasingly popular technique for voice rehabilitation in alaryngeal patients. Although primary voice puncture is being practised, the creation of the tracheo-oesophageal fistula is performed in the majority of patients as a secondary procedure. We describe a technique of secondary tracheo-oesophageal puncture using the flexible endoscope which can be performed under local anaesthetic and sedation. The technique overcomes the difficulty of passing a rigid oesophagoscope or forceps to the level of the tracheostome in a scarred and irradiated neck. The new technique also obviates the need for general anaesthesia. We have successfully used the technique in three patients.

An audit of endoscopic sinus surgery.

AIM OF STUDY: A prospective study was carried out to evaluate the results of endoscopic sinus surgery based on symptom score and endoscopic findings and to evaluate the prognostic factors using an audit form designed by IS Mackay of London. METHODS: Consecutive cases undergoing endoscopic sinus surgery were entered into the study. Pre-operative symptom, computer tomographic and endoscopic scores were recorded. Operations were also evaluated objectively; post-operative symptom and endoscopic scores were recorded at 3, 6 and 12 months. Cases lost to follow-up were interviewed over the telephone and offered free endoscopic assessments. Those who required revision surgery were considered failures and re-entered into the study. RESULTS: The study comprised 113 cases (108 patients, 60 males and 48 females) with ages ranging from 14 to 80 years (mean 40.4). There were 52 with chronic rhinosinusitis, 46 with nasal polyps, 7 with tumours/inverted papillomata, 5 with acute complicated sinusitis and 3 with fungal sinusitis. Of these, 81.9% of patients with chronic rhinosinusitis or polyps showed an overall improvement of symptoms. Nasal obstruction showed the greatest improvement, followed by rhinorrhoea, loss of smell and headaches and facial pain. Endoscopic improvement was greatest in polyps (83.3%) and oedema (87.0%) but less for discharge (59.4%). CONCLUSIONS: Our results compared well with international series. Computer tomography scoring and the number of revision operations emerged as potential prognostic indicators requiring further evaluation.

The anatomy of the Fossa of Rosenmuller--its possible influence on the detection of occult nasopharyngeal carcinoma.

The Fossa of Rosenmuller (FOR) is a well established site of origin of nasopharyngeal carcinoma (NPC). Detection of early NPC requires a sound knowledge of the anatomy of the FOR. The authors study the anatomy of the FOR with the aid of CT Scan and discuss the possible influence of the anatomy of the FOR on the detection of occult NPC. This paper reveals that there are cases of postnasal space which cannot be fully inspected clinically due to the peculiar anatomy of the FOR.

Allergen skin test and total IgE in adults with rhinitis in Singapore.

The aim of this study was to determine the allergen skin test positivity and total serum IgE of adult patients in Singapore with clinical features suggestive of allergic rhinitis. The study was carried out prospectively from January to August 1990. All patients had one or more of three symptoms (1) rhinorrhoea or nasal congestion, (2) itching nose or throat and (3) sneezing, as well as pale edematous nasal mucosa. Twenty inhalant allergens (Greers Laboratory, USA) were used for skin prick test (SPT). Serum total IgE was measured using 3M FAST test. Eighty-five consecutive patients, 54 males and 31 females, were studied. Their mean age (SD) was 26.8 (6.1) years. More than half (55.3%) had severe symptoms affecting work. Twenty percent did not have any positive skin reaction compared with 44.9% of age-matched healthy controls; 62.4% had 2 or more positive reactions compared to only 37.2% of controls. These differences were statistically significant (p < 0.002). The two most commonly, positive allergens were Dermatophagoides farinae (76.5%) and house dust (61.2%). No significant difference was found in the skin test positivity between males and females. Forty-three patients also had serum total IgE measurement and their geometric mean IgE was 240 IU/I which was significantly higher than the geometric mean IgE of healthy controls (88 IU/I, P = 0.0005).

Population structure and phylogeography in Nassau grouper (Epinephelus striatus), a mass-aggregating marine fish.

To address patterns of genetic connectivity in a mass-aggregating marine fish, we analyzed genetic variation in mitochondrial DNA (mtDNA), microsatellites, and single nucleotide polymorphisms (SNPs) for Nassau grouper (Epinephelus striatus). We expected Nassau grouper to exhibit genetic differentiation among its subpopulations due to its reproductive behavior and retentive oceanographic conditions experienced across the Caribbean basin. All samples were genotyped for two mitochondrial markers and 9 microsatellite loci, and a subset of samples were genotyped for 4,234 SNPs. We found evidence of genetic differentiation in a Caribbean-wide study of this mass-aggregating marine fish using mtDNA (FST = 0.206, p<0.001), microsatellites (FST = 0.002, p = 0.004) and SNPs (FST = 0.002, p = 0.014), and identified three potential barriers to larval dispersal. Genetically isolated regions identified in our work mirror those seen for other invertebrate and fish species in the Caribbean basin. Oceanographic regimes in the Caribbean may largely explain patterns of genetic differentiation among Nassau grouper subpopulations. Regional patterns observed warrant standardization of fisheries management and conservation initiatives among countries within genetically isolated regions.

More-powerful virus inhibitors from structure-based analysis of HEV71 capsid-binding molecules.

Enterovirus 71 (HEV71) epidemics in children and infants result mainly in mild symptoms; however, especially in the Asia-Pacific region, infection can be fatal. At present, no therapies are available. We have used structural analysis of the complete virus to guide the design of HEV71 inhibitors. Analysis of complexes with four 3-(4-pyridyl)-2-imidazolidinone derivatives with varying anti-HEV71 activities pinpointed key structure-activity correlates. We then identified additional potentially beneficial substitutions, developed methods to reliably triage compounds by quantum mechanics-enhanced ligand docking and synthesized two candidates. Structural analysis and in vitro assays confirmed the predicted binding modes and their ability to block viral infection. One ligand (with IC50 of 25 pM) is an order of magnitude more potent than the best previously reported inhibitor and is also more soluble. Our approach may be useful in the design of effective drugs for enterovirus infections.