Slow recruitment in the HIMALAIA study:lessons for future clinical trials in patients with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage based on feasibility data

Background : Our randomized clinical trial on induced hypertension in patients with delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) was halted prematurely due to unexpected slow recruitment rates. This raised new questions regarding recruitment feasibility. As our trial can therefore be seen as a feasibility trial, we assessed the reasons for the slow recruitment, aiming to facilitate the design of future randomized trials in aSAH patients with DCI or other critically ill patient categories. Methods : Efficiency of recruitment and factors influencing recruitment were evaluated, based on the patient flow in the two centers that admitted most patients during the study period. We collected numbers of patients who were screened for eligibility, provided informed consent, and developed DCI and who eventually were randomized. Results : Of the 862 aSAH patients admitted in the two centers during the course of the trial, 479 (56%) were eligible for trial participation of whom 404 (84%) were asked for informed consent. Of these, 188 (47%) provided informed consent, of whom 50 (27%) developed DCI. Of these 50 patients, 12 (24%) could not be randomized due to a logistic problem or a contraindication for induced hypertension emerging at the time of randomization, and four (8%) were missed for randomization. Eventually, 34 patients were randomized and received intervention or control treatment. Conclusions : Enrolling patients in a randomized trial on a treatment strategy for DCI proved unfeasible: only 1 out of 25 admitted and 1 out of 14 eligible patients could eventually be randomized. These rates, caused by a large proportion of ineligible patients, a small proportion of patients providing informed consent, and a large proportion of patients with contraindications for treatment, can be used to make sample size calculations for future randomized trials in DCI or otherwise critically ill patients. Facilitating informed consent through improved provision of information on risks, possible benefits, and study procedures may result in improved enrolment

Induced hypertension for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage a randomized clinical trial

Background and Purpose-Induced hypertension is widely used to treat delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage, but a literature review shows that its presumed effectiveness is based on uncontrolled caseseries only. We here report clinical outcome of aneurysmal subarachnoid hemorrhage patients with DCI included in a randomized trial on the effectiveness of induced hypertension. Methods-Aneurysmal subarachnoid hemorrhage patients with clinical symptoms of DCI were randomized to induced hypertension or no induced hypertension. Risk ratios for poor outcome (modified Rankin Scale score >3) at 3 months, with 95% confidence intervals, were calculated and adjusted for age, clinical condition at admission and at time of DCI, and amount of blood on initial computed tomographic scan with Poisson regression analysis. Results-The trial aiming to include 240 patients was ended, based on lack of effect on cerebral perfusion and slow recruitment, when 21 patients had been randomized to induced hypertension, and 20 patients to no hypertension. With induced hypertension, the adjusted risk ratio for poor outcome was 1.0 (95% confidence interval, 0.6-1.8) and the risk ratio for serious adverse events 2.1 (95% confidence interval, 0.9-5.0). Conclusions-Before this trial, the effectiveness of induced hypertension for DCI in aneurysmal subarachnoid hemorrhage patients was unknown because current literature consists only of uncontrolled case series. The results from our premature halted trial do not add any evidence to support induced hypertension and show that this treatment can lead to serious adverse events

The distance to the giant elliptical galaxy NGC 5128

The distance to NGC 5128, the central galaxy of the Centaurus group and the nearest giant elliptical to us, has been determined using two independent distance indicators: the Mira period-luminosity (PL) relation and the luminosity of the tip of the red giant branch (RGB). The data were taken at two different locations in the halo of NGC 5128 with the ISAAC near-IR array on ESO VLT. From more than 20 hours of observations with ISAAC a very deep Ks-band luminosity function was constructed. The tip of the RGB is detected at Ks=21.24 \pm 0.05 mag. Using an empirical calibration of the K-band RGB tip magnitude, and assuming a mean metallicity of [M/H]=-0.4 dex and reddening of E(B-V)=0.11, a distance modulus of NGC 5128 of (m-M)_0=27.87 \pm 0.16 was derived. The comparison of the H-band RGB tip magnitude in NGC 5128 and the Galactic Bulge implies a distance modulus of NGC 5128 of (m-M)_0=27.9 \pm 0.2 in good agreement with the K-band RGB tip measurement. The population of stars above the tip of the RGB amounts to 2176 stars in the outer halo field and 6072 stars in the inner halo field. The large majority of these sources belong to the asymptotic giant branch (AGB) population in NGC 5128 with numerous long period variables. Mira variables were used to determine the distance of NGC 5128 from a period-luminosity relation calibrated using the Hipparcos parallaxes and LMC Mira period-luminosity relation in the K-band. This is the first Mira period-luminosity relation outside the Local Group. A distance modulus of 27.96 \pm 0.11 was derived, adopting the LMC distance modulus of 18.50 \pm 0.04. The mean of the two methods yields a distance modulus to NGC 5128 of 27.92 \pm 0.19 corresponding to D=3.84 \pm 0.35 Mpc.Comment: 11 pages, 8 figures; A&A in pres

Stellar populations in NGC 5128 with the VLT: evidence for recent star formation

We resolve stars of the nearest giant elliptical galaxy NGC 5128 using VLT with FORS1 and ISAAC. We construct deep U, V and Ks color-magnitude and color-color diagrams in two different halo fields (in the halo and in the north-eastern diffuse shell). In the outer, shell field, at ~14 kpc from the center of the galaxy, there is a significant recent star formation with stars as young as 10 Myr, approximately aligned with the prominent radio and x-ray jet from the nucleus of the host AGN. Ionized gas filaments are evident in ultraviolet images near the area where neutral HI and CO molecular gas was previously observed. The underlying stellar population of the halo of the giant elliptical is predominantly old with a very broad metallicity distribution. The presence of an extended giant branch reaching M_bol=-5 mag suggests the existence of a significant intermediate-age AGB population in the halo of this galaxy.Comment: 18 pages, 18 figures; to be published in A&A; high res. version at http://www.eso.org/~mrejkuba/cenA_starsVLT.p

Age and context of the oldest known hominin fossils from Flores

Recent excavations at the early Middle Pleistocene site of Mata Menge in the So\u27a Basin of central Flores, Indonesia, have yielded hominin fossils1 attributed to a population ancestral to Late Pleistocene Homo floresiensis2. Here we describe the age and context of the Mata Menge hominin specimens and associated archaeological findings. The fluvial sandstone layer from which the in situ fossils were excavated in 2014 was deposited in a small valley stream around 700 thousand years ago, as indicated by 40Ar/39Ar and fission track dates on stratigraphically bracketing volcanic ash and pyroclastic density current deposits, in combination with coupled uranium-series and electron spin resonance dating of fossil teeth. Palaeoenvironmental data indicate a relatively dry climate in the So\u27a Basin during the early Middle Pleistocene, while various lines of evidence suggest the hominins inhabited a savannah-like open grassland habitat with a wetland component. The hominin fossils occur alongside the remains of an insular fauna and a simple stone technology that is markedly similar to that associated with Late Pleistocene H. floresiensis

The Tully-Fisher relations of early-type spiral and S0 galaxies

We demonstrate that the comparison of Tully-Fisher relations (TFRs) derived from global HI line widths to TFRs derived from the circular velocity profiles of dynamical models (or stellar kinematic observations corrected for asymmetric drift) is vulnerable to systematic and uncertain biases introduced by the different measures of rotation used. We therefore argue that to constrain the relative locations of the TFRs of spiral and S0 galaxies, the same tracer and measure must be used for both samples. Using detailed near-infrared imaging and the circular velocities of axisymmetric Jeans models of 14 nearby edge-on Sa-Sb spirals and 14 nearby edge-on S0s drawn from a range of environments, we find that S0s lie on a TFR with the same slope as the spirals, but are on average 0.53+/-0.15 mag fainter at Ks-band at a given rotational velocity. This is a significantly smaller offset than that measured in earlier studies of the S0 TFR, which we attribute to our elimination of the bias associated with using different rotation measures and our use of earlier type spirals as a reference. Since our measurement of the offset avoids systematic biases, it should be preferred to previous estimates. A spiral stellar population in which star formation is truncated would take ~1 Gyr to fade by 0.53 mag at Ks-band. If S0s are the products of a simple truncation of star formation in spirals, then this finding is difficult to reconcile with the observed evolution of the spiral/S0 fraction with redshift. Recent star formation could explain the observed lack of fading in S0s, but the offset of the S0 TFR persists as a function of both stellar and dynamical mass. We show that the offset of the S0 TFR could therefore be explained by a systematic difference between the total mass distributions of S0s and spirals, in the sense that S0s need to be smaller or more concentrated than spirals.Comment: Accepted for publication in MNRAS; 17 pages; v2 incorporates minor proof corrections and updated reference

The formation of disc galaxies in a LCDM universe

We study the formation of disc galaxies in a fully cosmological framework using adaptive mesh refinement simulations. We perform an extensive parameter study of the main subgrid processes that control how gas is converted into stars and the coupled effect of supernovae feedback. We argue that previous attempts to form disc galaxies have been unsuccessful because of the universal adoption of strong feedback combined with high star formation efficiencies. Unless extreme amounts of energy are injected into the interstellar medium during supernovae events, these star formation parameters result in bulge dominated S0/Sa galaxies as star formation is too efficient at z~3. We show that a low efficiency of star-formation more closely models the subparsec physical processes, especially at high redshift. We highlight the successful formation of extended disc galaxies with scale lengths r_d=4-5 kpc, flat rotation curves and bulge to disc ratios of B/D~1/4. Not only do we resolve the formation of a Milky Way-like spiral galaxy, we also observe the secular evolution of the disc as it forms a pseudo-bulge. The disc properties agree well with observations and are compatible with the photometric and baryonic Tully-Fisher relations, the Kennicutt-Schmidt relation and the observed angular momentum content of spiral galaxies. We conclude that underlying small-scale star formation physics plays a larger role than previously considered in simulations of galaxy formation.Comment: Published in MNRA

Photometric Scaling Relations for Bulges of Galaxies

We study the photometric parameters of the bulges of galaxies of different Hubble types including ellipticals, lenticulars, early and late type spirals and early type dwarf galaxies. Analyzing the distributions of various photometric parameters, and two- and three-dimensional correlations between them, we find that there is a difference in the correlations exhibited by bright (M_K < -22) and faint bulges, irrespective of their Hubble type. Importantly, the bright bulges, which include typically E/S0 galaxies and bulges of early type spirals, are tightly distributed around a common photometric plane (PP), while their fainter counter parts, mainly bulges of late type spirals and dwarf galaxies show significant deviation from the planar distribution. We show that the specific entropy, determined from the bulge structural parameters, systematically increases as we move from late to early Hubble types. We interpret this as evidence for hierarchical merging and passive evolution scenarios for bright and faint bulges respectively.Comment: 27 pages, 16 figures, accepted in A&

The initial mass function of the rich young cluster NGC 1818 in the Large Magellanic Cloud

We use deep Hubble Space Telescope photometry of the rich, young (~20-45 Myr-old) star cluster NGC 1818 in the Large Magellanic Cloud to derive its stellar mass function (MF) down to ~0.15 Msun. This represents the deepest robust MF thus far obtained for a stellar system in an extragalactic, low-metallicity ([Fe/H]~-0.4 dex) environment. Combining our results with the published MF for masses above 1.0 Msun, we obtain a complete present-day MF. This is a good representation of the cluster's initial MF (IMF), particularly at low masses, because our observations are centred on the cluster's uncrowded half-mass radius. Therefore, stellar and dynamical evolution of the cluster will not have affected the low-mass stars significantly. The NGC 1818 IMF is well described by both a lognormal and a broken power-law distribution with slopes of Gamma=0.46+/-0.10 and Gamma~-1.35 (Salpeter-like) for masses in the range from 0.15 to 0.8 Msun and greater than 0.8 Msun, respectively. Within the uncertainties, the NGC 1818 IMF is fully consistent with both the Kroupa solar-neighbourhood and the Chabrier lognormal mass distributions.Comment: 11 pages, 9 figures, accepted by MNRA

Development of a quality indicator set to measure and improve quality of ICU care for patients with traumatic brain injury.

BACKGROUND: We aimed to develop a set of quality indicators for patients with traumatic brain injury (TBI) in intensive care units (ICUs) across Europe and to explore barriers and facilitators for implementation of these quality indicators. METHODS: A preliminary list of 66 quality indicators was developed, based on current guidelines, existing practice variation, and clinical expertise in TBI management at the ICU. Eight TBI experts of the Advisory Committee preselected the quality indicators during a first Delphi round. A larger Europe-wide expert panel was recruited for the next two Delphi rounds. Quality indicator definitions were evaluated on four criteria: validity (better performance on the indicator reflects better processes of care and leads to better patient outcome), feasibility (data are available or easy to obtain), discriminability (variability in clinical practice), and actionability (professionals can act based on the indicator). Experts scored indicators on a 5-point Likert scale delivered by an electronic survey tool. RESULTS: The expert panel consisted of 50 experts from 18 countries across Europe, mostly intensivists (N = 24, 48%) and neurosurgeons (N = 7, 14%). Experts agreed on a final set of 42 indicators to assess quality of ICU care: 17 structure indicators, 16 process indicators, and 9 outcome indicators. Experts are motivated to implement this finally proposed set (N = 49, 98%) and indicated routine measurement in registries (N = 41, 82%), benchmarking (N = 42, 84%), and quality improvement programs (N = 41, 82%) as future steps. Administrative burden was indicated as the most important barrier for implementation of the indicator set (N = 48, 98%). CONCLUSIONS: This Delphi consensus study gives insight in which quality indicators have the potential to improve quality of TBI care at European ICUs. The proposed quality indicator set is recommended to be used across Europe for registry purposes to gain insight in current ICU practices and outcomes of patients with TBI. This indicator set may become an important tool to support benchmarking and quality improvement programs for patients with TBI in the future