Abstract
The current COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We demonstrate that despite the large size of the viral RNA genome (~30 kb), ...infectious full-length cDNA is readily assembled in vitro by a circular polymerase extension reaction (CPER) methodology without the need for technically demanding intermediate steps. Overlapping cDNA fragments are generated from viral RNA and assembled together with a linker fragment containing CMV promoter into a circular full-length viral cDNA in a single reaction. Transfection of the circular cDNA into mammalian cells results in the recovery of infectious SARS-CoV-2 virus that exhibits properties comparable to the parental virus in vitro and in vivo. CPER is also used to generate insect-specific Casuarina virus with ~20 kb genome and the human pathogens Ross River virus (Alphavirus) and Norovirus (Calicivirus), with the latter from a clinical sample. Additionally, reporter and mutant viruses are generated and employed to study virus replication and virus-receptor interactions.
Teff (Eragrostis tef cv. Moxie), a warm-season annual grass, could be an excellent forage for beef cattle. However, there is limited information on its nutritive value to cattle when harvested at ...different stages of maturity. Thus, the objective of this research was to determine the effect of feeding teff hay harvested at the boot (BT), early-heading (EH), or late-heading (LH) stages of maturity on nutrient intake, ruminal fermentation characteristics, omasal nutrient flow, and N utilization in beef cattle. Six ruminally cannulated beef heifers (mean initial BW ± SD, 476 ± 32.6) were used in a replicated 3 × 3 Latin square design with 28-d periods (18 d for adaptation and 10 d for measurements). Dry matter intake was measured daily. Indwelling pH loggers were used to measure ruminal pH from days 21 to 28. Ruminal fluid and omasal digesta were collected from days 26 to 28 to determine fermentation characteristics and omasal nutrient flow. Fecal and urine samples to quantify N excretion were also collected (days 26 to 28). Blood samples for plasma urea-N (PUN) determination were collected 3 h post-feeding on day 28. There were no changes (P > 0.28) in the ADF or NDF content of teff with advancing maturity, but indigestible NDF increased (P < 0.01) with increasing maturity. Maturity had no effect (P ≥ 0.14) on DMI, and ruminal total short-chain fatty acid (SCFA) concentration, pH, digestibility, and outflow of DM, OM, NDF, ADF, and CP. However, the CP content of BT hay was greater (P < 0.01) than for EH and LH hay (18.1, 14.1, and 11.5%, respectively, DM basis), and this resulted in the higher CP intake (P < 0.01) for heifers fed the BT than the EH and LH hay. Consequently, ruminal ammonia-N (NH3-N) concentration was greater (P < 0.01) for heifers fed BT than EH and LH hay, thereby possibly explaining the tendency for a decrease (P = 0.08) in PUN concentration, and a decrease (P < 0.01) in the excretion of total N, urine N, and urea-N (UUN) with advancing maturity. However, fecal N excretion (g/d) did not differ (P = 0.76). In conclusion, despite a decrease in CP intake and ruminal NH3-N concentration, feeding beef heifers EH and LH compared to BT teff hay did not compromise ruminal digestion and outflow of DM, OM, NDF, ADF, and CP, and microbial protein synthesis. Advancing maturity in teff hay also resulted in a decrease in the excretion of total N and urine N and UUN when fed to cattle.
IMPORTANCE: Venous thromboembolism (VTE) is a common complication of acute illness, and its prevention is a ubiquitous aspect of inpatient care. A multicenter blinded, randomized trial compared the ...effectiveness of the most common pharmocoprevention strategies, unfractionated heparin (UFH) and the low-molecular-weight heparin (LMWH) dalteparin, finding no difference in the primary end point of leg deep-vein thrombosis but a reduced rate of pulmonary embolus and heparin-induced thrombocytopenia among critically ill medical-surgical patients who received dalteparin. OBJECTIVE: To evaluate the comparative cost-effectiveness of LMWH vs UFH for prophylaxis against VTE in critically ill patients. DESIGN, SETTING, AND PARTICIPANTS: Prospective economic evaluation concurrent with the Prophylaxis for Thromboembolism in Critical Care Randomized Trial (May 2006 to June 2010). The economic evaluation adopted a health care payer perspective and in-hospital time horizon; derived baseline characteristics and probabilities of intensive care unit and in-hospital events; and measured costs among 2344 patients in 23 centers in 5 countries and applied these costs to measured resource use and effects of all enrolled patients. MAIN OUTCOMES AND MEASURES: Costs, effects, incremental cost-effectiveness of LMWH vs UFH during the period of hospitalization, and sensitivity analyses across cost ranges. RESULTS: Hospital costs per patient were $39 508 (interquartile range IQR, $24 676 to $71 431) for 1862 patients who received LMWH compared with $40 805 (IQR, $24 393 to $76 139) for 1862 patients who received UFH (incremental cost, −$1297 IQR, −$4398 to $1404; P = .41). In 78% of simulations, a strategy using LMWH was most effective and least costly. In sensitivity analyses, a strategy using LMWH remained least costly unless the drug acquisition cost of dalteparin increased from $8 to $179 per dose and was consistent among higher- and lower-spending health care systems. There was no threshold at which lowering the acquisition cost of UFH favored prophylaxis with UFH. CONCLUSIONS AND RELEVANCE: From a health care payer perspective, the use of the LMWH dalteparin for VTE prophylaxis among critically ill medical-surgical patients was more effective and had similar or lower costs than the use of UFH. These findings were driven by lower rates of pulmonary embolus and heparin-induced thrombocytopenia and corresponding lower overall use of resources with LMWH.
Lumpy skin disease (LSD) is an infectious disease of cattle and water buffalo caused by lumpy skin disease virus (LSDV). It is primarily transmitted mechanically by biting insects. LSDV has spread ...from Africa to the Middle-East, the Balkans, Caucasus, Russia, Kazakhstan, China, Asia and India, suggesting that a wide variety of arthropod vectors are capable of mechanical transmission. In 2022, LSD was detected in Indonesia, heightening awareness for Australia’s livestock industries. To better understand the risk of LSDV incursion to Australia we undertook a quantitative risk assessment (QRA) looking at windborne dispersal of arthropod vectors, assuming a hypothetical situation where LSD is endemic in south-east Asia and Papua New Guinea. We estimated the risk of LSDV incursion to be low, with a median incursion rate of one incursion every 403 years, based on a model where several infectious insects (i.e. a ‘small batch’ of 3–5) must bite a single bovine to transmit infection. The incursion risk increases substantially to one incursion every 7–8 years if a bite from a single insect is sufficient for transmission. The risk becomes negligible (one incursion every 20,706 years) if bites from many insects (i.e. a ‘large batch’ of 30–50 insects) are necessary. Critically, several of our parameter estimates were highly uncertain during sensitivity analyses. Thus, a key outcome of this QRA was to better prioritise surveillance activities and to understand the key research gaps associated with LSDV in the Australasian context. The current literature shows that multiple vectors are required for successful bovine-to-vector transmission of LSDV, suggesting that our estimate of one outbreak every 403 years more accurately represents the risk to Australia; however, the role of single insects in transmission has not yet been evaluated. Similarly, attempts to transmit LSDV between bovines by Culicoides have not been successful, although midges were the highest risk vector category in our model due to the high vector-to-host ratio for midges compared to other vector categories. Our findings provide further insight into the risk of LSD to Australian cattle industries and identify the Tiwi Islands and areas east of Darwin as priority regions for LSDV surveillance, especially between December and March.
•We estimated the risk of LSDV incursion into Australia via windborne dispersal of arthropod vectors.•Incursion risk appears to be low assuming that bites from several infectious insects are required for successful infection.•Incursion risk increases substantially if a bite from a single insect is sufficient for transmission.•Priority regions for LSDV surveillance including the Tiwi Islands and east of Darwin, especially from December to March.
Ultrawideband (UWB) systems require band notch filters in order to prevent sensitive components, within the front-end of the receiver, from being overloaded by strong signals. Recently, it has been ...shown that these filters can be integrated into the UWB antenna, to great advantage. This communication presents a new method for forming a notch band within the frequency response of a UWB antenna. An open loop notch band resonator is located on the back of the substrate, used to support the UWB monopole. The act of separating the resonator from the antenna means that they can now be designed in isolation, using the standard approach described in the literature, and then combined. A prototype was constructed and good agreement has been obtained between simulation and measurement. The radiation patterns are consistent over the frequency range of interest.
We conducted a genome-wide association study of 299,983 tagging SNPs for chronic lymphocytic leukemia (CLL) and performed validation in two additional series totaling 1,529 cases and 3,115 controls. ...We identified six previously unreported CLL risk loci at 2q13 (rs17483466; P = 2.36 × 10−10), 2q37.1 (rs13397985, SP140; P = 5.40 × 10−10), 6p25.3 (rs872071, IRF4; P = 1.91 × 10−20), 11q24.1 (rs735665; P = 3.78 × 10−12), 15q23 (rs7176508; P = 4.54 × 10−12) and 19q13.32 (rs11083846, PRKD2; P = 3.96 × 10−9). These data provide the first evidence for the existence of common, low-penetrance susceptibility to a hematological malignancy and new insights into disease causation in CLL.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The characteristics of detached macroalgae (drift) in nearby highly eutrophic and mesotrophic estuaries in south-western Australia are compared to elucidate the magnitude and types of changes that ...occur in macroalgal drift when estuaries receive excessive nutrient input. Drift characteristics in the large basins of the microtidal, eutrophic Peel-Harvey and mesotrophic Swan-Canning, which is not subjected to large nutrient inputs directly from agricultural land, differed markedly. Biomass (dry weight) in mesotrophic estuary was dominated by rhodophytes (92%), particularly Laurencia and Hypnea, and in eutrophic estuary by opportunistic chlorophytes (68%), especially Chaetomorpha and Ulva. Prevalence and biomass of drift were far greater in the eutrophic estuary, particularly during summer and autumn when macroalgal growth rose sharply. Macroalgal biomass in the eutrophic estuary was positively related to salinity. These results facilitate predictions of how climatic and other anthropogenic changes influence extent of macroalgal growth and thus change the estuarine environment.
•Macrophyte drift in nearby microtidal mesotrophic and eutrophic estuaries compared•Rhodophytes dominant in mesotrophic estuary and chlorophytes in eutrophic estuary•Biomass 23 times greater in eutrophic estuary, due to high summer and autumn values•Drift prevalence and dry weight in both estuaries increased from winter to autumn•Biomass positively related to salinity in both mesotrophic and eutrophic estuaries
Oligodeoxynucleotides incorporating internucleotide phosphoroselenolate linkages have been prepared under solid-phase synthesis conditions using dimer phosphoramidites. These dimers were constructed ...following the high yielding Michaelis-Arbuzov (M-A) reaction of nucleoside
H
-phosphonate derivatives with 5′-deoxythymidine-5′-selenocyanate and subsequent phosphitylation. Efficient coupling of the dimer phosphoramidites to solid-supported substrates was observed under both manual and automated conditions and required only minor modifications to the standard DNA synthesis cycle. In a further demonstration of the utility of M-A chemistry, the support-bound selenonucleoside was reacted with an
H
-phosphonate and then chain extended using phosphoramidite chemistry. Following initial unmasking of methyl-protected phosphoroselenolate diesters, pure oligodeoxynucleotides were isolated using standard deprotection and purification procedures and subsequently characterised by mass spectrometry and circular dichroism. The CD spectra of both modified and native duplexes derived from self-complementary sequences with A-form, B-form or mixed conformational preferences were essentially superimposable. These sequences were also used to study the effect of the modification upon duplex stability which showed context-dependent destabilisation (−0.4 to −3.1 °C per phosphoroselenolate) when introduced at the 5′-termini of A-form or mixed duplexes or at juxtaposed central loci within a B-form duplex (−1.0 °C per modification). As found with other nucleic acids incorporating selenium, expeditious crystallisation of a modified decanucleotide A-form duplex was observed and the structure solved to a resolution of 1.45 Å. The DNA structure adjacent to the modification was not significantly perturbed. The phosphoroselenolate linkage was found to impart resistance to nuclease activity.
Stable selenium-modified DNA which maintains the native tertiary structure has been prepared under automated conditions enabling SAD X-ray crystallography.
A meta-analysis was performed on quantitative EEG (QEEG) studies that evaluated attention-deficit hyperactivity disorder (ADHD) using the criteria of the DSM-IV (Diagnostic and Statistical Manual of ...Mental Disorders, 4th edition). The nine eligible studies (N = 1498) observed QEEG traits of a theta power increase and a beta power decrease, summarized in the theta/beta ratio with a pooled effect size of 3.08 (95% confidence interval, 2.90, 3.26) for ADHD versus controls (normal children, adolescents, and adults). By statistical extrapolation, an effect size of 3.08 predicts a sensitivity and specificity of 94%, which is similar to previous results 86% to 90% sensitivity and 94% to 98% specificity. It is important to note that the controlled group studies were often with retrospectively set limits, and that in practice the sensitivity and specificity results would likely be more modest. The literature search also uncovered 32 pre-DSM-IV studies of ADHD and EEG power, and 29 of the 32 studies demonstrated results consistent with the meta-analysis. The meta-analytic results are also supported by the observation that the theta/beta ratio trait follows age-related changes in ADHD symptom presentation (Pearson correlation coefficient, 0.996, P = 0.004). In conclusion, this meta-analysis supports that a theta/beta ratio increase is a commonly observed trait in ADHD relative to normal controls. Because it is known that the theta/beta ratio trait may arise with other conditions, a prospective study covering differential diagnosis would be required to determine generalizability to clinical applications. Standardization of the QEEG technique is also needed, specifically with control of mental state, drowsiness, and medication.
•Competing approaches to food security exist, with nontrivial differences.•We used a “conceptual triangulation” to explore four divergent approaches.•We found synergies that illuminate food ...availability and access challenges.•Results justify cross-disciplinary approaches to food security intervention.
Motivated by donor interest in innovative thinking on food security, we conducted an interdisciplinary, triangulation analysis of four divergent conceptual frameworks, each relevant to diagnosing food insecurity in developing countries. We found notable tensions as well as synergistic interactions between agroecology, agricultural innovation systems, social–ecological systems, and political ecology. Cross-framework interactions enhance our understanding of how sectoral and macro-economic development strategies impact on livelihoods, availability, and access. Re-invigorated, more profound dialog between divergent conceptual frameworks enables diagnosis of complex food insecurity problems, and context-specific interventions and innovations. Informed use of divergent approaches constitutes a new ambition for research and practice.
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