Two faces of temporal binding: Action- and effect-binding are not correlated.

Research on the sense of agency has proliferated a range of explicit and implicit measures. However, the relation of different measures is poorly understood with especially mixed findings on the correlation between explicit judgments of agency and the implicit perceptual bias of temporal binding. Here, we add to the conundrum by showing that the two sub-components of temporal binding - action-binding and effect-binding, respectively - are not correlated across participants either, suggesting independent processes for both components. Research on inter-individual differences regarding the sense of agency is thus well-advised to rely on other implicit measures until the phenomenon of temporal binding is better understood.

The effects of action choice on temporal binding, agency ratings, and their correlation.

The sense of agency, i.e., the feeling of control over one's own actions and their consequences in the environment, is a crucial part of action taking. In experimental studies, agency is most commonly measured either directly via explicit agency ratings or indirectly via implicit measures, e.g., temporal binding. In order to aid our interpretation of previous and future results, several studies have focused on relating implicit and explicit measures of agency to one another. However, possibly due to different methodological issues, results have been far from conclusive. In the present study, we therefore contribute to this discussion by further characterizing temporal binding and explicit agency ratings in their response to action choice as an experimental manipulation in a high-powered design, and by studying how temporal binding and agency ratings are related in different experimental conditions. Furthermore, we discuss the possible influence of the specific agency question regarding the participants' ratings.

Optical isolator using an atomic vapor in the hyperfine Paschen-Back regime.

A light, compact optical isolator using an atomic vapor in the hyperfine Paschen-Back regime is presented. Absolute transmission spectra for experiment and theory through an isotopically pure 87Rb vapor cell show excellent agreement for fields of 0.6 T. We show π/4 rotation for a linearly polarized beam in the vicinity of the D2 line and achieve an isolation of 30 dB with a transmission >95%.

Core biological marker candidates of Alzheimer's disease - perspectives for diagnosis, prediction of outcome and reflection of biological activity.

Alzheimer's disease (AD) is a complex neurodegenerative dementing illness. Over the past few years, however, remarkable advances have taken place in understanding both the genetic and molecular biology with the intracellular processing of amyloid and tau and the changes leading to the pathologic formation of extracellular amyloid plaques and the intraneuronal aggregation of hyperphosphorylated tau into neurofibrillary tangles. This progress in our understanding of the molecular pathology has set the stage for clinically meaningful advances in the development of biomarkers. Emerging diagnostic methods that are based on biochemical and imaging biomarkers of disease specific pathology hold the potential to provide effective measures of natural history (marker of disease that is predictive of outcome), biological activity (such as magnitude and frequency of response correlating with drug potency) and markers of surrogate endpoints (single or composite marker that accounts for clinical benefit of the therapy). Markers of biological activity should be also evaluated regarding their value to reflect disease progression, heterogeneity of the clinical population, for early decision making and characterization of new treatments. We focussed on the current status of core analytes which provide reasonable evidence for association with key mechanisms of pathogenesis or neurodegeneration in AD. In addition, feasibility was important, such as availability of a validated assay for the biological measure in question, with properties that included high precision and reliability of measurement, reagents and standards well described. On this basis we reviewed the body of literature that has examined CSF total tau (t-tau) and beta-amyloid 1-42 (Abeta(1-42)), phosphorylated tau (p-tau) and beta-amyloid-antibodies as diagnostic tests for AD versus clinically representative comparison groups. Measurement of t-tau and Abeta(1-42) in the CSF seems useful to discriminate early and incipient AD from age-associated memory-impairment, depression, and some secondary dementias. First studies showed that measurement of p-tau proteins significantly improves early and differential diagnosis, as well as disease prediction in subjects at risk for AD and comes closest to fulfilling proposed criteria of a biological marker for AD. However, the nature of the majority of reported findings are still preliminary and retrospective. General issues for biomarkers have to be adequately addressed, such as sensitivity of the method, frequency of assessments, stability of the method, standardization of methods and dynamic range. There is still a partial lack of comparison patient populations that must be addressed in future studies. International dementia networks have been recently established to advance the establishment of core biomarker candidates of AD as potential surrogate endpoints for clinical trials and their clinical use for predictive and diagnostic purposes.

Menstrual synchrony and cycle variability: a reply to Schank (2000).

Menstrual synchrony has been measured by a change over time, to capture the "process" of synchronization or by examining a sample of women who have been together for a number of months ("state" synchrony). We have proposed and used a method for calculating "state" synchrony. On the basis of the results of a computer simulation, Schank (Schank, J.C., 2000. Menstrual-cycle variability and measurement: further cause for doubt. Psychoneuroendocrinology 25, 837-847) argues that our method is biased towards finding synchrony and that the degree of error is an increasing function of cycle variability. We show that Schank's model is based on unfounded assumptions. Contrary to Schank's assertion, on which much of the critique is based, there is no evidence that cycle variability is actually large in samples with "state" synchrony. Our reports are valid; and our method is supported both by convergent validity and by the use of statistical "random control" groups.

Potency estimation of recombinant factor VIII: effect of assay method and standard.

Large potency discrepancies between the chromogenic and one-stage clotting methods have been reported for patients' plasma samples following the infusion of recombinant factor VIII (rFVIII) concentrates. We have investigated the potency estimation of two different full-length rFVIII concentrates using both assay methods relative to both plasma and concentrate standards. Potencies by the chromogenic method were significantly higher (53% and 45%) than potencies by the one-stage clotting method when a plasma standard was used. In contrast, there was no significant potency difference between methods when a concentrate standard was used. Time-course studies into thrombin and activated factor X (FXa) generation, in modified clotting and chromogenic methods, respectively, revealed that the two rFVIII concentrates behaved very similarly to the concentrate standard, whereas the plasma standard showed slightly more rapid thrombin generation and markedly slower FXa generation. The different behaviour of rFVIII and plasma FVIII in the chromogenic method is proposed as the main cause of the methods-based potency discrepancy. The results support the use of a concentrate standard to measure rFVIII in post-infusion plasma.

Phospholipid binding of factor VIII in different therapeutic concentrates.

Binding to anionic phospholipid (PL) is essential for the biological function of factor VIII (FVIII). We have developed a method to study the level of PL binding of FVIII in a variety of therapeutic concentrates, using the BIACORETM system which utilizes the Surface Plasmon Resonance (SPR) phenomenon. A HPA sensor chip was employed on to which synthetic phospholipid unilamellar vesicles were adsorbed to form a 3:1 phosphatidylcholine: phosphatidylserine lipid monolayer. Using this surface the interaction of unlabelled FVIII in concentrates was observed from which direct kinetic data (kon, koff and KD values) were obtained in real-time. Marked differences in the binding to PL, as measured by KD values, between different products were observed. These fell into three categories: two recombinant FVIII products showed high affinities for PL with KD values around 0. 05-0.14 nM; four high-purity plasma derived products, two prepared by monoclonal antibody and two prepared by ion-exchange chromatography, had 6-8-fold lower affinities, and two intermediate-purity products had 34-60-fold lower affinities with KD values in the nM region. Measurements of kon and koff values for each product showed that the differences in the KD values expressed were primarily due to the differences in their respective kon values, although the recombinant products showed changes in the koff values. The study showed that the assessment of binding to PL by FVIII in concentrates was possible without prior purification and gave KD values in the range reported previously for other methods. The difference between the products requires further investigation but may be partly due to other proteins present, in particular the content and quality of von Willebrand factor which is known to affect PL binding of FVIII.

Human menstrual synchrony in families and among close friends: examining the importance of mutual exposure.

Human menstrual synchrony was examined in a sample of 73 urban households with a relatively high degree of mutual contact and interaction but less than that of a previously studied, possibly unique sample of Bedouin families with an extremely high degree of contact, interaction, and sexual segregation (A. Weller & Weller, 1997). In addition, for the first time, menstrual synchrony was studied among best friends who did not live together and among sisters who did versus did not share a bedroom. A very high degree of synchrony was found among families (51%) and among sisters (51%), and a relatively high degree of synchrony was found among close friends (30%). The results suggest that synchrony can be attained without sleeping in the same bedroom or even in the same house. The findings also suggest that an effective range of mutual exposure is an attribute of human menstrual synchrony; below or above this range, the phenomenon may not occur.

Menstrual synchrony in a sample of working women.

Menstrual synchrony has been typically studied among women who live together: dormitory roommates or family members sharing a bedroom or living in the same house. The current study examined menstrual synchrony in 51 pairs of women working together under conditions optimally conducive to synchrony. They had been together for at least 1 year, shared a relatively small office, worked there all day full time and contact with other people during the day was minimal. Prospective records of three menstrual dates showed a significant degree of synchrony for each of the 3 months. Menstrual onsets of close friends tended to occur on the average within 3.5-4.3 days of each other while onsets of co-workers who were not close friends were significantly more broadly ranged (7.7-9.0 days of each other). This is the first unequivocal demonstration of menstrual synchrony outside of the household.

An international collaborative study on the INR calibration of freeze-dried reference plasmas.

A study was carried out to calibrate potential European Reference Plasmas for prothrombin time (PT) standardization. The International Normalized Ratio (INR) values of three freeze-dried candidate plasmas (one pooled normal and two pools from anticoagulated patients) were determined in 20 laboratories using six thromboplastin reagents comprising three International Reference Thromboplastins (human, rabbit and bovine), two recombinant human reagents and one placental human reagent. Interlaboratory variability of INR estimation was low with geometric coefficients of variation (gcv) <10% except in one case. Significant differences in mean INR were found between the different thromboplastins with lowest INR values found with the bovine reagent. INR values from the International rabbit and human reagents differed by <6% and were combined to give proposed assigned INR values. Significant differences in INR estimates from four thromboplastins of human origin may indicate that single assigned INR values are not applicable for use with all thromboplastin reagents. Field trials to assess the validity of single assigned INR values in clinical practice are required.

Rational-emotive behavior therapy and the formation of stimulus equivalence classes.

Stimulus equivalence is a behavioral approach to analyzing the "meaning" of stimulus sets and has an implication for clinical psychology. The formation of three-member (A --> B --> C) stimulus equivalence classes was used to investigate the effects of three different sets of sample and comparison stimuli on emergent behavior. The three stimulus sets were composed of Rational-Emotive Behavior Therapy (REBT)-related words, non-REBT emotionally charged words, and a third category of neutral words composed of flower labels. Sixty-two women and men participated in a modified matching-to-sample experiment. Using a mixed cross-over design, and controlling for serial order effects, participants received conditional training and emergent relationship training in the three stimulus set conditions. Results revealed a significant interaction between the formation of stimulus equivalence classes and stimulus meaning, indicating consistently biased responding in favor of reaching criterion responding more slowly for REBT-related and non-REBT emotionally charged words. Results were examined in the context of an analysis of the importance of stimulus meaning on behavior and the relation of stimulus meaning to behavioral and cognitive theories, with special appraisal given to the influence of fear-related discriminative stimuli on behavior.

Assessment of menstrual regularity and irregularity using self-reports and objective criteria.

To assess subjective and objective definitions of menstrual regularity, and the relationship between them, 114 university students (mean age 20.3 years) prospectively recorded eight consecutive menstrual dates and reported whether they considered themselves 'regular' or 'irregular'. The percentage of women who reported being menstrually 'regular' or menstrually 'irregular' was compared with a classification developed according to a criterion based upon the results of their prospective menstrual records. According to self-reports and objective measures of regularity, a similar portion of the women (about 70%) were regular. But when cross-classifying regularity and non-regularity by the two procedures, it was found that only 44% of those who defined themselves as irregular were likewise defined by the objective criteria, whereas 82% of the women who defined themselves as regular were also deemed so by the objective criteria. It is concluded that some women will, and others will not, construe 'variability' as 'irregularity'.

Prolonged and very intensive contact may not be conductive to menstrual synchrony.

Menstrual synchrony was not found for 30 cohabiting lesbian couples (mean time living together, 35 months), for whom 3 months of menstrual data were collected prospectively. A combined analysis with two previous studies of lesbian couples (Trevathan, W, Burleson, NH, Gregory, L (1993) No evidence for menstrual synchrony in lesbian couples. Psychoneuroendocrinology 18, 425-431; Weller, A, Weller, L (1992) Menstrual synchrony in female couples. Psychoneuroendocrinology 17, 171-177) also failed to reveal synchrony. These data are considered together with a previous study of Bedouin couples which found only a moderate degree of synchrony (Weller, A, Weller, L (1997a) Menstrual synchrony under optimal conditions: Bedouin families. J Comp Psychol 111, 143-151). When women live together for an extensive period of time and have intensive social contact among them, the intensive contact may not be conducive to menstrual synchrony.

Gender differences in the sexual rating of words.

The present study investigated whether gender-based differences in the rating of sexual words still exist in the late 1990s. Men and women evaluated 400 English-language words on the characteristics of sexual charge and sexual ambiguity. Data gathered from these ratings were compared with other factors such as religious involvement, sexual experience, sex guilt, and social desirability. Men and women did not differ in their sexual ratings of the list. However, because the list contained a large number of words that had no sexual content at all, gender differences were examined for ratings of a sample of 30 sexually ambiguous words. As hypothesized, men rated these words as significantly more sexual than women. Significant gender differences were found on a number of sexuality and personality measures. Women were more religious than men, and religiosity was significantly correlated with most of the other measures. Women also had higher social desirability scores, which implies that they may have been responding in a socially desirable manner and were not completely honest. Overall, gender differences followed gender-oriented stereotypes: (a) Women have greater sexual guilt than men, (b) women are less sexually arousable or more "erotophobic," and (c) women are less comfortable answering questions about their sexuality and rating words.

Menstrual synchrony under optimal conditions: Bedouin families.

Ovarian cycles of females living and interacting together have been shown to synchronize in a number of species. In humans, the related phenomenon of menstrual synchrony has been reported among roommates and best friends. Menstrual data were collected prospectively for 3 months from 27 Bedouin nuclear families living under conditions optimally conducive for synchrony: (a) women living together for many years, (b) a highly sexually segregated society, (c) standard living conditions, and (d) minimal use of oral contraceptives. Results show unequivocally the existence of menstrual synchrony: A 20%-25% shift toward synchrony was found for sisters-roommates, sisters-roommates who are close friends, and the family (all women in the family between 13 and 50 years of age).

Localisation and expression of metallothionein immunoreactivity in the developing sheep brain.

Metallothioneins are small cysteine-rich proteins that bind heavy metals. In higher mammals there are complex families of metallothionein isoforms, which are well characterised at the DNA level but less so in terms of their cellular expression and function. In particular, little is known about the localisation of metallothionein in the developing mammalian brain. In this study using sheep fetuses, we have shown that metallothionein 1 and 2 isoform expression undergoes shifts in regional and cellular localisation during development of the brain. Metallothionein 1 and 2 expression is first detected by embryonic days E72 E73 (gestation is 150 days) at the mRNA level and the metallothionein protein is observed in cells of the proliferating ventricular zones. Subsequent expression is detected in radial glial cells, oligodendrocytes and astrocytes in several regions of the brain, most notably the cerebral cortex. In the adult brain, metallothionein is expressed in astrocytes but not in oligodendrocytes. Double-labelling immunohistochemistry using the glial fibrillary acidic protein (GFAP) an astrocyte marker, and metallothionein revealed that although there is an overlap in the profiles of the two proteins, there is no simple correlation in their expression. These observations are consistent with metallothionein, under physiological conditions, being regulated mainly by intracellular factors.

Menstrual variability and the measurement of menstrual synchrony.

While the timing of menstrual cycles must be modifiable in order for the phenomenon of menstrual synchrony to occur, cycle variability and the occurrence of irregularly long or short cycles complicate the measurement of the process of synchronization over time and of determining whether synchrony exists for women who have lived together for a long period of time. The paper examines how each of five different ways of measuring menstrual synchrony (utilized in the literature) deals with menstrual variability and irregular cycles. On the basis of this analysis, the mathematical concept of "the limit of a sequence,' and analysis of data according to these five different approaches, we recommend the approach in which women record their onset dates after they have been together for a prolonged period of time. The observed onset differences between the women are then compared to expected onset differences, based on the assumption of random onset occurrence. A significant influence of irregular cycle lengths on synchrony was not found in this data set and in the other studies which examined this issue. Research to date has focused on a relatively narrow aspect of menstrual regularity and synchrony and has failed to emphasize the coupled pattern of events over time as well as to analyze menstrual synchrony as a cyclic system.

Menstrual synchrony: only in roommates who are close friends?

This study examined menstrual synchrony among roommates residing in 20 university housing units. Menstrual synchrony was examined for roommates who were close friends and roommates who were not close friends, and by housing unit. The impact of personality, social-interaction and menstrual-related factors was also studied. To avoid limitations found in previous studies, (i) data were collected prospectively and (ii) over the entire academic year; (iii) high participation rate was obtained (86%); and (iv) women who used oral contraceptives were excluded. Menstrual synchrony was found among roommates who were close friends. Synchrony was not found for roommates who were not close friends, nor by housing units. The phenomenon of menstrual synchrony may more likely occur among close friends and women with intensive social contact than under the conditions common to university dormitories.

Menstrual synchrony: agenda for future research.

While many studies have confirmed McClintock's (1971) finding of human menstrual synchrony, it is also clear that menstrual synchrony does not always occur. To better understand the mechanisms and functions of this phenomenon, this paper suggests directions for future research aimed at delineating the context and conditions under which menstrual synchrony occurs. It is proposed that the following research issues be explored: multiple sources of social influence; quality of social relationships; analyzing couple (or group) data; who synchronizes to whom?; group size; putative pheromones; age and age diversity; and contraceptive practices.