A Note on the Toxicity of Chloropicrin Vapors to Gloeophyllum Saepiarium and Poria sp. in Wood

Southern pine wafers infected with Gloeophyllum saepiarium and Poria sp. were exposed to a range of chloropicrin vapor concentrations for 4, 8, 12, 16, and 24 h. The minimum lethal dosages of chloropicrin for both fungi were determined at each exposure period. The range of lethal concentration/time values, calculated at each exposure period, was small for Poria sp. but much broader for G. saepiarium over the 24-h test limits. This difference indicates that increasing the length of exposure to chloropicrin has a greater affect on G. saepiarium (susceptibility increases) than on Poria sp. (susceptibility remains relatively constant)

Evaluation of Encapsulated and Gelled Chloropicrin Formulations for Use in Wood Poles

Gelling (increasing a fluid's viscosity) and encapsulation were evaluated as means to improve the handling properties of the fumigant chloropicrin during application in the remedial preservative treatment of poles and other timbers. Several gelling agents, at concentrations of < 5% (w/w), were capable of increasing the viscosity of chloropicrin above 100,000 centipoise. The form of the dispensed gel allowed for a reduced surface area during application (when compared to liquid chloropicrin) and volatility of the gelled formulation was effectively reduced. However, addition of gelling agents to chloropicrin did not reduce the relative volatility from equivalent exposed surface areas. An evaluation of methods for dispensing one gelled formulation identified a modified pressure cylinder as a means for safer and easier application of chloropicrin compared with currently used methods. Polymer tubes for encapsulation were also evaluated as a means of handling and dispensing both liquid and gelled chloropicrin

Modeling solutions to Tanzania's physician workforce challenge.

BACKGROUND:There is a great need for physicians in Tanzania. In 2012, there were approximately 0.31 physicians per 10,000 individuals nationwide, with a lower ratio in the rural areas, where the majority of the population resides. In response, universities across Tanzania have greatly increased the enrollment of medical students. Yet evidence suggests high attrition of medical graduates to other professions and emigration from rural areas where they are most needed. OBJECTIVE:To estimate the future number of physicians practicing in Tanzania and the potential impact of interventions to improve retention, we built a model that tracks medical students from enrollment through clinical practice, from 1990 to 2025. DESIGN:We designed a Markov process with 92 potential states capturing the movement of 25,000 medical students and physicians from medical training through employment. Work possibilities included clinical practice (divided into rural or urban, public or private), non-clinical work, and emigration. We populated and calibrated the model using a national 2005/2006 physician mapping survey, as well as graduation records, graduate tracking surveys, and other available data. RESULTS:The model projects massive losses to clinical practice between 2016 and 2025, especially in rural areas. Approximately 56% of all medical school students enrolled between 2011 and 2020 will not be practicing medicine in Tanzania in 2025. Even with these losses, the model forecasts an increase in the physician-to-population ratio to 1.4 per 10,000 by 2025. Increasing the absorption of recent graduates into the public sector and/or developing a rural training track would ameliorate physician attrition in the most underserved areas. CONCLUSIONS:Tanzania is making significant investments in the training of physicians. Without linking these doctors to employment and ensuring their retention, the majority of this investment in medical education will be jeopardized

Bound Chlorinated Residue in Chloropicrin-Treated Douglas-Fir

Douglas-fir wafers exposed to chloropicrin vapors, then aerated and heated or extracted with acetone, were analyzed under a scanning electron microscope equipped with an energy dispersive X-ray analyzer. Chlorinated residues appeared to be most concentrated in the middle lamellae and in areas where wood extractives were located, which indicates that the residues were selectively binding to phenolic materials. Thin layer chromatography of acetone extracts of the treated wood suggested that chlorinated residues were binding to extractives, particularly to a portion of the phenolic extractive dihydro-quercetin. Analysis of a mixture of vanillin (a phenolic lignin derivative) and chloropicrin showed the presence of two other compounds. Mass spectroscopy tentatively identified these as CCl3-vanillin and NO2-vanillin. This identification suggests that the chloropicrin molecule was fragmented and that the two components were chemically linked to the vanillin molecule at an unspecified point. The data suggest an explanation for the presence of a phenolic-bound chlorinated residue in chloropicrin-treated wood

E-Liquid Autofluorescence can be used as a Marker of Vaping Deposition and Third-Hand Vape Exposure

In the past 5 years, e-cigarette use has been increasing rapidly, particularly in youth and young adults. Due to the novelty of e-cigarettes (e-cigs) and e-cigarette liquids (e-liquids), research on their chemo-physical properties is still in its infancy. Here, we describe a previously unknown and potentially useful property of e-liquids, namely their autofluorescence. We performed an emission scan at 9 excitation wavelengths common to fluorescent microscopy and found (i) that autofluorescence differs widely between e-liquids, (ii) that e-liquids are most fluorescent in the UV range (between 350 and 405 nm) and (iii) fluorescence intensity wanes as the emission wavelength increases. Furthermore, we used the autofluorescence of e-liquids as a marker for tracking e-cig aerosol deposition in the laboratory. Using linear regression analysis, we were able to quantify the deposition of a "vaped" e-liquid onto hard surfaces. Using this technique, we found that every 70 mL puff of an e-cigarette deposited 0.019% e-liquid (v/v) in a controlled environment. Finally, we vaped a surface in the laboratory and used our method to detect e-cig aerosol third-hand exposure. In conclusion, our data suggest that e-cigarette autofluorescence can be used as a marker of e-cigarette deposition

1863-11-09 D.S. Goodell recommends Orderly Christopher C. Gray for promotion

https://digitalmaine.com/cw_me_4th_regiment_corr/1432/thumbnail.jp

Phycomyces

This monographic review on a fungus is not addressed to mycologists. None of the authors has been trained or has otherwise acquired a general proficiency in mycology. They are motivated by a common interest in the performances of signal handling exhibited by the sense organs of all organisms and by the desire to attack these as yet totally obscure aspects of molecular biology by the study of a microorganism with certain desirable properties. The sporangiophore of the fungus Phycomyces is a gigantic, single-celled, erect, cylindrical, aerial hypha. It is sensitive to at least four distinct stimuli: light, gravity, stretch, and some unknown stimulus by which it avoids solid objects. These stimuli control a common output, the growth rate, producing either temporal changes in growth rate or tropic responses. We are interested in the output because it gives us information about the reception of the various signals. In the absence of external stimuli, the growth rate is controlled by internal signals keeping the network of biochemical processes in balance. The external stimuli interact with the internal signals. We wish to inquire into the early steps of this interaction. For light, for instance, the cell must have a receptor pigment as the first mediator. What kind of a molecule is this pigment? Which organelle contains it? What chemical reaction happens after a light quantum has been absorbed? And how is the information introduced by this primary photochemical event amplified in a controlled manner and processed in the next step? How do a few quanta or a few molecules trigger macroscopic responses? Will we find ourselves confronted with devices wholly distinct from anything now known in biology

Clinical actionability of comprehensive genomic profiling for management of rare or refractory cancers

Background. The frequency with which targeted tumor sequencing results will lead to implemented change in care is unclear. Prospective assessment of the feasibility and limitations of using genomic sequencing is critically important. Methods. A prospective clinical study was conducted on 100 patients with diverse-histology, rare, or poor-prognosis cancers to evaluate the clinical actionability of a Clinical Laboratory Improvement Amendments (CLIA)-certified, comprehensive genomic profiling assay (FoundationOne), using formalin-fixed, paraffin-embedded tumors. The primary objectives were to assess utility, feasibility, and limitations of genomic sequencing for genomically guided therapy or other clinical purpose in the setting of a multidisciplinary molecular tumor board. Results. Of the tumors from the 92 patients with sufficient tissue, 88 (96%) had at least one genomic alteration (average 3.6, range 0–10). Commonly altered pathways included p53 (46%), RAS/RAF/MAPK (rat sarcoma; rapidly accelerated fibrosarcoma; mitogen-activated protein kinase) (45%), receptor tyrosine kinases/ligand (44%), PI3K/AKT/mTOR (phosphatidylinositol-4,5-bisphosphate 3-kinase; protein kinase B; mammalian target of rapamycin) (35%), transcription factors/regulators (31%), and cell cycle regulators (30%). Many low frequency but potentially actionable alterations were identified in diverse histologies. Use of comprehensive profiling led to implementable clinical action in 35% of tumors with genomic alterations, including genomically guided therapy, diagnostic modification, and trigger for germline genetic testing. Conclusion. Use of targeted next-generation sequencing in the setting of an institutional molecular tumor board led to implementable clinical action in more than one third of patients with rare and poor-prognosis cancers. Major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access. Early and serial sequencing in the clinical course and expanded access to genomically guided early-phase clinical trials and targeted agents may increase actionability. Implications for Practice: Identification of key factors that facilitate use of genomic tumor testing results and implementation of genomically guided therapy may lead to enhanced benefit for patients with rare or difficult to treat cancers. Clinical use of a targeted next-generation sequencing assay in the setting of an institutional molecular tumor board led to implementable clinical action in over one third of patients with rare and poor prognosis cancers. The major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access both on trial and off label. Approaches to increase actionability include early and serial sequencing in the clinical course and expanded access to genomically guided early phase clinical trials and targeted agents

Molecular Signatures of Proliferation and Quiescence in Hematopoietic Stem Cells

Stem cells resident in adult tissues are principally quiescent, yet harbor enormous capacity for proliferation to achieve self renewal and to replenish their tissue constituents. Although a single hematopoietic stem cell (HSC) can generate sufficient primitive progeny to repopulate many recipients, little is known about the molecular mechanisms that maintain their potency or regulate their self renewal. Here we have examined the gene expression changes that occur over a time course when HSCs are induced to proliferate and return to quiescence in vivo. These data were compared to data representing differences between naturally proliferating fetal HSCs and their quiescent adult counterparts. Bioinformatic strategies were used to group time-ordered gene expression profiles generated from microarrays into signatures of quiescent and dividing stem cells. A novel method for calculating statistically significant enrichments in Gene Ontology groupings for our gene lists revealed elemental subgroups within the signatures that underlie HSC behavior, and allowed us to build a molecular model of the HSC activation cycle. Initially, quiescent HSCs evince a state of readiness. The proliferative signal induces a preparative state, which is followed by active proliferation divisible into early and late phases. Re-induction of quiescence involves changes in migratory molecule expression, prior to reestablishment of homeostasis. We also identified two genes that increase in both gene and protein expression during activation, and potentially represent new markers for proliferating stem cells. These data will be of use in attempts to recapitulate the HSC self renewal process for therapeutic expansion of stem cells, and our model may correlate with acquisition of self renewal characteristics by cancer stem cells