The Relationship Between Health Department Accreditation and Workforce Satisfaction, Retention, and Training Needs

BACKGROUND: To improve quality and consistency of health departments, a voluntary accreditation process was developed by the Public Health Accreditation Board. Understanding accreditation's role as a mediator in workforce training needs, satisfaction, and awareness is important for continued improvement for governmental public health. OBJECTIVE: To compare differences in training needs, satisfaction/intent to leave, and awareness of public health concepts for state and local health department staff with regard to their agency's accreditation status. DESIGN: This cross-sectional study considered the association between agency accreditation status and individual perceptions of training needs, satisfaction, intent to leave, and awareness of public health concepts, using 2017 Public Health Workforce Interests and Needs Survey (PH WINS) data. Respondents were categorized on the basis of whether their agencies (at the time of survey) were (1) uninvolved in accreditation, (2) formally involved in accreditation, or (3) accredited. RESULTS: Multivariate logistic regression models found several significant differences, including the following: individuals from involved state agencies were less likely to report having had their training needs assessed; staff from accredited and involved agencies identified more gaps in selected skills; and employees of accredited agencies were more aware of quality improvement. While state employees in accredited and formally involved agencies reported less job satisfaction, there were no significant differences in intent to leave or burnout. Differences were identified concerning awareness of various public health concepts, especially among respondents in state agencies. CONCLUSIONS: While some findings were consistent with past research (eg, link between accreditation and quality improvement), others were not (eg, job satisfaction). Several self-reported skill gaps were unanticipated, given accreditation's emphasis on training. Potentially, as staff are exposed to accreditation topics, they gain more appreciation of skills development needs. Findings suggest opportunities to strengthen workforce development components when revising accreditation measures

De Novo SOX6 Variants Cause a Neurodevelopmental Syndrome Associated with ADHD, Craniosynostosis, and Osteochondromas

Introduction: The SOX gene family consists of twenty transcription factors that play a pivotal role in cell fate and differentiation during the development of many organ systems. Within these SRY-related (SOX) genes is a highly conserved high mobility group (HMG) domain that has been shown to be critical for DNA binding and bending, nuclear trafficking, and protein-protein interactions. Mutations within this transcription factor family have been associated with rare congenital disorders, known as SOXopathies. These mutations are commonly de novo, heterozygous and inactivating, and exhibit gene haploinsufficiency. Of these twenty transcription factors, SOX6 is known to be involved in chondrocyte differentiation and development of the central nervous system. Although there have been reports of SOX6 variants causing adult pathological conditions, there has yet to be a well-established association between SOX6 variants and a developmental syndrome. Objectives: The objective of this study was to use clinical and genetic data to examine SOX6 mutations found in 19 individuals demonstrating developmental delay and to test the transcriptional activity of the 4 missense variants in vitro to determine if SOX6 haploinsufficiency leads to a neurodevelopmental SOXopathy. Methods: Nineteen individuals were identified as carriers of SOX6 variants, confirmed by molecular karyotyping, whole-exome sequencing, or whole-genome sequencing. Clinical pathogenicity was predicted and assessed in silico and in vitro. Expression plasmids for SOX6 missense variants were generated by PCR mutagenesis. The four missense variants generated were: p.Trp161Cys, p.Met605Thr, p.Trp639Arg, and p.Ser746Leu, with p.Met605Thr and p.Trp639Arg located within the HMG domain. For reporter assays, HEK293 cells were transfected in triplicate cultures with 3.5 µL ViaFect Transfection Reagent and a total of 1000ng of DNA. SOX6 intracellular localization was tested by transfecting either HEK293 or COS-1 cells and cytoplasmic and nuclear extracts were prepared for Western Blot analysis. Whole cell extracts transfected with respective WT-SOX6 or variant plasmid were also prepared for a dimerization assay. SOX6’s ability to bind DNA was also tested in an electrophoretic mobility shift assay (EMSA). Results: Study cohort consisted of 19 individuals from 17 unrelated families originating in Belgium, Canada, France, Germany, the Netherlands, Slovenia, the UK, and the US. These individuals shared milestone delays and intellectual disability, and exhibited abnormalities including mild dysmorphism, craniosynostosis, and osteochondromas. Immunoblots of nuclear and cytoplasmic extracts showed all variants were efficiently expressed however p.Met605Thr and p.Trp639Arg were not translocated or retained into the nucleus as efficiently as WT-SOX6 and the other two missense variants. The EMSA showed that proteins outside of the HMG domain behaved like WT-SOX6, but p.Met605Thr and p.Trp639Arg failed to bind the DNA probe. Reporter assay activity showed that the two variants outside of the HMG domain p.Trp161Cys and p.Ser746Leu displayed similar or slightly higher activity compared to WT-SOX6 while the two variants p.Met605Thr and p.Trp639Arg showed diminished reporter activity. Conclusions: These findings provide evidence that SOX6 variants cause a SOXopathy, which has been designated in Online Mendelian Inheritance in Man (OMIM) as #618971 Tolchin-Le Caignec syndrome (TOLCAS)

Integrated genomic characterization of pancreatic ductal adenocarcinoma

We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead