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The role of gamification and active learning has been common topics of conversation in higher education for many years. These learning tools have been correlated with a multitude of positive effects, including increased student engagement, collaboration, and motivation to learn. This article explores the role of gamification and active learning in a virtual setting using a gamified Harry Potter-themed final examination review session for first-year osteopathic medical students. We also discuss how gamification can be used to improve the connectivity and wellness of students as they attend classes almost entirely online during the COVID-19 global pandemic. Supplementary Information The online version contains supplementary material available at 10.1007/s40670-022-01501-4.

We present results from a new data set, the Statistics of Income Mobility Panel, that has been assembled from tax and other administrative sources to provide evidence on economic mobility and persistence in the United States. This data set allows us to take on the methodological problems that have complicated previous efforts to estimate intergenerational earnings and income elasticities. We find that the elasticities for women’s income, men’s income, and men’s earnings are as high as all but the highest of the previously reported survey-based estimates. Because the intergenerational curves are especially steep within the parental-income region defined by the 50th to 90th percentiles, approximately two-thirds of the inequality between poor and well-off families is passed on to the next generation. This extreme persistence cannot be attributed to any single factor. Instead, the U.S. is exceptional with respect to virtually all factors governing intergenerational persistence, including the returns to human capital, the amount of public investment in the human capital of low-income children, the amount of socioeconomic segregation, and the progressiveness of the tax-and-transfer system. For each of these four factors, the U.S. has opted for policies that are mobility-reducing, with the implication that any substantial increase in mobility will likely require a wide-ranging package of reforms that cut across many institutions.

Incorporating contemporary fiction into educational activities that are interactive and memorable creates a positive learning environment for students. The current article describes how our medical school created a Harry Potter-themed educational event to review didactic material before a final exam. Students were sorted into Hogwarts houses and collected house points in the 8 themed classrooms that reviewed material for the individual disciplines. The event also included a Quidditch tournament and a Yule Ball. The event received positive feedback from students, encouraging the school’s faculty to look for other opportunities to create similar educational experiences during preclinical medical education.

This study investigated faculty members' perceptions of program community and what they do to support it in online graduate programs. Researchers developed and administered an online survey to ascertain perceptions of program community among education and engineering faculty members at United States, land‐grant, research‐extensive universities. Three hundred forty‐four faculty members responded. Most participants thought that fostering community beyond courses was important. Faculty members used a variety of strategies to accomplish this task, including social media, synchronous communication and advising, face‐to‐face socials and orientations, and cohort models. Yet, many also relied on classroom strategies. Several participants indicated that they and their students lacked the time, resources or interest to pursue program community and that geographical distance and university reward policies complicated its establishment. Differences via discipline, gender and years of online teaching experience were also reported. [ABSTRACT FROM AUTHOR]

The objective was to evaluate a novel intervention that integrates a psychological, values-based approach with coordinated care management. This paper describes an integrated comprehensive health record system to enhance engagement with a subset of those with complex needs; those who are high-needs, high-cost (HNHC). Patients are selected after conducting data analysis on the most costly and complex patients of a payer system that works with HNHC patients. Specifically, the Patient Care Intervention Center in Houston TX, applies the values-based intervention to HNHC patients. This pilot study reports data from 18 HNHC patients over 6 months; specifically, outcomes related to daily functioning, depression, working alliance, stages of change, and overall well-being. Additionally, this paper reports preliminary findings from qualitative monitoring of provider experiences implementing the values-based approach and integrated evaluation. HNHC patients improved their daily functioning over 4 months but no other significant changes were found over time. Patients self-reported mild depression, strong working alliances with their provider, being in the contemplation phase of change, and moderate well-being. There also was variation when patients completed the assessments and data points were collected. Although this is a small sample and short time frame, preliminary results suggest that the intervention has a positive impact on HNHC patient daily functioning. Provider accounts of the implementation describe using the evaluation items to inform their interactions with patients, and also suggest that patient literacy level impacts when data can be collected. Other changes to the approach are suggested.

Germline SAMD9 and SAMD9L mutations cause a spectrum of multisystem disorders that carry a markedly increased risk of developing myeloid malignancies with somatic monosomy 7. Here, we describe 16 siblings, the majority of which were phenotypically normal, from 5 families diagnosed with myelodysplasia and leukemia syndrome with monosomy 7 (MLSM7; OMIM 252270) who primarily had onset of hematologic abnormalities during the first decade of life. Molecular analyses uncovered germline SAMD9L (n = 4) or SAMD9 (n = 1) mutations in these families. Affected individuals had a highly variable clinical course that ranged from mild and transient dyspoietic changes in the bone marrow to a rapid progression of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with monosomy 7. Expression of these gain-of-function SAMD9 and SAMD9L mutations reduces cell cycle progression, and deep sequencing demonstrated selective pressure favoring the outgrowth of clones that have either lost the mutant allele or acquired revertant mutations. The myeloid malignancies of affected siblings acquired cooperating mutations in genes that are also altered in sporadic cases of AML characterized by monosomy 7. These data have implications for understanding how SAMD9 and SAMD9L mutations contribute to myeloid transformation and for recognizing, counseling, and treating affected families.

Myelodysplastic syndromes (MDS) are uncommon in children and have a poor prognosis. In contrast to adult MDS, little is known about the genomic landscape of pediatric MDS. Here, we describe the somatic and germline changes of pediatric MDS using whole exome sequencing, targeted amplicon sequencing, and/or RNA-sequencing of 46 pediatric primary MDS patients. Our data show that, in contrast to adult MDS, Ras/MAPK pathway mutations are common in pediatric MDS (45% of primary cohort), while mutations in RNA splicing genes are rare (2% of primary cohort). Surprisingly, germline variants in SAMD9 or SAMD9L were present in 17% of primary MDS patients, and these variants were routinely lost in the tumor cells by chromosomal deletions (e.g., monosomy 7) or copy number neutral loss of heterozygosity (CN-LOH). Our data confirm that adult and pediatric MDS are separate diseases with disparate mechanisms, and that SAMD9/SAMD9L mutations represent a new class of MDS predisposition., Myelodysplastic syndromes (MDS) are uncommon in children and have poor prognosis. Here, the authors interrogate the genomic landscape of MDS, confirming adult and paediatric MDS are separate diseases with disparate mechanisms, and highlighting that SAMD9/SAMD9L mutations represent a new class of MDS predisposition.

Esophageal atresia (EA) is an uncommon congenital anomaly which is often associated with a tracheoesophageal fistula. An isolated EA is a rarer anomaly and its diagnosis has implications for the ongoing treatment and outcome of the infant. For the first time, we report a case of a premature newborn with a pure EA and a tracheal diverticulum, containing both respiratory and esophageal mucosa. We have termed this an aborted trachea-esophageal fistula. Recognition of these very rare variations of foregut anomalies may contribute to our understanding of their pathogenesis.

This study examined (a) the associations between family hostility (husband-wife marital hostility and child hostility) and middle-aged husbands' and wives' depressive symptoms over an 11-year time period and (b) the moderating influence of couples' marital integration on these associations as measured by their joint activity. Higher order family-level latent constructs captured chronic husband-wife (marital) hostility using husbands' and wives' reports of chronic hostile interactions from 1990 to 1992, while a higher order latent construct of chronic child hostility toward parents was measured using parental reports of children's hostile behaviors from 1990 to 1992. Structural equation modeling with data from 370 families depicted the longitudinal impact of family hostility on depressive symptoms of both husbands and wives in 2001 after accounting for earlier levels of depressive symptoms in 1991. Separate models were fit for couples with high and low levels of marital integration. For couples who experienced low levels of marital integration, chronic marital hostility and child hostility were related to depressive symptoms in husbands and wives. However, for those with high marital integration, these influences were largely diminished. (PsycINFO Database Record

Germline SAMD9L mutation is a recently recognized cause of constitutional bone marrow failure with a unique propensity for clonal evolution to myelodysplastic syndrome (MDS) with monosomy 7. It is now known that a clinical syndrome originally described in the 1970s as Ataxia-Pancytopenia Syndrome is caused by missense mutation in SAMD9L, and subsequent case series have demonstrated diverse clinical outcomes in patients with germline SAMD9L mutations. SAMD9L is located on chromosome 7, and gain-of-function mutations in SAMD9L is thought to decrease cell proliferation by inhibiting the normal cell cycle. In patients with SAMD9L mutations, the development of a monosomy 7 clone then rescues the inhibitory effect of mutant SAMD9L but can result in progression to acute leukemia. Interestingly, there are also reports of transient monosomy 7 due to uniparental disomy occurring in the monosomy 7 clone resulting in normal hematopoiesis. We describe the case of a male patient who presented at age 8-months of age with fever, hypotension, and pancytopenia. Bone marrow biopsy was hypocellular with debris-laden histiocytes. Diagnostic evaluation included normal chromosome stability testing (DEB and MMC), normal telomere length testing, and normal gene panels for inherited bone marrow failure and primary HLH. Patient, then, had spontaneous count recovery on day 41 of illness with progressive improvement becoming transfusion independent without any further infections. Repeat bone marrow biopsy 1 month after count recovery demonstrated dysplasia and cytogenetic evaluation revealed monosomy 7 in 11 out of 20 metaphases. Whole exome sequencing demonstrated a novel mutation in SAMD9L. Parents were analyzed for the SAMD9L mutation which were negative. Repeat bone marrow evaluation at 4, 7, and 10 months after presentation continued to demonstrate dysplasia and monosomy 7. After 12 months of observation, decision was made to perform a bone marrow transplant but the patient died from diffuse alveolar hemorrhage shortly after engraftment. EdU incorporation assay showed that 293T cells expressing SAMD9L V1551L mutation exhibit a cell cycle arrest phenotype as shown by the lack of cells in S phase compared to cells expressing the normal SAMD9L protein or empty vector. Furthermore, Digital droplet PCR (ddPCR) with wild type- and mutation-specific primers was used to quantify the percent of mutant allele in the patients' fibroblasts, whole blood, granulocytes, lymphocytes and lymphocyte cell cultures over 12 weeks. The patient's whole blood DNA had a low fraction of the mutation (26.8%), supporting the cytogenetic finding of mosaic monosomy 7. Interestingly, lymphocyte cell line generated from the patient's blood showed a higher fraction of mutation in about 40-45% similar to what is seen in fibroblasts which suggests that the patient's monosomy 7 clone which rescued the neutrophil count seems to preferentially contribute to the myeloid lineage versus the lymphocyte lineage. We have further developed induced pluripotent stem cells from this patient to further explore this question. In summary, our case describes a novel SAMD9L heterozygous missense mutation (p.Val1551Leu) resulting in gain-of-function mutation which inhibits cellular proliferation resulting in bone marrow failure. This case highlights the new insights offered through the use of whole exome sequencing and also the difficulty of making the clinical decision to treat with bone marrow transplant in the setting of multiple reports of disease remission via self-correction. If we are able to identify the clone giving rise to mature cells and quantify it over time, we may be able to provide a more informed recommendation regarding bone marrow transplant versus observation. Disclosures No relevant conflicts of interest to declare.

The purpose of this study was to define the mutations causing familial monosomy 7 with myelodysplastic syndrome (MDS) and/or acute myeloid leukemia (AML). We have previously reported frequent germline mutations in the genes SAMD9 and SAMD9L in pediatric MDS. We obtained samples on 32 individuals in 7 families with multiple siblings affected with MDS/AML and monosomy 7. We conducted targeted sequencing of genes frequently mutated in MDS/AML and amplicon sequencing of SAMD9 and SAMD9L. We performed cell cycle analysis assays on SAMD9/9L mutations to study their effects on cell proliferation. Our data show that 5 of the 7 families have germline pathologic mutations in SAMD9 (n=1) and SAMD9L (n=4), with significant clinical variability in the phenotypes displayed, ranging from transient monosomy 7 to overt AML with monosomy 7. Consistent with previous data, the mutant SAMD9 or SAMD9L allele was underrepresented in the bone marrow. This decrease in the mutant allele paralleled the extent of monosomy 7, suggesting that only the wild-type allele was retained in cells with monosomy 7. Functional analysis revealed that all germline SAMD9/9L mutations displayed a gain-of-function ability to suppress cell cycle progression. The patients with more aggressive disease were found to harbor somatic mutations in SETBP1, ETV6 or RUNX1. In many individuals we found additional somatic revertant mutations in cis with the germline mutation, which overcame the growth-suppressive effects of the germline mutation. Our data show that germline mutations in SAMD9/9L represent a new class of predisposition genes for familial monosomy 7 with MDS/AML and should be screened for in all children with MDS. Citation Format: Victoria Bryant, Jasmine Wong, Jason Schwartz, Tamara Lamprecht, Jing Ma, Charles Mullighan, Mignon Loh, Kevin Shannon, Jeffery Klco. SAMD9/SAMD9L mutations in familial monosomy 7 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2063.

Today many significant scientific discoveries are achieved through complex and distributed scientific computations that are structured and represented as scientific workflows. Although atomicity is a well studied topic in transaction processing and business workflows, such an important capability needs to be revisited in a scientific workflow environment. Firstly, the semantics of atomicity needs to be defined in a dataflow-oriented scientific workflow model, particularly for pipelined execution of hierarchical scientific workflows. Secondly, in a scientific workflow environment, atomic regions are specified or inferred dynamically as needed and are committed implicitly, which are in contrast to a priori well-defined transaction boundaries and explicit commits in transaction processing and business workflows. Finally, although atomicity and provenance are related to each other, their interactions and relationships have never been explored in the literature. In this paper, we propose: (i) an architecture for scientific workflow management systems that supports both provenance and atomicity; (ii) a dataflow-oriented atomicity model that supports the notions of commit and abort; and (iii) a dataflow-oriented provenance model that supports querying and visualizing provenance.

The majority of constitutional reciprocal translocations appear to be unique rearrangements arising from independent events. However, a small number of translocations are recurrent, most significantly the t(11;22)(q23;q11). Among large series of translocations there may be multiple independently ascertained cases with the same cytogenetic breakpoints. Some of these could represent additional recurrent rearrangements, alternatively they could be identical by descent (IBD) or have subtly different breakpoints when examined under higher resolution. We have used molecular breakpoint mapping and haplotyping to determine the origin of three pairs of reciprocal constitutional translocations, each with the same cytogenetic breakpoints. FISH mapping showed one pair to have different breakpoints and thus to be distinct rearrangements. Another pair of translocations were IBD with identical breakpoint intervals and highly conserved haplotypes on the derived chromosomes. The third pair, t(4;11)(p16.2;p15.4), had the same breakpoint intervals by aCGH and fosmid mapping but had very different haplotypes, therefore they represent a novel recurrent translocation. Unlike the t(11;22)(q23;q11), the formation of the t(4;11)(p16.2;p15.4) may have involved segmental duplications and sequence homology at the breakpoints. Additional examples of recurrent translocations could be identified if the resources were available to study more translocations using the approaches described here. However, like the t(4;11)(p16.2;p15.4), such translocations are likely to be rare with the t(11;22) remaining the only common recurrent constitutional reciprocal translocation.

Human chromosome 2 contains large blocks of segmental duplications (SDs), both within and between proximal 2p and proximal 2q, and these may contribute to the frequency of the common variant inversion inv(2)(p11.2q13). Despite their being cytogenetically homogeneous, we have identified four different breakpoint combinations by fluorescence in situ hybridization mapping of 40 cases of inv(2)(p11.2q13) of European origin. For the vast majority of inversions (35/40), the breakpoints fell within the same spanning BACs, which hybridized to both 2p11.2 and 2q13 on the normal and inverted homologues. Sequence analysis revealed that these BACs contain a significant proportion of intrachromosomal SDs with sequence homology to the reciprocal breakpoint region. In contrast, BACs spanning the rare breakpoint combinations contain fewer SDs and with sequence homology only to the same chromosome arm. Using haplotype analysis, we identified a number of related family subgroups with identical or very closely related haplotypes. However, the majority of cases were not related, demonstrating for the first time that the inv(2)(p11.2q13) is a truly recurrent rearrangement. Therefore, there are three explanations to account for the frequent observation of the inv(2)(p11.2q13): the majority have arisen independently in different ancestors, while a minority either have been transmitted from a common founder or have different breakpoints at the molecular cytogenetic level. Udgivelsesdato: 2007-Oct

Review of: "With Malice toward Some: Treason and Loyalty in the Civil War Era," by William A. Blair.

A significant proportion of both pericentric and paracentric inversions have recurrent breakpoints and so could either have arisen through multiple independent events or be identical by descent (IBD) with a single common ancestor. Of two common variant inversions previously studied, the inv(2)(p11q13) was genuinely recurrent while the inv(10)(p11.2q21.2) was IBD in all cases tested. Excluding these two variants we have ascertained 257 autosomal inversion probands at the Wessex Regional Genetics Laboratory. There were 104 apparently recurrent inversions, representing 35 different breakpoint combinations and we speculated that at least some of these had arisen on more than one occasion. However, haplotype analysis identified no recurrent cases among eight inversions tested, including the variant inv(5)(p13q13). The cases not IBD were shown to have different breakpoints at the molecular cytogenetic level. No crossing over was detected within any of the inversions and the founder haplotypes extended for variable distances beyond the inversion breakpoints. Defining breakpoint intervals by FISH mapping identified no obvious predisposing elements in the DNA sequence. In summary the vast majority of human inversions arise as unique events. Even apparently recurrent inversions, with the exception of the inv(2)(p12q13), are likely to be either derived from a common ancestor or to have subtly different breakpoints. Presumably the lack of selection against most inversions allows them to accumulate and disperse amongst different populations over time.

Several clinical studies have shown a correlation between elevated c-Myc levels and a better response to chemotherapy. Although elevated c-Myc might indirectly cause such chemosensitivity, it is possible that a direct effect is occurring due to underlying molecular mechanisms. The purpose of the current study was to determine whether c-Myc overexpression could acutely cause chemosensitivity. The c-Myc protein is known to activate DNA replication origins, but the mechanism for this is unknown. Origins are regulated by the loading of MCM2-7 hexamers, which form the core of the helicase that starts the initiation of replication. Mammalian cells load more MCM complexes than are necessary to complete one round of replication. The excess MCM complexes function as backups to allow recovery of replication when forks stall during drug treatment. Consistent with this, we found that loss of Mcm4 or Mcm7 sensitizes PDAC cell lines to 5-FU and Gemcitabine, two S phase stress drugs that are used to treat PDAC patients but are not highly effective on their own. Similar to depletion of backup MCM complexes via loss of Mcm4 or Mcm7, elevated c-Myc expression over-activates backup MCMs, leaving fewer available to recover from drug treatment. Cells containing overexpressed c-Myc display increased chemosensitivity to Gemcitabine that is not seen in cells containing normal c-Myc levels or a non-functional c-Myc mutant. These results demonstrate that reduction in backup MCM complexes, either by direct downregulation or by oncogene driven over-activation (via c-Myc), render cells sensitive to chemotherapy drugs. These results suggest that development of drugs that target MCM functionality may be useful in combination with S-phase stress drugs currently used in the clinic. These results also demonstrate that c-Myc has the ability to acutely cause chemosensitivity and c-Myc elevated tumors may respond better to chemotherapy due to the c-Myc effects on MCM complexes. Citation Format: Victoria Bryant, Mark G. Alexandrow. The c-Myc oncogene over-activates dormant replication origins and sensitizes cancer cells to chemotherapy drugs. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3519. doi:10.1158/1538-7445.AM2014-3519

Analyses of primary infections of Nematospiroides dubius in male and female laboratory mice show that on days 4–6 post-infection worms occupy up to 50% of the small intestine but as the age of the infection increases worm populations are highly aggregated in relation to the anterior sections of the small intestine. Individual worms are also shown to be aggregated with respect to each other. Between days 42 and 60 postinfection, although the pattern of distribution of N. dubius along the small intestine does not significantly change, survival of worms is influenced by both age and sex of ASH/CSI S.P.F. mice, reasons for which are discussed in the light of previous work on primary infections of N. dubius in other strains of laboratory mice

The growth of the three free-living stages ofN. dubiuswas measured in terms of dry and fresh weight. Changes in body water content during moulting were demonstrated by variations in dry weight when expressed as a percentage of fresh weight. The respiration rate of the larvae increased until they became infective, after which time it decreased until five days later no oxygen consumption could be recorded. The inability of all larval stages to withstand anaerobic conditions indicated that their metabolism was essentially aerobic. The relationship between body size and metabolic rate was established for each stage and its significance in relation to the life-cycle discussed.

The growth of male and female parasitic stages ofNematospiroides dubiusfrom male and female ASH/CS1 mice was measured in terms of dry weight. No sex-linked resistance of mice to infection withN. dubiuswas apparent, as growth was the same in both sexes of host. The growth rate did not alter when moulting occurred.All parasitic stages ofN. dubiusconsumed oxygenin vitroand oxygen was also shown to be necessary for motility and survival.The relationship between body size and metabolic rate was established for male and female parasiticN. dubiusand thebvalues indicated that aerobic metabolism is of functional importance to this species.The size/metabolism relationship for the whole life-cycle was established.

1. The number and duration of free-living and parasitic stages of N. dubius has been determined.2. The results have been discussed in relation to previous accounts of the life cycle, and some of the discrepancies explained.