Automated Retinopathy of Prematurity Case Detection with Convolutional Neural Networks

Retinopathy of Prematurity (ROP) is an ocular disease observed in premature babies, considered one of the largest preventable causes of childhood blindness. Problematically, the visual indicators of ROP are not well understood and neonatal fundus images are usually of poor quality and resolution. We investigate two ways to aid clinicians in ROP detection using convolutional neural networks (CNN): (1) We fine-tune a pretrained GoogLeNet as a ROP detector and with small modifications also return an approximate Bayesian posterior over disease presence. To the best of our knowledge, this is the first completely automated ROP detection system. (2) To further aid grading, we train a second CNN to return novel feature map visualizations of pathologies, learned directly from the data. These feature maps highlight discriminative information, which we believe may be used by clinicians with our classifier to aid in screening

Control over phase separation and nucleation using a laser-tweezing potential

Control over the nucleation of new phases is highly desirable but elusive. Even though there is a long history of crystallization engineering by varying physicochemical parameters, controlling which polymorph crystallizes or whether a molecule crystallizes or forms an amorphous precipitate is still a poorly understood practice. Although there are now numerous examples of control using laser-induced nucleation, the absence of physical understanding is preventing progress. Here we show that the proximity of a liquid–liquid critical point or the corresponding binodal line can be used by a laser-tweezing potential to induce concentration gradients. A simple theoretical model shows that the stored electromagnetic energy of the laser beam produces a free-energy potential that forces phase separation or triggers the nucleation of a new phase. Experiments in a liquid mixture using a low-power laser diode confirm the effect. Phase separation and nucleation using a laser-tweezing potential explains the physics behind non-photochemical laser-induced nucleation and suggests new ways of manipulating matter

Dual-gated bilayer graphene hot electron bolometer

Detection of infrared light is central to diverse applications in security, medicine, astronomy, materials science, and biology. Often different materials and detection mechanisms are employed to optimize performance in different spectral ranges. Graphene is a unique material with strong, nearly frequency-independent light-matter interaction from far infrared to ultraviolet, with potential for broadband photonics applications. Moreover, graphene's small electron-phonon coupling suggests that hot-electron effects may be exploited at relatively high temperatures for fast and highly sensitive detectors in which light energy heats only the small-specific-heat electronic system. Here we demonstrate such a hot-electron bolometer using bilayer graphene that is dual-gated to create a tunable bandgap and electron-temperature-dependent conductivity. The measured large electron-phonon heat resistance is in good agreement with theoretical estimates in magnitude and temperature dependence, and enables our graphene bolometer operating at a temperature of 5 K to have a low noise equivalent power (33 fW/Hz1/2). We employ a pump-probe technique to directly measure the intrinsic speed of our device, >1 GHz at 10 K.Comment: 5 figure

Phytochemicals as antibiotic alternatives to promote growth and enhance host health

There are heightened concerns globally on emerging drug-resistant superbugs and the lack of new antibiotics for treating human and animal diseases. For the agricultural industry, there is an urgent need to develop strategies to replace antibiotics for food-producing animals, especially poultry and livestock. The 2nd International Symposium on Alternatives to Antibiotics was held at the World Organization for Animal Health in Paris, France, December 12-15, 2016 to discuss recent scientific developments on strategic antibiotic-free management plans, to evaluate regional differences in policies regarding the reduction of antibiotics in animal agriculture and to develop antibiotic alternatives to combat the global increase in antibiotic resistance. More than 270 participants from academia, government research institutions, regulatory agencies, and private animal industries from >25 different countries came together to discuss recent research and promising novel technologies that could provide alternatives to antibiotics for use in animal health and production; assess challenges associated with their commercialization; and devise actionable strategies to facilitate the development of alternatives to antibiotic growth promoters (AGPs) without hampering animal production. The 3-day meeting consisted of four scientific sessions including vaccines, microbial products, phytochemicals, immune-related products, and innovative drugs, chemicals and enzymes, followed by the last session on regulation and funding. Each session was followed by an expert panel discussion that included industry representatives and session speakers. The session on phytochemicals included talks describing recent research achievements, with examples of successful agricultural use of various phytochemicals as antibiotic alternatives and their mode of action in major agricultural animals (poultry, swine and ruminants). Scientists from industry and academia and government research institutes shared their experience in developing and applying potential antibiotic-alternative phytochemicals commercially to reduce AGPs and to develop a sustainable animal production system in the absence of antibiotics.Fil: Lillehoj, Hyun. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Liu, Yanhong. University of California; Estados UnidosFil: Calsamiglia, Sergio. Universitat Autònoma de Barcelona; EspañaFil: Fernandez Miyakawa, Mariano Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Patobiología; ArgentinaFil: Chi, Fang. Amlan International; Estados UnidosFil: Cravens, Ron L.. Amlan International; Estados UnidosFil: Oh, Sungtaek. United States Department of Agriculture. Agricultural Research Service; ArgentinaFil: Gay, Cyril G.. United States Department of Agriculture. Agricultural Research Service; Argentin

Natural variation in life history and aging phenotypes is associated with mitochondrial DNA deletion frequency in Caenorhabditis briggsae

<p>Abstract</p> <p>Background</p> <p>Mutations that impair mitochondrial functioning are associated with a variety of metabolic and age-related disorders. A barrier to rigorous tests of the role of mitochondrial dysfunction in aging processes has been the lack of model systems with relevant, naturally occurring mitochondrial genetic variation. Toward the goal of developing such a model system, we studied natural variation in life history, metabolic, and aging phenotypes as it relates to levels of a naturally-occurring heteroplasmic mitochondrial <it>ND5 </it>deletion recently discovered to segregate among wild populations of the soil nematode, <it>Caenorhabditis briggsae</it>. The normal product of <it>ND5 </it>is a central component of the mitochondrial electron transport chain and integral to cellular energy metabolism.</p> <p>Results</p> <p>We quantified significant variation among <it>C. briggsae </it>isolates for all phenotypes measured, only some of which was statistically associated with isolate-specific <it>ND5 </it>deletion frequency. We found that fecundity-related traits and pharyngeal pumping rate were strongly inversely related to <it>ND5 </it>deletion level and that <it>C. briggsae </it>isolates with high <it>ND5 </it>deletion levels experienced a tradeoff between early fecundity and lifespan. Conversely, oxidative stress resistance was only weakly associated with <it>ND5 </it>deletion level while ATP content was unrelated to deletion level. Finally, mean levels of reactive oxygen species measured <it>in vivo </it>showed a significant non-linear relationship with <it>ND5 </it>deletion level, a pattern that may be driven by among-isolate variation in antioxidant or other compensatory mechanisms.</p> <p>Conclusions</p> <p>Our findings suggest that the <it>ND5 </it>deletion may adversely affect fitness and mitochondrial functioning while promoting aging in natural populations, and help to further establish this species as a useful model for explicit tests of hypotheses in aging biology and mitochondrial genetics.</p

Age and growth of Cape stumpnose Rhabdosargus holubi (Pisces: Sparidae) in the Eastern Cape, South Africa

Rhabdosargus holubi (Steindachner, 1881) is a small (maximum size = 450 mm total length; Heemstra and Heemstra 2004) sparid that is distributed along the south-east coast of Africa from St Helena Bay, South Africa, to Maputo, Mozambique (Götz and Cowley 2013). Spawning occurs in the nearshore marine environment primarily during winter, specifically May–August in KwaZulu-Natal (KZN) (Wallace 1975) and July–February in the South-Eastern Cape (Whitfield 1998). Individuals reach 50% sexual maturity at approximately 150 mm standard length (SL) in the Eastern Cape (Whitfield 1998). The early life stages are transported by the south-westward-flowing Agulhas Current, and recruit as post-flexion larvae and early juveniles into estuaries during late winter and early summer (Blaber 1974). The warm temperatures and high nutrient levels in estuaries favour fast growth (Blaber 1973a), and fish spend their first year of life in these environments, migrating back out to sea after reaching approximately 120 mm SL. Some individuals remain trapped in closed estuaries, where they may reach sizes greater than 200 mm SL (James et al. 2007a). Rhabdosargus holubi is the dominant estuarine-dependent marine teleost species recorded in permanently open and temporarily open/closed estuaries in the warm-temperate region, which spans the south, south-east and east coast of South Africa (Harrison 2005). The species is also an important component of the linefishery in many SouthAfrican estuaries (10–15.6% by number) (Pradervand and Baird 2002), particularly in Eastern Cape estuaries (Cowley et al. 2003). These figures underestimate the presence of R. holubi, as most individuals making use of estuaries are young, feeding predominately on filamentous macroalgae and diatom flora, and are generally too small to be caught with hook and line (De Wet and Marais 1990). James et al. (2007b) showed that R. holubi made up 34–92% of the annual seine-net catch in the East Kleinemonde Estuary. Rhabdosargus holubi is also important in the KZN shorebased linefishery, representing 4.6% of the total landed catch (Dunlop and Mann 2012)

Intrauterine Growth Retarded Progeny of Pregnant Sows Fed High Protein:Low Carbohydrate Diet Is Related to Metabolic Energy Deficit

High and low protein diets fed to pregnant adolescent sows led to intrauterine growth retardation (IUGR). To explore underlying mechanisms, sow plasma metabolite and hormone concentrations were analyzed during different pregnancy stages and correlated with litter weight (LW) at birth, sow body weight and back fat thickness. Sows were fed diets with low (6.5%, LP), adequate (12.1%, AP), and high (30%, HP) protein levels, made isoenergetic by adjusted carbohydrate content. At −5, 24, 66, and 108 days post coitum (dpc) fasted blood was collected. At 92 dpc, diurnal metabolic profiles were determined. Fasted serum urea and plasma glucagon were higher due to the HP diet. High density lipoprotein cholesterol (HDLC), %HDLC and cortisol were reduced in HP compared with AP sows. Lowest concentrations were observed for serum urea and protein, plasma insulin-like growth factor-I, low density lipoprotein cholesterol, and progesterone in LP compared with AP and HP sows. Fasted plasma glucose, insulin and leptin concentrations were unchanged. Diurnal metabolic profiles showed lower glucose in HP sows whereas non-esterified fatty acids (NEFA) concentrations were higher in HP compared with AP and LP sows. In HP and LP sows, urea concentrations were 300% and 60% of AP sows, respectively. Plasma total cholesterol was higher in LP than in AP and HP sows. In AP sows, LW correlated positively with insulin and insulin/glucose and negatively with glucagon/insulin at 66 dpc, whereas in HP sows LW associated positively with NEFA. In conclusion, IUGR in sows fed high protein∶low carbohydrate diet was probably due to glucose and energy deficit whereas in sows with low protein∶high carbohydrate diet it was possibly a response to a deficit of indispensable amino acids which impaired lipoprotein metabolism and favored maternal lipid disposal

A predictive score for retinopathy of prematurity in very low birth weight preterm infants

Aims This study describes the development of a score based on cumulative risk factors for the prediction of severe retinopathy of prematurity (ROP) comparing the performance of the score against the birth weight (BW) and gestational age (GA) in order to predict the onset of ROP.Methods A prospective cohort of preterm infants with BWp1500 g and/or GAp32 weeks was studied. the score was developed based on BW, GA, proportional weight gain from birth to the 6th week of life, use of oxygen in mechanical ventilation, and need for blood transfusions from birth to the 6th week of life. the score was established after linear regression, considering the impact of each variable on the occurrences of any stage and severe ROP. Receiver operating characteristic (ROC) curves were used to determine the best sensitivity and specificity values for the score. All variables were entered into an Excel spreadsheet (Microsoft) for practical use by ophthalmologists during screening sessions.Results the sample included 474 patients. the area under the ROC curve for the score was 0.77 and 0.88 to predict any stage and severe ROP, respectively. These values were significantly higher for the score than for BW (0.71) and GA (0.69) when measured separately.Conclusions ROPScore is an excellent index of neonatal risk factors for ROP, which is easy to record and more accurate than BW and GA to predict any stage ROP or severe ROP in preterm infants. the scoring system is simple enough to be routinely used by ophthalmologists during screening examination for detection of ROP. Eye (2012) 26, 400-406; doi: 10.1038/eye. 2011.334; published online 23 December 2011Hosp Clin Porto Alegre, Dept Ophthalmol, BR-90035903 Porto Alegre, RS, BrazilUniv Fed Rio Grande do Sul, Dept Ophthalmol, Sch Med, Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, Dept Ophthalmol, Sch Med, São Paulo, BrazilUniv Fed Rio Grande do Sul, Dept Paediat, Newborn Sect, Sch Med, Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, Dept Ophthalmol, Sch Med, São Paulo, BrazilWeb of Scienc

Mitochondrial DNA Variant Discovery and Evaluation in Human Cardiomyopathies through Next-Generation Sequencing

Mutations in mitochondrial DNA (mtDNA) may cause maternally-inherited cardiomyopathy and heart failure. In homoplasmy all mtDNA copies contain the mutation. In heteroplasmy there is a mixture of normal and mutant copies of mtDNA. The clinical phenotype of an affected individual depends on the type of genetic defect and the ratios of mutant and normal mtDNA in affected tissues. We aimed at determining the sensitivity of next-generation sequencing compared to Sanger sequencing for mutation detection in patients with mitochondrial cardiomyopathy. We studied 18 patients with mitochondrial cardiomyopathy and two with suspected mitochondrial disease. We “shotgun” sequenced PCR-amplified mtDNA and multiplexed using a single run on Roche's 454 Genome Sequencer. By mapping to the reference sequence, we obtained 1,300× average coverage per case and identified high-confidence variants. By comparing these to >400 mtDNA substitution variants detected by Sanger, we found 98% concordance in variant detection. Simulation studies showed that >95% of the homoplasmic variants were detected at a minimum sequence coverage of 20× while heteroplasmic variants required >200× coverage. Several Sanger “misses” were detected by 454 sequencing. These included the novel heteroplasmic 7501T>C in tRNA serine 1 in a patient with sudden cardiac death. These results support a potential role of next-generation sequencing in the discovery of novel mtDNA variants with heteroplasmy below the level reliably detected with Sanger sequencing. We hope that this will assist in the identification of mtDNA mutations and key genetic determinants for cardiomyopathy and mitochondrial disease