Turing's Genius - Defining an apt microcosm.

Alan Turing (1912–1954) is widely acknowledged as a genius. As well as codebreaking during World War II and taking a pioneering role in computer hardware design and software after the War, he also wrote three important foundational papers in the fields of theoretical computer science, artificial intelligence, and mathematical biology. He has been called the father of computer science, but he also admired by mathematicians, philosophers, and perhaps more surprisingly biologists, for his wide-ranging ideas. His influence stretches from scientific to cultural and even political impact. For all these reasons, he was a true polymath. This paper considers the genius of Turing from various angles, both scientific and artistic. The four authors provide position statements on how Turing has influenced and inspired their work, together with short biographies, as a starting point for a panel session and visual music performance

Layer-by-layer surface modification of poly(ether sulfone) membranes using polyelectrolytes and AgCl/TiO2 xerogels

In this study, the layer-by-layer (LbL) assembly method was employed to modify a commercial polyethersulfone (PES) membrane by successive adsorption of chitosan and alginate as cationic and anionic polyelectrolytes. To enhance anti-biofouling property, pure, PEG mixed and PEGylated AgCl/TiO2 xerogels were incorporated solely in the top layer of the LbL-modified membranes. Organic and biological foulings were addressed separately using alginate and Escherichia coli bacteria suspensions as the organic and biological model foulants, respectively. LbL-modifying the commercial PES membrane successively with chitosan and alginate polyelectrolyte multilayers prevented organic fouling extensively. In addition, we found that AgCl/TiO2-incorporated membranes show higher water permeability and improved resistance to biological fouling as compared to the PES membrane. Silver amounts in consecutively collected permeate samples were quantified by ICP-MS analysis to assess the stability of AgCl/TiO2-incorporated layers. Silver loss per filtration cycle followed an increasing trend initially, up to a filtration volume totaling 3000L/m2, leading to 4.2% reduction in the immobilized silver amount. After that, silver loss per filtration cycle stabilized at ~7.44μg/L, which extrapolates to ~265 days time-span for the remaining silver to be released at a filtration rate of ~1000L/m2 h. Antibacterial activity tests showed that AgCl/TiO2-incorporated layers do not permit bacterial growth on the membrane surface.European Union (246039

Risk factors for delayed presentation and referral of symptomatic cancer: Evidence for common cancers

Background:It has been suggested that the known poorer survival from cancer in the United Kingdom, compared with other European countries, can be attributed to more advanced cancer stage at presentation. There is, therefore, a need to understand the diagnostic process, and to ascertain the risk factors for increased time to presentation.Methods:We report the results from two worldwide systematic reviews of the literature on patient-mediated and practitioner-mediated delays, identifying the factors that may influence these.Results:Across cancer sites, non-recognition of symptom seriousness is the main patient-mediated factor resulting in increased time to presentation. There is strong evidence of an association between older age and patient delay for breast cancer, between lower socio-economic status and delay for upper gastrointestinal and urological cancers and between lower education level and delay for breast and colorectal cancers. Fear of cancer is a contributor to delayed presentation, while sanctioning of help seeking by others can be a powerful mediator of reduced time to presentation. For practitioner delay, ‘misdiagnosis’ occurring either through treating patients symptomatically or relating symptoms to a health problem other than cancer, was an important theme across cancer sites. For some cancers, this could also be linked to inadequate patient examination, use of inappropriate tests or failing to follow-up negative or inconclusive test results.Conclusion:Having sought help for potential cancer symptoms, it is therefore important that practitioners recognise these symptoms, and examine, investigate and refer appropriately. © 2009 Cancer Research UK All rights reserved

Initial Medical Attention on Patients with Early-Stage Non-Small Cell Lung Cancer

Detection of early stage non-small cell lung cancer (NSCLC) is commonly believed to be incidental. Understanding the reasons that caused initial detection of these patients is important for early diagnosis. However, these reasons are not well studied.We retrospectively reviewed medical records of patients diagnosed with stage I or II NSCLC between 2000 and 2009 at UT MD Anderson Cancer Center. Information on suggestive LC-symptoms or other reasons that caused detection were extracted from patients' medical records. We applied univariate and multivariate analyses to evaluate the association of suggestive LC-symptoms with tumor size and patient survival.Of the 1396 early stage LC patients, 733 (52.5%) presented with suggestive LC-symptoms as chief complaint. 347 (24.9%) and 287 (20.6%) were diagnosed because of regular check-ups and evaluations for other diseases, respectively. The proportion of suggestive LC-symptom-caused detection had a linear relationship with the tumor size (correlation 0.96; with p<.0001). After age, gender, race, smoking status, therapy, and stage adjustment, the symptom-caused detection showed no significant difference in overall and LC-specific survival when compared with the other (non-symptom-caused) detection.Symptoms suggestive of LC are the number one reason that led to detection in early NSCLC. They were also associated with tumor size at diagnosis, suggesting early stage LC patients are developing symptoms. Presence of symptoms in early stages did not compromise survival. A symptom-based alerting system or guidelines may be worth of further study to benefit NSCLC high risk individuals

Regional Management Units for Marine Turtles: A Novel Framework for Prioritizing Conservation and Research across Multiple Scales

Background: Resolving threats to widely distributed marine megafauna requires definition of the geographic distributions of both the threats as well as the population unit(s) of interest. In turn, because individual threats can operate on varying spatial scales, their impacts can affect different segments of a population of the same species. Therefore, integration of multiple tools and techniques - including site-based monitoring, genetic analyses, mark-recapture studies and telemetry - can facilitate robust definitions of population segments at multiple biological and spatial scales to address different management and research challenges. Methodology/Principal Findings: To address these issues for marine turtles, we collated all available studies on marine turtle biogeography, including nesting sites, population abundances and trends, population genetics, and satellite telemetry. We georeferenced this information to generate separate layers for nesting sites, genetic stocks, and core distributions of population segments of all marine turtle species. We then spatially integrated this information from fine-to coarse-spatial scales to develop nested envelope models, or Regional Management Units (RMUs), for marine turtles globally. Conclusions/Significance: The RMU framework is a solution to the challenge of how to organize marine turtles into units of protection above the level of nesting populations, but below the level of species, within regional entities that might be on independent evolutionary trajectories. Among many potential applications, RMUs provide a framework for identifying data gaps, assessing high diversity areas for multiple species and genetic stocks, and evaluating conservation status of marine turtles. Furthermore, RMUs allow for identification of geographic barriers to gene flow, and can provide valuable guidance to marine spatial planning initiatives that integrate spatial distributions of protected species and human activities. In addition, the RMU framework - including maps and supporting metadata - will be an iterative, user-driven tool made publicly available in an online application for comments, improvements, download and analysis

Genetic Detection and Characterization of Lujo Virus, a New Hemorrhagic Fever–Associated Arenavirus from Southern Africa

Lujo virus (LUJV), a new member of the family Arenaviridae and the first hemorrhagic fever–associated arenavirus from the Old World discovered in three decades, was isolated in South Africa during an outbreak of human disease characterized by nosocomial transmission and an unprecedented high case fatality rate of 80% (4/5 cases). Unbiased pyrosequencing of RNA extracts from serum and tissues of outbreak victims enabled identification and detailed phylogenetic characterization within 72 hours of sample receipt. Full genome analyses of LUJV showed it to be unique and branching off the ancestral node of the Old World arenaviruses. The virus G1 glycoprotein sequence was highly diverse and almost equidistant from that of other Old World and New World arenaviruses, consistent with a potential distinctive receptor tropism. LUJV is a novel, genetically distinct, highly pathogenic arenavirus

Estimating total body water content in suckling and lactating llamas (Lama glama) by isotope dilution

Total body water (TBW) in 17 suckling and six lactating llamas was estimated from isotope dilution at three different post natum and lactation stages using both 18O and deuterium oxide (D2O). In total, 69 TBW measurements were undertaken. While TBW in lactating dams, expressed in kilogram, remained stable during the three measurement periods (91.8 ± 15.0 kg), the body water fraction (TBW expressed in percent of body mass) increased slightly (P = 0.042) from 62.9% to 65.8%. In contrast, TBW (kilogram) in suckling llamas increased significantly (P < 0.001) with age and decreased slightly when expressed as a percentage of body mass (P = 0.016). Relating TBW to body mass across all animals yielded a highly significant regression equation (TBW in kilogram = 2.633 + 0.623 body mass in kilogram, P < 0.001, n = 69) explaining 99.5% of the variation. The water fraction instead decreased in a curve linear fashion with increasing body mass (TBW in percent of body mass = 88.23 body mass in kilogram−0.064, P < 0.001, R2 = 0.460). The present results on TBW can serve as reference values for suckling and lactating llamas, e.g., for the evaluation of fluid losses during disease. Additionally, the established regression equations can be used to predict TBW from body mass, providing that the body masses fall inside the range of masses used to derive the equations

Probiotics, prematurity and neurodevelopment: Follow-up of a randomised trial

Objective: To determine the impact of one probiotics combination on the neurodevelopment of very preterm children at 2&ndash;5 years corrected gestational age (CA). Design: Follow-up study of survivors of a double-blinded, placebo-controlled, randomised trial of probiotic effects on late-onset sepsis in very preterm infants that found reduced necrotising enterocolitis. Setting: 10 tertiary perinatal centres in Australia and New Zealand. Patients: 1099 very preterm infants born &lt;32 weeks&rsquo; gestation and weighing &lt;1500 g. Intervention: Probiotics (Bifidobacterium infantis, Streptococcus thermophilus and Bifidobacterium lactis) or placebo administered from birth until discharge home or term CA, whichever came sooner. Main outcome measures: Major neurodevelopmental impairment comprised any of moderate/severe cerebral palsy (Gross Motor Function Classification System score 2&ndash;5), motor impairment (Bayley-III Motor Composite Scale &lt;&ndash;2SD or Movement Assessment Battery for Children &lt;15th centile if ≫42 months&rsquo; CA), cognitive impairment (Bayley-III Composite Cognitive or Language Scales &lt;&ndash;2SD or Wechsler Preschool and Primary Scale of Intelligence Full Scale Intelligence Quotient &lt;&ndash;2SD if ≫42 months&rsquo; CA), blindness or deafness. Results: Outcome data were available for 735 (67%) participants, with 71 deaths and 664/1028 survivors assessed at a mean age of 30 months. Survival free of major neurodevelopmental impairment was comparable between groups (probiotics 281 (75.3%) vs placebo 271 (74.9%); relative risk 1.01 (95% CI 0.93 to 1.09)). Rates of deafness were lower in probiotic-treated children (0.6% vs 3.4%). Conclusion: Administration of the probiotics combination Bifidobacterium infantis, Streptococcus thermophilus and Bifidobacterium lactis to very preterm babies from soon after birth until discharge home or term CA did not adversely affect neurodevelopment or behaviour in early childhood

β-Catenin Loss in Hepatocytes Promotes Hepatocellular Cancer after Diethylnitrosamine and Phenobarbital Administration to Mice

Hepatocellular Carcinoma (HCC) is the fifth most common cancer worldwide. β-Catenin, the central orchestrator of the canonical Wnt pathway and a known oncogene is paramount in HCC pathogenesis. Administration of phenobarbital (PB) containing water (0.05% w/v) as tumor promoter following initial injected intraperitoneal (IP) diethylnitrosamine (DEN) injection (5 µg/gm body weight) as a tumor inducer is commonly used model to study HCC in mice. Herein, nine fifteen-day male β-catenin knockout mice (KO) and fifteen wild-type littermate controls (WT) underwent DEN/PB treatment and were examined for hepatic tumorigenesis at eight months. Paradoxically, a significantly higher tumor burden was observed in KO (p<0.05). Tumors in KO were β-catenin and glutamine synthetase negative and HGF/Met, EGFR & IGFR signaling was unremarkable. A significant increase in PDGFRα and its ligand PDGF-CC leading to increased phosphotyrosine-720-PDGFRα was observed in tumor-bearing KO mice (p<0.05). Simultaneously, these livers displayed increased cell death, stellate cell activation, hepatic fibrosis and cell proliferation. Further, PDGF-CC significantly induced hepatoma cell proliferation especially following β-catenin suppression. Our studies also demonstrate that the utilized DEN/PB protocol in the WT C57BL/6 mice did not select for β-catenin gene mutations during hepatocarcinogenesis. Thus, DEN/PB enhanced HCC in mice lacking β-catenin in the liver may be due to their ineptness at regulating cell survival, leading to enhanced fibrosis and regeneration through PDGFRα activation. β-Catenin downregulation also made hepatoma cells more sensitive to receptor tyrosine kinases and thus may be exploited for therapeutics

Regional block versus general anaesthesia for caesarean section and neonatal outcomes: a population-based study

<p>Abstract</p> <p>Background</p> <p>Anaesthesia guidelines recommend regional anaesthesia for most caesarean sections due to the risk of failed intubation and aspiration with general anaesthesia. However, general anaesthesia is considered to be safe for the foetus, based on limited evidence, and is still used for caesarean sections.</p> <p>Methods</p> <p>Cohorts of caesarean sections by indication (that is, planned repeat caesarean section, failure to progress, foetal distress) were selected from the period 1998 to 2004 (<it>N </it>= 50,806). Deliveries performed under general anaesthesia were compared with those performed under spinal or epidural, for the outcomes of neonatal intubation and 5-minute Apgar (Apgar5) <7.</p> <p>Results</p> <p>The risk of adverse outcomes was increased for caesarean sections under general anaesthesia for all three indications and across all levels of hospital. The relative risks were largest for low-risk planned repeat caesarean deliveries: resuscitation with intubation relative risk was 12.8 (95% confidence interval 7.6, 21.7), and Apgar5 <7 relative risk was 13.4 (95% confidence interval 9.2, 19.4). The largest absolute increase in risk was for unplanned caesareans due to foetal distress: there were five extra intubations per 100 deliveries and six extra Apgar5 <7 per 100 deliveries.</p> <p>Conclusion</p> <p>The infants most affected by general anaesthesia were those already compromised <it>in utero</it>, as evidenced by foetal distress. The increased rate of adverse neonatal outcomes should be weighed up when general anaesthesia is under consideration.</p