Effect of treatment delay on disease severity and need for resuscitation in porcine fecal peritonitis.

Early treatment in sepsis may improve outcome. The aim of this study was to evaluate how the delay in starting resuscitation influences the severity of sepsis and the treatment needed to achieve hemodynamic stability.

Clinical presentation and diagnostic delay in bullous pemphigoid: a prospective nationwide cohort

Prospective systematic analyses of the clinical presentation of bullous pemphigoid (BP) are lacking. Little is known about the time required for its diagnosis. Knowledge of the disease spectrum is important for diagnosis, management and inclusion of patients in therapeutic trials.

Brown Capuchins (Cebus apella) Exhibit Self-Control on a Delay of Gratification Food Exchange Task When Food Options Differ Qualitatively

Self-control allows an individual to obtain a more preferred outcome by forgoing an immediate interest. Self-control is an advanced cognitive process because it involves the ability to weigh the costs and benefits of impulsive versus restrained behavior, determine the consequences of such behavior, and make decisions based on the most advantageous course of action. Self-control has been thoroughly explored in Old World primates, but less so in New World monkeys. There are many ways to test self-control abilities in non-human primates, including exchange tasks in which an animal must forgo an immediate, less preferred reward to receive a delayed, more preferred reward. I examined the self-control abilities of six capuchin monkeys using a task in which a monkey was given a less preferred food and was required to wait a delay interval to trade the fully intact less preferred food for a qualitatively higher, more preferred food. Partially eaten pieces of the less preferred food were not rewarded, and delay intervals increased on an individual basis based on performance. All six monkeys were successful in inhibiting impulsivity and trading a less preferred food for a more preferred food at the end of a delay interval. The maximum duration each subject postponed gratification instead of responding impulsively was considered their delay tolerance. This study was the first to show that monkeys could inhibit impulsivity in a delay of gratification food exchange task in which the immediate and delayed food options differed qualitatively and a partially eaten less preferred food was not rewarded with the more preferred food at the end of a delay interval. These results show that New World monkeys possess advanced cognitive abilities similar to those of Old World primates.

Executive functions of children born very preterm--deficit or delay?

This cross-sectional study examined the performance of children born very preterm and/or at very low birth weight (VPT/VLBW) and same-aged term-born controls in three core executive functions: inhibition, working memory, and shifting. Children were divided into two age groups according to the median (young, 8.00-9.86 years; old, 9.87-12.99 years). The aims of the study were to investigate whether (a) VPT/VLBW children of both age groups performed poorer than controls (deficit hypothesis) or caught up with increasing age (delay hypothesis) and (b) whether VPT/VLBW children displayed a similar pattern of performance increase in executive functions with advancing age compared with the controls. Fifty-six VPT/VLBW children born in the cohort of 1998-2003 and 41 healthy-term-born controls were recruited. All children completed tests of inhibition (Color-Word Interference Task, Delis-Kaplan Executive Function System (D-KEFS)), working memory (Digit Span Backwards, HAWIK-IV), and shifting (Trail Making Test, Number-Letter Sequencing, D-KEFS). Results revealed that young VPT/VLBW children performed significantly poorer than the young controls in inhibition, working memory, and shifting, whereas old VPT/VLBW children performed similar to the old controls across all three executive functions. Furthermore, the frequencies of impairment in inhibition, working memory and shifting were higher in the young VPT/VLBW group compared with the young control group, whereas frequencies of impairment were equal in the old groups. In both VPT/VLBW children and controls, the highest increase in executive performance across the ages of 8 to 12 years was observed in shifting, followed by working memory, and inhibition.

GH mutant (R77C) in a pedigree presenting with the delay of growth and pubertal development: structural analysis of the mutant and evaluation of the biological activity

A heterozygous missense mutation in the GH-1 gene converting codon 77 from arginine (R) to cysteine (C), which was previously reported to have some GH antagonistic effect, was identified in a Syrian family. The index patient, a boy, was referred for assessment of his short stature (-2.5 SDS) at the age of 6 years. His mother and grandfather were also carrying the same mutation, but did not differ in adult height from the other unaffected family members. Hormonal examination in all affected subjects revealed increased basal GH, low IGF-I concentrations, and subnormal IGF-I response in generation test leading to the diagnosis of partial GH insensitivity. However, GH receptor gene (GHR) sequencing demonstrated no abnormalities. As other family members carrying the GH-R77C form showed similar alterations at the hormonal level, but presented with normal final height, no GH therapy was given to the boy, but he was followed through his pubertal development which was delayed. At the age of 20 years he reached his final height, which was normal within his parental target height. Functional characterization of the GH-R77C, assessed through activation of Jak2/Stat5 pathway, revealed no differences in the bioactivity between wild-type-GH (wt-GH) and GH-R77C. Detailed structural analysis indicated that the structure of GH-R77C, in terms of disulfide bond formation, is almost identical to that of the wt-GH despite the introduced mutation (Cys77). Previous studies from our group demonstrated a reduced capability of GH-R77C to induce GHR/GH-binding protein (GHBP) gene transcription rate when compared with wt-GH. Therefore, reduced GHR/GHBP expression might well be the possible cause for the partial GH insensitivity found in our patients. In addition, this group of patients deserve further attention because they could represent a distinct clinical entity underlining that an altered GH peptide may also have a direct impact on GHR/GHBP gene expression causing partial GH insensitivity. This might be responsible for the delay of growth and pubertal development. Finally, we clearly demonstrate that GH-R77C is not invariably associated with short stature, but that great care needs to be taken in ascribing growth failure to various heterozygous mutations affecting the GH-IGF axis and that careful functional studies are mandatory.

Does diagnostic delay result in decreased survival in paediatric brain tumours?

To study the hypothesis that a delay in the diagnosis of paediatric brain tumours results in decreased survival outcome probability, we compared the prediagnostic period of 315 brain tumour patients (median age 6.7 years, range, 0 to 16 years) with progression-free and overall survival. The median prediagnostic symptomatic interval was 60 days (range, 0 to 3,480 days), with a median parental delay of 14 days (range, 0 to 1,835 days) and a median doctor's delay of 14 days (range, 0 to 3,480 days). The prediagnostic symptomatic interval correlated significantly with the patient age, tumour histology, tumour location and year of diagnosis, but not with gender. We then grouped the patients according to histology (low-grade glioma [n=77], medulloblastoma [n=57], high-grade glioma [n=40], craniopharyngioma [n=27], ependymoma [n=20] and germ cell tumours [n=18]). Contrary to common belief, long prediagnostic symptomatic interval or long doctor's delay did not result in decreased survival outcome probability in any of these groups. The effect of tumour biology on survival seems to be dominant and overwhelms any possible opposing effect on survival of a delay in diagnosis.

Information processing in long delay memory-guided saccades: further insights from TMS

The performance of memory-guided saccades with two different delays (3 s and 30 s of memorisation) was studied in eight subjects. Single pulse transcranial magnetic stimulation (TMS) was applied simultaneously over the left and right dorsolateral prefrontal cortex (DLPFC) 1 s after target presentation. In both delays, stimulation significantly increased the percentage of error in amplitude of memory-guided saccades. Furthermore, the interfering effect of TMS was significantly higher in the short delay compared to that of the long delay paradigm. The results are discussed in the context of a mixed model of spatial working memory control including two components: First, serial information processing with a predominant role of the DLPFC during the early period of memorisation and, second, parallel information processing, which is independent from the DLPFC, operating during longer delays.

Application of Time-Delay Estimation to Mixed Reality Multisensor Tracking

Spatial tracking is one of the most challenging and important parts of Mixed Reality environments. Many applications, especially in the domain of Augmented Reality, rely on the fusion of several tracking systems in order to optimize the overall performance. While the topic of spatial tracking sensor fusion has already seen considerable interest, most results only deal with the integration of carefully arranged setups as opposed to dynamic sensor fusion setups. A crucial prerequisite for correct sensor fusion is the temporal alignment of the tracking data from several sensors. Tracking sensors are typically encountered in Mixed Reality applications, are generally not synchronized. We present a general method to calibrate the temporal offset between different sensors by the Time Delay Estimation method which can be used to perform on-line temporal calibration. By applying Time Delay Estimation on the tracking data, we show that the temporal offset between generic Mixed Reality spatial tracking sensors can be calibrated. To show the correctness and the feasibility of this approach, we have examined different variations of our method and evaluated various combinations of tracking sensors. We furthermore integrated this time synchronization method into our UBITRACK Mixed Reality tracking framework to provide facilities for calibration and real-time data alignment.

Development of a Mathematical Model for the Calculation of the Tool Appropriation Delay depending on the Tool Inventory

Compliance with punctual delivery under the high pressure of costs can be implemented through the optimization of the in-house tool supply. Within the Transfer Project 13 of the Collaborative Research Centre 489 using the example of the forging industry, a mathematical model was developed which determines the minimum inventory of forging tools required for production, considering the tool appropriation delay.

Diagnostic delay in Crohn's disease is associated with a complicated disease course and increased operation rate

OBJECTIVES The impact of diagnostic delay (a period from appearance of first symptoms to diagnosis) on the clinical course of Crohn's disease (CD) is unknown. We examined whether length of diagnostic delay affects disease outcomes. METHODS Data from the Swiss IBD cohort study were analyzed. Patients were recruited from university centers (68%), regional hospitals (14%), and private practices (18%). The frequencies of occurrence of bowel stenoses, internal fistulas, perianal fistulas, and CD-related surgery (intestinal and perianal) were analyzed. RESULTS A total of 905 CD patients (53.4% female, median age at diagnosis 26 (20-36) years) were stratified into four groups according to the quartiles of diagnostic delay (0-3, 4-9, 10-24, and ≥25 months, respectively). Median diagnostic delay was 9 (3-24) months. The frequency of immunomodulator and/or antitumor necrosis factor drug use did not differ among the four groups. The length of diagnostic delay was positively correlated with the occurrence of bowel stenosis (odds ratio (OR) 1.76, P=0.011 for delay of ≥25 months) and intestinal surgery (OR 1.76, P=0.014 for delay of 10-24 months and OR 2.03, P=0.003 for delay of ≥25 months). Disease duration was positively associated and non-ileal disease location was negatively associated with bowel stenosis (OR 1.07, P<0.001, and OR 0.41, P=0.005, respectively) and intestinal surgery (OR 1.14, P<0.001, and OR 0.23, P<0.001, respectively). CONCLUSIONS The length of diagnostic delay is correlated with an increased risk of bowel stenosis and CD-related intestinal surgery. Efforts should be undertaken to shorten the diagnostic delay.

Implementing fisher Black's simple discounting rule

We propose a simple implementation of Black’s (1988) elegant rule for discounting uncertain future cash flows. Black’s rule avoids the thorny problem of estimating an appropriate risk-adjusted discount rate. Instead, the rule calls for discounting conditional mean cash flows at appropriate riskless interest rates. Our contribution in this article is to describe and illustrate a method of estimating the conditional mean cash flows called for in Black’s rule. The method is quite flexible with respect to the types of information available concerning the distributions of future cash flows. We argue that this approach to computing present values offers a theoretically sound and generally feasible addition to the toolbox of financial managers.

Delay in diagnosis of eosinophilic esophagitis increases risk for stricture formation in a time-dependent manner

BACKGROUND & AIMS Development of strictures is a major concern for patients with eosinophilic esophagitis (EoE). At diagnosis, EoE can present with an inflammatory phenotype (characterized by whitish exudates, furrows, and edema), a stricturing phenotype (characterized by rings and stenosis), or a combination of these. Little is known about progression of stricture formation; we evaluated stricture development over time in the absence of treatment and investigated risk factors for stricture formation. METHODS We performed a retrospective study using the Swiss EoE Database, collecting data on 200 patients with symptomatic EoE (153 men; mean age at diagnosis, 39 ± 15 years old). Stricture severity was graded based on the degree of difficulty associated with passing of the standard adult endoscope. RESULTS The median delay in diagnosis of EoE was 6 years (interquartile range, 2-12 years). With increasing duration of delay in diagnosis, the prevalence of fibrotic features of EoE, based on endoscopy, increased from 46.5% (diagnostic delay, 0-2 years) to 87.5% (diagnostic delay, >20 years; P = .020). Similarly, the prevalence of esophageal strictures increased with duration of diagnostic delay, from 17.2% (diagnostic delay, 0-2 years) to 70.8% (diagnostic delay, >20 years; P < .001). Diagnostic delay was the only risk factor for strictures at the time of EoE diagnosis (odds ratio = 1.08; 95% confidence interval: 1.040-1.122; P < .001). CONCLUSIONS The prevalence of esophageal strictures correlates with the duration of untreated disease. These findings indicate the need to minimize delay in diagnosis of EoE.