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The file attached to this record is the author's final peer reviewed version. The proposed novel idea is concerned with the investigation on a probability of sub-atomic quantum communication between the chemical substances by use of “interferometric Quantum eraser” pattern analysis, which would be the first step towards the further comprehensive study on a similar natural communications between the medications and diseased organic tissues. The hypothesis is based on the idea that, sub-atomic particles like photons attempt to access or gain complementary information causing their “wave-particle duality” shifting which is used to observe their time-sequenced activities. Such information would probably be provided by sub-atomic quantum communication action demonstrated between the substances in a chemical reaction. Similarly, the medications may have curing effects on a diseased organic tissue after such “natural” communication, by which a complementary information is transferred from the sub-atomic properties of chemical substance to the diseased organic tissue at same level for the treatment.

Genetic analysis is now an integral part of glioma diagnosis and an essential aid to stratification of patient care (Louis et al., 2016). University Hospital Southampton is expanding its test repertoire to reflect these needs. The sensitive and specific technology of droplet digital PCR (ddPCR) can move Isocitrate Dehydrogenase (IDH) mutation testing away from current subjective immunohistochemistry (IHC) methodology. In a small study, 26 cases were tested by IHC, ddPCR and Sanger sequencing. Twenty cases were concordant for IDH R132H by IHC and ddPCR analysis, whilst three cases harboured the rarer IDH R132 or IDH2 variants, not evaluated by these two tests. However, three remaining IHC-IDH1 R132H negative cases were positive for IDH1 R132H by ddPCR, illustrating an improved sensitivity for IDH mutation testing using the digital PCR platform. Generic testing workflow for ddPCR, that meets ISO 15189 accreditation standards, facilitates a quick test work up for Single Nucleotide variant (SNV) mutation analysis. This can support clinical decision making vis-à-vis targeted therapy options and potential clinical trials entry. The use of microsatellite markers analysis provides an alternative method for the evaluation of 1p19q deletion characteristics. Investigation of O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status using high resolution melt (HRM) brings this test in to our standard molecular laboratory workflow. Molecular testing for MGMT methylation status delivers results with fast turnaround time, supporting timely, evidence-based decisions for Temozolomide treatment. The PCR-based nature of these analyses have minimal tissue requirements and this suite of tests can be run on a single sample. Participation in the 100,000 genomes project is providing whole genome data with which to explore a ‘one stop shop’ approach to glioma molecular testing. In combination with DNA methylome analysis, we wish to evaluate the clinical utility of a pan-genome analysis for our glioma diagnostic and prognostic support service.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. The aim of this study was to enhance the kinetic solubility and dissolution rate of ibuprofen by co-milling with different excipients and to establish the underlying mechanism(s) for such enhancement. In the first-part, two excipients (HPMC and soluplus) were selected from seven, and the optimal ball-milling parameters of speed and time (18 Hz, 15 min) were determined based on solubility-enhancement and flow-ability criteria. In the second-part, co-milling of different weight-ratios of ibuprofen-to-excipient was carried out and solubility and dissolution rates were determined. Mechanisms of biopharmaceutical enhancement were studied by SEM, laser diffraction, DSC, and FTIR analysis of the co-mixtures. Ibuprofen solubility (0.09 mg/mL for un-milled) was increased by factors of 4–5 and 10–20 for HPMC and soluplus, respectively. The weakening of crystals, stabilization of the amorphous phase and an increase in solid-state hydrogen bonding are the likely mechanisms for this enhancement. Reductions in Q70% dissolution time were also observed, by a factor of 4 and 7 for ibuprofen:HMPC and ibuprofen:soluplus co-milled mixtures, respectively. Although, there were similar reductions in particle size, dispersibility and degree of amorphization in both mixtures, the higher dissolution rate for soluplus, over that for HPMC, must be due to the additional solubilization contribution to the kinetic solubility provided by soluplus.

Background The measurement of sedation KPIs in colonoscopy varies between JETS certification criteria and recent UK standards. To align standards in preparation for the National Endoscopy Database (NED), changes were recently made on JETS: 1) measuring average sedation doses, when used, with mean vs. median, and 2) reducing the maximum recommended midazolam dose in patients aged 70+from mean of 2.5 mg to median of 2 mg. We aimed to explore the impact of these changes on trainee outcomes of exceeding recommended average doses. Methods Sedation KPIs for midazolam [M], fentanyl [F] and pethidine [P] were extracted from the JETS e-Portfolios of trainees awarded provisional colonoscopy certification (PCC) between June 2011–2016, and stratified by drug and age ( Results 733 trainees performed 36 650 procedures with M (75.6%), F (49.6%) and P (25.3%). Normality testing indicated the skewed distribution of sedation doses, which supported the use of medians. At trainee-level, changing mean to median resulted in smaller average doses of M, F and P for patients aged Conclusions The JETS sedation KPIs have aligned with UK standards. As this may affect trainee outcome, all colonoscopy trainees and trainers should take note and exercise caution with sedation use, particularly in elderly patients.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. The process of milling often results in amorphization and the physical stability of amorphous phase is linked with its molecular dynamics. This study focuses on a propensity of two disaccharides (lactose and sucrose) to amorphize on ball milling and the stability of the resultant amorphous phase. The amorphous content in milled sugars is estimated by Differential Scanning Calorimetry (DSC) and the stability was measured in terms of the tendency to recrystallize by Broadband Dielectric Spectroscopy (BDS). The results show that the amorphous content increases with milling time and is greater for lactose than sucrose. At the same degree of amorphization, sucrose recrystallize at temperature ∼15 °C higher than lactose, indicating higher stability. The molecular dynamics (beta relaxation process), suggest that milled sucrose is more stable with higher activation energy (∼9 kJ mol−1) than that of lactose. The moisture content of amorphous phase also impacts its molecular dynamics in terms of increase in activation energy as the moisture decrease with increasing the milling times. The study suggests a greater stability of amorphous sucrose and susceptibility of milled lactose to recrystallize, however, on extended milling when the moisture content decreases, lactose was seen to become relatively more stable.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. The current paper continues our study on the ability of L-arginine to prevent/reduce the aggregation of proteins that results from the various stresses during the lyophilisation and/or storage of lyophilized protein-based products. The first part of our study, i.e. formulation development, was devoted to the rational design and optimization of an L-arginine containing lyophilized formulation which can resist the natural tendency of L-arginine to absorb atmosphere moisture. Mannitol and trehalose were chosen among other excipients to be included in the protein-based formulation, as mannitol in a combination with L-arginine has been shown to reduce moisture sorption while trehalose provides a degree of lyoprotection. In the present study, a number of formulations, which comprised bovine serum albumin (BSA) with and without L-arginine, and with five different ratios of trehalose-to-mannitol (from 30:70 to 80:20) were lyophilised and assessed. The internal structures and the moisture sorption/retention of the lyophilized formulations were characterised. To study the effect of L-arginine on BSA solid-phase stability, the lyophilized powder was exposed to accelerated storage conditions (high moisture (75% RH) and temperature (22 or 45 °C)) for up to 24 h. The lyophilized BSA formulations were then reconstituted and solution-state protein aggregation assessed by turbidimetry at 360 nm and fluorescence spectroscopy using the thioflavin T assay. It was demonstrated that L-arginine can be used in protein-based freeze-dried formulations to significantly reduce the aggregation of protein during the manufacturing, storage and subsequent reconstitution. The results also revealed the importance of a sufficient amount of mannitol in the arginine-containing formulations.

The ITS protocol detailed here is designed to amplify fungal microbial eukaryotic lineages using paired-end community sequencing on the Illumina platform with primersITS1f-ITS2 (EMP.ITSkabir).

The 16S protocol detailed here is designed to amplify prokaryotes (bacteria and archaea) using paired-end 16S community sequencing on the Illumina platform. Primers515F-806R target the V4 region of the 16S SSU rRNA. For running these libraries on the MiSeq and HiSeq, please make sure you read the supplementary methods of Caporaso et al. (2012). You will need to make your sample more complex by adding 5-10% PhiX to your run.

The 18S protocol detailed here is designed to amplify eukaryotes broadly with a focus on microbial eukaryotic lineages. The primers target the 18S SSU rRNA and are based on those of Amaral-Zettler et al. (2009). The constructs are designed to be used with the Illumina platform. For running these libraries on the MiSeq and HiSeq, please make sure you read the supplementary methods of Caporaso et al. (2012). You will need to make your sample more complex by adding 5-10% PhiX to your run. The outlines of the protocol are the same as the 16S protocol, but different primers, PCR conditions, and sequencing primers are used. In addition, we have designed a blocking primer that reduces the amplification of vertebrate host DNA to be used on host-associated samples, especially those that have a low eukaryotic biomass. Blocking primer strategy is based on Vestheim et al. (2008).

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the URI link. Open access journal This study aimed to develop methodologies for the fabrication and testing of side by side layers freeze dried (lyophilized) orally disintegrating tablets (ODT) for same or different phase formulation. These side by side layers tablets will provide opportunities for combination therapies for patients who experience swallowing difficulty (e.g. geriatrics and paediatrics) and might enhance the bioavailability and incompatibility of some drugs. Two different solutions (A and B) were prepared separately and each solution was to create a different formulated layer to obtain different release profiles. The first layer was fabricated by injecting the solution A to an empty tablet blister to the half and freezing at -80°C for one hour in an external freezer. After the first layer was completely frozen, the solution B was injected into the rest half of the tablet blister and frozen at -80°C for one hour in an external freezer to create the second layer. Then, frozen side by side layers tablet was freeze dried and the resulting multilayer tablets were investigated. The study has shown that side by side layers freeze dried orally disintegrating tablets can be fabricated and formulated for same or different phase and with different disintegrating time for each layer to provide different release profiles. The optimization of adhesion between layers is required. The study has also shown that concentrations of gelatin and mannitol can affect the formulation characteristics.

Increased engagement in the cash economy is influencing a shift from traditional agroforestry gardening systems to monoculture cash cropping in many areas of Melanesia. This shift in farming practices is resulting in unsustainable practices such as increased clearing of native forests in key catchment areas. Yet there is still no consensus on how to successfully integrate the cash economy and political institutions to work within communal structures sustainably. Understanding the role of formal and informal institutions can reveal how best cultural values, the cash economy and governance can support sustainable development and resilience. Rural smallholders livelihoods and their engagement with formal and informal institutions were explored in 12 villages across the SANMA province in Vanuatu. The rural communities with the most diverse livelihood opportunities were those with good access to land, services (such as roads, regional and international markets, medical centres and education) and social support...

Riparian forests are precious, complex habitats fostering high biodiversity where effective monitoring of habitat quality is particularly important. We present a composite indicator, referred to as Riparian Forest composite Indicator: focus on Structure (RFI_S), for the assessment of habitat quality and identification of ‘hot-spot’ areas where conservation actions need to be taken. The RFI_S is composed of seven indicators derived from very high resolution (VHR) satellite imagery and LiDAR data, calculated on patch level. These indicators assess four important attributes of riparian forest quality: (1) tree species composition, (2) vertical forest structure, (3) horizontal forest structure and (4) water regime. For the aggregation of the RFI_S, two different weighting schemes, expert-based and statistical weighting, are applied. Forest patches with high cumulative RFI_S values represent patches of good habitat quality. These patches are primarily found along water bodies, reflecting the importance of water bodies for the structural complexity, an optimum water regime and tree species composition. For forest patches of low habitat quality the RFI_S helps to design suitable measures to improve habitat quality status through its decomposability into the underlying indicators. A sensitivity analysis to test the robustness of the RFI_S shows that the indicator variance in terrain roughness has the strongest influence on the composite indicator. Finally, a comparison with an existing expert-based map on conservation status reveals the potential of a complementary quantitative assessment of habitat quality in the study site. We hence conclude that the RFI_S has a high capability to support sustainable forest management complementing regularly gathered in situ data.

The quantification of crystallinity is necessary in order to be able to control the milling process. The use of thermal analysis for this assessment presents certain challenges, particularly in the case of crystal hydrates. In this study, the residual crystallinity on ball milling of lactose monohydrate (LMH), for periods up to 90 min, was evaluated by thermo-analytical techniques (TGA, DSC) and terahertz spectroscopy (THz). In general, the results from one of the DSC analysis and the THz measurements agree showing a monotonous decrease in relative residual crystallinity with milling time (∼80% reduction after 60 min milling) and a slight increase at the 90 min time point. However, the estimates from TGA and two other methods of analyzing DSC curve do not agree with the former techniques and show variability with significantly higher estimates for crystallinity. It was concluded that, the thermal techniques require more complex treatment of the data in the evaluation of changes in crystallinity of a milled material (in particular to account for the de-vitrification and mutarotation of the material that inevitably occurs during the measurement cycle) while the analysis of THz data is more straightforward, with the measurement having no impact on the native state of the material.

The quantification of crystallinity is necessary in order to be able to control the milling process. In this study, the changes in the amount of residual crystallinity of ball-milled anhydrous β-lactose (β-LA), for periods up to 60 min, were evaluated by differential scanning calorimetry (DSC) and by terahertz pulsed spectroscopy. The percentage of residual crystallinity using DSC was estimated by two methods: The first method was based on the measurement of the melting of the crystalline part, while the second was based on the measurement of the devitrification of the amorphous part. Peaks in THz spectra, related to the residual crystalline material were analyzed by two methods: (1) area under peak and (2) partial least square. The milled samples of β-LA show a monotonic decrease in crystallinity with milling time, although the quantitative analysis performed by different techniques reveals very different results. THz technique gives significantly lower estimates for % crystallinity (in the early time period) than that calculated from the DSC data, possibly because of the recrystallization of amorphous form during sample preparation. The comparison of residual crystallinity of β-LA with its hydrated counterpart [i.e., α-lactose monohydrate (α-LMH)] has shown that the amount of amorphous material produced from the α-LMH is 20–30 % greater than from β-LA at extended milling times (i.e. 60 min).

Objective: To discuss common pitfalls and useful tips in designing a quantitative research study, the importance and process of ethical approval, and consideration of funding. Conclusions: Through careful planning, based on formulation of a research question, early career researchers can design and conduct quantitative research projects within the framework of the Scholarly Project or in their own independent projects.

General internal medicine (GIM) training, usually as part of a dual accreditation programme, is increasingly challenging to deliver as a result of increased numbers of acute admissions, changes to consultant input into medical 'on call' and the reduction in the numbers of units taking unselected medical patients. GIM has become synonymous with acute medical take, reducing the scope of programmes to deliver a true general medical experience. The role of the 'medical registrar' is reported to be increasingly unpopular with trainees. Differing models of the delivery of training are in place. We have carried out a two-stage questionnaire in order to determine the views of both trainees and trainers on different models of training and their deliverability. The first stage defined the key areas of concern for trainees and the second focused on these areas and the ability of local education providers to deliver an expanded GIM programme. Our data suggest that trainees would value a face-to-face annual review of competence progression (ARCP) for GIM, separate from their specialty ARCP, and would support more structured blocks of GIM training in order to allow later specialty-focused training. However, -significant concerns were raised about the ability of many units to deliver such training beyond the acute medical 'take'.

Objectives: Research can seem daunting, especially for trainees and early career researchers. This paper focuses on how to formulate and begin a research project such as the RANZCP Scholarly Project. Methods: We outline an approach to framing a research question, developing theses and hypotheses, choosing a supervisor and conducting a literature review. Conclusions: Through systematic planning early career researchers and other clinicians can plan and conduct research suitable for the Scholarly Project or other research activity.

SAQs and answers are ONLINE for RCP fellows and collegiate members Candidates are asked to choose the best answer from the five possible answers. This best of five format is used in many medical examinations; however, the questions are not intended to be representative of those used in the MRCP(UK

A veterinary pioneer and a pathfinder in One Health, he enjoyed teaching and never lost enthusiasm for his research projects; he was also well versed in the arts.

This study aims to investigate the application of impedance spectroscopy using fixed electrode geometries on a standard glass vial in the characterisation of the freezing process of solutions at different fill liquid volumes. Impedance spectra (between 10 and 10(6) Hz) were recorded every 3 min, during the freezing cycle on a solution of 30 mg/mL sucrose contained within 10 mL glass vials having an electrode system (two thin copper foils: w, 18 mm; h, 5 mm) affixed to the external surface of the vial. A fill factor (Φ) was defined in terms of the relative height of the solution volume to the height of the electrodes from the base of the vial. Solution volumes of 1.5 to 5 mL (corresponding to Φ= 0.5-1.6) were investigated to establish the applicability of having a fixed electrode geometry for a range of solution volumes. A linear relationship between the time duration of the ice formation/solidification phase and the fill factor suggests that fixed electrode geometries may be used to investigate a range of fill volumes. The benefit of this approach is that it does not invade the solution and hence records the freezing process without providing additional nucleation sites and in a manner which is representative of the entire fill volume.

Objectives: This paper, written by the RANZCP Committee for Research, provides an outline for how to survive in research, considering the ingredients likely to contribute to success, the role of supportive structures and the expected challenges. Learning how to survive in research is relevant for both trainees and for Fellows undertaking research at any stage of their career. Conclusions: Intellectual curiosity, perseverance, frustration tolerance, patience and humility are key for success as a researcher. Selection of the right supervisor is important, as is development and maintenance of a good working supervisor/supervisee relationship. The personal benefits of undertaking research include flexibility in work hours, and improved skills in writing, oral presentations, objectivity, critical thinking, problem solving and project management.

Impedance spectroscopy has been used for the measurement of the glass transition of a 10 % maltodextrin solution contained within a glass vial, with externally attached electrodes. Features of the pseudo-relaxation process, associated with the composite impedance of the glass vial-solution assembly, were characterised by the peak amplitude, C peak ″ , and peak frequency, f peak , of the capacitance spectra and the equivalent circuit elements that model the impedance spectra (i.e. the solution resistance and solution capacitance) and monitored every 3 min during re-heating of the solution. The time derivatives of all four parameters studied provided a glass transition in close agreement with DSC measurements (−17 °C) and at a precision of ±0.5 °C. The temperature dependencies of the solution resistance and peak frequency were then characterised with the Arrhenius and Vogel – Fulcher – Tammann fit functions, at temperatures below and above T g , respectively. The energy of activation (below T g ) was estimated at ∼20 kJ mol −1 , and the fragility index ( I f ) of the glass forming liquid (above T g ) was estimated at 0.9. The significance of the fragility index to the development, optimisation and control of the freeze-drying cycle is highlighted.

In rapidly disintegrating tablets (RDTs) manufactured by freeze-drying processes, the % crystallinity of the freeze-dried matrix underpins the physical properties such as mechanical strength and dissolution profile. This study examines the feasibility of using terahertz pulsed spectroscopy (TPS) as an off-line tool (in the first instance) for assessing the degree of crystallinity in co-freeze dried amino-acid/gelatine mixtures.Three amino acids (l-alanine, serine and proline) were studied by TPS (in the wave number range of 3-100cm(-1)) both in the pure crystalline form and in the form of a co-freeze-dried matrix with gelatin (in weight fractions of 10:90, 30:70, 50:50, and 70:30).In co-freeze dried proline/gelatin matrix no crystallinity was observed using TPS, whereas ~62±1% (n=3) and 72±0.5% (n=3) crystallinity was observed in the co-freeze dried alanine/gelatin matrix (50% w/w and 70% w/w, respectively). Similarly, ~41±0.5% (n=3) and ~80±0.5% (n=3) crystallinity was observed in the serine/gelatin matrix (30% w/w and 50% w/w respectively).The potential for using TPS as a quantitative in-line tool for determining the degree of crystallinity in a range of complex systems such as RDTs, conventional tablets, sprayed dried micro particles, is suggested from these results.

The aim of this work was to develop a minimally invasive, impedance spectroscopy method as a novel process analytical technology for monitoring the freeze drying process. This involved the application of planar electrodes, mounted externally to a conventional glass freeze-drying vial, coupled to a high-impedance analyser. The pseudo-relaxation process arising from the composite impedance of the glass wall and product interface was recorded over a frequency range 101–106 Hz for a surrogate formulation comprising 2.5% sucrose. Features of the process (i.e. the peak amplitude, C ″ peak and characteristic peak frequency, fpeak) were monitored along with the product temperature data during the entire cycle. It was demonstrated that fpeak is strongly coupled to the temperature of the product (through the dependence of the product temperature on the electrical resistance of the product) whereas C ″ peak is dependent on the extent of ice sublimation and hence can be used to measure the rate of drying and end point of primary drying. This feature provides a distinct advantage over thermocouple measurements which are restricted to end point detection only. The potential to predict the end point of a cycle from C ″ peak vs. time profiles is highlighted in this work.

Objective To identify whether regular aspirin use protects against esophageal adenocarcinoma (EA) and if so, the effect of the duration and frequency of drug exposure. Methods Studies were selected from five journal/trial databases based on defined inclusion and exclusion criteria; most notably, the provision of multivariate EA odds ratios (ORs) in those taking regular aspirin. A subgroup analysis was then performed by stratifying the results according to the frequency and duration of aspirin use. The reliability of these investigations was assessed by calculating study heterogeneity and observing any elements of publication bias. Results Nine studies were selected for the main analysis, of which five were included in the frequency analysis and three assessed the duration of aspirin use. Data pooling revealed a statistically significant EA OR of 0.671 (95% CI 0.526-0.856, P = 0.001) among all aspirin users, suggesting a protective effect. The results for duration and frequency did not reach statistical significance but nonetheless suggested possible benefits of longer, more frequent drug regimens that may be statistically confirmed by studies of larger sample sizes. Funnel plots and statistical tests demonstrated a minimal impact of publication bias on our results. Conclusion Aspirin use confers a significant protective effect against EA with a suggestion that the degree of protection may be increased by the longer duration and higher frequency of usage.

Objective The textural structure of “skin age” related sub-skin components enables us to identify and analyse their unique characteristics, thus making substantial progress towards establishing an accurate skin age model. Methods This is achieved by a two stage process. First by the application of textural analysis using laser speckle imaging, which is sensitive to textural effects within the λ=650 nm spectral band region. In the second stage a Bayesian inference method is used to select attributes from which a predictive model is built. Results This technique enables us to contrast different skin age models, such as the laser-speckle effect against the more widely used normal light (LED) imaging method, whereby it is shown that our laser speckle based technique yields better results Conclusion The method introduced here is non-invasive, low-cost and capable of operating in real-time; having the potential to compete against high-cost instrumentation such as confocal microscopy or similar imaging devices used for skin age identification purposes. This article is protected by copyright. All rights reserved.

Despite the growing promotion of the “open data” movement, the collection, cleaning, management, interpretation, and dissemination of open data is laborious and cost intensive, particularly for non-profits with limited resources. In this paper, we describe how non-profit organizations (NPOs) use open data, building on prior literature that focuses on understanding challenges that NPOs face. Based on 15 interviews of staff from 10 NPOs, our results suggest that NPOs use data to develop narratives to build a case for support from grantors and other stakeholders. We then present empirical results based on the usage of a data portal we created, which suggests that technologies should be designed to not only make data accessible, but also to facilitate communication and support relationships between expert data analysts and NPOs.

An integrated remote sensing approach quantified saltmarsh dynamics in response to a sudden change in surface elevation due to a saltmarsh restoration scheme. The biogeomorphological relationship between surface elevation and saltmarsh presence occurs over the long-term so can be difficult to observe, though the ‘managed realignment’ of coastal defences provides a unique experimental opportunity to study this relationship. Realignment at Freiston Shore, Lincolnshire, UK in August 2002 caused a sudden and high-magnitude sediment input into the local coastal system, significantly increasing the intertidal surface elevation. The resulting impacts on the external, fronting saltmarsh were quantified by aerial photography and airborne multispectral imagery. Algal and pioneer saltmarsh boundary positions were calculated from 1984 to 2006, with the latter zone migrating slowly seaward pre-realignment (3.8 m a−1), but advancing significantly post-realignment (21.3 m a−1). Classification of five-year multispectral imagery accurately showed subtle changes in vegetation community composition within these boundaries. The realignment site was also colonized rapidly compared to other restoration sites, due to its high starting surface elevation. This study shows how, with sufficient sediment input and accommodation space, coastal management decisions can release intertidal surfaces from physical constraints to saltmarsh colonization.

Background Critical values are required to be phoned 24/7. Other abnormal results fall short of the thresholds used to define critical values and may only be required to be phoned during the day. Community-based requestors prefer not to be contacted unless a result is critical and contacting them requires substantial staff resource. It is common practice to add tests to requests to expedite diagnosis or clarify the significance of a particular result using algorithms. Methods We devised algorithms for reflex addition of tests which allowed the differentiation of significantly abnormal results as either critical values or those that only require day phoning. Results Algorithms identified 158 out of 309 tests as being critical (51%) over nine months. Reflex addition of serum bicarbonate identified 4% of serum glucose (24.9–37.9 mmol/L) as critical. Use of estimated glomerular filtration rate by reflex addition of serum creatinine identified 68% of serum lithium (1.49–1.99 mmol/L) as critical. Addition of serum potassium, calcium and magnesium identified 21% of serum digoxin (>2.49 nmol/L) as critical and addition of serum potassium and calcium to all samples with serum magnesium ( 4999 μ/L. Conclusions Use of reflex tests helped inform a phoning system based on the division of results into critical values and non-emergency abnormal values. This avoids disturbing requestors unnecessarily and conserves staff time at night.

DNA sequencing continues to decrease in cost with the Illumina HiSeq2000 generating up to 600 Gb of paired-end 100 base reads in a ten-day run. Here we present a protocol for community amplicon sequencing on the HiSeq2000 and MiSeq Illumina platforms, and apply that protocol to sequence 24 microbial communities from host-associated and free-living environments. A critical question as more sequencing platforms become available is whether biological conclusions derived on one platform are consistent with what would be derived on a different platform. We show that the protocol developed for these instruments successfully recaptures known biological results, and additionally that biological conclusions are consistent across sequencing platforms (the HiSeq2000 versus the MiSeq) and across the sequenced regions of amplicons. © 2012 International Society for Microbial Ecology All rights reserved.

Geographic object-based image analysis (GEOBIA) has become an area of increasing research interest in the field of remote sensing. Land Cover Map 2000 (LCM2000) of the United Kingdom represents an early use of such techniques to create a national mapping product. The work described here makes use of the object-level metadata created in the production process of LCM2000 to assess uncertainty within the database. Many mapping applications using GEOBIA techniques use segmentation algorithms to generate parcels from imagery that have a similar spectral response. These parcels are then classified to create the final map product. Here we show that by recording detailed metadata at the object level the final map can still be analysed further to assess the uncertainty in the classification of the parcel, or to re-evaluate parcels or groups of parcels for a new system of classification, by developing criteria for classification. This can be done not only using the parcels own metadata but also that from the immediate locality. Breaking down the spatial unit of the parcel, using a region-growing technique, prevents the user from being constrained by the parcels once they have been generated and potentially increases the power of any uncertainty analysis using the available metadata in a potentially more informative way. The example presented here uses these techniques to assess the potential extent of woodland within the area of the National Forest. The technique shows considerable promise in analysing greater complexity in land cover than is possible from a standard land cover map. Object-level metadata can be used to provide an analysis of uncertainty in classification and re-evaluate one parcel in the light of the properties of its neighbours. This can identify the areas where classification uncertainty may be problematic to a user and also the areas that could be more accurately described using mixed classes to represent the heterogeneity at the location.

This paper presents the results of a dielectric spectroscopy study of freeze-dried lactose with a range of moisture contents. Dielectric properties were measured over a wide range of frequency (10−1 to 106 Hz) and temperature (−120 °C to 120 °C). Four relaxation processes were analysed with respect to moisture content and corresponding relaxation mechanisms were suggested. Two processes (γ and β) were observed in the sub-Tg range of temperature and another two processes were observed near to and above the glass transition temperature, Tg. The relatively high-frequency γ-process was ascribed to the mobility of pendant hydroxymethyl groups and exhibited only a weak dependence on moisture content. The most moisture sensitive process was the second sub-Tg (Johari–Goldstein) β-process, whereby the relaxation time changed by 2 orders of magnitude as the moisture was increased by 7%. Also the third process (α-relaxation, near Tg) was sensitive to moisture content and was in good agreement with DSC data measured for freeze-dried lactose. The fourth process was a proton percolation process at the micro-crystals formed at the surface of amorphous particles during heating at the temperatures higher than Tg and shows the moisture dependence.

e14091Background: Allele-specific copy number analysis of tumors (ASCAT) is a quantitative method of assessing copy number variations that accounts for non-aberrant cell contributions and tumor plo...

The main research group is CCI in collaboration with HLS (School of Pharmacy) Open Access article In dermatology, one of the most common causes of skin abnormality is an unusual change in skin lesion structure which may exhibit very subtle physical deformation of its 3D shape. However the geometrical sensitivity of current cost-effective inspection and measurement methods may not be sufficient to detect such small progressive changes in skin lesion structure at micro-scale. Our proposed method could provide a low-cost, non-invasive solution by a compact system solution to overcome these shortcomings by using close-range photogrammetric imaging techniques to build a 3D surface model for a continuous observation of subtle changes in skin lesions and other features. https://www.ias-iss.org/ojs/IAS/article/view/1730/1059

International audience; BIOPRESS (Linking Pan-European land cover change to pressures on Biodiversity'), a European Commission funded Global Monitoring for Environment and Security' project, produced land cover change information (19502000) for Europe from aerial photographs and tested if this information is suitable for monitoring habitats and biodiversity. The methods and results related to the land cover change work are summarised. Changes in land cover were established through 73 window and 59 transect samples distributed across Europe. Although the sample size was too small and biased to represent the spatial variability observed in Europe, the work highlighted the importance of method consistency, the choice of nomenclature and spatial scale. The results suggest different processes are taking place in different parts of Europe: the Boreal and Alpine regions are dominated by forest management; abandonment and intensification are mainly encountered in the Mediterranean; urbanisation and drainage are more characteristic of the Continental and Atlantic regions.

In this paper we revisit some long-standing questions regarding the origins and structure of China Coast Pidgin (CCP), also known as Chinese Pidgin English. We first review the historical context of the China Trade which formed the ecology for the development of CCP. We then review the available sources, focusing on newly transcribed data from Chinese-language instructional materials. These sources provide fresh evidence for grammatical structure in CCP, and demonstrate strong influence from Cantonese as the major substrate language. Comparison with English-language sources shows systematic contrasts which point to likely variation between Anglophone and Sinophone lects, as in the case of wh-questions which show regular wh-fronting in English sources and pervasive use of wh-in-situ in Chinese sources. This conclusion helps to resolve the debate over the Sinitic features of CCP.

Candidates for cardiac bypass surgery often experience cognitive decline. Such decline is likely to affect their everyday cognitive functioning. The aim of the present study was to compare cardiac patients' ratings of their everyday cognitive functioning against significant others' ratings and selected neuropsychological tests. Sixty-nine patients completed a battery of standardised cognitive tests. Patients and significant others also completed the Everyday Function Questionnaire independently of each other. Patient and significant other ratings of patients' everyday cognitive difficulties were found to be similar. Despite the similarities in ratings of difficulties, some everyday cognitive tasks were attributed to different processes. Patients' and significant others' ratings were most closely associated with the neuropsychological test of visual memory. Tests of the patients' verbal memory and fluency were only related to significant others' ratings. Test scores of attention and planning were largely unrelated to ratings by either patients or their significant others.

A strong preference for using the right foot for skilled activities parallels a similar side bias for hand use. However, many neuropsychologists, sports scientists and sports commentators argue that right-foot bias in soccer is reduced or even eliminated by practice. This sort of plasticity is an important component of the principle genetic theories of handedness, yet very little is known about the relative asymmetries in the many unipedal skills required in soccer at amateur or professional levels. The first study examined self-report of hand and foot bias in a sample (n=400) of amateur soccer players, in addition to information about their practice with the non-preferred foot. A second study quantified foot use on the pitch in a large sample (n=426) of professional soccer players. The majority of the amateurs reported a right-foot bias that is very similar to that seen in the general population ( approximately 80%). However they only endorse strong biases for "closed" (self-paced) soccer actions like penalty and other free kicks, which give players unlimited time and space for preparation and execution. Although there was a very slight tendency for less right-foot bias in the professionals ( approximately 75%), as assessed by actual foot use rather than questionnaire, few players show anything like what could be described as two-footed play. This bias, unlike in the reports of amateurs, were for all of the behaviours investigated, not just so-called "skilled" behaviours. Finally, when outcomes of preferred and non-preferred foot behaviours were contrasted, the professionals were remarkably adept on those rare occasions when they use their non-preferred foot, suggesting that skill cannot explain asymmetry of choice. These results are discussed in terms of 1) limitations of self-report on questionnaires for predicting actual on the field behaviour, 2) the surprising absence of plasticity in foot use, given the importance of learning, experience and culture in models of handedness and footedness, and 3) a left hemisphere lateralised intentional system as important for the selection of movements as for their execution.

Fraud and corruption in the public sector have become issues of increasing importance for the government in the United Kingdom. Numerous initiatives have emerged ranging from high profile publicity campaigns against benefit fraud and tax evasion to the establishment of specialist bodies, such as the NHS Counter Fraud and Security Management Service (NHSCFSMS). One of the most interesting developments, however, has been the emergence of the ‘counter fraud specialist (CFS)’ across central and local government, as well as the private sector. These are specially trained civilian personnel who are tasked to prevent, investigate and secure sanctions against fraudsters. They undertake common training packages and are accredited by the Counter Fraud Professional Accreditation Board (CFPAB). This paper first outlines the emergence of the CFS; then draws upon the results of recent survey data to discuss some of their characteristics. The paper also considers some of the main issues raised by the growth of the CFS including the possible emergence of an embryonic ‘fraud police’, the indirect ‘load shedding’ of fraud investigation and the governance of this new breed of policing personnel.

BIOPRESS-Linking pan-European land cover change to pressures on biodiversity-is a European Community Framework 5 project, which aims to develop a standardised product that will link quantified historical (1950-2000) land cover change to pressures on biodiversity. It exploits archived historic and recent aerial photographs (a data source that has remained consistent over the last 60 years) to assess land cover change around Natura 2000 sites within 30×30 km windows and 15×2 km transects. The CORINE (Coordination of Information on the Environment) land cover mapping methodology has been adapted for use with aerial photographs. Sample sites are mapped to CORINE Land Cover (CLC) classes, and then backdated to assess change. Results from eight UK transects (and associated windows) are presented. Changes in land cover classes are interpreted as pressures: urbanisation, intensification, abandonment, afforestation, deforestation and drainage. Urbanisation was the major pressure in all but two transects (both in the uplands), and intensification was of similar importance in most transects. Afforestation was a significant pressure in two transects. In six out of the eight transects, annual change was greater in the 1990-2000 period than in the 1950-1990 period. The methodology has been demonstrated to provide quantitative results of long-term land cover change in the UK rural landscape at a spatial scale that is relevant to management decisions. The methods are transferable and applicable to a wide range of landscape studies.

An ecotone is a zone of vegetation transition between two communities, often resulting from a natural or anthropogenic environmental gradient. In remotely sensed imagery, an ecotone may appear as an edge, a boundary of mixed pixels or a zone of continuous variation, depending on the spatial scale of the vegetation communities and their transition zone in relation to the spatial resolution of the imagery. Often in image classification, an ecotone is either ignored if it falls within a width of one or two pixels, or part of it may be mapped as a separate vegetation community if it covers an area of several pixel widths. A soft classification method, such as probability mapping, is inherently appealing for mapping vegetation transition. Ideally, the probability of membership each pixel has to each vegetation class corresponds with the proportional composition of vegetation classes per pixel. In this paper we investigate the use of class probability mapping to produce a softened classification of an alpine treeline ecotone in Austria using a SPOT 5 HRG image. Here the transition with altitude is from dense subalpine forest to treeless alpine meadow and herbaceous vegetation. The posterior probabilities from a Maximum Likelihood algorithm are shown to reflect the land-cover composition of mixed pixels in the ecotone. The relationships between the posterior probability of class membership for the two end-member classes of ‘scrub and forest’ and ‘non-forest vegetation’ and the percentage ground cover of these vegetation classes (enumerated in 15 quadrats from 1:1500 aerial photographs) were highly significant: r2 = 0.83 and r2 = 0.85 respectively (p < 0.001, n = 15). We identify thresholds (alpha-cuts) in the posterior probabilities of class membership of ‘scrub and forest’ and ‘non-forest vegetation’ to map the alpine treeline ecotone as a transition zone of five intermediate vegetation classes between the end-member communities. In addition, we investigate the representation of the ecotone as a ratio between the posterior probabilities of ‘scrub and forest’ and ‘non-forest vegetation’. This displays the vegetation transition without imposing subjective boundaries, and has greater emphasis on the ecotone transition rather than on the end-member communities. We comment on the fitness for purpose of the different ways investigated for representing the alpine treeline ecotone.

Earth Observation (EO) data is seen as a major source of information to characterise the Earth's surface, but is conventionally analysed using pixel-based approaches that do not incorporate the concept of landscape features or real-world objects. The UK land cover maps to date have been developed in an attempt to exploit landscape features to improve the quality and accuracy of their derived products. For Land Cover Map 2007 (LCM2007) landscape features will be derived from a generalised version of OS MasterMap to capture the required real-world objects. This paper describes the generalisation process that aligns the scale of the landscape features with the information content of high spatial resolution EO data as the first step in the production of LCM2007.

BACKGROUND There is presently no treatment for scalp scars that is fully satisfactory. The modalities of treatment currently in use are surgery, hair transplantation, and micropigmentation. Scalp implantation with artificial hair fibers is used by some physicians as an adjunctive treatment. OBJECTIVE The objective was to assess the utility of artificial hair fibers to treat scalp scars. METHODS Data were collected by the principal author from 10 hair restoration practitioners who tested polyamide hair fiber (Biofibre CE 0373/TGA by Medicap Ltd., Carpi (MO), Italy) implantation for scalp scars. RESULTS Artificial hair fiber implantation occurred between June 1996 and December 2000, and observations continued until December 2004. Data from 54 scars from 44 patients treated showed: (1) no complications in 49 scars (90.7%); (2) mild adverse outcomes in 4 scars (7.4%)-temporary superficial inflammation-infection that subsided following topical cortisone and local/systemic antibiotic treatment; and (3) moderately adverse outcomes in 1 scar (1.9%)-significant inflammation and generalized infection requiring removal of artificial implant to alleviate. Occasional minor skin reactions, sebum plugs, and hyperseborrhea were successfully controlled and well accepted by patients. Fiber fall rate was 20% on average per annum. CONCLUSION Data show that polyamide hair fiber restoration can be considered an adjunctive treatment for scalp scars in selected cases.