The Fueling Diagram: Linking Galaxy Molecular-to-Atomic Gas Ratios to Interactions and Accretion

To assess how external factors such as local interactions and fresh gas accretion influence the global ISM of galaxies, we analyze the relationship between recent enhancements of central star formation and total molecular-to-atomic (H2/HI) gas ratios, using a broad sample of field galaxies spanning early-to-late type morphologies, stellar masses of 10^(7.2-11.2) Msun, and diverse stages of evolution. We find that galaxies occupy several loci in a "fueling diagram" that plots H2/HI vs. mass-corrected blue-centeredness, a metric tracing the degree to which galaxies have bluer centers than the average galaxy at their stellar mass. Spiral galaxies show a positive correlation between H2/HI and mass-corrected blue-centeredness. When combined with previous results linking mass-corrected blue-centeredness to external perturbations, this correlation suggests a link between local galaxy interactions and molecular gas inflow/replenishment. Intriguingly, E/S0 galaxies show a more complex picture: some follow the same correlation, some are quenched, and a distinct population of blue-sequence E/S0 galaxies (with masses below key transitions in gas richness) defines a separate loop in the fueling diagram. This population appears to be composed of low-mass merger remnants currently in late- or post-starburst states, in which the burst first consumes the H2 while the galaxy center keeps getting bluer, then exhausts the H2, at which point the burst population reddens as it ages. Multiple lines of evidence suggest connected evolutionary sequences in the fueling diagram. In particular, tracking total gas-to-stellar mass ratios within the diagram provides evidence of fresh gas accretion onto low-mass E/S0s emerging from central starbursts. Drawing on a comprehensive literature search, we suggest that virtually all galaxies follow the same evolutionary patterns found in our broad sample.Comment: 24 pages, 11 figures (table 4 available at http://user.physics.unc.edu/~dstark/table4_csv.txt), accepted for publication in Ap

Gas Mass Fractions and Star Formation in Blue-Sequence E/S0 Galaxies

Recent work has identified a population of low-redshift E/S0 galaxies that lie on the blue sequence in color vs. stellar mass parameter space, where spiral galaxies typically reside. While high-mass blue-sequence E/S0s often resemble young merger or interaction remnants likely to fade to the red sequence, we focus on blue-sequence E/S0s with lower stellar masses (< a few 10^10 M_sun), which are characterized by fairly regular morphologies and low-density field environments where fresh gas infall is possible. This population may provide an evolutionary link between early-type galaxies and spirals through disk regrowth. Focusing on atomic gas reservoirs, we present new GBT HI data for 27 E/S0s on both sequences as well as a complete tabulation of archival HI data for other galaxies in the Nearby Field Galaxy Survey. Normalized to stellar mass, the atomic gas masses for 12 of the 14 blue-sequence E/S0s range from 0.1 to >1.0. These gas-to-stellar mass ratios are comparable to those of spiral and irregular galaxies and have a similar dependence on stellar mass. Assuming that the HI is accessible for star formation, we find that many of our blue-sequence E/S0s can increase in stellar mass by 10-60% in 3 Gyr in both of two limiting scenarios, exponentially declining star formation and constant star formation. In a constant star formation scenario, about half of the blue-sequence E/S0s require fresh gas infall on a timescale of <3 Gyr to avoid exhausting their atomic gas reservoirs and evolving to the red sequence. We present evidence that star formation in these galaxies is bursty and likely involves externally triggered gas inflows. Our analysis suggests that most blue-sequence E/S0s are indeed capable of substantial stellar disk growth on relatively short timescales. (abridged)Comment: ApJ, accepted, 26 pages with 12 figures (5 color), 5 table

The loss of a fellow service member: Complicated grief in postâ 9/11 service members and veterans with combatâ related posttraumatic stress disorder

Bereavement is a potent and highly prevalent stressor among service members and veterans. However, the psychological consequences of bereavement, including complicated grief (CG), have been minimally examined. Loss was assessed in 204 postâ 9/11, when service members and veterans with combatâ related posttraumatic stress disorder (PTSD) took part in a multicenter treatment study. Those who reported the loss of an important person completed the inventory of complicated grief (ICG; nâ =â 160). Over three quarters (79.41%) of the sample reported an important lifetime loss, with close to half (47.06%) reporting the loss of a fellow service member (FSM). The prevalence of CG was 24.75% overall, and nearly one third (31.25%) among the bereaved. CG was more prevalent among veterans who lost a fellow service member (FSM) (41.05%, nâ =â 39) compared to those bereaved who did not (16.92%, nâ =â 11; ORâ =â 3.41, 95% CI: 1.59, 7.36). CG was associated with significantly greater PTSD severity, functional impairment, traumaâ related guilt, and lifetime suicide attempts. Complicated grief was prevalent and associated with adverse psychosocial outcomes in veterans and service members with combatâ related PTSD. Clinicians working with this population should inquire about bereavement, including loss of a FSM, and screen for CG. Additional research examining CG in this population is needed.The loss of a fellow service member occurs commonly and is associated with complicated grief (CG) amongst service members and veterans with combatâ related posttraumatic stress disorder (PTSD). The presence of CG in this study was associated with more severe PTSD, guilt, and lifetime suicide attempts, as well as poorer functioning.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139942/1/jnr24094_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139942/2/jnr24094.pd

Understanding the impact of complicated grief on combat related posttraumatic stress disorder, guilt, suicide, and functional impairment in a clinical trial of post‐9/11 service members and veterans

BackgroundComplicated grief (CG) is a bereavement‐specific syndrome distinct from but commonly comorbid with posttraumatic stress disorder (PTSD). While bereavement is common among military personnel (Simon et al., 2018), there is little research on the impact of CG comorbidity on PTSD treatment outcomes.MethodsTo evaluate the impact of comorbid CG on PTSD treatment outcomes we analyzed data from a randomized trial comparing prolonged exposure, sertraline, and their combination in veterans with a primary diagnosis of combat‐related PTSD (n = 194). Assessment of PTSD, trauma‐related guilt, functional impairment, and suicidal ideation and behavior occurred at baseline and weeks 6, 12, and 24 during the 24‐week trial.ResultsCG was associated with lower PTSD treatment response (odds ratio (OR) = 0.29, 95% confidence interval (CI) [0.12, 0.69], p = 0.005) and remission (OR = 0.28, 95% CI [0.11, 0.71], p = 0.007). Those with CG had greater severity of PTSD (p = 0.005) and trauma‐related guilt (<0.001) at baseline and endpoint. In addition, those with CG were more likely to experience suicidal ideation during the study (CG: 35%, 14/40 vs. no CG 15%, 20/130; OR = 3.01, 95% CI [1.29, 7.02], p = 0.011).ConclusionsComorbid CG is associated with elevated PTSD severity and independently associated with poorer endpoint treatment outcomes in veterans with combat‐related PTSD, suggesting that screening and additional intervention for CG may be needed.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153078/1/da22911_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153078/2/da22911.pd

Synthesis and in vitro and in vivo characterization of highly β1-Selective β-Adrenoceptor partial agonists

β-Adrenoceptor antagonists boast a 50-year use for symptomatic control in numerous cardiovascular diseases. One might expect highly selective antagonists are available for the human β-adrenoceptor subtype involved in these diseases, yet few truly β1-selective molecules exist. To address this clinical need, we re-evaluated LK 204-545 (1),1 a selective β1-adrenoceptor antagonist, and discovered it possessed significant partial agonism. Removal of 1’s aromatic nitrile afforded 19, a ligand with similar β1-adrenoceptor selectivity and partial agonism (log KD of −7.75 and −5.15 as an antagonist of functional β1- and β2-mediated responses, respectively, and 34% of the maximal response of isoprenaline (β1)). In vitro β-adrenoceptor selectivity and partial agonism of 19 were mirrored in vivo. We designed analogues of 19 to improve affinity, selectivity, and partial agonism. Although partial agonism could not be fully attenuated, SAR suggests that an extended alkoxyalkoxy side chain, alongside substituents at the meta- or para-positions of the phenylurea, increases ligand affinity and β1- selectivity

Novel selective β1-adrenoceptor antagonists for concomitant cardiovascular and respiratory disease

β-Blockers reduce mortality and improve symptoms in people with heart disease. However, current clinically available β-blockers have poor selectivity for the cardiac β1-adrenoceptor (AR) over the lung β2-AR. Unwanted β2-blockade risks causing life-threatening bronchospasm and a reduction in the efficacy of β2-agonist emergency rescue therapy. Thus current life-prolonging β-blockers are contraindicated in people with both heart disease and asthma. Here we describe NDD-713 and NDD-825, novel highly β1-selective neutral antagonists with good pharmaceutical properties that can potentially overcome this limitation. Radioligand binding studies and functional assays using human receptors expressed in CHO cells demonstrate that NDD-713 and NDD-825 have nanomolar β1-AR affinity, greater than 500-fold β1-AR vs β2-AR selectivity and no agonism. Studies in conscious rats demonstrated that they are orally bioavailable and cause pronounced β1-mediated reduction of heart rate while showing no effect on β2-mediated hindquarters vasodilatation. The compounds also have good disposition properties and show no adverse toxicological effects. They potentially offer a truly cardioselective β-blocker therapy for the large number of people with heart and respiratory, or peripheral vascular comorbidities

Laboratory demonstration of a prozone-like effect in HRP2-detecting malaria rapid diagnostic tests: implications for clinical management

Background: Malaria rapid diagnostic tests (RDTs) are now widely used for prompt on-site diagnosis in remote endemic areas where reliable microscopy is absent. Aberrant results, whereby negative test results occur at high parasite densities, have been variously reported for over a decade and have led to questions regarding the reliability of the tests in clinical use. Methods. In the first trial, serial dilutions of recombinant HRP2 antigen were tested on an HRP2-detectiing RDT. In a second trial, serial dilutions of culture-derived Plasmodium falciparum parasites were tested against three HRP2-detecting RDTs. Results: A prozone-like effect occurred in RDTs at a high concentration of the target antigen, histidine-rich protein-2 (above 15,000 ng/ml), a level that corresponds to more than 312000 parasites per L. Similar results were noted on three RDT products using dilutions of cultured parasites up to a parasite density of 25%. While reduced line intensity was observed, no false negative results occurred. Conclusions: These results suggest that false-negative malaria RDT results will rarely occur due to a prozone-like effect in high-density infections, and other causes are more likely. However, RDT line intensity is poorly indicative of parasite density in high-density infections and RDTs should, therefore, not be considered quantitative. Immediate management of suspected severe malaria should rely on clinical assessment or microscopy. Evaluation against high concentrations of antigen should be considered in malaria RDT product development and lot-release testing, to ensure that very weak or false negative results will not occur at antigen concentrations that might be seen clinically

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis