History of Licensure in Several Occupations in the Health Professions

The origin of licensure in the medical professions is outlined beginning in Europe around the first century with the examination of potential physicians by the most respected physician in the land. Guilds developed and licensing bodies became university medical faculties. Prussia was the firet country to require specific courses for license eligibility whereas state control first developed in Germany. Americans fluctuated among various licensing methods until the 1700s when state boards were established. Professional standards, including licensure, for allied health professions have typically followed the lead of physicians. The origins, advantages and disadvantages of licensure in several of these occupations are reviewed also

One-pot thiol–amine bioconjugation to maleimides: simultaneous stabilisation and dual functionalisation

Maleimide chemistry is widely used in the site-selective modification of proteins. However, hydrolysis of the resultant thiosuccinimides is required to provide robust stability to the bioconjugates. Herein, we present an alternative approach that affords simultaneous stabilisation and dual functionalisation in a one pot fashion. By consecutive conjugation of a thiol and an amine to dibromomaleimides, we show that aminothiomaleimides can be generated extremely efficiently. Furthermore, the amine serves to deactivate the electrophilicity of the maleimide, precluding further reactivity and hence generating stable conjugates. We have applied this conjugation strategy to peptides and proteins to generate stabilised trifunctional conjugates. We propose that this stabilisation-dual modification strategy could have widespread use in the generation of diverse conjugates

The Response of Electron Pitch Angle Distributions to the Upper Limit on Stably Trapped Particles

We use Van Allen Probes electron data during 70 geomagnetic storms to examine the response of equatorial pitch angle distributions (PADs) at L* = 4.0–4.5 to a theoretical upper limit on stably trapped particle fluxes. Of the energies examined, 54 and 108 keV electron PADs isotropize to a previously assumed level within 6 hr of reaching the limit, near-identically across all 70 storms, consistent with rapid pitch angle scattering due to chorus wave interactions. In around 30% of events, 54 keV electrons completely exceed the KP limit, before being quickly subdued. 470 and 749 keV PADs show clear indications of an upper limit, though less aligned with the calculated limit used here. The consistency of an absolute upper limit shown across all events demonstrates the importance of this phenomena in both the limiting effect on electron flux and consistently influencing electron PAD evolution during geomagnetic storms. These results also highlight the need for further investigation, particularly related to the limiting of higher energy electrons

Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid.

Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5-20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of D-glucose was lower than D-fructose. However, uptake of D-glucose was higher than D-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection

Ethics of AI in Education: Towards a Community-Wide Framework

While Artificial Intelligence in Education (AIED) research has at its core the desire to support student learning, experience from other AI domains suggest that such ethical intentions are not by themselves sufficient. There is also the need to consider explicitly issues such as fairness, accountability, transparency, bias, autonomy, agency, and inclusion. At a more general level, there is also a need to differentiate between doing ethical things and doing things ethically, to understand and to make pedagogical choices that are ethical, and to account for the ever-present possibility of unintended consequences. However, addressing these and related questions is far from trivial. As a first step towards addressing this critical gap, we invited 60 of the AIED community’s leading researchers to respond to a survey of questions about ethics and the application of AI in educational contexts. In this paper, we first introduce issues around the ethics of AI in education. Next, we summarise the contributions of the 17 respondents, and discuss the complex issues that they raised. Specific outcomes include the recognition that most AIED researchers are not trained to tackle the emerging ethical questions. A well-designed framework for engaging with ethics of AIED that combined a multidisciplinary approach and a set of robust guidelines seems vital in this context

New Bifunctional Chelators Incorporating Dibromomaleimide Groups for Radiolabeling of Antibodies with Positron Emission Tomography Imaging Radioisotopes

Positron Emission Tomography (PET) imaging with antibody-based contrast agents frequently uses the radioisotopes [{64}^Cu]Cu^{2+} and [{89}^Zr]Zr^{4+}. The macrobicyclic chelator commonly known as sarcophagine (sar) is ideal for labeling receptor-targeted biomolecules with [{64}^Cu]Cu^{2+}. The siderophore chelator, desferrioxamine-B (dfo), has been widely used to incorporate [{89}^Zr]Zr^{4+}, respectively, in near quantitative radiochemical yield (>99%). Serum stability studies, in vivo PET imaging, and biodistribution analyses using these radiolabeled immunoconjugates demonstrate that both [{64}^Cu]Cu-sar–dtm–trastuzumab and [{89}^Zr]Zr-dfo–dtm–trastuzumab possess high stability in biological milieu. Dibromomaleimide technology can be easily applied to enable stable, site-specific attachment of radiolabeled chelators, such as sar and dfo, to native interstrand disulfide regions of antibodies, enabling tracking of antibodies with PET imaging

Opportunities for improving pLDH-based malaria diagnostic tests

<p>Abstract</p> <p>Background</p> <p>Monoclonal antibodies to <it>Plasmodium </it>lactate dehydrogenase (pLDH) have been previously used to format immunochromatographic tests for the diagnosis of malaria. Using pLDH as an antigen has several advantages as a sensitive measure of the presence of parasites within patient blood samples. However, variable results in terms of specificity and sensitivity among different commercially available diagnostic kits have been reported and it has not been clear from these studies whether the performance of an individual test is due simply to how it is engineered or whether it is due to the biochemical nature of the pLDH-antibody reaction itself.</p> <p>Methods</p> <p>A series of systematic studies to determine how various pLDH monoclonal antibodies work in combination was undertaken. Different combinations of anti-pLDH monoclonal antibodies were used in a rapid-test immunochromatographic assay format to determine parameters of sensitivity and specificity with regard to individual <it>Plasmodium </it>species.</p> <p>Results</p> <p>Dramatic differences were found in both species specificity and overall sensitivity depending on which antibody is used on the immunochromatographic strip and which is used on the colorimetric colloidal-gold used for visual detection.</p> <p>Discussion</p> <p>The results demonstrate the feasibility of different test formats for the detection and speciation of malarial infections. In addition, the data will enable the development of a universal rapid test algorithm that may potentially provide a cost-effective strategy to diagnose and manage patients in a wide range of clinical settings.</p> <p>Conclusion</p> <p>These data emphasize that using different anti-pLDH antibody combinations offers a tractable way to optimize immunochromatographic pLDH tests.</p