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Abstract Background Headache is a pain disorder present in populations world-wide with a higher incidence in females. Specifically, the incidences of medication overuse headache (MOH) have increased worldwide. Comorbidities of MOH include photosensitivity, anxiety, “brain fog”, and decreased physical activity. The FDA-approved long-lasting selective β2-adrenergic receptor agonist, formoterol, is currently approved for use in severe asthma and chronic obstructive pulmonary disease. Recently, interest in repurposing formoterol for use in other disorders including Alzheimer’s disease, and neuropathic pain after spinal cord injury and traumatic brain injury has gained traction. Thus, revisiting known side-effects of formoterol, like headache and anxiety, could inform treatment paradigms. The endocannabinoid (eCB) system is implicated in the etiology of preclinical headache, with observed decreases in the circulating levels of endogenous cannabinoids, referred to as Clinical Endocannabinoid Deficiency. As cross-talk between the eCB system and adrenergic receptors has been reported, this study investigated the role of the eCB system and ability of formoterol to induce headache-like periorbital allodynic behavior. Methods Female 8-week-old C57Bl/6J mice were treated daily with formoterol (0.3 mg/kg, i.p.) for up to 42-days, during which they were assessed for periorbital allodynia, open field/novel object recognition, and photosensitivity. At the end of the study, the periaqueductal grey (PAG), a brain region known to contribute to both headache induction and maintenance, was collected and subjected to LC-MS to quantify endocannabinoid levels. Results Mice exhibited periorbital allodynia at nearly all time points tested and photosensitivity from 28-days onward. Levels of endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), along with cannabinoid receptor 1 (CB1R) expression were altered by both age and upon treatment with formoterol. Administration of FAAH/MAGL inhibitors, to target the eCB system, and a non-selective cannabinoid receptor agonist, WIN 55,212 reversed the formoterol-induced periorbital allodynia. Conclusions These results suggest that formoterol is dysregulates eCB tone to drive headache-like periorbital allodynic behaviors. These results could help inform preventative treatment options for individuals receiving formoterol, as well as provide information on the interaction between the eCB and adrenergic system. Graphical Abstract

Abstract Background Opioid use disorder (OUD) remains a significant public health issue as the number of opioid-related overdose deaths continues to reach new highs each year. Buprenorphine/Naloxone is a medication that has been shown to be highly effective for the treatment of OUD. However, the clinical management of patients on this medication is challenging as many patients discontinue treatment prematurely. We conducted a qualitative study focusing on experienced prescribers of buprenorphine to learn about what they believe are key challenges in prescribing this medication to patients with OUD and related strategies for improving treatment outcomes. Methods We conducted two rounds of interviews with 12 prescribers who were either trained as a primary care physician, nurse practitioner, or physician assistant. These prescribers were recruited from an academically-based treatment program, a community health center, and a commercial substance use disorder treatment facility. Interview data were coded and analyzed in accordance with a grounded theory approach. Results Key findings and related recommendations emerged for patient monitoring, integration of behavioral health with prescribing, patient volume requirements, and use of telehealth. Conclusion The interviews generated a number of recommendations for improving patient outcomes from buprenorphine treatment. Some of these recommendations can be implemented quite readily whereas others entail more substantial resources and time commitments.

The acceptability of school-based interventions has been regularly examined among teachers and parents; however, students are less frequently assessed despite being the recipients of most interventions. Although recent studies have begun exploring how different student characteristics (e.g., gender) and types of acceptability assessments (e.g., dynamic) impact students' ratings, no studies have examined the role of intervention dosage despite early conceptual models highlighting the linkage between intervention acceptability, dosage, adherence, and effectiveness. This study explored 255 third-grade students' intervention dosage and acceptability ratings within the context of a class-wide writing intervention administered over 7 weeks. Results indicated that most students received a high number of intervention sessions throughout the study and rated the intervention as moderately acceptable. There was a statistically significant gender difference in students' postintervention acceptability ratings, with female students rating the class-wide writing intervention higher than male students. In addition, intervention dosage was a statistically significant predictor of students' postintervention acceptability ratings, although gender did not moderate these findings.

The present study examined the physiological impact of a school based sprint interval training (SIT) intervention in replacement of standard physical education (SPE) class on cardio-respiratory fitness (CRF) and glucose homeostasis during the semester following summer vacation. Participants (n=49) were randomly allocated to either intervention (SIT; n=26, aged 16.9 ± 0.3 yrs) or control group who underwent standard physical education (SPE; n=23, aged 16.8 ± 0.6 yrs). CRF (VO2max) and glucose homeostasis were obtained prior-to and following 7 weeks of SIT exercise. Significant group x time interaction was observed for CRF (P

We report a woman with primary amenorrhoea and infertility associated with an isolated deficiency of pituitary FSH that does not respond to GnRH administration. Serum inhibin B was undetectable and antimullerian hormone (AMH) was within the normal range. Ultra sound examination revealed a small uterus and small ovaries with few small follicles. We identified an homozygous 1-bp (G) deletion at codon 79 in FSHbeta gene suggesting a complete loss of function. The patient underwent studies of ovarian responsiveness to recombinant human FSH according to the following protocol: 150UI/d for five days following by 75 UI/d for 10 days. Estradiol plasma level started to increase from day 5 associated to a sharp increase of inhibine B and a decrease of LH. During the same time, we observed an excessive development of multiple follicles resulting in an arrest of the treatment to avoid hyperstimulation. The present study confirm that follicles up to 5 mm in diameter had developed in the absence of FSH and that FSH is required for the growth of follicles beyond the two-layer granulose stage.

Climate change is a critical scientific and social issue of our time, yet the topic is not frequently discussed by the general public. Additionally, misconceptions about the topic persist. One important aspect of climate change is the greenhouse effect. This activity adds a greenhouse gas discussion to an existing module about molecular shape and modeling. The module links the greenhouse effect to climate change. The activity has been used in several introductory chemistry settings. A discussion of student-generated answers and student-reported learning gains is presented.

Background Ventricular repolarization time (ECG QT and JT intervals) is associated with malignant arrhythmia. Genome‐wide association studies have identified 230 independent loci for QT and JT; however, 50% of their heritability remains unexplained. Previous work supports a causal effect of lower serum calcium concentrations on longer ventricular repolarization time. We hypothesized calcium interactions with QT and JT variant associations could explain a proportion of the missing heritability. Methods and Results We performed genome‐wide calcium interaction analyses for QT and JT intervals. Participants were stratified by their calcium level relative to the study distribution (top or bottom 20%). We performed a 2‐stage analysis (genome‐wide discovery [N=62 532] and replication [N=59 861] of lead variants) and a single‐stage genome‐wide meta‐analysis (N=122 393, [European ancestry N=117 581, African ancestry N=4812]). We also calculated 2‐degrees of freedom joint main and interaction and 1‐degree of freedom interaction P values. In 2‐stage and single‐stage analyses, 50 and 98 independent loci, respectively, were associated with either QT or JT intervals (2‐degrees of freedom joint main and interaction P value

Background: The majority of stroke patients are discharged home dependent on informal caregivers, usually family members, to provide assistance with activities of daily living (ADL), including bathing, dressing and toileting. Many caregivers feel unprepared for this role and this may have a detrimental effect on both the patient and caregiver. Objective: To evaluate whether or not a structured, competency-based training programme for caregivers [the London Stroke Carer Training Course (LSCTC)] improved physical and psychological outcomes for patients and their caregivers after disabling stroke, and to determine if such a training programme is cost-effective. Design: A pragmatic, multicentre, cluster randomised controlled trial. Setting: Stratified randomisation of 36 stroke rehabilitation units (SRUs) to the intervention or control group by geographical region and quality of care. Participants: A total of 930 stroke patient and caregiver dyads were recruited. Patients were eligible if they had a confirmed diagnosis of stroke, were medically stable, were likely to return home with residual disability at the time of discharge and had a caregiver available, willing and able to provide support after discharge. The caregiver was defined as the main person – other than health, social or voluntary care provider – helping with ADL and/or advocating on behalf of the patient. Intervention: The intervention (the LSCTC) comprised a number of caregiver training sessions and competency assessment delivered by SRU staff while the patient was in the SRU and one recommended follow-up session after discharge. The control group continued to provide usual care according to national guidelines. Recruitment was completed by independent researchers and participants were unaware of the SRUs' allocation. Main outcome measures: The primary outcomes were self-reported extended ADL for the patient and caregiver burden measured at 6 months after recruitment. Secondary outcomes included quality of life, mood and cost-effectiveness, with final follow-up at 12 months. Results: No differences in primary outcomes were found between the groups at 6 months. Adjusted mean differences were –0.2 points [95% confidence interval (CI) –3.0 to 2.5 points; p = 0.866; intracluster correlation coefficient (ICC) = 0.027] for the patient Nottingham Extended Activities of Daily Living score and 0.5 points (95% CI –1.7 to 2.7 points; p = 0.660; ICC = 0.013) for the Caregiver Burden Scale. Furthermore, no differences were detected in any of the secondary outcomes. Intervention compliance varied across the units. Half of the participating centres had a compliance rating of > 60%. Analysis showed no evidence of higher levels of patient independence or lower levels of caregiver burden in the SRUs with better levels of intervention compliance. The economic evaluation suggests that from a patient and caregiver perspective, health and social care costs, societal costs and outcomes are similar for the intervention and control groups at 6 months, 12 months and over 1 year. Conclusions: We have conducted a robust multicentre, cluster randomised trial, demonstrating for the first time that this methodology is feasible in stroke rehabilitation research. There was no difference between the LSCTC and usual care with respect to improving stroke patients' recovery, reducing caregivers' burden, or improving other physical and psychological outcomes, nor was it cost-effective compared with usual care. Compliance with the intervention varied, but analysis indicated that a dose effect was unlikely. It is possible that the immediate post-stroke period may not be the ideal time for the delivery of structured training. The intervention approach might be more relevant if delivered after discharge by community-based teams. Trial registration: Current Controlled Trials ISRCTN49208824. Funding: This project was funded by the MRC and is managed by the NIHR (project number 09/800/10) on behalf of the MRC–NIHR partnership, and will be published in full in Health Technology Assessment; Vol. 17, No. 46. See the NIHR Journals Library website for further project information.

We have conducted 0D, 1D, 2D, and 3D simulations of an idealized coaxial impedance-matched Marx generator (IMG) [Phys. Rev. Accel. Beams 20, 040402 (2017)PRABCJ2469-988810.1103/PhysRevAccelBeams.20.040402]. The 0D calculations were conducted with a four-element circuit model; the 1D, 2D, and 3D calculations were conducted with highly resolved, fully electromagnetic representations. The IMG consists of 30 stages distributed axially and connected electrically in series. Each stage is powered by two bricks separated by 180° and connected electrically in parallel. Each brick comprises two opposite-polarity capacitors in series with a single switch. The bricks drive an internal impedance-matched coaxial transmission line terminated by a resistive load. The simulations neglect effects due to the switch-triggering circuit, the capacitor-charging circuit, external conducting boundaries, and reactive components of the load. We find dimensionality does not significantly affect the electrical power delivered by the IMG to its load: peak load powers estimated by the 0D, 1D, 2D, and 3D simulations agree to within 1%. The 3D calculations demonstrate that electromagnetic power radiated by the bricks, and axial gaps between stages, reduces the peak load power by less than ∼1%. Each simulation assumes the load impedance is 34% above that at which the load power is maximized. Operating an IMG with such an overmatched load offers several advantages while decreasing the peak load power by only 2%. The 0D, 1D, 2D, and 3D models outlined herein could be adapted to assess computationally competing IMG designs, and conduct a variety of numerical IMG experiments, before an IMG is constructed.

While systemic shortcomings in meeting the needs of individuals with progressive chronic illnesses at the end of life have been well documented, there is growing interest in improving both care and quality of life for persons with advanced chronic obstructive pulmonary disease (COPD). For instance, the American Thoracic Society has issued an official statement on palliative care for patients with respiratory diseases, affirming that the prevention, relief, reduction and soothing of symptoms “without affecting a cure” must become an integral component of standard care. A recent Medline search located 1015 articles related to palliative or end-of-life care for people with COPD published between 2001 and 2008, compared with only 336 articles published before 2001. To address the needs of Canadian patients, an interdisciplinary consensus meeting, funded by the Canadian Institutes of Health Research and supported by the Canadian Thoracic Society, the Canadian Respiratory Health Professionals and the Canadian Lung Association was convened in Toronto, Ontario, on November 22, 2008, to begin examining the quality of end-of-life care for individuals with COPD in Canada. The present report summarizes the background to and outcomes of this consensus meeting.

In a survey of career awareness among high school seniors in Northern California, almost all students agreed that career is an important consideration for them, and about two-thirds reported that they had decided on an occupational field. However, only about half reported that they were comfortable with their current career decision-making, had a clear idea of their own interests and abilities, or had sufficient knowledge about potential occupations. Minority students tended to express greater needs with regard to career exploration than white students. Compared to other groups, significantly fewer Latino males had made an occupational decision. Part-time work during the students' senior year did not appear to hinder school grades or school engagement. In fact, working was associated with generally higher levels of career awareness, especially regarding the importance of career planning. However, part-time work was associated with increases in reported stress levels.