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1.
Mar Pollut Bull ; 197: 115712, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37922756

ABSTRACT

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.


Subject(s)
Mercury , Sea Lions , Selenium , Water Pollutants, Chemical , Animals , Female , Male , Humans , Mercury/analysis , Mexico , Water Pollutants, Chemical/analysis , Hair/chemistry
2.
Phys Rev Lett ; 131(8): 082502, 2023 Aug 25.
Article in English | MEDLINE | ID: mdl-37683153

ABSTRACT

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.

4.
Dalton Trans ; 48(2): 673-687, 2019 Jan 02.
Article in English | MEDLINE | ID: mdl-30547163

ABSTRACT

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.

5.
Opt Quantum Electron ; 49(2): 47, 2017.
Article in English | MEDLINE | ID: mdl-32269407

ABSTRACT

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.

6.
J Neonatal Perinatal Med ; 9(4): 377-383, 2016.
Article in English | MEDLINE | ID: mdl-28009333

ABSTRACT

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.


Subject(s)
Anthropometry/methods , Body Weight , High-Frequency Ventilation/instrumentation , Respiratory Distress Syndrome, Newborn/therapy , Anthropometry/instrumentation , Female , Humans , Incubators, Infant , Infant, Extremely Low Birth Weight , Infant, Newborn , Infant, Premature , Male , Pilot Projects , Respiration, Artificial/instrumentation
7.
BMJ Open Diabetes Res Care ; 4(1): e000160, 2016.
Article in English | MEDLINE | ID: mdl-27110366

ABSTRACT

OBJECTIVE: Hypoglycemia is a serious complication of diabetes treatment. This retrospective observational study characterized hypoglycemia-related hospital emergency room (ER) and inpatient (in-pt) admissions and identified risk factors for 30-day all-cause and hypoglycemia-related readmission. RESEARCH DESIGN AND METHODS: 4476 hypoglycemia-related ER and in-pt encounters with discharge dates from 1/1/2009 to 3/31/2014 were identified in a large, multicenter electronic health record database. Outcomes were 30-day all-cause ER/hospital readmission and hypoglycemia-related readmission. Multivariable logistic regression methods identified risk factors for both outcomes. RESULTS: 1095 (24.5%) encounters had ER/hospital all-cause readmission within 30 days and 158 (14.4%) of these were hypoglycemia-related. Predictors of all-cause 30-day readmission included recent exposure to a hospital/nursing home (NH)/skilled nursing facility (SNF; OR 1.985, p<0.001); age 25-34 and 35-44 (OR 2.334 and 1.996, respectively, compared with age 65-74, both p<0.001); and African-American (AA) race versus all other race categories (OR 1.427, p=0.011). Other factors positively associated with readmission include chronic obstructive pulmonary disease, cerebrovascular disease, cardiac dysrhythmias, congestive heart disease, hypertension, and mood disorders. Predictors of readmissions attributable to hypoglycemia included recent exposure to a hospital/NH/SNF (OR 2.299, p<0.001), AA race (OR 1.722, p=0.002), age 35-44 (OR 3.484, compared with age 65-74, p<0.001), hypertension (OR 1.891, p=0.019), and delirium/dementia and other cognitive disorders (OR 1.794, p=0.038). Obesity was protective against 30-day hypoglycemia-related readmission (OR 0.505, p=0.017). CONCLUSIONS: Factors associated with 30-day all-cause and hypoglycemia-related readmission among patients with diabetic hypoglycemia include recent exposure to hospital/SNF/NH, adults <45 years, AAs, and several cardiovascular and respiratory-related comorbid conditions.

8.
Epidemiol Infect ; 144(3): 537-47, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26168005

ABSTRACT

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.


Subject(s)
General Practice/statistics & numerical data , Influenza A virus , Influenza B virus , Influenza, Human/epidemiology , Otitis Media/epidemiology , Primary Health Care/statistics & numerical data , Adolescent , Adult , Age Factors , Aged , Anti-Bacterial Agents , Child , Child, Preschool , Comorbidity , Databases, Factual , Drug Prescriptions/statistics & numerical data , Humans , Incidence , Infant , Infant, Newborn , Influenza Vaccines , Influenza, Human/prevention & control , Influenza, Human/virology , Middle Aged , Otitis Media/drug therapy , Otitis Media/virology , Seasons , United Kingdom/epidemiology , Vaccination/statistics & numerical data , Young Adult
9.
Occup Med (Lond) ; 65(7): 578-84, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26272380

ABSTRACT

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.


Subject(s)
Cold Injury/diagnosis , Cold Temperature , Severity of Illness Index , Skin Temperature , Skin/pathology , Thermography , Adolescent , Adult , Black People , Foot , Freezing , Hand , Humans , Immersion , Male , Reference Values , Regional Blood Flow , Reproducibility of Results , Stress, Physiological , Syndrome , White People , Young Adult
10.
Sci Rep ; 5: 13203, 2015 Aug 20.
Article in English | MEDLINE | ID: mdl-26289621

ABSTRACT

We demonstrate a semiconductor PCSEL array that uniquely combines an in-plane waveguide structure with nano-scale patterned PCSEL elements. This novel geometry allows two-dimensional electronically controllable coherent coupling of remote vertically emitting lasers. Mutual coherence of the PCSEL elements is verified through the demonstration of a two-dimensional Young's Slits experiment. In addition to allowing the all-electronic control of the interference pattern, this type of device offers new routes to power and brightness scaling in semiconductor lasers, and opportunities for all-electronic beam steering.

11.
Br J Radiol ; 88(1049): 20140831, 2015 May.
Article in English | MEDLINE | ID: mdl-25710361

ABSTRACT

OBJECTIVE: Variability in the measurement of left ventricular (LV) parameters in cardiovascular imaging has typically been assessed over a short time interval, but clinicians most commonly compare results from studies performed a year apart. To account for variation in technical, procedural and biological factors over this time frame, we quantified the within-subject changes in LV volumes, LV mass (LVM) and LV ejection fraction (EF) in a well-defined cohort of healthy adults at 12 months. METHODS: Cardiac MR (CMR) was performed in 42 healthy control subjects at baseline and at 1 year (1.5 T Magnetom® Avanto; Siemens Healthcare, Erlangen, Germany). Analysis of steady-state free precession images was performed manually offline (Argus software; Siemens Healthcare) for assessment of LV volumes, LVM and EF by a single blinded observer. A random subset of 10 participants also underwent repeat imaging within 7 days to determine short-term interstudy reproducibility. RESULTS: There were no significant changes in any LV parameter on repeat CMR at 12 months. The short-term interstudy biases were not significantly different from the long-term changes observed at 1 year. The smallest detectable change (SDC) for LVEF, end-diastolic volume, end-systolic volume and LVM that could be recognized with 95% confidence were 6%, 13 ml, 7 ml and 6 g, respectively. CONCLUSION: The variability in CMR-derived LV measures arising from technical, procedural and biological factors remains minimal at 12 months. Thus, for patients undergoing repeat annual assessment by CMR, even small differences in LV function, size and LVM (which are greater than the SDC) may be attributed to disease-related factors. ADVANCES IN KNOWLEDGE: The reproducibility and reliability of CMR data at 12 months is excellent allowing clinicians to be confident that even small changes in LV structure and function over this time frame are real.


Subject(s)
Cardiac-Gated Imaging Techniques/methods , Heart Ventricles/anatomy & histology , Magnetic Resonance Imaging, Cine/methods , Stroke Volume/physiology , Ventricular Function, Left/physiology , Female , Healthy Volunteers , Humans , Image Interpretation, Computer-Assisted , Longitudinal Studies , Male , Middle Aged , Prospective Studies , Reproducibility of Results
12.
J Biopharm Stat ; 25(4): 619-34, 2015.
Article in English | MEDLINE | ID: mdl-24906015

ABSTRACT

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.


Subject(s)
Clinical Competence/statistics & numerical data , Statistics as Topic/methods , Statistics, Nonparametric , Touch , Clinical Competence/standards , Humans , Single-Blind Method
13.
Anaesthesia ; 70(1): 18-25, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25267415

ABSTRACT

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.


Subject(s)
Cricoid Cartilage , Intubation, Intratracheal/instrumentation , Respiratory Aspiration of Gastric Contents/prevention & control , Anesthesiology/education , Education, Medical, Continuing/methods , Equipment Design , Humans , Intubation, Intratracheal/adverse effects , Intubation, Intratracheal/methods , Pressure , Reproducibility of Results , Respiratory Aspiration of Gastric Contents/etiology , Teaching Materials
14.
Anaesthesia ; 69(7): 735-45, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24810765

ABSTRACT

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.


Subject(s)
Health Care Surveys/methods , Health Care Surveys/statistics & numerical data , Intensive Care Units/statistics & numerical data , Medication Errors/statistics & numerical data , Patient Safety/statistics & numerical data , Critical Care/statistics & numerical data , England , Humans , Safety Management/statistics & numerical data
15.
J Hosp Infect ; 82(3): 203-6, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23009802

ABSTRACT

A novel audio-visual computerized infection control initiative was designed, installed and tested in the neonatal intensive care unit at a busy teaching hospital, with the primary aim of improving visitors' adherence to hand hygiene and infection control procedures. The system has proved to be reliable, self-administering, inexpensive, requires no prior education or training, is rapidly deployable and can be used immediately. A measurable improvement in visitors' handwashing technique and recall of infection control instructions was seen after introduction of this initiative. This system provides a new opportunity to educate and promote infection control measures to visitors.


Subject(s)
Infection Control/methods , Intensive Care Units, Neonatal , Reminder Systems , Automation/methods , Guideline Adherence/statistics & numerical data , Hand Disinfection , Hospitals, Teaching , Humans , Infant, Newborn
16.
Anaesthesia ; 67(7): 706-13, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22506637

ABSTRACT

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.


Subject(s)
Critical Care/statistics & numerical data , Intensive Care Units/statistics & numerical data , Patient Safety/statistics & numerical data , Critical Care/standards , England/epidemiology , Humans , Intensive Care Units/standards , Medical Audit , Medical Errors/statistics & numerical data , Patient Safety/standards , Pressure Ulcer/epidemiology , Retrospective Studies , Safety Management/organization & administration
17.
Child Care Health Dev ; 37(2): 184-94, 2011 Mar.
Article in English | MEDLINE | ID: mdl-20533916

ABSTRACT

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.


Subject(s)
Behavior Control , Child Behavior Disorders/etiology , Developmental Disabilities/psychology , Mothers/psychology , Parenting/psychology , Attitude to Health , Child , Child Behavior Disorders/psychology , Female , Humans , Male , Psychometrics
18.
Lab Chip ; 11(3): 466-73, 2011 Feb 07.
Article in English | MEDLINE | ID: mdl-21088765

ABSTRACT

Time-lapse live cell imaging is a powerful tool for studying signaling network dynamics and complexity and is uniquely suited to single cell studies of response dynamics, noise, and heritable differences. Although conventional imaging formats have the temporal and spatial resolution needed for such studies, they do not provide the simultaneous advantages of cell tracking, experimental throughput, and precise chemical control. This is particularly problematic for system-level studies using non-adherent model organisms such as yeast, where the motion of cells complicates tracking and where large-scale analysis under a variety of genetic and chemical perturbations is desired. We present here a high-throughput microfluidic imaging system capable of tracking single cells over multiple generations in 128 simultaneous experiments with programmable and precise chemical control. High-resolution imaging and robust cell tracking are achieved through immobilization of yeast cells using a combination of mechanical clamping and polymerization in an agarose gel. The channel and valve architecture of our device allows for the formation of a matrix of 128 integrated agarose gel pads, each allowing for an independent imaging experiment with fully programmable medium exchange via diffusion. We demonstrate our system in the combinatorial and quantitative analysis of the yeast pheromone signaling response across 8 genotypes and 16 conditions, and show that lineage-dependent effects contribute to observed variability at stimulation conditions near the critical threshold for cellular decision making.


Subject(s)
Immobilization/methods , Microfluidics/instrumentation , Microfluidics/methods , Saccharomyces cerevisiae/cytology , Algorithms , Diffusion , Dimethylpolysiloxanes/chemistry , High-Throughput Screening Assays , Lab-On-A-Chip Devices , Nylons/chemistry , Polymerization , Signal Transduction , Single-Cell Analysis
19.
J Vet Pharmacol Ther ; 33(4): 376-82, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20646200

ABSTRACT

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.


Subject(s)
Animals, Newborn/metabolism , Anti-Bacterial Agents/pharmacokinetics , Horses/metabolism , Organometallic Compounds/pharmacokinetics , Pyrones/pharmacokinetics , Actinomycetales Infections/drug therapy , Actinomycetales Infections/veterinary , Administration, Oral , Animals , Anti-Bacterial Agents/blood , Female , Half-Life , Horse Diseases/drug therapy , Male , Mass Spectrometry/veterinary , Methylcellulose , Organometallic Compounds/blood , Pneumonia, Bacterial/drug therapy , Pneumonia, Bacterial/veterinary , Pyrones/blood , Rhodococcus equi/drug effects
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