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Automated preprocessing methods are critically needed to process the large publicly-available EEG databases, but the optimal approach remains unknown because we lack data quality metrics to compare them. Here, we designed a simple yet robust EEG data quality metric assessing the percentage of significant channels between two experimental conditions within a 100 ms post-stimulus time range. Because of volume conduction in EEG, given no noise, most brain-evoked related potentials (ERP) should be visible on every single channel. Using three publicly available collections of EEG data, we showed that, with the exceptions of high-pass filtering and bad channel interpolation, automated data corrections had no effect on or significantly decreased the percentage of significant channels. Referencing and advanced baseline removal methods were significantly detrimental to performance. Rejecting bad data segments or trials could not compensate for the loss in statistical power. Automated Independent Component Analysis rejection of eyes and muscles failed to increase performance reliably. We compared optimized pipelines for preprocessing EEG data maximizing ERP significance using the leading open-source EEG software: EEGLAB, FieldTrip, MNE, and Brainstorm. Only one pipeline performed significantly better than high-pass filtering the data.

BackgroundTreatment of multidrug-resistant tuberculosis requires long-term therapy with a combination of multiple second-line drugs. These drugs are associated with numerous adverse events that can cause severe morbidity, such as deafness, and in some instances can lead to death. Our aim was to estimate the absolute and relative frequency of adverse events associated with different tuberculosis drugs to provide useful information for clinicians and tuberculosis programmes in selecting optimal treatment regimens.MethodsWe did a meta-analysis using individual-level patient data that were obtained from studies that reported adverse events that resulted in permanent discontinuation of anti-tuberculosis medications. We used a database created for our previous meta-analysis of multidrug-resistant tuberculosis treatment and outcomes, for which we did a systematic review of literature published between Jan 1, 2009, and Aug 31, 2015 (updated April 15, 2016), and requested individual patient-level information from authors. We also considered for this analysis studies contributing patient-level data in response to a public call made by WHO in 2018. Meta-analysis for proportions and arm-based network meta-analysis were done to estimate the incidence of adverse events for each tuberculosis drug.Findings58 studies were identified, including 50 studies from the updated individual patient data meta-analysis for multidrug-resistant tuberculosis treatment. 35 of these studies, with 9178 patients, were included in our analysis. Using meta-analysis of proportions, drugs with low risks of adverse event occurrence leading to permanent discontinuation included levofloxacin (1·3% [95% CI 0·3-5·0]), moxifloxacin (2·9% [1·6-5·0]), bedaquiline (1·7% [0·7-4·2]), and clofazimine (1·6% [0·5-5·3]). Relatively high incidence of adverse events leading to permanent discontinuation was seen with three second-line injectable drugs (amikacin: 10·2% [6·3-16·0]; kanamycin: 7·5% [4·6-11·9]; capreomycin: 8

Current machine learning classifiers have successfully been applied to whole-genome sequencing data to identify genetic determinants of antimicrobial resistance (AMR), but they lack causal interpretation. Here we present a metabolic model-based machine learning classifier, named Metabolic Allele Classifier (MAC), that uses flux balance analysis to estimate the biochemical effects of alleles. We apply the MAC to a dataset of 1595 drug-tested Mycobacterium tuberculosis strains and show that MACs predict AMR phenotypes with accuracy on par with mechanism-agnostic machine learning models (isoniazid AUC = 0.93) while enabling a biochemical interpretation of the genotype-phenotype map. Interpretation of MACs for three antibiotics (pyrazinamide, para-aminosalicylic acid, and isoniazid) recapitulates known AMR mechanisms and suggest a biochemical basis for how the identified alleles cause AMR. Extending flux balance analysis to identify accurate sequence classifiers thus contributes mechanistic insights to GWAS, a field thus far dominated by mechanism-agnostic results.

The traditional goals of Crohn's disease therapy, to induce and maintain clinical remission, have not clearly changed its natural history. In contrast, emerging evidence suggests that achieving and maintaining mucosal healing may alter the natural history of Crohn's disease, as it has been associated with more sustained clinical remission and reduced rates of hospitalization and surgical resection. Induction and maintenance of mucosal healing should therefore be a goal toward which therapy is now directed. Unresolved issues pertain to the benefit of achieving mucosal healing at different stages of the disease, the relationship between mucosal healing and transmural inflammation, the intensity of treatment needed to achieve mucosal healing when it has not been obtained using standard therapy, and the means by which mucosal healing is defined using current endoscopic disease activity indices. The main clinical challenge relates to defining the means of achieving high rates of mucosal healing in clinical practice. Copyright © 2013 Crohn's & Colitis Foundation of America, Inc.

The traditional goals of Crohn's disease therapy, to induce and maintain clinical remission, have not clearly changed its natural history. In contrast, emerging evidence suggests that achieving and maintaining mucosal healing may alter the natural history of Crohn's disease, as it has been associated with more sustained clinical remission and reduced rates of hospitalization and surgical resection. Induction and maintenance of mucosal healing should therefore be a goal toward which therapy is now directed. Unresolved issues pertain to the benefit of achieving mucosal healing at different stages of the disease, the relationship between mucosal healing and transmural inflammation, the intensity of treatment needed to achieve mucosal healing when it has not been obtained using standard therapy, and the means by which mucosal healing is defined using current endoscopic disease activity indices. The main clinical challenge relates to defining the means of achieving high rates of mucosal healing in clinical practice. Copyright © 2013 Crohn's & Colitis Foundation of America, Inc.

Prognostic factors for postoperative recurrence of Crohn's disease (CD) have been widely investigated but not yet clearly identified. PURPOSE: Aim of this study was, therefore, to analyze the association between demographic, clinical, laboratory, and surgical characteristics of patients and the cumulative probability of endoscopic postoperative recurrence. METHODS: The study was performed in 110 patients who were enrolled in the Italian multicenter, randomized, controlled trial on the effectiveness of 5-aminosalicylic acid (5-ASA) in the prevention of postoperative recurrence in CD. Patients had undergone their first intestinal resection for CD of the terminal ileum with or without involvement of cecum ascending colon. Recurrence was defined on the basis of endoscopy. The following variables were evaluated as potential prognostic factors: gender, age, years since diagnosis, clinical course (perforative and non-perforative), Crohn's Disease Activity Index score, white blood count, erythrocyte sedimentation rate, C-reactive protein, and orosomucoids assessed before the operation. Timing of operation (elective or urgent), type of anastomosis (end-to-end, end-to-side, side-to-side), and prophylactic treatment were also evaluated. Colon ileoscopy was performed at 6, 12, 24, and 36 months after operation. The association between variables and the cumulative proportion of recurrence was analyzed both by univariate analysis (life table method, log-rank test) and multivariate regression analysis (Cox's model, stepwise procedure). RESULTS: Results of this study indicate that, of the features considered before surgery, only leukocytosis (white blood count, >9,000 ml) was significantly associated with an increased risk of recurrence (P < 0.05) at univariate analysis. This finding was not confirmed by multivariate analysis. A trend toward a higher risk of recurrence for patients who have had a resection with end-to-end anastomosis compared with those who have had a resection and

METHODS: A multicentre randomized controlled trial was conducted to evaluate the efficacy of oral mesalazine (5-aminosalicylic acid) for the prevention of post-operative recurrence in 110 patients operated on for Crohn's disease by first intestinal resection. Patients were randomly allocated to receive 2.4 g/day of mesalazine, or no treatment at all. The protocol included colonoscopy with ileoscopy at 6 months and yearly thereafter. Recurrence was defined on the basis of endoscopic criteria and classified as mild or severe. RESULTS: The demographic and pre-trial characteristics were very similar in the two groups of patients. The cumulative proportion of recurrence at 6, 12 and 24 months was significantly lower in the mesalazine group than in untreated group (P = 0.002). At 24 months the cumulative proportions of endoscopic recurrence were 0.52 +/- 0.12 (+/- S.E.M.) and 0.85 (+/- 0.07), respectively. At the same time the cumulative proportions of symptomatic recurrence were 0.18 +/- 0.09 and 0.41 +/- 0.09 (P = 0.006). The cumulative proportions of the severe recurrence was also significantly lower in the mesalazine group (0.17 +/- 0.09 vs. 0.38 +/- 0.09; P = 0.021). CONCLUSIONS: The preliminary results of this study show that administration of oral mesalazine soon after surgery is effective in preventing post-operative endoscopic recurrence in Crohn's disease over a 2-year period. It is estimated that this treatment prevents 39% of all recurrences and 55% of the severe recurrences

In an uncontrolled trial, patients with IgA nephropathy (IgAN) were treated with drugs that can alter the intestinal mucosal permeability to food antigens. These drugs are known to ameliorate urinary abnormalities and histological lesions of IgAN associated with ulcerative colitis or Crohn's disease [5-aminosalicylic acid (5-ASA)] or to prevent, in mice, the induction of IgAN-like disease by oral immunization [disodium cromoglycate (SCG)]. Nine patients [serum creatinine (s-Cr) less than 2 mg/dl; 24-hour proteinuria higher than 1.5 g, but not nephrotic) were treated with 5-ASA (2.4 g/day for 6 months); 9 similar patients were treated with SCG (400 mg/day for 6 months); the follow-up extended to 6 months after stopping therapy. The 5-ASA group showed a slight but not significant decrease in s-Cr, 24-hour/proteinuria, IgA circulating immune complexes (IgA-CIC) and IgA rheumatoid factor (IgA-RF); serum beta 2-microglobulin and serum IgA were unchanged; 2 of 9 treated patients showed, after 6 months of therapy, a reduction in proteinuria of more than 50% that lasted for the subsequent 18 months. The SCG-treated group showed a slight but not significant increase in 24-hour proteinuria and a significant decrease in serum IgA; unchanged were s-Cr, IgA-CIC, IgA-RF, serum beta 2-microglobulin; no patient treated with SCG showed a reduction in proteinuria of more than 50%. At the dosages and for the periods used, 5-ASA and SCG did not show a significant influence on clinical and laboratory parameters of disease in IgAN; other trials with increased dosages are warranted to definitely ascertain the possible therapeutic role of these drugs in IgAN

Human erythrocytes were treated with the toxic pesticide DDVP (0,0 dimethyl -0-2,2-dichlorovinylphosphate). This caused an inhibition of the enzyme, acetylcholinesterase, contained in the erythrocytes of 88.8% on the average. The cells were washed and treated with four widely used acetylcholinesterase reactivators, and the activity of the enzyme was then measured. TMB-4 and Toxogonin proved to be more effective than 2-PAM or 2-PAS as reactivators., Trans. of Gigiena Primeneniya, Toksiklogiya Pestitsidov i Klinika Otravlenii (USSR) n8 p267-270 1970, by Markowitz