Palliative Care: A Novel Solution to the Healthcare Crisis. Syracuse Seminar Series on Aging.

Palliative care is specialized healthcare for anyone who is diagnosed with a serious and life-threatening illness, starting when they get the diagnosis, regardless of the prognosis. Although hospice is a form of palliative care, most palliative care is not end-of-life care or hospice, a common misperception that deters many people from using palliative care when they would benefit from it. Palliative care improves quality of care, reduces hospital costs, and helps clinicians address the needs and wants of patients and their families, which is why I refer to it as a 'novel' solution to the longstanding healthcare crisis.palliative care, hospice, patient autonomy, access to information, pain, distress, serious illness, cancer, depression, physical discomfort, medical education,

Element Abundances in a Gas-rich Galaxy at z = 5: Clues to the Early Chemical Enrichment of Galaxies

Element abundances in high-redshift quasar absorbers offer excellent probes of the chemical enrichment of distant galaxies, and can constrain models for population III and early population II stars. Recent observations indicate that the sub-damped Lyman-alpha (sub-DLA) absorbers are more metal-rich than DLA absorbers at redshifts 0$<$$z$$<$3. It has also been suggested that the DLA metallicity drops suddenly at $z$$>$4.7. However, only 3 DLAs at $z$$>$4.5 and none at $z$$>$3.5 have "dust-free" metallicity measurements of undepleted elements. We report the first quasar sub-DLA metallicity measurement at $z$$>$3.5, from detections of undepleted elements in high-resolution data for a sub-DLA at $z$=5.0. We obtain fairly robust abundances of C, O, Si, and Fe, using lines outside the Lyman-alpha forest. This absorber is metal-poor, with O/H]=-2.00$\pm$0.12, which is $\gtrsim$4$\sigma$ below the level expected from extrapolation of the trend for $z$$<$3.5 sub-DLAs. The C/O ratio is 1.8$^{+0.4}_{-0.3}$ times lower than in the Sun. More strikingly, Si/O is 3.2$^{+0.6}_{-0.5}$ times lower than in the Sun, while Si/Fe is nearly (1.2$^{+0.4}_{-0.3}$ times) solar. This absorber does not display a clear alpha/Fe enhancement. Dust depletion may have removed more Si from the gas phase than is common in the Milky Way interstellar medium, which may be expected if high-redshift supernovae form more silicate-rich dust. C/O and Si/O vary substantially between different velocity components, indicating spatial variations in dust depletion and/or early stellar nucleosynethesis (e.g., population III star initial mass function). The higher velocity gas may trace an outflow enriched by early stars.Comment: 42 pages including 9 figures, accepted for publication in Ap

Keck and VLT Observations of Super-damped Lyman-alpha Absorbers at z=2=2.5: Constraints on Chemical Compositions and Physical Conditions

We report Keck/ESI and VLT/UVES observations of three super-damped Lyman-alpha quasar absorbers with H I column densities log N(HI) >= 21.7 at redshifts z=2-2.5. All three absorbers show similar metallicities (-1.3 to -1.5 dex), and dust depletion of Fe, Ni, and Mn. Two of the absorbers show supersolar [S/Zn] and [Si/Zn]. We combine our results with those for other DLAs to examine trends between N(HI), metallicity, dust depletion. A larger fraction of the super-DLAs lie close to or above the line [X/H]=20.59-log N(HI) in the metallicity vs. N(HI) plot, compared to the less gas-rich DLAs, suggesting that super-DLAs are more likely to be rich in molecules. Unfortunately, our data for Q0230-0334 and Q0743+1421 do not cover H2 absorption lines. For Q1418+0718, some H2 lines are covered, but not detected. CO is not detected in any of our absorbers. For DLAs with log N(HI) < 21.7, we confirm strong correlation between metallicity and Fe depletion, and find a correlation between metallicity and Si depletion. For super-DLAs, these correlations are weaker or absent. The absorbers toward Q0230-0334 and Q1418+0718 show potential detections of weak Ly-alpha emission, implying star formation rates of about 1.6 and 0.7 solar masses per year, respectively (ignoring dust extinction). Upper limits on the electron densities from C II*/C II or Si II*/Si II are low, but are higher than the median values in less gas-rich DLAs. Finally, systems with log N(HI) > 21.7 may have somewhat narrower velocity dispersions delta v_90 than the less gas-rich DLAs, and may arise in cooler and/or less turbulent gas.Comment: 57 pages, 15 figures. Accepted for publication in Ap

Haematopoietic stem cells require a highly regulated protein synthesis rate

Many aspects of cellular physiology remain unstudied in somatic stem cells. For example, there are almost no data on protein synthesis in any somatic stem cell. We found that the amount of protein synthesized per hour in haematopoietic stem cells (HSCs) in vivo was lower than in most other haematopoietic cells, even if we controlled for differences in cell cycle status or forced HSCs to undergo self-renewing divisions. Reduced ribosome function in Rpl24Bst/+ mice further reduced protein synthesis in HSCs and impaired HSC function. Pten deletion increased protein synthesis in HSCs but also reduced HSC function. Rpl24Bst/+ cell-autonomously rescued the effects of Pten deletion in HSCs, blocking the increase in protein synthesis, restoring HSC function, and delaying leukaemogenesis. Pten deficiency thus depletes HSCs and promotes leukaemia partly by increasing protein synthesis. Either increased or decreased protein synthesis impairs HSC function

Identification of a lineage of multipotent hematopoietic progenitors

All multipotent hematopoietic progenitors in C57BL-Thy-1.1 bone marrow are divided among three subpopulations of Thy-1.1^(lo) Sca-1^+ Lin^(-/lo) c-kit^+ cells: long-term reconstituting Mac-1^-CD4^-c-kit^+ cells and transiently reconstituting Mac-1^(lo)CD4^-or Mac-1^(lo) CD4^(lo) cells. This study shows that the same populations, with similar functional activities, exist in mice whose hematopoietic systems were reconstituted by hematopoietic stem cells after lethal irradiation. We demonstrate that these populations form a lineage of multipotent progenitors from long-term self-renewing stem cells to the most mature multipotent progenitor population. In reconstituted mice, Mac-1- CD4^-c-kit^+ cells gave rise to Mac-1^(lo)CD4^- cells, which gave rise to Mac-1^(lo)CD4^(lo) cells. Mac-1^- CD4^-c-kit^+ cells had long-term self-renewal potential, with each cell being capable of giving rise to more than 10^4 functionally similar Mac-1^-CD4^-c-kit^+ cells. At least half of Mac-1^(lo)CD4^- cells had transient self-renewal potential, detected in the spleen 7 days after reconstitution. Mac-1^(lo)CD4^(lo) cells did not have detectable self-renewal potential. The identification of a lineage of multipotent progenitors provides an important tool for identifying genes that regulate self-renewal and lineage commitment

Expression of TIM3/VISTA checkpoints and the CD68 macrophage-associated marker correlates with anti-PD1/PDL1 resistance: implications of immunogram heterogeneity.

Although immunotherapies have achieved remarkable salutary effects among subgroups of advanced cancers, most patients do not respond. We comprehensively evaluated biomarkers associated with the "cancer-immunity cycle" in the pan-cancer setting in order to understand the immune landscape of metastatic malignancies as well as anti-PD-1/PD-L1 inhibitor resistance mechanisms. Interrogation of 51 markers of the cancer-immunity cycle was performed in 101 patients with diverse malignancies using a clinical-grade RNA sequencing assay. Overall, the immune phenotypes demonstrated overexpression of multiple checkpoints including VISTA (15.8% of 101 patients), PD-L2 (10.9%), TIM3 (9.9%), LAG3 (8.9%), PD-L1 (6.9%) and CTLA4 (3.0%). Additionally, aberrant expression of macrophage-associated markers (e.g. CD68 and CSF1R; 11-23%), metabolic immune escape markers (e.g. ADORA2A and IDO1; 9-16%) and T-cell priming markers (e.g. CD40, GITR, ICOS and OX40; 4-31%) were observed. Most tumors (87.1%, 88/101) expressed distinct immune portfolios, with a median of six theoretically actionable biomarkers (pharmacologically tractable by Food and Drug Administration approved agents [on- or off-label] or with agents in clinical development). Overexpression of TIM-3, VISTA and CD68 were significantly associated with shorter progression-free survival (PFS) after anti-PD-1/PD-L1-based therapies (among 39 treated patients) (all P &lt;&nbsp;.01). In conclusion, cancer-immunity cycle biomarker evaluation was feasible in diverse solid tumors. High expression of alternative checkpoints TIM-3 and VISTA and of the macrophage-associated markers CD68 were associated with significantly worse PFS after anti-PD-1/PD-L1-based therapies. Most patients had distinct and complex immune expression profiles suggesting the need for customized combinations of immunotherapy

Provisional BioBrick Language (PoBoL)

This BioBricks Foundation Request for Comments (BBF RFC) describes a semantic markup language for publishing and sharing information about BioBricks on the World Wide Web. This BBF RFC includes the recommendation for the minimal information expected when creating a Provisional BioBrick Language (PoBoL) description of BioBricks and for the implementation of the language using Web Ontology Language (OWL)