Creating a Computational Model of Prion Disease in the Human Neocortex

One way to study disease is to model specific biological reactions or processes involved in the generation of the disease in terms of a system of differential equations. The equations, called kinetic rate laws, are often non-linear and high order, making them difficult to solve. By approximating equations in complex biological networks as linear first order reactions, we can solve large sets of equations using computational software, such as MATLAB, to determine general trends in the change of molecular concentrations over time. These trends can tell us details about the disease and direct us toward areas worthy of further investigation. We can gain additional information concerning the potential behavior of a disease by superimposing its signaling network over a spatial approximation. In our work, we were able to generate a representation of a small volume of the human neocortex by modeling neurons cylinders. Cylinders act as a reliable model to describe the approximate radial symmetry of neurons. We also derived probability density equations for the dendrites and axons of each neuros. The model system is flexible so that any set of differential equations can be superimposed onto it. We plan to run our own devised system of equations for prion disease on the spatial model to see how its results differ from those produced by the kinetic equations alone

Advancing Employment Equity in Alabama

This report, Advancing Employment Equity in Alabama, offers a framework to guide policymakers as they consider how to best connect residents to good jobs that pay family-sustaining wages and remove the barriers that have held back far too many for far too long. The Alabama Asset Building Coalition is prepared to be a partner in this effort and further our mission of building an economic foundation that allows underserved Alabamians to reach their highest potential and secure their financial future

Boosting Economic Growth in Mississippi through Employment Equity

This brief describes why employment equity is critical to Mississippi's economic future and lays out a policy roadmap toachieve employment equity. It is based on data analysis and modeling of a "full-employment economy" (defined as when everyone who wants a job can find one), which was conducted by the Program for Environmental and Regional Equity (PERE) at the University of Southern California, and on policy research and focus groups conducted by PolicyLink and the Mississippi Low-Income Child Care Initiative (MLICCI)

Advancing Employment Equity in Rural North Carolina

This brief describes why employment equity in rural North Carolina is critical to the state's economic future and lays out a policy roadmap to achieving employment equity. This roadmap is based on data analysis and modeling of a "full-employmentfor-all economy" (defined as an economy in which everyone who wants a job can find one) that was conducted by the Program for Environmental and Regional Equity (PERE) at the University of Southern California as well as policy research and focus groups conducted by PolicyLink, Rural Forward, and the North Carolina Budget and Tax Center

Gender Gap in Industry Payments to Urologists

Background: The Open Payments Program (OPP) was established in 2013 under the Sunshine Act, which mandated that medical device and pharmaceutical manufacturers submit public records of any financial incentive given to physicians. The study aim is to characterize the gap in general and research payments between male and female urologists over the past 7 years. Methods: The study sample included all urologists in the US who received at least one general (GP) or research payment from 2015 to 2021. In order to identify urologists’ genders, the OPP was matched with the National Provider Index dataset. Payments to male versus female urologists were analyzed by geography, year, payment type, subspecialty, and industry payer with nominal payments adjusted to the base year’s US dollar using the Bureau of Labor Statistics’ Consumer Price Index – Urban (CPI-U). Results: 1,351,533 payments to 13,678 urologists were analyzed. Of them, 11,926 urologists were male, and 1,752 were female with an average general payment of $17,683.18 to male urologists compared to$5,825.09 to female urologists. Women not only received fewer consultant, royalty/license, speaker, and equity payments, but also received less per transaction in these categories. Conclusions: This study is the first to characterize differences in both research and general payments between male and female urologists. Further studies are needed to understand and interpret the unequal relationships between male and female urologists with industry. Industry should actively work to equitably engage female urologists in consultancies, speaking engagements, and research

Adaptation of the Systematic Review Framework to the Assessment of Toxicological Test Methods: Challenges and Lessons Learned With the Zebrafish Embryotoxicity Test

Systematic review methodology is a means of addressing specific questions through structured, consistent, and transparent examinations of the relevant scientific evidence. This methodology has been used to advantage in clinical medicine, and is being adapted for use in other disciplines. Although some applications to toxicology have been explored, especially for hazard identification, the present preparatory study is, to our knowledge, the first attempt to adapt it to the assessment of toxicological test methods. As our test case, we chose the zebrafish embryotoxicity test (ZET) for developmental toxicity and its mammalian counterpart, the standard mammalian prenatal development toxicity study, focusing the review on how well the ZET predicts the presence or absence of chemical-induced prenatal developmental toxicity observed in mammalian studies. An interdisciplinary team prepared a systematic review protocol and adjusted it throughout this piloting phase, where needed. The final protocol was registered and will guide the main study (systematic review), which will execute the protocol to comprehensively answer the review question. The goal of this preparatory study was to translate systematic review methodology to the assessment of toxicological test method performance. Consequently, it focused on the methodological issues encountered, whereas the main study will report substantive findings. These relate to numerous systematic review steps, but primarily to searching and selecting the evidence. Applying the lessons learned to these challenges can improve not only our main study, but may also be helpful to others seeking to use systematic review methodology to compare toxicological test methods. We conclude with a series of recommendations that, if adopted, would help improve the quality of the published literature, and make conducting systematic reviews of toxicological studies faster and easier over time

Clinimetrics of the Lanarkshire Oximetry Index for patients with leg ulcers: A systematic review and meta‐analysis

Ankle Brachial Pressure Index (ABPI) measurement has long been considered the gold standard of vascular assessment for people with lower limb ulceration. Despite this, only around 15% of patients in the United Kingdom who require an ABPI measurement undergo the assessment. The Lanarkshire Oximetry Index (LOI) is a cheaper and arguably more accessible approach to vascular assessment and was initially proposed as an alternative to the ABPI in 2000. No synthesis of evidence related to the LOI has been performed since its introduction into the literature. Primary studies were sought to determine the clinimetric properties of the LOI and its level of agreement with ABPI assessments. Systematic searches of MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials, BNI, ProQuest Health and Medicine, Science Direct, Google Scholar and the British Library (online search) were conducted. Reference lists of identified studies were also reviewed to identify additional studies. Three primary studies met the inclusion criteria, reporting data from 307 patients and 584 limbs assessed using both the LOI and ABPI. All three studies reported fair to moderate kappa values for interrater reliability (κ = 0.290–0.747) and statistically significant positive correlation coefficients (r = 0.37, p < 0.001 in two studies) between the LOI and ABPI. The combined data from the three studies indicated a sensitivity of 52% (41.78–62.1, 95% confidence interval [CI]) and specificity of 96.08% (93.4–97.9, 95% CI) for the LOI using the ABPI as a reference. Additional data are required to indicate the safety of the LOI in practice. Data are also required to determine if the LOI is more acceptable to clinicians compared to the ABPI and whether there are any barriers/enablers to its implementation in practice. Given the relatively low specificity of the LOI, it may be beneficial to combine measurement of the LOI with a subjective clinical risk assessment tool to improve the sensitivity of this alternative approach to vascular assessment

IgG4 inhibits peanut-induced basophil and mast cell activation in peanut-tolerant children sensitized to peanut major allergens

BackgroundMost children with detectable peanut-specific IgE (P-sIgE) are not allergic to peanut. We addressed 2 non–mutually exclusive hypotheses for the discrepancy between allergy and sensitization: (1) differences in P-sIgE levels between children with peanut allergy (PA) and peanut-sensitized but tolerant (PS) children and (2) the presence of an IgE inhibitor, such as peanut-specific IgG4 (P-sIgG4), in PS patients.MethodsTwo hundred twenty-eight children (108 patients with PA, 77 PS patients, and 43 nonsensitized nonallergic subjects) were studied. Levels of specific IgE and IgG4 to peanut and its components were determined. IgE-stripped basophils or a mast cell line were used in passive sensitization activation and inhibition assays. Plasma of PS subjects and patients submitted to peanut oral immunotherapy (POIT) were depleted of IgG4 and retested in inhibition assays.ResultsBasophils and mast cells sensitized with plasma from patients with PA but not PS patients showed dose-dependent activation in response to peanut. Levels of sIgE to peanut and its components could only partially explain differences in clinical reactivity between patients with PA and PS patients. P-sIgG4 levels (P = .023) and P-sIgG4/P-sIgE (P < .001), Ara h 1–sIgG4/Ara h 1–sIgE (P = .050), Ara h 2–sIgG4/Ara h 2–sIgE (P = .004), and Ara h 3–sIgG4/Ara h 3–sIgE (P = .016) ratios were greater in PS children compared with those in children with PA. Peanut-induced activation was inhibited in the presence of plasma from PS children with detectable P-sIgG4 levels and POIT but not from nonsensitized nonallergic children. Depletion of IgG4 from plasma of children with PS (and POIT) sensitized to Ara h 1 to Ara h 3 partially restored peanut-induced mast cell activation (P = .007).ConclusionsDifferences in sIgE levels and allergen specificity could not justify the clinical phenotype in all children with PA and PS children. Blocking IgG4 antibodies provide an additional explanation for the absence of clinical reactivity in PS patients sensitized to major peanut allergens