Are we overusing IVF?

Peer reviewedPublisher PD

The blood-brain barrier in multiple sclerosis: microRNAs as key regulators

Multiple sclerosis (MS) is a progressive inflammatory disease of the central nervous system (CNS) leading to severe neurological deficits. To date, no treatment is available that halts disease progression, but clinical symptoms can be generally improved by therapies involving anti-inflammatory and/or immune modulatory reagents, which may cause off-target effects. Therefore, there remains a high and unmet need for more selective treatment strategies in MS. An early event in MS is a diminished function of the blood-brain barrier (BBB) which consists of specialized brain endothelial cells (BECs) that are supported in their barrier function by surrounding glial cells. Leakage and inflammation of the BECs in MS patients facilitate the massive influx of leukocytes into the brain parenchyma, which in turn induces irreversible demyelination, tissue damage and axonal dysfunction. Identification of ways to restore BBB function and promote its immune quiescence may therefore lead to the development of novel therapeutic regimes that not only specifically reduce leukocyte entry into the central nervous system but also restore the disturbed brain homeostasis. However, the complex network of molecular players that leads to BBB dysfunction in MS is yet to be fully elucidated. Recent discoveries unravelled a critical role for microRNAs (miRNAs) in controlling the function of the barrier endothelium in the brain. Here we will review the current knowledge on the involvement of BBB dysfunction in MS and the central role that miRNAs play in maintaining BBB integrity under inflammatory conditions

Improving predictive performance on survival in dairy cattle using an ensemble learning approach

Cow survival is a complex trait that combines traits like milk production, fertility, health and environmental factors such as farm management. This complexity makes survival difficult to predict accurately. This is probably the reason why few studies attempted to address this problem and no studies are published that use ensemble methods for this purpose. We explored if we could improve prediction of cow survival to second lactation, when predicted at five different moments in a cow's life, by combining the predictions of multiple (weak) methods in an ensemble method. We tested four ensemble methods: majority voting rule, multiple logistic regression, random forest and naive Bayes. Precision, recall, balanced accuracy, area under the curve (AUC) and gains in proportion of surviving cows in a scenario where the best 50% were selected were used to evaluate the ensemble model performance. We also calculated correlations between the ensemble models and obtained McNemar's test statistics. We compared the performance of the ensemble methods against those of the individual methods. We also tested if there was a difference in performance metrics when continuous (from 0 to 1) and binary (0 or 1) prediction outcomes were used. In general, using continuous prediction output resulted in higher performance metrics than binary ones. AUCs for models ranged from 0.561 to 0.731, with generally increasing performance at moments later in life. Precision, AUC and balanced accuracy values improved significantly for the naive Bayes and multiple logistic regression ensembles in at least one data set, although performance metrics did remain low overall. The multiple logistic regression ensemble method resulted in equal or better precision, AUC, balanced accuracy and proportion of animals surviving on all datasets and was significantly different from the other ensembles in three out of five moments. The random forest ensemble method resulted in the least significant improvement over the individual methods

The star formation histories of galaxies in different stages of pre-processing in the Fornax A group

We study the recent star formation histories of ten galaxies in the Fornax A galaxy group, on the outskirts of the Fornax cluster. The group galaxies are gas-rich, and their neutral atomic hydrogen (HI) was studied in detail with observations from the MeerKAT telescope. This allowed them to be classified into different stages of pre-processing (early, ongoing, advanced). We use long-slit spectra obtained with the South African Large Telescope (SALT) to analyse stellar population indicators to constrain quenching timescales and to compare these to the HI gas content of the galaxies. The H$\alpha$ equivalent width, EW(H$\alpha$), suggest that the pre-processing stage is closely related to the recent (< 10 Myr) specific Star Formation Rate (sSFR). The early-stage galaxy (NGC 1326B) is not yet quenched in its outer parts, while the ongoing-stage galaxies mostly have a distributed population of very young stars, though less so in their outer parts. The galaxies in the advanced stage of pre-processing show very low recent sSFR in the outer parts. Our results suggest that NGC 1326B, FCC 35 and FCC 46 underwent significantly different histories from secular evolution during the last Gyr. The fact that most galaxies are on the secular evolution sequence implies that pre-processing has a negligible effect on these galaxies compared to secular evolution. We find EW(H$\alpha$) to be a useful tool for classifying the stage of pre-processing in group galaxies. The recent sSFR and HI morphology show that galaxies in the Fornax A vicinity are pre-processing from the outside in.Comment: 17 pages, accepted for publication in MNRA

An Exploration of the Tully-Fisher Relation for Extreme Late-Type Spiral Galaxies

This paper explores the adherence of 47 extreme late-type galaxies to the B- and V-band Tully-Fisher relations defined by a sample of local calibrators. In both bands we find the mean luminosity at a given line width for extreme late-type spirals to lie below that predicted by standard Tully-Fisher relations. While many of the extreme late-type spirals do follow the Tully-Fisher relation to within our observational uncertainties, most of these galaxies lie below the normal, linear Tully-Fisher relation, and some are underluminous by more than 2 sigma (i.e. >1.16 magnitudes in V). This suggests a possible downward curvature of the Tully-Fisher relation for some of the smallest and faintest rotationally supported disk galaxies. This may be a consequence of the increasing prevalence of dark matter in these systems. We find the deviation from the Tully-Fisher relation to increase with decreasing luminosity and decreasing optical linear size in our sample, implying that the physically smallest and faintest spirals may be a structurally and kinematically distinct class of objects.Comment: 32 pages, 13 figures; to appear in the November A

Correction to:Oral esketamine for treatment-resistant depression: rationale and design of a randomized controlled trial

After publication of our article [1] we were notified that Figure 1 was wrongly presented

Oral esketamine for treatment-resistant depression:rationale and design of a randomized controlled trial

BACKGROUND: There is an urgent need to develop additional treatment strategies for patients with treatment-resistant depression (TRD). The rapid but short-lived antidepressant effects of intravenous (IV) ketamine as a racemic mixture have been shown repeatedly in this population, but there is still a paucity of data on the efficacy and safety of (a) different routes of administration, and (b) ketamine's enantiomers esketamine and arketamine. Given practical advantages of oral over IV administration and pharmacodynamic arguments for better antidepressant efficacy of esketamine over arketamine, we designed a study to investigate repeated administration of oral esketamine in patients with TRD. METHODS: This study features a triple-blind randomized placebo-controlled trial (RCT) comparing daily oral esketamine versus placebo as add-on to regular antidepressant medications for a period of 6 weeks, succeeded by a follow-up of 4 weeks. The methods support examination of the efficacy, safety, tolerability, mechanisms of action, and economic impact of oral esketamine in patients with TRD. DISCUSSION: This is the first RCT investigating repeated oral esketamine administration in patients with TRD. If shown to be effective and tolerated, oral esketamine administration poses important advantages over IV administration. TRIAL REGISTRATION: Dutch Trial Register, NTR6161. Registered 21 October 2016

CO(1-0), CO(2-1) and Neutral Gas in NGC 6946: Molecular Gas in a Late-Type, Gas Rich, Spiral Galaxy

We present "On The Fly" maps of the CO(1-0) and CO(2-1) emission covering a 10' X 10' region of the NGC 6946. Using our CO maps and archival VLA HI observations we create a total gas surface density map, Sigma_gas, for NGC 6946. The predominantly molecular inner gas disk transitions smoothly into an atomic outer gas disk, with equivalent atomic and molecular gas surface densities at R = 3.5' (6 kpc). We estimate that the total H2 mass is 3 X 10^9 Mo, roughly 1/3 of the interstellar hydrogen gas mass, and about 2% of the dynamical mass of the galaxy at our assumed distance of 6 Mpc. The value of the CO(2-1)/CO(1-0) line ratio ranges from 0.35 to 2; 50% of the map is covered by very high ratio, >1, gas. The very high ratios are predominantly from interarm regions and appear to indicate the presence of wide-spread optically thin gas. Star formation tracers are better correlated with the total neutral gas disk than with the molecular gas by itself implying SFR is proportional to Sigma_gas. Using the 100 FIR and 21 cm continuum from NGC 6946 as star formation tracers, we arrive at a gas consumption timescale of 2.8 Gyr, which is relatively uniform across the disk. The high star formation rate at the nucleus appears to be due to a large accumulation of molecular gas rather than a large increase in the star formation efficiency. The mid-plane gas pressure in the outer (R > 10 kpc) HI arms of NGC 6946 is close to the value at the radial limit (10 kpc) of our observed CO disk. If the mid-plane gas pressure is a factor for the formation of molecular clouds, these outer HI gas arms should contain molecular gas which we do not see because they are beyond our detection limit

The Updated Zwicky Catalog (UZC)

The Zwicky Catalog of galaxies (ZC), with m_Zw<=15.5mag, has been the basis for the Center for Astrophysics (CfA) redshift surveys. To date, analyses of the ZC and redshift surveys based on it have relied on heterogeneous sets of galaxy coordinates and redshifts. Here we correct some of the inadequacies of previous catalogs by providing: (1) coordinates with <~2 arcsec errors for all of the Nuzc catalog galaxies, (2) homogeneously estimated redshifts for the majority (98%) of the data taken at the CfA (14,632 spectra), and (3) an estimate of the remaining "blunder" rate for both the CfA redshifts and for those compiled from the literature. For the reanalyzed CfA data we include a calibrated, uniformly determined error and an indication of the presence of emission lines in each spectrum. We provide redshifts for 7,257 galaxies in the CfA2 redshift survey not previously published; for another 5,625 CfA redshifts we list the remeasured or uniformly re-reduced value. Among our new measurements, Nmul are members of UZC "multiplets" associated with the original Zwicky catalog position in the coordinate range where the catalog is 98% complete. These multiplets provide new candidates for examination of tidal interactions among galaxies. All of the new redshifts correspond to UZC galaxies with properties recorded in the CfA redshift compilation known as ZCAT. About 1,000 of our new measurements were motivated either by inadequate signal-to-noise in the original spectrum or by an ambiguous identification of the galaxy associated with a ZCAT redshift. The redshift catalog we include here is ~96% complete to m_Zw<=15.5, and ~98% complete (12,925 galaxies out of a total of 13,150) for the RA(1950) ranges [20h--4h] and [8h--17h] and DEC(1950) range [-2.5d--50d]. (abridged)Comment: 34 pp, 7 figs, PASP 1999, 111, 43

The Fine-Scale Structure of the neutral Interstellar Medium in nearby Galaxies

We present an analysis of the properties of HI holes detected in 20 galaxies that are part of "The HI Nearby Galaxy Survey" (THINGS). We detected more than 1000 holes in total in the sampled galaxies. Where they can be measured, their sizes range from about 100 pc (our resolution limit) to about 2 kpc, their expansion velocities range from 4 to 36 km/s, and their ages are estimated to range between 3 and 150 Myr. The holes are found throughout the disks of the galaxies, out to the edge of the HI; 23% of the holes fall outside R25. We find that shear limits the age of holes in spirals (shear is less important in dwarf galaxies) which explains why HI holes in dwarfs are rounder, on average than in spirals. Shear, which is particularly strong in the inner part of spiral galaxies, also explains why we find that holes outside R25 are larger and older. We derive the scale height of the HI disk as a function of galactocentric radius and find that the disk flares up in all galaxies. We proceed to derive the surface and volume porosity (Q2D and Q3D) and find that this correlates with the type of the host galaxy: later Hubble types tend to be more porous. The size distribution of the holes in our sample follows a power law with a slope of a ~ -2.9. Assuming that the holes are the result of massive star formation, we derive values for the supernova rate (SNR) and star formation rate (SFR) which scales with the SFR derived based on other tracers. If we extrapolate the observed number of holes to include those that fall below our resolution limit, down to holes created by a single supernova, we find that our results are compatible with the hypothesis that HI holes result from star formation.Comment: 142 pages, 55 figures, accepted for publication in the Astronomical Journa