Optimizing the timing of highest hydrocortisone dose in children and adolescents with 21-hydroxylase deficiency

Context Hydrocortisone treatment of young patients with 21-hydroxylase deficiency (21OHD) is given thrice-daily, but there is debate about the optimal timing of highest hydrocortisone dose, either mimicking the physiological diurnal rhythm (morning), or optimally suppressing androgen activity (evening). Objective We aimed to compare two standard hydrocortisone timing strategies, either highest dosage in the morning or evening, with respect to hormonal status throughout the day, nocturnal blood pressure, sleep and activity scores. Design and setting Six-week cross-over study. Patients Thirty-nine patients (4-19 years) with 21OHD. Interventions Patients were treated for three weeks with highest hydrocortisone dose in the morning, followed by three weeks with highest dose in the evening (n=21), or vice-versa (n=18). Androstenedione (A4) and 17-hydroxyprogesterone (17OHP) levels were quantified in saliva collected at 5.00am; 7.00am; 3.00pm; and 11.00pm during the last two days of each treatment period. Main outcome measure Comparison of saliva 17OHP and A4 levels between two treatment strategies. Results Administration of the highest dose in the evening resulted in significantly lower 17OHP levels at 5.00am, whereas the highest dose in the morning resulted in significantly lower 17OHP and A4 levels in the afternoon. The two treatment dose regimens were comparable with respect to averaged daily hormone levels, nocturnal blood pressure, and activity- and sleep scores. Conclusion No clear benefit for either treatment schedule was established. Given the variation in individual responses we recommend to individually optimize dose distribution and monitoring disease control at multiple timepoints.

Evaluation of Blossom Thinning Spray Timing Strategies in Apple

In the eastern USA and several other apple-growing regions, apple blossom thinning using lime sulfur is a relatively new crop load management strategy. This study sought to evaluate how application timing of lime sulfur + stylet oil blossom thinning sprays would influence thinning efficacy and crop safety of ‘Gala’ apples. This project occurred at two locations in the USA, Winchester, Virginia, and Mills River, North Carolina, during the 2019 growing season. Two main timing strategies were assessed: (1) model-guided sprays with the pollen tube growth model (PTGM), (2) fixed spray intervals with the first spray applied at a specified percentage of open bloom (20% vs. 80%), and the second spray applied at a reapplication interval (48 h vs. 72 h). Model-guided and 20% open bloom + 48-h treatments reduced fruit set and increased fruit weight, diameter, and length at both sites. Treatments with a delayed first spray at 80% open bloom or a more extended second reapplication of 72 h were generally ineffective. There was no conclusive evidence that lime sulfur + stylet oil blossom thinning spray timing influenced russet incidence/severity or leaf phytotoxicity. This study demonstrated that effective and safe blossom thinning can be obtained from applying two sprays at 20% open bloom and 48 h thereafter or using the PTGM.

Impact of Turning Lane Storage Length and Turning Proportions on Throughput at Oversaturated Signalized Intersections

During oversaturated conditions, common objectives of signal timing are to maximize vehicle throughput and manage queues. A common response to increases in vehicle volumes is to increase the cycle length. Because the clearance intervals are displayed less frequently with longer cycle lengths and fewer cycles, more of the total time is used for green indications, which implies that the signal timing is more efficient. However, previous studies have shown that throughput reaches a peak at a moderate cycle length and extending the cycle length beyond this actually decreases the total throughput. Part of the reason for this is that spillback caused by the turning traffic may cause starvation of the through lanes resulting in a reduction of the saturation flow rate within each lane. Gaps created by the turning traffic after a lane change may also reduce the saturation flow rate. There is a relationship between the proportions of turning traffic, the storage length of turning lanes, and the total throughput that can be achieved on an approach for a given cycle length and green time. This study seeks to explore this relationship to yield better signal timing strategies for oversaturated operations. A microsimulation model of an oversaturated left-turn movement with varying storage lengths and turning proportions is used to determine these relationships and establish a mathematical model of throughput as a function of the duration of green, storage length, and turning proportion. The model outcomes are compared against real-world data.

Historical Trends in Expressive Timing Strategies: Chopin's Etude, Op. 25 no. 1

Studies of early 20th-century performance practice tend to focus on features that are alien to late 20th- and early 21st-century ears. Empirical analysis of timing in recordings of Chopin's Etude, Op. 25 no. 1—a piece for which performance style has remained relatively static—suggests how some foundational rules of phrasing and expressive nuance have changed over the history of recorded music. Melody note onsets were marked manually in 127 commercial recordings dating from 1909 to 2016. Overall, the data do not show an increase or decrease over time in the amount of tempo fluctuation. Independently of a tendency to use slower tempi, pianists changed the way they employ rubato. Several factors contribute to a trend whereby the fourth beat is lengthened at the expense of the second and third beats: an increase in phrase-final lengthening, an increase in the use of tempo arching for shorter groups of measures, and a tendency to delay the arrival of an accented dissonance or change of harmony instead of lengthening the melody inter-onset interval that contains it. The data illustrate nearly imperceptible shifts in interpretation and suggest that some practices thought to be the bedrock of expressive performance may be historically conditioned.

Effects of Stimulus Intensity and Frequency on the Force and Timing of Sensorimotor Synchronisation

We report an experiment to investigate possible vestibular effects on finger tapping to an auditory anapaest rhythm. In a sample of 10 subjects, index finger acceleration and tapping force were recorded along with extensor/flexor activity and the associated electroencephalographic activity measured at central and cerebellar surface electrodes. In a prior session with a standard short air-conducted 500-Hz pip, vestibular evoked myogenic potential thresholds were measured and subsequently used to set the acoustic intensity. During the main experiment subjects were asked to synchronise tapping to the pips arranged in the anapaest at two different frequencies, 500 Hz vs 5 kHz, so that only the low-frequency high-intensity condition was a vestibular, as well as an auditory stimulus. We hypothesised that a vestibular effect would manifest in an interaction between the frequency and intensity factors for a range of dependent measures of tapping performance. No clear evidence was found for vestibular effects, but this was likely due to the confounding effects of an independent effect of intensity and the relative weakness of the acoustic vestibular stimulus. However, the data did show novel evidence for two distinct timing processes for the flexion and extension stages of a tap cycle and two distinct timing strategies, which we refer to as ‘staccato’ and ‘legato’, characterised by different profiles of force and extension.

Day-of-the-week effect: A sectoral analysis of Pakistan stock exchange

This study scrutinizes the day-of-the-week effect anomaly in the context of market and industry analysis of the Pakistan stock exchange. For this purpose, daily closing prices of KSE-100, KSE-30, and KSE-All Share Index from January 01, 2009 to December 31, 2018, have been used. Similarly, sector returns are also calculated, taking average log-returns of selected sample firms. To analyze the data ordinary least squares (OLS) regression, general generalized autoregressive conditional heteroscedasticity (GARCH) (1,1) as well as asymmetric threshold GARCH (TGARCH) and exponential GARCH (EGARCH) models have been employed to model the leverage effect of good and bad news on market volatility. The results indicate the evidence of daily seasonality, with significant Monday and Wednesday effect in PSX indices returns as well as in most of the industry returns. Monday is found to be the day with the highest average returns with the highest return volatility. The findings of the study reveal that there exists a weak form of inefficiency in the Pakistan Stock Market, which implies the possibility of earning abnormal returns by investors using timing strategies. In terms of return predictability, this study is essential for international and domestic investors and it may affect their investment strategy and return management. The results might be interesting to the financial experts as they ponder the available conditions in the capital market for financial decision-making. This study is one of its first kind that includes both indices as well as industry returns for analysis of manufacturing industries in Pakistan stock exchange.

Eastern Yin-Yang Model of Change

Chinese cultural yin-yang view of change offers a rich understanding of organizational change process, actions, and context. Based on a “becoming” ontology, this yin-yang view assumes the reality to be an “ever-changing flow” rather than an event with clear beginning and ending points. By highlighting the concept of momentum, it encourages people to achieve a successful change by implementing various timing strategies such as momentum-seizing, momentum-entraining, and momentum-creating. Some ongoing studies on the yin-yang view of change are reviewed, including cultural beliefs in continuous change, momentum as driver of the change process, change agency as paradoxical leadership, and dialectical change with mutual transformation. The chapter illustrates the yin-yang model of change through the case of the Chengdu Bus Group that contributes novel insights into the previous literature on organizational change. It also summarizes the possible strengths and criticisms of this yin-yang view and puts forward some suggestions for future studies.

Internal crisis communication : the effects of negative employee-organization relationships and negative emotions on reputation and employees' unsupportive behavior

This study examines the role that negative employee-organization relationships (NEORs) play in determining crisis outcomes (organization's internal reputation and employees' unsupportive behavior). Moreover, the study aims to determine whether the timing of the communication message and the response strategies used in the message affect crisis outcomes. Finally, the role of negative emotions is investigated as mediating variables to explain the relationship between NEORs, crisis response strategies, and crisis timing strategies on crisis outcomes. This study employed an online experiment with 2 (crisis response strategy: rebuilding vs. defensive) x 2 (timing: stealing thunder vs. thunder) between-subjects factorial design with a total of 465 participants recruited from Amazon's market research tool, MTurk. The findings indicate that NEORs affect internal reputation negatively and increase the likelihood of unsupportive behavior. Timing does not affect the relationship between NEORs and crisis outcomes. Rebuilding strategies help in overcoming employees' unwillingness to support the organization during a crisis. Lastly, negative emotions influenced the effect of NEORs on the crisis outcomes. Both theoretical and practical implications are discussed.