Dead in the water: The fate of copepod carcasses in the York River estuary, Virginia

Using laboratory and field experiments we investigated three fates of copepod carcass organic matter in the York River estuary, Virginia: ingestion by planktivores (necrophagy), microbial decomposition, and removal by gravitational settling in the presence of turbulence (sinking). The ctenophore Mnemiopsis leidyi ingested live copepods and carcasses indiscriminately in feeding experiments. Microbial decomposition led to ca. 50% of carcass dry weight loss within 8 h after death. Carcass settling velocities in still water were ca. 0.1 cm s(-1), implying short residence time (hours) in the shallow estuary. However, turbulent mixing kept carcasses in suspension much of the time, reducing sinking losses. Rates of carcass organic matter removal were combined in a simple mathematical model predicting the fate of estuarine copepod carcasses. When sinking was considered, it removed a large fraction of carcass organic matter (\u3e= 58% for copepodites, \u3e= 35% for nauplii), with most of the remainder being removed by microbial decomposition. In the absence of sinking losses, necrophagy became proportionally more important in removing carcass organic matter (\u3e= 49%, except in summer)

Validating self-report of diabetes use by participants in the 45 and up study: A record linkage study

Background: Prevalence studies usually depend on self-report of disease status in survey data or administrative data collections and may over- or under-estimate disease prevalence. The establishment of a linked data collection provided an opportunity to explore the accuracy and completeness of capture of information about diabetes in survey and administrative data collections. Methods. Baseline questionnaire data at recruitment to the 45 and Up Study was obtained for 266,848 adults aged 45 years and over sampled from New South Wales, Australia in 2006-2009, and linked to administrative data about hospitalisation from the Admitted Patient Data Collection (APDC) for 2000-2009, claims for medical services (MBS) and pharmaceuticals (PBS) from Medicare Australia data for 2004-2009. Diabetes status was determined from response to a question 'Has a doctor EVER told you that you have diabetes' (n = 23,981) and augmented by examination of free text fields about diagnosis (n = 119) or use of insulin (n = 58). These data were used to identify the sub-group with type 1 diabetes. We explored the agreement between self-report of diabetes, identification of diabetes diagnostic codes in APDC data, claims for glycosylated haemoglobin (HbA1c) in MBS data, and claims for dispensed medication (oral hyperglycaemic agents and insulin) in PBS data. Results: Most participants with diabetes were identified in APDC data if admitted to hospital (79.3%), in MBS data with at least one claim for HbA1c testing (84.7%; 73.4% if 2 tests claimed) or in PBS data through claim for diabetes medication (71.4%). Using these alternate data collections as an imperfect 'gold standard' we calculated sensitivities of 83.7% for APDC, 63.9% (80.5% for two tests) for MBS, and 96.6% for PBS data and specificities of 97.7%, 98.4% and 97.1% respectively. The lower sensitivity for HbA1c may reflect the use of this test to screen for diabetes suggesting that it is less useful in identifying people with diabetes without additional information. Kappa values were 0.80, 0.70 and 0.80 for APDC, MBS and PBS respectively reflecting the large population sample under consideration. Compared to APDC, there was poor agreement about identifying type 1 diabetes status. Conclusions: Self-report of diagnosis augmented with free text data indicating diabetes as a chronic condition and/or use of insulin among medications used was able to identify participants with diabetes with high sensitivity and specificity compared to available administrative data collections. © 2013 Comino et al.; licensee BioMed Central Ltd

Impact of diabetes on hospital admission and length of stay among a general population aged 45 year or more: A record linkage study

© 2015 Comino et al. Background: The increased prevalence of diabetes and its significant impact on use of health care services, particularly hospitals, is a concern for health planners. This paper explores the risk factors for all-cause hospitalisation and the excess risk due to diabetes in a large sample of older Australians. Methods: The study population was 263,482 participants in the 45 and Up Study. The data assessed were linked records of hospital admissions in the 12 months following completion of a baseline questionnaire. All cause and ambulatory care sensitive admission rates and length of stay were examined. The associations between demographic characteristics, socioeconomic status, lifestyle factors, and health and wellbeing and risk of hospitalisation were explored using zero inflated Poisson (ZIP) regression models adjusting for age and gender. The ratios of adjusted relative rates and 95% confidence intervals were calculated to determine the excess risk due to diabetes. Results: Prevalence of diabetes was 9.0% (n = 23,779). Age adjusted admission rates for all-cause hospitalisation were 631.3 and 454.8 per 1,000 participant years and the mean length of stay was 8.2 and 7.1 days respectively for participants with and without diabetes. In people with and without diabetes, the risk of hospitalisation was associated with age, gender, household income, smoking, BMI, physical activity, and health and wellbeing. However, the increased risk of hospitalisation was attenuated for participants with diabetes who were older, obese, or had hypertension or hyperlipidaemia and enhanced for those participants with diabetes who were male, on low income, current smokers or who had anxiety or depression. Conclusions: This study is one of the few studies published to explore the impact of diabetes on hospitalisation in a large non-clinical population, the 45 and Up Study. The attenuation of risk associated with some factors is likely to be due to correlation between diabetes and factors such as age and obesity. The increased risk in association with other factors such as gender and low income in participants with diabetes is likely to be due to their synergistic influence on health status and the way services are accessed

Whole-genome sequencing and epidemiological analysis do not provide evidence for cross-transmission of mycobacterium abscessus in a cohort of pediatric cystic fibrosis patients

Mycobacterium abscessus has emerged as a major pathogen in cystic fibrosis (CF) patients and has been associated with poor clinical outcomes, particularly following lung transplant. We investigated the acquisition of this bacterium in a cohort of pediatric CF patients

Real-time intrafraction motion monitoring in external beam radiotherapy

© 2019 Institute of Physics and Engineering in Medicine. Radiotherapy (RT) aims to deliver a spatially conformal dose of radiation to tumours while maximizing the dose sparing to healthy tissues. However, the internal patient anatomy is constantly moving due to respiratory, cardiac, gastrointestinal and urinary activity. The long term goal of the RT community to 'see what we treat, as we treat' and to act on this information instantaneously has resulted in rapid technological innovation. Specialized treatment machines, such as robotic or gimbal-steered linear accelerators (linac) with in-room imaging suites, have been developed specifically for real-time treatment adaptation. Additional equipment, such as stereoscopic kilovoltage (kV) imaging, ultrasound transducers and electromagnetic transponders, has been developed for intrafraction motion monitoring on conventional linacs. Magnetic resonance imaging (MRI) has been integrated with cobalt treatment units and more recently with linacs. In addition to hardware innovation, software development has played a substantial role in the development of motion monitoring methods based on respiratory motion surrogates and planar kV or Megavoltage (MV) imaging that is available on standard equipped linacs. In this paper, we review and compare the different intrafraction motion monitoring methods proposed in the literature and demonstrated in real-time on clinical data as well as their possible future developments. We then discuss general considerations on validation and quality assurance for clinical implementation. Besides photon RT, particle therapy is increasingly used to treat moving targets. However, transferring motion monitoring technologies from linacs to particle beam lines presents substantial challenges. Lessons learned from the implementation of real-time intrafraction monitoring for photon RT will be used as a basis to discuss the implementation of these methods for particle RT

3D Growth of Cancer Cells Elicits Sensitivity to Kinase Inhibitors but Not Lipid Metabolism Modifiers

Tumor cells exhibit altered lipid metabolism compared with normal cells. Cell signaling kinases are important for regulating lipid synthesis and energy storage. How upstream kinases regulate lipid content, versus direct targeting of lipid-metabolizing enzymes, is currently unexplored. We evaluated intracellular lipid concentrations in prostate and breast tumor spheroids, treated with drugs directly inhibiting metabolic enzymes fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC), diacylglyceride acyltransferase (DGAT), and pyruvate dehydrogenase kinase (PDHK), or cell signaling kinase enzymes PI3K, AKT, and mTOR with lipidomic analysis. We assessed whether baseline lipid profiles corresponded to inhibitors' effectiveness in modulating lipid profiles in three-dimensional (3D) growth and their relationship to therapeutic activity. Inhibitors against PI3K, AKT, and mTOR significantly inhibited MDA-MB-468 and PC3 cell growth in two-dimensional (2D) and 3D spheroid growth, while moderately altering lipid content. Conversely, metabolism inhibitors against FASN and DGAT altered lipid content most effectively, while only moderately inhibiting growth compared with kinase inhibitors. The FASN and ACC inhibitors' effectiveness in MDA-MB-468, versus PC3, suggested the former depended more on synthesis, whereas the latter may salvage lipids. Although baseline lipid profiles did not predict growth effects, lipid changes on therapy matched the growth effects of FASN and DGAT inhibitors. Several phospholipids, including phosphatidylcholine, were also upregulated following treatment, possibly via the Kennedy pathway. As this promotes tumor growth, combination studies should include drugs targeting it. Two-dimensional drug screening may miss important metabolism inhibitors or underestimate their potency. Clinical studies should consider serial measurements of tumor lipids to prove target modulation. Pretherapy tumor classification by de novo lipid synthesis versus uptake may help demonstrate efficacy

Articulation and growth of skeletal elements in balanid barnacles (Balanidae, Balanomorpha, Cirripedia)

The morphology and ultrastructure of the shells of two balanid species have been examined, paying special attention to the three types of boundaries between plates: (i) radii-parietes, (ii) alae-sheaths, and (iii) parietes-basal plate. At the carinal surfaces of the radii and at the rostral surfaces of the alae, there are series of crenulations with dendritic edges. The crenulations of the radius margins interlock with less prominent features of the opposing paries margins, whereas the surfaces of the longitudinal abutments opposing the ala margins are particularly smooth. The primary septa of the parietes also develop dendritic edges, which abut the internal surfaces of the primary tubes of the base plates. In all cases, there are chitino-proteinaceous organic membranes between the abutting structures. Our observations indicate that the very edges of the crenulations and the primary septa are permanently in contact with the organic membranes. We conclude that, when a new growth increment is going to be produced, the edges of both the crenulations and the primary septa pull the viscoelastic organic membranes locally, with the consequent formation of viscous fingers. For the abutting edges to grow, calcium carbonate must diffuse across the organic membranes, but it is not clear how growth of the organic membranes themselves is accomplished, in the absence of any cellular tissue.This research was funded by projects CGL2017-85118-P (A.G.C., C.S. and C.G.) and CGL2015-64683-P (A.B.R.N.) of the Spanish Ministerio de Economía, Industria y Competitividad, the Unidad Científica de Excelencia UCE-PP2016-05 of the University of Granada (A.G.C. and A.B.R.N.) and the Research Group RNM363 of the Junta de Andalucía (A.G.C.). N.A.L. acknowledges support from CONICYT-Chile through grant nos. FONDECYT 1140938, PCI REDES 170106 and PIA ANILLOS ACT172037, for international collaborative research with A.G.C. and A.B.R.N

Structural similarity assessment for drug sensitivity prediction in cancer

<p>Abstract</p> <p>Background</p> <p>The ability to predict drug sensitivity in cancer is one of the exciting promises of pharmacogenomic research. Several groups have demonstrated the ability to predict drug sensitivity by integrating chemo-sensitivity data and associated gene expression measurements from large anti-cancer drug screens such as NCI-60. The general approach is based on comparing gene expression measurements from sensitive and resistant cancer cell lines and deriving drug sensitivity profiles consisting of lists of genes whose expression is predictive of response to a drug. Importantly, it has been shown that such profiles are generic and can be applied to cancer cell lines that are not part of the anti-cancer screen. However, one limitation is that the profiles can not be generated for untested drugs (i.e., drugs that are not part of an anti-cancer drug screen). In this work, we propose using an existing drug sensitivity profile for drug A as a substitute for an untested drug B given high structural similarities between drugs A and B.</p> <p>Results</p> <p>We first show that structural similarity between pairs of compounds in the NCI-60 dataset highly correlates with the similarity between their activities across the cancer cell lines. This result shows that structurally similar drugs can be expected to have a similar effect on cancer cell lines. We next set out to test our hypothesis that we can use existing drug sensitivity profiles as substitute profiles for untested drugs. In a cross-validation experiment, we found that the use of substitute profiles is possible without a significant loss of prediction accuracy if the substitute profile was generated from a compound with high structural similarity to the untested compound.</p> <p>Conclusion</p> <p>Anti-cancer drug screens are a valuable resource for generating omics-based drug sensitivity profiles. We show that it is possible to extend the usefulness of existing screens to untested drugs by deriving substitute sensitivity profiles from structurally similar drugs part of the screen.</p

Active wetting of epithelial tissues

Development, regeneration and cancer involve drastic transitions in tissue morphology. In analogy with the behavior of inert fluids, some of these transitions have been interpreted as wetting transitions. The validity and scope of this analogy are unclear, however, because the active cellular forces that drive tissue wetting have been neither measured nor theoretically accounted for. Here we show that the transition between 2D epithelial monolayers and 3D spheroidal aggregates can be understood as an active wetting transition whose physics differs fundamentally from that of passive wetting phenomena. By combining an active polar fluid model with measurements of physical forces as a function of tissue size, contractility, cell-cell and cell-substrate adhesion, and substrate stiffness, we show that the wetting transition results from the competition between traction forces and contractile intercellular stresses. This competition defines a new intrinsic lengthscale that gives rise to a critical size for the wetting transition in tissues, a striking feature that has no counterpart in classical wetting. Finally, we show that active shape fluctuations are dynamically amplified during tissue dewetting. Overall, we conclude that tissue spreading constitutes a prominent example of active wetting --- a novel physical scenario that may explain morphological transitions during tissue morphogenesis and tumor progression