Impact of calibration algorithms on hypoglycaemia detection in newborn infants using continuous glucose monitors

invited, 6-pagesNeonatal hypoglycaemia is a common condition that can cause seizures and serious brain injury in infants. It is diagnosed by blood glucose (BG) measurements, often taken several hours apart. Continuous glucose monitoring (CGM) devices can potentially improve hypoglycaemia detection, while reducing the number of BG measurements. Calibration algorithms convert the sensor signal into the CGM output. Thus, these algorithms can have a direct impact on measures used to quantify excursions from normal glycaemic levels. The aim of this study was to quantify the effects of calibration sensor error and non-linear filtering of CGM data on measures of hypoglycaemia (defined as BG < 2.6mmol/L) in neonates. CGM data was recalibrated using an algorithm that explicitly recognised the high accuracy of BG measurements available in this study. Median filtering was also implemented either before or after recalibration. Results for the entire cohort show an increase in the total number of hypoglycaemic events (161 to 193), duration of hypoglycaemia (2.2 to 2.6% of total data), and hypoglycaemic index (4.9 to 7.1µmol/L) after recalibration. With the addition of filtering, the number of hypoglycaemic events was reduced (193 to 131), with little or no change to the other metrics. These results show how reference sensor error and thus calibration algorithms play a significant role in quantifying hypoglycaemia. In particular, metrics such as counting the number of hypoglycaemic events were particularly sensitive to recalibration and filtering effects. While this conclusion might be expected, its potential impact is quantified here, in this case for at-risk neonates for whom hypoglycaemia carries potential long-term negative outcomes

Duplex-derived Evidence of Reflux After Varicose Vein Surgery: Neoreflux or Neovascularisation?

AbstractBackgroundrecurrent varicose veins remain a problem in surgical practice despite improvements to the preoperative investigation of, and surgery for varicose veins. Neovascularisation accounts for some cases of recurrence within a few years of surgery, but other factors relating to disease progression must also play a part. We investigated whether new venous reflux (neoreflux) could occur in the early postoperative period (within 6 weeks) following successful varicose vein surgery.Methodseighteen-month prospective observational study in the dedicated vascular surgery unit of a university teaching hospital. Forty-six patients, with primary saphenofemoral junction reflux, awaiting varicose vein surgery were chosen consecutively from the waiting list. All saphenofemoral surgery was performed in a standardised fashion. Assessments were performed prior to, at 6 weeks and at 1 year after surgery. Duplex ultrasound was used to identify and locate sites of reflux.Resultsneoreflux was present at the 6-week postoperative scan in nine limbs after varicose vein surgery (19.6%), and resolved in 55.6% of patients within 1 year. Neovascularisation was noted in two limbs at the 1-year scan.Conclusionnew sites of reflux, which may resolve spontaneously, occur in the early postoperative period despite adequate varicose vein surgery. It is our hypothesis that this is a manifestation of the effect of altered venous haemodynamics in a system of susceptible veins

Low density lipoprotein quality and discordance with apolipoprotein B in intensively controlled Type 1 diabetes: Any relationship with nutrition?

Type 1 diabetes (T1D) is partly characterised by a higher prevalence of cardiovascular disease (CVD). Despite low density lipoprotein cholesterol (LDL-C) being a commonly treated target, apolipoprotein B (Apo B) has been shown to be a superior predictor of CVD and discordance between these two markers may predispose patients to altered risk(1). The distribution of LDL-C also contributes to these risks, with LDL III & IV fractions possessing greater atherogenic potential(2). Few studies have investigated LDL-C quality and its discordance with Apo B in relation to the nutritional intake of patients with intensively controlled Type 1 diabetes. The aim of this study was to address this dearth of research. Following ethical approval and informed consent 28 patients (32 % male; 68 % female) (mean age 48 ± 15) were asked to complete a food frequency questionnaire (FFQ), donate a sample of blood and allow the authors access to their medical records to determine HbA1c. The initial FFQ responses were processed using FETA software. The blood sample was analysed for LDL-C, constituent subfractions and Apo B. All data were interrogated using descriptive statistics. Dichotomous dependent variables pertaining to LDL-C and Apo B were compared using McNemar’s test and correlations between dietary variables were determined with Spearman’s rho test. Significant differences were shown between LDL-C categories when compared to Apo B (p = 0·039) and the majority of patients (46·4 %) presented LDL-C >2·0 mmol/L and Apo B >80 mg/dL (Fig. 1). Although not discordant, these findings still suggest an increased risk according to recommendations(3). Closer inspection of results revealed that individuals with raised LDL-C typically had an abundance of LDL I & II fractions which may somewhat reduce this risk (Fig. 2). Spearman’s correlation applied to the whole population produced no relationship between diet and LDL-C or Apo B; however, when focussing on the predominant ‘at risk’ cluster significant and strong relationships between LDL-C and total carbohydrate (R2 = 0·835; p = <0·001) and sucrose (R2 = 0·758; p = 0·003) were found. No hypoglycaemia data were collected and the authors tentatively speculate that these relationships may be a consequence of its treatment. In the light of the small sample size a further more comprehensive investigation with an appropriately powered sample would be beneficial

LIMITATIONS TO EXERCISE TOLERANCE IN TYPE 1 DIABETES: THE ROLE OF PULMONARY OXYGEN UPTAKE KINETICS AND PRIMING EXERCISE

We compared the time constant (τ_V ̇ O2) of the fundamental phase of pulmonary oxygen uptake (V ̇O2) kinetics between young adult males with type 1 diabetes and healthy controls. We also assessed the impact of priming exercise on τ_V ̇ O2, critical power, and muscle deoxygenation in a subset of participants with type 1 diabetes. 17 males with type 1 diabetes and 17 healthy male controls performed moderate-intensity exercise to determine τ_V ̇ O2. A subset of 7 participants with type 1 diabetes performed an additional eight visits, whereby critical power, τ_V ̇ O2 and muscle deoxyhaemoglobin + myoglobin ([HHb+Mb]; via near-infrared spectroscopy) kinetics (described by a time constant, τ[HHb+Mb]) were determined with (PRI) and without (CON) a prior 6-minute bout of heavy exercise. τ_V ̇ O2 was greater in participants with type 1 diabetes compared to controls (type 1 diabetes: 50±13 vs. control: 32±12 s; P<0.001). Critical power was greater in PRI compared to CON (PRI: 161±25 W vs. CON: 149±22 W; P<0.001), whereas τ_V ̇ O2 (PRI: 36±15 vs. CON: 50±21 s; P=0.006) and τ[HHb+Mb] (PRI: 10±5 vs. CON: 17±11 s; P=0.037) were reduced in PRI compared to CON. Type 1 diabetes patients showed slower pulmonary V ̇O2 kinetics when compared to controls; priming exercise speeded V ̇O2 and [HHb + Mb] kinetics, and increased critical power in a subgroup with type 1 diabetes. These data therefore represent the first characterisation of the power-duration relationship in type 1 diabetes, and the first experimental evidence that τ_V ̇ O2 is an independent determinant of critical power in this population

The influence of continuous subcutaneous insulin infusion therapy vs. multiple daily injections upon the diet of those with Type 1 diabetes: A food diary investigation

There exist a number of therapeutic options for the management of Type 1 diabetes (T1D). Multiple daily injections (MDI) are one such treatment and involve 4-5 daily subcutaneous injections of insulin. This frequently used approach is widely regarded as an effective method of controlling glycaemia; however, if a patient continues to suffer disabling episodes of hypoglycaemia, or if HbA1c remains above 8.5% continuous subcutaneous insulin infusion (CSII) may instead be recommended1. This therapy employs a small programmable pump device to facilitate the administration of insulin to the patient via a cannula. Various advantages of CSII have been documented compared to MDI, including improvements in glycaemic control and reduced incidence of both hypoglycaemia and the dawn phenomenon. An additional attribute, characterised by the flexible nature of the therapy, is that a liberalised diet may be enjoyed by patients, which in turn may infer potential nutrition and quality of life aberrations. This phenomenon is surprisingly under researched and further investigations to inform both treatment and risk would therefore be beneficial. Following ethical approval and informed consent patients with T1D using either CSII or MDI from the Royal Liverpool Hospital were asked to complete a 5 day weighed food diary. Dietplan 6 software was used to process the responses and demographic data from participants’ medical records were added to the dataset. All data were then interrogated using descriptive statistics and any non-normal data were transformed logarithmically before further enquiry with t-tests or analysed non-parametrically with Mann-Whitney-U-tests. The sample comprised of 20 patients (35% male, 65% female) with 11 using CSII and 9 using MDI. The patients’ mean age was 49±16 years and the majority were overweight or obese (72.7% CSII, 55.6% MDI). Nutrient Amount per day (CSII group) Amount per day (MDI group) % energy intake per day (CSII group) % energy intake per day (MDI group) Energy 1866.6 Kcal 2110.5 Kcal N/A N/A Protein 69.0 g/day 89.9 g/day 14.8 17.0 Total CHO 232.3 g/day 251.8 g/day 46.7 44.7 Total sugars 99.8 g/day 88.6 g/day 20.0 15.7 Total fat 73.5 g/day 80.1 g/day 35.4 34.2 Saturated fat 31.6 g/day 29.8 g/day 15.2 12.7 Table. Selected food diary results from patients using CSII and MDI compared to reference nutrient intakes. Results showed mean energy intake was below the reference nutrient intake (RNI) for the CSII group; potentially suggestive of underreporting (Table)3. Patients using both CSII and MDI consumed protein above the RNI; however, this macronutrient contributed towards 14.8% of the daily energy intake of patients using CSII and 17.0% of those using MDI3. Total carbohydrate (CHO) consumption was below the RNI of 50%; however, it should be noted that consumption of total sugars was above the RNI for males and females in both groups4. Previous research by the authors suggesting habitual fruit consumption, particularly in those using CSII, may explain this5. Total fat and saturated fat consumption was mostly synonymic with RNI’s. Although no statistically significant associations were seen between any of the variables and the diets of the two populations appeared largely homogenous it is reassuring that no detrimental changes occurred. Despite this further analysis of total energy, protein and CHO quality is warranted

GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients

GPIHBP1, a GPI-anchored protein of capillary endothelial cells, binds lipoprotein lipase (LPL) within the subendothelial spaces and shuttles it to the capillary lumen. The GPIHBP1-bound LPL is essential for the margination of triglyceride-rich lipoproteins (TRLs) along capillaries, allowing the lipolytic processing of TRLs to proceed. In peripheral tissues, the intravascular processing of TRLs by the GPIHBP1-LPL complex is crucial for generating lipid nutrients for adjacent parenchymal cells. GPIHBP1 is absent in capillaries of the brain, which uses glucose for fuel; however, GPIHBP1 is expressed in capillaries of mouse and human gliomas. Importantly, the GPIHBP1 in glioma capillaries captures locally produced LPL. We document, by NanoSIMS imaging, that TRLs marginate along glioma capillaries and that there is uptake of TRL-derived lipid nutrients by surrounding glioma cells. Thus, GPIHBP1 expression in gliomas facilitates TRL processing and provides a source of lipid nutrients for glioma cells

Water as a catalytic switch in the oxidation of aryl alcohols by polymer incarcerated rhodium nanoparticles

One of the major goals in the oxidation of organic substrates, and especially for alcohol oxidation, is the use of molecular oxygen as the oxidant under mild conditions. Here we report the synthesis and testing of Rh polymer incarcerated catalysts, using a metal so far not used for alcohol oxidation reactions, in which the catalytic activity towards aryl alcohol oxidation, for substrates like 1-phenylethanol and benzyl alcohol, is switched on by the addition of water as co-solvent in toluene. This is done by using air as oxidant at atmospheric pressure, in one of the mildest reaction conditions reported for this class of reaction. The promoting effect of water to higher conversions was observed also for rhodium over alumina supported catalysts, which were used as a benchmark allowing in all cases high conversion and selectivity to the ketone or the aldehyde within a short reaction time. The effect of water was explained as a medium capable to promote the oxidation of the alcohol to the ketone in a biphasic system assisted by phase transfer catalysis. This is particularly relevant for alcohols like 1-phenylethanol or benzyl alcohol that are not soluble in water at room temperature, and for which alternative oxidation routes are needed, as well as to switch on the catalytic activity of metal nanoparticles in a facile and green manner for the activation of molecular oxygen. Aliphatic alcohols like 1-octanol and 3-octanol were also tested, still showing Rh based catalysts as promising materials for this reaction if toluene only was used as solvent instead

Measurement of the cross section for isolated-photon plus jet production in pp collisions at √s=13 TeV using the ATLAS detector

The dynamics of isolated-photon production in association with a jet in proton–proton collisions at a centre-of-mass energy of 13 TeV are studied with the ATLAS detector at the LHC using a dataset with an integrated luminosity of 3.2 fb−1. Photons are required to have transverse energies above 125 GeV. Jets are identified using the anti- algorithm with radius parameter and required to have transverse momenta above 100 GeV. Measurements of isolated-photon plus jet cross sections are presented as functions of the leading-photon transverse energy, the leading-jet transverse momentum, the azimuthal angular separation between the photon and the jet, the photon–jet invariant mass and the scattering angle in the photon–jet centre-of-mass system. Tree-level plus parton-shower predictions from Sherpa and Pythia as well as next-to-leading-order QCD predictions from Jetphox and Sherpa are compared to the measurements

A search for resonances decaying into a Higgs boson and a new particle X in the XH → qqbb final state with the ATLAS detector

A search for heavy resonances decaying into a Higgs boson (H) and a new particle (X) is reported, utilizing 36.1 fb−1 of proton–proton collision data at collected during 2015 and 2016 with the ATLAS detector at the CERN Large Hadron Collider. The particle X is assumed to decay to a pair of light quarks, and the fully hadronic final state is analysed. The search considers the regime of high XH resonance masses, where the X and H bosons are both highly Lorentz-boosted and are each reconstructed using a single jet with large radius parameter. A two-dimensional phase space of XH mass versus X mass is scanned for evidence of a signal, over a range of XH resonance mass values between 1 TeV and 4 TeV, and for X particles with masses from 50 GeV to 1000 GeV. All search results are consistent with the expectations for the background due to Standard Model processes, and 95% CL upper limits are set, as a function of XH and X masses, on the production cross-section of the resonance