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We implemented a cross-sectional study in Tana River County, Kenya, a Rift Valley fever (RVF)-endemic area, to quantify the strength of association between RVF virus (RVFv) seroprevalences in livestock and humans, and their respective intra-cluster correlation coefficients (ICCs). The study involved 1932 livestock from 152 households and 552 humans from 170 households. Serum samples were collected and screened for anti-RVFv immunoglobulin G (IgG) antibodies using inhibition IgG enzyme-linked immunosorbent assay (ELISA). Data collected were analysed using generalised linear mixed effects models, with herd/household and village being fitted as random variables. The overall RVFv seroprevalences in livestock and humans were 25.41% (95% confidence interval (CI) 23.49–27.42%) and 21.20% (17.86–24.85%), respectively. The presence of at least one seropositive animal in a household was associated with an increased odds of exposure in people of 2.23 (95% CI 1.03–4.84). The ICCs associated with RVF virus seroprevalence in livestock were 0.30 (95% CI 0.19–0.44) and 0.22 (95% CI 0.12–0.38) within and between herds, respectively. These findings suggest that there is a greater variability of RVF virus exposure between than within herds. We discuss ways of using these ICC estimates in observational surveys for RVF in endemic areas and postulate that the design of the sentinel herd surveillance should consider patterns of RVF clustering to enhance its effectiveness as an early warning system for RVF epidemics.
Cryo-electron microscopy (cryo-EM) is a powerful tool for macromolecular to near-atomic resolution structure determination in the biological sciences. The specimen is maintained in a near-native environment within a thin film of vitreous ice and imaged in a transmission electron microscope. The images can then be processed by a number of computational methods to produce three-dimensional information. Recent advances in sample preparation, imaging, and data processing have led to tremendous growth in the field of cryo-EM by providing higher resolution structures and the ability to investigate macromolecules within the context of the cell. Here, we review developments in sample preparation methods and substrates, detectors, phase plates, and cryo-correlative light and electron microscopy that have contributed to this expansion. We also have included specific biological applications.
BACKGROUND: IGTS is a rare phenomenon of paradoxical germ cell tumor (GCT) growth during or following treatment despite normalization of tumor markers. We sought to evaluate the frequency, clinical characteristics and outcome of IGTS in patients in 21 North-American and Australian institutions. METHODS: Patients with IGTS diagnosed from 2000-2017 were retrospectively evaluated. RESULTS: Out of 739 GCT diagnoses, IGTS was identified in 33 patients (4.5%). IGTS occurred in 9/191 (4.7%) mixed-malignant GCTs, 4/22 (18.2%) immature teratomas (ITs), 3/472 (0.6%) germinomas/germinomas with mature teratoma, and in 17 secreting non-biopsied tumours. Median age at GCT diagnosis was 10.9 years (range 1.8-19.4). Male gender (84%) and pineal location (88%) predominated. Of 27 patients with elevated markers, median serum AFP and Beta-HCG were 70 ng/mL (range 9.2-932) and 44 IU/L (range 4.2-493), respectively. IGTS occurred at a median time of 2 months (range 0.5-32) from diagnosis, during chemotherapy in 85%, radiation in 3%, and after treatment completion in 12%. Surgical resection was attempted in all, leading to gross total resection in 76%. Most patients (79%) resumed GCT chemotherapy/radiation after surgery. At a median follow-up of 5.3 years (range 0.3-12), all but 2 patients are alive (1 succumbed to progressive disease, 1 to malignant transformation of GCT). CONCLUSION: IGTS occurred in less than 5% of patients with GCT and most commonly after initiation of chemotherapy. IGTS was more common in patients with IT-only on biopsy than with mixed-malignant GCT. Surgical resection is a principal treatment modality. Survival outcomes for patients who developed IGTS are favourable.
Herbicide resistance, and in particular multiple-herbicide resistance, poses an ever-increasing threat to food security. A biotype of junglerice [Echinochloa colona (L.) Link] with resistance to four herbicides, imazamox, fenoxaprop-P-ethyl, quinclorac, and propanil, each representing a different mechanism of action, was identified in Sunflower County, MS. Dose responses were performed on the resistant biotype and a biotype sensitive to all four herbicides to determine the level of resistance. Application of a cytochrome P450 inhibitor, malathion, with the herbicides imazamox and quinclorac resulted in increased susceptibility in the resistant biotype. Differential gene expression analysis of resistant and sensitive plants revealed that 170 transcripts were upregulated in resistant plants relative to sensitive plants and 160 transcripts were upregulated in sensitive plants. In addition, 507 transcripts were only expressed in resistant plants and 562 only in sensitive plants. A subset of these transcripts were investigated further using quantitative PCR (qPCR) to compare gene expression in resistant plants with expression in additional sensitive biotypes. The qPCR analysis identified two transcripts, a kinase and a glutathione S-transferase that were significantly upregulated in resistant plants compared with the sensitive plants. A third transcript, encoding an F-box protein, was downregulated in the resistant plants relative to the sensitive plants. As no cytochrome P450s were differentially expressed between the resistant and sensitive plants, a single-nucleotide polymorphism analysis was performed, revealing several nonsynonymous point mutations of interest. These candidate genes will require further study to elucidate the resistance mechanisms present in the resistant biotype.
To determine the scope, source, and mode of transmission of a multifacility outbreak of extensively drug-resistant (XDR) Acinetobacter baumannii.
SETTING AND PARTICIPANTS
Residents and patients in skilled nursing facilities, long-term acute-care hospital, and acute-care hospitals.
A case was defined as the incident isolate from clinical or surveillance cultures of XDR Acinetobacter baumannii resistant to imipenem or meropenem and nonsusceptible to all but 1 or 2 antibiotic classes in a patient in an Oregon healthcare facility during January 2012–December 2014. We queried clinical laboratories, reviewed medical records, oversaw patient and environmental surveillance surveys at 2 facilities, and recommended interventions. Pulsed-field gel electrophoresis (PFGE) and molecular analysis were performed.
We identified 21 cases, highly related by PFGE or healthcare facility exposure. Overall, 17 patients (81%) were admitted to either long-term acute-care hospital A (n=8), or skilled nursing facility A (n=8), or both (n=1) prior to XDR A. baumannii isolation. Interfacility communication of patient or resident XDR status was not performed during transfer between facilities. The rare plasmid-encoded carbapenemase gene blaOXA-237 was present in 16 outbreak isolates. Contact precautions, chlorhexidine baths, enhanced environmental cleaning, and interfacility communication were implemented for cases to halt transmission.
Interfacility transmission of XDR A. baumannii carrying the rare blaOXA-237 was facilitated by transfer of affected patients without communication to receiving facilities.
New simultaneous X-ray and radio observations of the archetypal mode-switching pulsar PSR B0943+10 have been carried out with XMM-Newton and the LOFAR, LWA and Arecibo radio telescopes in November 2014. They allowed us to better constrain the X-ray spectral and variability properties of this pulsar and to detect, for the first time, the X-ray pulsations also during the X-ray-fainter mode. The combined timing and spectral analysis indicates that unpulsed non-thermal emission, likely of magnetospheric origin, and pulsed thermal emission from a small polar cap are present during both radio modes and vary in a correlated way.
We have mapped the nearby (z=0.018), active galaxy NGC 1275 (3C84) at 6 different epochs from 1981 to 1986 at 1.3 cm (22.3 GHz) with a global VLBI array of seven telescopes. We find a long-lived knot of emission separating from the brightest radio component with a projected velocity = 0.4 6±0.12 h−1 c. This knot moves through diffuse emission that also moves away from the main component with a slower projected velocity of 0.33±0.12 h−1 c. We show that the knot and diffuse emission result from two separate events that occurred around 1959 and 1968.
Six radio telescopes were operated as the first southern hemisphere VLBI array in April and May 1982. Observations were made at 2.3 and 8.4 Ghz. This array produced VLBI images of 28 southern hemisphere radio sources, high accuracy VLBI geodesy between southern hemisphere sites, and subarcsecond radio astrometry of celestial sources south of declination −45 degrees. This paper discusses only the astrophysical aspects of the experiment.
We are investigating complete samples of southern hemisphere flat spectrum extra-galactic radio sources drawn from the Parkes 2.7 GHz Survey (see Bolton et al. 1979 and references therein). These samples are being used for a variety of investigations, including a determination of the space distribution and luminosity function of radio QSOs, their radio size distribution, as well as the structures of the individual sources. Accurate positions are being determined, as well, in order to establish an extra-galactic position reference frame in the southern hemisphere.
VLBI observations of the nucleus of Centaurus A were made in April, 1982 at two frequencies with an array of five Australian radio antennas as part of the Southern Hemisphere VLBI Experiment (SHEVE). Observations were undertaken at 2.29 GHz with all five antennas, while only two were operational at 8.42 GHz. The 2.29 GHz data yielded significant information on the structure of the nuclear jet. At 8.42 GHz a compact unresolved core was detected as well.
Recent cases of acute kidney injury due to Seoul hantavirus infection from exposure to wild or pet fancy rats suggest this infection is increasing in prevalence in the UK. We conducted a seroprevalence study in England to estimate cumulative exposure in at-risk groups with contact with domesticated and wild rats to assess risk and inform public health advice. From October 2013 to June 2014, 844 individual blood samples were collected. Hantavirus seroprevalence amongst the pet fancy rat owner group was 34.1% (95% CI 23·9–45·7%) compared with 3·3% (95% CI 1·6–6·0) in a baseline control group, 2·4% in those with occupational exposure to pet fancy rats (95% CI 0·6–5·9) and 1·7% with occupational exposure to wild rats (95% CI 0·2–5·9). Variation in seroprevalence across groups with different exposure suggests that occupational exposure to pet and wild rats carries a very low risk, if any. However incidence of hantavirus infection among pet fancy rat owners/breeders, whether asymptomatic, undiagnosed mild viral illness or more severe disease may be very common and public health advice needs to be targeted to this at-risk group.
Aberrant microbiota composition and function have been linked to several pathologies, including type 2 diabetes. In animal models, prebiotics induce favourable changes in the intestinal microbiota, intestinal permeability (IP) and endotoxaemia, which are linked to concurrent improvement in glucose tolerance. This is the first study to investigate the link between IP, glucose tolerance and intestinal bacteria in human type 2 diabetes. In all, twenty-nine men with well-controlled type 2 diabetes were randomised to a prebiotic (galacto-oligosaccharide mixture) or placebo (maltodextrin) supplement (5·5 g/d for 12 weeks). Intestinal microbial community structure, IP, endotoxaemia, inflammatory markers and glucose tolerance were assessed at baseline and post intervention. IP was estimated by the urinary recovery of oral 51Cr-EDTA and glucose tolerance by insulin-modified intravenous glucose tolerance test. Intestinal microbial community analysis was performed by high-throughput next-generation sequencing of 16S rRNA amplicons and quantitative PCR. Prebiotic fibre supplementation had no significant effects on clinical outcomes or bacterial abundances compared with placebo; however, changes in the bacterial family Veillonellaceae correlated inversely with changes in glucose response and IL-6 levels (r −0·90, P=0·042 for both) following prebiotic intake. The absence of significant changes to the microbial community structure at a prebiotic dosage/length of supplementation shown to be effective in healthy individuals is an important finding. We propose that concurrent metformin treatment and the high heterogeneity of human type 2 diabetes may have played a significant role. The current study does not provide evidence for the role of prebiotics in the treatment of type 2 diabetes.
A population of junglerice from Sunflower County, MS, exhibited resistance to fenoxaprop-P-ethyl. An 11-fold difference in ED50 (the effective dose needed to reduce growth by 50%) values was observed when comparing the resistant population (249 g ae ha–1) with susceptible plants (20 g ae ha–1) collected from a different field. The resistant population was controlled by clethodim and sethoxydim at the field rate. Sequencing of the acetyl coenzyme A carboxylase, which encodes the enzyme targeted by fenoxaprop-P-ethyl, did not reveal the presence of any known resistance-conferring point mutations. An enzyme assay confirmed that the acetyl coenzyme A carboxylase in the resistant population is herbicide sensitive. Further investigations with two cytochrome P450 inhibitors, malathion and piperonyl butoxide, and a glutathione-S-transferase inhibitor, 4-chloro-7-nitrobenzofurazan, did not indicate involvement of any metabolic enzymes inhibited by these compounds. The absence of a known target-site point mutation and the sensitivity of the ACCase enzyme to herbicide show that fenoxaprop-P-ethyl resistance in this population is due to a non–target-site mechanism or mechanisms.
The anticipated release of EnlistTM cotton, corn, and soybean cultivars likely will increase the use of 2,4-D, raising concerns over potential injury to susceptible cotton. An experiment was conducted at 12 locations over 2013 and 2014 to determine the impact of 2,4-D at rates simulating drift (2 g ae ha−1) and tank contamination (40 g ae ha−1) on cotton during six different growth stages. Growth stages at application included four leaf (4-lf), nine leaf (9-lf), first bloom (FB), FB + 2 wk, FB + 4 wk, and FB + 6 wk. Locations were grouped according to percent yield loss compared to the nontreated check (NTC), with group I having the least yield loss and group III having the most. Epinasty from 2,4-D was more pronounced with applications during vegetative growth stages. Importantly, yield loss did not correlate with visual symptomology, but more closely followed effects on boll number. The contamination rate at 9-lf, FB, or FB + 2 wk had the greatest effect across locations, reducing the number of bolls per plant when compared to the NTC, with no effect when applied at FB + 4 wk or later. A reduction of boll number was not detectable with the drift rate except in group III when applied at the FB stage. Yield was influenced by 2,4-D rate and stage of cotton growth. Over all locations, loss in yield of greater than 20% occurred at 5 of 12 locations when the drift rate was applied between 4-lf and FB + 2 wk (highest impact at FB). For the contamination rate, yield loss was observed at all 12 locations; averaged over these locations yield loss ranged from 7 to 66% across all growth stages. Results suggest the greatest yield impact from 2,4-D occurs between 9-lf and FB + 2 wk, and the level of impact is influenced by 2,4-D rate, crop growth stage, and environmental conditions.
The Infrared Space Observatory (ISO) is opening the 2.5 to 200 μm band for detailed infrared spectroscopy. Concentrating on ionic and molecular emission lines observed with the Short Wavelength Spectrometer (SWS) we discuss ISO's first results on Galactic and extragalactic sources.
Invasive pneumococcal disease (IPD), caused by infection with Streptococcus pneumoniae, has a substantial global burden. There are over 90 known serotypes of S. pneumoniae with a considerable body of evidence supporting serotype-specific mortality rates immediately following IPD. This is the first study to consider the association between serotype and longer-term mortality following IPD. Using enhanced surveillance data from the North East of England we assessed both the short-term (30-day) and longer-term (⩽7 years) independent adjusted associations between individual serotypes and mortality following IPD diagnosis using logistic regression and extended Cox proportional hazards models. Of the 1316 cases included in the analysis, 243 [18·5%, 95% confidence interval (CI) 16·4–20·7] died within 30 days of diagnosis. Four serotypes (3, 6A, 9N, 19 F) were significantly associated with overall increased 30-day mortality. Effects were observable only for older adults (⩾60 years). After extension of the window to 12 months and 36 months, one serotype was associated with significantly increased mortality at 12 months (19 F), but no individual serotypes were associated with increased mortality at 36 months. Two serotypes had statistically significant hazard ratios (HR) for longer-term mortality: serotype 1 for reduced mortality (HR 0·51, 95% CI 0·30–0·86) and serotype 9N for increased mortality (HR 2·30, 95% CI 1·29–4·37). The association with serotype 9N was no longer observed after limiting survival analysis to an observation period starting 30 days after diagnosis. This study supports the evidence for associations between serotype and short-term (30-day) mortality following IPD and provides the first evidence for the existence of statistically significant associations between individual serotypes and longer-term variation in mortality following IPD.