This lesson opens with an introduction of how to program the Micro:bit using block code to play music using the piano keyboard embedded in the music section of Micro:bit Make Code. In this lesson, students explore how to make music using this feature and learn how to program the Micro:bit using MakeCode to incorporate rests and different notes (quarter, half, and full) to replicate nursery rhymes or popular songs. The lesson concludes with a discussion of the challenges/limitations of coding the Micro:bit to play music. Students also shared their musical creations with their peers through a “Name that Tune” game where they attempted to guess which popular song or nursery rhyme their peers had replicated in MakeCode. Time: 30-45 minutes

OBJECTIVE:Altitude-related and exercise-related elevations in blood pressure (BP) increase the likelihood of developing pulmonary hypertension and high-altitude illness during high-altitude sojourn. This study examined the antihypertensive effect and potential exercise benefit of the angiotensin II receptor antagonist losartan when taken at altitude.METHODS:Twenty participants, paired for age and ACE genotype status, completed a double-blinded, randomised study, where participants took either losartan (100 mg/day) or placebo for 21 days prior to arrival at 5035 m (Whymper Hut, Mt Chimborazo, Ecuador). Participants completed a maximal exercise test on a supine cycle ergometer at sea level (4 weeks prior) and within 48 hours of arrival to 5035 m (10-day ascent). Power output, beat-to-beat BP, oxygen saturation (SpO2) and heart rate (HR) were recorded during exercise, with resting BP collected from daily medicals during ascent. Before and immediately following exercise at 5035 m, extravascular lung water prevalence was assessed with ultrasound (quantified via B-line count).RESULTS:At altitude, peak power was reduced relative to sea level (p<0.01) in both groups (losartan vs placebo: down 100±29 vs 91±28 W, p=0.55), while SpO2 (70±6 vs 70±5%, p=0.96) and HR (146±21 vs 149±24 bpm, p=0.78) were similar between groups at peak power, as was the increase in systolic BP from rest to peak power (up 80±37 vs 69±33 mm Hg, p=0.56). Exercise increased B-line count (p<0.05), but not differently between groups (up 5±5 vs 8±10, p=0.44).CONCLUSION:Losartan had no observable effect on resting or exercising BP, exercise-induced symptomology of pulmonary hypertension or performance at 5035 m.

This paper examines the ways in which Lovecraft’s notorious homophobia has been queered by the recently consolidated subgenre of male/male (m/m) romance in which two male protagonists overcome obstacles to ultimately find love and “happily ever after.” Focusing on trans writer Jordan L. Hawk’s multi-volume paranormal-historical m/m romance series, Whyborne & Griffin (2012–19), it approaches Hawk’s stories of romantically paired paranormal investigators operating in Lovecraftian settings as critical meditations on the surprising proximity between horror and erotic pleasure in Lovecraft’s own stories. Hawk’s critical queering of Lovecraft in these works is characterized above all by ambivalence: on the one hand, the horrors of Lovecraft’s materialist vision are allegorized as a metaphor for homophobia; on the other hand, they also function as ciphers for the lovers’ objectively represented and celebrated queer pleasure. This semantic ambiguity, it argues, is rooted in Lovecraft’s own contradictory poetics of abjection, whose valences it inverts, placing the accent on erotic desublimation rather than phobic recoil. Ultimately, the essay locates Hawk’s rewriting of Lovecraft’s obsession with monstrous genealogies within contemporary inclusive discourses of the queer family—discourses which extend in the case of this series to the queerness of m/m popular romance fans.

When comics fandom emerged as a distinct media-oriented community in the 1960s, one of the things it brought with it from science-fiction fandoms was the convention. Buoyed by the synergistic relationship between Hollywood and the San Diego Comic-Con and the growing prominence of ‘geek’ culture, comic conventions, comic art festivals and related media fandom events across North America have enjoyed enhanced prestige, attention and attendance over the last fifteen to twenty years. But what kind of event are these ‘con events’? This article builds on a cultural mapping survey of convention organizers. The survey’s goal was to suggest something of the scope and diversity of the contemporary sector. Behind this variation, we define the con event as an organizational and cultural form that is (1) oriented to media, (2) audience-facing and (3) concerned with circulation.

IntroductionProteinuria increases at altitude and with exercise, potentially as a result of hypoxia. Using urinary alpha-1 acid glycoprotein (α1-AGP) levels as a sensitive marker of proteinuria, we examined the impact of relative hypoxia due to high altitude and blood pressure-lowering medication on post-exercise proteinuria.MethodsTwenty individuals were pair-matched for sex, age and ACE genotype. They completed maximal exercise tests once at sea level and twice at altitude (5035 m). Losartan (100 mg/day; angiotensin-receptor blocker) and placebo were randomly assigned within each pair 21 days before ascent. The first altitude exercise test was completed within 24–48 hours of arrival (each pair within ~1 hour). Acetazolamide (125 mg two times per day) was administrated immediately after this test for 48 hours until the second altitude exercise test.ResultsWith placebo, post-exercise α1-AGP levels were similar at sea level and altitude. Odds ratio (OR) for increased resting α1-AGP at altitude versus sea level was greater without losartan (2.16 times greater). At altitude, OR for reduced post-exercise α1-AGP (58% lower) was higher with losartan than placebo (2.25 times greater, p=0.059) despite similar pulse oximetry (SpO2) (p=0.95) between groups. Acetazolamide reduced post-exercise proteinuria by approximately threefold (9.3±9.7 vs 3.6±6.0 μg/min; p=0.025) although changes were not correlated (r=−0.10) with significant improvements in SpO2 (69.1%±4.5% vs 75.8%±3.8%; p=0.001).DiscussionProfound systemic hypoxia imposed by altitude does not result in greater post-exercise proteinuria than sea level. Losartan and acetazolamide may attenuate post-exercise proteinuria, however further research is warranted.

Purpose Impella (Abiomed Inc, Danvers, MA) is a temporary mechanical support device being more frequently used in INTERMACS 1 patients bridged to LVAD implantation. The device is percutaneously inserted across the aortic valve, and although case reports describe the development of aortic incompetence (AI) after its use, there is no data on the incidence of AI in patients with Impella support as a bridge to LVAD implantation. Methods We reviewed all patients undergoing primary LVAD implantation at a large academic center from January 2015 onwards, and identified those classified as INTERMACS 1. We then divided them by method of pre-implantation support, comparing those supported with Impella as temporary mechanical support to those supported by either VA ECMO or IABP. We reviewed transthoracic echocardiography preoperatively, as well as at 1 week, 1, 3, 6, 9 and 12 months post-LVAD implantation. Patients with concomitant Aortic Valve Replacement were excluded. Results A total of 155 patients were reviewed, of which 45 patients were identified as INTERMACS 1. A total of 179 echoes were analysed. Twelve patients were supported with Impella prior to LVAD implant - of which six patients were supported with Impella alone (5 with Impella CP, 1 with Impella 5) and six with Impella in conjunction with VA ECMO (3 with Impella 2.5, 2 with Impella CP and 1 with Impella 5). One of the patients supported with Impella died within three days of LVAD implant and was excluded from analysis. Post LVAD implant, mild or moderate AI developed in 82% of patients supported with Impella (9 of 11) compared to 43% of those without Impella (13 of 30) [p = 0.038]. There was no difference in severity or incidence of AI based on type of Impella device or type of LVAD used. Conclusion In our cohort, patients supported with Impella as a bridge to durable LVAD have higher risk of developing AI. Further studies are needed to identify risk factors and develop strategies to mitigate this risk as the use of Impella becomes more widespread.

The field of ecology is poised to substantially contribute to the creation of a socially and environmentally equitable urban future. To realize this contribution, the field of ecology must create strategies that ensure inclusion of underrepresented minorities so that a broad array of experiences and ideas collectively address challenges inherent to a sustainable urban future. Despite efforts to recruit and retain underrepresented racial minorities (URM) in the sciences, graduation rates have only slightly increased over the last several decades. While research mentoring programs at the undergraduate level do increase retention of URM already majoring in the sciences, influences that develop before college may inhibit URM from electing to study the sciences or pursue ecology-related careers in the first place. To increase diversity in the field of ecology, it is, therefore, critical to reach students before they make decisions about college. Compared with the country as a whole, cities larger than 400 000 tend to have K-12 public school populations that are more racially diverse. In cities, place-based learning—where students are engaged as participant learners in local community and environmental issues—has been successfully used for out-of-school urban environmental education programming to foster pro-environmental attitudes, foster science identity and teach scientific knowledge. Utilizing a near-peer, relational mentoring model, we argue that pre-college urban ecology research mentoring provides a place-based, authentic research experience that strengthens URM science identity and intent to pursue ecology-related majors.

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Abstract Background The long-acting injectable antipsychotic aripiprazole once-monthly 400 mg (AOM 400) was recently approved for maintenance treatment of bipolar I disorder (BP-I). The purpose of this study was to evaluate the safety, tolerability, and efficacy of AOM 400 as long-term maintenance treatment for BP-I. Methods This open-label multicenter study evaluated the effectiveness of AOM 400 as maintenance treatment for BP-I by assessing safety and tolerability (primary objective) and efficacy (secondary objective). The study enrolled AOM 400-naive (“de novo”) patients as well as AOM 400-experienced (“rollover”) patients with BP-I from a lead-in randomized, placebo-controlled clinical trial that demonstrated the efficacy of AOM 400 in the maintenance treatment of BP-I (Calabrese et al. in J Clin Psychiatry 78:324–331, 2017). Safety variables included frequency and severity of treatment-emergent adverse events (TEAEs) and TEAEs resulting in study discontinuation. Efficacy was assessed by the proportion of patients maintaining stability throughout the maintenance phase, as well as mean changes from baseline in Young Mania Rating Scale (YMRS), Montgomery–Asberg Depression Rating Scale, and Clinical Global Impressions for Bipolar Disorder–Severity of Illness Scale (CGI-BP-S) total scores. Patient acceptability and tolerability of treatment was assessed using the Patient Satisfaction with Medication Questionnaire-Modified. Results Of 464 patients entering the maintenance phase, 379 (82%) were de novo and 85 (18%) were rollover. TEAEs were more common in de novo than rollover patients. The overall discontinuation rate due to TEAEs was 10.3% (48/464). Improvements in YMRS and CGI-BP-S total scores were maintained during the study, and the vast majority of both de novo (87.0%) and rollover (97.6%) patients maintained stability through their last visit. Overall, the need for rescue medication during the maintenance phase was minimal (< 10% of patients). Patient satisfaction levels were high, with both de novo and rollover patients rating the side effect burden of AOM 400 as greatly improved relative to previous medications. Conclusion AOM 400 was safe, effective, and well tolerated by both de novo and AOM 400-experienced patients with BP-I for long-term maintenance treatment. Trial registration ClinicalTrials.gov, NCT01710709

Background: Effects of maintenance treatment with aripiprazole once-monthly 400 mg (AOM 400) on symptoms and functioning were assessed in adults with bipolar I disorder (BP-I) after a manic episode. Methods: Patients were stabilized on oral aripiprazole, cross-titrated to AOM 400, then randomized in a 52-week, double-blind, placebo-controlled, withdrawal phase. Prespecified secondary outcomes are reported: time to hospitalization for mood episode, Young Mania Rating Scale (YMRS), Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impression-Bipolar scale, Functioning Assessment Short Test (FAST), and Brief Quality of Life in Bipolar Disorder questionnaire. Time to hospitalization for mood episode was analyzed using log-rank test and changes from baseline using mixed model for repeated measures or analysis of covariance. Results: AOM 400 significantly increased time to hospitalization for any mood episode versus placebo (P=0.0002). YMRS total scores decreased with oral aripiprazole; improvements were maintained with AOM 400. After randomization, YMRS scores changed little with AOM 400 but worsened with placebo (P=0.0016), and MADRS scores, already low at trial initiation, did not differ between groups. FAST score improvements were maintained with AOM 400 but not placebo (P=0.0287). Limitations: Results are generalizable to patients with BP-I stabilized on aripiprazole following a manic episode. Conclusions: Patients with BP-I experiencing an acute manic episode exhibited symptomatic and functional improvements during stabilization with oral aripiprazole and AOM 400 that were maintained with continued AOM 400 treatment but not placebo. AOM 400 is the first once-monthly long-acting injectable antipsychotic to demonstrate efficacy in maintenance treatment of the manic phase of BP-I.

Long before the prosecution of individuals for witchcraft was rendered a legal impossibility in the states of modern Europe, the judicial and executive institutions of those states and their precursors were decisive in both legitimating and moderating, facilitating and constraining the detection, trial, and execution of alleged witches. If we are to impute more than unresolved cognitive dissonance to this paradoxical relationship of the apparatus of state to the perceived reality and threat of witchcraft, then the preconditions and contextual factors predicating that relationship bear investigation. This paper identifies genealogical traces of criminological, political, social, and religious thought embedded within several pivotal bodies of early-modern law pertaining to witchcraft, and attempts to infer the cultural, institutional, and textual sources and conditions from which they derive.

Background: Aripiprazole once-monthly 400 mg (AOM 400), an atypical long-acting injectable antipsychotic, has demonstrated efficacy and safety in maintenance treatment of bipolar I disorder (BP-I). We further assess safety and tolerability and characterize adverse events (AEs) across the duration of aripiprazole exposure. Methods: Patients with BP-I were stabilized on oral aripiprazole (2-8 weeks), AOM 400 (12-28 weeks), followed by 1:1 randomization of patients meeting stability criteria to a 52-week, double-blind, placebo-controlled withdrawal phase. Treatment-emergent AEs (TEAEs) were collected across study phases. AEs were counted in a phase if they were drug-related and continued from the baseline of that phase. A separate analysis on new-onset akathisia was conducted. Results: Among TEAEs occurring in >= 10% of patients during all study phases were akathisia (23.3%) and weight increased (10.6%). Median time to akathisia onset was 20 days after starting oral aripiprazole; median duration was 29 days for the first occurrence; 21/168 patients (12.5%) reporting akathisia experienced >1 episode. Episodes of new-onset akathisia decreased over time, with few events reported in the randomized phase. Weight gain was minimal with oral aripiprazole, generally starting within 3 months after the first AOM 400 injection, and appearing to plateau at 36 weeks. The mean weight gain within any study phase was <= 1.0 kg. Potentially clinically significant changes in metabolic parameters were uncommon. Limitations: Patients on placebo had AOM 400 exposure before randomization. Conclusion: These findings suggest that AEs with AOM 400 treatment were time-limited and support AOM 400 as a well-tolerated maintenance treatment of BP-I.

OBJECTIVE:To evaluate efficacy, safety, and tolerability of long-acting injectable antipsychotic aripiprazole once-monthly 400 mg (AOM 400) as maintenance treatment for bipolar I disorder (BP-I). METHODS:In a double-blind, placebo-controlled, 52-week randomized withdrawal study conducted from August 2012 to April 2016, patients with a DSM-IV-TR diagnosis of BP-I currently experiencing a manic episode were stabilized sequentially on oral aripiprazole and AOM 400 and then randomized to AOM 400 or placebo. The primary end point was time from randomization to recurrence of any mood episode. Other end points included proportion of patients with recurrence of any mood episode and recurrence by mood episode type. RESULTS:Of 266 randomized patients, 64 (48.1%) of 133 in the AOM 400 group and 38 (28.6%) of 133 in the placebo group completed the study. AOM 400 significantly delayed the time to recurrence of any mood episode compared with placebo (hazard ratio: 0.45; 95% CI, 0.30 to 0.68; P < .0001). Significantly fewer patients (P < .0001) experienced recurrence of any mood episode with AOM 400 (35/132; 26.5%) compared with placebo (68/133; 51.1%), with the effects observed predominantly on manic episodes (P < .0001). Patients were not depressed at study entry, and between-group differences in depressive episodes were not significant (P < .864). The treatment-emergent adverse events (incidence > 5%) that were reported at higher rates with AOM 400 than placebo were weight increase, akathisia, insomnia, and anxiety. CONCLUSIONS:AOM 400 delayed the time to and reduced the rate of recurrence of mood episodes and was generally safe and well tolerated. These findings support the use of AOM 400 for maintenance treatment of BP-I. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT01567527.

BACKGROUNDVery‐low density lipoprotein receptor (VLDLR) is a member of the low‐density lipoprotein receptor family highly expressed in adipose tissue. It binds a variety of ligands including apolipoprotein E‐containing triglyceride‐rich lipoproteins, and plays a significant role in the catabolism of triglyceride‐rich lipoproteins. The role of VLDLR had been demonstrated in cell culture and animal models, but little is known about its regulation in human. The objective of this study was to assess the impact of obesity on VLDLR expression in adipose tissue, and to evaluate the role of VLDLR in human adipocyte differentiation and lipid deposition.SUBJECTS AND SAMPLESPaired subcutaneous and visceral adipose tissue aliquots, as well as blood samples, were obtained from a total of 76 subjects, 16 lean (body mass index: BMI ≤ 24.9 kg/m2), 18 overweight (25 ≤ BMI ≤ 29.9 kg/m2) and 42 obese and morbid obese (BMI ≥ 30 kg/m2) subjects. Concentration of plasma lipids (triglycerides, free fatty acids and cholesterol) and glucose was measured enzymatically. Blood insulin level was assayed by enzyme‐linked immunosorbent assay, and homeostasis model assessment of insulin resistance (HOMA‐IR) was determined. Adipocyte size was examined in hematoxylin and eosin‐stained sections, and VLDLR expression was analyzed in adipose tissue using Western blotting and RT‐PCR. In addition, VLDLR expression was examined in isolated pre‐adipocytes before differentiation and during differentiation to mature adipocytes.RESULTSCompared to lean subjects, VLDLR protein level and mRNA abundance in subcutaneous adipose tissue, was up‐regulated in overweight (+46%) and obese subjects (+119%). Similarly, VLDLR expression was up‐regulated in visceral fat but to lesser extent than subcutaneous fat. The abundance of VLDLR mRNA in subcutaneous adipose tissue was positively (p < 0.05) associated with BMI and HOMA‐IR, but not with blood lipids. In addition, VLDLR expression in subcutaneous fat was significantly (p<0.05) associated with increased adipocyte size and triglyceride content. In pre‐adipocytes, VLDLR protein level was virtually inexistent, but increased gradually during differentiation to reach a maximum level in mature adipocytes. Moreover, induction of VLDLR expression in differentiated adipocytes was associated with increased deposition of triglycerides derived mainly from VLDL.CONCLUSIONThe study indicates that obesity up‐regulates VLDLR expression in adipose tissue, and that induction of VLDLR expression during pre‐adipocyte differentiation is associated with increased lipid deposition suggesting a possible role of VLDLR in adipose tissue expansion in human.Support or Funding InformationHackensack University Medical Center

Recent scholarship has adduced convincing evidence that, underlying the late medieval and early modern discourse on witchcraft and diabolism, there lay not only popular folkloric and religious beliefs, but also real practical activities by which individuals made manifest their malicious intent toward others, as well as subjective experiences of interaction with supernatural entities, some of which were interpreted as the Christian Devil. This hypothesis raises a number of hermeneutic questions concerning how the social and material conditions predicating concrete acts of maleficium related to practitioners' social psychology and moral self-construction. Through the interpretive frame of Friedrich Nietzsche's antithesis of 'master' and 'slave' moralities, this paper argues that the Christian theological and cultural context of early modern Europe primed individuals to experience the constraints and stresses of everyday life in vividly moralized terms, and to strategically negotiate their own personal advantage by realigning themselves within this moral order.