Law Of Initial Value Research Articles

Testosterone replacement therapy: association with mortality in high-risk patient subgroups.

We describe studies determining the association between testosterone therapy (TTh) and mortality. We used a registry database of 737 men with adult-onset testosterone deficiency defined as presenting with low serum total testosterone (TT) levels ≤12.1nmol/L and associated symptoms over a near 10-year follow-up. We compared associations between testosterone undecanoate (TU), cardio-metabolic risk factors and mortality using non-parametric statistics followed by separate Cox regression models to determine if any association between TU and morality was independent of age and cardio-metabolic risk factors. Finally, the association between TU and mortality was studied in men stratified by cardio-metabolic risk. During a median follow-up interquartile range (IQR) of 114 (84-132) months, 94 of the 737 men died. TU (ref: non-treatment) was associated with mortality; hazard ratio=0.23, 95% confidence intervals=0.14-0.40. Cox's regression models showed the above association to be independent of baseline age, waist circumference, hemoglobin A1c, lipids, blood pressure, smoking, and type 2 diabetes. These variables remained associated with mortality. We finally stratified the men by the high-risk baseline variables and established that the association between mortality and TU was only evident in men at higher risk. A possible explanation could lie with the "law of initial value," where greater improvements are evident following treatment in patients with worse baseline values. This study with long follow-up confirms that TTh is associated with lower mortality in men with adult-onset TD. This association was evident only in men with greater cardio-metabolic risk factors who demonstrated greater benefit.

The perception and response of T cells to a changing environment are based on the law of initial value.

αβ T cells are critical components of the adaptive immune system and are capable of inducing sterilizing immunity after pathogen infection and eliminating transformed tumor cells. The development and function of T cells are controlled through the T cell antigen receptor, which recognizes peptides displayed on major histocompatibility complex (MHC) molecules. Here, we review how T cells generate the ability to recognize self-peptide-bound MHC molecules and use signals derived from these interactions to instruct cellular development, activation thresholds, and functional specialization in the steady state and during immune responses. We argue that the basic tenants of T cell development and function follow Weber-Fetcher's law of just noticeable differences and Wilder's law of initial value. Together, these laws argue that the ability of a system to respond and the quality of that response are scalable to the basal state of that system. Manifestation of these laws in T cells generates clone-specific activation thresholds that are based on perceivable differences between homeostasis and pathogen encounter (self versus nonself discrimination), as well as poised states for subsequent differentiation into specific effector cell lineages.

Predictors of blood pressure response after renal denervation beyond pretreatment blood pressure

Abstract Background The principle of initial value (Wilder's law of initial value) proposes that the “direction of response of body function to any agent depends to a large degree on the initial value of that function”. Indeed, in several trials on renal denervation (RDN), pre-treatment blood pressure (BP) has been consistently and repeatedly found to predict the decrease in BP after RDN. Efforts to discover further statistically significant and clinically meaningful predictors of BP response to RDN failed. Objective By use of a new methodological approach, we aimed to determine predictors of BP response after RDN in patients with resistant hypertension. Methods The study population comprised 266 patients with resistant hypertension (mean age 62 years, 34% females, mean BMI 30.5 kg/m2, 27% had coronary heart disease, 42% had diabetes mellitus and 61% had hypercholesterolaemia) who underwent radiofrequency RDN with the Symplicity catheter at the Universities of Homburg and Erlangen. Clinical data including 24h ambulatory BP (ABP) were obtained prior to, and 3, 6 and 12 months after RDN. The primary parameter of response was defined as change in 24-hour systolic ABP after 6 months from pre-treatment values. As expected, change in 24h systolic ABP correlated with pre-treatment 24h systolic ABP (r2 linear = 0.225, p<0.001), with change in 24h systolic ABP = 73.82 + 0.55 x pre-treatment 24h systolic ABP. To overcome the predominant role of the pre-treatment BP that may mask other factors, we calculated for each individual patient the “expected systolic ABP decrease” by applying this regression equation and the “excessive systolic ABP decrease” by subtracting the measured from expected change in 24h systolic ABP. We divided the study population into 2 groups (above [responders] and below [non-responders] of the median change in excessive 24h systolic ABP. Results Neither pre-treatment 24h systolic or diastolic ABP, nor office systolic or diastolic BP differed between the two groups (all p>0.20). Following RDN, 24h systolic ABP decreased in the responders by −23.3±16 vs non-responders +1.4±11 mmHg at 6 month, and 24h systolic ABP values were also significantly lower in responders at 3 and 12 months (all p<0.001), without difference in number of antihypertensive drugs between the groups. Of all clinical variables at baseline, office heart rate (65.6 vs 68.7±12 bpm, p=0.024) and HbA1c (6.07±0.88 vs. 6.37±1.23%, p=0.035) were lower in responders compared with non-responders. Finally, a multiple regression analysis confirmed that pre-treatment 24h systolic ABP (beta +0.565, p<0001), HbA1c (beta −0.167, p=0.004) and office HR (beta +0.106, p=0.057) were independent predictors of decrease in 24h systolic ABP. Conclusion In patients with resistant hypertension, lower HbA1c and office HR were identified as predictors of BP response in addition to pre-treatment BP. This finding may help to identify hypertensive patients who benefit most from RDN. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Extramural grant provided vy Medtronic INc

Antihypertensive drug effects according to the pretreatment self-measured home blood pressure: the HOMED-BP study

ObjectivesTo clarify whether or not the antihypertensive drug effect is proportional to the baseline pretreatment self-measured home blood pressure (HBP) in accordance with the law of initial value (Wilder’s law).DesignA...

Baseline Response Levels are a Nuisance in Infant Contingency Learning

The impact of differences in level of baseline responding on contingency learning in the first year was examined by considering the response acquisition of infants classified into baseline response quartiles. Whereas the three lower baseline groups showed the predicted increment in responding to a contingency, the highest baseline responders did not. Instead, they responded less in the contingency period relative to baseline. In extinction, the four baseline quartile groups failed to differ. The findings are considered in the context of the law of initial value, and some potential reasons for the effect of baseline responding on contingency learning are discussed. These studies show that variability in baseline responding may compromise our understanding of contingency detection especially for infants with high baseline response levels. Copyright © 2014 John Wiley & Sons, Ltd.

Elucidation of the physiological adjustment effect of forest therapy.

The aim of this study was to elucidate the physiological adjustment effect of forest therapy based on the Law of Initial Value. The experiments were conducted in nine forest and urban areas in Japan during the period from 2011 to 2012. There were 12 male Japanese university students participating in each of the nine experiments (total, 108 participants). Of these, 98 subjects (mean age ± standard deviation, 21.4 ± 1.6 years) were analyzed. The subjects were instructed to view a real forest landscape or urban area for 15 min. The systolic blood pressure, diastolic blood pressure, and pulse rate of each subject were measured. We analyzed the correlation between the initial values (after city viewing) and the differences in values between the two environments (after forest viewing-after city viewing). There was a negative correlation between the initial values and the differences in values between the two environments. The subjects whose initial systolic blood pressure, diastolic blood pressure, and pulse rate were high showed marked decreases in these parameters as their response after viewing the forest environment, whereas those whose initial systolic blood pressure, diastolic blood pressure, and pulse rate were low showed increases in these parameters as their response. These results support the premise that the physiological effect of a forest environment can differ depending on a subject's initial response values. Moreover, it was clear that forest therapy caused physiological adjustment, normalizing blood pressure and pulse rate.

Applying Psychophysiological Measures to Marketing and Advertising Research Problems

Abstract Applications of psychophysiological measures to the problem of evaluating advertising and marketing stimuli are reviewed. It is suggested that most of these applications have been simplistic and based on the erroneous concept of a unitary activation continuum. Fundamental principles of psychophysiology have routinely been ignored in such applications. Among these principles are (1) the law of initial values, (2) individual response stereotypy, (3) stimulus-response specificity, and (4) directional fractionation of response. Methodological controls which should be observed when using psychophysiological measures are reviewed. While it is concluded that psychophysiological measures are not a ready solution for problems related to the evaluation of the relative efficacy of marketing and advertising stimuli, certain applications of psychophysiological measures to marketing and advertising research appear viable.

Mathematical Coupling and the True Role of Baseline Severity in Acute Mania Trials

Recently two meta-analyses concerning medication in acutemania were published, one of them in Neuropsychophar-macology (Tarr et al, 2011; Yildiz et al, 2011). Both of themreport an analysis of change vs initial severity. This kindof analysis has already been reported by a number ofmeta-analyses of medication in unipolar depression. In oneof them, the authors reported a significant relationshipbetween change in raw YMRS score and baseline raw YMRSscore for all treatment arms combined (Tarr et al, 2011).However, in the second one, the authors used Hedges’ geffect size vs baseline score as percentage of maximum,and reported that higher baseline mania ratings predictedgreater improvement with drug but not with placebo(Yildiz et al, 2011). The meta-analytic studies on unipolardepression suggested that medication might not work formildly depressed patients and hence they should not beprescribed, and as similar findings and conclusions seem toemerge from the meta-analysis of acute mania trials, itseems important to tackle again this issue.The relation between baseline disease severity and treat-ment effect has a generic name in the statistical literature, therelation between change and initial value (Blomqvist, 1977),because treatment effect is evaluated by measuring thechange of variables from their initial (baseline) values. Inpsychology, it is also well known as the ‘law of initial value’(Jin, 1992).The use of effect size concept (Cohen’s d or Hedges’ g)ismore suitable in comparison with raw score as it controlsfor the variability within studies, and maybe to some extentfor the floor and ceiling effects, which every psychometricscale score manifests at very-low or very-high values.Mathematical coupling occurs when ‘one variable directlyor indirectly contains the whole or part of another’ (Tu andGilthorpe, 2007). As change scores are the pretreatmentscores minus the post-treatment scores, they contain thepretreatment scores. Mathematical coupling can lead toan artificially inflated association between initial valueand change score, when correlation or regression is used(Tu et al, 2004).Although there is some concern that group scores arenot affected by the mathematical coupling to the extentindividual scores are, still the use of standard regres-sion and correlation methods should be consideredinappropriate. The use of the effect size g in the y axis byYildiz et al protected their analysis from the mathematicalcoupling effect. Thus, their results should be consideredcloser to reality whereas Tarr’s should be considerederroneous.DISCLOSUREBoth authors have received support concerning travel andaccommodation expenses from various pharmaceuticalcompanies in order to participate in medical congresses.Dr Fountoulakis has also received honoraria for lecturesfrom the Astra-Zeneca, Janssen-Cilag, Eli-Lilly and aresearch grant from the Pfizer Foundation. Dr Kontis hasreceived honoraria for lecturing by Janssen, Pfizer, andBristol-Myers Squibb.REFERENCES

Ethnic differences in thermoregulatory responses during resting, passive and active heating: application of Werner’s adaptation model

For the coherent understanding of heat acclimatization in tropical natives, we compared ethnic differences between tropical and temperate natives during resting, passive and active heating conditions. Experimental protocols included: (1) a resting condition (an air temperature of 28°C with 50% RH), (2) a passive heating condition (28°C with 50% RH; leg immersion in a hot tub at a water temperature of 42°C), and (3) an active heating condition (32°C with 70% RH; a bicycle exercise). Morphologically and physically matched tropical natives (ten Malaysian males, MY) and temperate natives (ten Japanese males, JP) participated in all three trials. The results saw that: tropical natives had a higher resting rectal temperature and lower hand and foot temperatures at rest, smaller rise of rectal temperature and greater temperature rise in bodily extremities, and a lower sensation of thirst during passive and active heating than the matched temperate natives. It is suggested that tropical natives' homeostasis during heating is effectively controlled with the improved stability in internal body temperature and the increased capability of vascular circulation in extremities, with a lower thirst sensation. The enhanced stability of internal body temperature and the extended thermoregulatory capability of vascular circulation in the extremities of tropical natives can be interpreted as an interactive change to accomplish a thermal dynamic equilibrium in hot environments. These heat adaptive traits were explained by Wilder's law of initial value and Werner's process and controller adaptation model.

Behavioral and brain temperature responses to salient environmental stimuli and intravenous cocaine in rats: effects of diazepam

While diazepam is an effective anxiolytic and somnolent drug in humans, its physiological and behavioral effects in animals are often variable. Differences in basal activity state (basal arousal) may be important in determining both this response variability and the pattern of drug influence on behavioral and physiological responses to natural arousing stimuli and other drugs. To evaluate the changes in brain, muscle, and skin temperatures, and in locomotion induced in rats by several arousing stimuli and intravenous (i.v.) cocaine; and to assess how these responses are modulated by diazepam at a relatively low dose (1 mg/kg, i.p.). Male rats were implanted with thermal probes in the nucleus accumbens (NAcc), temporal muscle, and subcutaneously, and equipped with a chronic i.v. catheter. They were exposed to 1-min tail-pinch, 1-min social interaction with another male and cocaine (1 mg/kg, i.v.) after administration of diazepam or saline. While the injection of either diazepam or saline resulted in similar locomotor activation and temperature responses, diazepam decreased basal brain and muscle temperatures for about 3 h; the temperature-decreasing effect of diazepam was oppositely related to basal brain temperature (r = -0.51). After diazepam, rats also showed weaker temperature and locomotor responses to both arousing stimuli; the effect was stronger for tail-pinch and for absolute temperature increases than relative changes. Although diazepam significantly decreased cocaine-induced locomotor activation, it had virtually no effects on cocaine-induced temperature responses in all locations. In accordance with the "law of initial values", the temperature-increasing effects of all tested arousing stimuli and temperature-decreasing effect of diazepam depend upon basal brain temperature. The greatest temperature effects are seen with arousing stimuli at low basal arousal (increases) and with diazepam at high basal arousal (decreases). This is a likely explanation for the variability seen with the physiological and behavioral effects of diazepam in animals.

Patient-Practitioner-Remedy (PPR) Entanglement, Part 7: A Gyroscopic Metaphor for the Vital Force and Its Use to Illustrate Some of the Empirical Laws of Homeopathy

Background: One of the principle obstacles to homeopathy’s general acceptance has been its perceived lack of sound theoretical basis within accepted deterministic bio-medical thought. This impasse might be circumvented if instead, appeal was made to the nondeterministic concepts of the physical sciences, e.g., quantum theory and its notions of entanglement, nonlocality, and uncertainty; Weak Quantum Theory (WQT) and Patient-Practitioner-Remedy (PPR) Entanglement representing two new complementary strands of thought with the potential to create a new theoretical basis for homeopathy. Objective: The goal of this present study was to generate a preliminary mathematical model of the action and reaction of the Vital Force to diseases and remedies within the developing contexts of WQT and PPR Entanglement, based on the metaphor of a hypothetical ‘quantized’ gyroscope as its physical representation. Methods: The physics of gyroscopic motion was combined with the quantum theory describing rotating objects (without some of its imposed limitations, e.g., Planck’s constant, in line with the relaxation of some of orthodox quantum theory’s axioms as proposed by WQT). Thus, increase or decrease in the rate of spin of the Vital Force’s hypothetical gyroscope was described in terms of quantized ‘shift operators’ constructed mathematically from the known ‘complementarity’ of a remedy’s primary and secondary symptoms, expressed in the notation of complex numbers. Ultimately, this generates a hypothetical ‘wave function’ for the Vital Force. Results: This hypothetical ‘wave function’ has been used to illustrate certain empirical observations of homeopathy and conventional medicine, e.g., the biphasal action of remedies encapsulated in the Arndt-Schulz Law, Wilder’s Law of Initial Value, and some of the results of homeopathic provings. Conclusion: This preliminary theoretical analysis suggests that perhaps these less well-known empirical observations should be reinvestigated and, if confirmed, could begin ultimately to provide a much-needed alternative to the doubleblind placebo-controlled trial as a means of investigating and testing the efficacy of homeopathy.

On statistical approaches to the study of the ?Law of Initial Values?

This paper is concerned with the well-known “Law of Initial Values” (Wilder, 1931, 1967). First, possible causes of this phenomenon of initial value dependence are discussed. The limitations of a structural relationships based method for testing its effect in empirical data sets in social and behavioral science research are next discussed. Within the popular structural equation modeling methodology, a multiple-indicator model is then focused on, which allows studying the “Law of Initial Values”. The described approach is illustrated using data from a cognitive intervention study (Baltes, Dittmann-Kohli & Kliegl, 1986).

Measurement of Change and the Law of Initial Values: A Computer Simulation Study

Computer simulations were used to examine the effect of a negative correlation between baseline and change on two measures of change: gain scores and covariance. When a negative correlation resulted from decreasing variance from pretest to posttest, as might be due to the presence of floors or ceilings (the Law of Initial Values) or skewness, gain scores were less powerful than covariance. However, when a negative correlation resulted from measurement error alone, the relative power of gain scores and covariance was unaffected. It was concluded that the correlation between baseline and change, by itself, does not invalidate the use of gain scores. However, when the negative correlation is accompanied by a decrease in variance from pretest to posttest, covariance is a superior index of change.

Origins of baseline variance and the Law of Initial Values.

The Law of Initial Value (LIV) asserts that the magnitude of a phasic psychophysiological response is dependent on the initial baseline level. Although results in accord with the LIV are often observed, exceptions are frequent, especially for between-subjects analyses. A general assumption in studies of the LIV is that a given baseline difference is equivalent regardless of its functional origin. The present study examined the relationships between basal heart period variance, arising from alternate sources, and the magnitude of the chronotropic response to a speech stressor. Results reveal that baseline differences due to orthostatic manipulations, which are known to be largely of autonomic origin, yielded larger LIV effects than did individual differences in basal heart period, which include a significant nonautonomic component. The minimal LIV-like effects of baseline differences associated with non-autonomic factors, relative to variations in autonomic control, may contribute to the inconsistent appearance of between-subjects LIV effects.

Effect of the dopamine D 2 antagonist sulpiride on event-related potentials and its relation to the law of initial value

Effects of the dopamine antagonist sulpiride on event-related potentials (ERPs) were investigated during an auditory odd ball task in 18 healthy volunteers. Sulpiride (150 or 300 mg) or an inactive placebo was administered according to a completely randomized double-blind cross-over design. ERPs were recorded 1 h after medication was given. Sulpiride shortened the P200 latency for frequent stimuli, but tended to increase the N200 and P300 latencies for rare stimuli. Although on the whole sulpiride had no effect on the amplitudes of the ERP components in the subjects, it increased the P300 amplitudes in the low P300 amplitude subjects and decreased them in the high P300 amplitude subjects. This tendency for a bidirectional response was also found for the N100 and N200 amplitudes. A single administration of 150 or 300 mg sulpiride is considered to affect the ERP latencies and amplitudes in healthy subjects, the bidirectional response that takes place being dependent on the difference in the initial values. The results of this study are discussed in relation to the ‘Law of initial value’.

Autonomic space and psychophysiological response.

Contemporary findings reveal that autonomic control of dually innervated target organs cannot adequately be viewed as a continuum extending from parasympathetic to sympathetic dominance. Rather, a two-dimensional autonomic space, bounded by sympathetic and parasympathetic axes, is the minimal representation necessary to characterize the multiple modes of autonomic control. We have previously considered the theoretical implications of this view and have developed quantitative conceptual models of the formal properties of autonomic space and its translation into target organ effects. In the present paper, we further develop this perspective by an empirical instantiation of the quantitative autonomic space model for the control of cardiac chronotropy in the rat. We show that this model (a) provides a more comprehensive characterization of cardiac response than simple measures of end-organ state, (b) permits a parsing of the multiple transformations underlying psychophysiological responses, (c) illuminates and subsumes psychophysiological principles, such as the Law of Initial Values, (d) reveals an interpretive advantage of expressing cardiac chronotropy in heart period rather than heart rate, and (e) has fundamental implications for the direction and interpretation of a broad range of psychophysiological studies.

Female sexual arousal and the law of initial value: Assessment at several phases of the menstrual cycle

Genital responses to erotic film and fantasy were recorded from 10 women at five phases of the menstrual cycle by means of vaginal photoplethysmography. Relationships between baseline (prestimulation) and difference (stimulation minus prestimulation) levels of response were examined. Neither vaginal blood volume nor average pulse amplitude conformed to the law of initial value ("the higher the baseline level, the less will be the difference score"). Baseline levels and difference scores generally were positively correlated at each phase of the menstrual cycle in the case of average pulse amplitude. For blood volume the correlations between baseline levels and difference scores were inconsistent in direction and small in magnitude, but trends differed between phases of the menstrual cycle. It is recommended that measures of female sexual arousal obtained through testing women who are at different phases of the cycle should not be aggregated unless it is established that the relationship between baseline levels and difference scores is uniform across phases.

Cardiac psychophysiology and autonomic space in humans: empirical perspectives and conceptual implications.

Contemporary findings reveal that autonomic control of dually innervated visceral organs does not lie along a single continuum extending from parasympathetic to sympathetic dominance. Rather, a bivariate autonomic space bounded by sympathetic and parasympathetic axes is the minimal representation necessary to capture the modes of autonomic control. We here empirically instantiate a quantitative bivariate model for the chronotropic control of the heart in humans. This model provides a more comprehensive characterization of psychophysiological response than simple measures of end-organ state and permits a differentiation of behavioral states and processes that would otherwise remain obscure. The model also illuminates and subsumes general principles such as the law of initial values and reveals a fundamental physiological rationale for the selection of heart period over heart rate as a metric for cardiac chronotropy. The present article also considers strategies for psychophysiological investigations within the autonomic space model, the limitations of these methods, and analytical tools for assessing their validity.

Toward a reconceptualization of the law of initial value.

The traditional model of the law of initial value (LIV), "the higher the initial value, the smaller the response to function-raising, the larger the response to function-depressing stimuli" (Wilder, 1967, p. viii), is critically reviewed. Statistically, the usage of rDX, bDX, and bYX as the indices of LIV contains a spurious X(Y-X) effect. Moreover, defining initial value as a synonym of baseline is too narrow to cover an organism's various states. The parameter of structural relationship beta e value and a null hypothesis test (beta e = 1) are recommended to examine initial-value dependency for different levels of initial value and trends of change. Data suggest that LIV should be revised as follows: The higher the initial value, the greater the organism's following reactivity, although a tendency to reversed responses may occur when the initial value reaches its upper extremity. Both phenomena are probably due to constitutional and homeostatic mechanisms, respectively.

The law of initial values: a four factor theory

The effects of four factors, measurement error, skewness, floor/ceiling effects, and reactivity, on the correlation between change and initial level were studied using computer simulations. A total of 24 conditions were simulated: the four factors being examined together with variations in the direction of change, level of measurement error and/or strength of effect. In each condition ten random samples of 50 cases were generated by SPSSX, and compute functions were used to model the effects of interest. Three factors were capable of producing a negative correlation (the Law of Initial Values, LIV): measurement error, skewness, and floor/ceiling effects. Two factors yielded a positive correlation (anti-LIV effect): reactivity and skewness. The issue of how to determine which factor is operating in a given situation is discussed.