Gullies on Mars could have formed by melting of water ice during periods of high obliquity.

Gullies on Mars resemble water-carved channels on Earth, but they are mostly at elevations where liquid water is not expected under current climate conditions. It has been suggested that sublimation of carbon dioxide ice alone could have formed Martian gullies. We used a general circulation model to show that the highest-elevation Martian gullies coincide with the boundary of terrain that experienced pressures above the triple point of water when Mars' rotational axis tilt reached 35°. Those conditions have occurred repeatedly over the past several million years, most recently ~630,000 years ago. Surface water ice, if present at these locations, could have melted when temperatures rose >273 kelvin. We propose a dual gully formation scenario that is driven by melting of water ice followed by carbon dioxide ice sublimation.

The incidence and prevalence of epilepsy in the United Kingdom 2013-2018: A retrospective cohort study of UK primary care data.

PURPOSE: The aim of this study was to update overall incidence and prevalence calculations for epilepsy of the United Kingdom (UK) and its constituent nations (England, Northern Ireland, Scotland, and Wales). METHODS: We used data from primary care practices contributing to the Clinical Practice Research Datalink (CRPD), based on the electronic health records of 14 million patients, representing approximately 20% of the population. CPRD contains data from two different health record systems: the Vision clinical system (CPRD GOLD database) and the EMIS Web® clinical system (CPRD Aurum database). We calculated incidence and prevalence rates with 95% confidence intervals (CIs). Data were stratified by age, gender, deprivation, country (England, Scotland, Wales and Northern Ireland) and region (England only). RESULTS: In the UK, the estimated overall point prevalence for epilepsy was 9.37 per 1000 persons / year (95% CI 9.34-9.40) and the overall estimated incidence rate was 42.68 per 100,000 person-years (95% 42.18-43.18) using the CPRD GOLD database. In England, the estimated incidence (37.41 (95% CI 36.96-37.83)) and prevalence (8.85 (95% CI 8.83-8.87)) was lower (combined databases) compared to figures for Scotland (incidence 47.76 (95% CI 46.15-49.42)); prevalence 10.13 (95% CI 10.06-10.20)) (CPRD GOLD only), Wales (incidence 54.84 (95% CI 52.79-56.95); prevalence 11.40 (95% CI 11.31-11.49)) (CPRD GOLD only) and Northern Ireland (incidence 46.18 (95% CI 43.13-49.90); prevalence 12.08 (95% CI 11.93-12.23))(combined databases). Prevalence and incidence were higher in more deprived regions. CONCLUSION: The prevalence and incidence of epilepsy in the UK is broadly in line with other high income countries, showing the usual pattern of high incidence in the young and the old, with a nadir in middle age. The prevalence of epilepsy has fallen slightly since 2011. There is significant geographical variation (between countries and between regions), and a suggestion of a relationship between deprivation and epilepsy which needs further investigation.

Advanced quantitative evaluation of PET systems using the ACR phantom and NiftyPET software.

PURPOSE: A novel phantom-imaging platform, a set of software tools, for automated and high-precision imaging of the American College of Radiology (ACR) positron emission tomography (PET) phantom for PET/magnetic resonance (PET/MR) and PET/computed tomography (PET/CT) systems is proposed. METHODS: The key feature of this platform is the vector graphics design that facilitates the automated measurement of the knife-edge response function and hence image resolution, using composite volume of interest templates in a 0.5 mm resolution grid applied to all inserts of the phantom. Furthermore, the proposed platform enables the generation of an accurate µ $\mu$ -map for PET/MR systems with a robust alignment based on two-stage image registration using specifically designed PET templates. The proposed platform is based on the open-source NiftyPET software package used to generate multiple list-mode data bootstrap realizations and image reconstructions to determine the precision of the two-stage registration and any image-derived statistics. For all the analyses, iterative image reconstruction was employed with and without modeled shift-invariant point spread function and with varying iterations of the ordered subsets expectation maximization (OSEM) algorithm. The impact of the activity outside the field of view (FOV) was assessed using two acquisitions of 30 min each, with and without the activity outside the FOV. RESULTS: The utility of the platform has been demonstrated by providing a standard and an advanced phantom analysis including the estimation of spatial resolution using all cylindrical inserts. In the imaging planes close to the edge of the axial FOV, we observed deterioration in the quantitative accuracy, reduced resolution (FWHM increased by 1-2 mm), reduced contrast, and background uniformity due to the activity outside the FOV. Although it slows convergence, the PSF reconstruction had a positive impact on resolution and contrast recovery, but the degree of improvement depended on the regions. The uncertainty analysis based on bootstrap resampling of raw PET data indicated high precision of the two-stage registration. CONCLUSIONS: We demonstrated that phantom imaging using the proposed methodology with the metric of spatial resolution and multiple bootstrap realizations may be helpful in more accurate evaluation of PET systems as well as in facilitating fine tuning for optimal imaging parameters in PET/MR and PET/CT clinical research studies.

Impact of Interventions on the Survival of Salmonella enterica I 4,[5],1 2:i:- in Pork.

ABSTRACT: A mixed culture of Salmonella enterica serovar I 4,[5],12:i:- isolates was compared with a mixed culture of reference Salmonella serovars and nonpathogenic Escherichia coli surrogates. The two groups of Salmonella were compared for their resistance to commonly used pork carcass interventions, survival in ground pork, and thermal resistance in ground pork. No differences in responses were observed between the two groups of Salmonella serovars and the nonpathogenic E. coli surrogates within intervention type. No differences in recovery and survival or in heat resistance were observed between the two groups of Salmonella serovars in pork that had been treated, ground, and stored at 5°C for 2 weeks. However, the heat resistance of both groups of Salmonella serovars decreased after refrigerated storage. Because no differences were observed between Salmonella serovar I 4,[5],12:i:- and the reference Salmonella serovars in response to interventions commonly used in the pork industry, Salmonella I 4,[5],12:i:- does not present a unique challenge to the pork industry.

Hesitancy around low-dose CT screening for lung cancer.

Lung cancer is the leading cause of cancer death worldwide. The absence of symptoms in early-stage (I/II) disease, when curative treatment is possible, results in >70% of cases being diagnosed at late stage (III/IV), when treatment is rarely curative. This contributes greatly to the poor prognosis of lung cancer, which sees only 16.2% of individuals diagnosed with the disease alive at 5 years. Early detection is key to improving lung cancer survival outcomes. As a result, there has been longstanding interest in finding a reliable screening test. After little success with chest radiography and sputum cytology, in 2011 the United States National Lung Screening Trial demonstrated that annual low-dose computed tomography (LDCT) screening reduced lung cancer-specific mortality by 20%, when compared with annual chest radiography. In 2020, the NELSON study demonstrated an even greater reduction in lung cancer-specific mortality for LDCT screening at 0, 1, 3 and 5.5 years of 24% in men, when compared to no screening. Despite these impressive results, a call to arms in the 2017 European position statement on lung cancer screening (LCS) and the widespread introduction across the United States, there was, until recently, no population-based European national screening programme in place. We address the potential barriers and outstanding concerns including common screening foes, such as false-positive tests, overdiagnosis and the negative psychological impact of screening, as well as others more unique to LDCT LCS, including appropriate risk stratification of potential participants, radiation exposure and incidental findings. In doing this, we conclude that whilst the evidence generated from ongoing work can be used to refine the screening process, for those risks which remain, appropriate and acceptable mitigations are available, and none should serve as barriers to the implementation of national unified LCS programmes across Europe and beyond.

In Vivo Assembly of a Genetically Encoded Artificial Metalloenzyme for Hydrogen Production.

The genetic encoding of artificial enzymes represents a substantial advantage relative to traditional molecular catalyst optimization, as laboratory-based directed evolution coupled with high-throughput screening methods can provide rapid development and functional characterization of enzyme libraries. However, these techniques have been of limited utility in the field of artificial metalloenzymes due to the need for in vitro cofactor metalation. Here, we report the development of methodology for in vivo production of nickel-substituted rubredoxin, an artificial metalloenzyme that is a structural, functional, and mechanistic mimic of the [NiFe] hydrogenases. Direct voltammetry on cell lysate establishes precedent for the development of an electrochemical screen. This technique will be broadly applicable to the in vivo generation of artificial metalloenzymes that require a non-native metal cofactor, offering a route for rapid enzyme optimization and setting the stage for integration of artificial metalloenzymes into biochemical pathways within diverse hosts.

Biomineralization of Dental Tissues Treated with Silver Diamine Fluoride.

Silver diamine fluoride (SDF) is a dental biomaterial used to arrest dental caries. To better understand SDF's mechanism of action, we examined the localization of silver within the tissues of SDF-treated teeth. Carious primary teeth fixed within 2 min of SDF application (SDF-minutes, n = 3), at 3 wk after SDF application in vivo (SDF-weeks, n = 4), and at 2 y after multiple SDF applications in vivo (SDF-multiple, n = 1) were investigated in this study. Carious primary teeth without SDF application (no-SDF, n = 3) served as controls. Mineral density and structural analyses were performed via micro-X-ray computed tomography and scanning electron microscopy. Elemental analyses were performed through X-ray fluorescence microprobe and energy-dispersive X-ray spectroscopic techniques. SDF-treated teeth revealed higher X-ray-attenuated surface and subsurface regions within carious lesions, and similar regions were not present in no-SDF teeth. Regions of higher mineral density correlated with regions of silver abundance in SDF-treated teeth. The SDF penetration depth was approximated to 0.5 ± 0.02 mm and 0.6 ± 0.05 mm (mean ± SD) for SDF-minutes and SDF-weeks specimens, respectively. A higher percentage of dentin tubular occlusion by silver or calcium phosphate particles was observed in primary teeth treated with SDF-weeks as compared with SDF-minutes. Elemental analysis also revealed zinc abundance in carious lesions and around the pulp chamber. SDF-weeks teeth had significantly increased tertiary dentin than SDF-minutes and no-SDF teeth. These results suggest that SDF treatment on primary teeth affected by caries promotes pathologic biomineralization by altering their physicochemical properties, occluding dentin tubules, and increasing tertiary dentin volume. These seemingly serendipitous effects collectively contribute to the cariostatic activity of SDF.

A qualitative study of the processes by which carers of people with dementia derive meaning from caring.

BACKGROUND: Most individuals with dementia live in the community, receiving care from family or lay carers. Carers' wellbeing, and the quality of the care they provide, partly depends on their ability to derive meaning from caring for someone with dementia. Both carers' previous relationship with their relative and the caregiving process itself contribute to this sense of meaning. However, it remains unclear why some carers derive meaning from these sources, whereas others do not. OBJECTIVE: To further explore the processes by which carers derive a sense of meaning from caring. METHODS: Representative case sampling was used to recruit a purposive sample of 20 carers for individuals living with dementia. In-depth semi-structured interviews were audio-recorded and transcribed, and analysed using pluralist qualitative methodology. RESULTS: A framework of three sources from which carers derived meaning from caring was identified, encompassing: carers' perceptions of how 'right' or 'symmetrical' caring felt in light of their current and previous relationship with the person with dementia; maintenance of a 'protected' sense of self within the care relationship; and carers' perceptions of their 'social connectedness' outside the relationships. CONCLUSION: Holistic assessment based on this framework could help to tailor individualised provision of support, foster resilience and safeguard carers' well-being.

A virtual patient model for mechanical ventilation.

BACKGROUND AND OBJECTIVES: Mechanical ventilation (MV) is a primary therapy for patients with acute respiratory failure. However, poorly selected ventilator settings can cause further lung damage due to heterogeneity of healthy and damaged alveoli. Varying positive-end-expiratory-pressure (PEEP) to a point of minimum elastance is a lung protective ventilator strategy. However, even low levels of PEEP can lead to ventilator induced lung injury for individuals with highly inflamed pulmonary tissue. Hence, models that could accurately predict peak inspiratory pressures after changes to PEEP could improve clinician confidence in attempting potentially beneficial treatment strategies. METHODS: This study develops and validates a physiologically relevant respiratory model that captures elastance and resistance via basis functions within a well-validated single compartment lung model. The model can be personalised using information available at a low PEEP to predict lung mechanics at a higher PEEP. Proof of concept validation is undertaken with data from four patients and eight recruitment manoeuvre arms. RESULTS: Results show low error when predicting upwards over the clinically relevant pressure range, with the model able to predict peak inspiratory pressure with less than 10% error over 90% of the range of PEEP changes up to 12 cmH2O. CONCLUSIONS: The results provide an in-silico model-based means of predicting clinically relevant responses to changes in MV therapy, which is the foundation of a first virtual patient for MV.

Do drugs offering only PFS maintain quality of life sufficiently from a patient's perspective? Results from AVALPROFS (Assessing the 'VALue' to patients of PROgression Free Survival) study.

PURPOSE: Trials of novel drugs used in advanced disease often show only progression-free survival or modest overall survival benefits. Hypothetical studies suggest that stabilisation of metastatic disease and/or symptom burden are worth treatment-related side effects. We examined this premise contemporaneously using qualitative and quantitative methods. METHODS: Patients with metastatic cancers expected to live > 6 months and prescribed drugs aimed at cancer control were interviewed: at baseline, at 6 weeks, at progression, and if treatment was stopped for toxicity. They also completed Functional Assessment of Cancer Therapy (FACT-G) plus Anti-Angiogenesis (AA) subscale questionnaires at baseline then monthly for 6 months. RESULTS: Ninety out of 120 (75%) eligible patients participated: 41 (45%) remained on study for 6 months, 36 progressed or died, 4 had treatment breaks, and 9 withdrew due to toxicity. By 6 weeks, 66/69 (96%) patients were experiencing side effects which impacted their activities. Low QoL scores at baseline did not predict a higher risk of death or dropout. At 6-week interviews, as the side effect severity increased, patients were significantly less inclined to view the benefit of cancer control as worthwhile (X2 = 50.7, P < 0.001). Emotional well-being initially improved from baseline by 10 weeks, then gradually returned to baseline levels. CONCLUSION: Maintaining QoL is vital to most patients with advanced cancer so minimising treatment-related side effects is essential. As side effect severity increased, drugs that controlled cancer for short periods were not viewed as worthwhile. Patients need to have the therapeutic aims of further anti-cancer treatment explained honestly and sensitively.

Damage Control Resuscitation Supplemented with Vasopressin in a Severe Polytrauma Model with Traumatic Brain Injury and Uncontrolled Internal Hemorrhage.

INTRODUCTION: Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of traumatic death worldwide and particularly on the battlefield. They are especially challenging when present simultaneously (polytrauma), and clear blood pressure end points during fluid resuscitation are not well described for this situation. The goal of this study is to evaluate for any benefit of increasing blood pressure using a vasopressor on brain blood flow during initial fluid resuscitation in a swine polytrauma model. MATERIALS AND METHODS: We used a swine polytrauma model with simultaneous TBI, femur fracture, and HS with uncontrolled noncompressible internal bleeding from an aortic tear injury. Five animals were assigned to each of three experimental groups (hydroxyethyl starch only [HES], HES + 0.4 U/kg vasopressin, and no fluid resuscitation [No Fluids]). Fluids were given as two 10 mL/kg boluses according to tactical field care guidelines. Primary outcomes were mean arterial blood pressure (MAP) and brain blood flow at 60 min. Secondary outcomes were blood flows in the heart, intestine, and kidney; arterial blood lactate level; and survival at 6 hr. Organ blood flow was measured using injection of colored microspheres. RESULTS: Five animals were tested in each of the three groups. There was a statistically significant increase in MAP with vasopressin compared with other experimental groups, but no significant increase in brain blood flow during the first 60 min of resuscitation. The vasopressin group also exhibited greater total internal hemorrhage volume and rate. There was no difference in survival at 6 hours. CONCLUSION: In this experimental swine polytrauma model, increasing blood pressure with vasopressin did not improve brain perfusion, likely due to increased internal hemorrhage. Effective hemostasis should remain the top priority for field treatment of the polytrauma casualty with TBI.

Burkitt non-Hodgkin lymphoma presenting with mental neuropathy ('numb chin' syndrome) in an HIV-positive patient.

Mental nerve neuropathy is usually due to local trauma or dental causes, but may be a manifestation of malignancy. A patient with virologically controlled human immunodeficiency virus (HIV) infection presented with a 'numb chin' on the background of long-standing night sweats, malaise and weight loss, worsening respiratory symptoms, and lymphadenopathy. Burkitt non-Hodgkin lymphoma was diagnosed from histology of a lymph node. Imaging (magnetic resonance imaging and 18fluorodeoxyglucose [FDG]-positron emission tomography-computed tomography [PET-CT]) showed abnormal intracranial enhancement of the right mandibular nerve and extensive 18FDG-avid lymphadenopathy above and below the diaphragm, focal lesions in the spleen and within the right mandible. The patient received chemotherapy and remains in clinical and radiological remission seven years later. This case highlights the need for clinicians to maintain a high index of suspicion for underlying malignancy when an HIV-infected patient presents with new onset of a 'numb chin'. Additionally, it demonstrates the importance of functional 18FDG-PET-CT and neuroimaging in order to identify site(s) of pathology.

Comparative effects of in ovo versus subcutaneous administration of the Marek's disease vaccine and pre-placement holding time on the processing yield of Ross 708 broilers.

Effects of the in ovo (i.o.) or subcutaneous (s.c.) method of administration (moa) of the Marek's disease (MD) vaccine and 4 or 18 h pre-placement holding time (pht) on the processing yield of male broilers through 49 d of age (doa) were investigated. Ross 708 broiler hatching eggs (3,900) were either i.o.-vaccinated at 18 d of incubation or chicks from eggs that were not i.o.-vaccinated were s.c.-vaccinated at hatch. The i.o. injections (50 µL) were delivered by a commercial multi-egg injector and s.c. injections (200 µL) were delivered by an automatic pneumatic s.c. injector. The pht was imposed on chicks after vaccination. Sixteen birds were initially assigned to each of 15 replicate floor pens belonging to each of the moa and pht combination groups and were grown out through 48 doa. At 48 doa, 6 birds were randomly selected from each replicate pen and were weighed and fasted for 16 h before being processed. At 49 doa, whole carcass, fat pad, breast muscle, and tenders muscles weights were recorded. Whole carcass weight as a percentage of live BW, and fat pad, breast muscle, and tenders muscles weights as percentages of both live and whole carcass weights were calculated. Upon subjection of the data to a 2 × 2 factorial analysis, only a main effect due to moa was observed for tenders muscles weight as a percentage of live and whole carcass weights. Tenders muscles weight as a percentage of both live (P ≤ 0.010) and whole carcass (P ≤ 0.004) weight was higher in birds hatched from eggs that received i.o. rather than s.c. vaccinations. In conclusion, in comparison to s.c. vaccination, i.o. vaccination increased relative tenders weight yield, whether or not broilers were held for 4 or 18 h prior to placement. Therefore, with regard to broiler processing yield, i.o. and s.c. vaccinations were safe for the administration of the MD vaccine, with i.o. vaccination displaying a slight potential advantage.

Simultaneous 68Ga DOTATATE Positron Emission Tomography/Magnetic Resonance Imaging in Meningioma Target Contouring: Feasibility and Impact Upon Interobserver Variability Versus Positron Emission Tomography/Computed Tomography and Computed Tomography/Magnetic Resonance Imaging.

AIMS: The increasing use of highly conformal radiation techniques to treat meningioma confers a greater need for accurate targeting. Several groups have shown that positron emission tomography/computed tomography (PET/CT) information alters meningioma targets contoured by single observers, but whether this translates into improved accuracy has not been defined. As magnetic resonance imaging (MRI) is the cornerstone of meningioma target contouring, simultaneous PET/MRI may be superior to PET/CT. We assessed whether 68Ga DOTATATE PET imaging (from PET/CT and PET/MRI) reduced interobserver variability (IOV) in meningioma target volume contouring. MATERIALS AND METHODS: Ten patients with meningioma underwent simultaneous 68Ga DOTATATE PET/MRI followed by PET/CT. They were selected as it was anticipated that target volume definition in their cases would be particularly challenging. Three radiation oncologists contoured target volumes according to an agreed protocol: gross tumour volume (GTV) and clinical target volume (CTV) on CT/MRI alone, CT/MRI+PET(CT) and CT/MRI+PET(MRI). GTV/CTV Kouwenhoven conformity levels (KCL), regions of contour variation and qualitative differences between PET(CT) and PET(MRI) were evaluated. RESULTS: There was substantial IOV in contouring. GTV mean KCL: CT/MRI 0.34, CT/MRI+PET(CT) 0.38, CT/MRI+PET(MRI) 0.39 (P = 0.06). CTV mean KCL: CT/MRI 0.31, CT/MRI+PET(CT) 0.35, CT/MRI+PET(MRI) 0.35 (P = 0.04 for all groups; P > 0.05 for individual pairs). One observer consistently contoured largest and one smallest. Observers rarely decreased volumes in relation to PET. Most IOV occurred in bone followed by dural tail, postoperative bed and venous sinuses. Tumour edges were qualitatively clearer on PET(MRI) versus PET(CT), but this did not affect contouring. CONCLUSION: IOV in contouring challenging meningioma cases was large and only slightly improved with the addition of 68Ga DOTATATE PET. Simultaneous PET/MRI for meningioma contouring is feasible, but did not improve IOV versus PET/CT. Whether volumes can be safely reduced according to PET requires evaluation.

Training in Clinical Oncology and the Transition from Trainee to Consultant: Results of the Royal College of Radiologists' 2015 Post-Certificate of Completion of Training Survey.

AIMS: To seek feedback from clinical oncologists as to their experiences of specialty training and, where applicable, the transition to working as a consultant in the National Health Service. MATERIALS AND METHODS: All clinical oncologists gaining a Certificate of Completion of Training between 1 July 2012 and 30 June 2014 were identified through records held by the Royal College of Radiologists and approached in May 2015 to take part in an online survey. RESULTS: The survey was completed by 38 of 80 clinical oncologists invited to take part (48% response rate). Most respondents (>87%) agreed that specialty training equipped them well with clinical skills in radiotherapy planning, systemic therapy and tumour site diagnosis and treatment. This fell to 58% with advanced radiotherapy techniques. Of the non-clinical skills, respondents felt training had equipped them less to deal with leadership and management (53%) and research (48%) than clinical governance (61%). Despite wanting to do so, 42% of respondents did not undertake any out-of-programme (OOP) activity to gain new skills. Most of those respondents who did undertake OOP activity agreed that it helped to prepare them for their first consultant post. There is broad support for the FRCR Examination. The First FRCR Examination modules in physics, pharmacology, tumour biology and radiobiology were seen to be very relevant to clinical practice by 50% or more of respondents. The Final FRCR Examination was seen as essential in a technical specialty like clinical oncology by 92% of respondents. Working as a new consultant, the survey revealed a heavy workload for most respondents, with 69% always or almost always working beyond contracted hours. Other issues of concern identified were discrepancies in advertised consultant job plans and ineffectiveness of the job plan review process. The trainee-consultant transition is often a difficult time, yet only 19% of respondents were allocated a formal mentor. Most respondents had to rely on informal arrangements in seeking support and advice from medical colleagues. CONCLUSIONS: In general, respondents were satisfied with their specialty training and the transition from training to working as a new consultant. Areas for possible improvement have been identified for employers as well as those involved in organising specialty training.

Insulin kinetics and the Neonatal Intensive Care Insulin-Nutrition-Glucose (NICING) model.

BACKGROUND: Models of human glucose-insulin physiology have been developed for a range of uses, with similarly different levels of complexity and accuracy. STAR (Stochastic Targeted) is a model-based approach to glycaemic control. Elevated blood glucose concentrations (hyperglycaemia) are a common complication of stress and prematurity in very premature infants, and have been associated with worsened outcomes and higher mortality. This research identifies and validates the model parameters for model-based glycaemic control in neonatal intensive care. METHODS: C-peptide, plasma insulin, and BG from a cohort of 41 extremely pre-term (median age 27.2 [26.2-28.7] weeks) and very low birth weight infants (median birth weight 839 [735-1000] g) are used alongside C-peptide kinetic models to identify model parameters associated with insulin kinetics in the NICING (Neonatal Intensive Care Insulin-Nutrition-Glucose) model. A literature analysis is used to determine models of kidney clearance and body fluid compartment volumes. The full, final NICING model is validated by fitting the model to a cohort of 160 glucose, insulin, and nutrition data records from extremely premature infants from two different NICUs (neonatal intensive care units). RESULTS: Six model parameters related to insulin kinetics were identified. The resulting NICING model is more physiologically descriptive than prior model iterations, including clearance pathways of insulin via the liver and kidney, rather than a lumped parameter. In addition, insulin diffusion between plasma and interstitial spaces is evaluated, with differences in distribution volume taken into consideration for each of these spaces. The NICING model was shown to fit clinical data well, with a low model fit error similar to that of previous model iterations. CONCLUSIONS: Insulin kinetic parameters have been identified, and the NICING model is presented for glycaemic control neonatal intensive care. The resulting NICING model is more complex and physiologically relevant, with no loss in bedside-identifiability or ability to capture and predict metabolic dynamics.