DHODH modulates transcriptional elongation in the neural crest and melanoma.

Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage.

HIV-1 utilizes the CXCR4 chemokine receptor to infect multipotent hematopoietic stem and progenitor cells.

HIV infection is characterized by gradual immune system collapse and hematopoietic dysfunction. We recently showed that HIV enters multipotent hematopoietic progenitor cells and establishes both active cytotoxic and latent infections that can be reactivated by myeloid differentiation. However, whether these multipotent progenitors include long-lived hematopoietic stem cells (HSCs) that could establish viral reservoirs for the life of the infected person remains unknown.

Palliative care consultation teams cut hospital costs for Medicaid beneficiaries.

Patients facing serious or life-threatening illnesses account for a disproportionately large share of Medicaid spending. We examined 2004-07 data to determine the effect on hospital costs of palliative care team consultations for patients enrolled in Medicaid at four New York State hospitals. On average, patients who received palliative care incurred $6,900 less in hospital costs during a given admission than a matched group of patients who received usual care.

Determinants of medical expenditures in the last 6 months of life.

Background: End-of-life medical expenditures exceed costs of care during other years, vary across regions, and are likely to be unsustainable. Identifying determinants of expenditure variation may reveal opportunities for reducing costs.

Objective: To identify patient-level determinants of Medicare expenditures at the end of life and to determine the contributions of these factors to expenditure variation while accounting for regional characteristics.

Resident perceptions of palliative care training in the emergency department.

Objectives: To characterize the level of formal training and perceived educational needs in palliative care of emergency medicine (EM) residents.

Methods: This descriptive study used a 16-question survey administered at weekly resident didactic sessions in 2008 to EM residency programs in New York City. Survey items asked residents to: (1) respond to Likert-scaled statements about the role of palliative care in the emergency department (ED); (2) quantify their level of formal training and personal comfort in symptom management, discussion of bad news and prognosis, legal issues, and withdrawing/withholding therapy; and (3) express their interest in future palliative care training.

Writing abstracts and developing posters for national meetings.

Presenting posters at national meetings can help fellows and junior faculty members develop a national reputation. They often lead to interesting and fruitful networking and collaboration opportunities. They also help with promotion in academic medicine and can reveal new job opportunities.

Palliative care needs of seriously ill, older adults presenting to the emergency department.

Objectives: The objective was to identify the palliative care needs of seriously ill, older adults in the emergency department (ED).

Methods: The authors conducted a cross-sectional structured survey. A convenience sample of 50 functionally impaired adults 65 years or older with coexisting cancer, congestive heart failure, end-stage liver or renal disease, stroke, oxygen-dependent pulmonary disease, or dementia was recruited from an urban academic tertiary care ED.

Human and rhesus macaque hematopoietic stem cells cannot be purified based only on SLAM family markers.

Various combinations of antibodies directed to cell surface markers have been used to isolate human and rhesus macaque hematopoietic stem cells (HSCs). These protocols result in poor enrichment or require multiple complex steps. Recently, a simple phenotype for HSCs based on cell surface markers from the signaling lymphocyte activation molecule (SLAM) family of receptors has been reported in the mouse.

Lkb1 regulates cell cycle and energy metabolism in haematopoietic stem cells.

Little is known about metabolic regulation in stem cells and how this modulates tissue regeneration or tumour suppression. We studied the Lkb1 tumour suppressor and its substrate AMP-activated protein kinase (AMPK), kinases that coordinate metabolism with cell growth. Deletion of the Lkb1 (also called Stk11) gene in mice caused increased haematopoietic stem cell (HSC) division, rapid HSC depletion and pancytopenia.

A strategy to advance the evidence base in palliative medicine: formation of a palliative care research cooperative group.

Background: Palliative medicine has made rapid progress in establishing its scientific and clinical legitimacy, yet the evidence base to support clinical practice remains deficient in both the quantity and quality of published studies. Historically, the conduct of research in palliative care populations has been impeded by multiple barriers including health care system fragmentation, small number and size of potential sites for recruitment, vulnerability of the population, perceptions of inappropriateness, ethical concerns, and gate-keeping.

Methods: A group of experienced investigators with backgrounds in palliative care research convened to consider developing a research cooperative group as a mechanism for generating high-quality evidence on prioritized, clinically relevant topics in palliative care.

Phenotypic heterogeneity among tumorigenic melanoma cells from patients that is reversible and not hierarchically organized.

We investigated whether melanoma is hierarchically organized into phenotypically distinct subpopulations of tumorigenic and nontumorigenic cells or whether most melanoma cells retain tumorigenic capacity, irrespective of their phenotype. We found 28% of single melanoma cells obtained directly from patients formed tumors in NOD/SCID IL2Rγ(null) mice. All stage II, III, and IV melanomas obtained directly from patients had common tumorigenic cells.

Lgi4 promotes the proliferation and differentiation of glial lineage cells throughout the developing peripheral nervous system.

The mechanisms that regulate peripheral nervous system (PNS) gliogenesis are incompletely understood. For example, gut neural crest stem cells (NCSCs) do not respond to known gliogenic factors, suggesting that yet-unidentified factors regulate gut gliogenesis. To identify new mechanisms, we performed gene expression profiling to identify factors secreted by gut NCSCs during the gliogenic phase of development.

The quality of emergency department pain care for older adult patients.

Objectives: To determine whether there are differences in emergency department (ED) pain assessment and treatment for older and younger adults.

Design: Retrospective observational cohort.

Setting: Urban, academic tertiary care ED during July and December 2005.

mTOR activation induces tumor suppressors that inhibit leukemogenesis and deplete hematopoietic stem cells after Pten deletion.

Pten deficiency depletes hematopoietic stem cells (HSCs) but expands leukemia-initiating cells, and the mTOR inhibitor, rapamycin, blocks these effects. Understanding the opposite effects of mTOR activation on HSCs versus leukemia-initiating cells could improve antileukemia therapies. We found that the depletion of Pten-deficient HSCs was not caused by oxidative stress and could not be blocked by N-acetyl-cysteine.

Geographic access to hospice in the United States.

Background: Despite a 41% increase in the number of hospices since 2000, more than 60% of Americans die without hospice care. Given that hospice care is predominantly home based, proximity to a hospice is important in ensuring access to hospice services. We estimated the proportion of the population living in communities within 30 and 60 minutes driving time of a hospice.

Prdm16 promotes stem cell maintenance in multiple tissues, partly by regulating oxidative stress.

To better understand the mechanisms that regulate stem cell identity and function, we sought to identify genes that are preferentially expressed by stem cells and critical for their function in multiple tissues. Prdm16 is a transcription factor that regulates leukaemogenesis, palatogenesis and brown-fat development, but which was not known to be required for stem cell function. We demonstrate that Prdm16 is preferentially expressed by stem cells throughout the nervous and haematopoietic systems and is required for their maintenance.

Impact of hospice disenrollment on health care use and medicare expenditures for patients with cancer.

Purpose: Patients with cancer represent the largest diagnostic group of hospice users, with 560,000 referred for hospice in 2008. Oncologists rely on hospice teams to provide care for patients who have completed disease-directed treatment and desire to remain at home. However, 11% to 15% of hospice users disenroll from hospice, and little is known about their health care use and Medicare expenditures.

FIP200 is required for the cell-autonomous maintenance of fetal hematopoietic stem cells.

Little is known about whether autophagic mechanisms are active in hematopoietic stem cells (HSCs) or how they are regulated. FIP200 (200-kDa FAK-family interacting protein) plays important roles in mammalian autophagy and other cellular functions, but its role in hematopoietic cells has not been examined. Here we show that conditional deletion of FIP200 in hematopoietic cells leads to perinatal lethality and severe anemia.

Temporal specification of blood progenitors from mouse embryonic stem cells and induced pluripotent stem cells.

The efficient and reproducible generation of differentiated progenitors from pluripotent stem cells requires the recapitulation of appropriate developmental stages and pathways. Here, we have used the combination of activin A, BMP4 and VEGF under serum-free conditions to induce hematopoietic differentiation from both embryonic and induced pluripotent stem cells, with the aim of modeling the primary sites of embryonic hematopoiesis. We identified two distinct Flk1-positive hematopoietic populations that can be isolated based on temporal patterns of emergence.

Hospital-based palliative care consultation: effects on hospital cost.

Context: Palliative care consultation teams in hospitals are becoming increasingly more common. Palliative care improves the quality of hospital care for patients with advanced disease. Less is known about its effects on hospital costs.

Determinants of treatment intensity for patients with serious illness: a new conceptual framework.

Background: Research during the past few decades has greatly advanced our understanding of the cost, quality, and variability of medical care at the end of life. The current health-care policy debate has focused considerable attention on the unsustainable rate of spending and wide regional variation associated with medical treatments in the last year of life. New initiatives aim to standardize quality and reduce over-utilization at the end of life.

An in vivo model to study and manipulate the hematopoietic stem cell niche.

Because the microenvironment that supports hematopoietic stem cell (HSC) proliferation and differentiation is not fully understood, we adapted a heterotopic bone formation model as a new approach for studying the HSC microenvironment in vivo. Endogenous HSCs homed to tissue-engineered ossicles and individually sorted HSCs from ossicles were able to reconstitute lethally irradiated mice. To further explore this model as a system to study the stem cell niche, ossicles were established with or without anabolic parathyroid hormone (PTH) treatment during the 4-week course of bone development.