Individuals with substance use disorders (SUDs) transition more quickly from goal-directed to habitual action-selection, but the neural mechanisms underlying this phenomenon remain unclear. Data from ...animal models suggest that drugs of abuse can modify the neurocircuits that regulate action-selection, enhancing circuits that drive inflexible, habit-based stimulus-response (S-R) action-selection and weakening circuits that drive flexible, goal-directed actions. Here, we tested the effect of bilateral 10-Hz transcranial alternating current stimulation (10Ηz-tACs) of the dorsolateral prefrontal cortex on action-selection in men and women with a SUD history and an age- and sex-matched control group. We tested the hypothesis that true 10Ηz-tACS versus active sham stimulation would reduce perseverative errors after changed response contingencies for well-learned S-R associations, reflecting reduced habit-based action-selection, specifically in the SUD group. We found that 10 Hz-tACS increased perseverative errors in the control group, but in the SUD group, 10 Hz-tACS effects on perseverative errors depended on substance abuse duration: a longer addiction history was associated with a greater reduction of perseverative errors. These results suggest that 10Ηz-tACs altered circuit level dynamics regulating behavioral flexibility, and provide a foundation for future studies to test stimulation site, frequency, and timing specificity. Moreover, these data suggest that chronic substance abuse is associated with altered circuit dynamics that are ameliorated by 10Ηz-tACs. Determining the generalizability of these effects and their duration merits investigation as a direction for novel therapeutic interventions. These findings are timely based on growing interest in transcranial stimulation methods for treating SUDs.
Treating the executive dysfunction associated with addiction is hampered by redundancies in pharmacological regulation of different behavioral control circuits. Thus, nonpharmacological interventions hold promise for addiction treatment. Here, we show that, among people with an addiction history, 10-Hz transcranial alternating current stimulation (10Hz-tACS) of the dorsolateral prefrontal cortex can reduce habitual actions. The fact that 10Hz-tACS can regulate behavioral flexibility suggests its possible utility in reducing harmful habitual actions.
Wilderness medicine (WM) graduate medical education (GME) fellowships were established in 2003. Outcomes and satisfaction of US WM GME fellowship alumni can inform prospective applicants and program ...directors of the strengths of fellowships and professional gaps in them.
A 34-question Qualtrics survey was emailed to 111 alumni from 17 institutions listed in the Wilderness Medical Society’s GME database in May 2019. Professional service, scholarship, and satisfaction were queried. Results are represented as percent response (n=answered affirmative) based on the number of respondents per question.
The survey response rate was 41% (n=46); 67% reported (n=31) Fellowship of the Academy of Wilderness Medicine recognition. Within the last 5 y, 71% (n=32) reported publications in WM. Free text entry questions had 78% (n=28) describe improved clinical skills, and 68% (n=26) were exposed to new career choices in fellowship. Those who rated exposure to a variety of WM knowledge and skills highly rated the overall fellowship experience higher (P<0.001), as did those reporting a higher number of WM publications (P=0.023). Nearly half, 48% (n=21), felt they could hold their current position without fellowship training. In hindsight, 76% (n=34) would follow the same professional path.
WM GME fellowship alumni reported high rates of professional engagement and scholarly productivity in the subspecialty. Responding alumni overwhelmingly rated the fellowship experience positively. Fellowships that ensure a wide exposure to experiences and foster scholarly productivity are more likely to yield professionally satisfied graduates.
We present the analysis of the approximately three-year long Rossi X-ray Timing Explorerd (RXTE) campaign for monitoring the canonical soft state black-hole candidates LMC X-1 and LMC X-3. In ...agreement with previous observations, we find that the spectra of both sources can be well-described by the sum of a multi-temperature disc blackbody and a power law. In contrast to LMC X-1, which does not exhibit any periodic spectral changes, we find that LMC X-3 exhibits strong spectral variability on time-scales of days to weeks. The variability pattern observed with the RXTE All Sky Monitor reveals that the variability is more complicated than the 99- or 198-d periodicity discussed by Cowley et al. For typical ASM count rates, the luminosity variations of LMC X-3 are due to changes of the phenomenological disc blackbody temperature, kTin, between ∼1 to ∼1.2keV. During episodes of especially low luminosity (ASM count rates ≲0.6countss−1; four such periods are discussed here), kTin strongly decreases until the disc component is undetectable, and the power law significantly hardens to a photon index of Γ ∼ 1.8. These changes are consistent with state changes of LMC X-3 from the soft state to the canonical hard state of galactic black holes. We argue that the long-term variability of LMC X-3 might be owing to a wind-driven limit cycle, such as that discussed by Shields et al.
Brain arteriovenous malformations (bAVMs) are infrequent disorders in the pediatric population. The rupture of a bAVM is a clinical emergency often followed by death. Autism spectrum disorder shares ...a number of symptoms with AVM malformation; this may impede antemortem diagnosis. An 11‐year‐old boy with autism spectrum disorder (ASD) without other medical history died suddenly. Initially, choking on a peanut butter sandwich was suspected; autopsy did not demonstrate aspiration, but identified a ruptured right cerebellar AVM, with the characteristic tortuous vessels. The histology on the lesion confirmed the presence of arterialized veins and showed gliotic tissue and hemosiderin‐laden macrophages, consistent with prior bleeding. BAVM pathogenesis is unknown; congenital disease may have several mechanisms including genetic predisposition and familial risk factors; development de novo may occur after hemorrhagic intracranial events such as surgical intervention and head trauma. ASD may present with overlapping symptoms of bAVM and may also interfere with expressing subtle neurologic symptoms to caretakers. ASD and AVM are rarely reported in association.
Abstract Background and aims Low vitamin D levels are associated with increased incidence of future cardiovascular events and are common in stroke patients. We tested whether vitamin D ...supplementation could reduce blood pressure and improve markers of vascular health in patients who had previously suffered a stroke. Methods and Results Randomised, placebo-controlled, double-blind trial. Community-dwelling patients with a history of stroke and baseline 25-hydroxyvitamin D levels <75 nmol/L received 100,000 units of oral vitamin D2 or placebo at baseline. Office and 24 h blood pressure, endothelial function measured by flow-mediated dilatation of the brachial artery, cholesterol, oxidised low density lipoprotein, B-type natriuretic peptide and heart rate turbulence were measured at baseline, 8 weeks and 16 weeks. 58 patients were randomised. Mean age was 67 years, mean baseline blood pressure 128/72 mmHg, mean baseline 25-hydroxyvitamin D level was 38 nmol/L. Serum 25-hydroxyvitamin D levels were higher in the intervention group at 8 weeks compared to placebo (54 vs 42 nmol/L, P = 0.002) and remained higher at 16 weeks. Office systolic and diastolic blood pressure showed no significant change between groups at 8 weeks (systolic 126.1 vs 131.3 mmHg; adjusted P = 0.97); (diastolic 73.1 vs 74.9 mmHg, adjusted P = 0.15). Flow mediated dilatation was significantly higher in the intervention group at 8 weeks (6.9% vs 3.7%, adjusted P = 0.007) but was not significantly different at 16 weeks. Conclusions High dose oral vitamin D supplementation did not improve blood pressure but produced short-term improvement in endothelial function in stroke patients with well-controlled baseline blood pressure. Clinical trials registration: ISRCTN28737567
The wettability of two powders has been assessed by three methods and values for surface energies have been determined. Two contact angle methods have been used, both of which are variations of the ...Wilhelmy plate approach. One method was to use compressed plates of powder, the other to stick uncompacted powder to a glass plate (as a support). It was found that the method using adhesion to the glass plate gave more realistic values for the surface energy of the powders than did the compacted plate approach. It can be concluded that the use of plates with powder adhered to the surface offers a significant advantage for contact angle assessment. The third method used was inverse gas chromatography, which has seen little application to date in the pharmaceutical sciences. It was found that the dispersion component of surface energy obtained by inverse gas chromatography (IGC) was almost identical to the equivalent (Lifshitz-van der Waals) term obtained by use of the contact angle data from the glass side method. The acid-base (polar) contributions to surface energy were not directly comparable, due to the different data manipulation methods associated with contact angle and IGC data. It can be concluded that the little used methods of adhering powder to an inert support for contact angle measurement and IGC have great promise as means of assessing the surface properties of powders. Both these techniques have the advantage of not requiring powder compaction (or any other surface damaging treatment) prior to use.
Millimeter and micron length scale particle–surface interactions are of fundamental importance in the modeling and actual field behavior of geotechnical composites incorporating non-dilative ...interface systems. The results of a basic experimental study to explain underlying causes of steady state strength behavior of these systems are presented. Single soda lime glass beads and natural subrounded quartz sand were placed in unlubricated sliding against manufactured materials consisting of high-density polyethylene, polyvinylchloride, fiber reinforced plastic, stainless steel and heat-treated steel. For high-density polyethylene and polyvinylchloride sheet materials steady state is reached after the rate of wear diminishes. In contrast, fiber reinforced plastic and steels exhibit a higher friction coefficient at large displacement than at peak due to interactions of the particle with the surface at the grain level. Initial peak and steady state friction coefficients depend primarily on the initial surface microtopography, grain shape, relative hardness of the particle and material pairing, normal stress and manufactured material morphology. The results give engineers an improved framework for assessing laboratory results and potential influence of wear on mechanical and hydraulic properties of construction materials.
Abstract Critiquing arguments is important for K‐12 science students to learn but not emphasized by the predominant claim‐evidence‐reasoning (CER) argumentation model. Drawing on the work of Yu and ...Zenker (2020), and Dove and Nussbaum (2018), we developed a tool for supplementing CER with critical questions (CQs) from philosophy that cover most, if not all, the logical dimensions of argument critique. Six middle school science teachers designed lessons involving argumentation, including the use of CQs. We assessed the effects on student self‐efficacy for engaging in argument critique, teacher self‐efficacy for using argument pedagogy, and teachers’ perceptions of the value of CQs. Qualitative data included teacher interviews, lesson transcripts, and student work samples. Quantitative data included surveys of student self‐efficacy administered at the beginning and end of the school year. There was evidence suggesting an increase over time in students’ confidence for engaging in argument critique and teachers’ confidence with argument pedagogy. However, only four of the six teachers were confident and skilled enough to include CQs in their lessons. Those who did use CQs tended to perceive them as providing a helpful structure for critique, prompts for deeper thinking, and a tool for fostering critical classroom norms. Discussion of CQs may have benefitted students’ writing by promoting peer critique and encouragement to elaborate. Overall, CQs afford students with a framework for judging argument strength. Scientific argumentation involving CQs provides a more contemporary philosophical basis for scientific argumentation than CER or the Toulmin model as it emphasizes the critical and dialogic nature of science.
Although the Toulmin model (
1958
) has dominated argumentation research, it does not provide many tools for evaluating argument quality. Towards that end, we draw on work in philosophy on argument ...schemes, and critical questions for evaluating those schemes. In our approach, we integrate the teaching of critical questions with argumentation vee diagrams (AVDs) and with oral and written discourse. AVDs are graphic organizers that prompt students to write arguments and counterarguments on different sides of the vee, and at the bottom of the vee, an integrative paragraph supporting a final conclusion. The present study was conducted in three sections of an undergraduate general education seminar. Two sections, comprising the experimental group, used AVDs containing a critical questions box reflecting questions for the
arguments from consequence
scheme (Walton,
1996
). One section used AVDs without the critical question box. Students completed AVDs prior and during class discussions on social issues (e.g., drug legalization). Over time, students in the experimental group included more refutations related to the critical questions compared to the control group. The effect transferred to an in-class essay where no question prompts were provided, but not to a course paper written on whistleblowing. However, students in the experimental condition did include in their papers more explicit mention of moral principles. We explain these effects in relation to argument schema theory, in particular the development and automatization of a weighing schema. The critical questions appeared to provide students with a structure for evaluating arguments and counterarguments.
Central core disease is a congenital myopathy with muscle weakness defined pathologically by the presence of extensive areas in muscle fibres that are devoid of oxidative enzyme activity. The gene ...responsible has been shown to be the ryanodine receptor 1 on chromosome 19q13 and mutations have now been identified in several patients. Some cases with the morphological defect remain molecularly undefined, particularly those studied before molecular studies were available. We have studied three families with congenital onset, each with a dominantly inherited mutation in a C-terminal exon of the ryanodine receptor 1. They illustrate the spectrum of pathology that can be observed in patients with the myopathic features of central core disease. We show that extensive fibrosis and fat may be present, type 1 fibre uniformity may occur in the absence of cores; cores may be central or peripheral, single or multiple; and that an appearance of multiple focal minicores might cause a diagnostic pathological dilemma. In addition, we show the value of immunocytochemistry in identifying cores, in particular the use of antibodies to desmin and γ-filamin.
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