Bayesian estimation of tobramycin exposure in cystic fibrosis

Fixed tobramycin (mg/kg) dosing is often inappropriate in patients with cystic fibrosis (CF), as pharmacokinetics are highly variable. The area under the concentration-time curve (AUC) is an exposure metric suited to monitoring in this population. Bayesian strategies to estimate AUC have been available for over 20 years but are not standard practice in the clinical setting. To assess their suitability for use in clinical practice, three AUC estimation methods using limited sampling were compared to measured true exposure by using intensive sampling tobramycin data. Adults prescribed once daily intravenous tobramycin had eight concentrations taken over 24 h. An estimate of true exposure within one dosing interval was calculated using the trapezoidal method and compared to three alternate estimates determined using (i) a two-sample log-linear regression (LLR) method (local hospital practice); (ii) a Bayesian estimate using one concentration (AUC(1)); and (iii) a Bayesian estimate using two concentrations (AUC(2)). Each method was evaluated against the true measured exposure by a Bland-Altman analysis. Twelve patients with a median (range) age and weight of 25 (18 to 36) years and 66.5 (51 to 76) kg, respectively, were recruited. There was good agreement between the true exposure and the three alternate estimates of AUC, with a mean AUC bias of < 10 mg/liter center dot h in each case, i.e., -8.2 (LLR), 3.8 (AUC(1)), and 1.0 (AUC(2)). Bayesian analysis-based and LLR estimation methods of tobramycin AUC are equivalent to true exposure estimation. All three methods may be suitable for use in the clinical setting; however, a one-sample Bayesian method may be most useful in ambulatory patients for which coordinating blood samples is difficult. Suitably powered, randomized clinical trials are required to assess patient outcomes

A Fully Differential Digital CMOS Pulse UWB Generator

A new fully-digital CMOS pulse generator for impulse-radio Ultra-Wide-Band (UWB) systems is presented. First, the shape of the pulse which best fits the FCC regulation in the 3.1-5 GHz sub-band of the entire 3.1-10.6 GHz UWB bandwidth is derived and approximated using rectangular digital pulses. In particular, the number and width of pulses that approximate an ideal template is found through an ad-hoc optimization methodology. Then a fully differential digital CMOS circuit that synthesizes the pulse sequence is conceived and its functionality demonstrated through post-layout simulations. The results show a very good agreement with the FCC requirements and a low power consumptio

Drought recorded by Ba/Ca in coastal benthic foraminifera

Increasing occurrences of extreme weather events, such as the 2018 drought over northern Europe, are a concerning issue under global climate change. High-resolution archives of natural hydroclimate proxies, such as rapidly accumulating sediments containing biogenic carbonates, offer the potential to investigate the frequency and mechanisms of such events in the past. Droughts alter the barium (Ba) concentration of near-continent seawater through the reduction in Ba input from terrestrial runoff, which in turn may be recorded as changes in the chemical composition (Ba/Ca) of foraminiferal calcium carbonates accumulating in sediments. However, so far the use of Ba/Ca as a discharge indicator has been restricted to planktonic foraminifera, despite the high relative abundance of benthic species in coastal, shallow-water sites. Moreover, benthic foraminiferal Ba/Ca has mainly been used in openocean records as a proxy for paleo-productivity. Here we report on a new geochemical data set measured from living (CTG-labeled) benthic foraminiferal species to investigate the capability of benthic Ba/Ca to record changes in river runoff over a gradient of contrasting hydroclimatic conditions. Individual foraminifera (Bulimina marginata, Non-ionellina labradorica) were analyzed by laser-ablation ICP-MS over a seasonal and spatial gradient within Gullmar Fjord, Swedish west coast, during 2018-2019. The results are compared to an extensive meteorological and hydrological data set, as well as sediment and pore-water geochemistry. Benthic foraminiferal Ba/Ca correlates significantly to riverine runoff; however, the signals contain both spatial trends with distance to Ba source and species-specific influences such as micro-habitat preferences. We deduce that shallow-infaunal foraminifera are especially suitable as proxy for terrestrial Ba input and discuss the potential influence of water-column and pore-water Ba cycling. While distance to Ba source, water depth, pore-water geochemistry, and species-specific effects need to be considered in interpreting the data, our results demonstrate confidence in the use of Ba/Ca of benthic foraminifera from near-continent records as a proxy for past riverine discharge and to identify periods of drought.Peer reviewe

Wildlife Damage to Seedlings in Reforested in Hardwood Sites in Mississippi

Herbivory assessments were conducted on seven reforested sites that were less than one year old in the following Mississippi counties: Bolivar, Leflore, and Attala. At each site, 100ft. x 100 ft. plots were established and randomly selected seedlings were marked and measured to determine seedling species, height, condition, survival, and type and extent of animal feeding sign. Surveys were conducted in March/April, May, and August 2004. Herbivory rates were highest during May with approximately 47% of seedlings showing signs of herbivory. In March/ April and August, the percentage of seedlings exhibiting signs of herbivory was 37% and 30%, respectively. Foraging by white-tailed deer (Odocoileus virginianus) was recorded on \u3e 90% of the damaged seedlings during each survey. Tree mortality for all study sites and tree species was negligible, with the highest amount (7%) recorded during August, despite the recorded rates of herbivory by white-tailed deer. Herbivory by rabbits (Sylvilagus spp.) and rodents occurred on approximately 6% of the seedlings throughout the 2004 growing season

Termination Casts: A Flexible Approach to Termination with General Recursion

This paper proposes a type-and-effect system called Teqt, which distinguishes terminating terms and total functions from possibly diverging terms and partial functions, for a lambda calculus with general recursion and equality types. The central idea is to include a primitive type-form "Terminates t", expressing that term t is terminating; and then allow terms t to be coerced from possibly diverging to total, using a proof of Terminates t. We call such coercions termination casts, and show how to implement terminating recursion using them. For the meta-theory of the system, we describe a translation from Teqt to a logical theory of termination for general recursive, simply typed functions. Every typing judgment of Teqt is translated to a theorem expressing the appropriate termination property of the computational part of the Teqt term.Comment: In Proceedings PAR 2010, arXiv:1012.455

Reducing Impacts of Double-crested Cormorants to Natural Resources in Central New York: A Review of a Collaborative Research, Management, and Monitoring Program

Double-crested Cormorants (Phalacrocorax auritus) have used central New York waters for breeding and stopover habitats during migration since 1984. In response to public concern over Oneida Lake, the United States Department of Agriculture Wildlife Services and the New York State Department of Environmental Conservation initiated an integrated research, management and monitoring program aimed at mitigating cormorant impacts to fisheries and other natural resources in 1998. The history of this program was reviewed and efforts to reduce negative impacts of the Double-crested Cormorant population in central New York described. Management was successful, as demonstrated by a substantial decrease in cormorant use of Oneida Lake during spring, summer and fall seasons, and the apparent recovery of certain sportfish populations. Research identified cormorant movement patterns within and among water bodies and documented cormorant responses to hazing and other management techniques. The cormorant management program in central New York was intended to keep cormorant use of Oneida Lake at a level that prevents unsustainable impacts to fisheries populations

Palliative care in motor neurone disease: where are we now?

Palliative care has a very important role in the care of patients with motor neurone disease and their families. There is increasing emphasis on the multidisciplinary assessment and support of patients within guidelines, supported by research. This includes the telling of the diagnosis, the assessment and management of symptoms, consideration of interventions, such as gastrostomy and ventilatory support, and care at the end of life. The aim of palliative care is to enable patients, and their families, to maintain as good a quality of life as possible and helping to ensure a peaceful death

Analysis of health impact assessment to outdoor and indoor air pollution in a prototype building in Madrid (Spain)

People spend major part of their time inside places such as homes and offices, so it is very important to know the indoor and outdoor pollution in this type of studies. The atmospheric dispersion model WRF/Chem is used to know the outdoor pollution and meteorological conditions with high spatial (1 km) and temporal (1-hour) resolution and the building energy model EnergyPlus to simulate the indoor contaminants. EnergyPlus model is used to investigate the dynamic behaviour of pollutants with a single package using a multizone approach. 2016 year is used for the simulations with hourly outputs. Outdoor and indoor pollutions are linked to through the simulated infiltration process. The evaluation of outdoor, indoor air quality and human health effects was carried out considering different exposure profiles, for people working and living in an office and house located in the same building in the Madrid city center. The study takes into account different ventilation modes in the building and indoor emission scenarios (oven for heating, cooking, photocopy machine, smoke cigarettes). Health impact assessment considered mortality and hospital admissions, associated with exposure to PM2.5 and NO2 taking into account the differences between the exposure profiles, which have been used to describe the time activity patterns of the people. The health impacts of emitting sources are highest in the warm months due to the operation of the air conditioning system. The health impact of indoor emission sources is higher than the outdoor pollution. People in the zone where the emitting sources are located would experience a mortality and morbidity of 2.5 times more than in the non-emitting zones

Defect physics and electronic properties of Cu₃PSe₄ from first principles

The p-type semiconductor Cu₃PSe₄ has recently been established to have a direct band gap of 1.4 eV and an optical absorption spectrum similar to GaAs [Foster et al., Appl. Phys. Lett. 99, 181903 (2011)], suggesting a possible application as a solar photovoltaic absorber. Here we calculate the thermodynamic stability, defect energies and concentrations, and several material properties of Cu₃PSe₄ using a wholly GGA+U method (the generalized gradient approximation of density functional theory with a Hubbard U term included for the Cu-d orbitals). We find that two low energy acceptor defects, the copper vacancy V[subscript Cu] and the phosphorus-on-selenium antisite P[subscript Se], establish the p-type behavior and likely prevent any n-type doping near thermal equilibrium. The GGA+U defect calculation method is shown to yield more accurate results than the more standard method of applying post-calculation GGA+U-based band-gap corrections to strictly GGA defect calculations