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Online education, also referred to as distance education, has been on a steady rise for over a decade, and California community colleges offer more online courses than any other public higher education institution. Although the success gap, as measured by course completion, between online and face-to-face learning is closing overall, online courses, specifically in California community colleges, continue to have lower success rates than the traditional in-person classes; furthermore, this disparity is exacerbated for students of color. One aspect that has been researched in this instructional modality has been the impact of social presence, or “the degree to which online participants feel connected to one another” (Whiteside, 2017, p. 4) in online courses. In addition, research specifically focused on community college students of color highlights the relational domain of teaching and learning as the foundation for success (Wood & Harris, 2015). This qualitative study sought to understand and amplify the experiences of students of color in online courses. This study utilized a dual-lens conceptual framework, which merged the Social Presence Model (Whiteside, 2015) with the Pyramid of Student Success for Men of Color in the Community Colleges (Wood and Harris, 2015). Together, they provided complementary lenses to examine how students of color experienced social presence in online courses, and how such experience related to their perceptions of feeling connected to the learning community and supported towards success in their online learning.Eleven study participants were interviewed in one-on-one semi-structured Zoom interviews. Thematic analysis revealed five main themes, including the magic of human connection, the importance of a warm welcome, the value of student-to-student interaction, the significance of instructor presence, and the clarity of content presentations. The findings give a window into the experiences of students of color in online courses, and

The inconsistent roll-out of New York State’s Culturally Responsive Sustaining Education (CRSE) Framework left principals in a Bronx district with insufficient capacity to fully leverage the framework. Taking an Improvement Science approach, the aim of this mixed methods case study research was to deepen the racial literacy and cultural competence of principals in service of implementing shared and inclusive curricula aligned with the Framework. The study used three change ideas implemented in a single six-month Plan-Do-Study-Act cycle: 1) building healthy racial identities through conversations about race, 2) building cultural competence through culturally responsive lessons, and 3) implementing district professional learning on Culturally Responsive School Leadership (CRSL). The study addressed the lack of instrumentation to measure racial literacy and cultural competence by creating two innovative instruments, available for other scholars, using evidence-based frameworks in the research literature: the CRSE Self-Reflection Survey and the Cultural Competence and Racial Literacy Reflection Survey. The study found that a collectivist approach to building the racial literacy of school leaders increased principals’ critical self-awareness and fostered the use of common language to engage in difficult conversations about race. Designing opportunities for leaders to authentically connect to the community deepened their understanding of how school policies must serve as a catalyst to affirm the identities of students and their families. Using teams as a shared site of learning, providing opportunities to critically self-reflect, and providing job-embedded support empowered principals to immerse themselves in the vision of the Framework. The researcher advocates that equity is integral, not optional.

This study examined whether living in a Medicaid-expanded state or having health insurance was associated with receipt of smoking cessation services or smoking behaviors among substance use disorder (SUD) treatment clients. In 2015 and 2016, 1702 SUD clients in 14 states were surveyed for health insurance status, smoking cessation services received in their treatment program, and smoking behaviors. Services and behaviors were then compared by state Medicaid expansion and health insurance status independently. Clients in Medicaid-expanded states were more likely to be insured (89.9% vs. 54.4%, p < 0.001) and to have quit smoking during treatment (AOR = 3.77, 95% CI = 2.47, 5.76). Insured clients had higher odds of being screened for smoking status in their treatment program and making quit attempts in the past year. Medicaid expansion supports greater health insurance coverage of individuals in SUD treatment and may enhance smoking cessation.

Smoke-free laws and policies have contributed significantly to the decline in smoking in the U.S, but are not often applied in high-prevalence smoking populations where they are most needed. Smoking among clients in publicly funded substance use disorder (SUD) treatment is 3-4 times higher than the general population, and little is known about tobacco policies programs have adopted. To identify the prevalence of tobacco-free grounds and other smoking policies in California's publicly funded, adult, residential SUD programs. Using a California DHCS contact list of 1,921 publicly funded, non-medical, SUD programs, 362 were eligible to participate in a brief semi-structured phone survey concerning indoor and outdoor smoking for staff and clients and other tobacco policies. Of 259 programs that completed the survey, 28 (10.8%) reported tobacco-free grounds. 91 (35.1%) expressed interest in implementing tobacco-free policies and 23 have plans to do so. Nearly all programs (n = 253, 97.7%) had some policy restricting e-cigarette use, and 110 (43.5%) of these reported a complete ban on e-cigarette use. 124 (47.9%) had policies prohibiting staff and clients smoking together. Most California residential SUD programs allow outdoor smoking for staff and clients and few have adopted tobacco-free grounds policies. Given the reported interest in adopting tobacco-free policies, the high density of smokers in the SUD population, and the association of tobacco-free policies with lower client and staff smoking rates, state licensing and regulatory agencies, as well as county health departments, should work with SUD programs to adopt tobacco-free policies.

This study aimed to genetically and clinically characterize a unique cohort of 25 individuals from 21 unrelated families with autosomal recessive nanophthalmos (NNO) and posterior microphthalmia (MCOP) from different ethnicities. An ophthalmological assessment in all families was followed by targeted MFRP and PRSS56 testing in 20 families and whole-genome sequencing in one family. Three families underwent homozygosity mapping using SNP arrays. Eight distinct MFRP mutations were found in 10/21 families (47.6%), five of which are novel including a deletion spanning the 5' untranslated region and the first coding part of exon 1. Most cases harbored homozygous mutations (8/10), while a compound heterozygous and a monoallelic genotype were identified in the remaining ones (2/10). Six distinct PRSS56 mutations were found in 9/21 (42.9%) families, three of which are novel. Similarly, homozygous mutations were found in all but one, leaving 2/21 families (9.5%) without a molecular diagnosis. Clinically, all patients had reduced visual acuity, hyperopia, short axial length and crowded optic discs. Retinitis pigmentosa was observed in 5/10 (50%) of the MFRP group, papillomacular folds in 12/19 (63.2%) of MCOP and in 3/6 (50%) of NNO cases. A considerable phenotypic variability was observed, with no clear genotype-phenotype correlations. Overall, our study represents the largest NNO and MCOP cohort reported to date and provides a genetic diagnosis in 19/21 families (90.5%), including the first MFRP genomic rearrangement, offering opportunities for gene-based therapies in MFRP-associated disease. Finally, our study underscores the importance of sequence and copy number analysis of the MFRP and PRSS56 genes in MCOP and NNO.

ObjectiveSpecialty addiction programs treat people who are addicted to alcohol, opioids, stimulants, and other drugs. This study identified the proportion of addiction program clients who received tobacco-related services and factors associated with receipt of such services.MethodsIn 2015 and 2016, clients (N=2,119) in 24 programs were surveyed for receipt of services aligning with three of the five As of tobacco cessation: ask, advise, assist. Multivariate analyses examined factors associated with receipt of each service.ResultsMost clients (76%) were asked about smoking. Among smokers (N=1,630), 53% were advised to quit, 41% received counseling, 26% received cessation medication, and 17% received counseling and medication. Clients were more likely to receive tobacco-related services if they wanted help quitting smoking or were enrolled in programs with tobacco-free grounds.ConclusionsThese correlational findings suggest that increasing client motivation to quit and implementing tobacco-free policies on the grounds of treatment centers may increase tobacco-related services in addiction treatment.

Smoking rates are high among low-income populations who seek care in safety-net clinics. While most safety-net clinics screen for cigarette smoking, there are substantial disparities in the delivery of smoking cessation counseling in these systems. We conducted a mixed method study between July 2016 and April 2017 to examine receipt of smoking cessation counseling and estimate recent cessation attempts among primary care patients in four safety-net clinics in San Francisco. We used the electronic health record (EHR) to examine receipt of cessation services and estimate cessation attempts, defined as transition from current to former smoking status during the 9-month study period. We conducted interviews with 10 staff and 16 patients to assess barriers to and facilitators of providing cessation services. Of the 3301 smokers identified via EHR, the majority (95.6%) received some type of cessation counseling during at least one clinical encounter, and 17.6% made a recent cessation attempt. Recent smoking cessation attempts and receipt of smoking cessation services differed significantly by clinic after adjusting for demographic factors. We identified patient and staff-level pre-disposing, reinforcing and enabling factors to increase delivery of cessation care, including increasing access to cessation medications and higher intensity counseling using a team-based approach. The EHR presents a useful tool to monitor patients' recent cessation attempts and access to cessation care. Combining EHR data with qualitative methods can help guide and streamline interventions to improve quality of cessation care and promote quit attempts among patients in safety-net settings.

BACKGROUND:This study examined the impact of a tobacco-free grounds (TFG) policy and the California $2.00/pack tobacco tax increase on tobacco use among individuals in residential substance use disorder (SUD) treatment. METHODS:We conducted three cross-sectional surveys of clients enrolled in three residential SUD treatment programs. Wave 1 (Pre-TFG) included 190 clients, wave 2 (post-TFG and pre-tax increase) included 200 clients, and wave 3 (post-tax increase) included 201 clients. Demographic and tobacco-use characteristics were first compared between waves using bivariate comparisons. Regression models were used to compare each outcome with survey wave as the predictor, while adjusting for demographic characteristics and nesting of participants within programs. RESULTS:Odds of clients being current smokers was lower (AOR = 0.43, 95%CI = 0.30,0.60) after implementation of TFG compared to baseline. Adjusted mean ratio (AMR) for cigarettes per day was lower post-TFG compared to baseline (AMR = 0.70, CI = 0.59, 0.83). There were no differences, across waves, in tobacco-related knowledge, attitudes, or services received by program clients, or use of nicotine replacement therapy. Increased cigarette taxation was not associated with reductions in client smoking. CONCLUSION:Implementation of a TFG policy was associated with a lower prevalence of client smoking among individuals in residential SUD treatment. Increased state cigarette excise taxes were not associated with a further reduction in client smoking in the presence of TFG policies, though this may have been confounded by relaxing of the TFG policy. SUD treatment programs should promote TFG policies and increase tobacco cessation services for clients.

Purpose: Most classical aniridia is caused by PAX6 haploinsufficiency. PAX6 missense variants can be hypomorphic or mimic haploinsufficiency. We hypothesized that missense variants also cause previously undescribed disease by altering the affinity and/or specificity of PAX6 genomic interactions. Methods: We screened PAX6 in 372 individuals with bilateral microphthalmia, anophthalmia, or coloboma (MAC) from the Medical Research Council Human Genetics Unit eye malformation cohort (HGUeye) and reviewed data from the Deciphering Developmental Disorders study. We performed cluster analysis on PAX6-associated ocular phenotypes by variant type and molecular modeling of the structural impact of 86 different PAX6 causative missense variants. Results: Eight different PAX6 missense variants were identified in 17 individuals (15 families) with MAC, accounting for 4% (15/372) of our cohort. Seven altered the paired domain (p.[Arg26Gln]x1, p.[Gly36Val]x1, p.[Arg38Trp]x2, p.[Arg38Gln]x1, p.[Gly51Arg]x2, p.[Ser54Arg]x2, p.[Asn124Lys]x5) and one the homeodomain (p.[Asn260Tyr]x1). p.Ser54Arg and p.Asn124Lys were exclusively associated with severe bilateral microphthalmia. MAC-associated variants were predicted to alter but not ablate DNA interaction, consistent with the electrophoretic mobility shifts observed using mutant paired domains with well-characterized PAX6-binding sites. We found no strong evidence for novel PAX6-associated extraocular disease. Conclusion: Altering the affinity and specificity of PAX6-binding genome-wide provides a plausible mechanism for the worse-than-null effects of MAC-associated missense variants., SCOPUS: ar.j, info:eu-repo/semantics/published

There are higher rates of menthol cigarette smoking within certain population subgroups. Limited research has examined menthol use among individuals in treatment for substance use disorders (SUD), a population with a high prevalence of cigarette smoking, poor smoking cessation outcomes, and high tobacco disease burden. Survey data were collected from 863 smokers sampled from 24 SUD treatment programs affiliated with the NIDA Clinical Trials Network (CTN) in the United States. Prevalence of menthol cigarette smoking was examined for the sample. Bivariate and multivariate analyses were used to examine demographic and tobacco use characteristics associated with menthol cigarette smoking. Overall, the prevalence of menthol smoking among individuals in SUD treatment was 53.3%. Smoking menthol versus non-menthol cigarettes was associated with being female (AOR=1.61, p=0.003), African American (AOR=7.89, p<0.001), Hispanic/Latino (AOR=3.39, p<0.001), and lower odds of having a college degree (AOR=0.49, p=0.015). Controlling for demographic factors, menthol smokers were more likely to report marijuana (AOR=3.33, p<0.007) as their primary drug compared to alcohol. Lastly, menthol smokers were more likely to report interest in getting help for quitting smoking (AOR=1.53, p=0.01), although they were not more likely to report making a past year quit attempt. In conclusion, use of menthol cigarettes was higher among smokers in SUD treatment than in general population smokers. Regulatory policies targeting the manufacture, marketing, or sale of menthol cigarettes may benefit vulnerable populations, including smokers in SUD treatment.

BackgroundDisparities in tobacco use prevalence, behaviors, and services have been identified among people of different racial and ethnic groups in the United States general population. Persons in addiction treatment have among the highest smoking prevalence of any population. However, little is known about racial and ethnic disparities in tobacco use prevalence, behaviors, and services among persons in addiction treatment.MethodsSurvey data were used from 1840 clients from 24 addiction treatment programs from the NIDA Clinical Trials Network. Multivariate regression analyses were conducted to assess associations between race/ethnicity (White, African American, Hispanic) and patterns of tobacco and other tobacco product use, as well as quitting behaviors and receipt of tobacco cessation services among current smokers (n = 1425) while in treatment.ResultsThere was no difference in cigarette smoking prevalence across racial/ethnic groups. In the multivariate models, Hispanics and African Americans, compared to Whites, were less likely to be daily smokers, use smokeless tobacco, or use e-cigarettes. African Americans and Hispanics reported more past-year quit attempts and higher use of menthol compared to Whites. Hispanics were more interested in quitting while in treatment than Whites. Contrary to expectations, African Americans reported receiving more tobacco cessation advice and services while in treatment than Whites.ConclusionsSome findings reflected broader population patterns (e.g., tobacco use behaviors, other tobacco product use), while others did not (e.g., no difference in tobacco use prevalence by race/ethnicity). The reasons for greater receipt of cessation services among African Americans are unclear. Findings indicate the need for continued engagement of African Americans and Hispanics in cessation services while in addiction treatment, and for addressing heavier tobacco use and lack of interest in cessation during treatment among White clients.

Bosma arhinia microphthalmia syndrome (BAMS) is an extremely rare and striking condition characterized by complete absence of the nose with or without ocular defects. We report here that missense mutations in the epigenetic regulator SMCHD1 mapping to the extended ATPase domain of the encoded protein cause BAMS in all 14 cases studied. All mutations were de novo where parental DNA was available. Biochemical tests and in vivo assays in Xenopus laevis embryos suggest that these mutations may behave as gain-of-function alleles. This finding is in contrast to the loss-of-function mutations in SMCHD1 that have been associated with facioscapulohumeral muscular dystrophy (FSHD) type 2. Our results establish SMCHD1 as a key player in nasal development and provide biochemical insight into its enzymatic function that may be exploited for development of therapeutics for FSHD.

We developed a variant database for diabetes syndrome genes, using the Leiden Open Variation Database platform, containing observed phenotypes matched to the genetic variations. We populated it with 628 published disease-associated variants (December 2016) for: WFS1 (n = 309), CISD2 (n = 3), ALMS1 (n = 268), and SLC19A2 (n = 48) for Wolfram type 1, Wolfram type 2, Alström, and Thiamine-responsive megaloblastic anemia syndromes, respectively; and included 23 previously unpublished novel germline variants in WFS1 and 17 variants in ALMS1. We then investigated genotype-phenotype relations for the WFS1 gene. The presence of biallelic loss-of-function variants predicted Wolfram syndrome defined by insulin-dependent diabetes and optic atrophy, with a sensitivity of 79% (95% CI 75%-83%) and specificity of 92% (83%-97%). The presence of minor loss-of-function variants in WFS1 predicted isolated diabetes, isolated deafness, or isolated congenital cataracts without development of the full syndrome (sensitivity 100% [93%-100%]; specificity 78% [73%-82%]). The ability to provide a prognostic prediction based on genotype will lead to improvements in patient care and counseling. The development of the database as a repository for monogenic diabetes gene variants will allow prognostic predictions for other diabetes syndromes as next-generation sequencing expands the repertoire of genotypes and phenotypes. The database is publicly available online at https://lovd.euro-wabb.org.

Children and adolescents with pre-existing conditions such as DNA repair defects or other primary immunodeficiencies have an increased risk of non-Hodgkin lymphoma. However, large-scale data on patients with non-Hodgkin lymphoma and their entire spectrum of pre-existing conditions are scarce. A retrospective multinational study was conducted by means of questionnaires sent out to the national study groups or centers, by the two largest consortia in childhood non-Hodgkin lymphoma, the European Intergroup for Childhood non-Hodgkin Lymphoma, and the international Berlin-Frankfurt-Münster Study Group. The study identified 213 patients with non-Hodgkin lymphoma and a pre-existing condition. Four subcategories were established: a) cancer predisposition syndromes (n=124, 58%); b) primary immunodeficiencies not further specified (n=27, 13%); c) genetic diseases with no increased cancer risk (n=40, 19%); and d) non-classifiable conditions (n=22, 10%). Seventy-nine of 124 (64%) cancer predispositions were reported in groups with more than 20 patients: ataxia telangiectasia (n=32), Nijmegen breakage syndrome (n=26), constitutional mismatch repair deficiency (n=21). For the 151 patients with a known cancer risk, 5-year event-free survival and overall survival rates were 40%±4% and 51%±4%, respectively. Five-year cumulative incidences of progression/relapse and treatment-related death as a first event were 22%±4% and 24%±4%, respectively. Ten-year incidence of second malignancy was 24%±5% and 7-year overall survival of the 21 patients with a second malignancy was 41%±11%. Patients with non-Hodgkin lymphoma and pre-existing conditions have an inferior survival rate with a large proportion of therapy-related deaths compared to patients with non-Hodgkin lymphoma and no pre-existing conditions. They may require special vigilance when receiving standard or modified/reduced-intensity chemotherapy or when undergoing allogeneic stem cell transplantation.

Non-Hodgkin lymphoma is the fourth most common malignancy in children, has an even higher incidence in adolescents, and is primarily represented by only a few histologic subtypes. Dramatic progress has been achieved, with survival rates exceeding 80%, in large part because of a better understanding of the biology of the different subtypes and national and international collaborations. Most patients with Burkitt lymphoma and diffuse large B-cell lymphoma are cured with short intensive pulse chemotherapy containing cyclophosphamide, cytarabine, and high-dose methotrexate. The benefit of the addition of rituximab has not been established except in the case of primary mediastinal B-cell lymphoma. Lymphoblastic lymphoma is treated with intensive, semi-continuous, longer leukemia-derived protocols. Relapses in B-cell and lymphoblastic lymphomas are rare and infrequently curable, even with intensive approaches. Event-free survival rates of approximately 75% have been achieved in anaplastic large-cell lymphomas with various regimens that generally include a short intensive B-like regimen. Immunity seems to play an important role in prognosis and needs further exploration to determine its therapeutic application. ALK inhibitor therapeutic approaches are currently under investigation. For all pediatric lymphomas, the intensity of induction/consolidation therapy correlates with acute toxicities, but because of low cumulative doses of anthracyclines and alkylating agents, minimal or no long-term toxicity is expected. Challenges that remain include defining the value of prognostic factors, such as early response on positron emission tomography/computed tomography and minimal disseminated and residual disease, using new biologic technologies to improve risk stratification, and developing innovative therapies, both in the first-line setting and for relapse.

Purpose: To improve the quality of life of military family caregivers to help manage stress and cope better. Design: Feasibility study using RE-AIM framework and mixed methods to adapt the evidence-based Stress-Busting Program to military context. Methods: Program content adapted to military context; 9-session intervention provided in small groups with two facilitators. Data collected at baseline, exit, and 2 months post-intervention, with interviews at one year post-intervention. Sample: Procedure: contact as many possible family caregivers of wounded warriors, self-identified as needing assistance with coping. Mostly female, White, and Hispanic spouses, 98 enrolled, 82 completed the intervention, 62 completed the full data collection. Analysis: Longitudinal cohort design using repeated measures. Because average scores of groups were not appropriate for analysis due to large variability of individual differences, each person served as own control; individual changes from baseline to post-intervention provided basis for assessment. Qualitative descriptive analysis of data collected on questionnaires, interviews, and facilitator notes. Findings: Caregivers reported study to be very effective; they acquired skills to change their behaviors, thinking, and family interactions, thereby improving their quality of life. It gave them permission to care for themselves; they shared these skills with their wounded warriors and family members. Caregivers had statistically significant decreases in perceived stress, depression, anxiety, and somatization; these findings were sustained two months post-intervention. A pattern of reduction in psychological symptoms was statistically significant at exit assessment and maintained at 2-month follow-up. Insomnia scores showed a statistically non-significant decline. Scores reflecting Spiritual Well-Being increased to statistical significance at 2-months.

In a phase 2 trial of panobinostat in 129 patients with relapsed or refractory Hodgkin lymphoma, exploratory analyses of chemokines and cytokines were prospectively performed in 109 patients to determine their association with clinical outcomes. Patients were categorized into two groups (reductions > median and reductions <= median) based on percentage change from baseline of log(10) transformed measurements. Thymus and activation-regulated chemokine (TARC) was most strongly associated with clinical outcome. Early reduction of TARC was observed in responding patients, with the greatest reduction at cycle 1, day 15 (C1D15). Of 93 patients with C1D15 samples, there were three complete and 25 partial responses. The group with TARC reductions > median at C1D15 had more responders (18 [39%] vs. 10 [21%]), longer progression-free survival (10.6 vs. 4.9 months), shorter time to response and longer overall survival than the group with reductions <= median. This study is registered at www. ClinicalTrials.gov, NCT00742027.

Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation (MCLMR) (MIM No.152950) is a rare autosomal dominant condition for which a causative gene has recently been identified. Mutations in the kinesin family member 11 (KIF11) gene have now been described in 16 families worldwide. This is a review of the condition based on the clinical features of 37 individuals from 22 families. This report includes nine previously unreported families and additional information for some of those reported previously. The condition arose de novo in 8/20 families (40%). The parental results were not available for two probands. The mutations were varied and include missense, nonsense, frameshift, and splice site and are distributed evenly throughout the KIF11 gene. In our cohort, 86% had microcephaly, 78% had an ocular abnormality consistent with the diagnosis, 46% had lymphoedema, 73% had mild-moderate learning difficulties, 8% had epilepsy, and 8% had a cardiac anomaly. We identified three individuals with KIF11 mutations but no clinical features of MCLMR demonstrating reduced penetrance. The variable expression of the phenotype and the presence of mildly affected individuals indicates that the prevalence may be higher than expected, and we would therefore recommend a low threshold for genetic testing.

Marinesco-Sjögren syndrome is a rare autosomal recessive multisystem disorder featuring cerebellar ataxia, early-onset cataracts, chronic myopathy, variable intellectual disability and delayed motor development. More recently, mutations in the SIL1 gene, which encodes an endoplasmic reticulum resident co-chaperone, were identified as the main cause of Marinesco-Sjögren syndrome. Here we describe the results of SIL1 mutation analysis in 62 patients presenting with early-onset ataxia, cataracts and myopathy or combinations of at least two of these. We obtained a mutation detection rate of 60% (15/25) among patients with the characteristic Marinesco-Sjögren syndrome triad (ataxia, cataracts, myopathy) whereas the detection rate in the group of patients with more variable phenotypic presentation was below 3% (1/37). We report 16 unrelated families with a total of 19 different SIL1 mutations. Among these mutations are 15 previously unreported changes, including single- and multi-exon deletions. Based on data from our screening cohort and data compiled from the literature we found that SIL1 mutations are invariably associated with the combination of a cerebellar syndrome and chronic myopathy. Cataracts were observed in all patients beyond the age of 7 years, but might be missing in infants. Six patients with SIL1 mutations had no intellectual disability, extending the known wide range of cognitive capabilities in Marinesco-Sjögren syndrome to include normal intelligence. Modestly constant features were somatic growth retardation, skeletal abnormalities and pyramidal tract signs. Examination of mutant SIL1 expression in cultured patient lymphoblasts suggested that SIL1 mutations result in severely reduced SIL1 protein levels irrespective of the type and position of mutations. Our data broaden the SIL1 mutation spectrum and confirm that SIL1 is the major Marinesco-Sjögren syndrome gene. SIL1 patients usually present with the characteristic triad but cataracts might be missi

The extent to which toxic leadership exists in the U.S. Army is a question that demands a thorough examination. While most publications on military leadership focus on the positive aspects of good leadership, this project examines the current literature on destructive leadership styles. The paper sought a definition of toxic leadership, consolidated expert views on the personal characteristics of toxic leaders, and compiled a taxonomy of 18 types of toxic leaders. The project serves as a review of toxic leadership in the U.S. Army. It derives insights into toxic leadership in the Army, why it exists, why it is tolerated, and what impact positive leadership may have on this phenomenon. The author discusses a number of personal characteristics that experts have attributed to toxic leaders, from least significant to most severe: incompetence, malfunctioning, maladjusted, sense of inadequacy, malcontent, irresponsible, amoral, cowardice, insatiable ambition, egotism, arrogance, selfish values, avarice and greed, lack of integrity, deception, malevolent, malicious, and malfeasance. The author then goes on to describe the 18 types of toxic leaders: the absentee leader, the incompetent leader, the codependent leader, the passive-aggressive leader, the busybody leader, the paranoid leader, the rigid leader, the controller leader, the compulsive leader, the intemperate leader, the enforcer leader, the narcissistic leader, the callous leader, the street fighter leader, the corrupt leader, the insular leader, the bully leader, and the evil leader.

This thesis evaluates the Acquisition Plans of two US Army Command, Control and Communications (C3) systems: Mobile Subscriber Equipment (MSE) and the Single Channel Ground and Airborne Radio System (SINCGARS), both of which are components of the Army Tactical Command and Control System (ATCCS). The study examines the defense acquisition process through the comparison of the Acquisition Plans and lessons learned for these two programs, and determines if there is an optimal strategy for the Army to use when acquiring tactical C3 systems. An analysis of the strengths and weaknesses of the two Acquisition Plans, and an evaluation of the similarities and differences of two programs, concludes that the MSE Acquisition Plan proved more successful than its SINCGARS counterparts because of its Non-Developmental Item approach. This study recommends maximum use of the NDI strategy for acquiring C3 systems whenever possible.

Congenital heart defects (CHDs) have a neonatal incidence of 0.8–1%. Despite abundant examples of monogenic CHD in humans and mice, CHD has a low absolute sibling recurrence risk (~2.7%), suggesting a considerable role for de novo mutations (DNMs) and/or incomplete penetrance. De novo protein-truncating variants (PTVs) have been shown to be enriched among the 10% of 'syndromic' patients with extra-cardiac manifestations. We exome sequenced 1,891 probands, including both syndromic CHD (S-CHD, n = 610) and nonsyndromic CHD (NS-CHD, n = 1,281). In S-CHD, we confirmed a significant enrichment of de novo PTVs but not inherited PTVs in known CHD-associated genes, consistent with recent findings. Conversely, in NS-CHD we observed significant enrichment of PTVs inherited from unaffected parents in CHD-associated genes. We identified three genome-wide significant S-CHD disorders caused by DNMs in CHD4, CDK13 and PRKD1. Our study finds evidence for distinct genetic architectures underlying the low sibling recurrence risk in S-CHD and NS-CHD.

This thesis evaluates the Acquisition Plans of two US Army Command, Control and Communications (C3) systems: Mobile Subscriber Equipment (MSE) and the Single Channel Ground and Airborne Radio System (SINCGARS), both of which are components of the Army Tactical Command and Control System (ATCCS). The study examines the defense acquisition process through the comparison of the Acquisition Plans and lessons learned for these two programs, and determines if there is an optimal strategy for the Army to use when acquiring tactical C3 systems. An analysis of the strengths and weaknesses of the two Acquisition Plans, and an evaluation of the similarities and differences of two programs, concludes that the MSE Acquisition Plan proved more successful than its SINCGARS counterparts because of its Non-Developmental Item approach. This study recommends maximum use of the NDI strategy for acquiring C3 systems whenever possible., http://archive.org/details/anevaluationndco1094530667, Captain, United States Army, Approved for public release; distribution is unlimited.

Congenital heart defects (CHDs) have a neonatal incidence of 0.8–1%. Despite abundant examples of monogenic CHD in humans and mice, CHD has a low absolute sibling recurrence risk (~2.7%), suggesting a considerable role for de novo mutations (DNMs) and/or incomplete penetrance. De novo protein-truncating variants (PTVs) have been shown to be enriched among the 10% of 'syndromic' patients with extra-cardiac manifestations. We exome sequenced 1,891 probands, including both syndromic CHD (S-CHD, n = 610) and nonsyndromic CHD (NS-CHD, n = 1,281). In S-CHD, we confirmed a significant enrichment of de novo PTVs but not inherited PTVs in known CHD-associated genes, consistent with recent findings. Conversely, in NS-CHD we observed significant enrichment of PTVs inherited from unaffected parents in CHD-associated genes. We identified three genome-wide significant S-CHD disorders caused by DNMs in CHD4, CDK13 and PRKD1. Our study finds evidence for distinct genetic architectures underlying the low sibling recurrence risk in S-CHD and NS-CHD.

Congenital heart defects (CHDs) have a neonatal incidence of 0.8–1%. Despite abundant examples of monogenic CHD in humans and mice, CHD has a low absolute sibling recurrence risk (~2.7%), suggesting a considerable role for de novo mutations (DNMs) and/or incomplete penetrance. De novo protein-truncating variants (PTVs) have been shown to be enriched among the 10% of 'syndromic' patients with extra-cardiac manifestations. We exome sequenced 1,891 probands, including both syndromic CHD (S-CHD, n = 610) and nonsyndromic CHD (NS-CHD, n = 1,281). In S-CHD, we confirmed a significant enrichment of de novo PTVs but not inherited PTVs in known CHD-associated genes, consistent with recent findings. Conversely, in NS-CHD we observed significant enrichment of PTVs inherited from unaffected parents in CHD-associated genes. We identified three genome-wide significant S-CHD disorders caused by DNMs in CHD4, CDK13 and PRKD1. Our study finds evidence for distinct genetic architectures underlying the low sibling recurrence risk in S-CHD and NS-CHD.

Congenital heart defects (CHDs) have a neonatal incidence of 0.8–1%. Despite abundant examples of monogenic CHD in humans and mice, CHD has a low absolute sibling recurrence risk (~2.7%), suggesting a considerable role for de novo mutations (DNMs) and/or incomplete penetrance. De novo protein-truncating variants (PTVs) have been shown to be enriched among the 10% of 'syndromic' patients with extra-cardiac manifestations. We exome sequenced 1,891 probands, including both syndromic CHD (S-CHD, n = 610) and nonsyndromic CHD (NS-CHD, n = 1,281). In S-CHD, we confirmed a significant enrichment of de novo PTVs but not inherited PTVs in known CHD-associated genes, consistent with recent findings. Conversely, in NS-CHD we observed significant enrichment of PTVs inherited from unaffected parents in CHD-associated genes. We identified three genome-wide significant S-CHD disorders caused by DNMs in CHD4, CDK13 and PRKD1. Our study finds evidence for distinct genetic architectures underlying the low sibling recurrence risk in S-CHD and NS-CHD.

Marinesco-Sjögren syndrome is a rare autosomal recessive multisystem disorder featuring cerebellar ataxia, early-onset cataracts, chronic myopathy, variable intellectual disability and delayed motor development. More recently, mutations in the SIL1 gene, which encodes an endoplasmic reticulum resident co-chaperone, were identified as the main cause of Marinesco-Sjögren syndrome. Here we describe the results of SIL1 mutation analysis in 62 patients presenting with early-onset ataxia, cataracts and myopathy or combinations of at least two of these. We obtained a mutation detection rate of 60% (15/25) among patients with the characteristic Marinesco-Sjögren syndrome triad (ataxia, cataracts, myopathy) whereas the detection rate in the group of patients with more variable phenotypic presentation was below 3% (1/37). We report 16 unrelated families with a total of 19 different SIL1 mutations. Among these mutations are 15 previously unreported changes, including single- and multi-exon deletions. Based on data from our screening cohort and data compiled from the literature we found that SIL1 mutations are invariably associated with the combination of a cerebellar syndrome and chronic myopathy. Cataracts were observed in all patients beyond the age of 7 years, but might be missing in infants. Six patients with SIL1 mutations had no intellectual disability, extending the known wide range of cognitive capabilities in Marinesco-Sjögren syndrome to include normal intelligence. Modestly constant features were somatic growth retardation, skeletal abnormalities and pyramidal tract signs. Examination of mutant SIL1 expression in cultured patient lymphoblasts suggested that SIL1 mutations result in severely reduced SIL1 protein levels irrespective of the type and position of mutations. Our data broaden the SIL1 mutation spectrum and confirm that SIL1 is the major Marinesco-Sjögren syndrome gene. SIL1 patients usually present with the characteristic triad but cataracts might be missi