Chain-Length-Dependent Termination in Radical Polymerization of Acrylates

The technique of SP PLP EPR, which is single-pulse pulsed-laser polymerization (SP PLP) in conjunction with electron paramagnetic resonance (EPR) spectroscopy, is used to carry out a detailed investigation of secondary (chain-end) radical termination of acrylates. Measurements are performed on methyl acrylate, n-butyl acrylate and dodecyl acrylate in bulk and in toluene solution at –40 °C. The reason for the low temperature is to avoid formation of mid-chain radicals, a complicating factor that has imparted ambiguity to the results of previous studies of this nature. Consistent with these previous studies, composite-model behavior for chain-length-dependent termination rate coefficients, kt i,i, is found in this work. However, lower and more reasonable values of α s, the exponent for variation of kt i,i at short chain lengths, are found in the present study. Most likely this is because of the absence of mid-chain radicals, thereby validating the methodology of this work. Family-type termination behavior is observed, with the following average parameter values adequately describing all results, regardless of acrylate or the presence of toluene: α s = 0.79, α l = 0.21 (long chains) and ic ≈ 30 (crossover chain length). All indications are that these values carry over to termination of acrylate chain-end radicals at higher, more practical temperatures. Further, these values largely make sense in terms of what is understood about the physical meaning of the parameters. Variation of the rate coefficient for termination between monomeric radicals, kt 1,1, is found to be well described by the simple Smoluchowski and Stokes-Einstein equations. This allows easy prediction of kt 1,1 for different alkyl acrylates, solvent and temperature. Through all this the unrivalled power of SP PLP EPR for measuring and understanding (chain-length-dependent) termination rate coefficients shines through

Recent Advances in the Understanding of Termination in Radical Polymerization from Using the SP-PLP-EPR Technique

Since at least the 1940s, workers have been seeking to understand the kinetics of the fundamental radical-polymerization reaction of termination. This quest has not proven to be easy. Just under a decade ago, two game-changing advances were made that have unleashed rapid progress in the field: (1) The so-called ‘composite model’ was proposed: short radicals and long radicals are characterized by different scaling-law behavior in their rate of termination. (2) Single-pulse pulsed-laser polymerization (SP PLP) was coupled with electron paramagnetic resonance (EPR) spectroscopy to produce a remarkably potent new method for measuring chain-length-dependent termination (CLDT) rate coefficients, in particular those of short radicals. Essentially without exception, the SP-PLP-EPR method has revealed termination behavior in accord with the composite model. Here we summarize three recent SP-PLP-EPR studies, all involving new directions for the application of this technique

Expanded roles of community health workers to sustain malaria services in the Asia-Pacific: A landscaping survey

Malaria Community Health Workers (CHWs) in the Greater Mekong Subregion (GMS) are an important component of malaria elimination efforts. As malaria declines with intensified efforts to eliminate by 2030, expanding their roles beyond malaria could help to sustain funding and provision of malaria services at the community level. Evidence of how programmes have implemented and managed CHWs performing both malaria and non-malaria roles across the Asia-Pacific region can provide insight into the viability of this strategy. A short survey was distributed to national malaria programmes and implementing organizations in the Asia-Pacific region in 2021–2022. The survey identified CHW programmes in the region, and collected information on malaria and non-malarial services provided by CHWs, characteristics of each identified programme, and the impact of COVID-19 on these programmes. 35 survey responses identified 28 programmes in 14 countries. The most frequently reported services provided by malaria CHWs were health promotion and education for malaria (13/14 countries) and other diseases (11/14); and COVID-19 related activities (10/14). Most programmes were financed wholly through donor funding (18/28 programmes), or donor plus government funding (6/28). Of 21 programmes which performed programme evaluation, only 2 evaluated their impacts on diseases beyond malaria. Declining donor funding, and COVID-19 related travel and activity restrictions were identified as implementation challenges. CHWs across the Asia Pacific provide a range of health services with malaria and are resilient under changing public health landscapes such as the COVID-19 pandemic. Further investigation into the impact of additional roles on malaria CHW performance and targeted health outcomes is needed to verify the benefits and feasibility of role expansion. As the GMS approaches elimination, and funding declines, verifying the cost effectiveness of malaria CHW programmes will be vital to persuade donors and countries to invest in malaria CHWs to sustain malaria services, and strengthen community-based health care

Prospective Cohort Study on Performance of Cerebrospinal Fluid (CSF) Xpert MTB/RIF, CSF Lipoarabinomannan (LAM) Lateral Flow Assay (LFA), and Urine LAM LFA for Diagnosis of Tuberculous Meningitis in Zambia.

Tuberculous meningitis (TBM) is a devastating infection of the central nervous system lacking an adequate point-of-care diagnostic test. We conducted a prospective cohort study of 550 Zambian adults with suspected TBM to determine the diagnostic accuracy of cerebrospinal fluid (CSF) Xpert MTB/RIF, CSF lipoarabinomannan (LAM), urine LAM, CSF total protein, and CSF glucose compared with the gold standard of CSF culture. We categorized patients with a positive CSF tuberculosis (TB) culture as definite TBM. We also assessed inpatient and 1-year mortality on definite TBM patients when CSF Xpert MTB/RIF results were available in real time to treating physicians relative to a historical comparison cohort in whom Xpert results were not available in real time. Of the 550 patients, 474 (86.2%) were HIV-infected and 105/550 (19.1%) had definite TBM based on a positive CSF culture. The sensitivity/specificity of the diagnostic tests were CSF Xpert MTB/RIF, 52.9%/94.2%; CSF LAM, 21.9%/94.2%; urine LAM, 24.1%/76.1%; and CSF glucose 100 mg/dl, 66.3%/90%. A model including CSF Xpert MTB/RIF, CSF LAM, CSF glucose, and CSF total protein demonstrated an area under the receiver operating curve of 0.90. The inpatient and 1-year mortality for definite TBM was 43% and 57%, respectively. There was low sensitivity for the diagnosis of TBM across all diagnostics tests. CSF Xpert MTB/RIF and CSF LAM are highly specific for the diagnosis of TBM. Despite the use of Xpert MTB/RIF for diagnostic purpose in real time, TBM was still associated with a high mortality in Zambian patients

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases