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Closed loop (CL) systems deliver insulin with a rapid onset and offset in action. Although favorable overall, the absence of a long-acting insulin increases the risk of diabetic ketoacidosis (DKA) which can occur with insulin delivery failure, acute illness, low carbohydrate diets, sodium glucose-linked transporter inhibitors, and high intensity exercise. A CL system relying entirely on interstitial glucose measurements may not provide an alert for DKA and many people with type 1 diabetes (T1D) do not carry a blood ketone meter and test-strips. Ketone sensing is theoretically feasible. A multianalyte platform incorporating a ketone sensor could provide an additional CL input without an increase in burden for the person with T1D, warning of impending DKA to allow remedial action to be taken. We outline the clinical case for inclusion of continuous ketone sensing as part of future CL systems.

Background: Experience from first-generation closed-loop (CL) systems informs refinements to enhance glucose control and user acceptance. A next-generation prototype enhanced-hybrid CL (E-HCL) system incorporates iterative changes to the Medtronic MiniMed 670G CL system, including automated correction boluses, lower target glucose level, and user enhancements. The aim was to explore safety, system performance, and glucose control using E-HCL in adults with type 1 diabetes. Methods: Twelve adults underwent this first in-human feasibility study. After a 1-week run-in using open-loop (OL), E-HCL was activated at the start of a supervised 1-week hotel phase, followed by 3 weeks free living at home. Supervised challenges included two meal interventions (unannounced and late meal bolus) and a sensor calibration intervention. Primary outcome was sensor glucose time-in-range (TIR); OL run-in and E-HCL at home were compared by Wilcoxon signed-rank test. Results: Twelve adults (seven men; median [interquartile range] age 48 [39, 57] years; HbA 1c 6.8 [6.2, 7.2]%, 51 [44, 55] mmol/mol; diabetes duration 31 [13, 41] years) completed the protocol. E-HCL resulted in greater TIR (85.3 [79.4, 88.4]% vs. 75.0 [66.6, 83.7]%, P  = 0.003) and lower mean sensor glucose (123.0 [119.3, 129.6] mg/dL vs. 143.5 [135.8, 154.5] mg/dL, P  = 0.002) than OL. Time spent <70 mg/dL increased using E-HCL (4.4 [3.3, 6.1]% vs. 3.0 [1.8, 3.8]%, P  = 0.02) with no difference in time <54 mg/dL ( P  = 0.64). Time in CL was 99.98 [99.0, 100.0]%. All participants were satisfied using E-HCL. Conclusions: In adults with well-controlled HbA 1c levels, a prototype E-HCL resulted in high TIR, few CL exits, and positive user experiences at the expense of increased hypoglycemia (<70 mg/dL). E-HCL represents a positive step in the journey toward optimizing glucose control in people living with type 1 diabetes.

Hybrid closed loop (HCL) insulin delivery with the Medtronic Minimed 670G system is effective and safe in people with type 1 diabetes (T1D). This study compared glucose control, closed loop (CL) exits, and alarm frequency with the standard HCL (s-HCL) versus enhanced HCL (e-HCL) Medtronic system. Pump-experienced T1D adults (n = 11; 9 female; mean [SD] age: 51 years [15 years]; HbA1c 7.5% [1.0%] or 58 mmol/mol [7.7 mmol/mol]) were assigned, in random order, s-HCL or e-HCL for 1 week each in a supervised live-in setting. e-HCL incorporated enhanced bolus reminders and iterative changes, broadening glucose and insulin delivery parameters permitting persistence in CL. For both s-HCL and e-HCL, insulin delivery was by a Medtronic pump with identical interventions (missed bolus, exercise, high-glycemic index, and high-fat meals), insulin action times, and insulin-carbohydrate ratios implemented. The primary outcome was continuous glucose monitoring time in target range. Analysis was by paired t-test for normally distributed data and Wilcoxon-signed rank test otherwise. e-HCL resulted in significantly fewer CL alerts and exits. Time in target and mean glucose favored e-HCL but did not reach statistical significance. No episodes of severe hypoglycemia or ketoacidosis occurred. Relative to s-HCL, e-HCL use significantly decreases CL exits and alerts, and tended to improve glycemia without compromising safety, despite multiple food and exercise challenges during the study. Longer term studies at home are merited.

Competing Interests: Conflict of interest: Barbora Paldus has received research support and honoraria from Medtronic, Novo-Nordisk and Sanofi. Melissa Lee has received research support and honoraria from Medtronic. David O’Neal has received research support and is on advisory boards for Medtronic, Novo-Nordisk and Sanofi. He has received honoraria from Medtronic, AMSL, Novo-Nordisk and Sanofi.

Introduction: Manual determination of insulin dosing largely fails to optimise glucose control in type 1 diabetes. Automated insulin delivery via closed-loop systems has improved glucose control in short-term studies. The objective of the present study is to determine the effectiveness of 6 months' closed-loop compared with manually determined insulin dosing on time-in-target glucose range in adults with type 1 diabetes., Methods and Analysis: This open-label, seven-centre, randomised controlled parallel group clinical trial will compare home-based hybrid closed-loop versus standard diabetes therapy in Australia. Adults aged ≥25 years with type 1 diabetes using intensive insulin therapy (via multiple daily injections or insulin pump, total enrolment target n=120) will undertake a run-in period including diabetes and carbohydrate-counting education, clinical optimisation and baseline data collection. Participants will then be randomised 1:1 either to 26 weeks of MiniMed 670G hybrid closed-loop system therapy (Medtronic, Northridge, CA, USA) or continuation of their current diabetes therapy. The hybrid closed-loop system delivers insulin automatically to address basal requirements and correct to target glucose level, while bolus doses for meals require user initiation and carbohydrate estimation. Analysis will be intention to treat, with the primary outcome time in continuous glucose monitoring (CGM) target range (3.9-10.0 mmol/L) during the final 3 weeks of intervention. Secondary outcomes include: other CGM parameters, HbA 1c , severe hypoglycaemia, psychosocial well-being, sleep, cognition, electrocardiography, costs, quality of life, biomarkers of vascular health and hybrid closed-loop system performance. Semistructured interviews will assess the expectations and experiences of a subgroup of hybrid closed-loop users., Ethics and Dissemination: The study has Human Research Ethics Committee approval. The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Results will be disseminated at scientific conferences and via peer-reviewed publications., Trial Registration Number: ACTRN12617000520336; Pre-results., Competing Interests: Competing interests: MIdB and NDC report receiving speaker honoraria from Medtronic. DJHW reports receiving speaker and advisory board honoraria from Medtronic. RWM reports receiving conference travel and accommodation support from Medtronic. JS reports that the ACBRD has received honoraria from Medtronic in relation to her speaking engagements and role in advisory boards. DNON reports receiving speaker honoraria and research grants from Medtronic., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

We describe the application of cavity ring-down spectroscopy (CRDS) to the detection of trace levels of ethylene in ambient air in a cold storage room of a fruit packing facility over a several month period. We compare these results with those obtained using gas chromatography (GC), the current gold standard for trace ethylene measurements in post-harvest applications. The CRDS instrument provided real-time feedback to the facility, to optimize the types of fruit stored together, and the amount of room ventilation needed to maintain sub-10 ppb ethylene levels for kiwi fruit storage. Our CRDS instrument achieved a detection limit of two parts-per-billion volume (ppbv) in 4.4 minutes of measurement time.

High fluences inside cavity ring-down spectroscopy optical resonators lend themselves to fluorescence or Raman spectroscopy. An instrument at 488 nm was developed to measure extinction, and fluorescence of aerosols. A detection limit of 6 x 10;-9 cm;-1Hz;-1/2 (0.6 Mm;-1Hz;-1/2) was achieved. The fluorescence spectral power collected from a single fluorescent microsphere was 10 to 20 pW/nm. This power is sufficient to obtain the spectrum of a single microsphere with a resolution of 10 nm and signal-to-noise ratio of ~10. The relative concentrations of two types of fluorescent microspheres were determined from a time-integrated fluorescence measurement of a mixture of both.