We present ALMA Band 9 observations of the C II158 μm emission for a sample of 10 main-sequence galaxies at redshift z ˜ 2, with typical stellar masses (log M⋆/M⊙ ˜ 10.0-10.9) and star formation ...rates (˜35-115 M⊙ yr-1). Given the strong and well-understood evolution of the interstellar medium from the present to z = 2, we investigate the behaviour of the C II emission and empirically identify its primary driver. We detect C II from six galaxies (four secure and two tentative) and estimate ensemble averages including non-detections. The C II-to-infrared luminosity ratio (C II/LIR) of our sample is similar to that of local main-sequence galaxies (˜2 × 10-3), and ˜10 times higher than that of starbursts. The C II emission has an average spatial extent of 4-7 kpc, consistent with the optical size. Complementing our sample with literature data, we find that the C II luminosity correlates with galaxies' molecular gas mass, with a mean absolute deviation of 0.2 dex and without evident systematics: the C II-to-H2 conversion factor (α _C II ˜ 30 M⊙/L⊙) is largely independent of galaxies' depletion time, metallicity, and redshift. C II seems therefore a convenient tracer to estimate galaxies' molecular gas content regardless of their starburst or main-sequence nature, and extending to metal-poor galaxies at low and high redshifts. The dearth of C II emission reported for z > 6-7 galaxies might suggest either a high star formation efficiency or a small fraction of ultraviolet light from star formation reprocessed by dust.
Gaucher Disease type 1 (GD1) is a lysosomal disorder that affects many systems. Therapy improves the principal manifestations of the condition and, as a consequence, many patients show a modified ...phenotype which reflects manifestations of their disease that are refractory to treatment. More generally, it is increasingly recognised that information as to how a patient feels and functions obtained by patient- reported outcome measurements (PROMs) is critical to any comprehensive evaluation of treatment. A new set of management goals for GD1 in which both trends are reflected is needed. To this end, a modified Delphi procedure among 25 experts was performed. Based on a literature review and with input from patients, 65 potential goals were formulated as statements. Consensus was considered to be reached when ≥75% of the participants agreed to include that specific statement in the management goals. There was agreement on 42 statements. In addition to the traditional goals concerning haematological, visceral and bone manifestations, improvement in quality of life, fatigue and social participation, as well as early detection of long-term complications or associated diseases were included. When applying this set of goals in medical practice, the clinical status of the individual patient should be taken into account.
With more than 240 million people infected, hepatitis B virus (HBV) is a major health concern. The inability to mimic the complexity of the liver using cell lines and regular primary human hepatocyte ...(PHH) cultures pose significant limitations for studying host/pathogen interactions. Here, we describe a 3D microfluidic PHH system permissive to HBV infection, which can be maintained for at least 40 days. This system enables the recapitulation of all steps of the HBV life cycle, including the replication of patient-derived HBV and the maintenance of HBV cccDNA. We show that innate immune and cytokine responses following infection with HBV mimic those observed in HBV-infected patients, thus allowing the dissection of pathways important for immune evasion and validation of biomarkers. Additionally, we demonstrate that the co-culture of PHH with other non-parenchymal cells enables the identification of the cellular origin of immune effectors, thus providing a valuable preclinical platform for HBV research.
Purpose
Cognitive impairment after critical illness is common and debilitating. We developed a cognitive therapy program for critically ill patients and assessed the feasibility and safety of ...administering combined cognitive and physical therapy early during a critical illness.
Methods
We randomized 87 medical and surgical ICU patients with respiratory failure and/or shock in a 1:1:2 manner to three groups: usual care, early once-daily physical therapy, or early once-daily physical therapy plus a novel, progressive, twice-daily cognitive therapy protocol. Cognitive therapy included orientation, memory, attention, and problem-solving exercises, and other activities. We assessed feasibility outcomes of the early cognitive plus physical therapy intervention. At 3 months, we also assessed cognitive, functional, and health-related quality of life outcomes. Data are presented as median (interquartile range) or frequency (%).
Results
Early cognitive therapy was a delivered to 41/43 (95 %) of cognitive plus physical therapy patients on 100 % (92–100 %) of study days beginning 1.0 (1.0–1.0) day following enrollment. Physical therapy was received by 17/22 (77 %) of usual care patients, by 21/22 (95 %) of physical therapy only patients, and 42/43 (98 %) of cognitive plus physical therapy patients on 17 % (10–26 %), 67 % (46–87 %), and 75 % (59–88 %) of study days, respectively. Cognitive, functional, and health-related quality of life outcomes did not differ between groups at 3-month follow-up.
Conclusions
This pilot study demonstrates that early rehabilitation can be extended beyond physical therapy to include cognitive therapy. Future work to determine optimal patient selection, intensity of treatment, and benefits of cognitive therapy in the critically ill is needed.
We investigate the relationship between stellar mass, metallicity and gas content for a magnitude- and volume-limited sample of 260 nearby late-type galaxies in different environments, from isolated ...galaxies to Virgo cluster members. We derive oxygen abundance estimates using new integrated, drift-scan optical spectroscopy and the base metallicity calibrations of Kewley & Ellison (2008, ApJ, 681, 1183). Combining these measurements with ultraviolet to near-infrared photometry and Hi 21 cm line observations, we examine the relations between stellar mass, metallicity, gas mass fraction and star formation rate. We find that, at fixed stellar mass, galaxies with lower gas fractions typically also possess higher oxygen abundances. We also observe a relationship between gas fraction and metal content, whereby gas-poor galaxies are typically more metal-rich, and demonstrate that the removal of gas from the outskirts of spirals may increase the observed average metallicity by ~0.1 dex. Although some cluster galaxies are gas-deficient objects, statistically the stellar-mass metallicity relation is nearly invariant to the environment, in agreement with recent studies. These results indicate that internal evolutionary processes, rather than environmental effects, play a key role in shaping the stellar mass-metallicity relation. In addition, we present metallicity estimates based on observations of 478 nearby galaxies.
We combine dust, atomic (H i) and molecular (H2) hydrogen mass measurements for 176 galaxies in the Herschel Reference Survey to investigate the effect of environment on the gas-to-dust mass (M
gas/M
...dust) ratio of nearby galaxies. We find that, at fixed stellar mass, the average M
gas/M
dust ratio varies by no more than a factor of ∼2 when moving from field to cluster galaxies, with Virgo galaxies being slightly more dust rich (per unit of gas) than isolated systems. Remarkably, once the molecular and atomic hydrogen phases are investigated separately, we find that H i-deficient galaxies have at the same time lower
$M_{\rm H\,\small {I}}/M_{\rm dust}$
ratio but higher
$M_{\rm H_{2}}/M_{\rm dust}$
ratio than H i-normal systems. In other words, they are poorer in atomic but richer in molecular hydrogen if normalized to their dust content. By comparing our findings with the predictions of theoretical models, we show that the opposite behaviour observed in the
$M_{\rm H\,\small {I}}/M_{\rm dust}$
and
$M_{\rm H_{2}}/M_{\rm dust}$
ratios is fully consistent with outside-in stripping of the interstellar medium (ISM), and is simply a consequence of the different distribution of dust, H i and H2 across the disc. Our results demonstrate that the small environmental variations in the total M
gas/M
dust ratio, as well as in the gas-phase metallicity, do not automatically imply that environmental mechanisms are not able to affect the dust and metal content of the ISM in galaxies.
Chronic lymphocytic leukemia (CLL) is a progressive malignancy of mature B-cells that involves the peripheral blood (PB), lymph nodes (LNs) and bone marrow (BM). Although the majority of CLL cells ...are in a resting state, small populations of proliferating cells exist; however, the anatomical site of active cell proliferation remains to be definitively determined. Based on findings that CLL cells in LNs have increased expression of B-cell activation genes, we tested the hypothesis that the fraction of 'newly born' cells would be highest in the LNs. Using a deuterium oxide (
H) in vivo labeling method in which patients consumed deuterated (heavy) water (
H
O), we determined CLL cell kinetics in concurrently obtained samples from LN, PB and BM. The LN was identified as the anatomical site harboring the largest fraction of newly born cells, compared to PB and BM. In fact, the calculated birth rate in the LN reached as high a 3.3% of the clone per day. Subdivision of the bulk CLL population by flow cytometry identified the subpopulation with the CXCR4
CD5
phenotype as containing the highest proportion of newly born cells within each compartment, including the LN, identifying this subclonal population as an important target for novel treatment approaches.
We investigate the properties of galaxies between the blue and the red sequence (i.e. the transition region, 4.5 < NUV −H < 6 mag) by combining ultraviolet (UV) and near-infrared imaging to 21-cm H i ...line observations for a volume-limited sample of nearby galaxies. We confirm the existence of a tight relation between colour and H i fraction across all the range of colours, although outside the blue cloud this trend becomes gradually weaker. Transition galaxies are divided into two different families, according to their atomic hydrogen content. ‘H i-deficient’ galaxies are the majority of transition galaxies in our sample. They are found in high-density environments and all their properties are consistent with a quenching of the star formation via gas stripping. However, while the migration from the blue cloud is relatively quick (i.e. ≲1 Gyr), a longer amount of time (a few Gyr at least) seems required to completely suppress the star formation and reach the red sequence. At all masses, migrating ‘H i-deficient’ galaxies are mainly discs, implying that the mechanism responsible for today's migration in clusters cannot have played a significant role in the creation of the red sequence at high redshift. Conversely, ‘H i-normal’ transition galaxies are a more heterogeneous population. A significant fraction of these objects show star formation in ring-like structures and evidence for accretion/minor-merging events suggesting that at least part of the H i reservoir has an external origin. The detailed evolution of such systems is still unclear, but our analysis suggests that, in at least two cases, galaxies might have migrated back from the red sequence after accretion events. Interestingly, the H i available may be sufficient to sustain star formation at the current rate for several billion years. Our study clearly shows the variety of evolutionary paths leading to the transition region and suggests that the transition galaxies may not be always associated with systems quickly migrating from the blue to the red sequence.
We use H Delta *a and far-ultraviolet (FUV, 1539 A) Galaxy Evolution Explorer (GALEX) data for a large sample of nearby objects to study the high-mass (m>= 2 M ) star formation activity of normal ...late-type galaxies. The data are corrected for dust attenuation using the most accurate techniques available at present, namely the Balmer decrement for H Delta *a data and the total far-infrared to FUV flux ratio for GALEX data. The sample shows a highly dispersed distribution in the H Delta *a to FUV flux ratio (log f(H Delta *a)/f(FUV) = 1.10 +/- 0.34 A) indicating that two of the most commonly used star formation tracers give star formation rates (SFRs) with uncertainties up to a factor of 2-3. The high dispersion is partly due to the presence of active galactic nuclei, where the UV and the H Delta *a emission can be contaminated by nuclear activity, highly inclined galaxies, for which the applied extinction corrections are probably inaccurate, or starburst galaxies, where the stationarity in the star formation history required for transforming H Delta *a and UV luminosities into SFRs is not satisfied. Excluding these objects, normal late-type galaxies have log f(H Delta *a)/f(FUV) = 0.94 +/- 0.16 A, which corresponds to an uncertainty of ~50% on the SFR. The H Delta *a to FUV flux ratio of the observed galaxies increases with their total stellar mass. If limited to normal star-forming galaxies, however, this relationship reduces to a weak trend that might be totally removed using different extinction correction recipes. In these objects, the H Delta *a to FUV flux ratio seems also barely related to the FUV - H color, the H-band effective surface brightness, the total star formation activity, and the gas fraction. The data are consistent with a Kroupa and Salpeter initial mass function (IMF) in the high-mass stellar range (m > 2 M ) and imply, for a Salpeter IMF, that the variations of the slope Delta *g cannot exceed 0.25, from Delta *g = 2.35 for massive galaxies to Delta *g = 2.60 in low luminosity systems. We show however that these observed trends, if real, can be due to the different micro-history of star formation in massive galaxies with respect to dwarf systems.
To identify the main causes of morbidity and mortality in patients with antiphospholipid syndrome (APS) during a 5-year period and to determine clinical and immunological parameters with prognostic ...significance.
The clinical and immunological features of a cohort of 1000 patients with APS from 13 European countries who had been followed up from 1999 to 2004 were analysed.
200 (20%) patients developed APS-related manifestations during the 5-year study period. Recurrent thrombotic events appeared in 166 (16.6%) patients and the most common were strokes (2.4% of the total cohort), transient ischaemic attacks (2.3%), deep vein thromboses (2.1%) and pulmonary embolism (2.1%). When the thrombotic events occurred, 90 patients were receiving oral anticoagulants and 49 were using aspirin. 31/420 (7.4%) patients receiving oral anticoagulants presented with haemorrhage. 3/121 (2.5%) women with only obstetric APS manifestations at the start of the study developed a new thrombotic event. A total of 77 women (9.4% of the female patients) had one or more pregnancies and 63 (81.8% of pregnant patients) had one or more live births. The most common fetal complications were early pregnancy loss (17.1% of pregnancies) and premature birth (35% of live births). 53 (5.3% of the total cohort) patients died. The most common causes of death were bacterial infection (21% of deaths), myocardial infarction (19%) and stroke (13%). No clinical or immunological predictor of thrombotic events, pregnancy morbidity or mortality was detected.
Patients with APS still develop significant morbidity and mortality despite current treatment (oral anticoagulants or antiaggregants, or both).