Fluence plays a critical role on the subsequent distribution of chemotherapy and tumor growth delay in murine mesothelioma xenografts pre-treated by photodynamic therapy.

BACKGROUND: The pre-conditioning of tumor vessels by low-dose photodynamic therapy (L-PDT) was shown to enhance the distribution of chemotherapy in different tumor types. However, how light dose affects drug distribution and tumor response is unknown. Here we determined the effect of L-PDT fluence on vascular transport in human mesothelioma xenografts. The best L-PDT conditions regarding drug transport were then combined with Lipoplatin(®) to determine tumor response. in vivo. Lasers Surg. Med. 47:323-330, 2015. © 2015 Wiley Periodicals, Inc. METHODS: Nude mice bearing dorsal skinfold chambers were implanted with H-Meso1 cells. Tumors were treated by Visudyne(®) -mediated photodynamic therapy with 100 mW/cm(2) fluence rate and a variable fluence (5, 10, 30, and 50 J/cm(2) ). FITC-Dextran (FITC-D) distribution was assessed in real time in tumor and normal tissues. Tumor response was then determined with best L-PDT conditions combined to Lipoplatin(®) and compared to controls in luciferase expressing H-Meso1 tumors by size and whole body bioluminescence assessment (n = 7/group). RESULTS: Tumor uptake of FITC-D following L-PDT was significantly enhanced by 10-fold in the 10 J/cm(2) but not in the 5, 30, and 50 J/cm(2) groups compared to controls. Normal surrounding tissue uptake of FITC-D following L-PDT was significantly enhanced in the 30 J/cm(2) and 50 J/cm(2) groups compared to controls. Altogether, the FITC-D tumor to normal tissue ratio was significantly higher in the 10 J/cm(2) group compared others. Tumor growth was significantly delayed in animals treated by 10 J/cm2-L-PDT combined to Lipoplatin(®) compared to controls. CONCLUSIONS: Fluence of L-PDT is critical for the optimal distribution and effect of subsequently administered chemotherapy. These findings have an importance for the clinical translation of the vascular L-PDT concept in the clinics. Lasers Surg. Med. 47:323-330, 2015.

Prediction in forensic science: a critical examination of common understandings

In this commentary, we argue that the term 'prediction' is overly used when in fact, referring to foundational writings of de Finetti, the correspondent term should be inference. In particular, we intend (i) to summarize and clarify relevant subject matter on prediction from established statistical theory, and (ii) point out the logic of this understanding with respect practical uses of the term prediction. Written from an interdisciplinary perspective, associating statistics and forensic science as an example, this discussion also connects to related fields such as medical diagnosis and other areas of application where reasoning based on scientific results is practiced in societal relevant contexts. This includes forensic psychology that uses prediction as part of its vocabulary when dealing with matters that arise in the course of legal proceedings.

Targeting Oxidative Stress and Aberrant Critical Period Plasticity in the Developmental Trajectory to Schizophrenia.

Schizophrenia is a neurodevelopmental disorder reflecting a convergence of genetic risk and early life stress. The slow progression to first psychotic episode represents both a window of vulnerability as well as opportunity for therapeutic intervention. Here, we consider recent neurobiological insight into the cellular and molecular components of developmental critical periods and their vulnerability to redox dysregulation. In particular, the consistent loss of parvalbumin-positive interneuron (PVI) function and their surrounding perineuronal nets (PNNs) as well as myelination in patient brains is consistent with a delayed or extended period of circuit instability. This linkage to critical period triggers (PVI) and brakes (PNN, myelin) implicates mistimed trajectories of brain development in mental illness. Strategically introduced antioxidant treatment or later reinforcement of molecular brakes may then offer a novel prophylactic psychiatry.

A pilot study identifying a set of microRNAs as precise diagnostic biomarkers of acute kidney injury

In the last decade, Acute Kidney Injury (AKI) diagnosis and therapy have not notably improved probably due to delay in the diagnosis, among other issues. Precocity and accuracy should be critical parameters in novel AKI biomarker discovery. microRNAs are key regulators of cell responses to many stimuli and they can be secreted to the extracellular environment. Therefore, they can be detected in body fluids and are emerging as novel disease biomarkers. We aimed to identify and validate serum miRNAs useful for AKI diagnosis and management. Using qRT-PCR arrays in serum samples, we determined miRNAs differentially expressed between AKI patients and healthy controls. Statistical and target prediction analysis allowed us to identify a panel of 10 serum miRNAs. This set was further validated, by qRT-PCR, in two independent cohorts of patients with relevant morbi-mortality related to AKI: Intensive Care Units (ICU) and Cardiac Surgery (CS). Statistical correlations with patient clinical parameter were performed. Our results demonstrated that the 10 selected miRNAs (miR-101-3p, miR-127-3p, miR-210-3p, miR-126-3p, miR-26b-5p, miR-29a-3p, miR-146a-5p, miR-27a-3p, miR-93-3p and miR-10a-5p) were diagnostic biomarkers of AKI in ICU patients, exhibiting areas under the curve close to 1 in ROC analysis. Outstandingly, serum miRNAs estimated before CS predicted AKI development later on, thus becoming biomarkers to predict AKI predisposition. Moreover, after surgery, the expression of the miRNAs was modulated days before serum creatinine increased, demonstrating early diagnostic value. In summary, we have identified a set of serum miRNAs as AKI biomarkers useful in clinical practice, since they demonstrate early detection and high diagnostic value and they recognize patients at risk.

Discrepancy between Visual Acuity and Microperimetry in AMD Patients: Visual Acuity Appears as an Inadequate Parameter to Test Macular Function.

BACKGROUND: Best corrected visual acuity (BCVA) of 0.8 or above in AMD patients can sometimes correspond to poor macular function inducing a serious visual handicap. Microperimetry can be used to objectivize this difference. PATIENTS AND METHODS: A retrospective study was undertaken on 233 files of AMD patients of whom 82 had had a microperimetry. BCVA was compared with microperimetry performance. All examinations were performed in an identical setting by the same team of 3 persons. RESULTS: Among the 82 patients included, 32 (39.0%) had a BCVA equal to or above 0.8 even though their microperimetry performance was lower than 200/560 db. 10 of them (12.2% of total) had an even poorer microperimetry below 120/560 db indicating poor macular function. CONCLUSIONS: More than a third of the AMD patients had a bad or very bad microperimetry performance in parallel with a good visual acuity. Microperimetry is a valuable tool to assess and follow real macular function in AMD patients when visual acuity alone can be misleading.

Assessing the sociology of sport: On sport organizations and critical knowledge

The purpose of this contribution is to analyse the trajectory, the challenges and the future of the sociology of sport on three levels: the internal dynamic within the specific sub-field of the sociology of sport, its interactions with sociology and sport sciences, and its relation with sport organizations. The paper notes that the changes of the trajectory of the sociology of sport, first leaning on the profession of physical education teacher and then to sport sciences, as important consequences. Because most of the sociologists specialized in sport are working in sport sciences departments, the most important consequence is the dependency on sport sciences rather than on sociology. Compared to other fields of sociology, it means challenging other sciences for recognition. The paper argues that to face the threat of a marginalization within the field of sport science, the future of sociology of sport could be to fight for an external recognition. Applying sociology could spread critical views that are necessary to sport organizations. It could also give sociologists access to very interesting data, which can help producing good research, and give it a greater legitimacy within sport sciences. However, it is a risky strategy because of the necessity for the sociologists to stay critical both on sporting organization and on their own work.

Management of severe blunt hepatic injury in the era of computed tomography and transarterial embolization: A systematic review and critical appraisal of the literature.

BACKGROUND: During the last decade, the management of blunt hepatic injury has considerably changed. Three options are available as follows: nonoperative management (NOM), transarterial embolization (TAE), and surgery. We aimed to evaluate in a systematic review the current practice and outcomes in the management of Grade III to V blunt hepatic injury. METHOD: The MEDLINE database was searched using PubMed to identify English-language citations published after 2000 using the key words blunt, hepatic injury, severe, and grade III to V in different combinations. Liver injury was graded according to the American Association for the Surgery of Trauma classification on computed tomography (CT). Primary outcome analyzed was success rate in intention to treat. Critical appraisal of the literature was performed using the validated National Institute for Health and Care Excellence "Quality Assessment for Case Series" system. RESULTS: Twelve articles were selected for critical appraisal (n = 4,946 patients). The median quality score of articles was 4 of 8 (range, 2-6). Overall, the median Injury Severity Score (ISS) at admission was 26 (range, 0.6-75). A median of 66% (range, 0-100%) of patients was managed with NOM, with a success rate of 94% (range, 86-100%). TAE was used in only 3% of cases (range, 0-72%) owing to contrast extravasation on CT with a success rate of 93% (range, 81-100%); however, 9% to 30% of patients required a laparotomy. Thirty-one percent (range, 17-100%) of patients were managed with surgery owing to hemodynamic instability in most cases, with 12% to 28% requiring secondary TAE to control recurrent hepatic bleeding. Mortality was 5% (range, 0-8%) after NOM and 51% (range, 30-68%) after surgery. CONCLUSION: NOM of Grade III to V blunt hepatic injury is the first treatment option to manage hemodynamically stable patients. TAE and surgery are considered in a highly selective group of patients with contrast extravasation on CT or shock at admission, respectively. Additional standardization of the reports is necessary to allow accurate comparisons of the various management strategies. LEVEL OF EVIDENCE: Systematic review, level IV.

Dysregulated ADAM10-Mediated Processing of APP during a Critical Time Window Leads to Synaptic Deficits in Fragile X Syndrome.

The Fragile X mental retardation protein (FMRP) regulates neuronal RNA metabolism, and its absence or mutations leads to the Fragile X syndrome (FXS). The β-amyloid precursor protein (APP) is involved in Alzheimer's disease, plays a role in synapse formation, and is upregulated in intellectual disabilities. Here, we show that during mouse synaptogenesis and in human FXS fibroblasts, a dual dysregulation of APP and the α-secretase ADAM10 leads to the production of an excess of soluble APPα (sAPPα). In FXS, sAPPα signals through the metabotropic receptor that, activating the MAP kinase pathway, leads to synaptic and behavioral deficits. Modulation of ADAM10 activity in FXS reduces sAPPα levels, restoring translational control, synaptic morphology, and behavioral plasticity. Thus, proper control of ADAM10-mediated APP processing during a specific developmental postnatal stage is crucial for healthy spine formation and function(s). Downregulation of ADAM10 activity at synapses may be an effective strategy for ameliorating FXS phenotypes.

A spatial modelling framework for assessing climate change impacts on freshwater ecosystems: Response of brown trout (Salmo trutta L.) biomass to warming water temperature

Mountain regions worldwide are particularly sensitive to on-going climate change. Specifically in the Alps in Switzerland, the temperature has increased twice as fast than in the rest of the Northern hemisphere. Water temperature closely follows the annual air temperature cycle, severely impacting streams and freshwater ecosystems. In the last 20 years, brown trout (Salmo trutta L) catch has declined by approximately 40-50% in many rivers in Switzerland. Increasing water temperature has been suggested as one of the most likely cause of this decline. Temperature has a direct effect on trout population dynamics through developmental and disease control but can also indirectly impact dynamics via food-web interactions such as resource availability. We developed a spatially explicit modelling framework that allows spatial and temporal projections of trout biomass using the Aare river catchment as a model system, in order to assess the spatial and seasonal patterns of trout biomass variation. Given that biomass has a seasonal variation depending on trout life history stage, we developed seasonal biomass variation models for three periods of the year (Autumn-Winter, Spring and Summer). Because stream water temperature is a critical parameter for brown trout development, we first calibrated a model to predict water temperature as a function of air temperature to be able to further apply climate change scenarios. We then built a model of trout biomass variation by linking water temperature to trout biomass measurements collected by electro-fishing in 21 stations from 2009 to 2011. The different modelling components of our framework had overall a good predictive ability and we could show a seasonal effect of water temperature affecting trout biomass variation. Our statistical framework uses a minimum set of input variables that make it easily transferable to other study areas or fish species but could be improved by including effects of the biotic environment and the evolution of demographical parameters over time. However, our framework still remains informative to spatially highlight where potential changes of water temperature could affect trout biomass. (C) 2015 Elsevier B.V. All rights reserved.-

Repetitive Deliberate Fires: Critical Review of the Situation and Proposal of a Follow-Up Process and Systematic Analysis

Deliberate fires appear to be borderless and timeless events creating a serious security problem. There have been many attempts to develop approaches to tackle this problem, but unfortunately acting effectively against deliberate fires has proven a complex challenge. This article reviews the current situation relating to deliberate fires: what do we know, how serious is the situation, how is it being dealt with, and what challenges are faced when developing a systematic and global methodology to tackle the issues? The repetitive nature of some types of deliberate fires will also be discussed. Finally, drawing on the reality of repetition within deliberate fires and encouraged by successes obtained in previous repetitive crimes (such as property crimes or drug trafficking), we will argue that the use of the intelligence process cycle as a framework to allow a follow-up and systematic analysis of fire events is a relevant approach. This is the first article of a series of three articles. This first part is introducing the context and discussing the background issues in order to provide a better underpinning knowledge to managers and policy makers planning on tackling this issue. The second part will present a methodology developed to detect and identify repetitive fire events from a set of data, and the third part will discuss the analyses of these data to produce intelligence.

β-Adrenergic modulation of skeletal muscle contraction: key role of excitation-contraction coupling.

Our aim is to describe the acute effects of catecholamines/β-adrenergic agonists on contraction of non-fatigued skeletal muscle in animals and humans, and explain the mechanisms involved. Adrenaline/β-agonists (0.1-30 μm) generally augment peak force across animal species (positive inotropic effect) and abbreviate relaxation of slow-twitch muscles (positive lusitropic effect). A peak force reduction also occurs in slow-twitch muscles in some conditions. β2 -Adrenoceptor stimulation activates distinct cyclic AMP-dependent protein kinases to phosphorylate multiple target proteins. β-Agonists modulate sarcolemmal processes (increased resting membrane potential and action potential amplitude) via enhanced Na(+) -K(+) pump and Na(+) -K(+) -2Cl(-) cotransporter function, but this does not increase force. Myofibrillar Ca(2+) sensitivity and maximum Ca(2+) -activated force are unchanged. All force potentiation involves amplified myoplasmic Ca(2+) transients consequent to increased Ca(2+) release from sarcoplasmic reticulum (SR). This unequivocally requires phosphorylation of SR Ca(2+) release channels/ryanodine receptors (RyR1) which sensitize the Ca(2+) -induced Ca(2+) release mechanism. Enhanced trans-sarcolemmal Ca(2+) influx through phosphorylated voltage-activated Ca(2+) channels contributes to force potentiation in diaphragm and amphibian muscle, but not mammalian limb muscle. Phosphorylation of phospholamban increases SR Ca(2+) pump activity in slow-twitch fibres but does not augment force; this process accelerates relaxation and may depress force. Greater Ca(2+) loading of SR may assist force potentiation in fast-twitch muscle. Some human studies show no significant force potentiation which appears to be related to the β-agonist concentration used. Indeed high-dose β-agonists (∼0.1 μm) enhance SR Ca(2+) -release rates, maximum voluntary contraction strength and peak Wingate power in trained humans. The combined findings can explain how adrenaline/β-agonists influence muscle performance during exercise/stress in humans.

Environmental control of the Pom1-dependent cell-size regulation pathway in fission yeast

Cells couple their growth and division rate in response to nutrient availability to maintain a constant size. This co-ordination happens either at the G1-S or the G2-M transition of the cell cycle. In the rod-shaped fission yeast, size regulation happens at the G2-M transition prior to mitotic commitment. Recent studies have focused on the role of the DYRK-family protein kinase Pom1, which forms gradients emanating from cell poles and inhibits the mitotic activator kinase Cdr2, present at the cell middle. Pom1 was proposed to inhibit Cdr2 until cells reached a critical size before division. However when and where Pom1 inhibits Cdr2 is not clear as medial Pom1 levels do not change during cell elongation. Here I show that Pom1 gradients are susceptible to environmental changes in glucose. Specifically, upon glucose limitation, Pom1 re-localizes from the poles to the cell sides where it delays mitosis through regulating Cdr2. This re-localization occurs due to microtubule de- stabilization and lateral catastrophes leading to transient deposition of the Pom1 gradient nucleator Tea4 along the cell cortex. As Tea4 localization to cell sides is sufficient to recruit Pom1, this explains the mechanism of Pom1 re-localization. Microtubule destabilization and consequently Tea4 and Pom1 spread depends on the activity of the cAMP-dependent Protein Kinase A (PKA/Pka1), as pka1 mutant cells have stable microtubules and retain polar Tea4 and Pom1 under limited glucose. PKA signaling negatively regulates the microtubule rescue factor CLASP/Cls1, thus reducing its ability to stabilize microtubules. Thus PKA signaling tunes CLASP activity to promote microtubule de-stabilization and Pom1 re-localization upon glucose limitation. I show that the side-localized Pom1 delays mitosis and balances the role of the mitosis promoting, mitogen-associated protein kinase (MAPK) protein Sty1. Thus Pom1 re-localization may serve to buffer cell size upon glucose limitation. -- Afin de maintenir une taille constante, les cellules régulent leur croissance ainsi que leur taux de division selon les nutriments disponibles dans le milieu. Dans la levure fissipare, cette régulation de la taille précède l'engagement mitotique et se fait à la transition entre les phases G2 à M du cycle cellulaire. Des études récentes se sont focalisées sur le rôle de la protéine Pom1, membre de la famille des DYRK kinase. Celle-ci forme un gradient provenant des pôles de la cellule et inhibe l'activateur mitotique Cdr2 présent au centre de la cellule. Le model propose que Pom1 inhibe Cdr2 jusqu'à atteindre une taille critique avant la division. Cependant quand et à quel endroit dans la cellulle Pom1 inhibe Cdr2 n'était pas clair car les niveaux médians de Pom1 ne changent pas au cours de la l'élongation des cellules. Dans cette étude, je montre que les gradients de Pom1 sont sensibles aux changements environnementaux du taux de glucose. Plus spécifiquement, en conditions limitantes de glucose, Pom1 se relocalise des pôles de la cellule pour se distribuer sur les côtés de celle-ci. Par conséquent, un délai d'entrée en mitose est observé dû à l'inhibition Cdr2 par Pom1. Cette délocalisation est due à la déstabilisation des microtubules qui va conduire à une déposition transitoire de Tea4, le nucléateur du gradient de Pom1, tout au long du cortex de la cellule. Comme la localisation de Tea4 sur les côtés de la cellule est suffisante pour recruter la protéine Pom1, ceci explique le mécanisme de relocalisation de celle-ci. La déstabilisation des microtubules et par conséquent la diffusion de Tea4 et Pom1 dépendent de l'activité de la protéine kinase A dépendante de l'AMP cyclique (PKA/Pka1). En absence de pka1, la stabilité des microtubules n'est pas affectée ce qui permet la rétention de Tea4 et Pom1 aux pôles de la cellule même en conditions limitantes de glucose. La signalisation via PKA régule négativement le facteur de sauvetage des microtubules CLASP/Cls1 et permet donc de réduire sa fonction de déstabilisation des microtubules. Ainsi la signalisation via PKA affine l'activité des CLASP pour promouvoir la déstabilisation des microtubules et la relocalisation de Pom1 en conditions limitantes de glucose. Je montre que la localisation sur les côtés retarde l'entrée en mitose et compense l'action de la protéine Sty1, connue pour être une MAPK qui induit l'entrée en mitose. Ainsi, la relocalisation de Pom1 pourrait servir à tamponner la taille de la cellule en condition limitantes de glucose. -- Various cell types in the environment such as bacterial, plant or animal cells have a distinct cellular size. Maintaining a constant cell size is important for fitness in unicellular organisms and for diverse functions in multicellular organisms. Cells regulate their size by coordinating their growth rate to their division rate. This coupling is important otherwise cells would get progressively smaller or larger after each successive cell cycle. In their natural environment cells may face fluctuations in the available nutrient supply. Thus cells have to coordinate their division rate to the variable growth rates shown under different nutrient conditions. During my PhD, I worked with a single-celled rod shaped yeast called the fission yeast. These cells are longer when the nutrient supply is abundant and shorter when the nutrient supply is scarce. A protein that senses changes in the external carbon source (glucose) is called Protein Kinase A (PKA). The rod shape of fission yeast cells is maintained thanks to a structural backbone called the cytoskeleton. One of the components of this backbone is called microtubules, which are small tube like structures spanning the length of the cell. They transport a protein called Tea4, which in turn is important for the proper localization of another protein Pom1 to the cell ends. Pom1 helps to maintain proper shape and size of these rod shaped yeast cells. My thesis work showed that upon reduction in the external nutrient (glucose) levels, microtubules become less stable and show an alteration in their organization. A significant percentage of the microtubules contact the side of the cell instead of touching only the cell tip. This leads to the spreading of the protein Pom1 away from the tips all around the cell periphery. This helps fission yeast cells to maintain the proper size required under these conditions of limited glucose supply. I further showed that the protein PKA regulates microtubule stability and organization and thus Pom1 spreading and maintenance of proper cell size. Thus my work led to the discovery of a novel pathway by which fission yeast cells maintain their size under limited supply of glucose. -- Divers types cellulaires dans l'environnement tels que les bactéries, les plantes ou les cellules animales ont une taille précise. Le maintien d'une taille cellulaire constante est importante pour le fitness des organismes unicellulaire ainsi que pour multiples fonctions dans les organismes multicellulaires. Les cellules régulent leur taille en coordonnant le taux de croissance avec le taux de division. Ce couplage est essentiel sinon les cellules deviendraient progressivement plus petites ou plus grandes après chaque cycle cellulaire. Dans leur habitat naturels les cellules peuvent faire face a des fluctuations dans le taux de nutriment disponible. Les cellules doivent donc coordonner leur taux de division aux taux variables de croissances perçus dans les différentes conditions nutritionnels. Pendant ma thèse, j'ai travaillée sur une levure unicellulaire, en forme de bâtonnet, nommé levure fissipare ou levure de fission. La taille de ces cellules est plus grande quand le taux de nutriments est grand et plus courte quand celui-ci est plus faible. Une protéine qui perçoit les changements dans le taux externe de la source de carbone (glucose) est nommée PKA pour protéine kinase A. La forme en bâtonnet de la cellule est due aux caractères structuraux du cytosquelette. Une composante importante de ce cytosquelette sont les microtubules, dont la structures ressemble à des petit tubes qui vont d'un bout à l'autre de la cellule. Ces microtubules transportent une protéine importante nommée Tea4 qui à leur tour importante pour la bonne localisation d'une autre protéine Pom1 aux extrémités de la cellule. La protéine Pom1 aide à maintenir la taille appropriée des levures fissipares. Mon travail de thèse a montré qu'en présence de taux faible de nutriments (glucose) les microtubules deviennent de moins en moins stables et montrent une désorganisation globale. Un pourcentage significatif des microtubules touche les côtés de la cellule aux lieu d'atteindre uniquement les extrémités. Ceci a pour conséquence une diffusion de Pom1 tout au long du cortex de la cellule. Ceci aide les levures fissipares à maintenir la taille appropriée pendant ce stress nutritionnel. De plus, je montre que PKA régule la stabilité et l'organisation des microtubules et par conséquent la diffusion de Pom1 et le maintien d'une taille constante. En conclusion, mon travail a conduit à la découverte d'un nouveau mécanisme par lequel la levure fissipare maintient sa taille dans des conditions limitantes en glucose.

Premature Discontinuation of Randomized Trials in Critical and Emergency Care: A Retrospective Cohort Study.

OBJECTIVES: Randomized clinical trials that enroll patients in critical or emergency care (acute care) setting are challenging because of narrow time windows for recruitment and the inability of many patients to provide informed consent. To assess the extent that recruitment challenges lead to randomized clinical trial discontinuation, we compared the discontinuation of acute care and nonacute care randomized clinical trials. DESIGN: Retrospective cohort of 894 randomized clinical trials approved by six institutional review boards in Switzerland, Germany, and Canada between 2000 and 2003. SETTING: Randomized clinical trials involving patients in an acute or nonacute care setting. SUBJECTS AND INTERVENTIONS: We recorded trial characteristics, self-reported trial discontinuation, and self-reported reasons for discontinuation from protocols, corresponding publications, institutional review board files, and a survey of investigators. MEASUREMENTS AND MAIN RESULTS: Of 894 randomized clinical trials, 64 (7%) were acute care randomized clinical trials (29 critical care and 35 emergency care). Compared with the 830 nonacute care randomized clinical trials, acute care randomized clinical trials were more frequently discontinued (28 of 64, 44% vs 221 of 830, 27%; p = 0.004). Slow recruitment was the most frequent reason for discontinuation, both in acute care (13 of 64, 20%) and in nonacute care randomized clinical trials (7 of 64, 11%). Logistic regression analyses suggested the acute care setting as an independent risk factor for randomized clinical trial discontinuation specifically as a result of slow recruitment (odds ratio, 4.00; 95% CI, 1.72-9.31) after adjusting for other established risk factors, including nonindustry sponsorship and small sample size. CONCLUSIONS: Acute care randomized clinical trials are more vulnerable to premature discontinuation than nonacute care randomized clinical trials and have an approximately four-fold higher risk of discontinuation due to slow recruitment. These results highlight the need for strategies to reliably prevent and resolve slow patient recruitment in randomized clinical trials conducted in the critical and emergency care setting.

Patient-centered Care in Maternity Services: A Critical Appraisal and Synthesis of the Literature.

BACKGROUND: Patient-centered care (PCC) has been recognized as a marker of quality in health service delivery. In policy documents, PCC is often used interchangeably with other models of care. There is a wide literature about PCC, but there is a lack of evidence about which model is the most appropriate for maternity services specifically. AIM: We sought to identify and critically appraise the literature to identify which definition of PCC is most relevant for maternity services. METHODS: The four-step approach used to identify definitions of PCC was to 1) search electronic databases using key terms (1995-2011), 2) cross-reference key papers, 3) search of specific journals, and 4) search the grey literature. Four papers and two books met our inclusion criteria. ANALYSIS: A four-criteria critical appraisal tool developed for the review was used to appraise the papers and books. MAIN RESULTS: From the six identified definitions, the Shaller's definition met the majority of the four criteria outlined and seems to be the most relevant to maternity services because it includes physiologic conditions as well as pathology, psychological aspects, a nonmedical approach to care, the greater involvement of family and friends, and strategies to implement PCC. CONCLUSION: This review highlights Shaller's definitions of PCC as the one that would be the most inclusive of all women using maternity services. Future research should concentrate on evaluating programs that support PCC in maternity services, and testing/validating this model of care.