Biomarkers lie at the heart of precision medicine, biodiversity monitoring, agricultural pathogen detection, amongst others. Surprisingly, while rapid genomic profiling is becoming ubiquitous, the development of biomarkers almost always involves the application of bespoke techniques that cannot be directly applied to other datasets. There is an urgent need for a systematic methodology to create biologically-interpretable molecular models that robustly predict key phenotypes. We therefore created SIMMS: an algorithm that fragments pathways into functional modules and uses these to predict phenotypes. We applied SIMMS to multiple data-types across four diseases, and in each it reproducibly identified subtypes, made superior predictions to the best bespoke approaches, and identified known and novel signaling nodes. To demonstrate its ability on a new dataset, we measured 33 genes/nodes of the PIK3CA pathway in 1,734 FFPE breast tumours and created a four-subnetwork prediction model. This model significantly out-performed existing clinically-used molecular tests in an independent 1,742-patient validation cohort. SIMMS is generic and can work with any molecular data or biological network, and is freely available at: https://cran.r-project.org/web/packages/SIMMS.
If the number of births per year at a clinic is divided by the number of available cardiotocographs, a variable is obtained, designated Q, which reflects the electronic fetal monitoring situation: the larger Q is, the more births per cardiotocograph, and the less satisfactory is the fetal monitoring situation. The smaller Q becomes, the greater the probability that every fetus can be monitored sub partu. Q has an empirical distribution pattern. The median of Q is between 139 and 215 births per year and per monitor, depending on the size of the clinic. There is a significant relationship between the monitoring value Q and the percentage frequency of cesarean and forceps deliveries: the higher the potential monitoring capacity, i.e., the smaller Q is, the higher the number of cesarean and forceps deliveries of a clinic. Intensive monitoring therefore increases the number of surgical deliveries, though no drop in the unadjusted perinatal mortality rate was observed. No association could be established between Q and the risk of fetal acidosis - possibly due to a lack of data. The conclusion drawn from these data is that the theoretical and practical training of obstetricians and midwives in cardiotocography should be further intensified.
Data from 690 clinics concerning obstetric management and intensive monitoring of the fetus sub partu were classified according to the type of hospital (e. g., municipal clinic, district hospital...) and the size of the hospital based on the number of births per year. On the basis of the annual number of births four groups (I-IV) were formed, each with 172 clinics. While the average number of surgical deliveries (cesarean, forceps, vacuum) is not related to the hospital (Table 3), it is related to the type of hospital (Table 6): the average number of cesarean deliveries is highest in university clinics (n = 24; 14.9%), and on average more forceps (6.5%) than vacuum extractions (5.7%) are performed. In all other hospitals vacuum extraction is clearly preferred (7-8%). The quotient Q of the annual number of births per CTG unit is not constant, but increases with the size of the clinic: In large hospitals (Group IV) significantly more births are monitored with a CTG unit (maximum 607, average 215), so that there is a numerical "monitoring deficit" as compared to smaller departments. The monitoring capability is numerically highest in the university clinics (Q = 147) and lowest in the academic teaching hospitals (Q = 192). The larger the clinic, the more frequently fetal blood is analyzed: the figure in large clinics is 40%. Small clinics are less familiar with this method (approx. 16%). The larger the clinic, the more often intrauterine catheters are used to measure labor; the figure rises from 7% to 29%.(ABSTRACT TRUNCATED AT 250 WORDS)
From October 1977 until March 1978 a prospective study was performed on 30 depressive patients of both sexes, age 20 to 60 years. In a double-blind design patients received either amitriptyline or trazodone for 28 days. The course of therapy was controlled six times by means of the Hamilton Rating Scale for Depression (HRS) and the Zerssen-Contentment Scale (BS). The following results were obtained: By the statistical analysis of the HRS scores no difference in the antidepressant properties of trazodone and amitriptyline can be demonstrated. The same result is obtained by use of the BS scores. Therefore the antidepressant efficacy of the two medications can be called equal. When comparing day 10 to day 0, a correlation between the two data pools of Rsp = 0.719 (p less than 0.01) according to Spearman was found. Upon comparing the 28th day with the pre-treatment day, Rsp is 0.809. When applying ANOVA no significant correlation for the pre-treatment day can be demonstrated (RL = 0.260); yet at the end of the study the correlation becomes extremely high (RL = 0.940, p less than 0.1). When considering each day of the study, RL results to be 0.808 (p less than 0.001). Thus, a high correlation can be demonstrated for the HRS and BS. The conclusion may be drawn that this design is of special value in comparing the antidepressant properties of new pharmacologic substances.
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