Validation, comparison, and combination of algorithms for automatic detection of pulmonary nodules in computed tomography images: The LUNA16 challenge

Automatic detection of pulmonary nodules in thoracic computed tomography (CT) scans has been an active area of research for the last two decades. However, there have only been few studies that provide a comparative performance evaluation of different systems on a common database. We have therefore set up the LUNA16 challenge, an objective evaluation framework for automatic nodule detection algorithms using the largest publicly available reference database of chest CT scans, the LIDC-IDRI data set. In LUNA16, participants develop their algorithm and upload their predictions on 888 CT scans in one of the two tracks: 1) the complete nodule detection track where a complete CAD system should be developed, or 2) the false positive reduction track where a provided set of nodule candidates should be classified. This paper describes the setup of LUNA16 and presents the results of the challenge so far. Moreover, the impact of combining individual systems on the detection performance was also investigated. It was observed that the leading solutions employed convolutional networks and used the provided set of nodule candidates. The combination of these solutions achieved an excellent sensitivity of over 95% at fewer than 1.0 false positives per scan. This highlights the potential of combining algorithms to improve the detection performance. Our observer study with four expert readers has shown that the best system detects nodules that were missed by expert readers who originally annotated the LIDC-IDRI data. We released this set of additional nodules for further development of CAD systems

Иммунно-нейроэндокринные взаимосвязи в развитии перименопаузальной патологии

Представлен современный патогенетический взгляд на происходящие в перименопаузальном периоде системные нарушения. Показано, что имунно-нейроэндокринный гомеостаз имеет определенные отличия в зависимости от клинической формы и степени тяжести перименопаузальных нарушений, что необходимо учитывать при проведении терапевтических мероприятий.Представлено сучасний патогенетичний погляд на системні порушення, що відбуваються в перименопаузальному періоді. Показано, що імунно-нейроендокринний гомеостаз має певні відмінності залежно від клінічної форми і ступеня тяжкості перименопаузальних порушень, що необхідно враховувати під час проведення терапевтичних заходів.A modern pathogenetic opinion about the systemic perimenopausal disorders is presented. It is shown that immunoneuroendocrine homeostatsis differs depending on the clinical form and degree of severity of perimenopausal disorders, which should be taken into consideration when taking therapeutic measures

Clinical practice. Diagnosis and treatment of cow’s milk allergy

Introduction Cow's milk allergy (CMA) is thought to affect 2-3% of infants. The signs and symptoms are nonspecific and may be difficult to objectify, and as the diagnosis requires cow's milk elimination followed by challenge, often, children are considered cow's milk allergic without proven diagnosis. Diagnosis Because of the consequences, a correct diagnosis of CMA is pivotal. Open challenges tend to overestimate the number of children with CMA. The only reliable way to diagnose CMA is by double-blind, placebo-controlled challenge (DBPCFC). Therapy At present, the only proven treatment consists of elimination of cow's milk protein from the child's diet and the introduction of formulas based on extensively hydrolysed whey protein or casein; amino acid-based formula is rarely indicated. The majority of children will regain tolerance to cow's milk within the first 5 years of life. Conclusions Open challenges can be used to reject CMA, but for adequate diagnosis, DBPCFC is mandatory. In most children, CMA can be adequately treated with extensively hydrolysed whey protein or casein formulas

Fetal and infant origins of asthma

Previous studies have suggested that asthma, like other common diseases, has at least part of its origin early in life. Low birth weight has been shown to be associated with increased risks of asthma, chronic obstructive airway disease, and impaired lung function in adults, and increased risks of respiratory symptoms in early childhood. The developmental plasticity hypothesis suggests that the associations between low birth weight and diseases in later life are explained by adaptation mechanisms in fetal life and infancy in response to various adverse exposures. Various pathways leading from adverse fetal and infant exposures to growth adaptations and respiratory health outcomes have been studied, including fetal and early infant growth patterns, maternal smoking and diet, children’s diet, respiratory tract infections and acetaminophen use, and genetic susceptibility. Still, the specific adverse exposures in fetal and early postnatal life leading to respiratory disease in adult life are not yet fully understood. Current studies suggest that both environmental and genetic factors in various periods of life, and their epigenetic mechanisms may underlie the complex associations of low birth weight with respiratory disease in later life. New well-designed epidemiological studies are needed to identify the specific underlying mechanisms. This review is focused on specific adverse fetal and infant growth patterns and exposures, genetic susceptibility, possible respiratory adaptations and perspectives for new studies

Operant learning and differential-reinforcement-of-low-rate 36-s responding in 5-HT1A and 5-HT1B receptor knockout mice.

Previous studies with mice lacking 5-HT(1A) (1AKO) and 5-HT(1B) (1BKO) receptors in hippocampus-dependent learning and memory paradigms, suggest that these receptors play an important role in learning and memory, although their precise role is unclear. In the present study, 1AKO and 1BKO mice were studied in operant behavioural paradigms of decision making and response inhibition, to further study the putative involvement of these receptors in prefrontal cortex-dependent learning and memory. Moreover, because 1AKO mice have been shown to exhibit an antidepressant-like phenotype and 1BKO mice to be more impulsive in ethological studies, mice were trained in a differential-reinforcement-of-low-rates (DRL) procedure. Overall, results indicate that 1AKO and 1BKO mice display subtle differences in operant paradigms of decision making and response inhibition compared to wild type (WT) mice. In addition, when responding under a DRL 36-s schedule had stabilised, 1BKO mice showed a phenotype indicative of increased impulsivity, whereas 1AKO mice did not differ from WT mice. In conclusion, 5-HT(1B) receptors appear to play an important role in impulsivity and a minor role in prefrontal cortex-dependent learning and memory as shown by the results obtained in serial reversal learning and extinction. In contrast, 5-HT(1A) receptors appear to be involved in facilitation of autoshaping, but their role in impulsivity and prefrontal cortex-dependent learning and memory appears to be limited

GABA(A)-benzodiazepine receptor complex sensitivity in 5-HT(1A) receptor knockout mice on a 129/Sv background.

Item does not contain fulltextPrevious studies in 5-HT(1A) receptor knockout (1AKO) mice on a mixed Swiss Websterx129/Sv (SWx129/Sv) and a pure 129/Sv genetic background suggest a differential gamma-aminobutyric acid (GABA(A))-benzodiazepine receptor complex sensitivity in both strains, independent from the anxious phenotype. To further investigate these discrepancies, various GABA(A)-benzodiazepine receptor ligands were tested in different behavioral paradigms in 1AKO and wild type (WT) mice on a 129/Sv background. 1AKO and WT mice responded comparably to alprazolam, flumazenil, alcohol and pentylenetetrazol as measured in the stress-induced hyperthermia paradigm. In addition, sedative-anesthetic effects of pentobarbital measured via the righting reflex were similar and a selected dose of diazepam exerted similar anxiolytic effects in both genotypes in the elevated plus maze. In conclusion, 1AKO mice on a 129/Sv background have undisturbed GABA(A)-benzodiazepine receptor sensitivity in contrast to those described on a mixed Swiss Websterx129/Sv background. The anxious phenotype of 1AKO mice seems to occur independent of the GABA(A)-benzodiazepine receptor complex functioning

Progesterone and the control of functional luteolysis, of secretion of prolactin and of pituitary LHRH responsiveness. A study with pseudopregnant rats kept in alternating and constant lighting conditions

The effect of exogenous progesterone (P) on the corpus luteum function (in terms of the secretion of P and 20-α-dihydroprogesterone (DHP), on the secretion of prolactin (Prl) and on the pituitary responsiveness to LHRH was studied in pseudopregnant (PSP) rats kept in alternating and constant lighting conditions (LD-PSP and LL-PSP rats, respectively). Rats were rendered pseudopregnant by appropriately timed stimulation of the cervix uteri (LL rats first received an ovulatory dose of hCG). LH responses were induced by constant rate infusion of LHRH (104 ng/hfor 21 h). P was delivered by subcutaneously inserted Silastic implants; control rats received sham implants. In both LD- and LL-PSP rats the plasma P and DHP levels were high on day 8 of PSP. On day 12, however, the plasma P levels had fallen but the DHP levels had risen, demonstrating that between days 8 and 12 functional luteolysis had occurred and that neither the production of P and DHP, nor the timing of luteolysis are under the control of the lighting conditions. On day 12 of PSP the pituitary responsiveness to LHRH was much higher than on day 8. Moreover, on days 8/9 of PSP peaks of Prl were seen in all rats, but on days 11/12 such peaks were largely absent. In LD-PSP rats ‘nocturnal’ Prl peaks were seen on days 8/9 in all 9 experimental animals, but ‘diurnal’ peaks were seen in only 4 of these animals. Also, the diurnal peaks were on average much lower than the nocturnal peaks. In LL-PSP rats we saw on days 8/9 over 24 h 2–3 irregularly timed peaks of Prl, which were not as high as the nocturnal peaks but higher than the diurnal peaks of LD-PSP rats. After implantation of two Silastic P implants into LD- and LL-PSP rats on day 6 of PSP, i.e. before functional luteolysis, the peaks of Prl and a low pituitary LHRH responsiveness were still present on day 12. Also, on day 12 the plasma concentrations of DHP were not increased in P-implanted rats. P implants inserted on day 11 (i.e. after functional luteolysis) did not prevent cessation of the appearance of Prl peaks and the rise of DHP secretion in both LD- and LL-PSP rats. Also, in LL-PSP rats which were on day 6 of PSP both ovariectomized and implanted with P, peaks of Prl were still observed on days 11/12, but in animals with sham implants peaks were absent. It thus appears that P is the corpus luteum factor which provides a permissive environment for the neural signal which causes the secretion of peaks of Prl. It is concluded that (1) during PSP and until functional luteolysis the relatively high P levels play a role in the maintenance of the secretion of peaks of Prl, and that (2) maintenance of the corpus luteum function by exogenous P (and thereby the maintenance of the state of low LHRH responsiveness) is due to P postponement of luteolysis

Comparison of four clinically validated testosterone LC-MS/MS assays: Harmonization is an attainable goal

IntroductionImmunoassays and liquid chromatography-tandem mass spectrometry assays are commonly employed in clinical laboratories for measurement of total testosterone in serum. Results obtained from either of these methodologies compare poorly due to differences in calibration and/or inadvertent detection of interfering substances by the immunoassays. Standardization efforts are underway, but recent studies indicate that accuracy remains an issue.MethodsThis study compares the results from four independently developed and validated LC-MS/MS assays for total testosterone. The calibration for each assay was verified using National Institute of Standards and Technology Standard Reference Material 971.ResultsInitially, one of the four assays had a mean percent difference of +11.44%, compared to the All Method Mean, but following re-verification of all five non-zero calibrator concentrations with the NIST SRM 971, the mean percent difference decreased to -4.88%. Subsequently, the agreement between all four assays showed a mean bias of <5% across the range of all testosterone concentrations (0.13-38.10 nmol/L; 3.7-1098 ng/dL), including at low concentrations of <1 nmol/L (<29 ng/dL).ConclusionsExcellent agreement between four independently developed LC-MS/MS assays demonstrates that harmonization using standard reference material is attainable. However, as we found in this study, to ensure accurate calibration it is critical to validate the concentrations of new lots of calibrators