Improving post-hypoglycaemic patient safety in the prehospital environment: a systematic review

To determine the extent to which post-hypoglycaemic patients with diabetes, who are prescribed oral hypoglycaemic agents (OHA) are at risk of repeat hypoglycaemic events (RHE) after being treated in the prehospital environment and whether they should be transported to hospital regardless of their post-treatment response, a systematic literature review was carried out using an overlapping retrieval strategy that included both published and unpublished literature. Retrieved papers were reviewed by each author for inclusion. Disagreements regarding inclusion were resolved through discussion. Ninety-eight papers and other relevant material were retrieved using the developed search strategy. Twenty-three papers and other relevant material were included in the final review. A narrative synthesis of the findings is presented. Although several case reports demonstrate the risks associated with repeat or prolonged hypoglycaemia, the review was unable to locate any specific high quality research in this area. Consequently, caution is required in interpreting the findings of the studies. Post-hypoglycaemic patients treated in the prehospital environment have a 2–7% risk of experiencing a RHE within 48 h. The literature retrieved in this study recognises the potential for OHA to cause RHE. However, the extent to which this occurs in practice remains unknown. This lack of evidence has led to the recommendation that conservative management, through admission to hospital, is appropriate. The review concludes with recommendations for both practice and research

Improving self-referral for diabetes care following hypoglycaemic emergencies: a feasibility study with linked patient data analysis

Background  Hypoglycaemia is a common and potentially life threatening consequence of insulin and sulphonylurea treated Diabetes. Some severe hypoglycaemic events result in emergency ambulance attendance. Many of these patients are treated at home and do not require immediate transportation to an Emergency Department. However only 27-37% of patients then follow up their care with a diabetes specialist. Consequently repeat severe hypoglycaemic events occur.  Methods  The intervention was implemented for 8months, using a prospective cohort design with a historic control, in one Scottish Health Board in 2012. Data was collected using postal survey questionnaires to patients and ambulance clinicians, telephone survey follow-up questions to patients. Scottish Ambulance Service electronic records were linked with the SCI-Diabetes database of patient records to enable objective measurement of follow-up behaviour.  Results  Ambulance clinicians’ (n = 92) awareness of the intervention was high and both the prompt card and telephone call components of the intervention were delivered to most eligible patients. The intervention was perceived as highly acceptable to patients (n = 37), and very useful by both patients and ambulance clinicians. However, comparison of patient follow-up behaviours using linked-data (n = 205), suggest that the intervention was unsuccessful in improving rates of patients’ following up their care.  Conclusions  This study shows that the intervention is implementable, highly acceptable to patients, and considered very useful by both patients and ambulance clinicians. However, preliminary evidence of effectiveness is not encouraging. The study’s novel use of linking existing clinical data for outcome measurement exposed challenges in the feasibility of using this data for intervention development and evaluation. Future research should examine challenges to the successful testing and effectiveness of the intervention. Revisions are likely to be required, both to study design and the optimisation of the intervention’s content and components

Cytochrome cM decreases photosynthesis under photomixotrophy in Synechocystis sp. PCC 6803

Photomixotrophy is a metabolic state that enables photosynthetic microorganisms to simultaneously perform photosynthesis and metabolism of imported organic carbon substrates. This process is complicated in cyanobacteria, since many, including Synechocystis sp. PCC 6803, conduct photosynthesis and respiration in an interlinked thylakoid membrane electron transport chain. Under photomixotrophy, the cell must therefore tightly regulate electron fluxes from photosynthetic and respiratory complexes. In this study, we demonstrate, via characterization of photosynthetic apparatus and the proteome, that photomixotrophic growth results in a gradual inhibition of QA- reoxidation in wild-type Synechocystis, which largely decreases photosynthesis over 3 d of growth. This process is circumvented by deleting the gene encoding cytochrome cM (CytM), a cryptic c-type heme protein widespread in cyanobacteria. The ΔCytM strain maintained active photosynthesis over the 3-d period, demonstrated by high photosynthetic O2 and CO2 fluxes and effective yields of PSI and PSII. Overall, this resulted in a higher growth rate compared to that of the wild type, which was maintained by accumulation of proteins involved in phosphate and metal uptake, and cofactor biosynthetic enzymes. While the exact role of CytM has not been determined, a mutant deficient in the thylakoid-localized respiratory terminal oxidases and CytM (ΔCox/Cyd/CytM) displayed a phenotype similar to that of ΔCytM under photomixotrophy. This, in combination with other physiological data, and in contrast to a previous hypothesis, suggests that CytM does not transfer electrons to these complexes. In summary, our data suggest that CytM may have a regulatory role in photomixotrophy by modulating the photosynthetic capacity of cells

Energetic responses to transient high temperature stress in cyanobacteria. A dynamic system examined in vivo

This thesis investigated the energetic response of a moderately thermophillic cyanobacterium, Thermosynechococcus elongatus BP.1 (BP.1), to high-temperature damage. Previous published work has investigated the physiological impacts of high-temperature stress on BP.1, and has focused primarily on understanding the absolute functional stability of discrete cellular components, exposed to high temperatures. The majority of this work was conducted in vitro, on isolated components, or through the addition of artificial electron donors and acceptors to cells. The results have clearly shown that photosystem two (PSII) is the thermally weakest cellular component of BP.1. Furthermore, the temperatures that inhibit PSII are very close to the optimal temperature for growth in this species. Strong evidence suggests that thylakoid components downstream of PSII, specifically photosystem one (PSI), and primary components of the electron transport chain, exhibit significantly greater tolerance to high temperatures than PSII. There has been no published work investigating the possible physiological significance of this. Furthermore, no data has been published on the tolerance to high temperatures of crucial cellular processes, carbon fixation and respiration. A key aim of the research was to identify whether any cellular functions, such as respiration, still operated in cells after high temperatures had inhibited PSII. To undertake this work, an in vivo methodology was developed to measure functionality of key cellular components, following high-temperature exposure. The method involved the integration of membrane inlet mass spectrometry (MIMS), including simultaneous gas flux measurements of CO2 and stable isotope differentiation of concurrent oxygen evolution and consumption fluxes, with pulse/probe spectroscopy of P700, the reaction-centre chlorophyll of PSI. Gas fluxes and P700 redox dynamics were measured from samples under steady state conditions of photosynthesis, following ten minutes of dark incubation across a range of damaging temperatures. The results showed clearly that respiratory systems, and probably CO2 fixation, were more stable than PSII. Furthermore, as PSII function declined to < 95 % of maximal rates, respiration was no longer inhibited by illumination. viii The P700 data indicated that PSI activity was maintained at a level that could not be supported solely by the remaining function of PSII, following high-temperature incubations. This suggested that published in vitro data, demonstrating greater thermal tolerance for PSI than PSII, may be functionally significant. Evidence that reductant sourced from respiration was driving PSI photochemistry, after PSII inhibition, was obtained. A hypothesis is proposed that the cyanobacterium utilises stored reductant to poise the thylakoid membrane for cyclic electron flux (CEF), once PSII is inhibited. The mechanism proposed in this thesis enables cells to maximise the utilisation of their stored energy, by enabling PSI to continue harnessing light energy if PSII is inhibited. A thylakoid proton gradient is maintained through PSI function, instead of standard chlororespiratory pathways that utilise a terminal oxidase. A new term, “delayed cyclic electron flux”, (CEFd) is proposed to describe this mechanism. It differentiates CEF around PSI, driven by PSII, from that supported by alternative sources of reductant, such as the respiratory complex succinate dehydrogenase (SDH). Delayed implies that the reductant has been stored in the cell

Evaluating the noise resilience of variational quantum algorithms

We simulate the effects of different types of noise in state preparation circuits of variational quantum algorithms. We first use a variational quantum eigensolver to find the ground state of a Hamiltonian in presence of noise, and adopt two quality measures in addition to the energy, namely fidelity and concurrence. We then extend the task to the one of constructing, with a layered quantum circuit ansatz, a set of general random target states. We determine the optimal circuit depth for different types and levels of noise, and observe that the variational algorithms mitigate the effects of noise by adapting the optimised parameters. We find that the inclusion of redundant parameterised gates makes the quantum circuits more resilient to noise. For such overparameterised circuits different sets of parameters can result in the same final state in the noiseless case, which we denote as parameter degeneracy. Numerically, we show that this degeneracy can be lifted in the presence of noise, with some states being significantly more resilient to noise than others. We also show that the average deviation from the target state is linear in the noise level, as long as this is small compared to a circuit-dependent threshold. In this region the deviation is well described by a stochastic model. Above the threshold, the optimisation can converge to states with largely different physical properties from the true target state, so that for practical applications it is critical to ensure that noise levels are below this threshold.Comment: 22 pages, 13 figure

Role and prevalence of impaired awareness of hypoglycaemia in ambulance service attendances to people who have had a severe hypoglycaemic emergency: a mixed-methods study

Objectives (1) To compare the experiences of people who are affected by diabetes-related hypoglycaemia and either do or do not require an emergency attendance and (2) to measure the prevalence of impaired awareness of hypoglycaemia in patients who are attended by an ambulance service due to a severe hypoglycaemic event.  Design A sequential mixed-methods study.  Setting A qualitative interview study was undertaken with 31 people with diabetes (types 1 and 2) resident in the central belt of Scotland. A national prevalence survey of 590 Scottish Ambulance Service patients who had recently experienced a severe hypoglycaemic emergency requiring ambulance clinicians attendance. Impaired awareness of hypoglycaemia was measured using two standardised measures.  Results Considerable differences in impaired awareness of hypoglycaemia were found in the experiences of participants who did or did not require the ambulance service to treat their severe hypoglycaemic events. Those who required an ambulance reported fewer warning signs and symptoms. The prevalence of impaired awareness of hypoglycaemia in ambulance service call-outs as assessed by two standardised measures was 53% and 60%, respectively.  Conclusions The prevalence of impaired awareness of hypoglycaemia among those who require an ambulance following a hypoglycaemic event is more than twice that found in the general population of people with diabetes. This may be because the experiences of impaired awareness in people who require an ambulance following a severe hypoglycaemic event differ to those who do not. This study provides important information to guide future prehospital clinical practice, and to develop and evaluate theoretically informed interventions. Improvements in prehospital care for this patient population could lead to global improvements in health outcomes and decreased service costs

BADGER - Blockchain Auditable Distributed (RSA) key GEneRation

Migration of security applications to the cloud poses unique challenges in key management and protection: asymmetric keys which would previously have resided in tamper-resistant, on-premise Hardware Security Modules (HSM) now must either continue to reside in non-cloud HSMs (with attendant communication and integration issues) or must be removed from HSMs and exposed to cloud-based threats beyond an organization\u27s control, e.g. accidental loss, warranted seizure, theft etc. Threshold schemes offer a halfway house between traditional HSM-based key protection and native cloud-based usage. Threshold signature schemes allow a set of actors to share a common public key, generate fragments of the private key and to collaboratively sign messages, such that as long as a sufficient quorum of actors sign a message, the partial signatures can be combined into a valid signature. However, threshold schemes, while being a mature idea, suffer from large protocol transcripts and complex communication-based requirements. This consequently makes it a more difficult task for a user to verify that a public key is, in fact, a genuine product of the protocol and that the protocol has been executed validly. In this work, we propose a solution to these auditability and verication problems, reporting on a prototype cloud-based implementation of a threshold RSA key generation and signing system tightly integrated with modern distributed ledger and consensus techniques

Evidence of Embodied Social Competence During Conversation in High Functioning Children with Autism Spectrum Disorder

Even high functioning children with Autism Spectrum Disorder (ASD) exhibit impairments that affect their ability to carry out and maintain effective social interactions in multiple contexts. One aspect of subtle nonverbal communication that might play a role in this impairment is the whole-body motor coordination that naturally arises between people during conversation. The current study aimed to measure the time-dependent, coordinated whole-body movements between children with ASD and a clinician during a conversational exchange using tools of nonlinear dynamics. Given the influence that subtle interpersonal coordination has on social interaction feelings, we expected there to be important associations between the dynamic motor movement measures introduced in the current study and the measures used traditionally to categorize ASD impairment (ADOS-2, joint attention and theory of mind). The study found that children with ASD coordinated their bodily movements with a clinician, that these movements were complex and that the complexity of the children’s movements matched that of the clinician’s movements. Importantly, the degree of this bodily coordination was related to higher social cognitive ability. This suggests children with ASD are embodying some degree of social competence during conversations. This study demonstrates the importance of further investigating the subtle but important bodily movement coordination that occurs during social interaction in children with ASD

New optical filamentary structures in Pegasus

Deep Halpha+[N II] CCD images have been obtained in the area of the Pegasus Constellation. The resulting mosaic covers an extent of ~7.5 degr x ~8.5 degr and filamentary and diffuse emission is discovered. Several long filaments (up to ~1 degr) are found within the field, while diffuse emission is present mainly in the central and northern areas. The filaments show variations in the intensity along their extent suggesting inhomogeneous interstellar clouds. Faint soft X-ray emission is also detected in the ROSAT All-Sky Survey. It is mainly concentrated in the central areas of our field and overlaps the optical emission. The low ionization images of [S II] of selected areas mainly show faint diffuse emission, while in the medium ionization images of [O III] diffuse and faint filamentary structures are present. Spectrophotometric observations have been performed on the brightest filaments and indicate emission from photoionized or shock-heated gas. The sulfur line ratios indicate electron densities below ~600 cm^{-3}, while the absolute Halpha emission lies in the range of 1.1 - 8.8 x 10^{-17} erg s^{-1} cm^{-2} arcsec^{-2}. The detected optical line emission could be part of a single or multiple supernova explosions.Comment: 13 pages, 7 figures, accepted for publication in A&

True oxygen reduction capacity during photosynthetic electron transfer in thylakoids and intact leaves

Photosynthetically derived H2O2 only accumulates at Photosystem I and may trigger cooperation with mitochondria during stress.Reactive oxygen species (ROS) are generated in electron transport processes of living organisms in oxygenic environments. Chloroplasts are plant bioenergetics hubs where imbalances between photosynthetic inputs and outputs drive ROS generation upon changing environmental conditions. Plants have harnessed various site-specific thylakoid membrane ROS products into environmental sensory signals. Our current understanding of ROS production in thylakoids suggests that oxygen (O-2) reduction takes place at numerous components of the photosynthetic electron transfer chain (PETC). To refine models of site-specific O-2 reduction capacity of various PETC components in isolated thylakoids of Arabidopsis thaliana, we quantified the stoichiometry of oxygen production and consumption reactions associated with hydrogen peroxide (H2O2) accumulation using membrane inlet mass spectrometry and specific inhibitors. Combined with P700 spectroscopy and electron paramagnetic resonance spin trapping, we demonstrate that electron flow to photosystem I (PSI) is essential for H2O2 accumulation during the photosynthetic linear electron transport process. Further leaf disc measurements provided clues that H2O2 from PETC has a potential of increasing mitochondrial respiration and CO2 release. Based on gas exchange analyses in control, site-specific inhibitor-, methyl viologen-, and catalase-treated thylakoids, we provide compelling evidence of no contribution of plastoquinone pool or cytochrome b6f to chloroplastic H2O2 accumulation. The putative production of H2O2 in any PETC location other than PSI is rapidly quenched and therefore cannot function in H2O2 translocation to another cellular location or in signaling