Pragmatic controlled clinical trials in primary care: the struggle between external and internal validity

BACKGROUND: Controlled clinical trials of health care interventions are either explanatory or pragmatic. Explanatory trials test whether an intervention is efficacious; that is, whether it can have a beneficial effect in an ideal situation. Pragmatic trials measure effectiveness; they measure the degree of beneficial effect in real clinical practice. In pragmatic trials, a balance between external validity (generalizability of the results) and internal validity (reliability or accuracy of the results) needs to be achieved. The explanatory trial seeks to maximize the internal validity by assuring rigorous control of all variables other than the intervention. The pragmatic trial seeks to maximize external validity to ensure that the results can be generalized. However the danger of pragmatic trials is that internal validity may be overly compromised in the effort to ensure generalizability. We are conducting two pragmatic randomized controlled trials on interventions in the management of hypertension in primary care. We describe the design of the trials and the steps taken to deal with the competing demands of external and internal validity. DISCUSSION: External validity is maximized by having few exclusion criteria and by allowing flexibility in the interpretation of the intervention and in management decisions. Internal validity is maximized by decreasing contamination bias through cluster randomization, and decreasing observer and assessment bias, in these non-blinded trials, through baseline data collection prior to randomization, automating the outcomes assessment with 24 hour ambulatory blood pressure monitors, and blinding the data analysis. SUMMARY: Clinical trials conducted in community practices present investigators with difficult methodological choices related to maintaining a balance between internal validity (reliability of the results) and external validity (generalizability). The attempt to achieve methodological purity can result in clinically meaningless results, while attempting to achieve full generalizability can result in invalid and unreliable results. Achieving a creative tension between the two is crucial

Close companions to Brightest Cluster Galaxies: Support for minor mergers and downsizing

We identify close companions of Brightest Cluster Galaxies (BCGs) for the purpose of quantifying the rate at which these galaxies grow via mergers. By exploiting deep photometric data from the CFHTLS, we probe the number of companions per BCG (Nc) with luminosity ratios down to those corresponding to potential minor mergers of 20:1. We also measure the average luminosity in companions per galaxy (Lc). We find that Nc and Lc rise steeply with luminosity ratio for both the BCGs, and a control sample of other bright, red, cluster galaxies. The trend for BCGs rises more steeply, resulting in a larger number of close companions. For companions within 50kpc of a BCG, Nc= 1.38+/-0.14 and Lc=(2.14+/-0.31)x10^(10)L_sun and for companions within 50kpc of a luminosity matched control sample of non-BCGs, Nc=0.87+/-0.08 and Lc=(1.48+/-0.20)x10^(10)L_sun. This suggests that the BCGs are likely to undergo more mergers compared to otherwise comparable luminous galaxies. Additionally, compared to a local sample of luminous red galaxies, the more distant sample presented in this study (with redshifts between 0.15-0.39,) shows a higher Nc, suggesting the younger and smaller BCGs are still undergoing hierarchical formation. Using the Millennium Simulations we model and estimate the level of contamination due to unrelated cluster galaxies. The contamination by interloping galaxies is 50% within projected separations of 50kpc, but within 30kpc, 60% of identified companions are real physical companions. We conclude that the luminosity of bound merger candidates down to luminosity ratios of 20:1 could be adding as much as 10% to the mass of a typical BCG over 0.5Gyr at redshifts of z~0.3.Comment: 10 pages, 7 figures. Accepted and to be published in MNRA

The Rise and Fall of Passive Disk Galaxies: Morphological Evolution Along the Red Sequence Revealed by COSMOS

The increasing abundance of passive "red-sequence" galaxies since z=1-2 is mirrored by a coincident rise in the number of galaxies with spheroidal morphologies. In this paper, however, we show that in detail the correspondence between galaxy morphology and color is not perfect, providing insight into the physical origin of this evolution. Using the COSMOS survey, we study a significant population of red sequence galaxies with disk-like morphologies. These passive disks typically have Sa-Sb morphological types with large bulges, but they are not confined to dense environments. They represent nearly one-half of all red-sequence galaxies and dominate at lower masses (log Mstar < 10) where they are increasingly disk-dominated. As a function of time, the abundance of passive disks with log Mstar < 11 increases, but not as fast as red-sequence spheroidals in the same mass range. At higher mass, the passive disk population has declined since z~1, likely because they transform into spheroidals. We estimate that as much as 60% of galaxies transitioning onto the red sequence evolve through a passive disk phase. The origin of passive disks therefore has broad implications for understanding how star formation shuts down. Because passive disks tend to be more bulge-dominated than their star-forming counterparts, a simple fading of blue disks does not fully explain their origin. We explore several more sophisticated explanations, including environmental effects, internal stabilization, and disk regrowth during gas-rich mergers. While previous work has sought to explain color and morphological transformations with a single process, these observations open the way to new insight by highlighting the fact that galaxy evolution may actually proceed through several separate stages.Comment: 16 pages, Accepted version to appear in Ap

Effects on Galaxy Evolution: Pair Interactions versus Environment

In a hierarchical universe, mergers may be an important mechanism not only in increasing the mass of galaxies but also in driving the color and morphological evolution of galaxies. We use a large sample of ~1000 simulated galaxies of stellar mass greater than 10^9.6 solar masses (for ~4800 observations at multiple redshifts) from a high-res (0.46 h^{-1} kpc) cosmological simulation to determine under what circumstances being a member of a pair influences galaxy properties at z <= 0.2. We identify gravitationally bound pairs, and find a relative fraction of blue-blue, red-red, and blue-red pairs that agrees with observations (Lin et al. 2010). Pairs tend to avoid the extreme environments of clusters and void centres. While pairs in groups can include galaxies that are both blue, both red, or one of each color, in the field it is rare for pair galaxies to both be red. We find that physically bound pairs closer than 250 h^{-1} kpc tend to have higher sSFRs than the galaxy population as a whole. However, the sSFR of a bound galaxy relative to galaxies in a comparable local density environment (determined by the distance to the fifth nearest neighbor, rho_5), differs depending on the local density. In regions of high rho_5 the bound population has a higher fraction of star-forming (bluer) galaxies, whereas there is very little difference between bound and unbound galaxies in low rho_5 regions. This effect on the star-forming fraction may be driven by the higher fraction of bound HI-rich galaxies compared to unbound galaxies, particularly at high local densities. It appears that being in a pair has an incremental, but not overwhelming, effect on the star formation rate of the paired galaxies, compared to the more pronounced trend where galaxies overall have low sSFR (are red) in clusters and higher sSFR (blue) at the centre of voids. This trend depends most strongly on rho_5.(abridged)Comment: Version 2; reorganized (some sections moved to appendix), edited for clarity (sections 6.1 and 7 heavily edited), figures edited, conclusions qualitatively unchanged but section edited. Accepted in MNRAS; 19 pages, 15 figure

The effects of the cluster environment on the galaxy mass-size relation in MACS J1206.2-0847

The dense environment of galaxy clusters strongly influences the nature of galaxies. Their abundance and diversity is imprinted on the stellar-mass–size plane. Here, we study the cause of the size distribution of a sample of 560 spectroscopic members spanning a wide dynamical range down to 108.5 M (log (M)-2) in the massive CLASH cluster MACSJ1206.2-0847 at z=0.44. We use Subaru SuprimeCam imaging covering the highest-density core out to the infall regions (3 virial radii) to look for cluster-specific effects on a global scale. We also compare our measurements to a compatible large field study in order to span extreme environmental densities. This paper presents the trends we identified for cluster galaxies divided by their colors into star forming and quiescent galaxies and into distinct morphological types (using Sérsic index and bulge/disk decompositions). We observed larger sizes for early-type galaxies and smaller sizes for massive late-type galaxies in clusters in comparison to the field. We attribute this to longer quenching timescales of more massive galaxies in the cluster. Our analysis further revealed an increasing importance of recently quenched transition objects (“red disks”), where the correspondence between galaxy morphology and color is out of sync. This is a virialized population with sizes similar to the quiescent, spheroid-dominated population of the cluster center, but with disks still in-tact, and found at higher cluster-centric radii. The mass-size relation of cluster galaxies may therefore be understood as the consequence of a mix of progenitors formed at different quenching epochs. We also investigate the stellar-mass–size relation as a representation of galaxy sizes smoothly decreasing as a function of bulge fraction. We find that at an identical bulge-to-total ratio and identical stellar mass, quiescent galaxies are smaller than star forming galaxies. This is likely because of a fading of the outskirts of the disk, which we saw in comparing sizes of their disk-components. Ram-pressure stripping of the cold gas and other forms of more gradual gas starvation are likely responsible for this observation

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Personal non-commercial use only

ABSTRACT. Objective. To assess driving problems experienced by patients with rheumatoid arthritis (RA) and to examine the relationship between functional status and driving difficulty. Methods. Using the South Eastern Ontario Medical Organization (SEAMO) database, we identified 721 patients with RA from both urban and rural backgrounds. They completed a cross-sectional, selfadministered mail survey that included the Health Assessment Questionnaire (HAQ-DI) and a comorbidity questionnaire. We assessed the proportion of drivers versus non-drivers and patients who reported difficulty driving and who used vehicle adaptations. Results. Survey response rate was 74% and 92.2% of the subjects were current drivers. Fifty percent of the current drivers reported a little difficulty, 6.8% reported quite a bit of difficulty, and 1.5% a great deal of difficulty driving. Major reasons given for why RA limited their driving were stiffness and pain. Frequent use of mobility aids (adjusted odds ratio, OR: 5.85), HAQ-DI ≥ 1 (adjusted OR: 3.40), and older age (adjusted OR: 1.04) were significant predictors of an individual with RA discontinuing driving. Higher levels of disability (HAQ-DI) were associated with a greater number of problems reported with driving and with curtailment of driving. A multivariate logistic regression determined that having a HAQ-DI ≥ 1 (adjusted OR: 4.3) and difficulties sitting in the vehicle (adjusted OR: 2.9) were associated with RA limiting driving. Conclusion. Over 50% of respondents reported some degree of difficulty driving due to their RA. Scores on HAQ-DI ≥ 1 were associated with difficulty driving. Further validation of our findings needs to be performed. (J Rheumatol 2005;32:2337-42

Anatomia do escapo floral de esp\ue9cies brasileiras de Paepalanthus subg\ueanero Platycaulon (Eriocaulaceae)

Foi estudada a anatomia dos escapos de 17 espécies de Paepalanthus subgênero Platycaulon, sendo 10 da sect. Divisi e sete da sect. Conferti. O trabalho foi realizado para caracterizar anatomicamente os escapos. como contribuição para o entendimento do grupo, uma vez que. morfologicamente, esse é o caráter laxonômico mais importante. Procurou-se, também, confirmar ou não o reconhecimento das duas seções dentro do subgênero. Para os estudos anatômicos utilizou-se material proveniente do Brasil, obtido de exsicatas de diferentes herbários e/ou coletado na Serra do Cipó, MG. Neste trabalho observou-se que Paepalanthus subg. Platycaulon é caracterizado morfologicamente por apresentar escapos pluricapitulados no ápice. Anatomicamente, as espécies estudadas da sect. Divisi apresentam escapos com vários cilindros vasculares, na região mediana e, ainda apresentam, em Paepalanthus vellozioides e P. spixianus, feixes vasculares corticais, características únicas na família. Diferentemente, as espécies avaliadas da sect. Conferti apresentam escapos com cilindro vascular único na região mediana, padrão análogo ao das demais Eriocaulaccae, e ainda apresentam, em Paepalanthus itatiaiensis, P. planifolius e P. paulensis, feixes vasculares medulares, que até então não haviam sido referidos para a família.The scape anatomy of 17 taxa of Paepalanthus subgenus Platycaylon were studied, being 10 taxa of sect. Divisi and seven of sect. Conferti. The study was carried out to see whether scape morphology and anatomy provide valid taxonomic characters at the subgeneric level in Paepalanthus and to lest a proposal to recognize two sections within Paepalanthus subgenus Platycaylon: sect. Divisi and sect. Conferti. The material for anatomical study was collected in Brazil, partly from herbarium specimens and partly from fresh material collected in the field, from the Serra do Cipó. Minas Gerais State. In this work, we observe that Paepalanthus subg. Platycaulon is characterized morphologically by its pluricapitulate scapes. Anatomycally, the studied species of the Divisi sect, are characterized by having separate vascular cylinders, and present cortical vascular bundles in Paepalanthus vellozioides and P. spixianus, being these characteristics unique to the family, while the scapes of the studied members of sect. Conferti display a continuous vascular cylinder, which is analogous with other groups within the Eriocaulaceac, and present pith vascular bundles in Paepalanthus itatiaiensis, P planifolius and P. paulensis, characteristics unique to the family

Crowded Field Galaxy Photometry: Precision Colors in the CLASH Clusters

We present a new method for photometering objects in galaxy clusters. We introduce a mode-filtering technique for removing spatially variable backgrounds, improving both detection and photometric accuracy (roughly halving the scatter in the red sequence compared to previous catalogs of the same clusters). This method is based on robustly determining the distribution of background pixel values and should provide comparable improvement in photometric analysis of any crowded fields. We produce new multiwavelength catalogs for the 25 CLASH cluster fields in all 16 bandpasses from the UV through the near IR, as well as rest-frame magnitudes. A comparison with spectroscopic values from the literature finds a ~30% decrease in the redshift deviation from previously-released CLASH photometry. This improvement in redshift precision, in combination with a detection scheme designed to maximize purity, yields a substantial upgrade in cluster member identification over the previous CLASH galaxy catalog. We construct luminosity functions for each cluster, reliably reaching depths of at least 4.5 mag below M* in every case, and deeper still in several clusters. We measure M* , $\alpha$, and their redshift evolution, assuming the cluster populations are coeval, and find little to no evolution of $\alpha$, $-0.9\lesssim\langle\alpha\rangle\lesssim -0.8$, and M* values consistent with passive evolution. We present a catalog of galaxy photometry, photometric and spectroscopic redshifts, and rest-frame photometry for the full fields of view of all 25 CLASH clusters. Not only will our new photometric catalogs enable new studies of the properties of CLASH clusters, but mode-filtering techniques, such as those presented here, should greatly enhance the data quality of future photometric surveys of crowded fields.Comment: 24 pages, 13 figures. Published in ApJ, 201