Inherently Governmental Functions and Other Work Reserved for Performance by Federal Government Employees: The Obama Administration’s Proposed Policy Letter

[Excerpt] On March 31, 2010, the Office of Federal Procurement Policy (OFPP) in the Office of Management and Budget (OMB) issued a proposed policy letter on inherently governmental functions and other “work reserved for performance by federal government employees.” While not final, the policy letter represents the Obama Administration’s proposed guidance for agencies determining (1) whether particular functions are inherently governmental and (2) when functions closely associated with the performance of inherently governmental functions and critical functions should be performed by government personnel. The proposed policy letter was, in part, issued under the authority of the Duncan Hunter National Defense Authorization Act for FY2009 (NDAA\u2709) and President Obama’s memorandum of March 4, 2009, on government contracting. Section 321 of NDAA\u2709 tasked OMB with (1) reviewing existing definitions of “inherently governmental function” to determine whether such definitions are “sufficiently focused” to ensure that only government personnel perform inherently governmental functions or “other critical functions necessary for the mission of a Federal department or agency;” (2) developing a “single consistent definition” of “inherently governmental function” that would address any deficiencies in the existing definitions, reasonably apply to all agencies, and ensure that agency personnel can identify positions that perform inherently governmental functions; (3) developing criteria for identifying critical functions” that should be performed by government personnel; and (4) developing criteria for identifying positions that government personnel should perform in order to ensure that agencies develop and maintain “sufficient organic expertise and technical capacity” to perform their missions and oversee contractors’ work. President Obama’s March 4, 2009, memorandum similarly charged OMB with clarifying when outsourcing is “appropriate.

Family Stories and Family Secrets

Families preserve and rewrite history in ways that pass on to the next generation a sense of family history based on what is known and what cannot be told. In this paper, we analyze New Zealand European adolescents’ stories about their parents’ childhood, exploring how these young people tell and do not tell family stories shrouded in secrecy. We identify three major ways in which families express secrets across the generations—through collusion, through confusion, and through whole-family secrets—and discuss the implications of each of these family practices for the preservation of family history

Band of mothers: Childbirth as a female bonding experience

Does the experience of childbirth create social bonds among first-time mothers? Previous research suggests that sharing emotionally intense or painful experiences with others leads to “identity fusion,” a visceral feeling of oneness with a group that predicts strong forms of prosocial action and self-sacrifice for other group members. This study compared identity fusion with other mothers during pregnancy versus after childbirth in a sample of 164 U.S. women. Eighty-nine mothers in our sample were pregnant with their firstborn, and 75 mothers had given birth to their firstborn up to 6 months prior to the time of data collection. Results demonstrated that identity fusion with other mothers was higher for postpartum mothers than for antenatal mothers. As predicted, among postpartum mothers, those who thought that their childbirth was more painful than a typical childbirth experience reported greater identity fusion with mothers who reported having had a very difficult birth. Postpartum mothers’ ruminative thought about the birth mediated the association between level of dysphoria and identity fusion, and identity fusion moderated the association between postpartum mothers’ ruminative and reflective thought about the birth and their posttraumatic growth in complex ways. These findings provide evidence that perceived sharedness of the childbirth experience and thoughts about the birth are important to the process of identity fusion with other mothers, and highlight the importance of post-event processing for psychological health

Mouse models of preterm birth: Suggested assessment and reporting guidelines

Preterm birth affects approximately 1 out of every 10 births in the United States, leading to high rates of mortality and long-term negative health consequences. To investigate the mechanisms leading to preterm birth so as to develop prevention strategies, researchers have developed numerous mouse models of preterm birth. However, the lack of standard definitions for preterm birth in mice limits our field\u27s ability to compare models and make inferences about preterm birth in humans. In this review, we discuss numerous mouse preterm birth models, propose guidelines for experiments and reporting, and suggest markers that can be used to assess whether pups are premature or mature. We argue that adoption of these recommendations will enhance the utility of mice as models for preterm birth

Transcriptional profiling of the ductus arteriosus: Comparison of rodent microarrays and human RNA sequencing

DA closure is crucial for the transition from fetal to neonatal life. This closure is supported by changes to the DA’s signaling and structural properties that distinguish it from neighboring vessels. Examining transcriptional differences between these vessels is key to identifying genes or pathways responsible for DA closure. Several microarray studies have explored the DA transcriptome in animal models but varied experimental designs have led to conflicting results. Thorough transcriptomic analysis of the human DA has yet to be performed. A clear picture of the DA transcriptome is key to guiding future research endeavors, both to allow more targeted treatments in the clinical setting, and to understand the basic biology of DA function. In this review, we use a cross-species cross-platform analysis to consider all available published rodent microarray data and novel human RNAseq data in order to provide high priority candidate genes for consideration in future DA studies

Coherence of Personal Narratives Across the Lifespan: A Multidimensional Model and Coding Method

Personal narratives are integral to autobiographical memory and to identity, with coherent personal narratives being linked to positive developmental outcomes across the lifespan. In this article, we review the theoretical and empirical literature that sets the stage for a new lifespan model of personal narrative coherence. This new model integrates context, chronology, and theme as essential dimensions of personal narrative coherence, each of which relies upon different developmental achievements and has a different developmental trajectory across the lifespan. A multidimensional method of coding narrative coherence (the Narrative Coherence Coding Scheme or NaCCS) was derived from the model and is described here. The utility of this approach is demonstrated by its application to 498 narratives that were collected in six laboratories from participants ranging in age from 3 years to adulthood. The value of the model is illustrated further by a discussion of its potential to guide future research on the developmental foundations of narrative coherence and on the benefits of personal narrative coherence for different aspects of psychological functioning

Effects of antenatal betamethasone on preterm human and mouse ductus arteriosus: comparison with baboon data.

BackgroundAlthough studies involving preterm infants ≤34 weeks gestation report a decreased incidence of patent ductus arteriosus after antenatal betamethasone, studies involving younger gestation infants report conflicting results.MethodsWe used preterm baboons, mice, and humans (≤276/7 weeks gestation) to examine betamethasone's effects on ductus gene expression and constriction both in vitro and in vivo.ResultsIn mice, betamethasone increased the sensitivity of the premature ductus to the contractile effects of oxygen without altering the effects of other contractile or vasodilatory stimuli. Betamethasone's effects on oxygen sensitivity could be eliminated by inhibiting endogenous prostaglandin/nitric oxide signaling. In mice and baboons, betamethasone increased the expression of several developmentally regulated genes that mediate oxygen-induced constriction (K+ channels) and inhibit vasodilator signaling (phosphodiesterases). In human infants, betamethasone increased the rate of ductus constriction at all gestational ages. However, in infants born ≤256/7 weeks gestation, betamethasone's contractile effects were only apparent when prostaglandin signaling was inhibited, whereas at 26-27 weeks gestation, betamethasone's contractile effects were apparent even in the absence of prostaglandin inhibitors.ConclusionsWe speculate that betamethasone's contractile effects may be mediated through genes that are developmentally regulated. This could explain why betamethasone's effects vary according to the infant's developmental age at birth

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease

Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in $\textit{CHM}$ in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.This work was supported by The National Institute for Health Research England (NIHR) for the NIHR BioResource – Rare Diseases project (grant number RG65966). The Moorfields Eye Hospital cohort of patients and clinical and imaging data were ascertained and collected with the support of grants from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, National Health Service Foundation Trust, and UCL Institute of Ophthalmology, Moorfields Eye Hospital Special Trustees, Moorfields Eye Charity, the Foundation Fighting Blindness (USA), and Retinitis Pigmentosa Fighting Blindness. M.M. is a recipient of an FFB Career Development Award. E.M. is supported by UCLH/UCL NIHR Biomedical Research Centre. F.L.R. and D.G. are supported by Cambridge NIHR Biomedical Research Centre

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups

Molecular and cellular impact of Psoriasin (S100A7) on the healing of human wounds

Psoriasin, which is also known as S100A7, is a member of the S100 protein family, a group of calcium‑responsive signalling proteins. Psoriasin expression remains high in patients with psoriasis, whereas it is downregulated in patients with invasive breast carcinoma. This observation suggests that this protein may be a notable marker of keratinocyte function and differentiation during wound healing. The aim of the present study was to determine the cellular impact of Psoriasin in keratinocytes, which are the primary cell type associated with wound healing. Psoriasin expression in wound tissues was examined using reverse transcription‑quantitative polymerase chain reaction and immunochemical staining. Knockdown of Psoriasin in HaCaT cells was performed using anti‑Psoriasin ribozyme transgenes and the effect on growth, adhesion and migration of keratinocytes was subsequently determined using in vitro cellular functional assays. Psoriasin expression is upregulated in wounds, particularly at the wound edges. The present study demonstrated that Psoriasin is expressed in keratinocytes and is a fundamental regulator of keratinocyte migration. Significant increases in the rate of keratinocyte adhesion, migration and growth were observed in Psoriasin‑deficient cells (P<0.01 vs. control). Application of small inhibitors identified the potential association of neural Wiskott‑Aldrich syndrome protein, focal adhesion primase and rho‑associated protein kinase signalling pathways with Psoriasin‑regulated cell adhesion and motility. In conclusion, Psoriasin serves an important role in the wound healing process, suggesting that it may be utilized as a potential wound healing biomarker