Learning with, about, and from COVID-19: An interprofessional global comparison of pandemic responses.

BACKGROUND AND PURPOSE: University of Kentucky developed a fully virtual course to educate global health learners about the COVID-19 pandemic and compare country responses to it. EDUCATIONAL ACTIVITY AND SETTING: Forty-three students participated in 13 weeks of synchronous interprofessional group meetings via Zoom (Zoom Video Communications, Inc) and asynchronous modules. Interprofessionality was intentional yet implicit, and a flipped classroom was utilized. Assessment was accomplished with one instrument measuring learning outcomes associated with select Consortium of Universities of Global Health Interprofessional Global Health Competencies, Association of American Colleges and Universities Global Learning Value Rubric competencies, and course satisfaction and effectiveness utilizing a retrospective pre-/post-methodology. FINDINGS: Positive pre-/post-change was observed in 10 survey items. Evaluation results concerning course structure and experience were uniformly high, with the key informant interview rated most helpful. Items with significant improvement included a better understanding of the student's place in the world; improved interprofessional communication skills; population health data skills; and understanding of health systems and entities that influence global health and development. Learners appreciated the value of interprofessional teamwork and gained a deeper understanding of the roles and training of colleagues from other programs, leading to a deeper understanding of the actions those professions may take within health systems. SUMMARY: The pivot to all online global health education was a viable solution to addressing the pause in global travel and study abroad experiences at University of Kentucky.

Patient-Reported Outcome Measures in Clinical High Risk for Psychosis: A Systematic Review.

A key issue in both research and clinical work with youth at clinical high risk (CHR) of psychosis is that there are clearly heterogenous clinical outcomes in addition to the development of psychosis. Thus, it is important to capture the psychopathologic outcomes of the CHR group and develop a core outcomes assessment set that may help in dissecting the heterogeneity and aid progress toward new treatments. In assessing psychopathology and often poor social and role functioning, we may be missing the important perspectives of the CHR individuals themselves. It is important to consider the perspectives of youth at CHR by using patient-reported outcome measures (PROMs). This systematic review of PROMs in CHR was conducted based on a comprehensive search of several databases and followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Sixty-four publications were included in the review examining PROMs for symptoms, functioning, quality of life, self-perceptions, stress, and resilience. Typically, PROMs were not the primary focus of the studies reviewed. The PROMs summarized here fit with results published elsewhere in the literature based on interviewer measures. However, very few of the measures used were validated for CHR or for youth. There are several recommendations for determining a core set of PROMs for use with CHR.

Cannabis use and attenuated positive and negative symptoms in youth at clinical high risk for psychosis.

Cannabis use is more prevalent among youth at clinical high-risk (CHR) for psychosis than healthy controls (HC). There is mixed evidence as to whether cannabis use is associated with increased severity of attenuated psychotic symptoms (APS) or whether current cannabis use is associated with the transition to psychosis. This study aims to assess cannabis use differences between CHR youth and HC and the impact of cannabis use on APS, clinical status, and transition to psychosis. Participants were from the North American Prodrome Longitudinal Study-3, a prospective longitudinal study including 710 individuals, age 12-30, meeting criteria for a psychosis risk syndrome based on the Structured Interview for Psychosis-Risk Syndromes, and 96 HC. Cannabis use, frequency, and severity of use were assessed with the Alcohol Use Scale/Drug Use Scale. Current and past cannabis use disorders were assessed with the Structured Clinical Interview for DSM-5. Compared to HC, CHR individuals reported significantly increased lifetime cannabis use, during the past six months, and at baseline; greater frequency and severity of cannabis use; and increased prevalence of cannabis use disorder. Relative to CHR youth without cannabis use, CHR cannabis users had significantly higher ratings on baseline grandiosity and lower 12-months social anhedonia. Severity of cannabis was unrelated to clinical status at 2-years, and it did not differentiate CHR individuals who transitioned to psychosis from those who did not. However, a major limitation was that the current number of CHR cannabis users was small, and survival analyses resulted in a smaller power than the 80 % recommended.

Predicting professional school performance with a unique lens: are there other cognitive predictors?

BACKGROUND: We investigated the associations between admissions criteria and performance in four cohorts of pre-dental MS in Oral Health Sciences (OHS) program at Boston University Schools of Medicine and Dental Medicine. Previously we have reported that OHS serves as a successful pre-dental pipeline program for students from underrepresented groups. METHODS: We evaluated academic variables that further affect overall graduate GPA and grades in the first year dental school courses taken by OHS students at Boston University between 2012 and 2016 as part of the MS curriculum. Demographic data, region of residency, undergraduate grade point average, number of science and math credits, major of study, dental admissions test scores and undergraduate institution were collected. The competitiveness of the undergraduate institution was scored based on Barron's Profiles of American Colleges. OHS-GPA was assessed and individual grades in two first year dental school courses taken as part of the OHS curriculum were collected. Analysis of variance, the Chi-square test and Fisher's Exact test were utilized to assess associations between academic performance parameters, successful program completion and matriculation to dental school. RESULTS: Results indicate that undergraduate major, age and number of science course credits taken had no impact on MS performance in the Boston University MS in Oral Health Sciences program; however, students who took an undergraduate course in Physiology performed better than those who did not (p = 0.034). This was not the case with courses in Cell Biology and Biochemistry. Students with DAT scores over 20 academic average (p = 0.001), 18 total science average (p = 0.001) and 22 reading comprehension (p = 0.004) performed better in dental school courses taken in OHS. CONCLUSION: We report that strong test scores, attending a mid or highly rigorous undergraduate institution and completion of an undergraduate Physiology course are positive predictors. We hope these findings will guide admission's decisions and improve recruitment to, and future success of, graduate student's pursuit of professional school. Understanding alternative predictors of success may help to reduce the intrinsic bias among applicants from underrepresented groups and continue to look beyond the DATs (or MCATs) to decrease the gap between professionals from underrepresented groups and those they serve.

Evaluating a Commonly Used Tool for Measuring Sport Specialization in Young Athletes.

CONTEXT: Sport specialization has been defined as year-round intensive training in a single sport to the exclusion of other sports. A commonly used survey tool created by Jayanthi et al, which classifies athletes as having a low, moderate, or high level of specialization, categorizes only athletes answering yes to "Have you quit other sports to focus on a main sport?" as highly specialized. We hypothesized that a measureable number of year-round, single-sport athletes have never played other sports and, therefore, may be inaccurately classified as moderately specialized when using this tool, even though most experts would agree they should be viewed as highly specialized. OBJECTIVE: To determine the proportion of athletes misclassified as moderately rather than highly specialized because they never played a previous sport. DESIGN: Cross-sectional study. SETTING: Hospital-based pediatric outpatient sports medicine clinic. PATIENTS OR OTHER PARTICIPANTS: Injured athletes aged 12 to 17 years who presented to the clinic between 2015 and 2017 and completed a sports-participation survey (n = 917). MAIN OUTCOME MEASURE(S): Sport-specialization level. RESULTS: Of 917 participants, 299 (32.6%) played a single sport more than 8 months per year, and 208/299 (69.6%) had previously quit other sports (highly specialized), whereas 91 (30.4%) had never played other sports (highly specialized and misclassified as moderate). Individual-sport athletes had a 2.03 times greater risk of being highly specialized and misclassified as moderate than team-sport athletes (relative risk = 2.03 [95% confidence interval = 1.37, 3.00]). Females had a 1.70 times greater risk of being misclassified as moderately specialized than males (relative risk 1.70 [95% confidence interval = 1.07, 2.70]). Of the 3 sports with the largest number of athletes, artistic gymnastics had the highest proportion (51.2%) who had never played other sports. CONCLUSIONS: The commonly used specialization survey misclassified a substantial number of highly specialized athletes as moderately specialized. Researchers should consider adding a fourth survey question, "Have you only ever played 1 sport?" to identify and better study this unique subset of misclassified athletes.

The Effects of Specialization and Sex on Anterior Y-Balance Performance in High School Athletes.

BACKGROUND: Sport specialization and movement asymmetry have been separately discussed as potential risk factors for lower extremity injury. Early specialization may lead to the development of movement asymmetries that can predispose an athlete to injury, but this has not been thoroughly examined. HYPOTHESIS: Athletes rated as specialized would exhibit greater between-limb anterior reach asymmetry and decreased anterior reach distance on the Y-balance test (YBT) as compared with nonspecialized high school athletes, and these differences would not be dependent on sex. STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 3. METHODS: Two hundred ninety-five athletes (117 male, 178 female; mean age, 15.6 ± 1.2 years) from 2 local high schools participating in basketball, soccer, volleyball, and tennis responded to a questionnaire regarding sport specialization status and performed trials of the YBT during preseason testing. Specialization was categorized according to 3 previously utilized specialization classification methods (single/multisport, 3-point scale, and 6-point scale), and interactions between specialization and sex with Y-balance performance were calculated using 2-way analyses of variance. RESULTS: Single-sport male athletes displayed greater anterior reach asymmetry than other interaction groups. A consistent main effect was observed for sex, with men displaying greater anterior asymmetry and decreased anterior reach distance than women. However, the interaction effects of specialization and sex on anterior Y-balance performance varied based on the classification method used. CONCLUSION: Single-sport male athletes displayed greater anterior reach asymmetry on the YBT than multisport and female athletes. Specialization classification method is important because the 6- and 3-point scales may not accurately identify balance abnormalities. Male athletes performed worse than female athletes on both of the Y-balance tasks. CLINICAL RELEVANCE: Clinicians should be aware that single-sport male athletes may display deficits in dynamic balance, potentially increasing their risk of injury.

Rescue of a Mouse Model of Spinal Muscular Atrophy With Respiratory Distress Type 1 by AAV9-IGHMBP2 Is Dose Dependent.

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is an autosomal recessive disease occurring during childhood. The gene responsible for disease development is a ubiquitously expressed protein, IGHMBP2. Mutations in IGHMBP2 result in the loss of α-motor neurons leading to muscle atrophy in the distal limbs accompanied by respiratory complications. Although genetically and clinically distinct, proximal SMA is also caused by the loss of a ubiquitously expressed gene (SMN). Significant preclinical success has been achieved in proximal SMA using viral-based gene replacement strategies. We leveraged the technologies employed in SMA to demonstrate gene replacement efficacy in an SMARD1 animal model. Intracerebroventricular (ICV) injection of single-stranded AAV9 expressing the full-length cDNA of IGHMBP2 in a low dose led to a significant level of rescue in treated SMARD1 animals. Consistent with drastically increased survival, weight gain, and strength, the rescued animals demonstrated a significant improvement in muscle, NMJ, motor neurons, and axonal pathology. In addition, increased levels of IGHMBP2 in lumbar motor neurons verified the efficacy of the virus to transduce the target tissues. Our results indicate that AAV9-based gene replacement is a viable strategy for SMARD1, although dosing effects and potential negative impacts of high dose and ICV injection should be thoroughly investigated.

Paleoceanography. Onset of Mediterranean outflow into the North Atlantic.

Sediments cored along the southwestern Iberian margin during Integrated Ocean Drilling Program Expedition 339 provide constraints on Mediterranean Outflow Water (MOW) circulation patterns from the Pliocene epoch to the present day. After the Strait of Gibraltar opened (5.33 million years ago), a limited volume of MOW entered the Atlantic. Depositional hiatuses indicate erosion by bottom currents related to higher volumes of MOW circulating into the North Atlantic, beginning in the late Pliocene. The hiatuses coincide with regional tectonic events and changes in global thermohaline circulation (THC). This suggests that MOW influenced Atlantic Meridional Overturning Circulation (AMOC), THC, and climatic shifts by contributing a component of warm, saline water to northern latitudes while in turn being influenced by plate tectonics.

Morpholino antisense oligonucleotides targeting intronic repressor Element1 improve phenotype in SMA mouse models.

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by the loss of Survival Motor Neuron-1 (SMN1). In all SMA patients, a nearly identical copy gene called SMN2 is present, which produces low levels of functional protein owing to an alternative splicing event. To prevent exon-skipping, we have targeted an intronic repressor, Element1 (E1), located upstream of SMN2 exon 7 using Morpholino-based antisense oligonucleotides (E1(MO)-ASOs). A single intracerebroventricular injection in the relatively severe mouse model of SMA (SMNΔ7 mouse model) elicited a robust induction of SMN protein, and mean life span was extended from an average survival of 13 to 54 days following a single dose, consistent with large weight gains and a correction of the neuronal pathology. Additionally, E1(MO)-ASO treatment in an intermediate SMA mouse (SMN(RT) mouse model) significantly extended life span by ∼700% and weight gain was comparable with the unaffected animals. While a number of experimental therapeutics have targeted the ISS-N1 element of SMN2 pre-mRNA, the development of E1 ASOs provides a new molecular target for SMA therapeutics that dramatically extends survival in two important pre-clinical models of disease.

Defining the therapeutic window in a severe animal model of spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by the loss of a single gene, Survival Motor Neuron-1 (SMN1). Administration of a self-complementary Adeno-Associated Virus vector expressing full-length SMN cDNA (scAAV-SMN) has proven an effective means to rescue the SMA phenotype in SMA mice, either by intravenous (IV) or intracerebroventricular (ICV) administration at very early time points. We have recently shown that ICV delivery of scAAV9-SMN is more effective than a similar dose of vector administered via an IV injection, thereby providing an important mechanism to examine a timeline for rescuing the disease and determining the therapeutic window in a severe model of SMA. In this report, we utilized a relatively severe mouse model of SMA, SMNΔ7. Animals were injected with scAAV9-SMN vector via ICV injection on a single day, from P2 through P8. At each delivery point from P2 through P8, scAAV9-SMN decreased disease severity. A near complete rescue was obtained following P2 injection while a P8 injection produced a ∼ 40% extension in survival. Analysis of the underlying neuromuscular junction (NMJ) pathology revealed that late-stage delivery of the vector failed to provide protection from NMJ defects despite robust SMN expression in the central nervous system. While our study demonstrates that a maximal benefit is obtained when treatment is delivered during pre-symptomatic stages, significant therapeutic benefit can still be achieved after the onset of disease symptoms.

Near resonance acoustic scattering from organized schools of juvenile Atlantic bluefin tuna (Thunnus thynnus).

Schools of Atlantic bluefin tuna (Thunnus thynnus) can exhibit highly organized spatial structure within the school. This structure was quantified for dome shaped schools using both aerial imagery collected from a commercial spotter plane and 400 kHz multibeam echo sounder data collected on a fishing vessel in 2009 in Cape Cod Bay, MA. Observations from one school, containing an estimated 263 fish within an approximately ellipsoidal volume of 1900 m(3), were used to seed an acoustic model that estimated the school target strength at frequencies between 10 and 2000 Hz. The fish's swimbladder resonance was estimated to occur at approximately 50 Hz. The acoustic model examined single and multiple scattering solutions and also a completely incoherent summation of scattering responses from the fish. Three levels of structure within the school were examined, starting with fish locations that were constrained by the school boundaries but placed according to a Poisson process, then incorporating a constraint on the distance to the nearest neighbor, and finally adding a constraint on the bearing to the nearest neighbor. Results suggest that both multiple scattering and spatial organization within the school should be considered when estimating the target strength of schools similar to the ones considered here.

Development and characterization of an SMN2-based intermediate mouse model of Spinal Muscular Atrophy.

Spinal Muscular Atrophy (SMA) is due to the loss of the survival motor neuron gene 1 (SMN1), resulting in motor neuron (MN) degeneration, muscle atrophy and loss of motor function. While SMN2 encodes a protein identical to SMN1, a single nucleotide difference in exon 7 causes most of the SMN2-derived transcripts to be alternatively spliced resulting in a truncated and unstable protein (SMNΔ7). SMA patients retain at least one SMN2 copy, making it an important target for therapeutics. Many of the existing SMA models are very severe, with animals typically living less than 2 weeks. Here, we present a novel intermediate mouse model of SMA based upon the human genomic SMN2 gene. Genetically, this model is similar to the well-characterized SMNΔ7 model; however, we have manipulated the SMNΔ7 transgene to encode a modestly more functional protein referred to as SMN read-through (SMN(RT)). By introducing the SMN(RT) transgene onto the background of a severe mouse model of SMA (SMN2(+/+);Smn(-/-)), disease severity was significantly decreased based upon a battery of phenotypic parameters, including MN pathology and a significant extension in survival. Importantly, there is not a full phenotypic correction, allowing for the examination of a broad range of therapeutics, including SMN2-dependent and SMN-independent pathways. This novel animal model serves as an important biological and therapeutic model for less severe forms of SMA and provides an in vivo validation of the SMN(RT) protein.