The RSNA Pediatric Bone Age Machine Learning Challenge.

Purpose The Radiological Society of North America (RSNA) Pediatric Bone Age Machine Learning Challenge was created to show an application of machine learning (ML) and artificial intelligence (AI) in medical imaging, promote collaboration to catalyze AI model creation, and identify innovators in medical imaging. Materials and Methods The goal of this challenge was to solicit individuals and teams to create an algorithm or model using ML techniques that would accurately determine skeletal age in a curated data set of pediatric hand radiographs. The primary evaluation measure was the mean absolute distance (MAD) in months, which was calculated as the mean of the absolute values of the difference between the model estimates and those of the reference standard, bone age. Results A data set consisting of 14 236 hand radiographs (12 611 training set, 1425 validation set, 200 test set) was made available to registered challenge participants. A total of 260 individuals or teams registered on the Challenge website. A total of 105 submissions were uploaded from 48 unique users during the training, validation, and test phases. Almost all methods used deep neural network techniques based on one or more convolutional neural networks (CNNs). The best five results based on MAD were 4.2, 4.4, 4.4, 4.5, and 4.5 months, respectively. Conclusion The RSNA Pediatric Bone Age Machine Learning Challenge showed how a coordinated approach to solving a medical imaging problem can be successfully conducted. Future ML challenges will catalyze collaboration and development of ML tools and methods that can potentially improve diagnostic accuracy and patient care. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Siegel in this issue.

Increased plasma levels of soluble TNF receptors 1 and 2 in bipolar depression and impact of lithium treatment.

OBJECTIVE: TNF system (TNF and its soluble receptors sTNFR1 and 2) has been investigated as a potential molecular target in bipolar disorder. The aim of the study was to compare plasma levels of these receptors in unmedicated bipolar depressed patients compared with healthy controls, and to evaluate the effects of a 6-week lithium treatment on sTNFR1 and sTNFR2 levels. METHODS: The study enrolled 29 patients with unmedicated bipolar disorder in a major depressive episode and 27 matched controls. Patients had blood collected at baseline and after 6 weeks of lithium treatment. The concentration of sTNFRs was measured by ELISA. RESULTS: sTNFR1 and sTNFR2 levels were significantly increased in bipolar depression in comparison with healthy subjects. Lithium treatment did not significantly change sTNFR1 and sTNFR2 levels from baseline to endpoint. There was no correlation between improvement in depressive symptoms and the change in sTNFR1 or sTNFR1 levels. CONCLUSION: These results reinforce the involvement of an activated immune response system in the pathophysiology of bipolar disorder, with no impact of lithium treatment on the related biomarkers.

Glutamatergic Modulators in Depression.

LEARNING OBJECTIVE: After participating in this activity, learners should be better able to evaluate the evidence supporting the antidepressant effects of glutamatergic modulators.Both preclinical and clinical studies have implicated glutamatergic system dysfunction in the pathophysiology of mood disorders such as bipolar depression and major depressive disorder. In particular, rapid reductions in depressive symptoms have been noted in response to subanesthetic doses of the glutamatergic modulator ketamine in subjects with major depressive disorder or bipolar depression. These results have prompted the repurposing or development of other glutamatergic modulators, both as monotherapy or adjunctive to other therapies. Here, we highlight the evidence supporting the antidepressant effects of various glutamatergic modulators, including (1) broad glutamatergic modulators (ketamine, esketamine, dextromethorphan, dextromethorphan-quinidine [Nuedexta], AVP-786, nitrous oxide [N2O], AZD6765), (2) subunit (NR2B)-specific N-methyl-D-aspartate (NMDA) receptor antagonists (CP-101,606/traxoprodil, MK-0657 [CERC-301]), (3) glycine-site partial agonists (D-cycloserine, GLYX-13, sarcosine, AV-101), and (4) metabotropic glutamate receptor modulators (AZD2066, RO4917523/basimglurant, JNJ40411813/ADX71149, R04995819 [RG1578]).

Effect of different sources of non-fiber carbohydrate on ruminal pH and in vitro digestibility of tropical forage / Efeito de diferentes fontes de carboidratos não-fibrosos sobre o pH ruminal e digestibilidade in vitro de forragens tropicais

The present study aimed to evaluate non-fiber carbohydrates (NFC) in sugarcane-based diets on rumen pH, and forage digestibility, and to describe NFC degradation curves. The study consisted of two trials. For the first trial, three rumen cannulated steers, BW of 350 ± 15 kg (mean ± SE), were assigned in a 3×3 Latin Square (LS) design. They were fed diets containing finely-ground (0.9 mm average particle size) corn (GC), steam-rolled corn (SRC), or pelleted citrus pulp (PCP). Each period had 14 d, with the first 12 for adaptation. The 13th d was for serial measurement of rumen pH, and the14th for rumen fluid collection and in vitro incubation for DM and NDF digestibility (IVDMD and IVNDFD) of bermudagrass hay (Hay), corn (CS), and sugarcane (SS) silages. In the second trial, rumen fluid of a cannulated bull, fed corn silage and a regular concentrate, was collected for in vitro digestion of NFC for multiple time points. The incubation results were used to adjust the NFC degradation curves, and calculate lag-time, feed fractions, and degradation rate. Data from first trial was analyzed in a 3×3 LS. The model for the digestibility parameters included fixed effects of forage (Feed), diets with NFC (Diet), and their interaction (Feed × Diet), and random effect of animal and period. The model for rumen pH included fixed effect of diet, time as repeated measures, animal and period as random effects. The significance was considered at probability ≤ 5% (α = 0.05). The NFC degradation curves were adjusted using the PROC NLIN procedure from SAS, and equation parameters compared using confidence intervals. There was a Diet × Time interaction on rumen pH (P = 0.04), where SRC decreased pH compared to PCP and GC diets at the time 6 h, only. There was no Feed × Diet interaction effect (P > 0.05) for any digestibility parameter. There was a Feed effect on both IVDMD and IVNDFD, either after 30 or 48 h incubation (P < 0.01). The CS had the greatest IVDMD, followed by SS and Hay, after 30 and 48 h of incubation. The CS had the greatest IVNDFD after 30 h, compared to SS and Hay. However, for IVNDFD after 48 h, CS presented the greatest mean, followed by SS and Hay. The rumen fluid from animals fed SRC decreased both IVDMD and IVNDFD (P < 0.05) of all roughages after 48 h. Results from the second trial showed that the PCP had lower Lag Time, B fraction and greater kd compared to both corn sources, and SRC had greater kd than GC. In conclusion, the SRC diet decreased rumen pH 6 h after feeding and, consequently, decreased fiber digestibility of the tropical forage sources evaluated. Although the PCP had lower lag time, and faster rate of degradation of B fraction, it did not negatively affect rumen pH or fiber digestibility of forage.(AU)

O presente estudo teve como objetivo avaliar os carboidratos não-fibrosos (CNF) em dietas à base de cana-de-açúcar sobre o pH ruminal e digestibilidade da forragem, e descrever as curvas de degradação dos CNF. O estudo foi composto de dois ensaios. No primeiro, três novilhos canulados no rúmen, com peso vivo de 350 ± 15 kg (Média ± DP), foram alocados em um quadrado latino (QL) 3×3, e alimentados com dietas contendo: milho moído (MM, tamanho de partículas 0,9 mm), laminado a vapor (MLV) ou polpa cítrica peletizada (PCP). Cada período tinha 14 d, sendo os primeiros 12 para adaptação e o 13º para a medição seriada do pH e o 14º para a coleta de líquido ruminal e incubação in vitro para digestibilidade da MS e FDN (DIVMS e DIVFDN) de feno de bermudagrass (Feno) e silagens de milho (SM) e cana (SC). No segundo ensaio, coletou-se fluido ruminal de um touro canulado, alimentado com silagem de milho e concentrado padrão, para digestão in vitro dos CNF em vários tempos. Esses resultados foram utilizados para ajustar as curvas de degradação dos CNF e calcular o tempo de colonização, frações alimentares e taxa de degradação. Os resultados do primeiro ensaio foram analisados em um QL 3×3. O modelo dos parâmetros de digestibilidade incluiu efeito fixo de forragem (Alimento), dieta com CNF (Dieta) e interação (Alimento × Dieta), e efeito aleatório de animal e período. O modelo para pH incluiu efeito fixo de Dieta, Tempo como medida repetida, animal e período como aleatórios. Foi considerada a probabilidade significativa de ≤ 5% (α = 0,05). As curvas de degradação dos CNF foram ajustadas pelo PROC NLIN do SAS, e parâmetros de equação comparados por intervalo de confiança. Houve interação Dieta × Tempo no pH ruminal (P = 0,04), onde o MLV diminuiu o pH comparado com PCP e MM apenas no tempo 6 h. Não houve interação Alimento × Dieta (P > 0,05) para nenhum parâmetro de digestibilidade. Houve efeito de Alimento sobre a DIVMS e DIVFDN, após 30 e 48 h de incubação (P < 0,01). A SM teve a maior DIVMS, seguido por SC e Feno, após 30 e 48 h de incubação. A SM teve a maior DIVFDN após 30 h, comparado com SC e Feno. No entanto, para DIVFDN após 48 h, a SM teve maior média, seguida da SC e Feno. O fluido ruminal de animais alimentados com MLV diminuiu a DIVMS e DIVFDN (P < 0.05) de todas as forragens, após 48 h. Resultados do segundo ensaio mostram que PCP diminuiu o tempo de colonização, fração B e aumentou a kd comparado com os dois milhos, e MLV apresentou maior kd que o MM. Em conclusão, a dieta com MLV diminuiu o pH ruminal no tempo 6 h e, consequentemente, diminuiu a DIVFDN das forragens avaliadas. Embora PCP tenha apresentado menor tempo de colonização e maior taxa de degradação da fração B, não afetou negativamente o pH do rúmen nem a digestibilidade da fibra das forragens. (au)

Lithium safety and tolerability in mood disorders: a critical review / Tolerabilidade e segurança do lítio em transtornos do humor: uma revisão crítica

Background: Lithium is a first-line treatment for bipolar disorder in all phases, also indicated as add-on drug for unipolar depression and suicide prevention. This study encompasses a broad critical review on the safety and tolerability of lithium for mood disorders. Methods: A computerized search for English written human studies was made in MEDLINE, using the keywords “lithium” and “mood disorders”, starting from July 1993 through July 2013 (n = 416). This initial search aimed to select clinical trials, prospective data, and controlled design studies of lithium treatment for mood disorders reporting adverse effects (n = 36). The final selection yielded 91 studies. Results: The most common general side effects in patients on lithium treatment were thirst, frequent urination, dry mouth, weight gain, fatigue and cognitive complaints. Lithium users showed a high prevalence of hypothyroidism, hyperparathyroidism, and decrease in urinary concentration ability. Reduction of glomerular filtration rate in patients using lithium was also observed, but in a lesser extent. The evidence of teratogenicity associated with lithium use is not well established. Anti-inflammatory non-steroidal drugs, thiazide diuretics, angiotensin-converting enzyme inhibitors, and alprazolam may increase serum lithium and the consequent risk for intoxication. Discussion: Short-term lithium treatment is associated with mild side effects. Medium and long-term lithium treatment, however, might have effects on target organs which may be prevented by periodical monitoring. Overall, lithium is still a safe option for the treatment of mood disorders...

Contexto: O lítio é um tratamento de primeira linha para o transtorno bipolar, em todas as fases, e também é indicado como terapia adjunta para a depressão unipolar e prevenção do suicídio. Este estudo abrange uma ampla revisão crítica sobre a segurança e a tolerabilidade do lítio para transtornos do humor. Métodos: Uma busca informatizada para estudos com humanos escritos em inglês foi feita no MEDLINE, usando as palavras-chave “lítio” e “transtornos de humor”, a partir de julho de 1993 a julho de 2013 (n = 416). Esta pesquisa inicial teve como objetivo selecionar ensaios clínicos, estudos prospectivos e estudos controlados com tratamento com lítio para transtornos de humor, relatando efeitos adversos (n = 36). A seleção final identificou 91 estudos. Resultados: Os efeitos colaterais mais comuns nos pacientes em tratamento com lítio foram sede, micção frequente, boca seca, ganho de peso, fadiga e queixas cognitivas. Usuários de lítio mostraram uma alta prevalência de hipotireoidismo, hiperparatireoidismo e diminuição da capacidade de concentração urinária. Também foi observada redução da taxa de filtração glomerular em pacientes utilizando lítio, mas em menor grau. A evidência de teratogenicidade associada com o uso de lítio não está bem estabelecida. Os medicamentos anti-inflamatórios não esteroides, diuréticos, inibidores da enzima de conversão da angiotensina e alprazolam podem aumentar o lítio sérico e o consequente risco de intoxicação. Conclusões: O tratamento de curto prazo com lítio está associado com efeitos colaterais leves. No entanto, tratamentos de médio a longo prazo com lítio podem ter efeitos sobre órgãos-alvo que podem ser prevenidos por acompanhamento periódico. Em geral, o lítio é ainda uma alternativa segura para o tratamento dos transtornos de humor...