Approximately 40% of U.S. residents rely on groundwater as a source of drinking water. Groundwater, especially unconfined sand and gravel aquifers, is vulnerable to contamination from septic systems ...and infiltration of wastewater treatment plant effluent. In this study, we characterized concentrations of pharmaceuticals, perfluorosurfactants, and other organic wastewater compounds (OWCs) in the unconfined sand and gravel aquifer of Cape Cod, Massachusetts, USA, where septic systems are prevalent. Raw water samples from 20 public drinking water supply wells on Cape Cod were tested for 92 OWCs, as well as surrogates of wastewater impact. Fifteen of 20 wells contained at least one OWC; the two most frequently-detected chemicals were sulfamethoxazole (antibiotic) and perfluorooctane sulfonate (perfluorosurfactant). Maximum concentrations of sulfamethoxazole (113ng/L) and the anticonvulsant phenytoin (66ng/L) matched or exceeded maximum reported concentrations in other U.S. public drinking water sources. The sum of pharmaceutical concentrations and the number of detected chemicals were both significantly correlated with nitrate, boron, and extent of unsewered residential and commercial development within 500m, indicating that wastewater surrogates can be useful for identifying wells most likely to contain OWCs. Septic systems appear to be the primary source of OWCs in Cape Cod groundwater, although wastewater treatment plants and other sources were potential contributors to several wells. These results show that drinking water supplies in unconfined aquifers where septic systems are prevalent may be among the most vulnerable to OWCs. The presence of mixtures of OWCs in drinking water raises human health concerns; a full evaluation of potential risks is limited by a lack of health-based guidelines and toxicity assessments.
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•We tested 20 public wells in a sand and gravel aquifer for 92 OWCs.•Pharmaceuticals and perfluorosurfactants were frequently detected.•Septic systems are the primary sources of OWCs into the aquifer.•Maximum concentrations of two pharmaceuticals are as high as other U.S. source waters.•Nitrate, boron, and extent of unsewered development correlate with OWC presence.
The purpose of this study was to evaluate the effect of use of dual-energy CT monochromatic imaging in the late hepatic arterial phase on hyperenhancing focal lesion detection and lesion conspicuity.
...This prospective study included 72 patients imaged with a single-source dual-energy CT scanner. Late arterial phase imaging was performed with dual energies of 140 and 80 kVp, and the portal venous and delayed phases were performed with a single energy of 120 kVp. Two deidentified image sets were created: set A consisted of 77-keV images only, and set B consisted of 40-, 50-, 70-, and 77-keV images and iodine-based contrast material decomposition images. Two independent reviewers identified hypervascular lesions and subjectively scored lesion conspicuity. Contrast-to-noise ratios were calculated, and radiation dose (volume CT dose index) was recorded.
The 128 lesions identified had a mean size of 1.7 ± 1.4 cm. There was no difference in lesion detection between the two reviewers or the two image sets. The contrast-to-noise ratio at 50 keV was 72% greater than that at 77 keV (p < 0.0001). Subjective conspicuity was statistically greatest at 50 keV (p < 0.0001). There was no statistical difference in mean volume CT dose index between the dual-energy (12.8 mGy) and the two single-energy (14.4 and 14.2 mGy) phases.
Viewing dual-energy CT images may result in the greatest subjective lesion conspicuity and measured contrast-to-noise ratio at 50 keV with equal detection of hyperenhancing liver lesions compared with viewing 77-keV images alone. In addition, the radiation doses of dual-energy CT may be similar to those of single-energy CT.
•Multimorbidity is a common feature of old age and is accompanied by polypharmacy.•Targeting the core processes of ageing offers a new drug discovery approach for multimorbidity.•Inhibiting ageing ...processes reduces multiple diseases in mouse models.•Current clinical trials with repurposed drugs have shown clinical benefit•Targeting specific ageing processes with novel drugs may allow a more precise intervention.
Patients with multimorbidities have shorter life expectancy and their clinical management is more complex and expensive for healthcare systems currently focused on treating single diseases. Given that age is the major risk factor for multimorbidity, the challenge of treating these patients will only increase in coming years. Here, we review the case for targeting the core processes that drive the ageing phenotype as a novel pharmaceutical approach to multimorbidity. There is growing evidence that targeting ageing mechanisms can reduce or delay age-related diseases in animal models, and the first reports of clinical trials are now appearing. Although these trials currently focus on repurposed drugs, we propose several novel targets that would more specifically target ageing processes and thereby reduce multimorbidity and polypharmacy in future generations.
Advanced age is the major risk factor for multimorbidity. Current clinical practice treats the individual age-related diseases, resulting in polypharmacy. Thus, targeting the biological processes that drive ageing could prevent both multimorbidity and polypharmacy.
The purpose of this study is to compare three CT image reconstruction algorithms for liver lesion detection and appearance, subjective lesion conspicuity, and measured noise.
Thirty-six patients with ...known liver lesions were scanned with a routine clinical three-phase CT protocol using a weight-based noise index of 30 or 36. Image data from each phase were reconstructed with filtered back projection (FBP), adaptive statistical iterative reconstruction (ASIR), and model-based iterative reconstruction (MBIR). Randomized images were presented to two independent blinded reviewers to detect and categorize the appearance of lesions and to score lesion conspicuity. Lesion size, lesion density (in Hounsfield units), adjacent liver density (in Hounsfield units), and image noise were measured. Two different unblinded truth readers established the number, appearance, and location of lesions.
Fifty-one focal lesions were detected by truth readers. For blinded reviewers compared with truth readers, there was no difference for lesion detection among the reconstruction algorithms. Lesion appearance was statistically the same among the three reconstructions. Although one reviewer scored lesions as being more conspicuous with MBIR, the other scored them the same. There was significantly less background noise in air with MBIR (mean ± SD, 2.1 ± 1.4 HU) than with ASIR (8.9 ± 1.9 HU; p < 0.001) or FBP (10.6 ± 2.6 HU; p < 0.001). Mean lesion contrast-to-noise ratio was statistically significantly higher for MBIR (34.4 ± 29.1) than for ASIR (6.5 ± 4.9; p < 0.001) or FBP (6.3 ± 6.0; p < 0.001).
In routine-dose clinical CT of the liver, MBIR resulted in comparable lesion detection, lesion characterization, and subjective lesion conspicuity, but significantly lower background noise and higher contrast-to-noise ratio compared with ASIR or FBP. This finding suggests that further investigation of the use of MBIR to enable dose reduction in liver CT is warranted.
Proliferative verrucous leukoplakia (PVL) is a rare form of oral leukoplakia with a relatively high transformation rate resulting in oral squamous cell carcinoma (OSCC). Molecular analysis of PVL at ...the genome level is limited and has only identified molecular similarities between PVL and OSCC. However, the clinical profile of PVL suggests that molecular differences may be more important.
Whole exome sequencing of 5 PVL-associated OSCC (PVL-OSCC) and paired blood samples was used to identify somatic mutations common to the tumors. Whole methylome analysis of samples from 4 PVL-associated OSCC and 3 OSCC of non-PVL origin samples was conducted to explore differential methylation.
In contrast to conventional OSCC, PVL-associated OSCC showed infrequent TP53 mutation and altered spectra of PIK3CA and NOTCH1 mutations. Unsupervised hierarchical clustering identified 63 probes that discriminated between PVL-associated OSCC and OSCC of non-PVL origin. Differences in methylation were most significant for divalent metal ion transport, particularly calcium movement.
Specific differences in mutation and methylation profiles between PVL-derived OSCC and OSCC of non-PVL origin suggest differences in their transformation pathways. Further studies of early PVL lesions may identify markers of transformation that are also applicable to more common oral premalignant disorders such as oral epithelial dysplasia.
Exposure to chemicals that cause rodent mammary gland tumors is common, but few studies have evaluated potential breast cancer risks of these chemicals in humans.
The goal of this review was to ...identify and bring together the needed tools to facilitate the measurement of biomarkers of exposure to potential breast carcinogens in breast cancer studies and biomonitoring.
We conducted a structured literature search to identify measurement methods for exposure biomarkers for 102 chemicals that cause rodent mammary tumors. To evaluate concordance, we compared human and animal evidence for agents identified as plausibly linked to breast cancer in major reviews. To facilitate future application of exposure biomarkers, we compiled information about relevant cohort studies.
Exposure biomarkers have been developed for nearly three-quarters of these rodent mammary carcinogens. Analytical methods have been published for 73 of the chemicals. Some of the remaining chemicals could be measured using modified versions of existing methods for related chemicals. In humans, biomarkers of exposure have been measured for 62 chemicals, and for 45 in a nonoccupationally exposed population. The Centers for Disease Control and Prevention has measured 23 in the U.S. population. Seventy-five of the rodent mammary carcinogens fall into 17 groups, based on exposure potential, carcinogenicity, and structural similarity. Carcinogenicity in humans and rodents is generally consistent, although comparisons are limited because few agents have been studied in humans. We identified 44 cohort studies, with a total of > 3.5 million women enrolled, that have recorded breast cancer incidence and stored biological samples.
Exposure measurement methods and cohort study resources are available to expand biomonitoring and epidemiology related to breast cancer etiology and prevention.
To model the cost-effectiveness of the TYRX Absorbable Antibacterial Envelope when used in patients at increased risk of cardiac implantable electronic device (CIED) infection in the context of 3 ...European healthcare systems: Germany, Italy, and England.
A decision tree model with a lifetime horizon was populated using data from the Worldwide Randomized Antibiotic Envelope Infection Prevention Trial, a large multicenter randomized controlled trial. Use of the antibacterial envelope adjunctive to standard of care was compared to standard of care infection prevention alone. Patients in the model were divided into subgroups based on presence of factors known to increase infection risk.
The antibacterial envelope had the most favorable cost-effectiveness profile when patients had previously experienced CIED infection, had a history of immunosuppressive therapy, or had a Prevention of Arrhythmia Device Infection Trial (PADIT) score indicating high risk of infection (scores ≥6) at cost-effectiveness thresholds of €50 000 in Germany (assumed in the absence of an official threshold), €40 000 in Italy, and £30 000 in England. Probabilistic sensitivity analysis indicated that the antibacterial envelope was likely to be cost-effective in patients with other risk factors (including replacement of high power CIEDs, generator replacement with lead modification, and PADIT scores indicating intermediate risk of infection) when used with some device types and in some countries.
The absorbable antibacterial envelope was associated with cost-effectiveness ratios below European benchmarks in selected patients at increased risk of infection, suggesting the envelope provides value for European healthcare systems by reducing CIED infections.
•The TYRXTM Absorbable Antibacterial Envelope adjunctive to standard of care has been demonstrated to be effective in reducing the risk of cardiac implantable electronic device infection in patients undergoing pocket or lead revision, generator replacement, system upgrade, or an initial cardiac resynchronization therapy defibrillator implantation.•This analysis is the first to use randomized controlled trial data to model the lifetime impact of using a cardiac absorbable antibacterial envelope adjunctive to standard of care infection prevention on healthcare resource use, costs, and patient outcomes in 3 European healthcare systems.•The TYRXTM Absorbable Antibacterial Envelope is cost-effective in selected patients at increased risk of infection when considering cost-effectiveness thresholds of €40 000 in Italy, £30 000 in England, and €50 000 (assumption) in Germany.
Differences in grass pollen allergen exposure across Australia Beggs, Paul J.; Katelaris, Constance H.; Medek, Danielle ...
Australian and New Zealand journal of public health,
February 2015, 2015-02, 2015-Feb, 2015-02-00, 20150201, 2015-02-01, Letnik:
39, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Allergic rhinitis and allergic asthma are important chronic diseases posing serious public health issues in Australia with associated medical, economic, and societal burdens. Pollen are significant ...sources of clinically relevant outdoor aeroallergens, recognised as both a major trigger for, and cause of, allergic respiratory diseases. This study aimed to provide a national, and indeed international, perspective on the state of Australian pollen data using a large representative sample.
Atmospheric grass pollen concentration is examined over a number of years within the period 1995 to 2013 for Brisbane, Canberra, Darwin, Hobart, Melbourne, and Sydney, including determination of the ‘clinical’ grass pollen season and grass pollen peak.
The results of this study describe, for the first time, a striking spatial and temporal variability in grass pollen seasons in Australia, with important implications for clinicians and public health professionals, and the Australian grass pollen‐allergic community.
These results demonstrate that static pollen calendars are of limited utility and in some cases misleading. This study also highlights significant deficiencies and limitations in the existing Australian pollen monitoring and data.
Establishment of an Australian national pollen monitoring network would help facilitate advances in the clinical and public health management of the millions of Australians with asthma and allergic rhinitis.
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