Human and bovine viruses in the Milwaukee River watershed: Hydrologically relevant representation and relations with environmental variables

AbstractTo examine the occurrence, hydrologic variability, and seasonal variability of human and bovine viruses in surface water, three stream locations were monitored in the Milwaukee River watershed in Wisconsin, USA, from February 2007 through June 2008. Monitoring sites included an urban subwatershed, a rural subwatershed, and the Milwaukee River at the mouth. To collect samples that characterize variability throughout changing hydrologic periods, a process control system was developed for unattended, large-volume (56–2800L) filtration over extended durations. This system provided flow-weighted mean concentrations during runoff and extended (24-h) low-flow periods. Human viruses and bovine viruses were detected by real-time qPCR in 49% and 41% of samples (n=63), respectively. All human viruses analyzed were detected at least once including adenovirus (40% of samples), GI norovirus (10%), enterovirus (8%), rotavirus (6%), GII norovirus (1.6%) and hepatitis A virus (1.6%). Three of seven bovine viruses analyzed were detected including bovine polyomavirus (32%), bovine rotavirus (19%), and bovine viral diarrhea virus type 1 (5%). Human viruses were present in 63% of runoff samples resulting from precipitation and snowmelt, and 20% of low-flow samples. Maximum human virus concentrations exceeded 300genomiccopies/L. Bovine viruses were present in 46% of runoff samples resulting from precipitation and snowmelt and 14% of low-flow samples. The maximum bovine virus concentration was 11genomiccopies/L. Statistical modeling indicated that stream flow, precipitation, and season explained the variability of human viruses in the watershed, and hydrologic condition (runoff event or low-flow) and season explained the variability of the sum of human and bovine viruses; however, no model was identified that could explain the variability of bovine viruses alone. Understanding the factors that affect virus fate and transport in rivers will aid watershed management for minimizing human exposure and disease transmission

Withdrawal from treatment as an outcome in the Isolde study of COPD

Objectives: To investigate the determinants of patient withdrawal from our study, and the effect of these withdrawals on the outcome of treatment with inhaled corticosteroids in patients with COPD. Design: A double-blind, placebo-controlled, randomized trial. Setting: Eighteen outpatient centers in the United Kingdom. Participants: Seven hundred fifty-one patients with stable COPD defined clinically as baseline postbronchodilator FEV1 > 0.8 L and < 85% predicted, FEV1/FVC ratio < 70%, and FEV1 change after albuterol < 10% of predicted. Intervention: Random assignment of either 500 micrograms bid of inhaled fluticasone propionate (FP)using a spacer device or an identical placebo inhaler. Treatment was continued for 3 years or until patients withdrew from follow-up. Measurements and results: Postbronchodilator FEV1 was measured on three occasions before randomization and every 3 months thereafter. Health status was assessed by the disease-specific St. George Respiratory Questionnaire (SGRQ) and the modified short-form 36 questionnaire (SF-36) at baseline and every 6 months. Three hundred thirty-nine patients withdrew, of whom 156 patients received FP. Prescription of frequent courses of oral prednisolone was the most common reason for withdrawing as specified in the protocol (69 patients in the FP group withdrew due to respiratory symptoms, compared with 93 patients in the placebo group). This explained the significantly greater dropout of placebo-treated patients that was most evident when FEV1 was < 50% predicted. Patients withdrawing had a significantly more rapid decline in health status, measured by both the SGRQ and the SF-36 (p < 0.001). Those withdrawing from the placebo group had a more rapid decline in FEV1 and more exacerbations than the FP-treated groups. Baseline FEV1 was lower in dropouts than in patients completing the study receiving placebo, but there was no difference between the respective groups receiving FP. Conclusions: Patients who withdrew from follow-up were those with the most rapidly deteriorating health status and lung function. Losing these patients from the final analysis can reduce the power of a study to achieve its primary end point

Prepyramid-to-pyramid transition of SiGe islands on Si(001)

The morphology of the first three-dimensional islands appearing during strained growth of SiGe alloys on Si(001) was investigated by scanning tunneling microscopy. High resolution images of individual islands and a statistical analysis of island shapes were used to reconstruct the evolution of the island shape as a function of size. As they grow, islands undergo a transition from completely unfacetted rough mounds (prepyramids) to partially {105} facetted islands and then they gradually evolve to {105} facetted pyramids. The results are in good agreement with the predictions of a recently proposed theoretical model

Factors Associated with Endocrine Therapy Non-Adherence in Breast Cancer Survivors

Background: For women with hormone receptor positive breast cancer, long-term endocrine therapy (ET) can greatly reduce the risk of recurrence, yet adherence is low- particularly among traditionally underserved populations. Methods: The Carolina Breast Cancer Study oversampled Black and young women (<50 years of age). Participants answered an ET-specific medication adherence questionnaire assessing reasons for non-adherence. We used principal factor analysis to identify latent factors describing ET non-adherence. We then performed multivariable regression to determine clinical and demographic characteristics associated with each ET non-adherence factor. Results: 1,231 women were included in analysis, 59% reported at least one barrier to ET adherence. We identified three latent factors which we defined as: habit - challenges developing medication-taking behavior; tradeoffs - high perceived side effect burden and medication safety concerns; and resource barriers - challenges related to cost or accessibility. Older age (50+) was associated with less reporting of habit (Adjusted Risk Ratio (aRR) 0.54[95% CI: 0.43-0.69] and resource barriers (aRR 0.66[0.43-0.997]), but was not associated with tradeoff barriers. Medicaid-insured women were more likely than privately-insured to report tradeoff (aRR:1.53 [1.10-2.13]) or resource barriers (aRR:4.43[2.49-6.57]). Black race was associated with increased reporting of all factors (habit: aRR 1.29[1.09-1.53]; tradeoffs: 1.32[1.09-1.60], resources: 1.65[1.18-2.30]). Conclusion: Barriers to ET adherence were described by three distinct factors, and strongly associated with sociodemographic characteristics. Barriers to ET adherence appear inadequately addressed for younger, Black, and publicly-insured breast cancer survivors. These findings underscore the importance of developing multi-faceted, patient-centered interventions that address a diverse range of barriers to ET adherence

Explosive Percolation in the Human Protein Homology Network

We study the explosive character of the percolation transition in a real-world network. We show that the emergence of a spanning cluster in the Human Protein Homology Network (H-PHN) exhibits similar features to an Achlioptas-type process and is markedly different from regular random percolation. The underlying mechanism of this transition can be described by slow-growing clusters that remain isolated until the later stages of the process, when the addition of a small number of links leads to the rapid interconnection of these modules into a giant cluster. Our results indicate that the evolutionary-based process that shapes the topology of the H-PHN through duplication-divergence events may occur in sudden steps, similarly to what is seen in first-order phase transitions.Comment: 13 pages, 6 figure

Cell adhesion molecule cadherin-6 function in zebrafish cranial and lateral line ganglia development

Cadherins regulate the vertebrate nervous system development. We previously showed that cadherin-6 message (cdh6) was strongly expressed in the majority of the embryonic zebrafish cranial and lateral line ganglia during their development. Here, we present evidence that cdh6 has specific functions during cranial and lateral line ganglia and nerve development. We analyzed the consequences of cdh6 loss-of-function on cranial ganglion and nerve differentiation in zebrafish embryos. Embryos injected with zebrafish cdh6 specific antisense morpholino oligonucleotides (MOs, which suppress gene expression during development; cdh6 morphant embryos) displayed a specific phenotype, including (i) altered shape and reduced development of a subset of the cranial and lateral line ganglia (e.g., the statoacoustic ganglion and vagal ganglion) and (ii) cranial nerves were abnormally formed. These data illustrate an important role for cdh6 in the formation of cranial ganglia and their nerves

Simvastatin suppresses experimental aortic aneurysm expansion

ObjectiveAbdominal aortic aneurysm (AAA) formation is a result of inflammation and extracellular matrix (ECM) remodeling mediated by matrix metalloproteinases (MMPs). Hydroxymethylglutaryl-coenzyme A inhibitors (statins), although clinically used as lipid-lowering agents, have also been demonstrated to have anti-inflammatory effects. This study was designed to determine whether the hydroxymethylglutaryl-coenzyme A inhibitor simvastatin suppresses aneurysm formation in an elastase-induced rat AAA model.MethodsAneurysms were created in adult male Wistar rats by infusion of elastase into isolated infrarenal aortic segments. The rats were randomized to receive either simvastatin (n = 17) or placebo (n = 17) by gastric lavage daily starting the day before surgery. The rats were euthanized and the infrarenal aortas harvested on postoperative day 7. Aortic diameters were measured before infusion, immediately after infusion, and at the time of harvesting. Protein expression was measured by immunoblot analysis. Gene expression profiling using Affymetrix U34A rat genome chips was performed to identify changes in gene expression caused by simvastatin treatment.ResultsMean aneurysm diameter was significantly less in the simvastatin treatment group compared with controls (3.4 ± 0.08 mm vs 4.3 ± 0.19 mm; P = .0001). MMP-9 and nuclear factor-κB protein levels were decreased in the aortas of simvastatin-treated animals. Gene microarray analysis revealed 315 genes with statistically significant changes in expression (P < .05) in the simvastatin group. Genes related to inflammation, ECM remodeling, and oxidative stress function were downregulated. These included genes for interleukin 1, interleukin 4, inducible nitric oxide synthase, P-selectin, platelet-derived growth factor α, tumor necrosis factor, and several chemokines.ConclusionsSimvastatin significantly suppresses experimental aneurysm expansion and reduces protein levels of MMP-9 and nuclear factor-κB. Gene array analysis provides evidence that several mediators of inflammation, matrix remodeling, and oxidative stress are downregulated by simvastatin treatment. This suggests that simvastatin inhibits AAA formation by blocking the expression of certain proinflammatory genes. Simvastatin may be useful as an adjuvant therapy to suppress the growth of small aneurysms.Clinical RelevanceHuman aortic aneurysms are characterized histologically by an inflammatory infiltrate with severe proteolytic destruction. Statins, although used clinically as lipid-lowering agents, have been shown to have anti-inflammatory effects. Simvastatin reduced experimental aneurysm size in this study. It seems that this reduction is mediated by interfering with multiple pathways, including oxidative stress, inflammation, and ECM and matrix remodeling. Further study into the effect of statins in reducing the growth of AAAs in patients is warranted

The Environmental Microbiology Minimum Information (EMMI) Guidelines: QPCR and dPCR Quality and Reporting for Environmental Microbiology

Real-time quantitative polymerase chain reaction (qPCR) and digital PCR (dPCR) methods have revolutionized environmental microbiology, yielding quantitative organism-specific data of nucleic acid targets in the environment. Such data are essential for characterizing interactions and processes of microbial communities, assessing microbial contaminants in the environment (water, air, fomites), and developing interventions (water treatment, surface disinfection, air purification) to curb infectious disease transmission. However, our review of recent qPCR and dPCR literature in our field of health-related environmental microbiology showed that many researchers are not reporting necessary and sufficient controls and methods, which would serve to strengthen their study results and conclusions. Here, we describe the application, utility, and interpretation of the suite of controls needed to make high quality qPCR and dPCR measurements of microorganisms in the environment. Our presentation is organized by the discrete steps and operations typical of this measurement process. We propose systematic terminology to minimize ambiguity and aid comparisons among studies. Example schemes for batching and combining controls for efficient work flow are demonstrated. We describe critical reporting elements for enhancing data credibility, and we provide an element checklist in the Supporting Information. Additionally, we present several key principles in metrology as context for laboratories to devise their own quality assurance and quality control reporting framework. Following the EMMI guidelines will improve comparability and reproducibility among qPCR and dPCR studies in environmental microbiology, better inform engineering and public health actions for preventing disease transmission through environmental pathways, and for the most pressing issues in the discipline, focus the weight of evidence in the direction toward solutions

Has NICE guidance changed the management of the suspected scaphoid fracture: A survey of UK practice

YesIntroduction: Despite scaphoid fractures being relatively uncommon pro-active treatment of suspected fractures has been seen as a risk management strategy. The poor positive predictive value of X-rays has led to published guidelines advocating MRI as a first-line or early imaging tool. It is unclear whether UK hospitals have been able to introduce early scanning and this national survey sought to establish the current management strategies for patients with a suspected scaphoid fracture. Method: An electronic survey of UK emergency departments (ED) was conducted to establish the initial and follow up strategies for patients with negative imaging. Comparison of first and second-line imaging modalities was undertaken together with review of the clinical speciality responsible for ongoing management. Results: 166 UK NHS Trusts were identified with emergency department facilities of which 66 (39.8%) responded. All sites perform an X-ray as the initial examination. For those with a negative examination ED follow up was the most common approach (54.6%), although many sites refer patients to other specialities including orthopaedics (39.4%) for follow up. The data demonstrated inconsistencies in the number of follow-up episodes and the different imaging investigations utilised. Frustration with the challenges presented by this patient cohort was evident. Conclusion: The suspected scaphoid fracture represents an ongoing challenge to the NHS with many resource intensive pathways reliant on access to complex imaging investigations. Implications for practice: Our study identified that UK Emergency Departments have limited early access to complex imaging for scanning of the scaphoid. A range of strategies are used for follow up of suspected scaphoid fractures and these are resource intensive. Overtreatment of patients with suspected scaphoid fracture is used as a risk management approach