Building ventilation as an effective disease intervention strategy on a large and dense social contact network

published_or_final_versio

Identification of early changes in specific symptoms that predict longer-term response to atypical antipsychotics in the treatment of patients with schizophrenia

<p>Abstract</p> <p>Background</p> <p>To identify a simple decision tree using early symptom change to predict response to atypical antipsychotic therapy in patients with (Diagnostic and Statistical Manual, Fourth Edition, Text Revised) chronic schizophrenia.</p> <p>Methods</p> <p>Data were pooled from moderately to severely ill patients (n = 1494) from 6 randomized, double-blind trials (N = 2543). Response was defined as a ≥30% reduction in Positive and Negative Syndrome Scale (PANSS) Total score by Week 8 of treatment. Analyzed predictors were change in individual PANSS items at Weeks 1 and 2. A decision tree was constructed using classification and regression tree (CART) analysis to identify predictors that most effectively differentiated responders from non-responders.</p> <p>Results</p> <p>A 2-branch, 6-item decision tree was created, producing 3 distinct groups. First branch criterion was a 2-point score decrease in at least 2 of 5 PANSS positive items (Week 2). Second branch criterion was a 2-point score decrease in the PANSS excitement item (Week 2). "Likely responders" met the first branch criteria; "likely non-responders" did not meet first or second criterion; "not predictable" patients did not meet the first but did meet the second criterion. Using this approach, response to treatment could be predicted in most patients (92%) with high positive predictive value (79%) and high negative predictive value (75%). Predictive findings were confirmed through analysis of data from 2 independent trials.</p> <p>Conclusions</p> <p>Using a data-driven approach, we identified decision rules using early change in the scores of selected PANSS items to accurately predict longer-term treatment response or non-response to atypical antipsychotic therapy. This could lead to development of a simple quantitative evaluation tool to help guide early treatment decisions.</p> <p>Trial Registration</p> <p>This is a retrospective, non-intervention study in which pooled results from 6 previously published reports were analyzed; thus, clinical trial registration is not required.</p

The limits of academic entrepreneurship: Conflicting expectations about commercialization and innovation in China\u27s nascent sector for advanced bio-energy technologies

Despite many years of substantial government research funding, advanced bio-energy technologies in China have seen limited commercial application. Chinese policy makers are increasingly critical of academic organizations for neglecting their role in the transfer of scientific results into industrial applications. We interviewed a selection of Chinese research groups working on bio-energy technologies, and asked them to describe their efforts at commercialization. We found that they focus their research on technological pathways with commercial potential, they patent and attempt to license their technologies, they are highly involved in large scale demonstration plants, and have created a number of new firms. Industry and government may have unrealistic expectations on the maturity and scale of technologies that academia can develop, however. These findings contrast with many earlier analyses of early commercialization stages of novel technologies, which have commonly identified lacking academic entrepreneurship as a root cause in stalling development

The relationship, structure and profiles of schizophrenia measurements: a post-hoc analysis of the baseline measures from a randomized clinical trial

<p>Background</p> <p>To fully assess the various dimensions affected by schizophrenia, clinical trials often include multiple scales measuring various symptom profiles, cognition, quality of life, subjective well-being, and functional impairment. In this exploratory study, we characterized the relationships among six clinical, functional, cognitive, and quality-of-life measures, identifying a parsimonious set of measurements.</p> <p>Methods</p> <p>We used baseline data from a randomized, multicenter study of patients diagnosed with schizophrenia, schizoaffective disorder, or schizophreniform disorder who were experiencing an acute symptom exacerbation (n = 628) to examine the relationship among several outcome measures. These measures included the Positive and Negative Syndrome Scale (PANSS), Montgomery-Asberg Depression Rating Scale (MADRS), Brief Assessment of Cognition in Schizophrenia Symbol Coding Test, Subjective Well-being Under Neuroleptics Scale Short Form (SWN-K), Schizophrenia Objective Functioning Instrument (SOFI), and Quality of Life Scale (QLS). Three analytic approaches were used: 1) path analysis; 2) factor analysis; and 3) categorical latent variable analysis. In the optimal path model, the SWN-K was selected as the final outcome, while the SOFI mediated the effect of the exogenous variables (PANSS, MADRS) on the QLS.</p> <p>Results</p> <p>The overall model explained 47% of variance in QLS and 17% of the variance in SOFI, but only 15% in SWN-K. Factor analysis suggested four factors: "Functioning," "Daily Living," "Depression," and "Psychopathology." A strong positive correlation was observed between the SOFI and QLS (r = 0.669), and both the QLS and SOFI loaded on the "Functioning" factor, suggesting redundancy between these scales. The measurement profiles from the categorical latent variable analysis showed significant variation in functioning and quality of life despite similar levels of psychopathology.</p> <p>Conclusions</p> <p>Researchers should consider collecting PANSS, SOFI, and SWN-K in their trials. This would allow a broad spectrum of assessments that would have the ability to capture a wide range of treatment outcomes and allow for a rich characterization of the subgroups involved. Additional research is needed to identify the critical cognitive measures.</p> <p>Trials registration</p> <p>Clinical trials registration: Predicting Response to Risperidone Treatment Through Identification of Early-onset of Antipsychotic Drug Action in Schizophrenia</p> <p>ClinicalTrials.gov identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00337662">NCT00337662</a>; <url>http://www.clinicaltrials.gov/</url></p

The POT1-TPP1 telomere complex is a telomerase processivity factor

Telomeres were originally defined as chromosome caps that prevent the natural ends of linear chromosomes from undergoing deleterious degradation and fusion events. POT1 ( protection of telomeres) protein binds the single-stranded G-rich DNA overhangs at human chromosome ends and suppresses unwanted DNA repair activities. TPP1 is a previously identified binding partner of POT1 that has been proposed to form part of a six-protein shelterin complex at telomeres. Here, the crystal structure of a domain of human TPP1 reveals an oligonucleotide/oligosaccharide-binding fold that is structurally similar to the beta-subunit of the telomere end-binding protein of a ciliated protozoan, suggesting that TPP1 is the missing beta-subunit of human POT1 protein. Telomeric DNA end-binding proteins have generally been found to inhibit rather than stimulate the action of the chromosome end-replicating enzyme, telomerase. In contrast, we find that TPP1 and POT1 form a complex with telomeric DNA that increases the activity and processivity of the human telomerase core enzyme. We propose that POT1 - TPP1 switches from inhibiting telomerase access to the telomere, as a component of shelterin, to serving as a processivity factor for telomerase during telomere extension.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62923/1/nature05454.pd

Quantitative analysis of late gadolinium enhancement in hypertrophic cardiomyopathy: comparison of diagnostic performance in myocardial fibrosis between gadobutrol and gadopentetate dimeglumine

The purpose of this study was to compare different semi-automated late gadolinium enhancement (LGE) quantification techniques using gadobutrol and gadopentetate dimeglumine contrast agents with regard to the diagnosis of fibrotic myocardium in patients with hypertrophic cardiomyopathy (HCM). Thirty patients with HCM underwent two cardiac MRI protocols with use of gadobutrol and gadopentetate dimeglumine. Contrast-tonoise ratio (CNR) between LGE area and remote myocardium (CNRremote), between LGE area and left ventricular blood pool (CNRpool), and signal-to-noise ratio (SNR) in LGE were compared. The presence and quantity of LGE were determined by visual assessment. With signal threshold versus reference mean (STRM) based thresholds of 2 SD, 5 SD, and 6 SD above the mean signal intensity (SI) of reference myocardium, the full-width at half-maximum (FWHM) technique was used. The volume and segments of the LGE area were compared between the two types of contrast agents. LGE was present in 26 of 30 (86.6%) patients in both protocols. The CNRremote of fibrotic myocardium in gadobutrol and gadopentetate dimeglumine agents was 26.82 ± 14.24 and 21.46 ± 10.59, respectively (P &lt; 0.05). The CNRpool was significantly higher in gadobutrol (9.32 ± 7.64 vs. 6.39 ± 6.11, P &lt; 0.05). The SNR was higher in gadobutrol (33.36 ± 14.35 vs. 27.53 ± 10.91, P &lt; 0.05). The volume of scar size in MR images acquired with gadobutrol were significantly higher than those with gadopentetate dimeglumine (P &lt; 0.05), and the STRM of 5 SD technique showed the greatest agreement with visual assessment (ICC = 0.99) in both examinations. There was no significant difference in fibrotic segments of the fibrotic myocardium in the LGE area (P &lt; 0.05). This study proved that the Gadobutrol was an effective contrast agent for LGE imaging with superior delineation of fibrotic myocardium as compared to gadopentetate dimeglumine. The 5 SD technique yields the closest approximation of the extent of LGE identified by visual assessment

Search for Gravitational Waves from Primordial Black Hole Binary Coalescences in the Galactic Halo

We use data from the second science run of the LIGO gravitational-wave detectors to search for the gravitational waves from primordial black hole (PBH) binary coalescence with component masses in the range 0.2--$1.0 M_\odot$. The analysis requires a signal to be found in the data from both LIGO observatories, according to a set of coincidence criteria. No inspiral signals were found. Assuming a spherical halo with core radius 5 kpc extending to 50 kpc containing non-spinning black holes with masses in the range 0.2--$1.0 M_\odot$, we place an observational upper limit on the rate of PBH coalescence of 63 per year per Milky Way halo (MWH) with 90% confidence.Comment: 7 pages, 4 figures, to be submitted to Phys. Rev.

Blood Banking in Living Droplets

Blood banking has a broad public health impact influencing millions of lives daily. It could potentially benefit from emerging biopreservation technologies. However, although vitrification has shown advantages over traditional cryopreservation techniques, it has not been incorporated into transfusion medicine mainly due to throughput challenges. Here, we present a scalable method that can vitrify red blood cells in microdroplets. This approach enables the vitrification of large volumes of blood in a short amount of time, and makes it a viable and scalable biotechnology tool for blood cryopreservation.National Institutes of Health (U.S.) (NIH R21 EB007707)Wallace H. Coulter FoundationUnited States. Army Medical Research and Materiel Command (Acquisition Activity Cooperative Agreement RO1 A1081534)Center for Integration of Medicine and Innovative TechnologyUnited States. Army Medical Research and Materiel Command (Acquisition Activity Cooperative Agreement R21 AI087107)United States. Army. Telemedicine & Advanced Technology Research Cente

Molecular evolution of vertebrate sex-determining genes

Y-linked Dmy (also called dmrt1bY) in the teleost fish medaka, W-linked Dm-W in the African clawed frog (Xenopus laevis), and Z-linked Dmrt1 in the chicken are all sex chromosome-linked Dmrt1 homologues required for sex determination. Dmy and Dm-W both are Dmrt1 palalogues evolved through Dmrt1 duplication, while chicken Dmrt1 is a Z-linked orthologue. The eutherian sex-determining gene, Sry, evolved from an allelic gene, Sox3. Here we analyzed the exon–intron structures of the Dmrt1 homologues of several vertebrate species through information from databases and by determining the transcription initiation sites in medaka, chicken, Xenopus, and mouse. Interestingly, medaka Dmrt1 and Dmy and Xenopus Dm-W and Dmrt1 have a noncoding-type first exon, while mouse and chicken Dmrt1 do not. We next compared the 5′-flanking sequences of the Dmrt1 noncoding and coding exons 1 of several vertebrate species and found conservation of the presumptive binding sites for some transcription factors. Importantly, based on the phylogenetic trees for Dmrt1 and Sox3 homologues, it was implied that the sex-determining gene Dmy, Dm-W, and Sry have a higher substitution rate than thier prototype genes. Finally, we discuss the evolutionary relationships between vertebrate sex chromosomes and the sex-determining genes Dmy/Dm-W and Sry, which evolved by neofunctionalization of Dmrt1 and Sox3, respectively, for sex determining function. We propose a coevolution model of sex determining gene and sex chromosome, in which undifferentiated sex chromosomes easily allow replacement of a sex-determining gene with another new one, while specialized sex chromosomes are restricted a particular sex-determining gene