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Inhibition of neuronal cyclooxygenase-2 (COX-2) and hence prostaglandin E2 (PGE2) synthesis by non-steroidal anti-inflammatory drugs has been suggested to protect neuronal cells in a variety of pathophysiological situations including Alzheimer's disease and ischemic stroke. Ascorbic acid (vitamin C) has also been shown to protect cerebral tissue in a variety of experimental conditions, which has been attributed to its antioxidant capacity. In the present study, we show that ascorbic acid dose-dependently inhibited interleukin-1beta (IL-1beta)-mediated PGE2 synthesis in the human neuronal cell line, SK-N-SH. Furthermore, in combination with aspirin, ascorbic acid augmented the inhibitory effect of aspirin on PGE2 synthesis. However, ascorbic acid had no synergistic effect along with other COX inhibitors (SC-58125 and indomethacin). The inhibition of IL-1beta-mediated PGE2 synthesis by ascorbic acid was not due to the inhibition of the expression of COX-2 or microsomal prostaglandin E synthase (mPGES-1). Rather, ascorbic acid dose-dependently (0.1-100 microM) produced a significant reduction in IL-1beta-mediated production of 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), a reliable indicator of free radical formation, suggesting that the effects of ascorbic acid on COX-2-mediated PGE2 biosynthesis may be the result of the maintenance of the neuronal redox status since COX activity is known to be enhanced by oxidative stress. Our results provide in vitro evidence that the neuroprotective effects of ascorbic acid may depend, at least in part, on its ability to reduce neuronal COX-2 activity and PGE2 synthesis, owing to its antioxidant properties. Further, these experiments suggest that a combination of aspirin with ascorbic acid constitutes a novel approach to render COX-2 more sensitive to inhibition by aspirin, allowing an anti-inflammatory therapy with lower doses of aspirin, thereby avoiding the side effects of the usually high dose aspirin treatment.

Prostaglandin E2 (PGE2), is a major prostanoid produced by the activity of cyclooxygenases (COX) in response to various physiological and pathological stimuli. PGE2 exerts its effects by activating four specific E-type prostanoid receptors (EP1, EP2, EP3 and EP4). In the present study, we analyzed the expression of the PGE2 receptor EP1 (mRNA and protein) in different regions of the adult rat brain (hippocampus, hypothalamus, striatum, prefrontal cerebral cortex, parietal cortex, brain stem and cerebellum) using reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and immunohistochemical methods. On a regional basis, levels of EP1 mRNA were the highest in parietal cortex and cerebellum. At the protein level, we found a very strong expression of EP1 in cerebellum as revealed by Western blotting experiments. Furthermore, the present study provides for the first time evidence that the EP1 receptor is highly expressed in the cerebellum, where the Purkinje cells displayed a very high immunolabeling of their perikaryon and dendrites as observed in the immunohistochemical analysis. Results from the present study indicate that the EP1 prostanoid receptor is expressed in specific neuronal populations, which possibly determine the region specific response to PGE2.

Newton's laws are a ubiquitous topic in introductory physics instruction. One common problem involves asking what will happen if you stick your finger into a cup of water sitting on a scale. A way to solve the problem would be to first recognize that the water exerts a buoyant force upward on the finger, which students can recognize as being the reason why they feel lighter when they are in a swimming pool. By Newton's third law, the finger must hence exert a downward-pointing force on the water (labeled F[subscript B]). Since the water is not accelerating, the normal force from the beaker acting upward on the water (FN2) must increase to equal the sum of the weight of the water (F[subscript W]) and F[subscript B] (Newton's second law). By Newton's third law, the water must exert a force equal to F[subscript N2] down on the beaker. However, since the beaker is not accelerating, Newton's second law tells us that the normal force from the scale is equal to this increased F[subscript N2]. Via these chains of Newton's second and third laws, we can see that the reading on the scale will increase.

In this article, we will present the HEC BB bag, a simple but elegant model originally invented to help students imagine how air molecules move around in vacuum. The HEC BB bag is made by packing 20 to 30 BBs in a resealable plastic bag of several tens of square centimeters (see Fig. 1). When inflated fully via a straw, the volume of the bag is about 5 L in volume (see below for specifications).

We aim to graphically analyze the depth of conceptual understanding behind the Force Concept Inventory (FCI) responses of students, focusing on three questions (questions 1, 15, and 28). In our study, we created and implemented subquestions to clarify and quantify the students' reasoning steps in reaching their responses to the original FCI questions. We used alluvial diagrams to visualize the responses of students on the subquestions and original FCI questions, representing the transition rates across the question options as flows. The flows represent common patterns of consistency and inconsistency in the students' conceptual understandings across the original FCI question and the subquestions. By combining subquestions and alluvial diagrams as we did, we are able to efficiently analyze the depth of understanding for a given situation and to visualize the existence of a specific misconception. For example, we found that even among those who correctly answered FCI question 15 about Newton's third law, many students incorrectly answered a corresponding subquestion asking about whether Newton's third law holds at the end of the interaction between the two objects. This misconception turned out to be fairly robust, as these same students had a similar answering pattern for question 28. Alluvial diagrams can be used for a broad range of applications, including analysis of multiple-tier tests, testlets (e.g., FCI questions 8 through 11), tests for representational consistency (e.g., a representational variant of the FCI), and so on.

Our study investigates whether confidence correlates with consistency in reasoning, specifically about radioactive decay. In prior work, we developed and tested a survey designed to measure consistency of student reasoning about radioactive decay by comparing responses to three prompts that are isomorphic, meaning that, despite having different surface features, they can all be answered appropriately with the understanding that radioactive decay occurs at random. In this paper, we compare (i) student patterns on these isomorphic prompts with (ii) confidence ratings that students provided together with their responses. Our research question is "to what extent does student confidence correlate with consistency in reasoning about radioactive decay?" We have found that there is no significant correlation, suggesting that more confident students are not more likely to be consistent. One reason why this finding is relevant is that the misconceptions model attributes consistency to student ideas (as opposed to the pieces model, which describes student ideas as potentially being context dependent). Our findings suggest that it is premature to describe a student idea as a misconception, even if the student is confident in that idea.

This paper presents improvements made to a computerized adaptive testing (CAT)-based version of the FCI (FCI-CAT) in regards to test security and test efficiency. First, we will discuss measures to enhance test security by controlling for item overexposure, decreasing the risk that respondents may (i) memorize the content of a pretest for use on the post-test or (ii) share information about the items with their classmates who take the assessment later. Second, we will discuss measures to enhance test efficiency, so that a shorter test length can yield a desired accuracy and precision of the measurement. Specifically, we utilized collateral information in the form of a pretest proficiency estimate of each respondent for selecting items and estimating respondent proficiency level in the post-test. To shorten the total testing time further, we also allowed the test lengths to be different for the pre- and post-test. To analyze how these improvements affect the accuracy and precision (which we measure in terms of root-mean-square error) of Cohen's d, we conducted a Monte Carlo simulation and a "post hoc" simulation. Then, we calculated the minimal test length of the FCI-CAT whose accuracy and precision are equivalent to that of the paper-and-pencil version of the FCI. Consequently, we obtained the following three findings: (i) By using collateral information, we can achieve the accuracy and precision of the full-length FCI with fewer items via the FCI-CAT. (ii) For a class size of 40, we can control for test security while still reducing the sum of the pre- and post-test lengths of the FCI-CAT to a total of 33 items (17 items on the pretest and 16 items on the post-test), thereby reducing the testing time to 55%. (iii) If one's goal is to maximize test efficiency, the pretest length should be slightly larger than the post-test length. On the other hand, if the goal is to maximize test security, the pretest length should be smaller and the post-test length should be larger. If one desires a balance of these two goals, it would be reasonable to choose equal pre- and post-test lengths.

AimsTo describe the real-world prevalence and consequences of hypertriglyceridaemia.Materials and methodsWe searched two large patient databases, the National Health and Nutrition Examination Survey (NHANES) database (2007-2014) and the Optum Research Database, as well as electronic medical records from two Kaiser Permanente regions.ResultsThe NHANES data showed that ~26% of US adults, including nearly one-third of statin users, had at least borderline hypertriglyceridaemia (triglycerides [TGs] ≥1.69 mmol/L), and ~40% of adults with diabetes had levels of ≥150 mg/dL despite statin use. The Optum analyses demonstrated that those with TG levels ≥1.69 mmol/L who were on statins had a significantly increased risk of composite initial major cardiovascular (CV) events (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.19-1.34; P

As a method to shorten the test time of the Force Concept Inventory (FCI), we suggest the use of computerized adaptive testing (CAT). CAT is the process of administering a test on a computer, with items (i.e., questions) selected based upon the responses of the examinee to prior items. In so doing, the test length can be significantly shortened. As a step to develop a CAT-based version of the FCI (FCI-CAT), we examined the optimal test length of the FCI-CAT such that accuracy and precision [which we measure in terms of bias, standard error, and root-mean-square error (RMSE)] of Cohen's d would be comparable to that of the full FCI for a given class size. First, we estimated the item parameters of the FCI items based on the three-parameter logistic model of item response theory, which are used in the algorithm of CAT. For this estimation, we used 2882 responses of Japanese university students. Second, we conducted a Monte Carlo simulation to analyze how the bias, standard error, and RMSE of Cohen's "d" depend upon the test length. Third, we conducted a "post hoc" simulation to examine the consistency of the Monte Carlo results with what would have been obtained using empirical responses. For this comparison, we used 86 pairs of pre- and post- test responses of Japanese university students. As a result, we found that for a class size of 40, we may reduce the test length of the FCI-CAT to 15-19 items, thereby reducing the test time of the FCI to 50%-63%, with an accompanying decrease in accuracy and precision of only 5%-10%. The results of the Monte Carlo study and the "post hoc" simulation were consistent, which supports the adequacy of our Monte Carlo study and its relevance in terms of administering the FCI-CAT in real classrooms.

In this literature review, we survey student naïve ideas (frequently referred to as 'misconceptions') that plausibly relate, at least in part, to difficulty in understanding probability. We collected diverse naïve ideas from a range of topics in physics: Non-linear Dynamics; Cosmology; Thermal Physics; Atomic, Nuclear, and Particle Physics; Elementary Particle Physics; Quantum Physics; and Measurements and Uncertainties. With rare exception, these naïve ideas are treated in the literature to be topic-specific. For example, the idea that 'only one measurement is needed because successive measurements will always yield the same result' is treated to be a misconception in Measurements and Uncertainties. In our review, however, we raise the possibility that these diverse naïve ideas have something in common: they are enabled, to varying degrees, by the stance that 'random is incompatible with predictions and laws' that researchers in mathematics education have documented. This is important, as it may inform instruction. Namely, it may be the case that it is more effective to treat this underlying cause of student difficulty, rather than the individual naïve ideas themselves.

Persistence of the rebound-competent viral reservoir (RCVR) within the CD4+ T cell compartment of people living with HIV remains a major barrier to HIV cure. Here, we determined the effects of the pan-lymphocyte-depleting monoclonal antibody (mAb) alemtuzumab on the RCVR in SIVmac239-infected rhesus macaques (RM) receiving antiretroviral therapy (ART). Alemtuzumab administered during chronic ART or at the time of ART initiation induced >95% depletion of circulating CD4+ T cells in peripheral blood and substantial CD4+ T cell depletion in lymph nodes. However, treatment was followed by proliferation and reconstitution of CD4+ T cells in blood, and despite ongoing ART, levels of cell-associated SIV DNA in blood and lymphoid tissues were not substantially different between alemtuzumab-treated and control RM after immune cell reconstitution, irrespective of the time of alemtuzumab treatment. Upon ART cessation, 19 of 22 alemtuzumab-treated RM and 13 of 13 controls rebounded in <28 days with no difference in the time to rebound between treatment groups. Time to rebound and reactivation rate was associated with plasma viral loads (pVLs) at time of ART initiation, suggesting lymphocyte depletion had no durable impact on the RCVR. However, 3 alemtuzumab-treated RM that had lowest levels of pre-ART viremia, failed to rebound after ART withdrawal, in contrast to controls with similar levels of SIV replication. These observations suggest that alemtuzumab therapy has little to no ability to reduce well-established RCVRs but may facilitate RCVR destabilization when pre-ART virus levels are particularly low. Author summary: A major challenge to curing HIV is the presence of cells with rebound-competent viral reservoirs (RCVR) capable of re-establishing systemic infection when ART is interrupted. CD4+ T cells harboring RCVR persist for life due to homeostatic mechanisms that allow them to proliferate and expand during ART. In this study, we explored whether pan-lymphocyte depletion with a licensed CD52-depleting monoclonal antibody called alemtuzumab, can eliminate or reduce RCVR in SIV-infected rhesus macaques (RM) when administered either at the time of ART initiation or during chronic ART administration. While alemtuzumab induced massive depletion of lymphocytes in blood, including >95% depletion of CD4+ T cells, there were no measurable effects of alemtuzumab on cell-associated viral loads during ART or SIV rebound dynamics following ART interruption in most RM. Three alemtuzumab-treated RM failed to manifest rebound viremia during extended follow up after ART withdrawal. However, these animals had the lowest levels of pre-ART SIV replication, suggesting that alemtuzumab may have been effective in RM with early and presumably smaller RCVR. Overall, our study highlights the current limitations of lymphocyte depletion strategies in facilitating the permanent disruption of RCVR, particularly once the RCVR is established above levels that induce consistent post-ART viremia. [ABSTRACT FROM AUTHOR]

The authors examined trends in school counselor consultation preparation using data collected from 238 program websites, 73 program survey responses, and 57 syllabi. The results indicated an emphasis on consultation content related to theories, stakeholders, and topics, rather than experiential practice. The findings suggest a need to incorporate and assess more application-specific consultation activities and assignments.

Professional problem-solving practice in physics and engineering relies on mathematical sense making--reasoning that leverages coherence between formal mathematics and conceptual understanding. A key question for physics education is how well current instructional approaches develop students' mathematical sense making. We introduce an assessment paradigm that operationalizes a typically unmeasured dimension of mathematical sense making: use of calculations on qualitative problems and use of conceptual arguments on quantitative problems. Three assessment items embodying this calculation-concept crossover assessment paradigm illustrate how mathematical sense making can positively benefit students' problem solving, leading to more efficient, insightful, and accurate solutions. These three assessment items were used to evaluate the efficacy of an instructional approach focused on developing students' mathematical sense making skills. In a quasi-experimental study, three parallel lecture sections of first-semester, introductory physics were compared: two mathematical sense making sections, one with an experienced instructor and one with a novice instructor, and a traditionally taught section, as a control group. Compared to the control group, mathematical sense making groups used calculation-concept crossover approaches more often and gave more correct answers on the crossover assessment items, but they did not give more correct answers to associated standard problems. In addition, although students' postcourse epistemological views on problem-solving coherence were associated with their crossover use, they did not fully account for the differences in crossover approach use between the mathematical sense making and control groups. These results demonstrate a new assessment paradigm for detecting a typically unmeasured dimension of mathematical sense making and provide evidence that a targeted instructional approach can enhance engagement with mathematical sense making in introductory physics.

Recently, Greta Thunberg has strongly increased environmental awareness with the climate strikes and the resulting Fridays for Future movement. But what does environmentally friendly behavior look like? In today's society, it is a sort of common sense that one should recycle. From an early age, we are taught in school that recycling conserves resources and energy. However, there are also skeptics of this "common sense." In 2004, for example, Penn and Teller dedicated an episode of their TV show to recycling. According to them, "[Recycling] increases energy use in transport, sorting, storing, and cleaning …. it takes more energy to recycle a plastic bottle than to make a new one, and that's not so good …. we're feeling good for no reason." We hope that when people start to question the validity of recycling that they will turn to their physical science teachers for help, and we hope that these teachers will be able to give an informed and educated answer. In this article, our goal is to provide physical science teachers with the information they need to defend the position that recycling plastic bottles is worthwhile, and to expose the myth that recycling plastic bottles is just "feeling good for no reason." Although the primary intention of this paper is to supplement content knowledge of physical science teachers regarding sustainability, it will conclude with some instructional suggestions of how students can be guided through debunking on their own the myth that recycling plastic bottles causes more harm than good.

The negative consequences associated with out-of-school suspension (OSS) are widely recognized, yet its commonly utilized counterpart, in-school suspension (ISS), has received little attention. This study examined school and student characteristics that predicted ISS and its links to academic outcomes, using the nationally representative High School Longitudinal Study of 2009. The sample included 11,860 public high school students, equating to a nationally representative sample of 2,993,918 students upon the application of primary sampling weights for each student and balanced repeated replicate weights to account for students nested in schools. Students who were Black, male, of lower socioeconomic status (SES), or placed in special education were significantly more likely to receive ISS. Further, ISS was associated with lower grade point averages and increased likelihood of high school dropout. These findings raise caution about the use of ISS, particularly as schools consider using ISS as an alternative to OSS.

In this study, we analyze the systematic error from false positives of the Force Concept Inventory (FCI). We compare the systematic errors of question 6 (Q.6), Q.7, and Q.16, for which clearly erroneous reasoning has been found, with Q.5, for which clearly erroneous reasoning has not been found. We determine whether or not a correct response to a given FCI question is a false positive using subquestions. In addition to the 30 original questions, subquestions were introduced for Q.5, Q.6, Q.7, and Q.16. This modified version of the FCI was administered to 1145 university students in Japan from 2015 to 2017. In this paper, we discuss our finding that the systematic errors of Q.6, Q.7, and Q.16 are much larger than that of Q.5 for students with mid-level FCI scores. Furthermore, we find that, averaged over the data sample, the sum of the false positives from Q.5, Q.6, Q.7, and Q.16 is about 10% of the FCI score of a midlevel student.