Rapid Effective Trace-Back Capability Value in Reducing the Cost of a Foot and Mouth Disease Event

This study evaluates how the availability of animal tracing affects the cost of a hypothetical Foot and Mouth Disease (FMD) outbreak in the Texas High Plains using alternative tracing scenarios. To accomplish this objective, the AusSpread epidemic disease spread model (Ward et al., 2006) is used to simulate a High Plains FMD outbreak under different animal tracing possibilities. A simple economic costing module (Elbakidze, 2008) is used to determine the savings in terms of animal disease mitigation costs from rapid, effective trace-back. The savings from increased traceability are then be compared to the cost of a functional National Animal Identification System (NAIS). Initial results indicate that rapid, effective tracing reduces the overall cost of disease outbreaks and that the benefits per animal in terms of reduced cost of an outbreak more than outweigh the annualized cost per animal of implementing a NAIS. A value of time related to controlling an outbreak is estimated to have increased benefits from an identification system that incorporates a rapid response capability. We also find the level of benefits vary depending on the location of initial infection and whether or not welfare slaughter occurs.Traceability, Foot and Mouth Disease, Economics, Agricultural and Food Policy, Livestock Production/Industries,

Low efficacy of the combination artesunate plus amodiaquine for uncomplicated falciparum malaria among children under 5 years in Kailahun, Sierra Leone.

OBJECTIVE: In 2004, Sierra Leone adopted artesunate plus amodiaquine as first-line antimalarial treatment. We evaluated the efficacy of this combination in Kailahun, where a previous study had shown 70.2% efficacy of amodiaquine in monotherapy. METHODS: Method and outcome classification of the study complied with WHO guidelines. Children 6-59 months with uncomplicated malaria were followed-up for 28 days. PCR genotyping was used to distinguish recrudescence from reinfection. Reinfections were reclassified as cured. RESULTS: Of 172 children who were referred to the study clinic, 126 satisfied inclusion criteria and were enrolled. No early treatment failures were reported. The day 14, efficacy was 98.2% (95% CI: 93.8-99.8). Of 65 recurrent parasitaemias analysed by PCR, 17 were recrudescences. The PCR-adjusted day 28 efficacy was 84.5% (95% CI: 76.4-90.7). All true failures occurred in the last 8 days of follow-up. Of 110 children who completed the 28-day follow-up, 54 (49.1%) experienced a novel infection. CONCLUSION: The efficacy of this combination was disappointing. The high reinfection rate suggested little prophylactic effect. In Kailahun a more efficacious combination might be necessary in the future. The efficacy of AS + AQ needs to be monitored in Kailahun and in the other regions of Sierra Leone

Core flexibility of a truncated metazoan mitochondrial tRNA

Secondary and tertiary structures of tRNAs are remarkably preserved from bacteria to humans, the notable exception being the mitochondrial (m) tRNAs of metazoans, which often deviate substantially from the canonical cloverleaf (secondary) or ‘L’-shaped (tertiary) structure. Many metazoan mtRNAs lack either the TψC (T) or dihydrouridine (D) loops of the canonical cloverleaf, which are known to confer structural rigidity to the folded structure. Thus, the absence of canonical TψC–D interactions likely results in greater dispersion of anticodon-acceptor interstem angle than for canonical tRNAs. To test this hypothesis, we have assessed the dispersion of the anticodon-acceptor angle for bovine mtRNASer(AGY), which lacks the canonical D arm and is thus incapable of forming stabilizing interarm interactions. Using the method of transient electric birefringence (TEB), and by changing the helical torsion angle between a core mtRNA bend and a second bend of known angle/rigidity, we have demonstrated that the core of mtRNASer(AGY) has substantially greater flexibility than its well-characterized canonical counterpart, yeast cytoplasmic tRNAPhe. These results suggest that increased flexibility, in addition to a more open interstem angle, would allow both noncanonical and canonical mtRNAs to utilize the same protein synthetic apparatus

Getting DNA twist rigidity from single molecule experiments

We use an elastic rod model with contact to study the extension versus rotation diagrams of single supercoiled DNA molecules. We reproduce quantitatively the supercoiling response of overtwisted DNA and, using experimental data, we get an estimation of the effective supercoiling radius and of the twist rigidity of B-DNA. We find that unlike the bending rigidity, the twist rigidity of DNA seems to vary widely with the nature and concentration of the salt buffer in which it is immerged

Torsional Directed Walks, Entropic Elasticity, and DNA Twist Stiffness

DNA and other biopolymers differ from classical polymers due to their torsional stiffness. This property changes the statistical character of their conformations under tension from a classical random walk to a problem we call the `torsional directed walk'. Motivated by a recent experiment on single lambda-DNA molecules [Strick et al., Science 271 (1996) 1835], we formulate the torsional directed walk problem and solve it analytically in the appropriate force regime. Our technique affords a direct physical determination of the microscopic twist stiffness C and twist-stretch coupling D relevant for DNA functionality. The theory quantitatively fits existing experimental data for relative extension as a function of overtwist over a wide range of applied force; fitting to the experimental data yields the numerical values C=120nm and D=50nm. Future experiments will refine these values. We also predict that the phenomenon of reduction of effective twist stiffness by bend fluctuations should be testable in future single-molecule experiments, and we give its analytic form.Comment: Plain TeX, harvmac, epsf; postscript available at http://dept.physics.upenn.edu/~nelson/index.shtm

The Mental and Physical Health of Mothers of Children with Special Health Care Needs in the United States

OBJECTIVE: To determine the prevalence of poor mental and physical health among mothers of children with special health care needs (CSHCN) and to determine the association between maternal health and the child\u27s number of special health care needs (SHCN) and severity of ability limitation. METHODS: We used the combined 2016-2018 National Survey of Children\u27s Health Dataset of 102,341 children ages 0-17 including 23,280 CSHCN. We used regression models to examine the associations of a child\u27s number of SHCN and ability limitations with maternal health. RESULTS: Twice as many mothers of CSHCN had poor mental and physical health compared to non-CSHCN (mental 10.3% vs. 4.0%, p \u3c .001; physical 11.9% vs 5.0%, p \u3c .001). In regression models, increased number of SHCN and severity of activity limitations were associated with significantly increased odds of poor maternal health. CONCLUSIONS FOR PRACTICE: Mothers of CSHCN have worse health compared to mothers of non-CSHCN, especially those who experience social disadvantage and those with children with complex SHCN or severe ability limitations. Interventions to improve the health of these particularly vulnerable caregivers of CSHCN are warranted

The quadruplex r(CGG)n destabilizing cationic porphyrin TMPyP4 cooperates with hnRNPs to increase the translation efficiency of fragile X premutation mRNA

The 5′ untranslated region of the FMR1 gene which normally includes 4–55 d(CGG) repeats expands to > 55–200 repeats in carriers of fragile X syndrome premutation. Although the levels of premutation FMR1 mRNA in carrier cells are 5–10-fold higher than normal, the amount of the product FMR protein is unchanged or reduced. We demonstrated previously that premutation r(CGG)n tracts formed quadruplex structures that impeded translation and lowered the efficiency of protein synthesis. Normal translation could be restored in vivo by the quadruplex r(CGG)n destabilizing action of CBF-A and hnRNP A2 proteins. Here we report that the quadruplex-interacting cationic porphyrin TMPyP4 by itself and in cooperation with CBF-A or hnRNP A2 also unfolded quadruplex r(CGG)n and increased the efficiency of translation of 5′-(CGG)99 containing reporter firefly (FL) mRNA. TMPyP4 destabilized in vitro a (CGG)33 intramolecular quadruplex structure and enhanced the translation of 5′-(CGG)99-FL mRNA in a rabbit reticulocyte lysate and in HEK293 cells. The efficiency of translation of (CGG)99-FL mRNA was additively increased in cells exposed to TMPyP4 together with CBF-A. Whereas low doses of TMPyP4, CBF-A or hnRNP A2 by themselves did not affect the in vivo utilization of (CGG)99-FL mRNA, introduction of TMPyP4 together with either protein synergistically augmented its translation efficiency

Case Report Monoclonal Gammopathy of Undetermined Significance (MGUS) in a Man with Fragile X-associated Tremor/Ataxia Syndrome

We report the clinical presentation and laboratory findings of a 69-year-old man with fragile X-associated tremor ataxia syndrome (FXTAS), a progressive neurodegenerative disorder, who was noted to have monoclonal gammopathy of undetermined significance (MGUS), a plasma cell proliferative disorder and a precursor disease of multiple myeloma. Both MGUS and FXTAS are associated with microRNA (miRNA) dysregulation. We speculate that individuals with FXTAS may be predisposed to MGUS and further studies are warranted regarding this association

Translation of the FMR1 mRNA is not influenced by AGG interruptions

The fragile X mental retardation 1 (FMR1) gene contains a CGG-repeat element within its 5′ untranslated region (5′UTR) which, for alleles with more than ∼40 repeats, increasingly affects both transcription (up-regulation) and translation (inhibition) of the repeat-containing RNA with increasing CGG-repeat length. Translational inhibition is thought to be due to impaired ribosomal scanning through the CGG-repeat region, which is postulated to form highly stable secondary/tertiary structure. One striking difference between alleles in the premutation range (55–200 CGG repeats) and those in the normal range (<∼40 repeats) is the reduced number/absence of ‘expansion stabilizing’ AGG interruptions in the larger alleles. Such interruptions, which generally occur every 9–11 repeats in normal alleles, are thought to disrupt the extended CGG-repeat hairpin structure, thus facilitating translational initiation. To test this hypothesis, we have measured the translational efficiency of CGG-repeat mRNAs with 0–2 AGG interruptions, both in vitro (rabbit reticulocyte lysates) and in cell culture (HEK-293 cells). We demonstrate that the AGG interruptions have no detectable influence on translational efficiency in either a cell-free system or cell culture, indicating that any AGG-repeat-induced alterations in secondary/tertiary structure, if present, do not involve the rate-limiting step(s) in translational initiation

Where do firms manage earnings?

Despite decades of research on how, why, and when companies manage earnings, there is a paucity of evidence about the geographic location of earnings management within multinational firms. In this study, we examine where companies manage earnings using a sample of 2,067 U.S. multinational firms from 1994 to 2009. We predict and find that firms with extensive foreign operations in weak rule of law countries have more foreign earnings management than companies with subsidiaries in locations where the rule of law is strong. We also find some evidence that profitable firms with extensive tax haven subsidiaries manage earnings more than other firms and that the earnings management is concentrated in foreign income. Apart from these results, we find that most earnings management takes place in domestic income, not foreign income.Arthur Andersen (Firm) (Arthur Andersen Faculty Fund