Bloom drivers of the potentially harmful dinoflagellate Prorocentrum minimum (Pavillard) Schiller in a south eastern temperate Australian estuary

© 2018 Elsevier Ltd Harmful algal blooms are an increasing concern in the estuarine reaches of the Hawkesbury-Nepean River, one of the largest coastal rivers systems in south eastern Australia. In the austral spring of 2016, an unprecedented bloom of the harmful mixotrophic dinoflagellate Prorocentrum minimum occurred in Berowra Creek (maximum cell abundance 1.9E+06 cells L−1, 89% of the total phytoplankton community), a major tributary of this river system. In response to this bloom, our study utilises an estuary-wide, thirteen-year time series of phytoplankton abundance and environmental data to examine the spatial and temporal patterns of this harmful alga and its potential bloom drivers in this system. P. minimum cell densities and environmental parameters varied over large spatial scales, with sites located in the main channel of the estuary significantly differing from those in the more urbanized tributary of Berowra Creek. Generalised additive modelling outputs suggested that blooms of P. minimum are complex, but generally corresponded to a spatial gradient of eutrophication and salinity, whereby P. minimum growth and concomitant high chlorophyll-a concentrations were enhanced at sites that were generally less saline and more eutrophic than others. Furthermore, temporal patterns suggested that blooms occurred abruptly and lasted up to three weeks, most often during the austral autumn to spring. While significant correlations were observed between rainfall and nutrients at all other sites, suggesting a pathway for nutrient availability, the association between rainfall and nutrient delivery was generally not observed in Berowra Creek (a 15-m deep site) suggesting that a continual supply of nutrients, coupled with unique bathymetry and water residence time at this site, are the most likely contributing factors to phytoplankton growth. This study presents the most comprehensive examination of P. minimum in any southern hemisphere estuary to date and highlights the importance of continued monitoring of HABs and the important role that anthropogenic inputs have in driving blooms of P. minimum in this oyster-growing river/estuary system

Wound bed preparation: A novel approach using HydroTherapy

Wounds that fail to heal quickly are often encountered by community nursing staff. An important step in assisting these chronic or stalled wounds progress through healing is debridement to remove devitalised tissue, including slough and eschar, that can prevent the wound from healing. A unique wound treatment called HydroTherapy aims to provide an optimal healing environment. The first step of HydroTherapy involves HydroClean plus™, this dressing enables removal of devitalised tissue through autolytic debridement and absorption of wound fluid. Irrigation and cleansing provided by Ringer’s solution from the dressing further removes any necrotic tissue or eschar. Once effective wound bed preparation has been achieved a second dressing, HydroTac™, provides an ongoing hydrated wound environment that enables re-epithelialisation to occur in an unrestricted fashion. This paper presents 3 case studies of slow healing wounds treated with HydroClean plus™ which demonstrates effective wound debridement

Management of small bowel volvulus in a patient with simultaneous pancreas-kidney transplantation (SPKT): a case report

There are several surgical complications which can occur following simultaneous pancreas-kidney transplantation (SPKT). Although intestinal obstruction is known to be a common complication after any type of abdominal surgery, the occurrence of small bowel volvulus, which is one of the rare causes of intestinal obstruction, following SPKT has not been published before. A 24-year-old woman suffering from type I diabetes mellitus with complications of nephropathy resulting in end stage renal disease (ESRD), neuropathy and retinopathy underwent SPKT. On the postoperative month 5, she was brought to the emergency service due to abdominal distention with mild abdominal pain. After laboratory research and diagnostic radiological tests had been carried out, she underwent exploratory laparotomy to determine the pathology for acute abdominal symptoms. Intra-operative observation revealed the presence of an almost totally ischemic small bowel which had occurred due to clockwise rotation of the mesentery. Initially, simple derotation was performed to avoid intestinal resection because of her risky condition, particularly for short bowel syndrome, and subsequent intestinal response was favorable. Thus, surgical treatment was successfully employed to solve the problem without any resection procedure. The patient's postoperative follow-up was uneventful and she was discharged from hospital on postoperative day 7. According to our clinical viewpoint, this study emphasizes that if there is even just a suspicion of acute abdominal problem in a patient with SPKT, surgical intervention should be promptly performed to avoid any irreversible result and to achieve a positive outcome

Structural Determinants of the Dictyostatin Chemotype for Tubulin Binding Affinity and Antitumor Activity Against Taxane- and Epothilone-Resistant Cancer Cells

A combined biochemical, structural, and cell biology characterization of dictyostatin is described, which enables an improved understanding of the structural determinants responsible for the high-affinity binding of this anticancer agent to the taxane site in microtubules (MTs). The study reveals that this macrolide is highly optimized for MT binding and that only a few of the structural modifications featured in a library of synthetic analogues resulted in small gains in binding affinity. The high efficiency of the dictyostatin chemotype in overcoming various kinds of clinically relevant resistance mechanisms highlights its potential for therapeutic development for the treatment of drug-resistant tumors. A structural explanation is advanced to account for the synergy observed between dictyostatin and taxanes on the basis of their differential effects on the MT lattice. The X-ray crystal structure of a tubulin−dictyostatin complex and additional molecular modeling have allowed the rationalization of the structure−activity relationships for a set of synthetic dictyostatin analogues, including the highly active hybrid 12 with discodermolide. Altogether, the work reported here is anticipated to facilitate the improved design and synthesis of more efficacious dictyostatin analogues and hybrids with other MT-stabilizing agents.We thank Peter T. Northcote for peloruside A, W.-S. Fang for Flutax-2, K. H. Altmann for epothilone D, Dr. Paraskevi Giannakakou (Weill Cornell Medical Center, New York) for the 1A9, PTX10, PTX22, and A8 cell lines, and Prof. Richard Ludueñ a (University of Texas) for the HeLa βIII-transfected cells. We thank Matadero INCOVA (Segovia) for the calf brains for tubulin purification. This work was supported in part by grants BIO2013-42984-R (J.F.D.) and SAF2012-39760-C02-02 (F.G.) from Ministerio de Economia y Competitividad, grant S2010/ ́ BMD-2457 BIPEDD2 from Comunidad Autonoma de Madrid ́ (F.G. and J.F.D.), and the Swiss National Science Foundation grants 310030B_138659 and 31003A_166608 (M.O.S.). The authors acknowledge networking contribution by the COST Action CM1407 “Challenging organic syntheses inspired by naturefrom natural products chemistry to drug discovery” and the COST action CM1470. I.P. thanks the EPSRC and AstraZeneca for funding, Dr. John Leonard (AstraZeneca) for useful discussions, Dr. Stuart Mickel (Novartis) for the provision of chemicals, and the EPSRC UK National Mass Spectrometry Facility at Swansea University for mass spectra

SAT Modulo Linear Arithmetic for Solving Polynomial

Polynomial constraint solving plays a prominent role in several areas of hardware and software analysis and verification, e.g., termination proving, program invariant generation and hybrid system verification, to name a few. In this paper we propose a new method for solving non-linear constraints based on encoding the problem into an SMT problem considering only linear arithmetic. Unlike other existing methods, our method focuses on proving satisfiability of the constraints rather than on proving unsatisfiability, which is more relevant in several applications as we illustrate with several examples. Nevertheless, we also present new techniques based on the analysis of unsatisfiable cores that allow one to efficiently prove unsatisfiability too for a broad class of problems. The power of our approach is demonstrated by means of extensive experiments comparing our prototype with state-of-the-art tools on benchmarks taken both from the academic and the industrial world

Structural Determinants of the Dictyostatin Chemotype for Tubulin Binding Affinity and Antitumor Activity Against Taxane- and Epothilone-Resistant Cancer Cells

A combined biochemical, structural, and cell biology characterization of dictyostatin is described, which enables an improved understanding of the structural determinants responsible for the high-affinity binding of this anticancer agent to the taxane site in microtubules (MTs). The study reveals that this macrolide is highly optimized for MT binding and that only a few of the structural modifications featured in a library of synthetic analogues resulted in small gains in binding affinity. The high efficiency of the dictyostatin chemotype in overcoming various kinds of clinically relevant resistance mechanisms highlights its potential for therapeutic development for the treatment of drug-resistant tumors. A structural explanation is advanced to account for the synergy observed between dictyostatin and taxanes on the basis of their differential effects on the MT lattice. The X-ray crystal structure of a tubulin−dictyostatin complex and additional molecular modeling have allowed the rationalization of the structure−activity relationships for a set of synthetic dictyostatin analogues, including the highly active hybrid 12 with discodermolide. Altogether, the work reported here is anticipated to facilitate the improved design and synthesis of more efficacious dictyostatin analogues and hybrids with other MT-stabilizing agents.We thank Peter T. Northcote for peloruside A, W.-S. Fang for Flutax-2, K. H. Altmann for epothilone D, Dr. Paraskevi Giannakakou (Weill Cornell Medical Center, New York) for the 1A9, PTX10, PTX22, and A8 cell lines, and Prof. Richard Ludueñ a (University of Texas) for the HeLa βIII-transfected cells. We thank Matadero INCOVA (Segovia) for the calf brains for tubulin purification. This work was supported in part by grants BIO2013-42984-R (J.F.D.) and SAF2012-39760-C02-02 (F.G.) from Ministerio de Economia y Competitividad, grant S2010/ ́ BMD-2457 BIPEDD2 from Comunidad Autonoma de Madrid ́ (F.G. and J.F.D.), and the Swiss National Science Foundation grants 310030B_138659 and 31003A_166608 (M.O.S.). The authors acknowledge networking contribution by the COST Action CM1407 “Challenging organic syntheses inspired by naturefrom natural products chemistry to drug discovery” and the COST action CM1470. I.P. thanks the EPSRC and AstraZeneca for funding, Dr. John Leonard (AstraZeneca) for useful discussions, Dr. Stuart Mickel (Novartis) for the provision of chemicals, and the EPSRC UK National Mass Spectrometry Facility at Swansea University for mass spectra

Promoter Methylation in Head and Neck Squamous Cell Carcinoma Cell Lines Is Significantly Different than Methylation in Primary Tumors and Xenografts

Studies designed to identify novel methylation events related to cancer often employ cancer cell lines in the discovery phase of the experiments and have a relatively low rate of discovery of cancer-related methylation events. An alternative algorithm for discovery of novel methylation in cancer uses primary tumor-derived xenografts instead of cell lines as the primary source of nucleic acid for evaluation. We evaluated DNA extracted from primary head and neck squamous cell carcinomas (HNSCC), xenografts grown from these primary tumors in nude mice, HNSCC-derived cell lines, normal oral mucosal samples, and minimally transformed oral keratinocyte-derived cell lines using Illumina Infinum Humanmethylation 27 genome-wide methylation microarrays. We found >2,200 statistically significant methylation differences between cancer cell lines and primary tumors and when comparing normal oral mucosa to keratinocyte cell lines. We found no statistically significant promoter methylation differences between primary tumor xenografts and primary tumors. This study demonstrates that tumor-derived xenografts are highly accurate representations of promoter methylation in primary tumors and that cancer derived cell lines have significant drawbacks for discovery of promoter methylation alterations in primary tumors. These findings also support use of primary tumor xenografts for the study of methylation in cancer, drug discovery, and the development of personalized cancer treatments

Transmission of Plasmodium vivax in South-Western Uganda: Report of Three Cases in Pregnant Women

Plasmodium vivax is considered to be rare in the predominantly Duffy negative populations of Sub-Saharan Africa, as this red blood cell surface antigen is essential for invasion by the parasite. However, despite only very few reports of molecularly confirmed P. vivax from tropical Africa, serological evidence indicated that 13% of the persons sampled in Congo had been exposed to P. vivax. We identified P. vivax by microscopy in 8 smears from Ugandan pregnant women who had been enrolled in a longitudinal study of malaria in pregnancy. A nested polymerase chain reaction (PCR) protocol was used to detect and identify the Plasmodium parasites present. PCR analysis confirmed the presence of P. vivax for three of the women and analysis of all available samples from these women revealed clinically silent chronic low-grade vivax infections for two of them. The parasites in one woman carried pyrimethamine resistance-associated double non-synonymous mutations in the P. vivax dihydrofolate reductase gene. The three women found infected with P. vivax were Duffy positive as were nine of 68 women randomly selected from the cohort. The data presented from these three case reports is consistent with stable transmission of malaria in a predominantly Duffy negative African population. Given the substantial morbidity associated with vivax infection in non-African endemic areas, it will be important to investigate whether the distribution and prevalence of P. vivax have been underestimated in Sub-Saharan Africa. This is particularly important in the context of the drive to eliminate malaria and its morbidity

SaS-BCI: A New Strategy to Predict Image Memorability and use Mental Imagery as a Brain-Based Biometric Authentication

Security authentication is one of the most important levels of information security. Nowadays, human biometric techniques are the most secure methods for authentication purposes that cover the problems of older types of authentication like passwords and pins. There are many advantages of recent biometrics in terms of security; however, they still have some disadvantages. Progresses in technology made some specific devices, which make it possible to copy and make a fake human biometric because they are all visible and touchable. According to this matter, there is a need for a new biometric to cover the issues of other types. Brainwave is human data, which uses them as a new type of security authentication that has engaged many researchers. There are some research and experiments, which are investigating and testing EEG signals to find the uniqueness of human brainwave. Some researchers achieved high accuracy rates in this area by applying different signal acquisition techniques, feature extraction and classifications using Brain–Computer Interface (BCI). One of the important parts of any BCI processes is the way that brainwaves could be acquired and recorded. A new Signal Acquisition Strategy is presented in this paper for the process of authorization and authentication of brain signals specifically. This is to predict image memorability from the user’s brain to use mental imagery as a visualization pattern for security authentication. Therefore, users can authenticate themselves with visualizing a specific picture in their minds. In conclusion, we can see that brainwaves can be different according to the mental tasks, which it would make it harder using them for authentication process. There are many signal acquisition strategies and signal processing for brain-based authentication that by using the right methods, a higher level of accuracy rate could be achieved which is suitable for using brain signal as another biometric security authentication

Analysing the Impact of Machine Learning to Model Subjective Mental Workload: A Case Study in Third-Level Education

Mental workload measurement is a complex multidisciplinary research area that includes both the theoretical and practical development of models. These models are aimed at aggregating those factors, believed to shape mental workload, and their interaction, for the purpose of human performance prediction. In the literature, models are mainly theory-driven: their distinct development has been influenced by the beliefs and intuitions of individual scholars in the disciplines of Psychology and Human Factors. This work presents a novel research that aims at reversing this tendency. Specifically, it employs a selection of learning techniques, borrowed from machine learning, to induce models of mental workload from data, with no theoretical assumption or hypothesis. These models are subsequently compared against two well-known subjective measures of mental workload, namely the NASA Task Load Index and the Workload Profile. Findings show how these data-driven models are convergently valid and can explain overall perception of mental workload with a lower error