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• Pediatric palliative care can be provided by a generalist hospital-at-home in France. • Generalist hospital-at-home facilities can successfully manage care across the lifespan. • Coordination, benevolence, and partnership are essential for successful care management. [ABSTRACT FROM AUTHOR]

The primary objective of this study is to determine the rate of spontaneous pregnancy after bilateral salpingectomy within two high volume tertiary health care centers. The secondary objective is to compare the calculated rate of pregnancy after BS with published rates of pregnancy after other methods of sterilization, such as bilateral tubal ligation. This is a retrospective chart review study. Two high volume tertiary health care centers Any patient who underwent bilateral salpingectomy for sterilization in the Indiana University Health or Eskenazi Health systems between January 2018 and September 2023. N/A. 2967 patients were identified as having undergone a procedure with a CPT code that represented tubal surgery (58600, 58605, 58611, 58661, 58670). Of these patients, 1028 were identified as having undergone a bilateral salpingectomy (including laparoscopic, postpartum, or at the time of cesarean section). 186 patients were excluded because of postmenopausal status, incomplete records, or being deceased within a year of their surgery. 14 patients were excluded because they were undergoing IVF after their surgery. Of the 1028 patients who underwent bilateral salpingectomy, 3 patients reported having a positive home pregnancy test. All 3 of these patients had negative pregnancy testing in the office shortly afterwards, thus, the rate of spontaneous pregnancy after bilateral salpingectomy in our study population was 0-0.3% over a 5-year period of time. Based on our data, the rate of spontaneous pregnancy after bilateral salpingectomy is 0-0.3%. This is lower than the published rate of pregnancy after all methods of sterilization of 1.33% by Peterson, et al 1996. This supports bilateral salpingectomy as a high-quality method of contraception and should encourage providers to perform salpingectomy when feasible. Future studies with a larger patient population and longer follow-up are needed to further support our findings. [ABSTRACT FROM AUTHOR]

Statins reduce the incidence of major cardiovascular events, but residual risk remains. The study examined the determinants of atherosclerotic statin nonresponse. This study aimed to investigate factors associated with statin nonresponse-defined atherosclerosis progression in patients treated with statins. The multicenter PARADIGM (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging) registry included patients who underwent serial coronary computed tomography angiography ≥2 years apart, with whole-heart coronary tree quantification of vessel, lumen, and plaque, and matching of baseline and follow-up coronary segments and lesions. Patients with statin use at baseline and follow-up coronary computed tomography angiography were included. Atherosclerotic statin nonresponse was defined as an absolute increase in percent atheroma volume (PAV) of 1.0% or more per year. Furthermore, a secondary endpoint was defined by the additional requirement of progression of low-attenuation plaque or fibro-fatty plaque. The authors included 649 patients (age 62.0 ± 9.0 years, 63.5% male) on statin therapy and 205 (31.5%) experienced atherosclerotic statin nonresponse. Age, diabetes, hypertension, and all atherosclerotic plaque features measured at baseline scan (high-risk plaque [HRP] features, calcified and noncalcified PAV, and lumen volume) were significantly different between patients with and without atherosclerotic statin nonresponse, whereas only diabetes, number of HRP features, and noncalcified and calcified PAV were independently associated with atherosclerotic statin nonresponse (odds ratio [OR]: 1.41 [95% CI: 0.95-2.11], OR: 1.15 [95% CI: 1.09-1.21], OR: 1.06 [95% CI: 1.02-1.10], OR: 1.07 [95% CI: 1.03-1.12], respectively). For the secondary endpoint (N = 125, 19.2%), only noncalcified PAV and number of HRP features were the independent determinants (OR: 1.08 [95% CI: 1.03-1.13] and OR: 1.21 [95% CI: 1.06-1.21], respectively). In patients treated with statins, baseline plaque characterization by plaque burden and HRP is associated with atherosclerotic statin nonresponse. Patients with the highest plaque burden including HRP were at highest risk for plaque progression, despite statin therapy. These patients may need additional therapies for further risk reduction. [Display omitted] [ABSTRACT FROM AUTHOR]

Design thinking (DT) is a widely-used innovation approach characterized by its experience-based character. It revolves around creating innovative solutions through extensive interaction among end-users, team members, and other stakeholders. However, traditional on-site, physical DT sessions are increasingly replaced by virtual sessions, potentially undermining the experiential nature of DT. This study examines the effects of changing from a physical to a virtual format on participants' experiences in DT processes as well as the resulting outcomes. To this end, we first identified two established complementary psychological theories—construal level theory and embodied cognition—that provide starting points for understanding the experiences of participants in physical and virtual DT formats. Next, we pursued an exploratory qualitative study by conducting 41 in-depth interviews with DT experts from research and practice. Our findings show that the DT format has profound effects across all phases of the DT process. From a theoretical perspective, we contribute by showing that changing the DT format to a virtual setting affects participants' cognitive experiences during all DT process phases and the respective outcomes. From a managerial perspective, we suggest a roadmap for designing a hybrid DT process that integrates the advantages of both physical and virtual DT formats. • We study the effects of virtual vs. physical DT formats on the DT process. • We use data from interviews with 41 DT experts from both research and practice. • We find distinct effects on participant experiences and outcomes in all DT phases. • We explore core mechanisms via construal level theory and embodied cognition. • We propose a hybrid DT process, integrating physical and virtual format benefits. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2009.10.036 Byline: Erich A. Nigg (1), Jordan W. Raff (2) Abstract: Centrioles are barrel-shaped structures that are essential for the formation of centrosomes, cilia, and flagella. Here we review recent advances in our understanding of the function and biogenesis of these organelles, and we emphasize their connection to human disease. Deregulation of centrosome numbers has long been proposed to contribute to genome instability and tumor formation, whereas mutations in centrosomal proteins have recently been genetically linked to microcephaly and dwarfism. Finally, structural or functional centriole aberrations contribute to ciliopathies, a variety of complex diseases that stem from the absence or dysfunction of cilia. Author Affiliation: (1) Biozentrum, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland (2) Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2008.05.039 Byline: Renata Basto (1), Kathrin Brunk (1), Tatiana Vinadogrova (2)(3), Nina Peel (1)(4), Anna Franz (1), Alexey Khodjakov (2)(3), Jordan W. Raff (1) Keywords: CELLCYCLE; CELLBIO Abstract: Centrosome amplification is a common feature of many cancer cells, and it has been previously proposed that centrosome amplification can drive genetic instability and so tumorigenesis. To test this hypothesis, we generated Drosophila lines that have extra centrosomes in [approximately equal to]60% of their somatic cells. Many cells with extra centrosomes initially form multipolar spindles, but these spindles ultimately become bipolar. This requires a delay in mitosis that is mediated by the spindle assembly checkpoint (SAC). As a result of this delay, there is no dramatic increase in genetic instability in flies with extra centrosomes, and these flies maintain a stable diploid genome over many generations. The asymmetric division of the larval neural stem cells, however, is compromised in the presence of extra centrosomes, and larval brain cells with extra centrosomes can generate metastatic tumors when transplanted into the abdomens of wild-type hosts. Thus, centrosome amplification can initiate tumorigenesis in flies. Author Affiliation: (1) The Gurdon Institute, Tennis Court Road, Cambridge CB2 1QN, UK (2) Wadsworth Center, New York State Department of Health, Albany, NY 12201, USA (3) Department of Biomedical Sciences, State University of New York, Albany, NY 12222, USA (4) Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA Article History: Received 20 February 2008; Revised 17 April 2008; Accepted 28 May 2008 Article Note: (miscellaneous) Published: June 12, 2008

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2006.05.025 Byline: Renata Basto (1), Joyce Lau (1), Tatiana Vinogradova (2)(3), Alejandra Gardiol (1), C. Geoffrey Woods (4), Alexey Khodjakov (2)(3), Jordan W. Raff (1) Abstract: Centrioles and centrosomes have an important role in animal cell organization, but it is uncertain to what extent they are essential for animal development. The Drosophila protein DSas-4 is related to the human microcephaly protein CenpJ and the C. elegans centriolar protein Sas-4. We show that DSas-4 is essential for centriole replication in flies. DSas-4 mutants start to lose centrioles during embryonic development, and, by third-instar larval stages, no centrioles or centrosomes are detectable. Mitotic spindle assembly is slow in mutant cells, and [approximately equal to]30% of the asymmetric divisions of larval neuroblasts are abnormal. Nevertheless, mutant flies develop with near normal timing into morphologically normal adults. These flies, however, have no cilia or flagella and die shortly after birth because their sensory neurons lack cilia. Thus, centrioles are essential for the formation of centrosomes, cilia, and flagella, but, remarkably, they are not essential for most aspects of Drosophila development. Author Affiliation: (1) The Gurdon Institute, Tennis Court Road, Cambridge CB2 1QN, UK (2) Wadsworth Center, New York State Department of Health, Albany, NY 12201, USA (3) Department of Biomedical Sciences, State University of New York, Albany, NY 12222, USA (4) Department of Medical Genetics, Cambridge Institute of Medical Research, Cambridge CB2 2XY, UK Article History: Received 13 December 2005; Revised 16 March 2006; Accepted 3 May 2006 Article Note: (miscellaneous) Published: June 29, 2006

Impact of free trade agreements on foreign direct investments and governments' tax policies is analyzed.

Oligodendrocyte precursor cells (OPCs) can be differentiated in culture into either oligodendrocytes or type-2 astrocytes (2As), depending on the culture conditions. Whereas oligodendrocyte development can occur in the absence of inducing signals, 2A development apparently cannot. Fetal calf serum (FCS) and bone morphogenetic proteins (BMPs) are powerful inducers of 2A development in culture, but there is no compelling evidence that OPCs develop into astrocytes in vivo. We show here that BMPs are made by glial cells in the developing rat optic nerve, raising the question of why 2As do not normally develop in the optic nerve. We demonstrate that the BMP antagonist Noggin is strongly expressed by both OPCs and type-1 astrocytes in the developing optic nerve. We also show that depletion of Noggin by a small interference RNA inhibits OPC proliferation and induces 2A differentiation in the presence of a low, non-2A-inducing concentration of FCS. By contrast, enforced expression of Noggin in OPCs blocks FCS-induced 2A differentiation. These findings suggest that BMPs in FCS are largely responsible for the 2A-inducing activity of FCS and that Noggin may normally inhibit the formation of 2As in the developing CNS. Keywords: Optic nerve; Oligodendrocyte precursor cells (OPCs); Type-1 astrocytes (1As); Type-2 astrocytes (2As); BMP4; Noggin

Trauma patients undergo routine contrast administration for diagnostic and therapeutic purposes. The aim of this study is to investigate the incidence and predictors of contrast-induced nephropathy requiring acute hemodialysis in the trauma population. Adult patients (age ≥16) were identified from the National Trauma Databank (2017–2018) and were grouped based on contrast received. The defined groups included no contrast, computed tomography intravascular contrast only, and angiography contrast. Patient demographic and clinical variables collected included vital signs (systolic blood pressure, pulse rate) recorded upon arrival to the emergency room, injury severity score, shock index, Glasgow Coma Scale, and mechanism. Outcome measures included mortality, hospital discharge disposition, intensive care unit and hospital length of stay, and need for hemodialysis. We performed a Poisson regression to assess relative risk for undergoing hemodialysis during hospital admission. In total, 1,850,460 patients were included in the analysis (no contrast: 1,189,209; computed tomography intravascular contrast only: 621,846; angiography: 39,405); 3,135 patients required hemodialysis during the admission. Patients with reduced Glasgow Coma Scale, higher injury severity score, higher shock index, and preexisting diabetes mellitus and hypertension were more likely to require hemodialysis. Poisson regression revealed the relative risk of requiring hemodialysis as 1.49 with computed tomography intravascular contrast only, 4.33 with angiography only, and 5.35 with consecutive computed tomography intravascular and angiography. Intravascular contrast administration through computed tomography and or angiography is independently associated with increased risk of requiring hemodialysis after a traumatic injury. Trauma surgeons should consider the necessity of contrast for each clinical situation and understand the potential for contrast-induced nephropathy. [ABSTRACT FROM AUTHOR]

We investigated adult rudiment induction in the direct-developing sea urchin Heliocidaris erythrogramma microsurgically. After removal of the archenteron (which includes presumptive coelomic mesoderm as well as presumptive endoderm) from late gastrulae, larval ectoderm develops properly but obvious rudiments (tube feet, nervous system, and adult skeleton) fail to form, indicating that coelomic mesoderm, endoderm, or both are required for induction of adult development. Recombination of ectoderm and archenteron rescues development. Implanted endoderm alone or left coelom alone each regenerate the full complement of archenteron derivatives; thus, they are uninformative as to the relative inductive potential of the two regions. However, in isolated ectoderm, more limited regeneration gives rise to larvae containing no archenteron derivatives at all, endoderm only, or both endoderm and left coelom. Adult nervous system begins to develop only in the latter, indicating that left coelom is required for the inductive signal. Isolated ectoderm develops a vestibule (the precursor of adult ectoderm) and correctly regulates vestibular expression of the ectodermal territory marker HeET-1, indicating that the early phase of vestibule development occurs autonomously; only later development requires the inductive signal. Another ectodermal marker, HEARS, is regulated properly in the larval ectoderm region, but not in the vestibule. HEARS regulation thus represents an early response to the inducing signal. We compare HEARS expression in H. erythrogramma with that in indirect developers and discuss its implications for modularity in the evolution of developmental mode. Key Words: induction; signaling; mesoderm; coelom; hydrocoel; vestibule; rudiment; modularity; skeletal patterning.

A cell-intrinsic timer helps control when rodent oligodendrocyte precursor cells (OPCs) exit the cell cycle and terminally differentiate when cultured in platelet-derived growth factor (PDGF) and thyroid hormone (TH). There is evidence that the cyclin-dependent kinase inhibitor (CKI) p27/Kip1 (p27) is a component of this TH-regulated timer, as it increases as OPCs proliferate and is required for the timer to operate accurately. Here, we provide evidence that another CKI, p18/INK (p18), may also be a component of the timer: it increases as OPCs proliferate, and its overexpression in OPCs accelerates the timer, causing the cells to differentiate prematurely. We also show that the overexpression of p27 accelerates the timer and that the increases in both p27 and p18 that occur in proliferating OPCs are controlled posttranscriptionally. By contrast, we show that the overexpression of either p18 or p27 in OPCs proliferating in PDGF and the absence of TH greatly slows the cell cycle but fails to accelerate the spontaneous differentiation that normally occurs independently of TH. Key Words: oligodendrocytes; p18; p27; Cdk inhibitor.

Developing cardiac myocytes divide a limited number of times before they stop and terminally differentiate, but the mechanism that stops their division is unknown. To help study the stopping mechanism, we defined conditions under which embryonic rat cardiac myocytes cultured in serum-free medium proliferate and exit the cell cycle on a schedule that closely resembles that seen in vivo. The culture medium contains FGF-1 and FGF-2, which stimulate cell proliferation, and thyroid hormone, which seems to be necessary for stable cell-cycle exit. Time-lapse video recording shows that the cells within a clone tend to divide a similar number of times before they stop, whereas cells in different clones divide a variable number of times before they stop. Cells cultured at 33 degrees C divide more slowly but stop dividing at around the same time as cells cultured at 37 degrees C, having undergone fewer divisions. Together, these findings suggest that an intrinsic timer helps control when cardiac myocytes withdraw from the cell cycle and that the timer does not operate by simply counting cell divisions. We provide evidence that the cyclin-dependent kinase inhibitors p18 and p27 may be part of the timer and that thyroid hormone may help developing cardiac myocytes stably withdraw from the cell cycle.

Oligodendrocyte precursor cells withdraw from the cell cycle and terminally differentiate after a limited number of cell divisions. The timing of cell-cycle withdrawal and differentiation is controlled by an intrinsic timer, which consists of a timing component that measures elapsed time and an effector component that arrests the cell cycle and initiates differentiation. The effector component can be triggered by either thyroid hormone (TH) or retinoic acid (RA). In this study we investigate how TH and RA act to trigger differentiation. We show the following: (1) Synthetic retinoids that can inhibit AP-1 transcription factors but do not activate gene transcription cannot trigger the effector mechanism, suggesting that TH and RA do not act only by inhibiting AP-1 activity as previously suggested. (2) Both TH and RA induce a transcriptionally dependent antigenic change in purified precursor cells within 2-4 h. (3) Unexpectedly, even before they differentiate, the precursor cells express ceramide galactosyltransferase (CGT), the enzyme that catalyzes the final step in the synthesis of galactocerebroside, an early marker of oligodendrocyte differentiation. (4) Neither TH nor RA directly activates the transcription of the CGT gene, a number of immediate early genes, or the genes that encode any of the known cyclin-dependent kinase inhibitors. (5) The withdrawal of the mitogen platelet-derived growth factor (PDGF), but not TH or RA treatment, causes a rapid decrease in c-fos, NGFI-A/Krox-24, and cyclin D2 mRNA, even though all three treatments trigger cell-cycle arrest and differentiation. (6) PDGF withdrawal and TH treatment, but not RA treatment, induce an increase in cyclin D3 mRNA within 4 h. Thus, we have not found any early changes in gene expression that occur with all three treatments that trigger oligodendrocyte differentiation.

During vertebrate development many types of precursor cells divide a limited number of times before they stop dividing and terminally differentiate. It is unclear what causes the cells to stop dividing when they do. We have been studying this problem in the oligodendrocyte cell lineage, which is responsible for myelination in the vertebrate central nervous system. Here we show for the first time that in clonal cultures of oligodendrocyte precursor cells purified from embryonic day 18 (E18) rat optic nerves the first oligodendrocytes develop within 3-4 days, equivalent to the time they first differentiate in the nerve, and that this timely differentiation depends on the presence of thyroid hormone. These findings suggest that a cell-intrinsic, thyroid-hormone-regulated timer determines when the first oligodendrocytes develop. Whereas the first oligodendrocytes develop asynchronously within clones, the vast majority develop after the first week in culture and do so more synchronously within clones. We show that [Beta]1 thyroid hormone receptors in the precursor cells increase in clonal cultures in the absence of thyroid hormone in parallel with the increasing sensitivity of the cells to the cell-cycle-arresting activity of thyroid hormone; moreover, the increase in [Beta]1 receptors, like the timer itself, is accelerated at 33 [degrees] C compared to 37 [degrees] C, suggesting that the increase in receptors may be part of the intrinsic timer. Finally, we show that the precursor cells do not divide indefinitely when stimulated to divide extensively in the absence of thyroid hormone but, instead, eventually stop dividing and either die or differentiate.