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Changes in Distribution and Frequency of Fungi Associated With a Foliar Disease Complex of Pyrethrum in Australia
Get PDFIn Australia, pyrethrum (Tanacetum cinerariifolium) is affected by a foliar disease complex that can substantially reduce green leaf area and yield. Historically, the most important foliar disease of pyrethrum in Australia has been ray blight, caused by Stagonosporopsis tanaceti, and other fungi generally of minor importance. Temporal fluctuations in the frequency of fungi associated with foliar disease were quantified in each of 83 fields in northern Tasmania, Australia, during 2012 and 2013. Sampling was conducted throughout winter (April to July), spring (August to September), and summer (November) representing different phenological stages. Microsphaeropsis tanaceti, the cause of tan spot, was the pathogen most prevalent and isolated at the highest frequency, irrespective of sampling period. The next most common species was S. tanaceti, whose isolation frequency was low in winter and increased in spring and summer. Known pathogens of pyrethrum, Alternaria tenuissima, Colletotrichum tanaceti, and Stemphylium botryosum were recovered sporadically and at low frequency. Two species of potential importance, Paraphoma chrysanthemicola and Itersonilia perplexans, were also found at low frequency. This finding suggests a substantial shift in the dominant pathogen associated with foliar disease, from S. tanaceti to M. tanaceti, and coincides with an increase in defoliation severity in winter, and control failures of the spring fungicide program. Factors associated with this finding were also investigated. Sensitivity of M. tanaceti and S. tanaceti populations to the fungicides boscalid and cyprodinil collected prior to and following disease control failures in the field were tested under in vitro conditions. A high proportion (60%) of the M. tanaceti isolates obtained from fields in which no response to the spring fungicide program was found were insensitive to 50 µg a.i./ml boscalid. This represented a 4.2-fold increase in the frequency of this phenotype within the M. tanaceti population over 2 years. No shifts in sensitivities to cyprodinil of M. tanaceti and S. tanaceti, or S. tanaceti to boscalid, were observed. Considering the increase in defoliation severity over winter, the benefits of applying fungicides in autumn, in addition to the commercial standard (spring only), were quantified in 14 individual field trials conducted in 2011 and 2012. Mixed-model analysis suggested fungicide application in autumn may improve pyrethrum growth during late winter and early spring, although effects on defoliation and yield were minimal. The increasing prevalence and isolation frequency of M. tanaceti and boscalid resistance within the population is of concern and highlights the urgent need for adoption of nonchemical methods for disease management in Australian pyrethrum fields.This is the publisher’s final pdf. The published article is copyrighted by American Phytopathological Society and can be found at: http://apsjournals.apsnet.org/loi/pdi
ChristensenJPharmCalciumChlorideNeonatalSupportingInformationDataStudy1.XLS
No full textBackground:
Previous studies of compatibility of calcium chloride (CaCl₂) and phosphates have not included particle counts in the range specified by the United States Pharmacopeia. Micro-flow imaging techniques have been shown to be comparable to light obscuration when determining particle count and size in pharmaceutical solutions.
Objective:
The purpose of this study was to do compatibility testing for parenteral nutrition (PN) solutions containing CaCl₂ using dynamic light scattering and micro-flow imaging techniques.
Methods:
Solutions containing TrophAmine (Braun Medical Inc, Irvine, CA), CaCl₂, and sodium phosphate (NaPhos) were compounded with and without cysteine. All solutions contained standard additives to neonatal PN solutions including dextrose, trace metals, and electrolytes. Control solutions contained no calcium or phosphate. Solutions were analyzed for particle size and particle count. Means of Z-average particle size and particle counts of controls were determined. Study solutions were compared to controls and United States Pharmacopeia (USP) Chapter 788 guidelines. The maximum amount of Phos that was compatible in solutions that contained at least 10 mmol/L of Ca in 2.5% amino acids (AA) was determined. Compatibility of these solutions was verified by performing analyses of 5 repeats of these solutions. Microscopic analyses of the repeats were also performed.
Results:
Amounts of CaCl₂ and NaPhos that were compatible in solutions containing 1.5%, 2%, 2.5%, and 3% AA were determined. The maximum amount of NaPhos that could be added to TrophAmine solutions of > = 2.5% AA containing at least 10 mmol/L of CaCl₂ was 7.5 mmol/L. Adding 50 mg/dL of cysteine increased the amount of NaPhos that could be added to solutions containing 10 mmol/L of CaCl₂ to 10 mmol/L.
Conclusion:
Calcium chloride can be added to neonatal PN solutions containing NaPhos in concentrations that can potentially provide an intravenous intake of adequate amounts of calcium and phosphorus
Metabolism and Excretion Rates of Parent and Hydroxy-PAHs in Urine Collected after Consumption of Traditionally Smoked Salmon for Native American Volunteers
Get PDFFew studies have been published on the excretion rates of parent polycyclic aromatic hydrocarbons (PAHs) and hydroxy-polycyclic aromatic hydrocarbons (OH-PAHs) following oral exposure. This study investigated metabolism and excretion rates of 4 parent PAHs and 10 OH-PAHs after the consumption of smoked salmon. Nine members of the Confederated Tribes of the Umatilla Indian Reservation consumed 50 g of traditionally smoked salmon with breakfast and five urine samples were collected during the following 24 hours. The concentrations of OH-PAHs increased from 43.9 µg/g creatinine for 2-OH-Nap to 349 ng/g creatinine for 1-OH-Pyr, 3
to 6 hr post-consumption. Despite volunteers following a restricted diet, there appeared to be a secondary source of naphthalene and fluorene, which led to excretion efficiencies greater than 100%. For the parent PAHs that were detected in urine, the excretion efficiencies ranged from 13% for phenanthrene (and its metabolite) to 240% for naphthalene (and its metabolites). The half-lives for PAHs ranged from 1.4 hr for retene to 3.3 hr for pyrene. The half-lives for OH-PAHs were higher and ranged from 1.7 hr for 9-OH-fluorene to 7.0 hr for 3-OH-fluorene. The concentrations of most parent PAHs, and their metabolites, returned to the background levels 24 hr post-consumption
SimonichStaciEnvironmentalMolecularToxicologyMetabolismExcretionRates(SupportingInformation).pdf
No full textFew studies have been published on the excretion rates of parent polycyclic aromatic hydrocarbons (PAHs) and hydroxy-polycyclic aromatic hydrocarbons (OH-PAHs) following oral exposure. This study investigated metabolism and excretion rates of 4 parent PAHs and 10 OH-PAHs after the consumption of smoked salmon. Nine members of the Confederated Tribes of the Umatilla Indian Reservation consumed 50 g of traditionally smoked salmon with breakfast and five urine samples were collected during the following 24 hours. The concentrations of OH-PAHs increased from 43.9 µg/g creatinine for 2-OH-Nap to 349 ng/g creatinine for 1-OH-Pyr, 3
to 6 hr post-consumption. Despite volunteers following a restricted diet, there appeared to be a secondary source of naphthalene and fluorene, which led to excretion efficiencies greater than 100%. For the parent PAHs that were detected in urine, the excretion efficiencies ranged from 13% for phenanthrene (and its metabolite) to 240% for naphthalene (and its metabolites). The half-lives for PAHs ranged from 1.4 hr for retene to 3.3 hr for pyrene. The half-lives for OH-PAHs were higher and ranged from 1.7 hr for 9-OH-fluorene to 7.0 hr for 3-OH-fluorene. The concentrations of most parent PAHs, and their metabolites, returned to the background levels 24 hr post-consumption
Financial Performance of a Mobile Pyrolysis System Used to Produce Biochar from Sawmill Residues
Get PDFPrimary wood products manufacturers generate significant amounts of woody biomass residues that can be used as feedstocks for distributed-scale thermochemical conversion systems that produce valuable bioenergy and bioproducts. However, private investment in these technologies is driven primarily by financial performance, which is often unknown for new technologies with limited industrial deployment. In this paper, we use shift-level production data collected during a 25-day field study to characterize the conversion rate and system productivity and costs for a commercially available pyrolysis system co-located at a sawmill, and then evaluate the net present value (NPV) of the operation in light of a cost structure that is realistic for the industry. Baseline costs on a feedstock throughput basis were estimated as 308.14 t⁻¹ for conversion, and 536,031 for a 10-year project period, while the best case scenario generated an NPV of $467,353. In general, NPV is highly sensitive to labor costs and biochar price, and less sensitive to fuel cost and interest rate. Results also show clear opportunities for technical and operational improvements that are expected to increase the financial viability of this system
Challenges in the Diagnosis and Treatment of Homozygous Familial Hypercholesterolemia
Get PDFHomozygous familial hypercholesterolemia (HoFH) is a rare, genetic disorder characterized by an absence or impairment of low-density lipoprotein receptor (LDLR) function resulting in significantly elevated low-density lipoprotein cholesterol (LDL-C) levels. The cholesterol exposure burden beginning in utero greatly increases the risk for atherosclerotic cardiovascular disease (ASCVD) and premature death. The genetic heterogeneity of HoFH results in a wide range of LDL-C levels among both untreated and treated patients. Diagnosis of HoFH should, therefore, be based on a comprehensive evaluation of clinical criteria and not exclusively LDL-C levels. As treatment goals, the European Atherosclerosis Society and International FH Foundation suggest target LDL-C levels of <100 mg/dL (<2.5 mmol/L) in adults or <70 mg/dL (<1.8 mmol/L) in adults with clinical coronary artery disease or diabetes. The National Lipid Association (NLA) recommends that LDL-C levels be reduced to <100 mg/dL (<2.5 mmol/L) or by at least ≥ 50 % from pretreatment levels. Conventional therapy combinations that lower atherogenic lipoproteins levels in the blood, such as statins, ezetimibe, bile acid sequestrants and niacin, as well as lipoprotein apheresis, are usually unable to reduce LDL-C levels to recommended targets. Two recently approved agents that reduce lipoprotein synthesis and secretion by the liver are lomitapide, a microsomal triglyceride transfer protein inhibitor, and mipomersen, an apolipoprotein B antisense oligonucleotide. The newly approved inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9), evolocumab, also shows promise for the management of FH. Because of the extremely high risk for ASCVD, HoFH patients should be identified early.This is the publisher’s final pdf. The published article is copyrighted by the author(s) and co-published by Springer and Adis. The published article can be found at: http://link.springer.com/journal/4026
HartungDanielPharmacyCostMulitpleSclerosis.pdf
No full textObjective: To examine the pricing trajectories in the United States of disease-modifying therapies (DMT) for multiple sclerosis (MS) over the last 20 years and assess the influences on rising prices.
Methods: We estimated the trend in annual drug costs for 9 DMTs using published drug pricing data from 1993 to 2013. We compared changes in DMT costs to general and prescription drug inflation during the same period. We also compared the cost trajectories for first-generation MS DMTs interferon (IFN)–β-1b, IFN-β-1a IM, and glatiramer acetate with contemporaneously approved biologic tumor necrosis factor (TNF) inhibitors.
Results: First-generation DMTs, originally costing 11,000, now cost about $60,000 per year. Costs for these agents have increased annually at rates 5 to 7 times higher than prescription drug inflation. Newer DMTs commonly entered the market with a cost 25%–60% higher than existing DMTs. Significant increases in the cost trajectory of the first-generation DMTs occurred following the Food and Drug Administration approvals of IFN-β-1a SC (2002) and natalizumab (reintroduced 2006) and remained high following introduction of fingolimod (2010). Similar changes did not occur with TNF inhibitor biologics during these time intervals. DMT costs in the United States currently are 2 to 3 times higher than in other comparable countries.
Conclusions: MS DMT costs have accelerated at rates well beyond inflation and substantially above rates observed for drugs in a similar biologic class. There is an urgent need for clinicians, payers, and manufacturers in the United States to confront the soaring costs of DMTs
Aerodynamic roughness height for gravel-mantled megaripples, with implications for wind profiles near TARs on Mars
Get PDFAerodynamic roughness heights of 1–3 cm were obtained from measured wind profiles collected among fields of gravel-mantled megaripples in the high desert of the Puna region of northwestern Argentina. Roughness height appears to be relatively insensitive to the angle at which the wind was incident upon the bedforms throughout the study sites. The results represent the first wind profiling measurements for large megaripples, but they also demonstrate the importance of a careful evaluation of many potential effects that can influence the utility of wind profiling data. The same effects that influence collection of fieldwork data must also be considered in any prediction of wind profiles anticipated to occur near Transverse Aeolian Ridges and other aeolian features on Mars that are intermediate in scale between wind ripples and small sand dunes
North Pacific deglacial hypoxic events linked to abrupt ocean warming
Get PDFMarine sediments from the North Pacific document two episodes of expansion and strengthening of the subsurface oxygen minimum zone (OMZ) accompanied by seafloor hypoxia during the last deglacial transition. The mechanisms driving this hypoxia remain under debate. We present a new high-resolution alkenone palaeotemperature reconstruction from the Gulf of Alaska that reveals two abrupt warming events of 4–5 degrees Celsius at the onset of the Bølling and Holocene intervals that coincide with sudden shifts to hypoxia at intermediate depths. The presence of diatomaceous laminations and hypoxia-tolerant benthic foraminiferal species, peaks in redox-sensitive trace metals, and enhanced ¹⁵N/¹⁴N ratio of organic matter, collectively suggest association with high export production. A decrease in ¹⁸O/¹⁶O values of benthic foraminifera accompanying the most severe deoxygenation event indicates subsurface warming of up to about 2 degrees Celsius. We infer that abrupt warming triggered expansion of the North Pacific OMZ through reduced oxygen solubility and increased marine productivity via physiological effects; following initiation of hypoxia, remobilization of iron from hypoxic sediments could have provided a positive feedback on ocean deoxygenation through increased nutrient utilization and carbon export. Such a biogeochemical amplification process implies high sensitivity of OMZ expansion to warming
Rationally engineered flavin-dependent oxidase reveals steric control of dioxygen reduction
Get PDFThe ability of flavoenzymes to reduce dioxygen varies greatly and is controlled by the protein environment that can cause either a rapid (oxidases) or sluggish (dehydrogenases) reaction. Previously, a “gatekeeper” amino acid residue was identified that controls the reactivity to dioxygen in proteins from the vanillyl alcohol oxidase superfamily of flavoenzymes. We have identified an alternate gatekeeper residue that similarly controls dioxygen reactivity in the grass pollen allergen Phl p 4, a member of this superfamily, which has glucose dehydrogenase activity and the highest redox potential measured in a flavoenzyme. A substitution at the alternate gatekeeper site (I153V) transformed the enzyme into an efficient oxidase by increasing dioxygen reactivity by a factor of 60,000. An inverse exchange (V169I) in the structurally related berberine bridge enzyme (BBE) lowered its dioxygen reactivity by a factor of 500. Structural and biochemical characterization of these and additional variants showed that our model enzymes have a cavity binding an anion and resembling the “oxyanion hole” in the proximity of the flavin ring. We showed also that steric control of access to this site is the most important parameter affecting dioxygen reactivity in BBE-like enzymes. Analysis of flavin-dependent oxidases from other superfamilies revealed similar structural features suggesting that dioxygen reactivity might be governed by a common mechanistic principle.This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by FEBS (Federation of European Biochemical Societies) and published by John Wiley & Sons, Inc. It can be found at: http://febs.onlinelibrary.wiley.com/hub/journal/10.1111/%28ISSN%291742-4658