Background: SMA affects individuals with a broad age range and spectrum of disease severity. Risdiplam (EVRYSDI®) is a centrally and peripherally distributed, oral SMN2 pre-mRNA splicing modifier. Methods: SUNFISH is a multicenter, two-part, randomized, placebo-controlled, double-blind study in patients with Types 2/3 SMA. Part 1 assessed the safety, tolerability and pharmacokinetics/pharmacodynamics of different risdiplam dose levels in patients with Types 2/3 SMA. Part 2 assessed the efficacy and safety of the selected dose of risdiplam versus placebo in Type 2 and non-ambulant Type 3 SMA. In Part 2, participants were treated with risdiplam or placebo for 12 months, then received risdiplam in a blinded manner until month 24. At month 24, patients were offered the opportunity to enter the open-label extension phase. Results: Change from baseline in MFM32 total score (Part 2- primary endpoint) in patients treated with risdiplam versus placebo was met at month 12. These increases in motor function were sustained in the second and third year after risdiplam treatment. Here we present 4-year efficacy and safety data from SUNFISH. Conclusions: SUNFISH is ongoing and will provide further long-term efficacy and safety data of risdiplam in a broad population of individuals with SMA.

While prior literature has largely focused on marriage effects during young adulthood, it is less clear whether these effects are as strong in middle adulthood. Thus, we investigated age differences in marriage effects on problem-drinking reduction. We employed parallel analyses with two independent samples (analytic-sample Ns of 577 and 441, respectively). Both are high-risk samples by design, with about 50% of participants having a parent with lifetime alcohol use disorder. Both samples have been assessed longitudinally from early young adulthood to the mid-to-late 30s. Separate parallel analyses with these two samples allowed evaluation of the reproducibility of results. Growth models of problem drinking tested marriage as a time-varying predictor and thereby assessed age differences in marriage effects. For both samples, results consistently showed marriage effects to be strongest in early young adulthood and to decrease somewhat monotonically thereafter with age, reaching very small (and nonsignificant) magnitudes by the 30s. Results may reflect that role transitions like marriage have more impact on problem drinking in earlier versus later adulthood, thereby highlighting the importance of life span developmental research for understanding problem-drinking desistance. Our findings can inform intervention strategies aimed at reducing problem drinking by jumpstarting or amplifying natural processes of adult role adaptation.

The extent of intertidal flats in the Yellow Sea region has declined significantly in the past few decades, resulting in severe population declines in several waterbird species. The Yellow Sea region holds the primary stopover sites for many shorebirds during their migration to and from northern breeding grounds. However, the functional roles of these sites in shorebirds’ stopover ecology remain poorly understood. Through field surveys between July and November 2015, we investigated the stopover and moult schedules of migratory shorebirds along the southern Jiangsu coast, eastern China during their southbound migration, with a focus on the ‘Critically Endangered’ Spoon-billed Sandpiper Calidris pygmaea and ‘Endangered’ Nordmann’s Greenshank Tringa guttifer. Long-term count data indicate that both species regularly occur in globally important number in southern Jiangsu coast, constituting 16.67–49.34% and 64.0–80.67% of their global population estimates respectively, and it is highly likely that most adults undergo their primary moult during this southbound migration stopover. Our results show that Spoon-billed Sandpiper and Nordmann’s Greenshank staged for an extended period of time (66 and 84 days, respectively) to complete their primary moult. On average, Spoon-billed Sandpipers and Nordmann’s Greenshanks started moulting primary feathers on 8 August ± 4.52 and 27 July ± 1.56 days respectively, and their moult durations were 72.58 ± 9.08 and 65.09 ± 2.40 days. In addition, some individuals of several other shorebird species including the ‘Endangered’ Great Knot Calidris tenuirostris, ‘Near Threatened’ Bar-tailed Godwit Limosa lapponica, ‘Near Threatened’ Eurasian Curlew Numenius arquata and Greater Sand Plover Charadrius leschenaultii also underwent primary moult. Our work highlights the importance of the southern Jiangsu region as the primary moulting ground for these species, reinforcing that conservation of shorebird habitat including both intertidal flats and supratidal roosting sites in this region is critical to safeguard the future of some highly threatened shorebird species.

Background: SMA is characterized by reduced levels of survival of motor neuron (SMN) protein from deletions and/or mutations of the SMN1 gene. While SMN1 produces full-length SMN protein, a second gene, SMN2, produces low levels of functional SMN protein. Risdiplam (RG7916/RO7034067) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates pre-mRNA splicing of SMN2 to increase SMN protein levels. Methods: SUNFISH (NCT02908685) is an ongoing multicenter, double-blind, placebo-controlled, operationally seamless study (randomized 2:1, risdiplam:placebo) in patients aged 2–25 years, with Type 2/3 SMA. Part 1 (n=51) assesses safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels. Pivotal Part 2 (n=180) assesses safety and efficacy of the risdiplam dose level selected based on Part 1 results. Results: Part 1 results showed a sustained, >2-fold increase in median SMN protein versus baseline following 1 year of treatment. Adverse events were mostly mild, resolved despite ongoing treatment and reflected underlying disease. No drug-related safety findings have led to withdrawal (data-cut 06/17/18). SUNFISH Part 1 exploratory endpoint results and Part 2 study design will also be presented. Conclusions: To date, no drug-related safety findings have led to withdrawal. Risdiplam led to sustained increases in SMN protein levels.

Innovation Concept: Transition to independent practice is challenging and early career physicians are more prone to burnout and error. Despite recommendations for formal mentorship to support physicians, only 43.6% of US academic Emergency Medicine departments have such programs. We describe an innovative mentorship program designed to support these early career physicians and enhance quality of care, career longevity, and wellness. We operationalized mentorship in which experienced, highly regarded, empathic mentors guide mentees in their personal and professional development. Methods: In this program two Emergency Physician mentors were teamed with each newly hired Emergency Physician. Mentees could request their own mentors, and teams were matched on the basis of shared personal and academic interests. Mentors received academic funding and training on good mentorship practice, roles and responsibilities, and feedback. Teams had to meet formally at least twice a year, with additional contact as needed. While mentees set the meeting agenda, teams were also encouraged to address four main areas. These areas were identified from a targeted needs assessment and literature review. They include: 1) clinical process and care, 2) departmental structure and culture, 3) teaching and scholarship, and 4) physician wellness. After meetings, mentees summarized and submitted the topics discussed and reflected on action plans. An oversight committee supported the program. Curriculum, Tool or Material: All nine (9) newly hired physicians joined the program in Fall 2018. As of December 2018, six (6) teams have had formal meetings. They discussed the following areas: clinical processes and care (50%), departmental structure and culture (100%), teaching and scholarship (67%), and physician wellness (100%). Other areas discussed include: academic career, financial planning, and networking. Teams spent 20-60% of the time formulating steps to achieve mentee career goals. They spent 40-60% of the time discussing skills and resources needed. End of year program evaluation will include outcomes such as satisfaction, value, effectiveness, projects, promotions, and awards. The results will shape future program design. Conclusion: We implemented a mentorship program for newly hired Emergency Physicians. As mentorship is integral to successful transition to independent practice, this program model could be highly beneficial to other academic Emergency Medicine departments.

Innovation Concept: Emergency medicine physicians must maintain a broad knowledge base and procedural skillset while fulfilling their academic roles as teachers, researchers and administrators. Most academic departments do not have a regular, affordable, formal continuing professional development (CPD) and faculty development (FD) curriculum for their staff. We set out to design and implement a novel continuous practice enhancement program to address this issue. Methods: Strategic planning by the Ottawa academic Department of EM identified CPD and FD as priorities. A program was created to support high quality, monthly CPD/FD courses provided by physicians. We had 5 goals: (1) enhance clinical and academic skills, (2) disseminate group best practices, (3) sustain skills in high impact/low frequency scenarios, (4) support physician academic careers, and (5) acquire new procedural skills. A CPD/FD Committee composed of local meded experts and experienced clinical teachers was tasked with overseeing the creation and evaluation of these sessions. Curriculum, Tool or Material: The longitudinal curriculum was informed by perceived needs (group survey), ascribed needs (M&M rounds, physician metrics and departmental leadership priorities) and participant feedback. The committee identified local experts to present on their areas of expertise in order to promote group best practice. Topics to-date have included clinical skills updates, teaching and coaching strategies and academic career planning. A comprehensive monthly simulation-based curriculum was rolled out simultaneously to give participants the opportunity to develop crisis resource management and critical care skills. Except for sessions requiring advanced equipment or cadavers, sessions are financed by academic funds and free for participants. Conclusion: Faculty academic learning and engagement is an important goal and participation in this curriculum is reviewed at each physician's annual reappointment. To-date, 18 physicians (21% of our group) have presented topics and 92% of physicians have participated in at least one session with 63% having attended three or more. Evaluations have been overwhelmingly positive, and a recent survey identified the CPD/FD program as a significant contributor to our physicians’ wellness. We introduced an innovative, structured CPD/FD program in response to perceived and ascribed needs of our physicians and departmental leadership. Our successful CPD/FD curriculum represents a model for other departments who are considering similar initiatives.

Background: Opportunistic infection should be considered when seeing neurological complications in the setting of immunosuppression. Accumulating evidence that enteroviral meningoencephalitis can occur after rituximab administration exists but differentiating it from non-infectious conditions can be challenging. Methods: Case report Results: We describe a 4 year-old-boy with a history of pulmonary capillaritis, treated with immunosuppressive therapy -including steroids, rituximab, and azathioprine. He developed mutism and ataxia after 18 months on rituximab. MRI Brain/Spine revealed extensive T2/FLAIR hyperintensities in the deep subcortical white matter, temporal lobes, globus pallidi, thalami, brainstem, and cerebellum; and swelling of the dorsal cervical cord, showing primarily grey matter involvement. IgG levels had a decreasing trend over the course of Rituximab. CSF, and subsequent brain biopsy, were both positive for enterovirus RNA by RT-PCR. He was thought to have enterovirus encephalitis secondary to rituximab therapy, and was treated with IVIG and fluoxetine. Conclusions: One should consider chronic opportunistic CNS infections in children treated with immunosuppressive therapy, and to consider chronic enterovirus infection when B-cell suppression has occurred. As rituximab is being increasingly used in the pediatric population, and is generally thought to be safe, attention should be paid to any child with chronic neurological signs, particularly younger children who may be at higher risk for chronic enterovirus infection.

Background: Graduating residents require general palliative care skills. In Canada, there is no standardized palliative care curriculum for specialty trained residents. The objective of this research is to develop an evidence-based palliative care curriculum designed to provide neurology residents with the general palliative care skills required for providing patient care along the continuum of life. Methods: A needs assessment was performed in Neurology at Western University using qualitative analysis techniques. Residents completed the following:. A curricular outline was developed based on the Kolb learning style inventory (LSI), a knowledge pre-test, the Palliative Medicine Comfort and Confidence Survey and a review of the literature. Two iterations of the curriculum have been developed. Results: Residents identified a need for additional training in supportive and palliative care skills. Based on the Kolb LSI, 9/16 (56.3%) of neurology residents are “accommodators”. General principles identified for inclusion included: symptom management, communication, psychosocial aspects of care, care coordination and access, and myths and pitfalls in palliative care. Conclusions: This project is designed to identify the current palliative educational needs for Neurology residents. The results suggest that specialty trained residents are receptive to embedding training in the principles of palliative care within their training programs.

Surgical experiments were conducted on cultured five-node apical rhizome segments of quackgrass. Removal of scale leaves promoted an initial burst of growth within the axillary buds but did not support the continued growth of buds as effectively as removal of the rhizome apex. Replacement of detached scale leaves over denuded buds temporarily repressed the promotive effect of scale leaf removal. Aqueous extracts of scale leaf material inhibited apical growth in rhizome segments but did not inhibit bud growth. Anatomical sections revealed that removal of scale leaves promoted development of buds: cells enlarged, vascular tissues differentiated, and new nodes began to form within 4 days of the removal of scale leaves. It is suggested that scale leaves contribute to apical dominance by inhibiting the initial development of axillary buds.

Introduction: Because major depressive disorder (MDD) is often chronic and recurrent, even pediatric patients who are treated successfully during an acute episode may need longer-term treatment. Yet, data on long-term treatment with antidepressants in pediatric MDD are limited.

Objective: To evaluate long-term effectiveness and safety of treatment with venlafaxine extended-release (ER) in children and adolescents with MDD.

Methods: Subjects (n=86) 7–17 years of age with MDD entered a multicenter, open-label study of flexible-dose venlafaxine ER for 6 weeks of acute treatment, followed by continuation treatment for up to 6 months total treatment. The primary efficacy variable was the Children's Depression Rating Scale-Revised (CDRS-R) total score (intent-to-treat population).

Results: Mean CDRS-R total score decreased from 60.1±10.0 at baseline to 36.3±13.1 at week 6, and to 33.8±15.0 at 6 months (last observation carried forward). Among completers (n=36), the mean CDRS-R total score was 24.3±7.6 at the end of 6 months of treatment. The most frequent treatment-emergent adverse events were headache (53%), nausea (26%), infection (24%), abdominal pain (22%), vomiting (21%), and pharyngitis (19%). Fifteen (17%) participants discontinued due to adverse events, 9 of whom did so within the first 6 weeks. Serious adverse events (suicide attempt [two], hostility [two], hallucinations, depression, and pharyngitis) occurred in seven patients. There were no suicides.

Conclusion: Most improvement with venlafaxine ER occurs during the first 6 weeks of treatment. Prescribers should be alert to signs of suicidal ideation and hostility in pediatric patients.

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.