bluuebunny/crossref_metadata_2025 huggingface dataset:
Reducing hospitalisation among people living with severe mental illness
Authors: McDermott Shannon , Bruce Jasmine , Muir Kristy , Ramia Ioana , Fisher Karen R. , Bullen Jane
Published: September 2015

Objective
People with severe mental illness have high rates of hospitalisation. The present study examined the role that permanent housing and recovery-oriented support can play in reducing the number and length of psychiatric hospital admissions for people with severe mental illness.

Methods
The study examined de-identified, individual-level health records of 197 people involved in the New South Wales Mental Health Housing and Accommodation Support Initiative (HASI) to compare changes in hospitalisation over a continuous 4-year period.

Results
On average, HASI consumers experienced significant reductions in the number of psychiatric hospital admissions and length of stay after entering the HASI program, and these reductions were sustained over the first 2 years in HASI. Male consumers and consumers under 45 years of age experienced the largest reductions in the number and length of hospital admissions.

Conclusions
The findings of the present study add support to the hypothesis that supported housing and recovery-oriented support can be effective approaches to reducing hospital admissions for people with chronic mental illness, and that these changes can be sustained over time.

What is known about this topic?
People living with severe mental illness are heavy users of health and hospitalisation services. Research into the effects of partnership programs on preventing unnecessary admissions is limited because of short periods of comparison and small sample sizes.

What does this paper add?
The present study extends previous research by analysing de-identified individual-level health records over a continuous 4-year period and showing that reductions in hospitalisation among people with severe mental illness can be sustained over time.

What are the implications for practitioners?
These findings provide further evidence that community-based recovery-oriented supported housing programs can assist consumers to manage their mental health and avoid hospital admissions. Although the provision of recovery-oriented community services requires an investment in community mental health, the reduction in consumers’ use of hospital services makes this investment worthwhile.
General practitioners’ relationship with preventive knowledge: a qualitative study
Authors: Bloy Géraldine , Rigal Laurent
Published: September 2015

General practitioners (GPs) do not provide enough preventive care. Nonetheless, without a detailed understanding of the logical processes that underlie their practices, it remains difficult to develop effective means of improvement. Their relationship to knowledge is one of three elements that strongly structure GPs’ preventive work (together with the doctor–patient relationship and the organisation of their professional space).The objective of this article was to explore the question of GPs’ relationship to knowledge about prevention. In 2010–2011, semi-directive interviews with a diverse sample of 100 GPs practising in the Paris metropolitan area were conducted. These interviews were coded according a reading grid that was developed collectively and analysed in the framework of grounded theory. The cognitive universe of GPs is neither homogeneous nor stable. It is composed of biomedical knowledge (delivered via guidelines, the professional press, opinion leaders and pharmaceutical companies), clinical knowledge (fed by individual situations from their daily experience and often conflicting with epidemiologic reasoning and data) and lay knowledge (from folk culture). Plunged into this complex cognitive universe that is difficult for them to master, doctors construct their own idiosyncratic preventive style by themselves, mostly in isolation. Two types of actions emerged as likely to help GPs better appropriate preventive knowledge: clarification of scientific data (especially from epidemiology and the social sciences) but also development of a collective analysis of the cognitive work required to integrate the different types of knowledge mobilised daily in their preventive practices.
Dr Google, porn and friend-of-a-friend: where are young men really getting their sexual health information?
Authors: Litras Amy , Latreille Sarah , Temple-Smith Meredith
Published: September 2015

Background Young men are vulnerable when it comes to sexual health. They attend the general practitioner (GP) less often than females and are less likely to be offered testing for sexually transmissible infections. Access to accurate health information and education is a cornerstone of primary prevention, yet we know very little about how, where and why young people obtain information about sexual health. Methods: One-on-one semi-structured interviews were conducted with 35 male students aged 16–19 years from two Victorian educational institutions for trade skills until data saturation was reached. Interviews were audio-recorded, transcribed and thematically analysed. Results: The young men were poorly informed about sexual health. Their existing knowledge mainly came from school-based sexual health education, which while valued, was generally poorly recalled and provided only a narrow scope of physiological information. Young men seek sexual health information from various sources including family, the Internet, friends and pornography, with information from the latter three sources perceived as unreliable. GPs were seen as a source of trust-worthy information but were not accessed for this purpose due to embarrassment. Young men preferred the GP to initiate such conversations. A desire for privacy and avoidance of embarrassment heavily influenced young men’s preferences and behaviours in relation to sexual health information seeking. Conclusions: The current available sources of sexual health information for young men are failing to meet their needs. Results identify potential improvements to school-based sexual education and online resources, and describe a need for innovative technology-based sources of sexual health education.
Structure-level fuel load assessment in the wildland–urban interface: a fusion of airborne laser scanning and spectral remote-sensing methodologies
Authors: Skowronski Nicholas S. , Haag Scott , Trimble Jim , Clark Kenneth L. , Gallagher Michael R. , Lathrop Richard G.
Published: September 2015

Large-scale fuel assessments are useful for developing policy aimed at mitigating wildfires in the wildland–urban interface (WUI), while finer-scale characterisation is necessary for maximising the effectiveness of fuel reduction treatments and directing suppression activities. We developed and tested an objective, consistent approach for characterising hazardous fuels in the WUI at the scale of individual structures by integrating aerial photography, airborne laser scanning and cadastral datasets into a hazard assessment framework. This methodology is appropriate for informing zoning policy questions, targeting presuppression planning and fuel reduction treatments, and assisting in prioritising structure defence during suppression operations. Our results show increased variability in fuel loads with decreasing analysis unit area, indicating that fine-scale differences exist that may be omitted owing to spatial averaging when using a coarser, grid-based approach. Analyses using a local parcel database indicate that approximately 75% of the structures in this study have ownership of less than 50% of the 30 m buffer around their building, illustrating the complexity of multiple ownerships when attempting to manage fuels in the WUI. Our results suggest that our remote-sensing approach could augment, and potentially improve, ground-based survey approaches in the WUI.
Multistep food plant processing at Grotta Paglicci (Southern Italy) around 32,600 cal B.P.
Authors: Mariotti Lippi Marta , Foggi Bruno , Aranguren Biancamaria , Ronchitelli Annamaria , Revedin Anna
Published: September 2015

Significance

The Early Gravettian inhabitants of Grotta Paglicci (sublayer 23 A) are currently the most ancient hunter–gatherers able to process plants to obtain flour. They also developed targeted technologies for complex processing of the plant portions before grinding. The present study testifies for the first time, to our knowledge, the performance of a thermal pretreatment that could have been crucial in a period characterized by a climate colder than the current one. The starch record on the Paglicci grinding stone is currently the most ancient evidence of the processing of
Avena
(oat).
Freshwater discharges drive high levels of methylmercury in Arctic marine biota
Authors: Schartup Amina T. , Balcom Prentiss H. , Soerensen Anne L. , Gosnell Kathleen J. , Calder Ryan S. D. , Mason Robert P. , Sunderland Elsie M.
Published: September 2015

Significance

Estuaries are the predominant hunting and fishing territory for northern indigenous populations whose way of life is threatened by both climate change and industrial development. Direct measurements and modeling conducted as part of this study show enhanced production of methylmercury, a potent neurotoxin, and uptake by plankton in stratified oxic seawater. Enhanced climate-driven stratification of ocean margin areas with sea-ice melt will likely elevate biological methylmercury concentrations in the Arctic. Elevated biological methylmercury levels will be exacerbated by hydroelectric development planned throughout many northern regions. Our experimental measurements indicate that, over the next decade, regional increases in methylmercury concentrations resulting from flooding associated with hydroelectric development will be greater than those expected from climate change.
Biochemical isolation of Argonaute protein complexes by Ago-APP
Authors: Hauptmann Judith , Schraivogel Daniel , Bruckmann Astrid , Manickavel Sudhir , Jakob Leonhard , Eichner Norbert , Pfaff Janina , Urban Marc , Sprunck Stefanie , Hafner Markus , Tuschl Thomas , Deutzmann Rainer , Meister Gunter
Published: September 2015

Significance

Small RNA-guided gene-silencing pathways regulate fundamental cellular processes. Small RNAs such as microRNAs (miRNAs) directly bind to a member of the Argonaute (Ago) protein family. In animals, Ago proteins interact with a member of the GW protein family (referred to as TNRC6A-C). Based on an Ago-interacting TNRC6 peptide, we have developed a method allowing for the efficient isolation and characterization of Ago protein complexes from any animal organism. We refer to this method as “Ago protein Affinity Purification by Peptides.” Our approach also allows for the identification of Ago-bound small RNAs as well as mRNAs. Expression of this peptide in living cells leads to global miRNA inactivation, thus providing a powerful tool to study miRNA function on various levels.
Piezo1 regulates mechanotransductive release of ATP from human RBCs
Authors: Cinar Eyup , Zhou Sitong , DeCourcey James , Wang Yixuan , Waugh Richard E. , Wan Jiandi
Published: September 2015

Significance

Mechanotransductive release of ATP from RBCs participates in the regulation of microvascular tone and plays essential roles in vascular physiopathology. The mechanism responsible for the release of ATP, however, is poorly understood. We show for the first time, to our knowledge, that Piezo1, the recently identified mechanically activated cation channel, regulates the mechanotransductive release of ATP from RBCs. In particular, we uncover the link between Piezo1, calcium influx, and ATP release and propose a previously unidentified mechanotransductive pathway that modulates the release of ATP from RBCs. The outcome of this study will allow the development of much needed approaches to regulate the release of ATP from RBCs and thus, impact significantly the fields of red cell research, cellular mechanosensing, and Piezo1 channels.
Single quantum dot controls a plasmonic cavity’s scattering and anisotropy
Authors: Hartsfield Thomas , Chang Wei-Shun , Yang Seung-Cheol , Ma Tzuhsuan , Shi Jinwei , Sun Liuyang , Shvets Gennady , Link Stephan , Li Xiaoqin
Published: September 2015

Significance

We experimentally demonstrate that a single semiconductor quantum dot placed in close proximity to a plasmonic cavity (i.e., a spherical metallic nanoparticle) can be used to control the scattering spectrum and anisotropy of the latter. The scattering spectrum of the hybrid structure features a Fano resonance mediated by single photon absorption/scattering. This result is highly counterintuitive because the scattering cross sections of these two nanoparticles differ by four orders of magnitude. Our work represents a critical step toward realizing quantum plasmonic nanostructures that are capable of producing scattered light, which, depending on its polarization state, obeys either quantum or classical statistics. Furthermore, our work enables a hybrid orientation sensor unaffected by photobleaching of quantum dots.
Ancient genomes link early farmers from Atapuerca in Spain to modern-day Basques
Authors: Günther Torsten , Valdiosera Cristina , Malmström Helena , Ureña Irene , Rodriguez-Varela Ricardo , Sverrisdóttir Óddny Osk , Daskalaki Evangelia A. , Skoglund Pontus , Naidoo Thijessen , Svensson Emma M. , Bermúdez de Castro José María , Carbonell Eudald , Dunn Michael , Storå Jan , Iriarte Eneko , Arsuaga Juan Luis , Carretero José-Miguel , Götherström Anders , Jakobsson Mattias
Published: September 2015

Significance

The transition from a foraging subsistence strategy to a sedentary farming society is arguably the greatest innovation in human history. Some modern-day groups—specifically the Basques—have been argued to be a remnant population that connect back to the Paleolithic. We present, to our knowledge, the first genome-wide sequence data from eight individuals associated with archaeological remains from farming cultures in the El Portalón cave (Atapuerca, Spain). These individuals emerged from the same group of people as other Early European farmers, and they mixed with local hunter–gatherers on their way to Iberia. The El Portalón individuals showed the greatest genetic affinity to Basques, which suggests that Basques and their language may be linked with the spread of agriculture across Europe.
Phospholipid dysregulation contributes to ApoE4-associated cognitive deficits in Alzheimer’s disease pathogenesis
Authors: Zhu Li , Zhong Minghao , Elder Gregory A. , Sano Mary , Holtzman David M. , Gandy Sam , Cardozo Christopher , Haroutunian Vahram , Robakis Nikolaos K. , Cai Dongming
Published: September 2015

Significance

The apolipoprotein E4 (ApoE4) genotype is the strongest genetic risk factor for developing Alzheimer’s disease (AD). However, the mechanisms that underlie this link between ApoE4 genotype and AD are not well understood. Our data in this paper are the first mechanistic studies to our knowledge that link ApoE4 genotype-specific changes in brain phospholipid homeostasis to ApoE4-increased susceptibility to develop AD. Our studies indicate previously unidentified therapeutic options for the treatment of AD, targeting ApoE4’s pathogenic nature.
In-depth study of
Mollivirus sibericum
, a new 30,000-y-old giant virus infecting
Acanthamoeba
Authors: Legendre Matthieu , Lartigue Audrey , Bertaux Lionel , Jeudy Sandra , Bartoli Julia , Lescot Magali , Alempic Jean-Marie , Ramus Claire , Bruley Christophe , Labadie Karine , Shmakova Lyubov , Rivkina Elizaveta , Couté Yohann , Abergel Chantal , Claverie Jean-Michel
Published: September 2015

Significance

The saga of giant viruses (i.e. visible by light microscopy) started in 2003 with the discovery of Mimivirus. Two additional types of giant viruses infecting
Acanthamoeba
have been discovered since: the Pandoraviruses (2013) and
Pithovirus sibericum
(2014), the latter one revived from 30,000-y-old Siberian permafrost. We now describe
Mollivirus sibericum
, a fourth type of giant virus isolated from the same permafrost sample. These four types of giant virus exhibit different virion structures, sizes (0.6–1.5 µm), genome length (0.6–2.8 Mb), and replication cycles. Their origin and mode of evolution are the subject of conflicting hypotheses. The fact that two different viruses could be easily revived from prehistoric permafrost should be of concern in a context of global warming.
Gut DNA viromes of Malawian twins discordant for severe acute malnutrition
Authors: Reyes Alejandro , Blanton Laura V. , Cao Song , Zhao Guoyan , Manary Mark , Trehan Indi , Smith Michelle I. , Wang David , Virgin Herbert W. , Rohwer Forest , Gordon Jeffrey I.
Published: September 2015

Significance

Childhood malnutrition is a global health problem not attributable to food insecurity alone. Sequencing DNA viruses present in fecal microbiota serially sampled from 0- to 3-y-old Malawian twin pairs, we identify age-discriminatory viruses that define a “program” of assembly of phage and eukaryotic components of the gut “virome” within and across pairs where both cotwins manifest healthy growth. This program is perturbed (delayed) in both members of discordant pairs where one cotwin develops severe acute malnutrition and the other appears healthy by anthropometry. This developmental delay is not repaired by therapeutic foods. These age- and disease-discriminatory viruses may help define familial risk for childhood malnutrition and provide a viral dimension for characterizing the developmental biology of our gut microbial “organ.”
Unique potential of 4-1BB agonist antibody to promote durable regression of HPV
+
tumors when combined with an E6/E7 peptide vaccine
Authors: Bartkowiak Todd , Singh Shailbala , Yang Guojun , Galvan Gloria , Haria Dhwani , Ai Midan , Allison James P. , Sastry K. Jagannadha , Curran Michael A.
Published: September 2015

Significance

Nearly all cervical, anal, vulvar, and penile cancer and up to half of oropharyngeal cancers are driven by the E6 and E7 oncoproteins of human papilloma virus (HPV). Therapeutic vaccination against these HPV proteins can slow disease progression in animal models and in patients, but is rarely curative. We demonstrate that coadministration of agonist antibodies targeting the T-cell costimulatory receptor 4-1BB and an intranasal HPV E6/E7 peptide vaccine promoted durable regression in 100% of animals bearing HPV
+
TC-1 tumors established in the female reproductive tract. The efficacy of 4-1BB in this system was unique among immune checkpoint antibodies and provides a paradigm for enhancement of therapeutic cancer vaccines with costimulatory agonist antibodies.
Transcellular spreading of huntingtin aggregates in theDrosophilabrain
Authors: Babcock Daniel T. , Ganetzky Barry
Published: September 2015

Significance

Propagation of protein aggregates throughout the nervous system is thought to play a significant role in the pathology of neurodegenerative diseases. Thus, understanding how this propagation is regulated is crucial for identifying potential therapeutic interventions. Here we use experimental advantages ofDrosophilato investigate aggregate spreading. We demonstrate that huntingtin, containing an expanded polyglutamine tract of 138 repeats, but not an unexpanded form, aggregates and spreads rapidly throughout the brain, resulting in loss of vulnerable neurons. Aggregate spreading and neuronal loss are impaired by blocking synaptic exocytosis in releasing cells or endocytic uptake in target cells. These studies enable screens for genetic and pharmacological modifiers that could ameliorate the deleterious effects of spreading in neurodegenerative diseases.
BMix: probabilistic modeling of occurring substitutions in PAR-CLIP data
Authors: Golumbeanu Monica , Mohammadi Pejman , Beerenwinkel Niko
Published: September 2015

Motivation : Photoactivatable ribonucleoside-enhanced cross-linking and immunoprecipitation (PAR-CLIP) is an experimental method based on next-generation sequencing for identifying the RNA interaction sites of a given protein. The method deliberately inserts T-to-C substitutions at the RNA-protein interaction sites, which provides a second layer of evidence compared with other CLIP methods. However, the experiment includes several sources of noise which cause both low-frequency errors and spurious high-frequency alterations. Therefore, rigorous statistical analysis is required in order to separate true T-to-C base changes, following cross-linking, from noise. So far, most of the existing PAR-CLIP data analysis methods focus on discarding the low-frequency errors and rely on high-frequency substitutions to report binding sites, not taking into account the possibility of high-frequency false positive substitutions.

Results : Here, we introduce BMix , a new probabilistic method which explicitly accounts for the sources of noise in PAR-CLIP data and distinguishes cross-link induced T-to-C substitutions from low and high-frequency erroneous alterations. We demonstrate the superior speed and accuracy of our method compared with existing approaches on both simulated and real, publicly available human datasets.

Availability and implementation : The model is freely accessible within the BMix toolbox at www.cbg.bsse.ethz.ch/software/BMix , available for Matlab and R.

Supplementary information:  Supplementary data is available at Bioinformatics online.

Contact : niko.beerenwinkel@bsse.ethz.ch
Hammock: a hidden Markov model-based peptide clustering algorithm to identify protein-interaction consensus motifs in large datasets
Authors: Krejci Adam , Hupp Ted R. , Lexa Matej , Vojtesek Borivoj , Muller Petr
Published: September 2015

Motivation: Proteins often recognize their interaction partners on the basis of short linear motifs located in disordered regions on proteins’ surface. Experimental techniques that study such motifs use short peptides to mimic the structural properties of interacting proteins. Continued development of these methods allows for large-scale screening, resulting in vast amounts of peptide sequences, potentially containing information on multiple protein-protein interactions. Processing of such datasets is a complex but essential task for large-scale studies investigating protein-protein interactions.

Results: The software tool presented in this article is able to rapidly identify multiple clusters of sequences carrying shared specificity motifs in massive datasets from various sources and generate multiple sequence alignments of identified clusters. The method was applied on a previously published smaller dataset containing distinct classes of ligands for SH3 domains, as well as on a new, an order of magnitude larger dataset containing epitopes for several monoclonal antibodies. The software successfully identified clusters of sequences mimicking epitopes of antibody targets, as well as secondary clusters revealing that the antibodies accept some deviations from original epitope sequences. Another test indicates that processing of even much larger datasets is computationally feasible.

Availability and implementation: Hammock is published under GNU GPL v. 3 license and is freely available as a standalone program (from http://www.recamo.cz/en/software/hammock-cluster-peptides/) or as a tool for the Galaxy toolbox (from https://toolshed.g2.bx.psu.edu/view/hammock/hammock). The source code can be downloaded from https://github.com/hammock-dev/hammock/releases.

Contact:  muller@mou.cz

Supplementary  information:  Supplementary data are available at Bioinformatics online.
ResiCon: a method for the identification of dynamic domains, hinges and interfacial regions in proteins
Authors: Dziubiński Maciej , Daniluk Paweł , Lesyng Bogdan
Published: September 2015

Motivation: Structure of most proteins is flexible. Identification and analysis of intramolecular motions is a complex problem. Breaking a structure into relatively rigid parts, the so-called dynamic domains, may help comprehend the complexity of protein’s mobility. We propose a new approach called ResiCon (Residue Contacts analysis), which performs this task by applying a data-mining analysis of an ensemble of protein configurations and recognizes dynamic domains, hinges and interfacial regions, by considering contacts between residues.

Results: Dynamic domains found by ResiCon are more compact than those identified by two other popular methods: PiSQRD and GeoStaS. The current analysis was carried out using a known reference set of 30 NMR protein structures, as well as molecular dynamics simulation data of flap opening events in HIV-1 protease. The more detailed analysis of HIV-1 protease dataset shows that ResiCon identified dynamic domains involved in structural changes of functional importance.

Availability and implementation: The ResiCon server is available at URL: http://dworkowa.imdik.pan.pl/EP/ResiCon.

Contact:  pawel@bioexploratorium.pl

Supplementary information:  Supplementary data are available at Bioinformatics online.
metaModules identifies key functional subnetworks in microbiome-related disease
Authors: May Ali , Brandt Bernd W. , El-Kebir Mohammed , Klau Gunnar W. , Zaura Egija , Crielaard Wim , Heringa Jaap , Abeln Sanne
Published: September 2015

Motivation: The human microbiome plays a key role in health and disease. Thanks to comparative metatranscriptomics, the cellular functions that are deregulated by the microbiome in disease can now be computationally explored. Unlike gene-centric approaches, pathway-based methods provide a systemic view of such functions; however, they typically consider each pathway in isolation and in its entirety. They can therefore overlook the key differences that (i) span multiple pathways, (ii) contain bidirectionally deregulated components, (iii) are confined to a pathway region. To capture these properties, computational methods that reach beyond the scope of predefined pathways are needed.

Results: By integrating an existing module discovery algorithm into comparative metatranscriptomic analysis, we developed metaModules, a novel computational framework for automated identification of the key functional differences between health- and disease-associated communities. Using this framework, we recovered significantly deregulated subnetworks that were indeed recognized to be involved in two well-studied, microbiome-mediated oral diseases, such as butanoate production in periodontal disease and metabolism of sugar alcohols in dental caries. More importantly, our results indicate that our method can be used for hypothesis generation based on automated discovery of novel, disease-related functional subnetworks, which would otherwise require extensive and laborious manual assessment.

Availability and implementation: metaModules is available at https://bitbucket.org/alimay/metamodules/

Contact:  a.may@vu.nl or s.abeln@vu.nl

Supplementary information:  Supplementary data are available at Bioinformatics online.
Desiderata for computable representations of electronic health records-driven phenotype algorithms
Authors: Mo Huan , Thompson William K , Rasmussen Luke V , Pacheco Jennifer A , Jiang Guoqian , Kiefer Richard , Zhu Qian , Xu Jie , Montague Enid , Carrell David S , Lingren Todd , Mentch Frank D , Ni Yizhao , Wehbe Firas H , Peissig Peggy L , Tromp Gerard , Larson Eric B , Chute Christopher G , Pathak Jyotishman , Denny Joshua C , Speltz Peter , Kho Abel N , Jarvik Gail P , Bejan Cosmin A , Williams Marc S , Borthwick Kenneth , Kitchner Terrie E , Roden Dan M , Harris Paul A
Published: September 2015

Background Electronic health records (EHRs) are increasingly used for clinical and translational research through the creation of phenotype algorithms. Currently, phenotype algorithms are most commonly represented as noncomputable descriptive documents and knowledge artifacts that detail the protocols for querying diagnoses, symptoms, procedures, medications, and/or text-driven medical concepts, and are primarily meant for human comprehension. We present desiderata for developing a computable phenotype representation model (PheRM).

Methods A team of clinicians and informaticians reviewed common features for multisite phenotype algorithms published in PheKB.org and existing phenotype representation platforms. We also evaluated well-known diagnostic criteria and clinical decision-making guidelines to encompass a broader category of algorithms.

Results We propose 10 desired characteristics for a flexible, computable PheRM: (1) structure clinical data into queryable forms; (2) recommend use of a common data model, but also support customization for the variability and availability of EHR data among sites; (3) support both human-readable and computable representations of phenotype algorithms; (4) implement set operations and relational algebra for modeling phenotype algorithms; (5) represent phenotype criteria with structured rules; (6) support defining temporal relations between events; (7) use standardized terminologies and ontologies, and facilitate reuse of value sets; (8) define representations for text searching and natural language processing; (9) provide interfaces for external software algorithms; and (10) maintain backward compatibility.

Conclusion A computable PheRM is needed for true phenotype portability and reliability across different EHR products and healthcare systems. These desiderata are a guide to inform the establishment and evolution of EHR phenotype algorithm authoring platforms and languages.
Patient and physician predictors of patient receipt of therapies recommended by a computerized decision support system when initially prescribed broad-spectrum antibiotics: a cohort study
Authors: Chow Angela LP , Lye David C. , Arah Onyebuchi A
Published: September 2015

Objective Antibiotic computerized decision support systems (CDSSs) were developed to guide antibiotic decisions, yet prescriptions of CDSS-recommended antibiotics have remained low. Our aim was to identify predictors of patients' receipt of empiric antibiotic therapies recommended by a CDSS when the prescribing physician had an initial preference for using broad-spectrum antibiotics.

Methods We conducted a prospective cohort study in a 1 500-bed tertiary-care hospital in Singapore. We included all patients admitted from October 1, 2011 through September 30, 2012, who were prescribed piperacillin-tazobactam or carbapenem for empiric therapy and auto-triggered to receive antibiotic recommendations by the in-house antibiotic CDSS. Relevant data on the patient, prescribing and attending physicians were collected via electronic linkages of medical records and administrative databases. To account for clustering, we used multilevel logistic regression models to explore factors associated with receipt of CDSS-recommended antibiotic therapy.

Results One-quarter of the 1 886 patients received CDSS-recommended antibiotics. More patients treated for pneumonia (33.2%) than sepsis (12.1%) and urinary tract infections (7.1%) received CDSS-recommended antibiotic therapies. The prescribing physician – but not the attending physician or clinical specialty – accounted for some (13.3%) of the variation. Prior hospitalization (odds ratio [OR] 1.32, 95% CI, 1.01-1.71), presumed pneumonia (OR 6.77, 95% CI, 3.28-13.99), intensive care unit (ICU) admission (OR 0.38, 95% CI, 0.21-0.66), and renal impairment (OR 0.70, 95% CI, 0.52-0.93) were factors associated with patients’ receipt of CDSS-recommended antibiotic therapies.

Conclusions We observed that ICU admission and renal impairment were negative predictors of patients’ receipt of CDSS-recommended antibiotic therapies. Patients admitted to ICU and those with renal impairment might have more complex clinical conditions that require a physician's assessment in addition to antibiotic CDSS.
Cardiac catheterization laboratory inpatient forecast tool: a prospective evaluation
Authors: Toerper Matthew F , Flanagan Eleni , Siddiqui Sauleh , Appelbaum Jeff , Kasper Edward K , Levin Scott
Published: September 2015

Objective To develop and prospectively evaluate a web-based tool that forecasts the daily bed need for admissions from the cardiac catheterization laboratory using routinely available clinical data within electronic medical records (EMRs).

Methods The forecast model was derived using a 13-month retrospective cohort of 6384 catheterization patients. Predictor variables such as demographics, scheduled procedures, and clinical indicators mined from free-text notes were input to a multivariable logistic regression model that predicted the probability of inpatient admission. The model was embedded into a web-based application connected to the local EMR system and used to support bed management decisions. After implementation, the tool was prospectively evaluated for accuracy on a 13-month test cohort of 7029 catheterization patients.

Results The forecast model predicted admission with an area under the receiver operating characteristic curve of 0.722. Daily aggregate forecasts were accurate to within one bed for 70.3% of days and within three beds for 97.5% of days during the prospective evaluation period. The web-based application housing the forecast model was used by cardiology providers in practice to estimate daily admissions from the catheterization laboratory.

Discussion The forecast model identified older age, male gender, invasive procedures, coronary artery bypass grafts, and a history of congestive heart failure as qualities indicating a patient was at increased risk for admission. Diagnostic procedures and less acute clinical indicators decreased patients’ risk of admission. Despite the site-specific limitations of the model, these findings were supported by the literature.

Conclusion Data-driven predictive analytics may be used to accurately forecast daily demand for inpatient beds for cardiac catheterization patients. Connecting these analytics to EMR data sources has the potential to provide advanced operational decision support.
Election Fraud: A Latent Class Framework for Digit-Based Tests
Authors: Medzihorsky Juraj
Published: September 2015

Digit-based election forensics (DBEF) typically relies on null hypothesis significance testing, with undesirable effects on substantive conclusions. This article proposes an alternative free of this problem. It rests on decomposing the observed numeral distribution into the “no fraud” and “fraud” latent classes, by finding the smallest fraction of numerals that needs to be either removed or reallocated to achieve a perfect fit of the “no fraud” model. The size of this fraction can be interpreted as a measure of fraudulence. Both alternatives are special cases of measures of model fit—theπ∗ mixture index of fit and the Δ dissimilarity index, respectively. Furthermore, independently of the latent class framework, the distributional assumptions of DBEF can be relaxed in some contexts. Independently or jointly, the latent class framework and the relaxed distributional assumptions allow us to dissect the observed distributions using models more flexible than those of existing DBEF. Reanalysis of Beber and Scacco's (2012) data shows that the approach can lead to new substantive conclusions.
The five-dimensional parameter space of grain boundaries
Authors: Sutton A. P. , Banks E. P. , Warwick A. R.
Published: September 2015

To specify a grain boundary at a macroscopic length scale requires the specification of five degrees of freedom. We use a specification in which three degrees of freedom associated with the boundary misorientation are in an orthogonal subspace from two associated with the mean boundary plane. By using Rodrigues vectors to describe rotations, we show how paths through these subspaces may be characterized. Some of these paths correspond to physical processes involving grain boundaries during microstructural evolution. Exploiting the orthogonality of the subspaces, a metric to measure ‘distance’ between two boundaries is defined in terms of the minimum set of rotations required to map one boundary on to the other. We compare our metric with others that have appeared. The existence of rotational symmetry in face-centred cubic crystals leads to as many as 2304 equivalent specifications of a boundary. We illustrate this multiplicity of descriptions for the (111) twin and a more general boundary. We present an algorithm to evaluate the geodesic distance between two boundaries, and apply it to identify the path along which the distance between these two boundaries is minimized. In general, the shortest path does not involve descriptions of boundary misorientations with the smallest misorientation angles.
Proposal of nine novel species of the genus Lysinimicrobium and emended description of the genus Lysinimicrobium
Authors: Hamada Moriyuki , Shibata Chiyo , Saitou Satomi , Tamura Tomohiko , Komaki Hisayuki , Ichikawa Natsuko , Oguchi Akio , Hosoyama Akira , Fujita Nobuyuki , Yamamura Hideki , Hayakawa Masayuki , Suzuki Ken-ichiro
Published: September 2015

Thirteen novel Gram-stain-positive bacteria were isolated from various samples collected from mangrove forests in Japan, and their taxonomic positions were investigated by a polyphasic approach. Phylogenetic analyses based on 16S rRNA gene sequence comparisons showed that the 13 isolates formed a single clade with Lysinimicrobium mangrovi HI08-69T, with a similarity range of 97.6–99.5 %. The peptidoglycan of the isolates was of the A4α type with an interpeptide bridge comprising Ser–Glu and an l-Ser residue at position 1 of the peptide subunit. The predominant menaquinone was demethylmenaquinone DMK-9(H4) and the major fatty acid was anteiso-C15 : 0. These chemotaxonomic characteristics corresponded to those of the genus Lysinimicrobium. On the basis of the phenotypic and phylogenetic data, along with average nucleotide identity values among the isolates, we concluded that the 13 isolates should be assigned to the following nine novel species of the genus Lysinimicrobium: Lysinimicrobium aestuarii sp. nov. (type strain HI12-104T = NBRC 109392T = DSM 28144T), Lysinimicrobium flavum sp. nov. (type strain HI12-45T = NBRC 109391T = DSM 28150T), Lysinimicrobium gelatinilyticum sp. nov. (type strain HI12-44T = NBRC 109390T = DSM 28149T), Lysinimicrobium iriomotense sp. nov. (type strain HI12-143T = NBRC 109399T = DSM 28146T), Lysinimicrobium luteum sp. nov. (type strain HI12-123T = NBRC 109395T = DSM 28147T), Lysinimicrobium pelophilum sp. nov. (type strain HI12-111T = NBRC 109393T = DSM 28148T), Lysinimicrobium rhizosphaerae sp. nov. (type strain HI12-135T = NBRC 109397T = DSM 28152T), Lysinimicrobium soli sp. nov. (type strain HI12-122T = NBRC 109394T = DSM 28151T) and Lysinimicrobium subtropicum sp. nov. (type strain HI12-128T = NBRC 109396T = DSM 28145T). In addition, an emended description of the genus Lysinimicrobium is proposed.
Eggerthella lenta bacteraemia in a patient with Caroli disease
Authors: Miguel Sahuquillo-Arce José , Guitián-Deltell Jorge , Falomir-Salcedo Patricia , Galiana-Sastre María , López-Andujar Rafael , López-Hontangas José Luis
Published: September 2015

Introduction:

Eggerthella lenta is an obligate anaerobic, non-spore-forming, Gram-positive rod found as a normal commensal of the human intestinal flora, which is capable of reducing digoxin into several metabolites. Disease caused by this micro-organism is unusual, although more frequent than reported.

Case presentation:

A 74-year-old man presented to the emergency room and was admitted with a mild acute cholangitis syndrome. One anaerobic blood culture became positive after 5 days of incubation. After an additional 5 days, the usual aerobic subcultures were negative, whereas anaerobically incubated Columbia blood agar presented tiny smooth colonies. The isolate was capable of reducing digoxin and was identified as Eggerthella lenta. Adequate antibiotic treatment with meropenem had been started and the patient recovered fully.

Conclusion:

We have described a patient with a potentially fatal bacteraemia with E. lenta that may have gone unnoticed. More case reports are necessary, not only to understand the pathogenicity and clinical course of infections by this neglected bacterium, but also to investigate its digoxin degradation and antimicrobial susceptibility variability.
Meningitis caused by Porphyromonas endodontalis detected by PCR amplification and sequencing of 16S rRNA genes direct from cerebrospinal fluid and cerebral tissue
Authors: New David W. , Pryce Todd M.
Published: September 2015

Introduction:

Porphyromonas endodontalis (formerly Bacteroides endontalis) is a black-pigmented, non-motile, obligate anaerobe. It has an established role in endodontal infections and has rarely been isolated from other sites. To the best of our knowledge, this is the first time that this organism has been detected as the sole cause of meningitis. This was made possible by the use of direct-on-sample 16S rRNA gene amplification and sequencing.

Case presentation:

We present a case of meningitis that progressed to a cerebral abscess in an elderly but otherwise immunocompetent male. Despite broad-spectrum antibiotic therapy, the patient died.

Conclusion:

Although anaerobic meningitis is rarely described, it should be considered if there are clinical and biochemical features of meningitis but no organism isolated on standard aerobic culture.
Neisseria elongata prosthetic valve endocarditis: case report and literature review
Authors: Sawas Tarek , Hong-Nguyen Yugenia , Woods Christian J.
Published: September 2015

Introduction:

Neisseria elongata, a Gram-variable, rod-shaped organism, was previously thought to be non-pathogenic. However, in recent years it has become increasingly recognized as a rare cause of infective endocarditis. Here, to the best of our knowledge, we describe the first case of bivalvular prosthetic valve endocarditis due to N. elongata.

Case Presentation:

A 55-year-old Taiwanese man with history of Streptococcus viridans endocarditis status post prosthetic mitral and aortic valve replacements presented with a 2-week history of progressive fatigue and altered mental status. He presented with fever, lethargy and shock. He was intubated and started on vasopressors. A systolic murmur was noted with leukocytosis and acute renal failure. He was started on broad-spectrum antibiotics. An initial trans-oesophageal echocardiogram (TOE) did not reveal vegetation, but showed an elevated aortic valve gradient of 70 mmHg consistent with severe aortic stenosis. A repeat TOE revealed multiple mobile and immobile mitral and aortic valve vegetations with an abscess extending toward the aortic valve. Three sets of positive blood cultures from admission identified N. elongata. Antibiotics were tailored to ceftriaxone. He underwent urgent aortic and mitral valve replacement. He completed a 6-week course of ceftriaxone. At discharge, two-dimensional echo revealed normal heart function with normal prosthetic mitral and aortic valves.

Conclusion:

N. elongata is an uncommon, but increasingly recognized, cause of infective endocarditis. It causes severe valvular destruction with systemic complications and often requires surgical intervention.
An Accurate Genetic Clock
Authors: Hamilton David H
Published: September 2015

Our method for “Time to most recent common ancestor” TMRCA of genetic trees for the first time deals with natural selection by apriori mathematics and not as a random factor. Bioprocesses such as “kin selection” generate a few overrepresented “singular lineages” while almost all other lineages terminate. This non-uniform branching gives greatly exaggerated TMRCA with current methods. Thus we introduce an inhomogenous stochastic process which will detect singular lineages by asymmetries, whose “reduction” then gives true TMRCA. This gives a new phylogenetic method for computing mutation rates, with results similar to “pedigree” (meiosis) data. Despite these low rates, reduction implies younger TMRCA, with smaller errors. We establish accuracy by a comparison across a wide range of time, indeed this is only y-clock giving consistent results for 500-15,000 ybp. In particular we show that the dominant European Y-haplotypes R1a1a & R1b1a2, expand from c4000BC, not reaching Anatolia before c3800BC. This contradicts previous clocks dating R1b1a2 to either the Neolithic Near East or Paleo-Europe. However our dates match R1a1a & R1b1a2 found in Yamnaya cemetaries of c3300BC by Nielsen et al (2015), Pääbo et al(2015), together proving R1a1a & R1b1a2 originates in the Russian Steppes.
Development of EST-SSR annotated database in olive (Olea europaea)
Authors: Adawy Sami S. , Mokhtar Morad M. , Alsamman Alsamman M. , Sakr Mahmoud M.
Published: September 2015

Olive tree (Olea europaeaL.) is one of the most important oil producing crops in the world and the genetic identification of several genotypes by using molecular markers is the first step in its breeding programs. A set of 1,801 well-informative EST-SSR primers targeting specific Olive genes included in different biological processes and pathways were generated using 11,215 Olive EST sequences acquired from the NCBI database. Our bioinformatics analytical procedure showed that 8295 SSR motifs were detected which belonged to different motif types with occurrences of 77.6%, 11.84%, 8.62%, 0.84%, 0.77% and 0.29% for Mononucleotide, trinucleotide, dinucleotide, hexanucleotide, pentanucleotide and tetranucleotide respectively. The appearance of the AAG/CTT repeat was highly represented in trinucleotide and the representation of AG/CT was high in dinucleotide repeats. Results obtained from functional annotation of olives EST sequences targeted with our primers set indicated that 78.5% of these sequences having homology with known proteins, while 4.2% was homologous to hypothetical, predicted, unnamed or uncharacterized proteins and the 17.3% sequences did not possess homology with any known proteins. Our EST-SSR primer set cover a total of 92 biological pathways such as carbohydrate metabolism pathway, energy metabolism& carbon fixation in photosynthetic organism pathway including 11 pathways associated with lipid metabolism. A twenty five randomly selected primers were applied to 9 Egyptian cultivated olive accessions to test its amplification and polymorphism detection efficacy. All tested primers were successfully amplified and only 10 exhibited detectable polymorphism.
Passenger DNA alterations reduce cancer fitness in cell culture and mouse models
Authors: McFarland Christopher D , Yaglom Julia A , Wojtkowiak Jonathan W , Scott Jacob G , Morse David L , Sherman Michael Y , Mirny Leonid A
Published: September 2015

Genomic instability causes cancers to acquire hundreds to thousands of mutations and chromosomal alterations during their somatic evolution. Most of these mutations and alterations are termed passengers because they do not confer cancer phenotypes. Evolutionary simulations and cancer genomic studies suggested that mildly-deleterious passengers accumulate, collectively slow cancer progression, reduce the fitness of cancer cells and enhance the effects of therapeutics. However, these effects of passengers and their impact on clinical variables remain limited to genomic analysis. Here, to assess passengers’ effect on cell fitness and cancer, we specifically introduced increasing passenger loads into human cell lines and mouse models. We found that passenger load dramatically reduced cancer cell’s fitness in every model investigated. Passengers’ average fitness cost of ∼3% per MB, indicates that genomic instability in cancer in patients can slow tumor growth and prevent metastatic progression. We conclude that genomic instability in cancer is a double-edged sword: it accelerates the accumulation of adaptive drivers, yet incurs a harmful passenger load that can outweigh drivers’ benefit. Passenger load could be a useful biomarker for tumor aggressiveness and response to mutagenic or passenger-exacerbating therapies, including anti-tumor immunity.