PICU mortality of children with cancer admitted to pediatric intensive care unit : a systematic review and meta-analysis

Background: Outcomes for children diagnosed with cancer have improved dramatically over the past 20 years. However, although 40% of pediatric cancer patients require at least one intensive care admission throughout their disease course, PICU outcomes and resource utilization by this population have not been rigorously studied in this specific group. Methods: Using a systematic strategy, we searched Medline, Embase, and CINAHL databases for articles describing PICU mortality of pediatric cancer patients admitted to PICU. Two investigators independently applied eligibility criteria, assessed data quality, and extracted data. We pooled PICU mortality estimates using random-effects models and examined mortality trends over time using meta-regression models. Results: Out of 1218 identified manuscripts, 31 studies were included covering 16,853 PICU admissions with the majority being retrospective in nature. Overall pooled weighted mortality was 27.8% (95% confidence interval (CI), 23.7-31.9%). Mortality decreased slightly over time when post-operative patients were excluded. The use of mechanical ventilation (odds ratio (OR): 18.49 [95% CI 13.79-24.78], p < 0.001), inotropic support (OR: 14.05 [95% CI 9.16-21.57], p < 0.001), or continuous renal replacement therapy (OR: 3.24 [95% CI 1.31-8.04], p = 0.01) was significantly associated with PICU mortality. Conclusions: PICU mortality rates of pediatric cancer patients are far higher when compared to current mortality rates of the general PICU population. PICU mortality has remained relatively unchanged over the past decades, a slight decrease was only seen when post-operative patients were excluded. This compared infavorably with the improved mortality seen in adults with cancer admitted to ICU, where research-led improvements have led to the paradigm of unlimited, aggressive ICU management without any limitations on resuscitations status, for a time-limited trial

Spatial and topological organization of DNA chains induced by gene co-localization

Transcriptional activity has been shown to relate to the organization of chromosomes in the eukaryotic nucleus and in the bacterial nucleoid. In particular, highly transcribed genes, RNA polymerases and transcription factors gather into discrete spatial foci called transcription factories. However, the mechanisms underlying the formation of these foci and the resulting topological order of the chromosome remain to be elucidated. Here we consider a thermodynamic framework based on a worm-like chain model of chromosomes where sparse designated sites along the DNA are able to interact whenever they are spatially close-by. This is motivated by recurrent evidence that there exists physical interactions between genes that operate together. Three important results come out of this simple framework. First, the resulting formation of transcription foci can be viewed as a micro-phase separation of the interacting sites from the rest of the DNA. In this respect, a thermodynamic analysis suggests transcription factors to be appropriate candidates for mediating the physical interactions between genes. Next, numerical simulations of the polymer reveal a rich variety of phases that are associated with different topological orderings, each providing a way to increase the local concentrations of the interacting sites. Finally, the numerical results show that both one-dimensional clustering and periodic location of the binding sites along the DNA, which have been observed in several organisms, make the spatial co-localization of multiple families of genes particularly efficient.Comment: Figures and Supplementary Material freely available on http://dx.doi.org/10.1371/journal.pcbi.100067

Internalisation Theory and outward direct investment by emerging market multinationals

The rise of multinational enterprises from emerging countries (EMNEs) poses an important test for theories of the multinational enterprise such as internalisation theory. It has been contended that new phenomena need new theory. This paper proposes that internalisation theory is appropriate to analyse EMNEs. This paper examines four approaches to EMNEs—international investment strategies, domestic market imperfections, international corporate networks and domestic institutions—and three case studies—Chinese outward FDI, Indian foreign acquisitions and investment in tax havens—to show the enduring relevance and predictive power of internalisation theory. This analysis encompasses many other approaches as special cases of internalisation theory. The use of internalisation theory to analyse EMNEs is to be commended, not only because of its theoretical inclusivity, but also because it has the ability to connect and to explain seemingly desperate phenomena

Intermittent control models of human standing: similarities and differences

Two architectures of intermittent control are compared and contrasted in the context of the single inverted pendulum model often used for describing standing in humans. The architectures are similar insofar as they use periods of open-loop control punctuated by switching events when crossing a switching surface to keep the system state trajectories close to trajectories leading to equilibrium. The architectures differ in two significant ways. Firstly, in one case, the open-loop control trajectory is generated by a system-matched hold, and in the other case, the open-loop control signal is zero. Secondly, prediction is used in one case but not the other. The former difference is examined in this paper. The zero control alternative leads to periodic oscillations associated with limit cycles; whereas the system-matched control alternative gives trajectories (including homoclinic orbits) which contain the equilibrium point and do not have oscillatory behaviour. Despite this difference in behaviour, it is further shown that behaviour can appear similar when either the system is perturbed by additive noise or the system-matched trajectory generation is perturbed. The purpose of the research is to come to a common approach for understanding the theoretical properties of the two alternatives with the twin aims of choosing which provides the best explanation of current experimental data (which may not, by itself, distinguish beween the two alternatives) and suggesting future experiments to distinguish between the two alternatives

Non-universal minimal Z' models: present bounds and early LHC reach

We consider non-universal 'minimal' Z' models, whose additional U(1) charge is a non-anomalous linear combination of the weak hypercharge Y, the baryon number B and the partial lepton numbers (L_e, L_mu, L_tau), with no exotic fermions beyond three standard families with right-handed neutrinos. We show that the observed pattern of neutrino masses and mixing can be fully reproduced by a gauge-invariant renormalizable Lagrangian, and flavor-changing neutral currents in the charged lepton sector are suppressed by a GIM mechanism. We then discuss the phenomenology of some benchmark models. The electrophilic B-3L_e model is significantly constrained by electroweak precision tests, but still allows to fit the hint of an excess observed by CDF in dielectrons but not in dimuons. The muonphilic B-3L_mu model is very mildly constrained by electroweak precision tests, so that even the very early phase of the LHC can explore significant areas of parameter space. We also discuss the hadrophobic L_mu-L_tau model, which has recently attracted interest in connection with some puzzling features of cosmic ray spectra.Comment: 29 pages, 13 figure

Optimal Homogenization of Perfusion Flows in Microfluidic Bio-Reactors: A Numerical Study

In recent years, the interest in small-scale bio-reactors has increased dramatically. To ensure homogeneous conditions within the complete area of perfused microfluidic bio-reactors, we develop a general design of a continually feed bio-reactor with uniform perfusion flow. This is achieved by introducing a specific type of perfusion inlet to the reaction area. The geometry of these inlets are found using the methods of topology optimization and shape optimization. The results are compared with two different analytic models, from which a general parametric description of the design is obtained and tested numerically. Such a parametric description will generally be beneficial for the design of a broad range of microfluidic bioreactors used for, e.g., cell culturing and analysis and in feeding bio-arrays

Multiplicity of young brown dwarfs in Cha I

How frequent are brown dwarf binaries? Do brown dwarfs have planets? Are current theoretical pre-main-sequence evolutionary tracks valid down to the substellar regime? - Any detection of a companion to a brown dwarf takes us one step forward towards answering these basic questions of star formation. We report here on a search for spectroscopic and visual companions to young brown dwarfs in the Cha I star forming cloud. Based on spectra taken with UVES at the VLT, we found significant radial velocity (RV) variations for five bona-fide and candidate brown dwarfs in Cha I. They can be caused by either a (substellar or planetary) companion or stellar activity. A companion causing the detected RV variations would have about a few Jupiter masses. We are planning further UVES observations in order to explore the nature of the detected RV variations. We also found that the RV dispersion is only ~ 2km/s indicating that there is probably no run-away brown dwarf among them. Additionally a search for companions by direct imaging with the HST and SOFI (NTT) has yielded to the detection of a few companion candidates in larger orbits.Comment: Conference proceeding "Origins of stars and planets: The VLT view", ESO, Garching, April 24-27 200

Elbow Joint Loads during Simulated Activities of Daily Living:Implications for Formulating Recommendations after Total Elbow Arthroplasty.

Background: Overloading of the elbow joint prosthesis following total elbow arthroplasty can lead to implant failure. Joint moments during daily activities are not well-contextualized for a prosthesis' failure limits and the effect of the current postoperative instruction on elbow joint loading is unclear. This study investigates the difference in elbow joint moments between simulated daily tasks and between flexion-extension, pronation-supination, varus-valgus movement directions. Additionally, the effect of the current postoperative instruction on elbow joint load is examined.Methods: Nine healthy participants (age 45.8 ± 17 years, 3 males) performed eight tasks; driving a car, opening a door, rising from chair, lifting, sliding, combing hair, drinking, emptying cup, without and with the instruction "not lifting more than 1 kg". Upper limb kinematics and hand contact forces were measured. Elbow joint angles and net moments were analyzed using inverse dynamic analysis, where the net moments are estimated from movement data and external forces.Results: Peak elbow joint moments differed significantly between tasks (p &lt; 0.01) and movement directions (p &lt; 0.01). The most and least demanding tasks were, rising from a chair (13.4 Nm extension, 5.0 Nm supination, 15.2 Nm valgus) and sliding (4.3 Nm flexion, 1.7 Nm supination, 2.6 Nm varus). Net moments were significantly reduced after instruction only in the chair task (p &lt; 0.01).Conclusion: This study analyzed elbow joint moments in different directions during daily tasks. The outcomes question whether postoperative instruction can lead to decreasing elbow loads. Future research might focus on reducing elbow loads in the flexion-extension and varus-valgus directions.<br/

Prognostic relevance of a T-type calcium channels gene signature in solid tumours: A correlation ready for clinical validation

BackgroundT-type calcium channels (TTCCs) mediate calcium influx across the cell membrane. TTCCs regulate numerous physiological processes including cardiac pacemaking and neuronal activity. In addition, they have been implicated in the proliferation, migration and differentiation of tumour tissues. Although the signalling events downstream of TTCC-mediated calcium influx are not fully elucidated, it is clear that variations in the expression of TTCCs promote tumour formation and hinder response to treatment.MethodsWe examined the expression of TTCC genes (all three subtypes; CACNA-1G, CACNA-1H and CACNA-1I) and their prognostic value in three major solid tumours (i.e. gastric, lung and ovarian cancers) via a publicly accessible database.ResultsIn gastric cancer, expression of all the CACNA genes was associated with overall survival (OS) among stage I-IV patients (all pConclusionsAlterations in CACNA gene expression are linked to tumour prognosis. Gastric cancer represents the most promising setting for further evaluation