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2,103 result(s) for "Lauer, J"
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Use of epigenetically modified bacteriophage and dual beta-lactams to treat a Mycobacterium abscessus sternal wound infection
Nontuberculous mycobacterium (NTM) infections are challenging to manage and are frequently non-responsive to aggressive but poorly-tolerated antibiotic therapies. Immunosuppressed lung transplant patients are susceptible to NTM infections and poor patient outcomes are common. Bacteriophages present an alternative treatment option and are associated with favorable clinical outcomes. Similarly, dual beta-lactam combinations show promise in vitro, but clinical use is sparse. We report here a patient with an uncontrolled Mycobacterium abscessus infection following a bilateral lung transplant and failed antibiotic therapy. Both smooth and rough colony morphotype strains were initially present, but treatment with two phages that kill the rough strain – including epigenetic-modification to overcome restriction – resulted in isolation of only the smooth strain. The rough and smooth strains have similar antibiotic susceptibilities suggesting that the phages specifically eliminated the rough strain. Dual beta-lactam therapy with meropenem and ceftazidime-avibactam provided further clinical improvement, and the phages act synergistically with meropenem in vitro. Cristinziano et al. report the use of bacteriophages and dual beta lactam antibiotics to treat a patient with a Mycobacterium abscessus sternal wound infection. One of the phages was epigenetically modified for specificity to the M. abscessus strain.
Development and validation of an open-source four-pole electrical conductivity, temperature, depth sensor for in situ water quality monitoring in an estuary
Most recent implementations of low-cost electrical conductivity (EC) sensors intended for water quality measurements are based on simple two-pole designs. However, in marine settings, EC often exceeds the range where two-pole sensors provide reliable results. We have developed a simple four-pole EC sensor that relies exclusively on analog-to-digital measurements made using readily available circuit boards (pyboard v.1.1 or Raspberry Pi Pico 2040) programmed using MicroPython. Other than resistors and graphite or wire electrodes, no other electronic components are required for the EC sensor. When combined with a pressure/temperature sensor (MS5803-05), an optional NTC thermistor, batteries, and a waterproof housing constructed using a PVC pipe and a 3-D-printed cap, the device becomes a working conductivity-temperature-depth sensor capable of extended field deployments. Construction is sufficiently simple that undergraduate science students can construct one during three 3-h lab periods. Lab calibrations performed on several prototypes at ECs between 0.18 and 45 mS/cm show that confidence limits as good as about ±3% of EC are possible. Re-calibration of several prototypes 1 year after initial calibration shows that long-term calibration drift is modest. Data collected by the prototypes over several tidal cycles in the Duwamish River, Washington, USA, are in agreement with data from a co-located commercial YSI-EX03 conductivity probe. When distributed across a constructed off-channel wetland in the Duwamish system, the sensors documented large amounts of spatial and temporal variability in EC, highlighting the importance of such wetlands for providing unique temperature/salinity environments potentially valuable for outmigrating juvenile salmon.
Defining community‐led monitoring and its role in programme‐embedded learning: lessons from the Citizen Science Project in Malawi and South Africa
Introduction Programme Science (PS) and community‐led monitoring (CLM) intersect in unexpected and promising ways. This commentary examines a CLM initiative in Malawi and South Africa to highlight the crucial role of CLM in bolstering the PS framework. By leveraging data sources often overlooked by conventional research and evaluation approaches, CLM emerges as a pivotal element in enhancing programme effectiveness. This paper delineates the fundamental principles of CLM, presents programme outcomes derived from CLM methodologies and contextualizes these findings within the broader framework of PS. Discussion The Citizen Science Project implements CLM continuously at 33 health facilities: 14 in Malawi (eight in Kasungu District and six in Dedza District), and 19 in South Africa (all in the West Rand District), representing a total catchment area of 989,848 people. Monitoring indicators are developed in an iterative process with community groups. The indicators are unique to each country, but both focus on the uptake of health services (quantitative) and barriers to access (qualitative). Monthly clinic records surveys capture 34 indicators in Malawi and 20 in South Africa and are supplemented by qualitative interviews with care recipients and healthcare workers. Qualitative interviews provide additional granularity and help confirm and explain the more macro trends in service coverage as described in quantitative data. The resulting data analysis reveals key themes that help stakeholders and decision‐makers to solve problems collaboratively. Noteworthy outcomes include a substantial increase in multi‐month dispensing of antiretroviral therapy (ART) during COVID‐19 (from 6% to 31%) with a subsequent recovery surpassing of HIV service benchmarks in Malawi post‐pandemic. Conclusions While quantifying direct impact remains challenging due to the project's design, CLM proves to be a robust methodology that generates credible data and produces impactful outcomes. Its potential extends beyond the health sector, empowering community leadership and fostering interventions aligned with community needs. As CLM continues to evolve, its integration into PS promises to improve relevance, quality and impact across diverse disciplines.
Synthetic Matrix Metalloproteinase-Sensitive Hydrogels for the Conduction of Tissue Regeneration: Engineering Cell-Invasion Characteristics
Synthetic hydrogels have been molecularly engineered to mimic the invasive characteristics of native provisional extracellular matrices: a combination of integrin-binding sites and substrates for matrix metalloproteinases (MMP) was required to render the networks degradable and invasive by cells via cell-secreted MMPs. Degradation of gels was engineered starting from a characterization of the degradation kinetics (kcatand Km) of synthetic MMP substrates in the soluble form and after crosslinking into a 3D hydrogel network. Primary human fibroblasts were demonstrated to proteolytically invade these networks, a process that depended on MMP substrate activity, adhesion ligand concentration, and network crosslinking density. Gels used to deliver recombinant human bone morphogenetic protein-2 to the site of critical defects in rat cranium were completely infiltrated by cells and remodeled into bony tissue within 4 wk at a dose of$5\\>\\mu g$per defect. Bone regeneration was also shown to depend on the proteolytic sensitivity of the matrices. These hydrogels may be useful in tissue engineering and cell biology as alternatives for naturally occurring extracellular matrix-derived materials such as fibrin or collagen.
Relationship Between Corn Vitreousness and Ruminal In Situ Starch Degradability
The objective of this experiment was to determine the relationship between corn kernel vitreousness and ruminal in situ starch degradation. Fourteen U.S. and five Brazilian corn hybrids cultivated in their respective countries were evaluated. The U.S. dent hybrids were harvested at one-half milk line, black layer, and 21 d after black layer stages of maturity. Brazilian flint hybrids were harvested only at the latest stage of maturity. Vitreousness was determined by manual dissection of the kernels. Ruminal in situ degradation of starch was determined in three lactating Holstein cows fitted with ruminal cannulae. Vitreousness of the five mature Brazilian hybrids averaged 73.1% (range of 64.2% to 80.0%), while vitreousness of the 14 mature U.S. hybrids averaged 48.2% (range of 34.9% to 62.3%). Within the 14 U.S. hybrids, average vitreousness increased from 42.8% to 48.2% as stage of maturity progressed from one-half milk line to 21 d after black layer. The correlation between kernel density and vitreousness was 0.87. The correlations between kernel vitreousness or density and ruminal starch availability were −0.93 and −0.87, respectively. With advancing maturity, kernel vitreousness and density increased while ruminal starch availability decreased. Kernel vitreousness and density may be useful parameters for which to select corn hybrids for high ruminal starch availability. Density may be a more practical measurement than vitreousness for screening large corn data sets.
Impaired Glucose Tolerance in Sleep Disorders
Recent epidemiological and experimental data suggest a negative influence of shortened or disturbed night sleep on glucose tolerance. Due to the high prevalence of sleep disorders this might be a major health issue. However, no comparative studies of carbohydrate metabolism have been conducted in clinical sleep disorders. We performed oral glucose tolerance tests (OGTT) and assessed additional parameters of carbohydrate metabolism in patients suffering from obstructive sleep apnea syndrome (OSAS, N = 25), restless legs syndrome (RLS, N = 18) or primary insomnia (N = 21), and in healthy controls (N = 33). Compared to controls, increased rates of impaired glucose tolerance were found in OSAS (OR: 4.9) and RLS (OR: 4.7) patients, but not in primary insomnia patients (OR: 1.6). In addition, HbA1c values were significantly increased in the same two patient groups. Significant positive correlations were found between 2-h plasma glucose values measured during the OGTT and the apnea-arousal-index in OSAS (r = 0.56; p<0.05) and the periodic leg movement-arousal-index in RLS (r = 0.56, p<0.05), respectively. Sleep duration and other quantitative aspects of sleep were similar between patient groups. Our findings suggest that some, but not all sleep disorders considerably compromise glucose metabolism. Repeated arousals during sleep might be a pivotal causative factor deserving further experimental investigations to reveal potential novel targets for the prevention of metabolic diseases.
Comparative efficiency of national health systems: cross national econometric analysis
Abstract Objective: To improve the evidence base for health policy by devising a method to measure and monitor the performance of health systems. Design: Estimation of the relation between levels of population health and the inputs used to produce health. Setting: 191 countries. Main outcome measure: Health system efficiency (performance). Results: Estimated efficiency varied from nearly fully efficient to nearly fully inefficient. Countries with a history of civil conflict or high prevalence of HIV and AIDS were less efficient. Performance increased with health expenditure per capita. Conclusions: Increasing the resources for health systems is critical to improving health in poor countries, but important gains can be made in most countries by using existing resources more efficiently. What is already known on this topic Evidence on the effectiveness of health system reforms is scarce Studies have not used a consistent framework for specifying goals or measuring outcomes What this study adds Countries with the best levels of health do not always have efficient health systems Efficiency is related to expenditure on health per capita, especially at low expenditure The methods of measuring performance provide a basis for identifying policies that improve health and for monitoring reforms
Critical Uncertainties and Gaps in the Environmental- and Social-Impact Assessment of the Proposed Interoceanic Canal through Nicaragua
The proposed interoceanic canal will connect the Caribbean Sea with the Pacific Ocean, traversing Lake Nicaragua, the major freshwater reservoir in Central America. If completed, the canal would be the largest infrastructure-related excavation project on Earth. In November 2015, the Nicaraguan government approved an environmental and social impact assessment (ESIA) for the canal. A group of international experts participated in a workshop organized by the Academy of Sciences of Nicaragua to review this ESIA. The group concluded that the ESIA does not meet international standards; essential information is lacking regarding the potential impacts on the lake, freshwater and marine environments, and biodiversity. The ESIA presents an inadequate assessment of natural hazards and socioeconomic disruptions. The panel recommends that work on the canal project be suspended until an appropriate ESIA is completed. The project should be resumed only if it is demonstrated to be economically feasible, environmentally acceptable, and socially beneficial.
Predicting Corn Grain Yield Using Silage Starch Content and Crop Adjuster Methods
Multi‐peril crop insurance (MPCI) requires that if corn (Zea mays L.) is insured for grain and the producer wants to use it for another purpose, that is, silage, the producer must have the corn grain yield appraised before corn silage harvest. This appraisal requires an adjuster to determine the weight of grain corn, and based on stage of maturity, apply a factor to convert the determined weight to the weight of mature corn at 155 g kg−1 moisture. This study was designed to test the hypothesis that corn grain yield can be estimated accurately before grain is combine harvested using the USDA–Risk Management Agency (RMA) methods and routine silage quality measurements for starch. Corn was established at two locations from 2006 to 2008. Management factors involving planting date, hybrid, and harvest timing were applied to create a range in yield and forage quality. Both RMA methods and the starch‐based method underestimated combine grain yield by 4 to 36% at silage harvest stages between 75 and 25% kernel milk (KM). At silage harvest, the starch method estimated final combine grain yield more accurately than the RMA maturity line weight (MLW) method, but when applied after silage harvest or just before grain harvest, the RMA Weight method was the better predictor of final combine grain yield. With careful assessment, starch‐analysis of silage theoretically could produce an equitable estimate of grain yield for insurance adjustments.