Summary Background Large ventral lateral clock neurons (lLNv) exhibit higher daytime light-driven spontaneous action potential firing rates in Drosophila, coinciding with wakefulness and locomotor activity behaviour. To determine whether the lLNv are involved in arousal and sleep/wake behaviour we examined the effects of altered electrical excitation of the LNv. Results LNv-hyperexcited flies reverse the normal day/night firing pattern, showing higher lLNv firing rates at night and pigment dispersing factor-mediated enhancement of nocturnal locomotor activity behaviour and reduced quantity and quality of sleep. lLNv hyperexcitation impairs sensory arousal, as shown by physiological and behavioural assays. lLNv hyperexcited flies lacking sLNv neurons exhibit robust hyperexcitation-induced increases in nocturnal behaviour, suggesting that the sLNv are not essential for mediation of arousal. Conclusions Light-activated lLNv neurons modulate behavioural arousal and sleep in Drosophila.

The celebrated Hermite–Hadamard and Ostrowski type inequalities have been studied extensively since they have been established. We find novel versions of the Hermite–Hadamard and Ostrowski type inequalities for the n-polynomial s-type convex functions in the frame of fractional calculus. Taking into account the new concept, we derive some generalizations that capture novel results under investigation. We present two different general techniques, for the functions whose first and second derivatives in absolute value at certain powers are n-polynomial s-type convex functions by employing $\mathcal{K}$ K -fractional integral operators have yielded intriguing results. Applications and motivations of presented results are briefly discussed that generate novel variants related to quadrature rules that will be helpful for in-depth investigation in fractal theory, optimization and machine learning.

IMPORTANCEOne of the main aims of research on nonmedical opioid use (NMOU) is to reduce the frequency of NMOU behaviors through interventions such as universal screening, reduced opioid exposure, and more intense follow-up of patients with elevated risk. The absence of data on the frequency of NMOU behavior is the major barrier to conducting research on NMOU.OBJECTIVE To determine the overall frequency of and the independent predictors for NMOU behavior. DESIGN, SETTING, AND PARTICIPANTSIn this prognostic study, 3615 patients with cancer were referred to the supportive care center at MD Anderson Cancer Center from March 18, 2016, to June 6, 2018. Patients were eligible for inclusion if they had cancer and were taking opioids for cancer pain for at least 1 week. Patients were excluded if they had no follow-up within 3 months of initial consultation, did not complete the appropriate questionnaire, or did not have scheduled opioid treatments. After exclusion, a total of 1554 consecutive patients were assessed for NMOU behavior using established diagnostic criteria. All patients were assessed using the Edmonton Symptom Assessment Scale, the Screener and Opioid Assessment for Patients with Pain (SOAPP), and the Cut Down, Annoyed, Guilty, Eye Opener-Adapted to Include Drugs (CAGE-AID) survey. Data were analyzed from January 6 to September 25, 2020.RESULTS A total of 1554 patients (median [interquartile range (IQR)] age, 61 [IQR,[52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69] years; 816 women [52.5%]; 1124 White patients [72.3%]) were evaluable for the study, and 299 patients (19.2%) had 1 or more NMOU behaviors. The median (IQR) number of NMOU behaviors per patient was 1 (IQR, 1-3). A total of 576 of 745 NMOU behaviors (77%) occurred by the first 2 follow-up visits. The most frequent NMOU behavior was unscheduled clinic visits for inappropriate refills (218 of 745 [29%]). Eighty-eight of 299 patients (29.4%) scored 7 or higher on SOAPP, and 48 (16.6%) scored at least 2 out of 4 points on the CAGE-AID survey. Results from the multivariate model suggest that marital status (single, hazard ratio [HR], 1.58; 95% CI, 1.15-2.18; P = .005; divorced, HR, 1.43; 95% CI, 1.01-2.03; P = .04), SOAPP score (positive vs negative, HR, 1.35; 95% CI, 1.04-1.74; P = .02), morphine equivalent daily dose (MEDD) (HR, 1.003; 95% CI, 1.002-1.004; P < .001), and Edmonton Symptom Assessment Scale pain level (HR, 1.11; 95% CI, 1.06-1.16; P < .001) were independently associated with the presence of NMOU behavior. In recursive partition analysis, single marital status, MEDD greater than 50 mg, and SOAPP scores greater than 7 were associated with a higher risk (56%) for the presence of NMOU behavior.CONCLUSIONS AND RELEVANCE This prognostic study of patients with cancer taking opioids for cancer pain found that 19% of patients developed NMOU behavior within a median duration of 8 weeks after initial supportive care clinic consultation. Marital status (single or divorced), SOAPP score greater than 7, higher levels of pain se...

We investigate a time scale version of two auxiliary functions for the class of convex functions. We derive several novel dynamic inequalities for these classes of convex functions. Applications of these consequences are taken into consideration in special means. Furthermore, illustrative examples are introduced to help our outcomes. Meanwhile, we communicate a few particular cases which may be deduced from our main outcomes.

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