Influence of gastric residual assessment in preterm neonates on time to achieve enteral feeding (the GRASS trial)-Multi-centre, assessor-blinded randomised clinical trial.

PURPOSE: Gastric residual measurement is routinely performed in premature infants prior to feeding despite a lack of evidence of benefit. We aimed to evaluate if the exclusion of routine gastric residual measurement and evaluation has an impact on the time taken to achieve full enteral feeding in preterm neonates. METHODS: International multi-centre randomised controlled trial. Clinically stable, appropriate for gestational age infants between 26+0 and 30+6 weeks of gestation and less than 1.5 kg birth weight were eligible. Infants were randomised to the intervention arm (no monitoring of gastric aspirates) or control arm (routine care). Primary outcome was the achievement of enteral feeds of 100 ml/kg/day by day 5 of life. RESULTS: Ninety-five infants were recruited with 88 included in an intention-to-treat analysis, 45 in the intervention arm and 43 in the control arm. There was no imbalance in baseline characteristics. Thirty-three (73.3%) infants in the intervention group and 32 infants (74.4%) in the control group reached full feeds by day 5 of life (p = 0.91) with no difference in median time to full feeds. There were no statistically significant differences in survival or the major morbidities of prematurity. CONCLUSION:  There was no difference in time to attainment of enteral feeds of 100 ml/kg/day in premature infants when gastric residuals were not monitored. In the absence of a clinical benefit to routine monitoring, it may be appropriate to discontinue this practice and only monitor residuals when clinical concern of feeding intolerance or gastrointestinal pathology arises in this group of patients. TRIAL REGISTRATION:  NCT03111329- https://clinicaltrials.gov/ . Registered 06/04/2017. WHAT IS KNOWN: • Previous randomized trials have shown little benefit to the performance of routine assessment of gastric residuals in preterm infants. Despite this, they continue to be performed due to concerns from observational data regarding development of NEC. Meta-analysis to date has failed to answer the question regarding NEC. WHAT IS NEW: • In very low birth weight infants who are fed using modern feeding practice of faster feed advancement, to minimize use of central access and parenteral nutrition, exclusion of routine checks of gastric residuals did not increase the proportion of infants reaching full enteral feeds by day 5. No harm was seen when residual checks were not performed. • In the absence of a clinical benefit to the routine performance of gastric residuals in very low birth weight infants, it may be appropriate to discontinue their use and instead check residuals when clinical concern of pathology arises.

Thermochemistry of Species in Gas-Phase Thermal Oxidation of C2 to C8 Perfluorinated Carboxylic Acids.

New thermochemical properties, Cp°(T), H°(T), S°(T), and G°(T), are predicted for 123 species involved in the thermal destruction of perfluorinated carboxylic acids (PFCAs) using computational quantum chemistry and ideal-gas statistical mechanics. Relevant species were identified from the development of mechanisms for the pyrolysis and oxidation of PFCAs of C2 to C8 in length. Partition functions were obtained from the results of calculations at the G4 level for species up to C4 in length and M06-2X-D3(0)/def2-QZVPP for species C5 to C8 in length. The 1D hindered-rotor approximation was used to correct for torsional modes in the larger species. Ideal-gas thermochemistry was computed and fitted to 7-parameter NASA polynomials over a 200-2500 K temperature range, and the data are provided in standardized format. To gauge the effects of both method and basis set choice, enthalpies of formation at 0 K are calculated from various other density functionals (including B3LYP and ωB97XD), basis sets, and composite model chemistries (CBS-QB3). They are benchmarked against data from the Active Thermochemical Tables, high-level ANL0 calculations from the literature, and G4 calculations from this work. The effects of internal rotations and other anharmonicities are discussed, and bond dissociation energies and reaction equilibria provide mechanistic insights.

The association between calf birth weight and the postcalving performance of its dairy dam in the absence of dystocia.

The objective of the study was to quantify the association between the birth weight of a calf and the subsequent performance of its dairy dam in the absence of any recorded calving assistance. A total of 11,592 lactation records from 4,549 spring-calving dairy cows were used. The association between a series of quantitative cow performance metrics (dependent variable) and calf birth weight (independent variable) was determined using linear mixed models; logistic regression was used where the dependent variable was binary. Nuisance factors in the models were calf sex, heterosis coefficient of both the cow and calf, dry period length immediately before the birth of the calf, cow age at calving relative to the median cow age per parity, breed proportion of the cow, cow live weight between 100 and 200 d of lactation relative to the mean cow weight per parity, and contemporary group. Calf birth weight was included in the model as either a continuous or a categorical variable. Primiparous and multiparous cows were analyzed separately. Mean (SD) calf birth weight was 36.2 (6.8) kg. In primiparous cows, calf birth weight was associated with milk yield in the first 60 d of lactation, calving to first service interval, calving body weight (BW), and both nadir BW and body condition score (BCS). In multiparous cows, calf birth weight was associated with total milk, fat, and protein yield in the first 60 and 305 d of lactation, peak milk yield, total milk solids, both calving and nadir BW, and BCS loss from calving to nadir. Relative to primiparous cows that gave birth to calves weighing 34 to 37 kg (i.e., population mean), their contemporaries who gave birth to calves that weighed 15 to 29 kg produced 9.82 kg more milk in the first 60 d of lactation, had a 2-d shorter interval to first service, and were 8.08 kg and 5.51 kg lighter at calving and nadir BW, respectively; the former was also 0.05 units lower in BCS (5-point scale, 1 = emaciated and 5 = obese) at nadir. Relative to multiparous cows that gave birth to calves that were 34 to 37 kg birth weight, multiparous cows that gave birth to calves that were 15 to 29 kg yielded 59.63 kg, 2.44 kg, and 1.76 kg less milk, fat, and protein, respectively, in the first 60 d of lactation; produced 17.69 kg less milk solids throughout the 305-d lactation; and were also 10.49 kg lighter at nadir and lost 0.01 units more BCS to nadir. In a separate series of analyses, sire breed was added to the model as a fixed effect with and without calf birth weight. When calf birth weight was not adjusted for, 60-d milk yield for multiparous cows who gave birth to calves sired by a traditional beef breed (i.e., Angus, Hereford) produced 59.63 kg more milk than multiparous cows who gave birth to calves sired by a Holstein-Friesian. Hence, calf birth weight is associated with some subsequent dam performance measures; however, where associations do exist, the effect is biologically small.

A coded aperture with sub-mean free-path thickness for neutron implosion geometry imaging on inertial confinement fusion and inertial fusion energy experiments.

Inertial confinement fusion and inertial fusion energy experiments diagnose the geometry of the fusion region through imaging of the neutrons released through fusion reactions. Pinhole arrays typically used for such imaging require thick substrates to obtain high contrast along with a small pinhole diameter to obtain high resolution capability, resulting in pinholes that have large aspect ratios. This leads to expensive pinhole arrays that have small solid angles and are difficult to align. Here, we propose a coded aperture with scatter and partial attenuation (CASPA) for fusion neutron imaging that relaxes the thick substrate requirement for good image contrast. These coded apertures are expected to scale to larger solid angles and are easier to align without sacrificing imaging resolution or throughput. We use Monte Carlo simulations (Geant4) to explore a coded aperture design to measure neutron implosion asymmetries on fusion experiments at the National Ignition Facility (NIF) and discuss the viability of this technique, matching the current nominal resolution of 10 µm. The results show that a 10 mm thick tungsten CASPA can image NIF implosions with neutron yields above 1014 with quality comparable to unprocessed data from a current NIF neutron imaging aperture. This CASPA substrate is 20 times thinner than the current aperture arrays for fusion neutron imaging and less than one mean free-path of 14.1 MeV neutrons through the substrate. Since the resolution, solid angle, and throughput are decoupled in coded aperture imaging, the resolution and solid angle achievable with future designs will be limited primarily by manufacturing capability.

Defining metabolic flexibility in hair follicle stem cell induced squamous cell carcinoma.

Among the numerous changes associated with the transformation to cancer, cellular metabolism is one of the first discovered and most prominent[1, 2]. However, despite the knowledge that nearly every cancer is associated with the strong upregulation of various metabolic pathways, there has yet to be much clinical progress on the treatment of cancer by targeting a single metabolic enzyme directly[3-6]. We previously showed that inhibition of glycolysis through lactate dehydrogenase (LDHA) deletion in cancer cells of origin had no effect on the initiation or progression of cutaneous squamous cell carcinoma[7], suggesting that these cancers are metabolically flexible enough to produce the necessary metabolites required for sustained growth in the absence of glycolysis. Here we focused on glutaminolysis, another metabolic pathway frequently implicated as important for tumorigenesis in correlative studies. We genetically blocked glutaminolysis through glutaminase (GLS) deletion in cancer cells of origin, and found that this had little effect on tumorigenesis, similar to what we previously showed for blocking glycolysis. Tumors with genetic deletion of glutaminolysis instead upregulated lactate consumption and utilization for the TCA cycle, providing further evidence of metabolic flexibility. We also found that the metabolic flexibility observed upon inhibition of glycolysis or glutaminolysis is due to post-transcriptional changes in the levels of plasma membrane lactate and glutamine transporters. To define the limits of metabolic flexibility in cancer initiating hair follicle stem cells, we genetically blocked both glycolysis and glutaminolysis simultaneously and found that frank carcinoma was not compatible with abrogation of both of these carbon utilization pathways. These data point towards metabolic flexibility mediated by regulation of nutrient consumption, and suggest that treatment of cancer through metabolic manipulation will require multiple interventions on distinct pathways.

Measuring gut perfusion and blood flow in neonates using ultrasound Doppler of the superior mesenteric artery: a narrative review.

The gut is a relatively silent organ in utero but takes on a major role after birth for the absorption and digestion of feed for adequate nutrition and growth. The neonatal circulation undergoes a transition period after birth, and gut perfusion increases rapidly to satisfy the oxygen demand and consumption. If this process is compromised at any stage, preterm and fetal growth restricted infants are at particular risk of gut tissue injury secondary to hypoxia, leading to necrotizing enterocolitis. Feeding can also be a challenge in these high-risk groups due to gut dysmotility. Superior mesenteric artery (SMA) Doppler is a safe, bedside investigation that could rapidly aid clinicians with feeding strategies and in monitoring high-risk infants. This article aims to establish normal patterns of gut blood flow velocity in neonates using SMA Doppler and reviews how it might be used clinically in pathologic states.

Background levels of body fluids and DNA on the shaft of the penis and associated underpants in the absence of sexual activity.

This study examines the background of blood, saliva, semen and autosomal DNA on penile swabs and underpants from males in the absence of recent sexual activity. Based on the data collected by the AFSP Body Fluid Forum, the results of this study show that; there is a very low expectation of detecting blood on penile swabs and male underpants; a low expectation of detecting saliva on penile swabs and male underpants; and spermatozoa would be expected in less than a quarter of penile swabs and three quarters of male underpants. As none of the samples had detectable levels of DNA which were suitable for meaningful comparison that did not match the donor or their partner, the expectation of detecting a DNA profile from the cellular background on penile swabs or underpants from a male who has not been involved in recent sexual intercourse is very low. The results of this study are extremely informative when evaluating the significance of blood, saliva, semen and DNA detected on the penile swabs and underpants of males in cases of alleged sexual assault.

Inactivation kinetics of a surrogate yield conservative predictions of foodborne pathogen reductions from low water activity foods of varying size and composition during low-temperature steam processing.

There is a growing interest in using models to predict foodborne pathogen inactivation as a way to validate or verify preventive controls. Unlike liquid foods, solid, low water activity foods (LWAF) are heterogenous in composition and structure and do not transfer heat uniformly. Using models constructed from one food to predict pathogen inactivation on another LWAF is complex and may not always be possible, even if the foods have similar composition. Using models constructed from inactivation kinetics of three foodborne pathogens and a surrogate from vacuum-steam-pasteurized (72 and 82 °C) whole macadamia nuts and dried apricot halves, 3-log reductions were predicted for the same pathogens and foods of reduced size. Model fits (First-order, Weibull, and Gompertz) were significantly impacted by the food type regardless of particle size. Despite the foods being identical in composition with particle size as the only altered characteristic, best-fit models accurately predicted the 3-log reductions only 50% of the time, but the surrogate inactivation models provided conservative predictions for pathogen reductions, highlighting that a surrogate's model may be a suitable tool for predicting pathogen reduction on LWAFs.

Climate and human mortality in Virginia, 2005-2020.

Using an extensive database of every resident death in Virginia from 2005 to 2020, climate-mortality relationships are examined for 12 climatically homogeneous regions within the Commonwealth. Each region is represented by a first-order weather station from which archived temperature and humidity data are used to generate a variety of biometeorologically relevant indices. Using these indices and other variables (such as air quality and heat and cold waves), daily mortality and climate relationships are modeled for each region over a 21-day lag period utilizing generalized additive models and distributed lag non-linear models. Optimal models are identified for each region, and a consensus model was also run based on maximum temperature to facilitate inter-regional comparisons. The relative risk of mortality varies markedly as a function of climate between regions, with U-shaped, J-shaped, and inverse linear relationships evident. Cold mortality exceeds heat mortality across most of Virginia (typical relative risks are 1.10 for cold and 1.03 for heat), with cold risks strongest at lags 3 to 10. Low temperatures (or low humidity) are protective at lags 0-2 days except in the colder, western parts of state. Heat mortality occurs at short lags (0-2 days) for three-fourths of the stations, but the spatial pattern is random. Mortality displacement is evident for most regions for several days following the heat-related spike. Although the use of region-specific models is justified, the simple consensus model based on a consistent set of predictors provides similar results.

Oxylipin status, before and after LC n-3 PUFA supplementation, has little relationship with skeletal muscle biology in older adults at risk of sarcopenia.

INTRODUCTION: Oxylipins form endogenously via the oxygenation of long-chain polyunsaturated fatty acids (LC PUFA). Several oxylipins are highly bioactive molecules and are believed to be key mediators of LC PUFA metabolism in the body. However, little is known in relation to whether oxylipins mediate alterations in skeletal muscle mass and function. The objective of this study was to determine if a relationship exists between the oxylipin profile and skeletal muscle biology in healthy older adults at risk of sarcopenia and determine if this changes in response to LC n-3 PUFA supplementation. MATERIALS AND METHODS: This exploratory study investigated the baseline correlations between LC n-3, n-6 and n-9 PUFA-derived oxylipins and markers of muscle biology. For this, the concentration of 79 free (i.e., non-esterified) oxylipins was quantified in human plasma by liquid chromatography-mass spectrometry (LC-MS) and retrospectively correlated to phenotypic outcomes obtained pre-intervention from the NUTRIMAL study (n = 49). After examining the baseline relationship, the potential effect of supplementation (LC n-3 PUFA or an isoenergetic control made of high-oleic sunflower and corn oil) was evaluated by correlating the change in oxylipins concentration and the change in markers of skeletal muscle biology. The relationship between oxylipins pre- and post-intervention and their parent PUFA were also examined. RESULTS: At baseline, the hydroxy product of mead acid (n-9 PUFA), 5-HETrE, was negatively correlated to the phenotypic parameters appendicular lean mass index (ALMI) (p = 0.003, r=-0.41), skeletal muscle mass index (SMMI) (p = 0.001, r=-0.46), handgrip strength (HGS) (p<0.001, r = 0.48) and isometric knee extension (p<0.001, r=-0.48). Likewise, LC n-6 PUFA hydroxy­PUFA were negatively correlated to HGS (i.e., 12-HETrE, p = 0.002, r=-0.42, and 5- and 11-HETE, p = 0.006, r=-0.47 and p<0.001, r=-0.50 respectively), single leg stand time (i.e., 12-HETrE, p = 0.006, r=-0.39 and 16-HETE, p = 0.002, r=-0.43), and five-time-sit-to-stand test (FTST) performance (16-HETE, p = 0.006, r = 0.39), and positively correlated to gait speed (i.e., 12-HETrE, p = 0.007, r = 0.38 and 16-HETE, p = 0.006, r = 0.39). LC n-3 PUFA supplementation increased eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derived oxylipins and reduced n-6 PUFA derived oxylipins. Parameters of skeletal muscle mass and strength were not significantly altered in either LC n-3 PUFA or placebo groups. Changes in plasma oxylipins concentrations were closely related to changes in their parent PUFA, assessed in the erythrocyte membrane, but were not associated with any changes in skeletal muscle parameters. DISCUSSION AND CONCLUSION: At baseline, the status n-9 (5-HETrE) and n-6 PUFA derivates [12-HETrE, and 5-, 11- and 16-HETE], but not n-3 PUFA derived oxylipins, were associated with poor skeletal muscle health parameters (i.e., mass and strength). However, these correlations were no longer present when correlating relative changes from pre to post timepoints. An independent cohort validation is needed to explore baseline correlations further. Further research is warranted to assess other biological mechanisms by which LC n-3 PUFA might affect muscle biology.

Relationship between clinical parameters and quality of life in primary Sjögren's Syndrome: a prospective study.

OBJECTIVES: To quantify the impact of dry eye disease (DED) on health and vision related quality of life (HR-QOL, VR-QOL) in patients with Primary Sjögren's Syndrome (pSS). METHODS: Thirty-four participants with a confirmed diagnosis of pSS as per the 2016 ACR EULAR criteria participated. Main outcome measures included ocular surface parameters and HR-QOL and VR-QOL questionnaires. Clinical examination included visual acuity, Schirmer I testing, ocular surface staining (OSS) and measurement of tear film breakup time. The questionnaires included Ocular Surface Disease Index, National Eye Institute Visual Function Questionnaire-25, Short Form-36 (SF-36) and EULAR Sjogren's Syndrome Patient Reported Index. RESULTS: Despite the majority of participants (28 female, 6 male, mean age 61.3 years) having attained LogMAR 0.3 or better visual acuity, participants scored low on VR-QOL measures, representing DED related fluctuation in functional vision. All participants suffered from moderate to severe DED. OSS did not correlate with DED symptoms or QOL parameters. Lubricant usage and symptom severity had a statistically moderate to strong negative correlation with VR-QOL and HR-QOL. This was most evident in relation to physical and physiological wellbeing. Compared with normative data, participants had a lower HR-QOL in all scales of the SF-36 ((MD = 9.91 ± 5.16); t(7) = 5.43, p = 0.001). CONCLUSIONS: Participants with pSS have a lower perceived QOL especially in relation to physical and mental wellbeing, correlating to severity of DED symptoms and treatment burden. Clinical signs do not align with symptoms. Therefore, clinicians should remain cognisant, adjusting treatment in accordance with patient reported perceptions.

The TGM2 inhibitor cysteamine hydrochloride does not impact corneal epithelial and stromal wound healing in vitro and in vivo.

Corneal wound healing is integral for resolution of corneal disease or for post-operative healing. However, corneal scarring that may occur secondary to this process can significantly impair vision. Tissue transglutaminase 2 (TGM2) inhibition has shown promising antifibrotic effects and thus holds promise to prevent or treat corneal scarring. The commercially available ocular solution for treatment of ocular manifestations of Cystinosis, Cystaran®, contains the TGM2 inhibitor cysteamine hydrochloride (CH). The purpose of this study is to assess the safety of CH on corneal epithelial and stromal wounds, its effects on corneal wound healing, and its efficacy against corneal scarring following wounding. Quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC) were first used to quantify and localize TGM2 expression in the cornea. Subsequently, (i) the in vitro effects of CH at 0.163, 1.63, and 16.3 mM on corneal epithelial cell migration was assessed with an epithelial cell migration assay, and (ii) the in vivo effects of application of 1.63 mM CH on epithelial and stromal wounds was assessed in a rabbit model with ophthalmic examinations, inflammation scoring, color and fluorescein imaging, optical coherence tomography (OCT), and confocal biomicroscopy. Post-mortem assessment of corneal tissue post-stromal wounding included biomechanical characterization (atomic force microscopy (AFM)), histology (H&E staining), and determining incidence of myofibroblasts (immunostaining against α-SMA) in wounded corneal tissue. TGM2 expression was highest in corneal epithelial cells. Application of the TGM2 inhibitor CH did not affect in vitro epithelial cell migration at the two lower concentrations tested. At 16.3 mM, decreased cell migration was observed. In vivo application of CH at 57 mM was well tolerated and did not adversely affect wound healing. No difference in corneal scarring was found between CH treated and vehicle control eyes. This study shows that the TGM2 inhibitor CH, at the FDA-approved dose, is well tolerated in a rabbit model of corneal wound healing and does not adversely affect epithelial or stromal wound healing. This supports the safe use of this medication in Cystinosis patients with open corneal wounds. CH did not have an effect on corneal scarring in this study, suggesting that Cystaran® administration to patients with corneal wounds is unlikely to decrease corneal fibrosis.

The evolution of the medical record from paper to digital: an ENT perspective.

OBJECTIVES: A national electronic health record is being procured for Health Service Executive hospitals in Ireland. A number of hospitals have implemented an electronic document management system. This study aimed to investigate the efficiency and safety of the electronic document management system in our centre. METHODS: A retrospective audit was performed of patients operated on at Galway University Hospital. The availability and location of patients' admission data on the electronic document management system were recorded. These data were analysed using Microsoft Excel software, version 16.45. RESULTS: The records of 100 patients were analysed. The main findings were: 5 per cent of operation notes were missing, 80 per cent were in the incorrect section, while 15 per cent were in the correct 'procedure' section on the electronic document management system. CONCLUSION: This study shows there is potential for error with 'paper-light' solutions, whereby delayed scanning, misfiling of scanned records and missing records may lead to significant delays in treatment and potential patient safety issues.

Birmingham hip resurfacing: a systematic review of outcomes at minimum 10-years follow-up.

Although controversy surrounding the use of metal-on-metal (MoM) arthroplasty implants continues to exist, satisfactory clinical and radiological outcomes have been reported following Birmingham Hip Resurfacing (BHR) at long-term follow-up, leading to an Orthopaedic Data Evaluation Panel (ODEP) rating of 13A. The purpose of this study was to systematically review the literature to evaluate the functional outcomes, radiological outcomes and revision rates following BHR at a minimum of 10 years follow-up. Using the PRISMA guidelines, two independent reviewers performed a literature search using Pubmed, Embase and Scopus databases. Only studies reporting on outcomes of BHR with a minimum of 10 years' follow-up were considered for inclusion. A total of 12 studies including 7132 hips (64.8% males), with mean follow-up of 11.5 years (10-15.3), met our inclusion criteria. Of included patients, 94.3% of patient underwent BHR for osteoarthritis at a mean age was 52.0 years (48-52). At final follow-up, 96% of patients reported being satisfied with their BHR, with mean Harris Hip Scores of 93.6 and Oxford Hip Scores of 16.5. Rates of radiological femoral neck narrowing of greater than 10% and non-progressive radiological loosening were reported as 2.0% and 3.8% respectively. At final follow-up, the overall revision rate was 4.9% (334/7132), deep infection rate was 0.4%, metal allergy/insensitivity rate was 1.6%, metal reaction rate was 0.3%, rate of peri-prosthetic fracture was 0.9% and aseptic loosening rates were 1.6%. This systematic review demonstrates that BHR results in satisfactory clinical outcomes, acceptable implant survivorship, low complication rates and modest surgical revision rates in the long-term at minimum 10-year follow-up.