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Filarial nematodes possess glutathione transferases (GSTs), ubiquitous enzymes with the potential to detoxify xenobiotic and endogenous substrates, and modulate the host immune system, which may aid worm infection establishment, maintenance and survival in the host. Here we have identified and characterized a σ class glycosylated GST (OoGST1), from the cattle-infective filarial nematode Onchocerca ochengi, which is homologous (99% amino acid identity) with an immunodominant GST and potential vaccine candidate from the human parasite, O. volvulus, (OvGST1b). Onchocerca ochengi native GSTs were purified using a two-step affinity chromatography approach, resolved by 2D and 1D SDS-PAGE and subjected to enzymic deglycosylation revealing the existence of at least four glycoforms. A combination of lectin-blotting and mass spectrometry (MS) analyses of the released N-glycans indicated that OoGST1 contained mainly oligomannose Man5GlcNAc2 structure, but also hybrid- and larger oligommanose-type glycans in a lower proportion. Furthermore, purified OoGST1 showed prostaglandin synthase activity as confirmed by Liquid Chromatography (LC)/MS following a coupled-enzyme assay. This is only the second reported and characterized glycosylated GST and our study highlights its potential role in host-parasite interactions and use in the study of human onchocerciasis.
Exotic annual grasses such as medusahead [Taeniatherum caput-medusae (L.) Nevski] and downy brome (Bromus tectorum L.) dominate millions of hectares of grasslands in the western United States. Applying picloram, aminopyralid, and other growth regulator herbicides at late growth stages reduces seed production of most exotic annual grasses. In this study, we applied aminopyralid to T. caput-medusae to determine how reducing seed production in the current growing season influenced cover in the subsequent growing season. At eight annual grassland sites, we applied aminopyralid at 55, 123, and 245 g ae ha−1 in spring just before T. caput-medusae heading. The two higher rates were also applied pre-emergence (PRE) in fall to allow comparisons with this previously tested timing. When applied in spring during the roughly 10-d period between the flag leaf and inflorescence first becoming visible, just 55 g ae ha−1 of aminopyralid greatly limited seed production and subsequently reduced T. caput-medusae cover to nearly zero. Fall aminopyralid applications were less effective against T. caput-medusae, even at a rate of 245 g ae ha−1. The growing season of application, fall treatments, but not spring treatments, sometimes reduced cover of desirable winter annual forage grasses. The growing season after application, both spring and fall treatments tended to increase forage grasses, though spring treatments generally caused larger increases. Compared with other herbicide treatment options, preheading aminopyralid treatments are a relatively inexpensive, effective approach for controlling T. caput-medusae and increasing forage production.
The History, Electrocardiogram (ECG), Age, Risk Factors, and Troponin (HEART) score is a decision aid designed to risk stratify emergency department (ED) patients with acute chest pain. It has been validated for ED use, but it has yet to be evaluated in a prehospital setting.
A prehospital modified HEART score can predict major adverse cardiac events (MACE) among undifferentiated chest pain patients transported to the ED.
A retrospective cohort study of patients with chest pain transported by two county-based Emergency Medical Service (EMS) agencies to a tertiary care center was conducted. Adults without ST-elevation myocardial infarction (STEMI) were included. Inter-facility transfers and those without a prehospital 12-lead ECG or an ED troponin measurement were excluded. Modified HEART scores were calculated by study investigators using a standardized data collection tool for each patient. All MACE (death, myocardial infarction [MI], or coronary revascularization) were determined by record review at 30 days. The sensitivity and negative predictive values (NPVs) for MACE at 30 days were calculated.
Over the study period, 794 patients met inclusion criteria. A MACE at 30 days was present in 10.7% (85/794) of patients with 12 deaths (1.5%), 66 MIs (8.3%), and 12 coronary revascularizations without MI (1.5%). The modified HEART score identified 33.2% (264/794) of patients as low risk. Among low-risk patients, 1.9% (5/264) had MACE (two MIs and three revascularizations without MI). The sensitivity and NPV for 30-day MACE was 94.1% (95% CI, 86.8-98.1) and 98.1% (95% CI, 95.6-99.4), respectively.
Prehospital modified HEART scores have a high NPV for MACE at 30 days. A study in which prehospital providers prospectively apply this decision aid is warranted.
The staffing of ambulances with different levels of Emergency Medical Service (EMS) providers is a difficult decision with evidence being mixed on the benefit of each model.
The objective of this study was to describe a pilot program evaluating alternative staffing on two ambulances utilizing the paramedic-basic (PB) model (staffed with one paramedic and one emergency medical technician[EMT]).
This was a retrospective study conducted from September 17, 2013 through December 31, 2013. The PB ambulances were compared to geographically matched ambulances staffed with paramedic-paramedic (PP ambulances). One PP and one PB ambulance were based at Station A; one PP and one PB ambulance were based at Station B. The primary outcome was total on-scene time. Secondary outcomes included time-to-electrocardiogram (EKG), time-to-intravenous (IV) line insertion, IV-line success rate, and percentage of protocol violations. Inclusion criteria were all patients requesting prehospital services that were attended to by these teams. Patients were excluded if they were not attended to by the study ambulance vehicles. Descriptive statistics were reported as medians and interquartile ranges (IQR). Proportions were reported with 95% confidence intervals (CI). The Mann-Whitley U test was used for significance testing (P<.05).
Median on-scene times at Station A for the PP ambulance were shorter than the PB ambulance team (PP: 10.1 minutes, IQR 6.0-15; PB: 13.0 minutes, IQR 8.1-18; P=.01). This finding also was noted at Station B (PP: 13.5 minutes, IQR 8.5-19; PB: 14.3 minutes, IQR 9.9-20; P=.01). There were no differences between PP and PB ambulance teams at Station A or Station B in time-to-EKG, time-to-IV insertion, IV success rate, and protocol violation rates.
In the setting of a well-developed EMS system utilizing an all-Advanced Life Support (ALS) response, this study suggests that PB ambulance teams may function well when compared to PP ambulances. Though longer scene times were observed, differences in time to ALS interventions and protocol violation rates were not different. Hybrid ambulance teams may be an effective staffing alternative, but decisions to use this model must address clinical and operational concerns.
CortezEJ, PanchalAR, DavisJE, KesegDP. The Effect of Ambulance Staffing Models in a Metropolitan, Fire-Based EMS System. Prehosp Disaster Med. 2017;32(2):175–179.
The spatial and temporal development of shear-induced overturning billows associated with breaking internal solitary waves is studied by means of a combined laboratory and numerical investigation. The waves are generated in the laboratory by a lock exchange mechanism and they are simulated numerically via a contour-advective semi-Lagrangian method. The properties of individual billows (maximum height attained, time of collapse, growth rate, speed, wavelength, Thorpe scale) are determined in each case, and the billow interaction processes are studied and classified. For broad flat waves, similar characteristics are seen to those in parallel shear flow, but, for waves not at the conjugate flow limit, billow characteristics are affected by the spatially varying wave-induced shear flow. Wave steepness and wave amplitude are shown to have a crucial influence on determining the type of interaction that occurs between billows and whether billow overturning can be arrested. Examples are given in which billows (i) evolve independently of one another, (ii) pair with one another, (iii) engulf/entrain one another and (iv) fail to completely overturn. It is shown that the vertical extent a billow can attain (and the associated Thorpe scale of the billow) is dependent on wave amplitude but that its value saturates once a given amplitude is reached. It is interesting to note that this amplitude is less than the conjugate flow limit amplitude. The number of billows that form on a wave is shown to be dependent on wavelength; shorter waves support fewer but larger billows than their long-wave counterparts for a given stratification.
We have obtained deep g, r, and i-band Subaru and ultra-deep 3.6 μm IRAC images of parts of the multiply-wrapped stellar stream around the nearby edge-on galaxy NGC 5907. We have fitted the surface brightness measurements of the stream with FSPS stellar population synthesis models to derive the metallicity and age of the brightest parts of the stream. The resulting relatively high metallicity ([Fe/H] = −0.3) is consistent with a major merger scenario but a satellite accretion event cannot be ruled out.
The Bovine Respiratory Disease Coordinated Agricultural Project (BRD CAP) is a 5-year project funded by the United States Department of Agriculture (USDA), with an overriding objective to use the tools of modern genomics to identify cattle that are less susceptible to BRD. To do this, two large genome wide association studies (GWAS) were conducted using a case:control design on preweaned Holstein dairy heifers and beef feedlot cattle. A health scoring system was used to identify BRD cases and controls. Heritability estimates for BRD susceptibility ranged from 19 to 21% in dairy calves to 29.2% in beef cattle when using numerical scores as a semi-quantitative definition of BRD. A GWAS analysis conducted on the dairy calf data showed that single nucleotide polymorphism (SNP) effects explained 20% of the variation in BRD incidence and 17–20% of the variation in clinical signs. These results represent a preliminary analysis of ongoing work to identify loci associated with BRD. Future work includes validation of the chromosomal regions and SNPs that have been identified as important for BRD susceptibility, fine mapping of chromosomes to identify causal SNPs, and integration of predictive markers for BRD susceptibility into genetic tests and national cattle genetic evaluations.
A number of copy number variants (CNVs) have been suggested as
susceptibility factors for schizophrenia. For some of these the data
remain equivocal, and the frequency in individuals with schizophrenia is
To determine the contribution of CNVs at 15 schizophrenia-associated loci
(a) using a large new data-set of patients with schizophrenia
(n = 6882) and controls (n = 6316),
and (b) combining our results with those from previous studies.
We used Illumina microarrays to analyse our data. Analyses were
restricted to 520 766 probes common to all arrays used in the different
We found higher rates in participants with schizophrenia than in controls
for 13 of the 15 previously implicated CNVs. Six were nominally
significantly associated (P<0.05) in this new
data-set: deletions at 1q21.1, NRXN1, 15q11.2 and
22q11.2 and duplications at 16p11.2 and the Angelman/Prader–Willi
Syndrome (AS/PWS) region. All eight AS/PWS duplications in patients were
of maternal origin. When combined with published data, 11 of the 15 loci
showed highly significant evidence for association with schizophrenia
We strengthen the support for the majority of the previously implicated
CNVs in schizophrenia. About 2.5% of patients with schizophrenia and 0.9%
of controls carry a large, detectable CNV at one of these loci. Routine
CNV screening may be clinically appropriate given the high rate of known
deleterious mutations in the disorder and the comorbidity associated with
these heritable mutations.
The Netherlands Twin Register (NTR) began in 1987 with data collection in twins and their families, including families with newborn twins and triplets. Twenty-five years later, the NTR has collected at least one survey for 70,784 children, born after 1985. For the majority of twins, longitudinal data collection has been done by age-specific surveys. Shortly after giving birth, mothers receive a first survey with items on pregnancy and birth. At age 2, a survey on growth and achievement of milestones is sent. At ages 3, 7, 9/10, and 12 parents and teachers receive a series of surveys that are targeted at the development of emotional and behavior problems. From age 14 years onward, adolescent twins and their siblings report on their behavior problems, health, and lifestyle. When the twins are 18 years and older, parents are also invited to take part in survey studies. In sub-groups of different ages, in-depth phenotyping was done for IQ, electroencephalography , MRI, growth, hormones, neuropsychological assessments, and cardiovascular measures. DNA and biological samples have also been collected and large numbers of twin pairs and parents have been genotyped for zygosity by either micro-satellites or sets of short nucleotide polymorphisms and repeat polymorphisms in candidate genes. Subject recruitment and data collection is still ongoing and the longitudinal database is growing. Data collection by record linkage in the Netherlands is beginning and we expect these combined longitudinal data to provide increased insights into the genetic etiology of development of mental and physical health in children and adolescents.
This study aims to evaluate changes in the durations of English National Health Service prescriptions, as indicated by the volumes of unit doses supplied between 1998 and 2009, and consider relevant policy implications.
Around the world, countries are seeking to manage the increase in medicines prescribing. In England, many primary care organisations, using limited supporting evidence of cost-effectiveness and clinical improvement, have sought to restrict the number of dosage units on a prescription to 28 days supply. This is based on a conviction that this reduces wastage costs.
Prescription Cost Analysis (PCA) statistics for England for the period January 1998 to December 2009 were used to analyse trends in the average number of unit doses (tablets or capsules) supplied per prescription for 11 drugs supplied in 34 different presentations.
The changes in prescription lengths observed between 1999 and 2009 ranged from +4.2% in the case of Amoxicillin 500 mg capsules to −41.3% in the case of Levothyroxine 50 μg tablets. All but four of the medicines selected showed statistically significant negative correlations (r > 0.8, P < 0.001) between the year of prescribing and the prescription length. If prescription lengths had been the same in 2009 as they were in 1999, then 33 million fewer prescription items would have been written for the preparations in this analysis. This shift across a range of medications suggests a generalised change in prescribing behaviour. The full balance of benefits and costs associated with this trend, as expressed via drug wastage avoided, patient (in)convenience experienced, professional time costs incurred or saved and positive or negative health outcome impacts, is not known. Although this study does not provide a definitive answer favouring prescription duration individualisation as opposed to standardisation, the available evidence indicates that policies that rigidly favour 28-day standard periods may require review.
With the desire to assess genetic variation across the lifespan in large-scale collaborative projects, one question is whether inference of copy number (CN) is sensitive to the source of material for deoxyribonucleic acid (DNA) analysis (e.g., blood and buccal) and another question is whether CN is stable as individuals age. Here, we address these questions by applying Affymetrix 6.0 single nucleotide polymorphism (SNP) micro-arrays to 1,472 DNA samples from 710 individuals from the Netherlands Twin Register, including twin and non-twin individuals (372 with buccal and blood derived DNA and 388 with longitudinal data). Similar concordance for CN and genotype inference between samples from the same individual [or from the monozygotic (MZ) co-twins] was found for blood and buccal tissues. There was a small but statistically significant decrease in across-tissue concordance compared with concordance of samples from the same tissue type. No temporal effect was seen on CN variation from the 388 individuals sampled at two time points ranging from 1 to 12 years apart. The majority of our individuals were sampled at age younger than 20 years. Genotype concordance was very high (R2 > 99%) between co-twins from 43 MZ pairs. For 75 dizygotic (DZ) pairs, R2 was ≈65%. CN estimates were highly consistent between co-twins from MZ pairs for both deletions (R2 ≈ 90%) and duplications (R2 ≈ 86%). For DZ, these were similar for within-individual comparisons, but naturally lower between co-twins (R2 ≈ 50–60%). These results suggest that DNA from buccal samples perform as well as DNA from blood samples on the current generation of micro-array technologies.
To detect an outbreak-related source of Legionella, control the outbreak, and prevent additional Legionella infections from occurring.
Design and Setting.
Epidemiologic investigation of an acute outbreak of hospital-associated Legionnaires disease among outpatients and visitors to a Wisconsin hospital.
Patients with laboratory-confirmed Legionnaires disease who resided in southeastern Wisconsin and had illness onsets during February and March 2010.
Patients with Legionnaires disease were interviewed using a hypothesis-generating questionnaire. On-site investigation included sampling of water and other potential environmental sources for Legionella testing. Case-finding measures included extensive notification of individuals potentially exposed at the hospital and alerts to area healthcare and laboratory personnel.
Laboratory-confirmed Legionnaires disease was diagnosed in 8 patients, all of whom were present at the same hospital during the 10 days prior to their illness onsets. Six patients had known exposure to a water wall-type decorative fountain near the main hospital entrance. Although the decorative fountain underwent routine cleaning and maintenance, high counts of Legionella pneumophila serogroup 1 were isolated from cultures of a foam material found above the fountain trough.
This outbreak of Legionnaires disease was associated with exposure to a decorative fountain located in a hospital public area. Routine cleaning and maintenance of fountains does not eliminate the risk of bacterial contamination. Our findings highlight the need to evaluate the safety of water fountains installed in any area of a healthcare facility.