5 year retrospective follow-up of new cases of Charcot neuroarthropathy - A single centre experience

Background: Few data describe the natural history of Charcot neuroarthropathy treated with a total contact plaster cast (TCC). Methods: A 5 year retrospective analysis of 50 patients presenting with an acute CN, Assessing time to clinical resolution into appropriate footwear and assessing if initial immobilisation device influenced resolution time. Results: During the study period 42 patients (84%) of patients went into remission, 2 died during their treatment, 4 had major amputations, in 2 patients treatment was ongoing. 36 patients were treated with combination offloading devices, 6 were treated with one modality only. Median time to resolution for patients initially treated with a TCC was not significantly shorter than for those treated with a removable below knee boot. 34.9% required re-casting due to clinical deterioration in the removable device. Conclusions: More precise measures of resolution of CN are needed to assess the impact of initial treatment modality on time to resolution

Laparoscopic repair of very large hiatus hernia with sutures versus absorbable mesh versus nonabsorbable mesh a randomized controlled trial

Author version made available in accordance with pubilsher policy. 12 month embargo applies from the date of publication (1 Feb 2015).Objective: Determine whether absorbable or non-absorbable mesh in repair of large hiatus hernias reduces the risk of recurrence, compared to suture repair. Summary Background Data: Repair of large hiatus hernia is associated with radiological recurrence rates of up to 30%, and to improve outcomes mesh repair has been recommended. Previous trials have shown less short term recurrence with mesh, but adverse outcomes limit mesh use. Methods: Multicentre prospective double blind randomized controlled trial of 3 methods of repair; sutures vs. absorbable mesh vs. non-absorbable mesh. Primary outcome - hernia recurrence assessed by barium meal X-ray and endoscopy at 6 months. Secondary outcomes - clinical symptom scores at 1, 3, 6 and 12 months. Results: 126 patients enrolled - 43 sutures, 41 absorbable mesh and 42 non-absorbable mesh. 96.0% were followed to 12 months, with objective follow-up data in 92.9%. A recurrent hernia (any size) was identified in 23.1% following suture repair, 30.8% - absorbable mesh, and 12.8% - non-absorbable mesh (p=0.161). Clinical outcomes were similar, except less heartburn at 3 & 6 months and less bloating at 12 months with non-absorbable mesh, and more heartburn at 3 months, odynophagia at 1 month, nausea at 3 & 12 months, wheezing at 6 months, and inability to belch at 12 months following absorbable mesh. The magnitude of the clinical differences were small. Conclusions: No significant differences were seen for recurrent hiatus hernia, and the clinical differences were unlikely to be clinically significant. Overall outcomes following sutured repair were similar to mesh repair

MiMiR - an integrated platform for microarray data sharing, mining and analysis

Background: Despite considerable efforts within the microarray community for standardising data format, content and description, microarray technologies present major challenges in managing, sharing, analysing and re-using the large amount of data generated locally or internationally. Additionally, it is recognised that inconsistent and low quality experimental annotation in public data repositories significantly compromises the re-use of microarray data for meta-analysis. MiMiR, the Microarray data Mining Resource was designed to tackle some of these limitations and challenges. Here we present new software components and enhancements to the original infrastructure that increase accessibility, utility and opportunities for large scale mining of experimental and clinical data.Results: A user friendly Online Annotation Tool allows researchers to submit detailed experimental information via the web at the time of data generation rather than at the time of publication. This ensures the easy access and high accuracy of meta-data collected. Experiments are programmatically built in the MiMiR database from the submitted information and details are systematically curated and further annotated by a team of trained annotators using a new Curation and Annotation Tool. Clinical information can be annotated and coded with a clinical Data Mapping Tool within an appropriate ethical framework. Users can visualise experimental annotation, assess data quality, download and share data via a web-based experiment browser called MiMiR Online. All requests to access data in MiMiR are routed through a sophisticated middleware security layer thereby allowing secure data access and sharing amongst MiMiR registered users prior to publication. Data in MiMiR can be mined and analysed using the integrated EMAAS open source analysis web portal or via export of data and meta-data into Rosetta Resolver data analysis package.Conclusion: The new MiMiR suite of software enables systematic and effective capture of extensive experimental and clinical information with the highest MIAME score, and secure data sharing prior to publication. MiMiR currently contains more than 150 experiments corresponding to over 3000 hybridisations and supports the Microarray Centre's large microarray user community and two international consortia. The MiMiR flexible and scalable hardware and software architecture enables secure warehousing of thousands of datasets, including clinical studies, from microarray and potentially other -omics technologies

Pre-therapy mRNA expression of TNF is associated with regimen-related gastrointestinal toxicity in patients with esophageal cancer: a pilot study

Author version made available following 12 month embargo from date of publication (27 March 2015) in accordance with publisher copyright policy.Purpose Esophageal cancer has a high mortality rate, and its multimodality treatment is often associated with significant rates of severe toxicity. Effort is needed to uncover ways to maximize effectiveness of therapy through identification of predictive markers of response and toxicity. As such, the aim of this study was to identify genes predictive of chemoradiotherapy-induced gastrointestinal toxicity using an immune pathway-targeted approach. Methods Adults with esophageal cancer treated with chemotherapy consisting of 5-fluorouracil and cisplatin and 45–50 Gy radiation were recruited to the study. Pre-therapy-collected whole blood was analyzed for relative expression of immune genes using real-time polymerase chain reaction (RT-PCR). Gene expression was compared between patients who experienced severe regimen-related gastrointestinal toxicity vs. those experiencing mild to moderate toxicity. Results Blood from 31 patients were analyzed by RT-PCR. Out of 84 immune genes investigated, TNF was significantly elevated (2.05-fold, p = 0.025) in the toxic group (n = 12) compared to the non-toxic group (n = 19). Nausea and vomiting was the most commonly documented severe toxicity. No associations between toxicity and response, age, sex, histology, or treatment were evident. Conclusions This study supports evidence of TNF as a predictive biomarker in regimen-related gastrointestinal toxicity. Confirming these findings in a larger cohort is warranted

A two-dimensional organic-exciton polariton lattice fabricated using laser patterning

Exciton-polaritons in 2D lattice geometries now attract considerable attention as systems in which to explore new physics. However, such structures are relatively difficult to fabricate as this can involve sophisticated milling or etching of cavity layers to create arrays of defects. Here, a straightforward technique is reported that allows rapid fabrication of 2D polariton lattices that operate at room temperature. Specifically, laser patterning has been used to write a 2D square lattice of defects into a sacrificial polymer layer. An organic microcavity structure is then built on top of the patterned polymer, with the morphology of the patterned polymer propagating through the subsequent layers and spatially modifying the optical path-length of the active cavity region. Using real- and momentum-space spectroscopy, the formation of gapped polaritonic band structures has been demonstrated at room temperature. The optical writing approach discussed here opens up the way for fabrication of more complex 2D-lattice geometries for studying topological physics at room temperature

Targeted genetic testing for familial hypercholesterolaemia using next generation sequencing:a population-based study

Background<p></p> Familial hypercholesterolaemia (FH) is a common Mendelian condition which, untreated, results in premature coronary heart disease. An estimated 88% of FH cases are undiagnosed in the UK. We previously validated a method for FH mutation detection in a lipid clinic population using next generation sequencing (NGS), but this did not address the challenge of identifying index cases in primary care where most undiagnosed patients receive healthcare. Here, we evaluate the targeted use of NGS as a potential route to diagnosis of FH in a primary care population subset selected for hypercholesterolaemia.<p></p> Methods<p></p> We used microfluidics-based PCR amplification coupled with NGS and multiplex ligation-dependent probe amplification (MLPA) to detect mutations in LDLR, APOB and PCSK9 in three phenotypic groups within the Generation Scotland: Scottish Family Health Study including 193 individuals with high total cholesterol, 232 with moderately high total cholesterol despite cholesterol-lowering therapy, and 192 normocholesterolaemic controls.<p></p> Results<p></p> Pathogenic mutations were found in 2.1% of hypercholesterolaemic individuals, in 2.2% of subjects on cholesterol-lowering therapy and in 42% of their available first-degree relatives. In addition, variants of uncertain clinical significance (VUCS) were detected in 1.4% of the hypercholesterolaemic and cholesterol-lowering therapy groups. No pathogenic variants or VUCS were detected in controls.<p></p> Conclusions<p></p> We demonstrated that population-based genetic testing using these protocols is able to deliver definitive molecular diagnoses of FH in individuals with high cholesterol or on cholesterol-lowering therapy. The lower cost and labour associated with NGS-based testing may increase the attractiveness of a population-based approach to FH detection compared to genetic testing with conventional sequencing. This could provide one route to increasing the present low percentage of FH cases with a genetic diagnosis

Potential Impact of Mediterranean Aquaculture on the Wild Predatory Bluefish

Aquaculture impacts on wild populations of fish have been considered principally due to farm escapes. The Bluefish Pomatomus saltatrix, which exhibits two distinct genetic units in the Mediterranean Sea, is a voracious predator and is attracted to aquaculture cages to prey on farmed fish, particularly Gilthead Seabream Sparus aurata and European Sea Bass Dicentrarchus labrax. We compared the genetic diversity of adult Bluefish caught inside one aquaculture farm located in Spanish waters of the western Mediterranean Sea with reference individuals of East and West Mediterranean stocks from the open sea. Bluefish were genetically assigned to their putative origin using seven microsatellite loci and mitochondrial cytochrome oxidase subunit I as molecular markers. As expected, most of the individuals caught from inside the fish farm cages were assigned to the local genetic population. However, between 7.14% and 11.9% of individuals were assigned to the distant and different genetic unit inhabiting Turkish waters, the East Mediterranean stock. The genetic membership of those individuals revealed some degree of interbreeding between the East and West Mediterranean Bluefish stocks. All results suggest that aquaculture acts as an attractor for Bluefish and could affect genetic diversity as well as phylogeography of this fish and maybe other similar species that aggregate around marine fish farms.We are very grateful to T. Ceyhan for providing the Bluefish samples from Turkey. The study was supported by the MICINN CGL-2009-08279 Grant (Spain) and the Asturian Grant GRUPIN2014-093. Laura Miralles held a PCTI Grant from the Asturias Regional Government, referenced BP 10-004. This is a contribution from the Marine Observatory of Asturias

IPCP: Immersive Parallel Coordinates Plots for Engineering Design Processes

Computational engineering design methods and tools are common practice in modern industry. Such approaches are integral in enabling designers to efficiently explore larger and more complex design spaces. However, at the same time, computational engineering design methods tend to dramatically increase the number of candidate solutions that decision-makers must interpret in order to make appropriate choices within a set of solutions. Since all candidate solutions can be represented in digital form together with their assessment criteria, evaluated according to some sort of simulation model, a natural way to explore and understand the complexities of the design problem is to visualize their multidimensional nature. The task now involves the discovery of patterns and trends within the multidimensional design space. In this work, we aim to enhance the design decision-making process by embedding visual analytics into an immersive virtual reality environment. To this end, we present a system called IPCP: immersive parallel coordinates plots. IPCP combines the well-established parallel coordinates visualization technique for high-dimensional data with immersive virtual reality. We propose this approach in order to exploit and discover efficient means to use new technology within a conventional decision-making process. The aim is to provide benefits by enhancing visualizations of 3D geometry and other physical quantities with scientific information. We present the design of this system, which allows the representation and exploration of multidimensional scientific datasets. A qualitative evaluation with two surrogate expert users, knowledgeable in multidimensional data analysis, demonstrate that the system can be used successfully to detect both known and previously unknown patterns in a real-world test dataset, producing an early indicative validation of its suitability for decision support in engineering design processes.Cambridge European and Trinity Hall; Engineering and Physical Sciences Research Council (EPSRC-1788814

Evaluation of MPA designs that protect highly mobile megafauna now and under climate change scenarios

Marine protected area (MPA) designs, including large-scale MPAs (LSMPAs; \u3e150,000 km2), mobile MPAs (fluid spatiotemporal boundaries), and MPA networks, may offer different benefits to species and could enhance protection by encompassing spatiotemporal scales of animal movement. We sought to understand how well LSMPAs could benefit nine highly-mobile marine species in the tropics now and into the future by: 1) evaluating current range overlap within a LSMPA; 2) evaluating range overlap under climate change projections; and 3) evaluating how well theoretical MPA designs benefit these nine species. We focused on Palmyra Atoll and Kingman Reef, a 2000 km2 area within the 1.2 million km2 U.S. Pacific Remote Islands Marine National Monument (PRIMNM) that contains marine megafauna (reef and pelagic fishes; sea turtles; seabirds; cetaceans) reflecting different behaviors and habitat use. Our approach is useful for evaluating the effectiveness of the Palmyra-Kingman MPA and PRIMNM in protecting these species, and tropical LSMPAs in general, and for informing future MPA design. Stationary MPAs provided protection at varying scales. Reef manta rays (Mobula alfredi), grey reef sharks (Carcharhinus amblyrhynchos), green sea turtles (Chelonia mydas), and bottlenose dolphins (Tursiops truncatus) had overall small ranges (\u3c100 km from Palmyra-Kingman) and could benefit from stationary MPAs that contained heterogenous reef habitats. Yellowfin tuna (Thunnus albacares), sooty terns (Onychoprion fuscatus), red-footed boobies (Sula sula), great frigatebirds (Fregata minor), and melon-headed whales (Peponocephala electra) navigated complex oceanographic processes and may benefit most from mobile MPAs that shift with features including thermal fronts, cyclic regions of elevated productivity, and eddies, if relationships with these features are established and predictable. All species had capacity to travel to nearby reef systems, illustrating potential benefits of MPA networks and protected corridors. Suitable habitats will likely contract for all species as warm water expands under climate change scenarios (species habitats were predicted to decrease by 4–49% at Palmyra-Kingman) and MPAs may not protect suitable habitats into the future. Species habitat requirements and movement ecologies are critical aspects of marine spatial planning, especially with respect to dynamic ocean processes and a changing climate

Mortality rates in transplant recipients and transplantation candidates in a high prevalence COVID-19 environment

Background: The risk of COVID-19 infection in transplant recipients (TRs) is unknown. Patients on dialysis may be exposed to greater risk of infection due to an inability to isolate. Consideration of these competing risks is important before restarting suspended transplant programs. This study compared outcomes in kidney and kidney/pancreas TRs with those on the waiting list, following admission with COVID-19 in a high-prevalence region. Methods: Audit data from all 6 London transplant centers were amalgamated. Demographic and laboratory data were collected and outcomes included mortality, intensive care (ITU) admission, and ventilation. Adult patients who had undergone a kidney or kidney/pancreas transplant, and those active on the transplant waiting list at the start of the pandemic were included. Results: One hundred twenty-one TRs and 52 waiting list patients (WL) were admitted to hospital with COVID-19. Thirty-six TR died (30%), while 14 WL patients died (27% P = 0.71). There was no difference in rates of admission to ITU or ventilation. Twenty-four percent of TR required renal replacement therapy, and 12% lost their grafts. Lymphocyte nadir and D-dimer peak showed no difference in those who did and did not die. No other comorbidities or demographic factors were associated with mortality, except for age (odds ratio of 4.3 [95% CI 1.8-10.2] for mortality if aged over 60 y) in TR. Conclusions: TRs and waiting list patients have similar mortality rates after hospital admission with COVID-19. Mortality was higher in older TRs. These data should inform decisions about transplantation in the COVID era