The Impact of a Regulatory Intervention on Resident-Centered Nursing Home Care: Rhode Island's Individualized Care Pilot

Evaluates a pilot project to promote resident-centered care through activities integrated with recertification inspections, including visits from a nonregulatory entity, and its impact on understanding, consideration, and implementation of practices

Consular Discretion in the Immigrant Visa-Issuing Process

This study examines the exercise of discretion by consular officers in deciding whether to issue or refuse immigrant visas in an effort to determine if these decisions are arbitrary or unlawful. The study begins by examining the procedures and factors mandated by the Immigration and Nationality Act for use in determining eligibility to immigrate. The study then discusses and compares the typical procedures and eligibility factors utilized by consular offices in the field. Next the study does an evaluation of extra-statutory factors affecting the consular officer\u27s determination including personal background, the effect of intermediaries, lack of time, the promotion system, and attitudes towards applicants and the immigration policy. The study concludes by making recommendations for limiting the discretion of consular officers in deciding whether to issue or refuse immigrant visas

Ruler Arrays Reveal Haploid Genomic Structural Variation

Despite the known relevance of genomic structural variants to pathogen behavior, cancer, development, and evolution, certain repeat based structural variants may evade detection by existing high-throughput techniques. Here, we present ruler arrays, a technique to detect genomic structural variants including insertions and deletions (indels), duplications, and translocations. A ruler array exploits DNA polymerase’s processivity to detect physical distances between defined genomic sequences regardless of the intervening sequence. The method combines a sample preparation protocol, tiling genomic microarrays, and a new computational analysis. The analysis of ruler array data from two genomic samples enables the identification of structural variation between the samples. In an empirical test between two closely related haploid strains of yeast ruler arrays detected 78% of the structural variants larger than 100 bp.United States. National Institutes of Health (Grant R01GM069676

α1-Adrenergic responsiveness in human skeletal muscle feed arteries: the impact of reducing extracellular pH

What is the central question of this study? In human arteries involved in the regulation of muscle blood flow, there is a lack of data about whether acidosis alters vascular sensitivity to vasoactive agents, as well as altering endothelium dependent vasorelaxation. Little is known about the interaction of metabolites and vascular function in human skeletal muscle feed arteries. • What is the main finding and its importance? Increasing acidosis attenuated the response and sensitivity of the arteries to phenylephrine; this effect was selective to the receptor over smooth muscle. Acidosis did not alter endothelium dependent vasorelaxation. Impaired vasoconstriction coupled with intact vasorelaxation, promotes decreased vascular tone with exposure to acidosis, and may contribute to sympatholysis during exercise

David Quentin Bowen: A memorial

The Quaternary community lost a giant and a leader on October 5, 2020, when David Quentin Bowen, known to many as “DQ” and founding editor of Quaternary Science Reviews, passed away in Cardiff. Born on February 14, 1938 in Llanelli, SouthWales, he received his PhD at University College London. David’s 50 years of contributions to our science cannot be adequately summarized in a brief memorial but past, present, and future generations of Quaternary scientists will long remember his landmark achievements in publishing, his scientific contributions, and his personal and professional class in all his endeavors

Exercise training improves vascular mitochondrial function

Exercise training is recognized to improve cardiac and skeletal muscle mitochondrial respiratory capacity; however, the impact of chronic exercise on vascular mitochondrial respiratory function is unknown. We hypothesized that exercise training concomitantly increases both vascular mitochondrial respiratory capacity and vascular function. Arteries from both sedentary (SED) and swim-trained (EX, 5 wk) mice were compared in terms of mitochondrial respiratory function, mitochondrial content, markers of mitochondrial biogenesis, redox balance, nitric oxide (NO) signaling, and vessel function. Mitochondrial complex I and complex I + II state 3 respiration and the respiratory control ratio (complex I + II state 3 respiration/complex I state 2 respiration) were greater in vessels from EX relative to SED mice, despite similar levels of arterial citrate synthase activity and mitochondrial DNA content. Furthermore, compared with the SED mice, arteries from EX mice displayed elevated transcript levels of peroxisome proliferative activated receptor-γ coactivator-1α and the downstream targets cytochrome c oxidase subunit IV isoform 1, isocitrate dehydrogenase (Idh) 2, and Idh3a, increased manganese superoxide dismutase protein expression, increased endothelial NO synthase phosphorylation (Ser1177), and suppressed reactive oxygen species generation (all P \u3c 0.05). Although there were no differences in EX and SED mice concerning endothelium-dependent and endothelium-independent vasorelaxation, phenylephrine-induced vasocontraction was blunted in vessels from EX compared with SED mice, and this effect was normalized by NOS inhibition. These training-induced increases in vascular mitochondrial respiratory capacity and evidence of improved redox balance, which may, at least in part, be attributable to elevated NO bioavailability, have the potential to protect against age- and disease-related challenges to arterial function

Early Agriculture in the Maya Lowlands

Wetland research in northern Belize provides the earliest evidence for development of agriculture in the Maya Lowlands. Pollen data confirm the introduction of maize and manioc before 3000 B.C. Dramatic deforestation, beginning ca. 2500 B.C. and intensifying in wetland environments ca. 1500-1300 B.C., marks an expansion of agriculture, which occurred in the context of a mixed foraging economy. By 1000 B.C. a rise in groundwater levels led farmers to construct drainage ditches coeval with the emergence of Maya complex society ca. 1000-400 B.C. Field manipulations often involved minor modifications of natural hummocks. Canal systems are not as extensive in northern Belize as previously reported, nor is there evidence of artificially raised planting platforms. By the Classic period, wetland fields were flooded and mostly abandoned

Approaches to quality improvement in nursing homes: Lessons learned from the six-state pilot of CMS's Nursing Home Quality Initiative

BACKGROUND: In November 2002, the Centers for Medicare & Medicaid Services (CMS) launched a Nursing Home Quality Initiative that included publicly reporting a set of Quality Measures for all nursing homes in the country, and providing quality improvement assistance to nursing homes nationwide. A pilot of this initiative occurred in six states for six months prior to the launch. METHODS: Review and analysis of the lessons learned from the six Quality Improvement Organizations (QIOs) that led quality improvement efforts in nursing homes from the six pilot states. RESULTS: QIOs in the six pilot states found several key outcomes of the Nursing Home Quality Initiative that help to maximize the potential of public reporting to leverage effective improvement in nursing home quality of care. First, public reporting focuses the attention of all stakeholders in the nursing home industry on achieving good quality outcomes on a defined set of measures, and creates an incentive for partnership formation. Second, publicly reported quality measures motivate nursing home providers to improve in certain key clinical areas, and in particular to seek out new ways of changing processes of care, such as engaging physicians and the medical director more directly. Third, the lessons learned by QIOs in the pilot of this Initiative indicate that certain approaches to providing quality improvement assistance are key to guiding nursing home providers' desire and enthusiasm to improve towards a using a systematic approach to quality improvement. CONCLUSION: The Nursing Home Quality Initiative has already demonstrated the potential of public reporting to foster collaboration and coordination among nursing home stakeholders and to heighten interest of nursing homes in quality improvement techniques. The lessons learned from this pilot project have implications for any organizations or individuals planning quality improvement projects in the nursing home setting

Parallel Germline Infiltration of a Lentivirus in Two Malagasy Lemurs

Retroviruses normally infect the somatic cells of their host and are transmitted horizontally, i.e., in an exogenous way. Occasionally, however, some retroviruses can also infect and integrate into the genome of germ cells, which may allow for their vertical inheritance and fixation in a given species; a process known as endogenization. Lentiviruses, a group of mammalian retroviruses that includes HIV, are known to infect primates, ruminants, horses, and cats. Unlike many other retroviruses, these viruses have not been demonstrably successful at germline infiltration. Here, we report on the discovery of endogenous lentiviral insertions in seven species of Malagasy lemurs from two different genera—Cheirogaleus and Microcebus. Combining molecular clock analyses and cross-species screening of orthologous insertions, we show that the presence of this endogenous lentivirus in six species of Microcebus is the result of one endogenization event that occurred about 4.2 million years ago. In addition, we demonstrate that this lentivirus independently infiltrated the germline of Cheirogaleus and that the two endogenization events occurred quasi-simultaneously. Using multiple proviral copies, we derive and characterize an apparently full length and intact consensus for this lentivirus. These results provide evidence that lentiviruses have repeatedly infiltrated the germline of prosimian species and that primates have been exposed to lentiviruses for a much longer time than what can be inferred based on sequence comparison of circulating lentiviruses. The study sets the stage for an unprecedented opportunity to reconstruct an ancestral primate lentivirus and thereby advance our knowledge of host–virus interactions

A distant trophoblast-specific enhancer controls HLA-G expression at the maternal–fetal interface

HLA-G, a nonclassical HLA molecule uniquely expressed in the placenta, is a central component of fetus-induced immune tolerance during pregnancy. The tissue-specific expression of HLA-G, however, remains poorly understood. Here, systematic interrogation of the HLA-G locus using massively parallel reporter assay (MPRA) uncovered a previously unidentified cis-regulatory element 12 kb upstream of HLA-G with enhancer activity, Enhancer L. Strikingly, clustered regularly-interspaced short palindromic repeats (CRISPR)/Cas9-mediated deletion of this enhancer resulted in ablation of HLA-G expression in JEG3 cells and in primary human trophoblasts isolated from placenta. RNA-seq analysis demonstrated that Enhancer L specifically controls HLA-G expression. Moreover, DNase-seq and chromatin conformation capture (3C) defined Enhancer L as a cell type-specific enhancer that loops into the HLA-G promoter. Interestingly, MPRA-based saturation mutagenesis of Enhancer L identified motifs for transcription factors of the CEBP and GATA families essential for placentation. These factors associate with Enhancer L and regulate HLA-G expression. Our findings identify long-range chromatin looping mediated by core trophoblast transcription factors as the mechanism controlling tissue-specific HLA-G expression at the maternal–fetal interface. More broadly, these results establish the combination of MPRA and CRISPR/Cas9 deletion as a powerful strategy to investigate human immune gene regulation