Direct comparison of runoff of residual and knockdown herbicides in sugarcane using a rainfall simulator finds large difference in runoff losses and toxicity relative to diuron.

Runoff losses of herbicides have rarely been compared simultaneously under the same conditions. Our aim was to directly compare herbicide runoff losses, normalised for the amount present (relative runoff loads) and in absolute terms. Toxicity and runoff concentrations were combined to provide a risk ranking relative to diuron. Four rainfall simulation trials were conducted in sugarcane in the Great Barrier Reef catchment. Herbicides studied were older PSII residuals (atrazine, ametryn, diuron, hexazinone), alternative residuals (isoxaflutole, imazapic, metribuzin, metolachlor, pendimethalin) and knockdown herbicides (glyphosate, 2,4-D, fluroxypyr) and the tracer bromide (Br). Simulations were conducted two days after spraying, before differences due to half-lives were apparent. Two trials had bare soil and two had sugarcane trash. Herbicide runoff losses and concentrations were closely related to the amount applied, runoff amounts and partitioning coefficients. Relative runoff losses and absolute losses were similar for most older and alternative residual herbicides, 2,4-D and Br. Glyphosate and pendimethalin relative runoff losses were low, due to greater sorption. Isoxaflutole, imazapic, and fluroxypyr are applied at much lower rates and runoff losses were low. Herbicides were lost in the dissolved phase, except pendimethalin. There was a large range in toxicity relative to diuron. There is a range of herbicide choices posing less offsite risk than diuron and ametryn, which have high application rates and high toxicity. Herbicide choice should consider application rate, runoff losses, sorption, and toxicity.

Identification of a novel specific small-molecule melanocortin-2-receptor antagonist.

The overproduction of adrenocorticotropic hormone (ACTH), in conditions such as Cushing's disease and congenital adrenal hyperplasia (CAH), leads to significant morbidity. Current treatment with glucocorticoids does not adequately suppress plasma ACTH, resulting in excess adrenal androgen production. At present, there is no effective medical treatment in clinical use that would directly block the action of ACTH. Such a therapy would be of great clinical value. ACTH acts via a highly selective receptor, the melanocortin-2 receptor (MC2R) associated with its accessory protein MRAP. ACTH is the only known naturally occurring agonist for this receptor. This lack of redundancy and the high degree of ligand specificity suggest that antagonism of this receptor could provide a useful therapeutic strategy in the treatment of conditions of ACTH excess. To this end, we screened an extensive library of low-molecular-weight drug-like compounds for MC2R antagonist activity using a high-throughput homogeneous time-resolved fluorescence cAMP assay in Chinese hamster ovary cells stably co-expressing human MC2R and MRAP. Hits that demonstrated MC2R antagonist properties were counter-screened against the ß2 adrenergic receptor and dose-response analysis undertaken. This led to the identification of a highly specific MC2R antagonist capable of antagonising ACTH-induced progesterone release in murine Y-1 adrenal cells and having selectivity for MC2R amongst the human melanocortin receptors. This work provides a foundation for the clinical investigation of small-molecule ACTH antagonists as therapeutic agents and proof of concept for the screening and discovery of such compounds.

Electronic medical record documentation of tobacco cessation support at eight community safety-net clinics with a high prevalence of tobacco use.

OBJECTIVES: The high prevalence of tobacco use at primary care safety-net clinics represents an opportunity to offer assistance with cessation. Documentation of smoking status, offering advice and medications, and referral to cessation services are important steps in supporting cessation attempts and are required elements by payors and accrediting agencies to demonstrate care quality. This study examines tobacco cessation support rates and patient characteristics using electronic medical record (EMR) data. METHODS: This cross-sectional study engaged eight community health centers affiliated with a county hospital system in NE Ohio where adult tobacco use rates exceed 30%. EMR data from June 2014 through May 2016 were analysed to assess rates of tobacco cessation counselling, order of cessation medications, or both. The association of tobacco cessation support with patient characteristics and quit attempts was assessed using multivariable logistic regression models. RESULTS: Among 21 702 current tobacco users, 74% had no intervention documented; 15.4% had counselling documented, 6.4% were prescribed tobacco cessation medication, and 4.2% had both documented. Males, those aged 18 to 34, and African Americans were more likely to have no documented intervention. Of current tobacco users with at least two visits, 5.6% had a quit attempt. Medication alone was associated with a greater likelihood of a quit attempt (AOR: 1.72 [95% CI: 1.36-2.17]) as well as counselling and medication combined (AOR: 1.95 [95% CI: 1.48-2.56]). CONCLUSIONS: Tobacco cessation support was lacking for 74% of current smokers and was less likely in subgroups including males, younger adults, and African Americans. Ordering tobacco cessation medication combined with counselling nearly doubled the likelihood of a quit attempt.

Bottom trawl fishing footprints on the world's continental shelves.

Bottom trawlers land around 19 million tons of fish and invertebrates annually, almost one-quarter of wild marine landings. The extent of bottom trawling footprint (seabed area trawled at least once in a specified region and time period) is often contested but poorly described. We quantify footprints using high-resolution satellite vessel monitoring system (VMS) and logbook data on 24 continental shelves and slopes to 1,000-m depth over at least 2 years. Trawling footprint varied markedly among regions: from <10% of seabed area in Australian and New Zealand waters, the Aleutian Islands, East Bering Sea, South Chile, and Gulf of Alaska to >50% in some European seas. Overall, 14% of the 7.8 million-km2 study area was trawled, and 86% was not trawled. Trawling activity was aggregated; the most intensively trawled areas accounting for 90% of activity comprised 77% of footprint on average. Regional swept area ratio (SAR; ratio of total swept area trawled annually to total area of region, a metric of trawling intensity) and footprint area were related, providing an approach to estimate regional trawling footprints when high-resolution spatial data are unavailable. If SAR was ≤0.1, as in 8 of 24 regions, there was >95% probability that >90% of seabed was not trawled. If SAR was 7.9, equal to the highest SAR recorded, there was >95% probability that >70% of seabed was trawled. Footprints were smaller and SAR was ≤0.25 in regions where fishing rates consistently met international sustainability benchmarks for fish stocks, implying collateral environmental benefits from sustainable fishing.

Recognizing millions of consistently unidentified spectra across hundreds of shotgun proteomics datasets.

Mass spectrometry (MS) is the main technology used in proteomics approaches. However, on average 75% of spectra analysed in an MS experiment remain unidentified. We propose to use spectrum clustering at a large-scale to shed a light on these unidentified spectra. PRoteomics IDEntifications database (PRIDE) Archive is one of the largest MS proteomics public data repositories worldwide. By clustering all tandem MS spectra publicly available in PRIDE Archive, coming from hundreds of datasets, we were able to consistently characterize three distinct groups of spectra: 1) incorrectly identified spectra, 2) spectra correctly identified but below the set scoring threshold, and 3) truly unidentified spectra. Using a multitude of complementary analysis approaches, we were able to identify less than 20% of the consistently unidentified spectra. The complete spectrum clustering results are available through the new version of the PRIDE Cluster resource (http://www.ebi.ac.uk/pride/cluster). This resource is intended, among other aims, to encourage and simplify further investigation into these unidentified spectra.

Development and validation of the Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) Questionnaire in patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) has a deleterious impact on health-related quality-of-life (HRQoL), but measuring this outcome is difficult. A comprehensive, validated, disease-specific questionnaire to measure the spectrum of QoL domains affected by AF and its treatment is not available. We developed and validated a 20-item questionnaire, Atrial Fibrillation Effect on QualiTy-of-life (AFEQT), in a 6-center, prospective, observational study. METHODS AND RESULTS: Factor analyses established 4 conceptual domains (Symptoms, Daily Activities, Treatment Concern, and Treatment Satisfaction) from which individual domain and global scores were calculated. Participants from 6 centers completed the AFEQT at baseline, at month 1, and at month 3. Psychometric analyses included internal consistency and known-group validity. Test-retest reliability was assessed by comparing 1-month changes in scores among those with no change in therapy. Effect size was used to assess responsiveness after intervention. Among 219 patients age 62±11.9 years, 94% completed the AFEQT at baseline and 3 months; 66% had paroxysmal, 24% persistent, 5% longstanding persistent, and 5% permanent AF. Internal consistency was >0.88 for all scales. Lower AFEQT scores were observed with increased AF severity, categorized as asymptomatic, mild, moderate and severe, respectively: 71.2±20.6, 71.3±19.2, 57.9±19.0, and 42.0±21.2. Intraclass correlations for Overall, Symptoms, Daily Activities, Treatment Concern, and Satisfaction scores were 0.8, 0.5, 0.8, 0.7, and 0.7, respectively. Changes in 3-month scores were larger after ablation than with pharmacological adjustments, and both were greater than those observed in stable patients. CONCLUSIONS: This initial validation of AFEQT supports its use as an outcome in studies and a means to clinically follow patients with AF.

Resiliency training for medical professionals.

For the past 10 years, the military medical system costs have increased by an estimated 167 percent. Behavioral health issues and physical ailments are major contributors to the increased costs. As a result, fatigue and burnout of medical professionals are growing concerns. The Army Medical Department (AMEDD) recognizes that physical and psychological stressors adversely impact personal well-being and organizational goals. Thus, an emphasis on enhancing the individual s resiliency framework is essential to the stamina and long-term endurance to sustain the continued provision of high quality medical care. To that end, the Army Medical Command (MEDCOM) has instituted the Provider Resiliency Program. The Professional Provider Resiliency Training (PPRT) conducted by the AMEDD Center and School should be a key element of the MEDCOM Provider Resiliency Program. The PPRT provides medical professionals the opportunity to significantly develop and enhance their resiliency skills. This article includes outcome data from 172 medical professionals who attended the PPRT. Specific focus is on their perspective about resiliency training. The findings in this article revealed that the doctors (100 percent), nurses (98 percent), behavioral health providers (90 percent) and other professionals (100 percent) who attended the PPRT course valued the training and indicated that they will use the learned mind-body resiliency techniques.

A free-enzyme catalyst for the bioremediation of environmental atrazine contamination.

Herbicide contamination from agriculture is a major issue worldwide, and has been identified as a threat to freshwater and marine environments in the Great Barrier Reef World Heritage Area in Australia. The triazine herbicides are of particular concern because of potential adverse effects, both on photosynthetic organisms and upon vertebrate development. To date a number of bioremediation strategies have been proposed for triazine herbicides, but are unlikely to be implemented due to their reliance upon the release of genetically modified organisms. We propose an alternative strategy using a free-enzyme bioremediant, which is unconstrained by the issues surrounding the use of live organisms. Here we report an initial field trial with an enzyme-based product, demonstrating that the technology is technically capable of remediating water bodies contaminated with the most common triazine herbicide, atrazine.

Os peroneum friction syndrome complicated by sesamoid fatigue fracture: a new radiological diagnosis? Case report and literature review.

Injuries to the peroneal tendons are relatively common worldwide but tendon rupture without significant trauma is uncommon. Ankle mechanics can be seriously affected by disruption of one or both of the peroneal tendons although complete rupture can also remain asymptomatic. Accessory ossicles are sesamoid bones and are common findings in routine radiology of the foot and ankle. Although in the vast majority these "os" are normal variants of anatomy, they can lead to painful syndromes and suffer fractures and even undergo degenerative changes in response to overuse and trauma. Although similar syndromes have been discussed in the surgical literature, there is a lack of literature describing the use of modern imaging in the accurate diagnosis and its subsequent assistance towards appropriate management of os peroneum friction syndrome complicated by sesamoid fatigue syndrome. This article presents the plain film, sonographic and magnetic resonance imaging findings in a case of os peroneum friction syndrome complicated by a sesamoid fatigue fracture as well as reviewing the pertinent literature.

A novel experimental design for comparative two-dimensional gel analysis: two-dimensional difference gel electrophoresis incorporating a pooled internal standard.

The comparison of two-dimensional (2-D) gel images from different samples is an established method used to study differences in protein expression. Conventional methods rely on comparing images from at least 2 different gels. Due to the high variation between gels, detection and quantification of protein differences can be problematic. Two-dimensional difference gel electrophoresis (Ettan trade mark DIGE) is an emerging technique for comparative proteomics, which improves the reproducibility and reliability of differential protein expression analysis between samples. In the application of DIGE different samples are labelled with mass and charge matched spectrally resolvable fluorescent dyes and are then separated on the same 2-D gel. Using an Escherichia coli lysate "spiked" with varying amounts of four different known proteins, we have tested a novel experimental design that exploits the sample multiplexing capabilities of DIGE, by including a standard sample in each gel. The standard sample comprises equal amounts of each sample to be compared and was found to improve the accuracy of protein quantification between samples from different gels allowing accurate detection of small differences in protein levels between samples.

Fluorescence two-dimensional difference gel electrophoresis and mass spectrometry based proteomic analysis of Escherichia coli.

Separation and relative quantitation of complex protein mixtures remain two of the most challenging aspects of proteomics. Here an advanced technique called fluorescence difference 2-D gel electrophoresis technology (2D-DIGE) has been applied to a model system study of the Escherichia coli proteome after benzoic acid treatment. The molecular weight and charge matched cyanine dyes enable pre-electrophoretic labelling of control and treated samples which are then mixed and run in the same gel. Pooled control and treated samples labelled with Cy trade mark 3 were used as an internal standard for both Cy5 labelled control and treated E. coli samples. Together with DeCyder trade mark imaging analysis software, more accurate quantitative analysis than conventional two-dimensional polyacrylamide gel electrophoresis was achieved. Using matrix-assisted laser desorption/ionization-time of flight and quadrupole-time of flight mass spectrometry a total of 179 differentially expressed protein spots were identified. These included enzymes, stress related and substrate (e.g. amino acids, maltose, ribose and TRP repressor) binding proteins. Of the spots analysed, 77% contained only one protein species per spot, hence the change in protein expression measured was solely attributed to the identified protein. Many membrane proteins and protein isoforms were identified indicating both adequate solubilization of E. coli samples and potential post-translational modification. The results indicate that the regulatory mechanisms following benzoic acid treatment of E. coli are far more complicated than hitherto expected.