Machine learning-driven clinical decision support system for concept-based searching: a field trial in a Norwegian hospital.

BACKGROUND: Natural language processing (NLP) based clinical decision support systems (CDSSs) have demonstrated the ability to extract vital information from patient electronic health records (EHRs) to facilitate important decision support tasks. While obtaining accurate, medical domain interpretable results is crucial, it is demanding because real-world EHRs contain many inconsistencies and inaccuracies. Further, testing of such machine learning-based systems in clinical practice has received limited attention and are yet to be accepted by clinicians for regular use. METHODS: We present our results from the evaluation of an NLP-driven CDSS developed and implemented in a Norwegian Hospital. The system incorporates unsupervised and supervised machine learning combined with rule-based algorithms for clinical concept-based searching to identify and classify allergies of concern for anesthesia and intensive care. The system also implements a semi-supervised machine learning approach to automatically annotate medical concepts in the narrative. RESULTS: Evaluation of system adoption was performed by a mixed methods approach applying The Unified Theory of Acceptance and Use of Technology (UTAUT) as a theoretical lens. Most of the respondents demonstrated a high degree of system acceptance and expressed a positive attitude towards the system in general and intention to use the system in the future. Increased detection of patient allergies, and thus improved quality of practice and patient safety during surgery or ICU stays, was perceived as the most important advantage of the system. CONCLUSIONS: Our combined machine learning and rule-based approach benefits system performance, efficiency, and interpretability. The results demonstrate that the proposed CDSS increases detection of patient allergies, and that the system received high-level acceptance by the clinicians using it. Useful recommendations for further system improvements and implementation initiatives are reducing the quantity of alarms, expansion of the system to include more clinical concepts, closer EHR system integration, and more workstations available at point of care.

Dietary Level of the Omega-3 Fatty Acids EPA and DHA Influence the Flesh Pigmentation in Atlantic Salmon.

Atlantic salmon with a start weight of 53 g were fed diets with different levels of EPA and DHA or a diet with 1 : 1 EPA+DHA (0%, 1.0%, and 2.0% of the diet). At 400 g, all fish groups were mixed and equally distributed in new tanks and fed three diets with 0.2%, 1.0%, or 1.7% of EPA+DHA. At 1200 g, the fish were transferred to seawater pens where they were fed the same three diets until they reached a slaughter size of 3.5 kg. The fillet concentration of astaxanthin and its metabolite idoxanthin was analysed before transfer to seawater pens at 1200 g and at slaughter. The fatty acid composition in the fillet was also analysed at the same time points. Salmon fed low levels of EPA and DHA had lower fillet astaxanthin concentration and higher metabolic conversion of astaxanthin to idoxanthin compared to salmon fed higher dietary levels of EPA and/or DHA. DHA had a more positive effect on fillet astaxanthin concentrations than EPA. There were positive correlations between fillet DHA, EPA, sum N-3 fatty acids, and fillet astaxanthin concentration. A negative correlation was found between the concentration of N-6 fatty acids in the fillet and the astaxanthin concentration.

Callisto: disk temperature at 3.71-centimeter wavelength.

We observed the radio emission of Callisto with a three-element interferometer at the time of the 1973 opposition of Jupiter. Special care was taken to remove the residual, unresolved contribution from Jupiter itself in the antenna side lobes. The resulting disk temperature at a wavelength of 3.71 centimeters, assuming a radius of 2500+/-75 kilometers for Callisto, was 101 degrees +/-25 degrees K. This temperature is much more consistent with emission from a simple dielectric sphere than the considerably higher temnperatures that have been reported for wavelengths of 3.5 and 8.2 millimeters.

High-resolution microwave images of saturn.

An analysis of high-resolution microwave images of Saturn and Saturn's individual rings is presented. Radio interferometric observations of Saturn taken at the Very Large Array in New Mexico at wavelengths of 2 and 6 centimeters reveal interesting new features in both the atmosphere and rings. The resulting maps show an increase in brightness temperature of about 3 K from equator to pole at both wavelengths, while the 6-centimeter map shows a bright band at northern mid-latitudes. The data are consistent with a radiative transfer model of the atmosphere that constrains the well-mixed, fully saturated, NH(3) mixing ratio to be 1.2 x 10(-4) in a region just below the NH(3) clouds, while the observed bright band indicates a 25 percent relative decrease of NH(3) in northern mid-latitudes. Brightness temperatures for the classical rings are presented. Ring brightness shows a variation with azimuth and is linearly polarized at an average value of about 5 percent. The variations in ring polarization suggest that at least 20 percent of the ring brightness is the result of a single scattering process.

Uranus: microwave images.

Observations of Uranus at wavelengths of 2 and 6 centimeters with the Very Large Array were made in 1980 and 1981. The resulting maps of brightness temperature show a subsolar symmetry at 2 centimeters but a near-polar symmetry at 6 centimeters. The 6-centimeter maps show an increase in temperature from equator to pole with some evidence for a warm "ring" surrounding the north pole. The disk-average temperatures (147 +/- 5 K and 230 +/- 6 K at 2 and 6 centimeters, respectively) are distinctly lower than recently reported values; these results suggest that the secular increase in temperature reported during the last 15 years has been reversed. The variations in brightness temperature probably reflect variations in ammonia abundance in the planet's atmosphere, but the mechanism driving these variations is still unclear.

Microwave measurements of carbon monoxide on titan.

The ratio of the flux density of Titan was measured in two 200-megahertz bands, one centered on the (1-0) rotation line of carbon monoxide at 115.3 gigahertz and the other 2600 megahertz lower. The measurements were made with a complex-correlation technique on the new millimeter-wavelength interferometer at the Owens Valley Radio Observatory, Big Pine, California. The excess flux in the carbon monoxide band is interpreted as a strong detection of carbon monoxide and a mixing ratio, assumed constant, of 6 x 10(-5). The brightness temperature of Titan at 112.6 gigahertz is 69 +/- 10 kelvins, consistent with atmospheric emission from just below the tropopause.

Design and synthesis of potent bradykinin agonists containing a benzothiazepine moiety.

A bradykinin analogue (H-Arg-Pro-Pro-Gly-Phe-Ser-D-BT-Arg-OH, 3) in which the Pro-Phe dipeptide was replaced by the (3S)[amino]-5-(carbonylmethyl)-2,3-dihydro-1, 5-benzothiazepin-4(5H)-one (D-BT) moiety has been synthesized. The same modification was performed on the potent bradykinin B(2) receptor antagonist HOE 140 (H-D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Tic-Oic-Arg-OH), in which the -D-Tic-Oic- moiety was replaced by D-BT to yield H-D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-BT-Arg-OH, 1 (JMV1116). These compounds were examined in vitro for their binding affinity toward bradykinin B(1) and B(2) receptors as well as for their ability to interfere with bradykinin-induced contraction of both human umbilical vein and rat uterus. The two compounds 3 and 1 competed with [(3)H]bradykinin binding to the human cloned B(2) receptor giving K(i) values of 13 +/- 2 and 0.7 +/- 0.1 nM, respectively. Unexpectedly, both compounds were full bradykinin B(2) receptor agonists on the human umbilical vein (pD(2) = 6.60 +/- 0.07 for 3 and 6.80 +/- 0.08 for 1) and rat uterus (pD(2) = 7.20 +/- 0.09 for 3 and 7.50 +/- 0.09 for 1) preparations with the same efficacy as bradykinin. In addition 1 induced a concentration-dependent phosphoinositide production in CHO cells expressing the human cloned B(2) receptor. These data provide evidence for a bioactive conformation of bradykinin constrained at the dipeptide Pro-Phe.

Synthesis and characterization of bradykinin B(2) receptor agonists containing constrained dipeptide mimics.

We have previously shown that substitution of the D-Tic-Oic dipeptide by a (3S)-[amino]-5-(carbonylmethyl)-2,3-dihydro-1, 5-benzothiazepin-4(5H)-one (D-BT) moiety in the bradykinin B(2) receptor antagonist HOE 140 resulted in a full potent and selective bradykinin B(2) receptor agonist (H-DArg-Arg-Pro-Hyp-Gly-Thi-Ser-D-BT-Arg-OH, JMV1116) exhibiting a high affinity for the human receptor (K(i) 0.7 nM). In the present study, we have investigated the effects of replacement of the D-Tic-Oic moiety by various constrained dipeptide mimetics. The resulting compounds were tested for their binding affinity toward the cloned human B(2) receptor and for their functional interaction with the bradykinin-induced contraction of isolated human umbilical vein. Subsequently, we have designed novel bradykinin B(2) receptor agonists which are likely to be resistant to enzymatic cleavage by endopeptidases and which might represent interesting new pharmacological tools. In an attempt to increase the potency of compound JMV1116, both its N-terminal part and the D-BT moiety were modified. Substitution of the D-arginine residue by a L-lysine residue led to a 10-fold more potent bradykinin B(2) ligand [compound 22 (JMV1465) (K(i) 0.07 nM)], retaining full agonist activity on human umbilical vein. Substitution of the D-BT moiety by a (3S)-[amino]-5-(carbonylmethyl)-2,3-dihydro-8-methyl-1, 5-benzothiazepin-4(5H)-one [D-BT(Me)] moiety led to compound 23 (JMV1609) which exhibited a higher agonist activity (pD(2) = 7.4) than JMV1116 (pD(2) = 6.8).

Degradation kinetics in aqueous solution of cefotaxime sodium, a third-generation cephalosporin.

The degradation kinetics of a 3- acetoxymethylcephalosporin , cefotaxime sodium salt, in aqueous solution investigated by HPLC under different conditions (pH, ionic strength, temperature) and using different buffers. The scheme of degradation involves a cleavage of the beta-lactam nucleus and the deacetylation of the side chain. In highly acidic medium, the deacetylated derivative is easily converted to the lactone. The degradation rate constants were calculated at three pH values (1.9, 4.0, and 9.0) by measuring the residual cephalosporin and the main decomposition products. The degradation pathway is both supported by the results of a primary salt effect and by the agreement between the theoretical pH-rate profile and the experimental values. In the pH range from 3.0 to 7.0, the main process is a slow water-catalyzed or spontaneous cleavage of the beta-lactam nucleus with intramolecular participation of the side chain amido fraction in the 7-position. In alkaline or strongly acidic medium, the hydrolysis is a base- or acid-catalyzed reaction. Of the buffer systems investigated, carbonate buffer (pH 8.5) and borate buffers (pH 9.5 and 10.0) are found to increase the degradation rates, while acetate buffer decreases the degradation rates. The apparent activation energies determined at different pH values are compatible with a solvolysis mechanism and similar to those previously given in the literature for other cephalosporins. Cefotaxime in aqueous solution is slightly less stable than the main cephalosporin derivatives, despite its high resistance to the beta-lactamases and its remarkable biological activity.

Overlapping ionization constants for cefotaxime.

The attribution of three ionization constants (2.1, 3.4, and 10.9) for cefotaxime has been made, based on potentiometric titration and UV absorption data simultaneously. Two overlapping constants were found (2.1 and 3.4) and attributed to the carboxyl group in the 4 position and to the aminothiazole nucleus, respectively.

Physicochemical and structural study of sulfamethazine.

We have shown by several physicochemical methods that the existence of different crystal habits for a given molecule does not necessarily imply polymorphism. For sulfamethazine, we found one polymorph, form 1, whose crystalline structure is published herein, and a methanol solvate.

Apparent digestibility coefficients and accumulation of astaxanthin E/Z isomers in Atlantic salmon (Salmo salar L.) and Atlantic halibut (Hippoglossus hippoglossus L.).

Apparent astaxanthin (3,3'-dihydroxy-beta,beta-carotene-4,4'-dione) digestibility coefficients (ADC) and carotenoid compositions of the muscle, liver, whole kidney and plasma were compared in Atlantic salmon (Salmo salar) and Atlantic halibut (Hippoglossus hippoglossus) fed a diet supplemented with 66 mg astaxanthin kg(-1) dry matter for 112 days. The astaxanthin source consisted of 75% all-E-, 3% 9Z- and 22% 13Z-astaxanthin, of (3R,3'R)-, (3R,3'S; meso)-, and (3S,3'S)-astaxanthin in a 1:2:1 ratio. The ADC of astaxanthin was significantly higher in Atlantic halibut than in Atlantic salmon after 56 and 112 days of feeding (P < 0.05). The ADC of all-E-astaxanthin was significantly higher than ADC of 9Z-astaxanthin (P < 0.05). Considerably more carotenoids were present in all plasma and tissue samples of salmon than in halibut. Retention of astaxanthin in salmon muscle was 3.9% in salmon and 0 in halibut. All-E-astaxanthin accumulated selectively in the muscle of salmon, and in plasma of salmon and halibut compared with diet. 13Z-astaxanthin accumulated selectively in liver and whole kidney of salmon and halibut, when compared with plasma. A reductive pathway for astaxanthin metabolism in halibut similar to that of salmon was shown by the presence of 3',4'-cis and trans glycolic isomers of idoxanthin (3,3',4'-trihydroxy-beta,beta-carotene-4'-one) in plasma, liver and whole kidney. In conclusion, the higher ADC of astaxanthin in halibut than Atlantic salmon may be explained by lower feed intake in halibut, and the lower retention of astaxanthin by a higher capacity to transform astaxanthin metabolically.

Synthesis and biological activities of some human gastrin analogs.

The synthesis of analogs of the C-terminal tridecapeptide of gastrin is described. These pseudopeptide analogs were obtained either by replacing the C-terminal phenylalanine amide with 2-phenylethylalcohol or with 2-phenylethylamine, or by replacing the peptide bond between Trp and Leu, or between Leu and Asp with an aminomethylene (CH2NH). The ability of these compounds to stimulate gastric acid secretion in anesthetized rats and to inhibit binding of labeled CCK-8 to isolated cells from rabbit fundic mucosa was tested. [desPhe13, Leu11]-HG-12-I-beta-phenylethylester 33, [desPhe13, Leu11]-HG-12-II-beta-phenylethylester 38, [desPhe13, Leu11]-HG-12-I-beta-phenylethylamide 32, and [desPhe13, Leu11]-HG-12-II-beta-phenylethylamide 37 acted as gastrin receptor antagonists, while [Trp10-psi(CH2NH)-Leu11]-HG-13-I 31 and [Trp10-psi(CH2NH)-Leu11]-HG-13-II 36 acted as agonists. Unexpectedly, [Leu11-psi(CH2NH)-Asp12]-HG-13-I 30 and [Leu11-psi (CH2NH)-Asp12]-HG-13-II 35 were almost devoid of affinity for the gastrin receptor.

Plasma ascorbic acid concentrations in healthy dogs.

Using a highly sensitive and selective analytical method and careful stability control, plasma concentrations of ascorbic acid were determined in German Shepherd Dogs, Labrador Retrievers and Siberian Huskies, a total 99 animals. Mean concentration was 35.9 micromol l(-1)(range 18.2-50.7), and no significant variation was observed neither between breeds nor between females and males. These and previous reported data on plasma ascorbic acid levels in dogs are discussed in the light of methodological aspects.

Pharmacokinetics in dogs after oral administration of two different forms of ascorbic acid.

The dog is able to synthesise ascorbic acid (AA), but is frequently given the vitamin in an attempt to improve health and performance. The pharmacokinetics of AA in this species, however, are not well studied. Using a selective analytical method and careful stability control, the pharmacokinetics of orally given AA was studied in 20 dogs, at two dosage levels (15 and 50 mg kg(-1)) and with two forms of supplement [crystalline AA and the vitamin C product Ester-C(Inter-Cal Corp., Prescott, AZ, USA)]. After oral administration, a rapid increase was found in the plasma level of AA, indicating a possible intestinal active transport mechanism in this species. The obtained C(max)and AUC values were found to increase in a non-linear fashion when the dose of AA was increased. The pharmacokinetic modeling of the elimination of AA was made difficult by a pronounced secondary peak appearing after about 9 hours. The comparison of crystalline AA and Ester-C did not indicate any significant differences in pharmacokinetic parameters between the two preparations of the vitamin.

Influence of bacitracin on microbial functions in the gastrointestinal tract of horses.

This study investigated the influence of zinc bacitracin on the intestinal flora of horses. The functionally active intestinal flora was examined in 6 horses during treatment with zinc bacitracin. Utilising gas chromatography, spectrophotometry, gel electrophoresis and paper chromatography, samples were analysed on biochemical markers reflecting the action of parts of the intestinal flora. The following 5 flora-related functions were studied in faecal samples and intestinal samples from different sections of the hindgut: conversion of cholesterol to coprostanol and of bilirubin to urobilinogens, degradation of mucin and of beta-aspartylglycine and inactivation of tryptic activity. Conversion to coprostanol, conversion to urobilinogens and degradation of mucin were affected by treatment of zinc bacitracin and conversion to coprostanol was most sensitive. All functions were normalised in a short time, in contrast to man and rats. Differences in environmental exposures are probably the reason for a more rapid normalisation of the intestinal flora functions in horses.

Individual degradation rate constants for cefotaxime, deacetylation profile.

The individual degradation rate constants for cefotaxime in aqueous solution were calculated within a pH range of 1.6-10.0 at 37 degrees C from high performance liquid chromatography data. This allowed the general degradation profile of cefotaxime to be decomposed into a degradation profile attributed to the opening of the beta-lactam nucleus and a degradation profile attributed to the deacetylation. From the calculations of the individual rate constants, the activity of degraded cefotaxime solutions could be predicted. In the pH range of injectable solutions of cefotaxime 5-7, roughly equivalent amounts of inactive beta-lactam cleavage products and deacetylated compound which has a different spectrum of antibacterial activity are formed.

Influence of zinc bacitracin and Bacillus licheniformis on microbial intestinal functions in weaned piglets.

The influence of zinc bacitracin (ZB) and of Bacillus licheniformis on host microbial-related functions in young piglets was investigated by applying the concept of microflora-associated characteristics. Six biochemical parameters were determined before and after weaning in faecal samples from piglets in four litters having access to a diet containing ZB, to a diet containing B. licheniformis, to a diet with both additives, or to a diet with no additives, from 3 weeks of age. Statistically significant differences were found in three of the intestinal functions investigated: formation of short-chain fatty acids (at 7 and 10 weeks of age). degradation of mucin (at 7 and 10 weeks of age) and conversion of bilirubin to urobilins (at 7 weeks of age). We also found age-dependent influences on the formation of short-chain fatty acids, on conversion of cholesterol to coprostanol and on conversion of bilirubin to urobilins. We conclude that a functional approach is appropriate for measuring exogenous influence(s) on the microbial intestinal metabolisms in weaned piglets.

[Cutaneous signs of Noonan's syndrome. Apropos of a case with ulerythema ophyogenes, disseminated pilar and sudoral keratosis and progressive alopecia]. / Les signes cutanés du syndrome de Noonan. A propos d'une observation avec ulérythème ophryogène, kératose pilaire et sudorale disséminée et alopécie progressive.

A case of typical Noonan syndrome (NS) with eye abnormalities, pterygium colli, cryptorchid testes, lymphoedema and asymmetrical cardiac septal hypertrophy is reported in a 8-month old infant. This case was particularly interesting since it included skin manifestations which enabled an early diagnosis to be made. Ulerythema ophryogenes has already been proposed as a cutaneous marker of NS, but the keratinization disorders in our patient also included disseminated keratosis of both hair follicles and sweat glands orifices. Abnormally brittle short curly hair has already been reported, but our patient exhibited progressive alopecia which is very rare in NS. Biochemical hair analysis did not show any abnormalities of aminoacids. All these features were suggestive of keratosis follicularis spinulosa decalvans. It therefore seems very likely that NS is associated with keratinization disorders but ulerythema ophryogenes might only be the limited form of these disorders. The other skin manifestations of NS are reviewed. Since the patient had 4 "café au lait" spots, the relation of NS with Von Recklinghausen syndrome, and neurofibromatosis-Noonan syndrome is discussed. Watson's Leopard and cardio-facial syndromes overlap with, and may represent subsets of NS.

[Antifungal activity of 5-benzilidene pyrrolone and furanone derivatives]. / Activité antifongique de dérivés benzilidène-5 pyrrolones et furannones.

The antifungal activity against Neurospora crassa of some 5-benzilidene pyrrolone and furanone derivatives was realised. Relations between the structure and this biological activity are established with Fujita-Ban and Hansch methods. The preponderant part of lipophilicity, resonance effect and E or Z configurations have been showed.