First Observation of Cyclotron Radiation from MeV-Scale e

We present an apparatus for detection of cyclotron radiation yielding a frequency-based ß^{±} kinetic energy determination in the 5 keV to 2.1 MeV range, characteristic of nuclear ß decays. The cyclotron frequency of the radiating ß particles in a magnetic field is used to determine the ß energy precisely. Our work establishes the foundation to apply the cyclotron radiation emission spectroscopy (CRES) technique, developed by the Project 8 Collaboration, far beyond the 18-keV tritium endpoint region. We report initial measurements of ß^{-}'s from ^{6}He and ß^{+}'s from ^{19}Ne decays to demonstrate the broadband response of our detection system and assess potential systematic uncertainties for ß spectroscopy over the full (MeV) energy range. To our knowledge, this is the first direct observation of cyclotron radiation from individual highly relativistic ß's in a waveguide. This work establishes the application of CRES to a variety of nuclei, opening its reach to searches for new physics beyond the TeV scale via precision ß-decay measurements.

Influenza-attributable burden in United Kingdom primary care.

Influenza is rarely laboratory-confirmed and the outpatient influenza burden is rarely studied due to a lack of suitable data. We used the Clinical Practice Research Datalink (CPRD) and surveillance data from Public Health England in a linear regression model to assess the number of persons consulting UK general practitioners (GP episodes) for respiratory illness, otitis media and antibiotic prescriptions attributable to influenza during 14 seasons, 1995-2009. In CPRD we ascertained influenza vaccination status in each season and risk status (conditions associated with severe influenza outcomes). Seasonal mean estimates of influenza-attributable GP episodes in the UK were 857 996 for respiratory disease including 68 777 for otitis media, with wide inter-seasonal variability. In an average season, 2·4%/0·5% of children aged <5 years and 1·3%/0·1% of seniors aged ⩾75 years had a GP episode for respiratory illness attributed to influenza A/B. Two-thirds of influenza-attributable GP episodes were estimated to result in prescription of antibiotics. These estimates are substantially greater than those derived from clinically reported influenza-like illness in surveillance programmes. Because health service costs of influenza are largely borne in general practice, these are important findings for cost-benefit assessment of influenza vaccination programmes.

Analysing Deviation-From-Target Data: Applying the Correct Force in Sellick's Maneuver.

The problem of comparing the deviation from a target of two or more treatments or procedures arises now and again in medicine. Practitioners usually carry out a t-test on a loss function such as absolute error. We have adapted and developed statistical methods to give a normative methodology for deviation-from-target problems and exemplify them by evaluating the performance of a tactile feedback device. Parametric and nonparametric analyses are compared and contrasted. We recommend nonparametric methods for inference about loss functions such as absolute error, with a permutation test for testing the hypothesis that the two methods perform identically, and the nonparametric bootstrap for deriving standard errors and confidence intervals on loss function ratios. We develop a new permutation test that can be used when the practitioner is unwilling to decide which loss function should be used. We recommend parametric analysis when more insight into how one method is superior is desired, or there are covariates, and discuss the complications. The results for our example are that the tactile sensing device reduces an upward bias in applied force, and more importantly reduces the spread (variance) of the applied force. It performs significantly better than manual force application.

A cricoid cartilage compression device for the accurate and reproducible application of cricoid pressure.

We describe the development and laboratory assessment of a refined prototype tactile feedback device for the safe and accurate application of cricoid pressure. We recruited 20 operating department practitioners and compared their performance of cricoid pressure on a training simulator using both the device and a manual unaided technique. The device significantly reduced the spread of the applied force: average (SE) root mean squared error decreased from 8.23 (0.48) N to 5.23 (0.32) N (p < 0.001). The average (SE) upwards bias in applied force also decreased, from 2.30 (0.74) N to 0.88 (0.48) N (p < 0.01). Most importantly, the percentage of force applications that deviated from target by more than 10 N decreased from 18% to 7% (p < 0.01). The device requires no prior training, is cheap to manufacture, is single-use and requires no power to operate, whilst ensuring that the correct force is always consistently applied.

Repeatability of a cold stress test to assess cold sensitization.

BACKGROUND: Non-freezing cold injury (NFCI) is a syndrome in which damage to peripheral tissues occurs without the tissues freezing following exposure to low ambient temperatures. AIMS: To assess the test-retest reliability of a cold stress test (CST) used to assess cold sensitization. METHODS: Volunteers with no self-reported history of NFCI undertook the CST on three occasions. Thermal images were taken of the foot and hand before, immediately after and 5min after immersion of the limb in cold water for 2min. Cold sensitization was graded by the two clinicians and the lead author. Spot temperatures from the toe and finger pads were recorded. RESULTS: There were 30 white and 19 black male participants. The ratings indicated substantial agreement [a Cohen's kappa (κ) value of 0.61-0.8] to within ± one grading category for the hands and feet of the white volunteers and the hands of the black volunteers. Limits of agreement (LoA) analysis for toe and finger pad temperatures indicated high agreement (absolute 95% LoA < 5.5°C). Test-retest reliability for the feet of the black volunteers was not supported by the gradings (κ = 0.38) and toe pad temperatures (absolute 95% LoA = 9.5°C and coefficient of variation = 11%). CONCLUSIONS: The test-retest reliability of the CST is considered adequate for the assessment of the cold sensitization of the hands and feet of white and the hands of black healthy non-patients. The study should be repeated with patients who have suffered a NFCI.

An analysis of patient safety incidents associated with medications reported from critical care units in the North West of England between 2009 and 2012.

Incident reporting is promoted as a key tool for improving patient safety in healthcare. We analysed 2238 patient safety incidents involving medications submitted from up to 29 critical care units each year in the North West of England between 2009 and 2012; 452 (20%) of these incidents led to harm to patients. Although 1461 (65%) incidents were judged to have been preventable, there was no reduction in the rate of incidents per 1000 days between 2009 and 2012 (5.9 in 2009, 6.6 in 2012). Furthermore, in the 2012 data, there were wide variations in the incident rates between units, the median (IQR [range]) rate per 1000 patient days for individual units being 6.8 (3.8-11.0 [1.3-37.1]). The variation in the percentage that could have been avoided was narrower, with a median (IQR [range]) of 70% (61-80% [38-100%]). The most commonly reported drugs were noradrenaline (161 incidents, 92 with harm), heparins (153 incidents, 29 with harm), morphine (131 incidents, 14 with harm) and insulin (111 incidents, 54 with harm). The administration of drugs was the stage in the process where incidents were most commonly reported; it was also the stage most likely to harm patients. We conclude that the wide range in reported rates between units, and the scope for preventing many incidents, suggest that quality improvement initiatives could improve medication safety in the units studied.

Mercury and selenium concentrations in lanugo of free-ranging California sea lions in the southern Gulf of California, Mexico.

Total mercury ([THg]) and selenium ([TSe]) concentrations were determined in California sea lion (Zalophus californianus) lanugo from the Gulf of California in 2021 and 2022. Relationships with sex, morphometrics, and year were evaluated. Following toxicological thresholds of concern for piscivorous mammals, most pups had a [THg] < 10 ppm, one pup (2021) had a [THg] > 20 ppm, no pups had a [THg] > 30 ppm. Females had significantly higher [TSe] than males; sex did not influence [THg]. [THg] and [TSe] in 2022 were significantly higher in the general population and male cohorts compared to 2021. Significant negative correlations were observed between [THg], [TSe], and morphometrics (2021). These results indicate that, compared to other pinniped species, regional California sea lions may have a decreased likelihood of experiencing Hg-related adverse health effects. Year-related changes in element concentrations suggest continued monitoring of this population to assess pinniped, environmental, and potentially, human health.

Review of patient safety incidents reported from critical care units in North-West England in 2009 and 2010.

We categorised and established the rates of patient safety incidents reported during 2009 and 2010 from critical care units in 12 hospital trusts in North-West England. We identified a total of 4219 incidents reported during 127, 467 calendar days of critical care with a median (IQR [range]) of 31 (26-45 [20-57]) incidents per 1000 days per trust. A median (IQR [range]) of 10 (7-13 [3.5-27]) incidents per 1000 days were associated with harm. Pressure sores were the most common cause of harm, with a median (IQR [range]) of 3.9 (1.0-6.6 [0-20.4]) incidents per 1000 days. Only 89 (2.1%) incidents described more than temporary harm, of which 12 were airway related incidents. Five incidents described the use of inappropriate arterial flush solutions. It is possible to compare rates of incident reporting in different trusts over time to determine if different methods of care are associated with different reporting rates. The wide range of reported pressure sore rates suggests that their incidence could be reduced.

Dynamic analysis of MAPK signaling using a high-throughput microfluidic single-cell imaging platform.

Cells have evolved biomolecular networks that process and respond to changing chemical environments. Understanding how complex protein interactions give rise to emergent network properties requires time-resolved analysis of cellular response under a large number of genetic perturbations and chemical environments. To date, the lack of technologies for scalable cell analysis under well-controlled and time-varying conditions has made such global studies either impossible or impractical. To address this need, we have developed a high-throughput microfluidic imaging platform for single-cell studies of network response under hundreds of combined genetic perturbations and time-varying stimulant sequences. Our platform combines programmable on-chip mixing and perfusion with high-throughput image acquisition and processing to perform 256 simultaneous time-lapse live-cell imaging experiments. Nonadherent cells are captured in an array of 2,048 microfluidic cell traps to allow for the imaging of eight different genotypes over 12 h and in response to 32 unique sequences of stimulation, generating a total of 49,000 images per run. Using 12 devices, we carried out >3,000 live-cell imaging experiments to investigate the mating pheromone response in Saccharomyces cerevisiae under combined genetic perturbations and changing environmental conditions. Comprehensive analysis of 11 deletion mutants reveals both distinct thresholds for morphological switching and new dynamic phenotypes that are not observed in static conditions. For example, kss1Delta, fus3Delta, msg5Delta, and ptp2Delta mutants exhibit distinctive stimulus-frequency-dependent signaling phenotypes, implicating their role in filtering and network memory. The combination of parallel microfluidic control with high-throughput imaging provides a powerful tool for systems-level studies of single-cell decision making.

Parental attributions of controllability as a moderator of the relationship between developmental disability and behaviour problems.

BACKGROUND: Children with developmental disabilities present behaviour problems to a greater extent than do typically developing children. Psychosocial models of child development suggest that parental attributions of child and adult controllability could moderate this relationship between child disability status and behaviour. METHODS: The influence of parental attributions of adult and child controllability on the relationship between problem behaviours and disability was explored in mothers of children with developmental disabilities (DD) (N = 20) with a mean age of 9 years 3 months (SD 24.6 months), and in mothers of typically developing (TD) children (N = 26) with a mean age of 9 years 4 months (standard deviation 23.7 months). The DD group comprised 11 children with autistic spectrum disorders or other communication impairments, three children with Down Syndrome, one with cerebral palsy, one with attentional problems, and four with specific or complex developmental problems. Child behaviour was measured by the Child Behaviour Checklist. Parental attributions were measured using a modified version of the Parent Attribution Test and mothers were divided into higher and lower controllability groups on the basis of their responses on this test. RESULTS: Multivariate analysis of variance found significant group × adult controllability interaction effects for 'aggressive behaviour', 'rule-breaking behaviour', as well as borderline significant effects for 'social problems' and 'other problems'. Simple effects analysis suggested that when mothers had lower attributions of adult controllability, there were indeed significantly more problem behaviours in the DD group, but when mothers had attributions of higher adult controllability there was no longer any significant difference in problematic behaviour between the two groups. CONCLUSIONS: Parental attributions of controllability may moderate the well-established effect of disability on problem behaviour. Implications for parent intervention programmes are discussed.

Colonization of Potato by Colletotrichum coccodes: Effect of Soil Infestation and Seed Tuber and Foliar Inoculation.

Colonization of potato (Solanum tuberosum) tissue, including roots, stolons, and above and below ground stems, by Colletotrichum coccodes, the causal agent of black dot, was evaluated following soil infestation, inoculation of seed tubers and foliage, and every combination thereof, in field trials over two growing seasons in North Dakota and Minnesota. A total of 107,520 isolations for C. coccodes performed across four site-years allowed for an extensive comparison of fungal colonization of the host plant and disease severity. The black dot pathogen was detected in potato stems at the first sampling date in all four site-years, as early as 14 days prior to emergence. Colonization of above and below ground stems occurred at a higher frequency than in roots and stolons in all four site-years, resulting in significantly higher relative area under the colonization progress curves (RAUCPCs) (α = 0.05). Although fungal colonization and disease incidence were higher in inoculated and/or infested treatments, sufficient natural inoculum was present to result in substantial levels of disease in noninoculated and noninfested plots. However, noninoculated and noninfested plots displayed the lowest RAUCPC values across three of four site-years and those treatments with multiple inoculation events tended to have higher RAUCPC values. Isolates belonging to vegetative compatibility group (VCG)2 and -5 were recovered from plants sampled in 2004 more frequently than isolates belonging to VCG1 and -3. A significant difference in disease incidence on stems was observed only in North Dakota in 2004 and Minnesota in 2003 (α = 0.05). Noninoculated and noninfested plots displayed the lowest disease incidence, whereas those treatments with more than one inoculation and/or infestation event tended to have higher disease incidence. Results of this study, including the disease severity and yield data, provide a better understanding of colonization of potato plants by C. coccodes and its impact.

Pharmacokinetics of an orally administered methylcellulose formulation of gallium maltolate in neonatal foals.

Gallium is a trivalent semi-metal with anti-microbial effects because of its incorporation into crucial iron-dependent reproductive enzyme systems. Gallium maltolate (GaM) provides significant gallium bioavailability to people and mice following oral administration and to neonatal foals following intragastric administration. To study the prophylactic and therapeutic effects of GaM against Rhodococcus equi pneumonia in foals, we developed a methylcellulose formulation of GaM (GaM-MCF) for oral administration to neonatal foals. Normal neonatal foals were studied. Six foals received 20 mg/kg and another six foals received 40 mg/kg of GaM-MCF orally. Serial serum samples were collected and serum gallium concentrations were determined using inductively coupled plasma mass spectroscopy. Gallium was rapidly absorbed (T(max) of 4 h), and a mean C(max) of 0.90 or 1.8 microg/mL was achieved in foals receiving 20 or 40 mg/kg respectively. Marked variability existed in C(max) among foals: only half of the foals receiving 20 mg/kg attained serum concentrations of >0.7 microg/mL, a level suggested to be therapeutic against R. equi by previous studies. Mean elimination half-life was 32.8 or 32.4 h for foals receiving 20 or 40 mg/kg respectively. The results of this study suggest that at least 30 mg/kg orally every 24 h should be considered in future pharmacodynamic and efficacy studies.

Maintenance on a ketogenic diet: voluntary exercise, adiposity and neuroendocrine effects.

BACKGROUND: Adherence to low-carbohydrate, ketogenic diets (KDs) has been associated with greater weight loss in the short-term than low-fat, calorie-restricted diets. However, consumption of KDs may result in decreased voluntary exercise and thus render long-term weight loss and maintenance of weight loss difficult. METHODS: Rats were maintained on either a non-ketogenic chow (CH) diet or a low-carbohydrate, KD for 6 weeks. Half of each dietary group was sedentary, whereas the other half was given access to a running wheel. Running wheel activity (total distance and meters per minute), plasma leptin and insulin, adiposity, and hypothalamic mRNA for neuropeptide Y and proopiomelanocortin (POMC) were measured to assess activity-related effects in animals maintained on KD. RESULTS: With access to a running wheel, rats on KD engaged in similar levels of voluntary activity as CH rats and both dietary groups decreased caloric intake. Caloric intake increased over time such that it was significantly greater than sedentary controls after 1 month of access to the wheels, however body weight remained decreased. Sedentary rats maintained on KD had increased adiposity and plasma leptin levels and decreased hypothalamic POMC mRNA, as compared to sedentary CH rats. KD rats with access to a running wheel had similar levels of adiposity and plasma leptin levels as CH rats with access to running wheels, but significantly increased POMC mRNA in the arcuate. CONCLUSION: We demonstrate that maintenance on KD does not inhibit voluntary activity in a running wheel. Furthermore, prevention of KD-related increased adiposity and plasma leptin, as measured in sedentary KD rats, significantly increases levels of the anorexigenic neuropeptide POMC mRNA.

Control of colonial hydroid macrofouling by free-field ultrasonic radiation.

Free-field ultrasonic radiation inhibited the feeding of the macrofouling hydroid Garveia franciscana by causing tentacle contraction at the sonic degasification threshold. Within the frequency range of 250 to 2000 kilohertz, the threshold sound intensity (sonic degasification threshold) that caused tentacle contraction was directly proportional to frequency, with the minimum observed being 0.6 watt per square centimeter at 250 kilohertz. A pulse length of 0.2 second and interpulse period of 102 seconds gave the lowest average power required to produce tentacle contraction at a peak pulse sound intensity of 6.2 watts per square centimeter with a frequency of 250 kilohertz. Twenty-four hour exposures to the sound regime caused destruction of the hydranths and regression of tissue in the stolons.

Asthma as a predictor of obstructive sleep apnea in urban African-American children.

BACKGROUND: Asthma is a known co-morbid factor in childhood obstructive sleep apnea (OSA); however, little is known about the effects that asthma might have on the severity of OSA. We hypothesize that children with concomitant asthma and OSA have more severe OSA. METHODS: We conducted a prospective study of 50 children with OSA diagnosed by polysomnography referred for tonsillectomy and adenoidectomy (T&A). The presence of concomitant asthma was determined by ISAAC questionnaire and spirometry. Atopy to common allergens was determined by skin prick testing. Due to the relatively small sample size, we limited hypothesis testing to cross tabulations with Fisher's Exact Test and t testing. We also employed a parsimonious ordinary least squares (OLS) regression assuming a large effect size. RESULTS: Subjects (n = 50) included 32 males and 41 African-Americans. Age at T&A was 9.3 +/- 3.4 years (mean +/- S.D). Thirty-two subjects reported a history of asthma during their lifetimes, but the ISAAC questionnaire detected only 30 subjects. Twenty-two subjects reported current asthma. Atopy was found in 27 subjects. Apnea-hypopnea index (AHI) was lower in the current asthma group than in the lifetime asthma group but did not reach statistical significance. However, AHI was significantly higher in subjects with poorly controlled asthma. Further, in a parsimonious OLS model controlling for sleep efficiency and age, a history of lifetime asthma increased the AHI by 8.8 (p < 0.05). DISCUSSION: In urban African-American children referred for T&A to treat OSA, a history of poorly controlled asthma is associated with more severe OSA.

Review of patient safety incidents submitted from Critical Care Units in England & Wales to the UK National Patient Safety Agency.

We reviewed and classified all patient safety incidents submitted from critical care units in England and Wales to the National Patient Safety Agency for the first quarter of 2008. A total of 6649 incidents were submitted from 141 organisations (median (range) 23 (1-268 incidents)); 786 were unrelated to the critical care episode and 248 were repeat entries. Of the remaining 5615 incidents, 1726 occurred in neonates or babies, 1298 were associated with temporary harm, 15 with permanent harm and 59 required interventions to maintain life or may have contributed to the patient's death. The most common main incident groups were medication (1450 incidents), infrastructure and staffing (1289 incidents) and implementation of care (1047 incidents). There were 2789 incidents classified to more than one main group. The incident analysis highlights ways to improve patient safety and to improve the classification of incidents.

Neptunium(iv)-hydroxamate complexes: their speciation, and kinetics and mechanism of hydrolysis.

Simple hydroxamic acids such as acteohydroxamic acid (AHA) have been identified as suitable reagents for the control of Pu and Np in advanced separation processes for nuclear fuel reprocessing such as the Advanced PUREX or UREX based recycle processes, due to their ability to strip the tetravalent form of Pu and Np from tri-butyl phosphate into nitric acid. However, both free and metal bound hydroxamates are known to undergo acid catalysed hydrolysis at low pH, the kinetics of which must be characterised before implementation of PUREX/UREX based reprocessing flowsheets. In support of this implementation, a comprehensive thermodynamic and kinetic model that describes both the complex speciation and hydrolysis of AHA in the presence of Np(iv) has been developed. The model has two unique features: (i) in the case of the hydrolysis reaction kinetics, the model includes the hydrolysis of not only free AHA but also both the mono- and bishydroxamato-Np(iv) complexes; (ii) for the associated speciation calculations, the model explicitly includes the ionic strength dependence of not only the mono- and bishydroxamato-Np(iv) complexes but also the mono- and bisnitrato neptunium(iv) and monohydroxoneptunium(iv) complexes. For the latter three species, respective SIT coefficients of Δε1,NO3 = -0.13 ± 0.03 kg mol-1, , Δε2,NO3 = -0.37 ± 0.13 kg mol-1, Δε1,OH = -0.36 kg mol-1 and log10 K01,OH = -1.23 were also determined. Using experimental data from a series of kinetic studies on the Np(iv)-AHA system, this model has been used to determine the rate constants for hydrolysis of mono- and bis-acetohydroxamatoneptunium(iv) at 25 °C for the first time. These were found to be 3.5 × 10-5 ± 2.5 × 10-5 dm3 mol-1 s-1 and 1.9 × 10-3 ± 1.3 × 10-3 dm3 mol-1 s-1, respectively. Comparison of these values with the rate constants for hydrolysis of free AHA indicates that complexation of AHA with Np(iv) increases the rate of hydroxamate hydrolysis - an observation that we attribute to the electron withdrawing effect of the metal centre within the Np(iv)-AHA complex increasing the susceptibility of the AHA carbonyl carbon to nucleophilic attack, the accepted first step in its mechanism of hydrolysis.

Electronic surveillance of wall-mounted soap and alcohol gel dispensers in an intensive care unit.

We describe a battery-powered recording device incorporating a force-sensitive resistor and a microcontroller that records depressions of wall-mounted soap and alcohol gel dispensers. The device has a two-second (2 s) lockout built into it, so that a single record is associated with a single hand-hygiene episode. Recorders were implanted within the wall-mounted dispensers found in two bed areas and the entrance of a 16-bedded intensive care unit. The use of the bed area dispensers was correlated (r) with the dependency of the patient in the open bed area (r=0.5, P<0.01), as assessed using the UK Department of Health critical care minimum data set. Both bed areas and the entrance dispensers showed wide but different fluctuations in use throughout the 24h day. The recording device may help in feedback about soap and gel use for hand-hygiene quality improvement and educational initiatives.

Optimisation of photonic crystal coupling through waveguide design.

This paper considers multiple structural designs for photonic crystal surface emitting lasers operating at key wavelengths. Initially a structure from Williams et al. is modelled, the structure is modified to include an additional GaAs waveguide layer (termed ballast layer) and to include an additional PC layer (termed double decker). These structures are modelled by a combination of coupling calculation and waveguide modelling and are compared to the original structure. We show that both of these schemes give an increase in coupling, but present fabrication challenges. Next, we model standard laser structures operating at key wavelengths (400 nm, 1.3 and 10 µm) where a photonic crystal is located above the active region and explore the effect of increasing thickness of photonic crystal. We find that increasing the thickness increases the coupling coefficient but not true for the full range of thicknesses considered. This study allows a more universal comparison of the use of all-semiconductor, or void containing PCSELs to be conducted and we find that the realisation of all semiconductor PCSELs covering a wide range of material and wavelengths are possible.

Optimizing care of ventilated infants by improving weighing accuracy on incubator scales.

OBJECTIVES: To determine the accuracy of weighing ventilated infants on incubator scales and whether the accuracy can be improved by the addition of a ventilator tube compensator (VTC) device to counterbalance the force exerted by the ventilator tubing. STUDY DESIGN: Body weights on integral incubator scales were compared in ventilated infants (with and without a VTC), with body weights on standalone electronic scales (true weight). Individual and series of trend weights were obtained on the infants. The method of Bland and Altman was used to assess the introduced bias. RESULTS: The study included 60 ventilated infants; 66% of them weighed <1000 g. A total of 102 paired-weight datasets for 30 infants undergoing conventional ventilation and 30 undergoing high frequency oscillator ventilation (HFOV) supported by a SensorMedics oscillator, (with and without a VTC) were obtained. The mean differences and (95% CI for the bias) between the integral and true scale weighing methods was 60.8 g (49.1 g to 72.5 g) without and -2.8 g (-8.9 g to 3.3 g) with a VTC in HFOV infants; 41.0 g (32.1 g to 50.0 g) without and -5.1 g (-9.3 g to -0.8 g) with a VTC for conventionally ventilated infants. Differences of greater than 2% were considered clinically relevant and occurred in 93.8% without and 20.8% with a VTC in HFOV infants and 81.5% without and 27.8% with VTC in conventionally ventilated infants. CONCLUSIONS: The use of the VTC device represents a substantial improvement on the current practice for weighing ventilated infants, particularly in the extreme preterm infants where an over- or underestimated weight can have important clinical implications for treatment. A large-scale clinical trial to validate these findings is needed.