Vector competence of Aedes aegypti, Culex tarsalis, and Culex quinquefasciatus from California for Zika virus.

Zika virus (ZIKV) has emerged since 2013 as a significant global human health threat following outbreaks in the Pacific Islands and rapid spread throughout South and Central America. Severe congenital and neurological sequelae have been linked to ZIKV infections. Assessing the ability of common mosquito species to transmit ZIKV and characterizing variation in mosquito transmission of different ZIKV strains is important for estimating regional outbreak potential and for prioritizing local mosquito control strategies for Aedes and Culex species. In this study, we evaluated the laboratory vector competence of Aedes aegypti, Culex quinquefasciatus, and Culex tarsalis that originated in areas of California where ZIKV cases in travelers since 2015 were frequent. We compared infection, dissemination, and transmission rates by measuring ZIKV RNA levels in cohorts of mosquitoes that ingested blood meals from type I interferon-deficient mice infected with either a Puerto Rican ZIKV strain from 2015 (PR15), a Brazilian ZIKV strain from 2015 (BR15), or an ancestral Asian-lineage Malaysian ZIKV strain from 1966 (MA66). With PR15, Cx. quinquefasciatus was refractory to infection (0%, N = 42) and Cx. tarsalis was infected at 4% (N = 46). No ZIKV RNA was detected in saliva from either Culex species 14 or 21 days post feeding (dpf). In contrast, Ae. aegypti developed infection rates of 85% (PR15; N = 46), 90% (BR15; N = 20), and 81% (MA66; N = 85) 14 or 15 dpf. Although MA66-infected Ae. aegypti showed higher levels of ZIKV RNA in mosquito bodies and legs, transmission rates were not significantly different across virus strains (P = 0.13, Fisher's exact test). To confirm infectivity and measure the transmitted ZIKV dose, we enumerated infectious ZIKV in Ae. aegypti saliva using Vero cell plaque assays. The expectorated plaque forming units PFU varied by viral strain: MA66-infected expectorated 13±4 PFU (mean±SE, N = 13) compared to 29±6 PFU for PR15-infected (N = 13) and 35±8 PFU for BR15-infected (N = 6; ANOVA, df = 2, F = 3.8, P = 0.035). These laboratory vector competence results support an emerging consensus that Cx. tarsalis and Cx. quinquefasciatus are not vectors of ZIKV. These results also indicate that Ae. aegypti from California are efficient laboratory vectors of ancestral and contemporary Asian lineage ZIKV

Fractal Weyl law for chaotic microcavities: Fresnel's laws imply multifractal scattering

We demonstrate that the harmonic inversion technique is a powerful tool to analyze the spectral properties of optical microcavities. As an interesting example we study the statistical properties of complex frequencies of the fully chaotic microstadium. We show that the conjectured fractal Weyl law for open chaotic systems [W. T. Lu, S. Sridhar, and M. Zworski, Phys. Rev. Lett. 91, 154101 (2003)] is valid for dielectric microcavities only if the concept of the chaotic repeller is extended to a multifractal by incorporating Fresnel's laws.Comment: 8 pages, 12 figure

An Economic Interpretation of Rhode Island’s 1788 Referendum on the Constitution

In their 1788 popular referendum, Rhode Island voters overwhelmingly rejected ratification of the Federal Constitution: 92 percent against and 8 percent for adoption. The town-by-town voter lists, correlated with tax and estate records, show that yea voters were significantly wealthier than “nay” voters. Available data also indicates that yea wealth was concentrated in personal estate rather than real estate. Both these findings support Charles Beard\u27s original economic interpretation of the Constitution. Our detailed data provides new evidence about town-level voters, supplementing the usual data Beard’s supporters and critics have used from state ratifying conventions and the Philadelphia constitutional convention. We trace the outlines of the scholarly debate, provide political and economic context for the Rhode Island referendum, report on our initial findings, and suggest further avenues of research and analysis

Extreme events and predictability of catastrophic failure in composite materials and in the Earth

Despite all attempts to isolate and predict extreme earthquakes, these nearly always occur without obvious warning in real time: fully deterministic earthquake prediction is very much a ‘black swan’. On the other hand engineering-scale samples of rocks and other composite materials often show clear precursors to dynamic failure under controlled conditions in the laboratory, and successful evacuations have occurred before several volcanic eruptions. This may be because extreme earthquakes are not statistically special, being an emergent property of the process of dynamic rupture. Nevertheless, probabilistic forecasting of event rate above a given size, based on the tendency of earthquakes to cluster in space and time, can have significant skill compared to say random failure, even in real-time mode. We address several questions in this debate, using examples from the Earth (earthquakes, volcanoes) and the laboratory, including the following. How can we identify ‘characteristic’ events, i.e. beyond the power law, in model selection (do dragon-kings exist)? How do we discriminate quantitatively between stationary and non-stationary hazard models (is a dragon likely to come soon)? Does the system size (the size of the dragon’s domain) matter? Are there localising signals of imminent catastrophic failure we may not be able to access (is the dragon effectively invisible on approach)? We focus on the effect of sampling effects and statistical uncertainty in the identification of extreme events and their predictability, and highlight the strong influence of scaling in space and time as an outstanding issue to be addressed by quantitative studies, experimentation and models

Context-dependent nature of destabilizing mutations on the stability of fkbp12

ABSTRACT: The context-dependent nature in which mutations affect protein stability was investigated using the FK506-binding protein, FKBP12. Thirty-four mutations were made at sites throughout the protein, including residues located in the hydrophobic core, the -sheet, and the solvent-exposed face of the R-helix. Urea-induced denaturation experiments were used to measure the change in stability of the mutants relative to that of the wild type (∆∆G U-F ). The results clearly show that the extent of destabilization, or stabilization, is highly context-dependent. Correlations were sought in order to link ∆∆G U-F to various structural parameters. The strongest correlation found was between ∆∆G U-F and N, the number of methyl-(ene) groups within a 6 Å radius of the group(s) deleted. For mutations of buried hydrophobic residues, a correlation coefficient of 0.73 (n ) 16,where n is the number of points) was obtained. This increased to 0.81 (n ) 24) on inclusion of mutations of partially buried hydrophobic residues. These data could be superimposed on data obtained for other proteins for which similarly detailed studies have been performed. Thus, the contribution to stability from hydrophobic side chains, independent of the extent to which a side chain is buried, can be estimated quantitatively using N. This correlation appears to be a general feature of all globular proteins. The effect on stability of mutating polar and charged residues in the R-helix and -sheet was also found to be highly context-dependent. Previous experimental and statistical studies have shown that specific side chains can stabilize the N-caps of R-helices in proteins. Substitutions of Ile56 to Thr and Asp at the N-cap of the R-helix of FKBP12, however, were found to be highly destabilizing. Thus, the intrinsic propensities of an amino acid for a particular element of secondary structure can easily be outweighed by tertiary packing factors. This study highlights the importance of packing density in determining the contribution of a residue to protein stability. This is the most important factor that should be taken into consideration in protein design. To design novel proteins, or rationally alter existing ones, a quantitative understanding of the factors that affect the stability of the native state is required. For proteins without disulfide bonds, noncovalent interactionsssuch as hydrophobic interactions, hydrogen bonds, and electrostatic interactionssdetermine protein stability (1). Protein engineering studies have provided an abundance of information on the relationship between protein structure and stability. Studies on hydrophobic groups (2-13) have shown that the packing of nonpolar groups and burial of hydrophobic surface area are the dominant forces in the stabilization of proteins. Studies on both fully and partially buried hydrophobic residues in barnase, CI2, and staphylococcal nuclease have shown correlations between the change in protein stability upon mutation (∆∆G U-F ) and both the packing density [number of methyl(ene) groups within a certain radius of the nonpolar groups removed

Zygapophysial joint blocks in chronic low back pain: a test of Revel's model as a screening test

BACKGROUND: Only controlled blocks are capable of confirming the zygapophysial joints (ZJ) as the pain generator in LBP patients. However, previous workers have found that a cluster of clinical signs ("Revel's criteria"), may be valuable in predicting the results of an initial screening ZJ block. It was suggested that these clinical findings are unsuitable for diagnosis, but may be of value in selecting patients for diagnostic blocks of the lumbar ZJ's. To constitute evidence in favour of a clinical management strategy, these results need confirmation. This study evaluates the utility of 'Revel's criteria' as a screening tool for selection of chronic low back pain patients for controlled ZJ diagnostic blocks. METHODS: This study utilized a prospective blinded concurrent reference standard related validity design. Consecutive chronic LBP patients completed pain drawings, psychosocial distress and disability questionnaires, received a clinical examination and lumbar zygapophysial blocks. Two reference standards were evaluated simultaneously: 1. 75% reduction of pain on a visual analogue scale (replication of previous work), and 2. abolition of the dominant or primary pain. Using "Revel's criteria" as predictors, logistic regression analyses were used to test the model. Estimates of sensitivity, specificity, predictive values and likelihood ratios for selected variables were calculated for the two proposed clinical strategies. RESULTS: Earlier results were not replicated. Sensitivity of "Revel's criteria" was low sensitivity (<17%), and specificity high (approximately 90%). Absence of pain with cough or sneeze just reached significance (p = 0.05) within one model. CONCLUSIONS: "Revel's criteria" are unsuitable as a clinical screening test to select chronic LBP patients for initial ZJ blocks. However, the criteria may have use in identifying a small subset (11%) of patients likely to respond to the initial block (specificity 93%)

Thromboelastometry and Platelet Function during Acclimatization to High Altitude

Interaction between hypoxia and coagulation is important given the increased risk of thrombotic diseases in chronically hypoxic patients who reside at sea level and in residents at high altitude. Hypoxia alters the proteome of platelets favouring a prothrombotic phenotype, but studies of activation and consumption of specific coagulation factors in hypoxic humans have yielded conflicting results. We tested blood from 63 healthy lowland volunteers acclimatizing to high altitude (5,200 m) using thromboelastometry and assays of platelet function to examine the effects of hypoxia on haemostasis. Using data from two separate cohorts of patients following identical ascent profiles, we detected a significant delay in clot formation, but increased clot strength by day 7 at 5,200 m. The latter finding may be accounted for by the significant rise in platelet count and fibrinogen concentration that occurred during acclimatization. Platelet function assays revealed evidence of platelet hyper-reactivity, with shortened PFA-100 closure times and increased platelet aggregation in response to adenosine diphosphate. Post-expedition results were consistent with the normalization of coagulation following descent to sea level. These robust findings indicate that hypoxia increases platelet reactivity and, with the exception of the paradoxical delay in thromboelastometry clotting time, suggest a prothrombotic phenotype at altitude. Further work to elucidate the mechanism of platelet activation in hypoxia will be important and could impact upon the management of patients with acute or chronic hypoxic respiratory diseases who are at risk of thrombotic events. Erratum to: Thromboelastometry and platelet function during acclimatisation to high altitude (doi: 10.1160/TH17-02-0138) http://eprints.whiterose.ac.uk/129510/ In the Original Article by Rocke et al. “Thromboelastometry and platelet function during acclimatization to high altitude” (Thromb Haemost 2018; 118: 063-071) after publication of the article it has come to the corresponding author's attention that an author was inadvertently omitted from the manuscript. The author, Martin MacInnis, made a significant contribution to: 1. initiating the coagulation research that led to the manuscript, 2. designing the research protocol and performing the initial data analysis, 3. recruiting volunteers, writing applications for ethical approval and making other logistical arrangements that were necessary to complete the study. Martin MacInnis has read and approved the published version of the manuscript. Furthermore, a middle initial was added to the updated list (Shona E. Main) and misspelling of Elizabeth Horn's surname was corrected. The amended author list is as above. https://doi.org

Effectiveness of physiotherapy exercise following hip arthroplasty for osteoarthritis: a systematic review of clinical trials

Background: Physiotherapy has long been a routine component of patient rehabilitation following hip joint replacement. The purpose of this systematic review was to evaluate the effectiveness of physiotherapy exercise after discharge from hospital on function, walking, range of motion, quality of life and muscle strength, for osteoarthritic patients following elective primary total hip arthroplasty. Methods: Design: Systematic review, using the Cochrane Collaboration Handbook for Systematic Reviews of Interventions and the Quorom Statement. Database searches: AMED, CINAHL, EMBASE, KingsFund, MEDLINE, Cochrane library (Cochrane reviews, Cochrane Central Register of Controlled Trials, DARE), PEDro, The Department of Health National Research Register. Handsearches: Physiotherapy, Physical Therapy, Journal of Bone and Joint Surgery (Britain) Conference Proceedings. No language restrictions were applied. Selection: Trials comparing physiotherapy exercise versus usual/standard care, or comparing two types of relevant exercise physiotherapy, following discharge from hospital after elective primary total hip replacement for osteoarthritis were reviewed. Outcomes: Functional activities of daily living, walking, quality of life, muscle strength and range of hip joint motion. Trial quality was extensively evaluated. Narrative synthesis plus meta-analytic summaries were performed to summarise the data. Results: 8 trials were identified. Trial quality was mixed. Generally poor trial quality, quantity and diversity prevented explanatory meta-analyses. The results were synthesised and meta-analytic summaries were used where possible to provide a formal summary of results. Results indicate that physiotherapy exercise after discharge following total hip replacement has the potential to benefit patients. Conclusion: Insufficient evidence exists to establish the effectiveness of physiotherapy exercise following primary hip replacement for osteoarthritis. Further well designed trials are required to determine the value of post discharge exercise following this increasingly common surgical procedure

The Bolocam Galactic Plane Survey IV: 1.1 and 0.35 mm Dust Continuum Emission in the Galactic Center Region

The Bolocam Galactic Plane Survey (BGPS) data for a six square degree region of the Galactic plane containing the Galactic center is analyzed and compared to infrared and radio continuum data. The BGPS 1.1 mm emission consists of clumps interconnected by a network of fainter filaments surrounding cavities, a few of which are filled with diffuse near-IR emission indicating the presence of warm dust or with radio continuum characteristic of HII regions or supernova remnants. New 350 {\mu}m images of the environments of the two brightest regions, Sgr A and B, are presented. Sgr B2 is the brightest mm-emitting clump in the Central Molecular Zone and may be forming the closest analog to a super star cluster in the Galaxy. The Central Molecular Zone (CMZ) contains the highest concentration of mm and sub-mm emitting dense clumps in the Galaxy. Most 1.1 mm features at positive longitudes are seen in silhouette against the 3.6 to 24 {\mu}m background observed by the Spitzer Space Telescope. However, only a few clumps at negative longitudes are seen in absorption, confirming the hypothesis that positive longitude clumps in the CMZ tend to be on the near-side of the Galactic center, consistent with the suspected orientation of the central bar in our Galaxy. Some 1.1 mm cloud surfaces are seen in emission at 8 {\mu}m, presumably due to polycyclic aromatic hydrocarbons (PAHs). A ~0.2\degree (~30 pc) diameter cavity and infrared bubble between l \approx 0.0\degree and 0.2\degree surrounds the Arches and Quintuplet clusters and Sgr A. The bubble contains several clumpy dust filaments that point toward Sgr A\ast; its potential role in their formation is explored. [abstract truncated]Comment: 76 pages, 22 figures, published in ApJ: http://iopscience.iop.org/0004-637X/721/1/137