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The Albuquerque Aztecs was a workforce identify used in the film, "Any Given Sunday," about fictional pro football groups. Prop (or proposition) betting shifts bettors' focus away from game outcomes and squarely on in-sport outcomes involving players or teams. The school undertook a feasibility study involving the costs concerned with such an improve. Tulane University Law School. Kansas Metropolis Chiefs quarterback Patrick Mahomes signed the biggest deal in NFL history, a 10-year contract valued at $450 million. These terms won’t be renegotiated until their contract comes up for renewal. https://yamcode.com/tips-on-how-to-make-your-nfl-eagles-appear-like-one-million-bucks They're the video games-within-the-video games - and they're among the fastest-rising NFL guess varieties in the case of total popularity. However, they're nonetheless not at the underside of the barrel with regards to paydays. Bettors can resolve on their alternative of Tremendous Bowl winner as far as 12 months prematurely, while individual awards markets can be found for most of the year. Futures markets are amongst the best of them all: Choose the player or staff you think will win, and in the event that they do, then your ticket is victorious. And no sport caters to the exhausting-core prop bettor just like the NFL, which presents lots of of prop markets for every game on the schedule.

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We have calculated the permanent dipole moment difference related to the lowest-energy transition using the Lippert-Matagaformalism and the 2PA sum-over-states approach to confirm this assumption. Moreover, we have estimated the fundamental limits for the 2PA cross-section in oligofluorenes.When an aqueous solution freezes at temperatures above the eutectic point, a freeze concentrated solution (FCS) is separated from the ice phase. Reactions of environmental importance often occur in the FCS and, in some cases, are accelerated compared to those in solution conditions. The pH of the FCS is an essential factor governing the thermodynamics and kinetics of the reactions occurring therein. It is known that freezing of aqueous NaCl causes an increase in the FCS pH, which arises from the difference in the partition to the ice phase between Na+ and Cl-. It has also been shown that H+ and other ions show surface-specific behaviors on ice. Although the details are not known, the ice/FCS interface can also affect the behaviors of ions. In this study, the pH distribution in the FCS is evaluated using ratiometric fluorescence microscopy, and the pH inhomogeneity is confirmed for frozen aqueous NaCl. However, interestingly, buffered solutions and frozen aqueous glycerol result in a uniform pH value. The pH in frozen NaCl is always higher near the ice/FCS interface than in the middle of the FCS vein.High-level electronic structure calculations were performed to analyze ground and excited states of neutral and cationic endohedral M@C20H20 (M = K, Rb, Ca, Sr) and M@C36H36 (M = Na, K, Rb). In their ground states, one or two electrons occupy a diffuse atomic s-type orbital, thus 1s1 and 1s2 superatomic electronic configurations are assigned for M = Na, K, Rb and M = Ca, Sr cases, respectively. These species populate 1p-, 1d-, 1f-superatomic orbitals in electronically excited states. The specific superatomic Aufbau model introduced for M@C20H20 (M = K, Rb) is 1s, 1p, 1d, 2s, 1f, 2p, 2d, 1g, 2f. On the other hand, excited electronic spectra of M@C20H20 (M = Ca, Sr) are rich in multireference characters. Excited states of bigger M@C36H36 molecules were investigated up to the 1d level and the transitions were found to require slightly higher energies compared to M@C20H20. These superatoms possess lower ionization potentials, hence can also be categorized as superalkalis.The 2-electron pathway of the oxygen reduction reaction is an unwanted process in the development of fuel cells. In contrast, it has gained the scientific community's attention due to its importance as a promising way of removing emergent pollutants and endocrine disruptors from water bodies and a more sustainable alternative for large-scale commercial hydrogen peroxide production. Cerium oxide has shown remarkable potential and selectivity experimentally for this mechanism, and its possible applications, exceeding the previous reference materials. In this work, we studied the 2-electron pathway for oxygen reduction on different ceria-cleaving directions (100), (110), (221), and (331) by first principles methods based on density functional theory. Our results show that the (100) surface is the most favorable for reduction, with the (331) crystallographic plane also showing potential for good catalytic activity. This fact could be essential for designing new nanostructures, with higher portions of those planes exposed, for higher catalytic activity.A refined technique for observing the complete evaporation behaviour of free-falling droplets, from droplet generation to complete solvent evaporation, with ultra-high time resolution is introduced and benchmarked. High-resolution phase-delay stroboscopic imaging is employed to simultaneously resolve the evolving droplet morphology, geometric and aerodynamic diameters, throughout the evaporative lifetime with a user-controlled less then μs timescale. This allows rapid, complex morphological changes, such as crystallisation events, to be clearly observed and the corresponding mechanisms to be inferred. The dried particles are sampled for offline SEM analysis and the observed morphologies compared to the inflight imaging. Density changes can be calculated directly from the deviation between the geometric and aerodynamic diameters. The full capabilities of the new technique are demonstrated by examination of the different evaporation behaviours and crystallisation mechanisms for aqueous sodium chloride droplets evaporating under different ambient relative humidity (RH) conditions. https://www.selleckchem.com/products/azd9291.html The crystallisation window, defined as the time taken from initial to complete crystallisation, is shown to be RH dependent, extending from 0.03 s at 20% RH and 0.13 s at 40% RH. The different crystallisation mechanisms observed during the experiments are also clearly reflected in the final structure of the dry particles, with multi-crystal structures produced at low RH compared to single-crystal structures at higher RH. It is anticipated that this technique will unlock measurements which explore the evaporation behaviour and crystallisation mechanisms for rapid, complex droplet drying events, and with increasingly non-ideal solutions, relevant to industrial applications.Microscopic-level understanding of the separation mechanism for two-dimensional (2D) membranes is an active area of research due to potential implications of this class of membranes for various technological processes. Helium (He) purification from the natural resources is of particular interest due to the shortfall in its production. In this work, we applied the ring polymer molecular dynamics (RPMD) method to graphdiyne (Gr2) and graphtriyne (Gr3) 2D membranes having variable pore sizes for the separation of He isotopes, and compare for the first time with rigorous quantum calculations. We found that the transmission rate through Gr3 is many orders of magnitude greater than Gr2. The selectivity of either isotope at low temperatures is a consequence of a delicate balance between the zero-point energy effect and tunneling of 4He and 3He. In particular, a remarkable tunneling effect is reported on the Gr2 membrane at 10 K, leading to a much larger permeation of the lighter species as compared to the heavier isotope. RPMD provides an efficient approach for studying the separation of He isotopes, taking into account quantum effects of light nuclei motions at low temperatures, which classical methods fail to capture.The reactions between substituted isocyanates (RNCO) and other small molecules (e.g. water, alcohols, and amines) are of significant industrial importance, particularly for the development of novel polyurethanes and other useful polymers. We present very high-level ab initio computations on the HNCO + H2O reaction, with results targeting the CCSDT(Q)/CBS//CCSD(T)/cc-pVQZ level of theory. Our results affirm that hydrolysis can occur across both the N[double bond, length as m-dash]C and C[double bond, length as m-dash]O bonds of HNCO via concerted mechanisms to form carbamate or imidic acid with ΔH0K barrier heights of 38.5 and 47.5 kcal mol-1. A total of 24 substituted RNCO + H2O reactions were studied. Geometries obtained with a composite method and refined with CCSD(T)/CBS single point energies determine that substituted RNCO species have a significant influence on these barrier heights, with an extreme case like fluorine lowering both barriers by close to 15 kcal mol-1 and most common alkyl substituents lowndicate that an additional RNCO molecule might catalyze imidic acid formation but have less influence on the efficiency of carbamate formation. We expect that these results lay a firm foundation for the experimental study of substituted isocyanates and their relationship to the energetic pathways of related systems.A route towards covalent functionalization of chemically inert 2H-MoS2 exploiting sulfur vacancies is explored by means of (TD)DFT and GW/BSE calculations. Functionalization via nitrogen incorporation at sulfur vacancies is shown to result in more stable covalent binding than via thiol incorporation. In this way, defective monolayer MoS2 is repaired and the quasiparticle band structure as well as the remarkable optical properties of pristine MoS2 are restored. Hence, defect-free functionalization with various molecules is possible. Our results for covalently attached azobenzene, as a prominent photo-switch, pave the way to create photoresponsive two-dimensional (2D) materials.The reaction of the D1-silylidyne radical (SiD; X2Π) with phosphine (PH3; X1A1) was conducted in a crossed molecular beams machine under single collision conditions. Merging of the experimental results with ab initio electronic structure and statistical Rice-Ramsperger-Kassel-Marcus (RRKM) calculations indicates that the reaction is initiated by the barrierless formation of a van der Waals complex (i0) as well as intermediate (i1) formed via the barrierless addition of the SiD radical with its silicon atom to the non-bonding electron pair of phosphorus of the phosphine. Hydrogen shifts from the phosphorous atom to the adjacent silicon atom yield intermediates i2a, i2b, i3; unimolecular decomposition of these intermediates leads eventually to the formation of trans/cis-phosphinidenesilyl (HSiPH, p2/p4) and phosphinosilylidyne (SiPH2, p3) via hydrogen deuteride (HD) loss (experiment 80 ± 11%, RRKM 68.7%) and d-trans/cis-phosphinidenesilyl (DSiPH, p2'/p4') plus molecular hydrogen (H2) (experiment 20 ± 7%, RRKM 31.3%) through indirect scattering dynamics via tight exit transition states. Overall, the study reveals branching ratios of p2/p4/p2'/p4' (trans/cis HSiPH/DSiPH) to p3 (SiPH2) of close to 4  1. The present study sheds light on the complex reaction dynamics of the silicon and phosphorous systems involving multiple atomic hydrogen migrations and tight exit transition states, thus opening up a versatile path to access the previously elusive phosphinidenesilyl and phosphinosilylidyne doublet radicals, which represent potential targets of future astronomical searches toward cold molecular clouds (TMC-1), star forming regions (Sgr(B2)), and circumstellar envelopes of carbon rich stars (IRC + 10216).Despite remarkable progress toward the understanding of the formation pathways leading to polycyclic aromatic hydrocarbons (PAHs) in combustion systems and in deep space, the complex reaction pathways leading to nitrogen-substituted PAHs (NPAHs) at low temperatures of molecular clouds and hydrocarbon-rich, nitrogen-containing atmospheres of planets and their moons like Titan have remained largely obscure. Here, we demonstrate through laboratory experiments and computations that the simplest prototype of NPAHs - quinoline and isoquinoline (C9H7N) - can be synthesized via rapid and de-facto barrier-less reactions involving o-, m- and p-pyridinyl radicals (C5H4N˙) with vinylacetylene (C4H4) under low-temperature conditions.We present an extensive study of the five-dimensional potential energy and induced dipole surfaces of the CH4-N2 complex assuming rigid-rotor approximation. Within the supermolecular approach, ab initio calculations of the interaction energies and dipoles were carried out at the CCSD(T)-F12 and CCSD(T) levels of theory using the correlation-consistent aug-cc-pVTZ basis set, respectively. Both potential energy and induced dipole surfaces inherit the symmetry of the molecular system and transform under the A1+ and A2+ irreducible representations of the molecular symmetry group G48, respectively. One can take advantage of the symmetry when fitting the surfaces; first, when constructing angular basis functions and second, when selecting the grid points. The approach to the construction of scalar and vectorial basis functions exploiting the eigenfunction method [Q. Chen, J. Ping and F. Wang, Group Representation Theory for Physicists, World Scientific, 2nd edn, 2002] is developed. We explore the use of Sobolev-type quadrature grids as building blocks of robust quadrature rules adapted to the symmetry of the molecular system.

Spasticity is a complex and common condition but there is a lack of 'real-world' data on goal setting and spasticity treatment, as well as identifying those features that might be associated with goal achievement. Our aim was to provide such data.

Prospective attenders at a multi-disciplinary spasticity clinic over 2 years followed for consecutive appointments. https://www.selleckchem.com/products/simufilam.html Patient demographics and doses of botulinum toxin injected were documented. Main outcome was achievement of a primary goal but secondary goals were also recorded. Independent variables were examined for association to the outcome.

A total of 606 goals were set in 224 patients. The majority (75.2%) were achieved with similar levels across active (72.5%), passive (75.7%) and pain (78.6%) goals. However, in terms of the primary goal, active primary goals were achieved less frequently (59.7%) than non-active primary goal (74.2%). A logistic regression confirmed that this was the only independent variable associated with primary goal achievement. The r treatment factors are associated with outcome prediction. Further work needs to identify features that may predict successful outcome.Nucleosynthetic isotope anomalies show that the first few million years of solar system history were characterized by two distinct cosmochemical reservoirs, CC (carbonaceous chondrites and related differentiated meteorites) and NC (the terrestrial planets and all other groups of chondrites and differentiated meteorites), widely interpreted to correspond to the outer and inner solar system, respectively. At some point, however, bulk CC and NC materials became mixed, and several dynamical models offer explanations for how and when this occurred. We use xenoliths of CC materials in polymict ureilite (NC) breccias to test the applicability of such models. Polymict ureilites represent regolith on ureilitic asteroids but contain carbonaceous chondrite-like xenoliths. We present the first 54Cr isotope data for such clasts, which, combined with oxygen and hydrogen isotopes, show that they are unique CC materials that became mixed with NC materials in these breccias. It has been suggested that such xenoliths were implanted into ureilites by outer solar system bodies migrating into the inner solar system during the gaseous disk phase ~3-5 Myr after CAI, as in the "Grand Tack" model. However, combined textural, petrologic, and spectroscopic observations suggest that they were added to ureilitic regolith at ~50-60 Myr after CAI, along with ordinary, enstatite, and Rumuruti-type chondrites, as a result of breakup of multiple parent bodies in the asteroid belt at this time. This is consistent with models for an early instability of the giant planets. The C-type asteroids from which the xenoliths were derived were already present in inner solar system orbits.
The molecular diagnosis of gliomas such as isocitrate dehydrogenase (IDH) status (wild-type [wt] or mutation [mut]) is especially important in the 2016 World Health Organization (WHO) classification. Positron emission tomography (PET) has afforded molecular and metabolic diagnostic imaging. The present study aimed to define the interrelationship between the 2016 WHO classification of gliomas and the integrated data from PET images using multiple tracers, including
F-fluorodeoxyglucose (
F-FDG),
C-methionine (
C-MET),
F-fluorothymidine (
F-FLT), and
F-fluoromisonidazole (
F-FMISO).

This retrospective, single-center study comprised 113 patients with newly diagnosed glioma based on the 2016 WHO criteria. Patients were divided into 4 glioma subtypes (Mut, Codel, Wt, and glioblastoma multiforme [GBM]). Tumor standardized uptake value (SUV) divided by mean normal cortical SUV (tumor-normal tissue ratio [TNR]) was calculated for
F-FDG,
C-MET, and
F-FLT. Tumor-blood SUV ratio (TBR) was calculated for
F-FMISO. To assess the diagnostic accuracy of PET tracers in distinguishing glioma subtypes, a comparative analysis of TNRs and TBR as well as the metabolic tumor volume (MTV) were calculated by Scheffe's multiple comparison procedure for each PET tracer following the Kruskal-Wallis test.

The differences in mean
F-FLT TNR and
F-FMISO TBR were significant between GBM and other glioma subtypes (
< .001). Regarding the comparison between Gd-T1WI volumes and
F-FLT MTVs or
F-FMISO MTVs, we identified significant differences between Wt and Mut or Codel (
< .01).

Combined administration of 4 PET tracers might aid in the preoperative differential diagnosis of gliomas according to the 2016 WHO criteria.
Combined administration of 4 PET tracers might aid in the preoperative differential diagnosis of gliomas according to the 2016 WHO criteria.
Metabolic reprogramming is a common feature in cancer, and it is critical to facilitate cancer cell growth.
and
mutations (
mut) are the most common genetic alteration in glioma grade II and III and secondary glioblastoma and these mutations increase reliance on glutamine metabolism, suggesting a potential vulnerability. In this study, we tested the hypothesis that the brain penetrant glutamine antagonist prodrug JHU-083 reduces glioma cell growth.

We performed cell growth, cell cycle, and protein expression in glutamine deprived or
(
) gene silenced glioma cells. We tested the effect of JHU-083 on cell proliferation, metabolism, and mTOR signaling in cancer cell lines. An orthotopic
glioma model was used to test the efficacy of JHU-083 in vivo.

Glutamine deprivation and
gene silencing reduced glioma cell proliferation in vitro in glioma cells. JHU-083 reduced glioma cell growth in vitro, modulated cell metabolism, and disrupted mTOR signaling and downregulated Cyclin D1 protein expression, through a mechanism independent of TSC2 modulation and glutaminolysis. IDH1R132H isogenic cells preferentially reduced cell growth and mTOR signaling downregulation. In addition, guanine supplementation partially rescued
mut glioma cell growth, mTOR signaling, and Cyclin D1 protein expression in vitro. Finally, JHU-083 extended survival in an intracranial
mut glioma model and reduced intracranial pS6 protein expression.

Targeting glutamine metabolism with JHU-083 showed efficacy in preclinical models of
mut glioma and measurably decreased mTOR signaling.
Targeting glutamine metabolism with JHU-083 showed efficacy in preclinical models of IDHmut glioma and measurably decreased mTOR signaling.The purpose of this study was to assess validity, stability and sensitivity, of 4 spectral parameters-median frequency (Fmed), mean frequency (Fmean), Dimitrov index (DI), and mean instant frequency (Fmi)-in measuring localized muscle fatigue in swimming and to investigate their correlation with the variations of kinematic data and mechanical fatigue. Electrophysiological measures of muscle fatigue were obtained in real-time during a 100 m front crawl test at maximum speed in 15 experienced swimmers, using surface electromyography in six muscles employed in front crawl, while kinematic data of swimming was measured from video analysis. Mechanical fatigue was measured as the difference between muscle strength prior to and immediately after the 100 m front crawl in a dry-land multi-stage isometric contraction test. Statistically significant fatigue (p less then 0.0001) was found for all spectral parameters in all muscles. Fmed and Fmean varied between 10 and 25%, DI between 50 and 150%, and Fmi between 5 and 10%. Strong correlation (Pearson r ≥ 0.5) with mechanical fatigue was found for all spectral parameters except for Fmi and it was strongest for Fmed and Fmean. From our study, it turns out that Fmed and Fmean are more valid and stable parameters to measure fatigue in swimming, while DI is more sensitive.A common practice in youth rugby union is to group players based on (bi)annual age with fixed cut-off dates. The overrepresentation of players born at the start of the cut-off date and the underrepresentation of players born toward the end of the cut-off date are termed relative age effects (RAEs). The aim of this study was to examine RAEs during entry into professional and international rugby union pathways in England, as well as comparing them to their respective senior cohort U15 Regional Academy Player (n = 1,114) vs. Senior Professional Player (n = 281) and U16-23 England Academy Player (n = 849) vs. Senior International Player (n = 48). Chi-square (χ2) analysis compared birth quarter (BQ) distributions against expected distributions. Odds ratios and 95% confidence intervals compared the likelihood of a BQ being selected. Findings revealed a significant overrepresentation of relatively older players compared with their relatively younger peers within both youth cohorts (P less then 0.001; BQ1 = 42.5% vs. BQ4 = 9.6%; BQ1 = 36.5% vs. BQ4 = 15.2%). In comparison, there was no significant difference in the BQ distributions within both senior cohorts. Further, BQ4s were 3.86 and 3.9 times more likely to achieve senior professional and international levels than BQ1s and BQ2s, respectively. It is suggested that relatively younger players may have a greater likelihood of achieving expertise following entry into a rugby union talent pathway due to benefitting from more competitive play against relatively older counterparts during their development (e.g., reversal effects; the underdog hypothesis). Moreover, possible solutions (e.g., age and anthropometric banding; playing-up and playing-down) are discussed to encourage practitioners and policy makers to create the most appropriate learning environment for every player.Fatigue with its underlying mechanisms and effects is a broadly discussed topic and an important phenomenon, particularly in endurance sports. Although several studies have already shown a variety of changes in running kinematics with fatigue, few of them have analyzed competitive runners and even fewer have focused on middle-distance running. Furthermore, the studies investigating fatigue-related changes have mostly reported the results in terms of discrete parameters [e.g., range of motion (RoM)] in the frontal or sagittal plane, and therefore potentially overlooked effects occurring in subphases of the gait cycle or in the transverse plane. On this basis, the goal of the present study was to analyze the effects of exhaustive middle-distance running on expert runners by means of both discrete parameters and time series analysis in 3D. In this study, 13 runners ran on a treadmill to voluntary exhaustion at their individually determined fatigue speeds which was held constant during the measurements. Kinematiccularly for comparisons with other group of runners (e.g., females or non-athletes) as well with other conditions (e.g., non-constant speed or interval training), and might be useful for the definition of training goals (e.g., functional core training).The objective of the research was to evaluate the perceptions about the psychological variables of cohesion and motivational climate that AGG gymnasts have about the context created by the coaches in their teams and to analyze in the different categories the optimism and competitive anxiety they face in competitive situations. In an attempt to clarify the psychosocial training patterns in this sport and the influence they have on the well-being of its practitioners, competitive anxiety, motivational climate, team cohesion and level of optimism were taken as dependent variables. The sample was made up of 98 national and international junior and senior athletes in the aesthetic gymnastics group aged 13 to 27 (M = 17.1; SD = 2.8). The Perceived Motivational Climate in Sport Questionnaire for motivational climate, the Sport Anxiety Scale-2 for competitive anxiety, the Group Environment Questionnaire for cohesion and the Revised Life Orientation Test for optimism were used in the evaluation. The results obtained show a positive and statistically significant correlation between anxiety and ego involvement, while, for task involvement, high levels of cohesion are associated with high levels of optimism (p = 0.

From 2326 studies screened, 15 met our inclusion criteria. Five categories of community intervention were identified advice services colocated in healthcare settings; link worker social prescribing; telephone debt advice; food insecurity interventions; and active labour market programmes. In general, the evidence for effective and cost-effective community interventions delivered to individuals experiencing financial insecurity was lacking. https://www.selleckchem.com/products/Cyclopamine.html From the small number of studies without a high risk of bias, there was some evidence that financial insecurity and associated mental health problems were amenable to change and differences by subpopulations were observed.

There is a need for well-controlled studies and trials to better understand effective ingredients and to identify those interventions warranting wider implementation.
There is a need for well-controlled studies and trials to better understand effective ingredients and to identify those interventions warranting wider implementation.The solar system's outer planets, and many of their moons, are dominated by matter from the H-C-N-O chemical space, based on solar system abundances of hydrogen and the planetary ices [Formula see text]O, [Formula see text], and [Formula see text] In the planetary interiors, these ices will experience extreme pressure conditions, around 5 Mbar at the Neptune mantle-core boundary, and it is expected that they undergo phase transitions, decompose, and form entirely new compounds. While temperature will dictate the formation of compounds, ground-state density functional theory allows us to probe the chemical effects resulting from pressure alone. These structural developments in turn determine the planets' interior structures, thermal evolution, and magnetic field generation, among others. Despite its importance, the H-C-N-O system has not been surveyed systematically to explore which compounds emerge at high-pressure conditions, and what governs their stability. Here, we report on and analyze an unbiased crystal structure search among H-C-N-O compounds between 1 and 5 Mbar. We demonstrate that simple chemical rules drive stability in this composition space, which explains why the simplest possible quaternary mixture HCNO-isoelectronic to diamond-emerges as a stable compound and discuss dominant decomposition products of planetary ice mixtures.Many bees possess a tongue resembling a brush composed of a central rod (glossa) covered by elongated papillae, which is dipped periodically into nectar to collect this primary source of energy. In vivo measurements show that the amount of nectar collected per lap remains essentially constant for sugar concentrations lower than 50% but drops significantly for a concentration around 70%. To understand this variation of the ingestion rate with the sugar content of nectar, we investigate the dynamics of fluid capture by Bombus terrestris as a model system. During the dipping process, the papillae, which initially adhere to the glossa, unfold when immersed in the nectar. Combining in vivo investigations, macroscopic experiments with flexible rods, and an elastoviscous theoretical model, we show that the capture mechanism is governed by the relaxation dynamics of the bent papillae, driven by their elastic recoil slowed down through viscous dissipation. At low sugar concentrations, the papillae completely open before the tongue retracts out of nectar and thus, fully contribute to the fluid capture. In contrast, at larger concentrations corresponding to the drop of the ingestion rate, the viscous dissipation strongly hinders the papillae opening, reducing considerably the amount of nectar captured. This study shows the crucial role of flexible papillae, whose aspect ratio determines the optimal nectar concentration, to understand quantitatively the capture of nectar by bees and how physics can shed some light on the degree of adaptation of a specific morphological trait.CB-5083 is an inhibitor of p97/valosin-containing protein (VCP), for which phase I trials for cancer were terminated because of adverse effects on vision, such as photophobia and dyschromatopsia. Lower dose CB-5083 could combat inclusion body myopathy with early-onset Paget disease and frontotemporal dementia or multisystem proteinopathy caused by gain-of-function mutations in VCP. We hypothesized that the visual impairment in the cancer trial was due to CB-5083's inhibition of phosphodiesterase (PDE)-6, which mediates signal transduction in photoreceptors. To test our hypothesis, we used in vivo and ex vivo electroretinography (ERG) in mice and a PDE6 activity assay of bovine rod outer segment (ROS) extracts. Additionally, histology and optical coherence tomography were used to assess CB-5083's long-term ocular toxicity. A single administration of CB-5083 led to robust ERG signal deterioration, specifically in photoresponse kinetics. Similar recordings with known PDE inhibitors sildenafil, tadalafil, vardenat reversible inhibitory action on phosphodiesterase-6, an essential enzyme in retinal photoreceptor function, but no long-term consequences on retinal function or structure.
We established Zambia's first neurology residency program at the University of Zambia School of Medicine and the University Teaching Hospital in Lusaka. We evaluated the feasibility and effectiveness of a modified Objective Structured Clinical Examination (OSCE) to assess clinical skills.

The neurology training program's three participants completed the OSCE exercise in February 2019. We used smartphones to videotape trainees performing a physical examination and oral presentation in the neurology clinic. Trainees and faculty reviewed the videos independently using a standardized rubric and then met for in-person feedback.

Three trainees completed pre- and post-OSCE surveys rating their confidence in elements of the history and examination. Trainees' average self-confidence scores improved from the pre- to post-OSCE survey in every category (pre-OSCE mean score 6.84, range 4.8-7.8, SD 0.92; post-OSCE mean score 7.9, range 5.67-9.33, SD 0.86). Qualitative feedback showed trainees found the OSCE helpful, routinely applied feedback, and would appreciate repeating OSCEs.