Action-effect knowledge transfers to similar effect stimuli.

The ability to anticipate the sensory consequences of our actions (i.e., action-effects) is known to be important for intentional action initiation and control. Learned action-effects can select the responses that previously have been associated with them. What has been largely unexplored is how learned action-effect associations can aid action selection for effects that have not previously associated with an action but are similar to learned effects. In two studies, we aimed to show that when presented new, unknown action-effects, participants select the responses that have previously been associated with similar action-effects. In the first study (n = 27), action-effect similarity was operationalized via stimuli belonging to the same or different categories as the previously learned action-effects. In the second study (n = 31), action-effect similarity was realized via stimuli that require comparable motor responses in real life. Participants first learned that specific responses are followed by specific visual effect stimuli. In the test phase, learned effect stimuli, new but similar effect stimuli and new but dissimilar effect stimuli were presented ahead of the response. The findings revealed that both learned effect stimuli and new similar effect stimuli affected response times, whereas new dissimilar effects did not. When a learned or a new similar effect was followed by a learned response, compared to an unlearned response, the responses were faster. We interpret these findings in terms of action-effect learning. The action-effect once bound to an action is used to select an action if a similar effect for which no action has been learned yet is presented. However, it is noteworthy that, due to our design, other explanations for the found transfer are conceivable. We address these limitations in the General Discussion.

Immediate action effects motivate actions based on the stimulus-response relationship.

The theory of event coding, an influential framework for action planning, suggests that humans first integrate stimulus, response, and action effect into representation (an event file) via their contingencies, and then, the activation of expected action effects drives the associated response. While previous studies have typically examined such functions of action effects after, rather than before or during, the acquirement of the representation, Eitam et al. (Exp Brain Res 229:475-484, 2013a) demonstrated that the presence of immediate feedback to action (i.e., action effects) can instantly elicit faster responses than delayed feedback. However, the underlying mechanism of this faciliatory effect remains unclear. Specifically, while the response-effect relationship has been highlighted, the role of stimuli has not been investigated. To address this issue, the present study conducted four experiments. We first reproduced the faciliatory effects of immediate action effects with between- and within-participants design (Experiments 1 and 2, respectively). Then, we assessed whether immediate action effects facilitate response speed, when stimuli (Experiment 3) and a combination of stimuli and responses (Experiment 4) determined the delay of action effects. The identical response was executed faster when driven by stimuli associated with immediate effects than by those associated with lagged effects. This result indicates that immediate action effects do not reinforce the execution of specific motor actions itself, but facilitate actions depending on the stimulus-response relationship. We discuss the potential mechanism of the facilitation effect.

Rapid saccadic categorization of other-race faces.

The human visual system is very fast and efficient at extracting socially relevant information from faces. Visual studies employing foveated faces have consistently reported faster categorization by race response times for other-race compared with same-race faces. However, in everyday life we typically encounter faces outside the foveated visual field. In study 1, we explored whether and how race is categorized extrafoveally in same- and other-race faces normalized for low-level properties by tracking eye movements of Western Caucasian and East Asian observers in a saccadic response task. The results show that not only are people sensitive to race in faces presented outside of central vision, but the speed advantage in categorizing other-race faces occurs astonishingly quickly in as little as 200 ms. Critically, this visual categorization process was approximately 300 ms faster than the typical button press responses on centrally presented foveated faces. Study 2 investigated the genesis of the extrafoveal saccadic response speed advantage by comparing the influences of the response modality (button presses and saccadic responses), as well as the potential contribution of the impoverished low-spatial frequency spectrum characterizing extrafoveal visual information processing. Button press race categorization was not significantly faster with reconstructed retinal-filtered low spatial frequency faces, regardless of the visual field presentation. The speed of race categorization was significantly boosted only by extrafoveal saccades and not centrally foveated faces. Race is a potent, rapid, and effective visual signal transmitted by faces used for the categorization of ingroup/outgroup members. This fast universal visual categorization can occur outside central vision, igniting a cascade of social processes.

Explicit instruction of rules interferes with visuomotor skill transfer.

In the present study, we examined the effects of explicit knowledge, obtained through instruction or spontaneous detection, on the transfer of visuomotor sequence learning. In the learning session, participants learned a visuomotor sequence, via trial and error. In the transfer session, the order of the sequence was reversed from that of the learning session. Before the commencement of the transfer session, some participants received explicit instruction regarding the reversal rule (i.e., Instruction group), while the others did not receive any information and were sorted into either an Aware or Unaware group, as assessed by interview conducted after the transfer session. Participants in the Instruction and Aware groups performed with fewer errors than the Unaware group in the transfer session. The participants in the Instruction group showed slower speed than the Aware and Unaware groups in the transfer session, and the sluggishness likely persisted even in late learning. These results suggest that explicit knowledge reduces errors in visuomotor skill transfer, but may interfere with performance speed, particularly when explicit knowledge is provided, as opposed to being spontaneously discovered.

Hypertensive disorders of pregnancy increase the risk for chronic kidney disease: A population-based retrospective study.

Hypertensive disorders of pregnancy (HDP) and chronic kidney disease (CKD) are well-known risk factors for cardiovascular disease (CVD) in later life. However, few studies have investigated the association of HDP with CKD. Moreover, these studies utilized either registry- or clinical-based data and did not include subclinical CKD patients. To address this gap in the literature, we investigated whether HDP is related to CKD, diagnosed based on the estimated glomerular filtration rate (eGFR), in later life. We designed a population-based, retrospective study, and reviewed the results of blood and physiological examinations as well as the results of pregnancy data available in patients' Maternity Health Record Books for 312 women. We identified 15 women with a diagnosis of CKD based on the eGFR, and 14 women with HDP. We found that women who experienced HDP had a high risk of CKD in later life compared with women without HDP (odds ratio (OR): 4.854; 95% confidence interval (CI): 1.042-22.621). Compared with normotensive women, those who were hypertensive at the time of the examination were significantly associated with CKD (OR: 3.109; 95% CI: 1.213-11.510). Awareness regarding the risk for CKD and CVD in a relatively young age can enable women to prevent diseases effectively.

Effects of learning duration on implicit transfer.

Implicit learning and transfer in sequence acquisition play important roles in daily life. Several previous studies have found that even when participants are not aware that a transfer sequence has been transformed from the learning sequence, they are able to perform the transfer sequence faster and more accurately; this suggests implicit transfer of visuomotor sequences. Here, we investigated whether implicit transfer could be modulated by the number of trials completed in a learning session. Participants learned a sequence through trial and error, known as the m × n task (Hikosaka et al. in J Neurophysiol 74:1652-1661, 1995). In the learning session, participants were required to successfully perform the same sequence 4, 12, 16, or 20 times. In the transfer session, participants then learned one of two other sequences: one where the button configuration Vertically Mirrored the learning sequence, or a randomly generated sequence. Our results show that even when participants did not notice the alternation rule (i.e., vertical mirroring), their total working time was less and their total number of errors was lower in the transfer session compared with those who performed a Random sequence, irrespective of the number of trials completed in the learning session. This result suggests that implicit transfer likely occurs even over a shorter learning duration.

Dynamic neural network reorganization associated with second language vocabulary acquisition: a multimodal imaging study.

It remains unsettled whether human language relies exclusively on innately privileged brain structure in the left hemisphere or is more flexibly shaped through experiences, which induce neuroplastic changes in potentially relevant neural circuits. Here we show that learning of second language (L2) vocabulary and its cessation can induce bidirectional changes in the mirror-reverse of the traditional language areas. A cross-sectional study identified that gray matter volume in the inferior frontal gyrus pars opercularis (IFGop) and connectivity of the IFGop with the caudate nucleus and the superior temporal gyrus/supramarginal (STG/SMG), predominantly in the right hemisphere, were positively correlated with L2 vocabulary competence. We then implemented a cohort study involving 16 weeks of L2 training in university students. Brain structure before training did not predict the later gain in L2 ability. However, training intervention did increase IFGop volume and reorganization of white matter including the IFGop-caudate and IFGop-STG/SMG pathways in the right hemisphere. These "positive" plastic changes were correlated with the gain in L2 ability in the trained group but were not observed in the control group. We propose that the right hemispheric network can be reorganized into language-related areas through use-dependent plasticity in young adults, reflecting a repertoire of flexible reorganization of the neural substrates responding to linguistic experiences.

Effects of learning with explicit elaboration on implicit transfer of visuomotor sequence learning.

Intervals between stimuli and/or responses have significant influences on sequential learning. In the present study, we investigated whether transfer would occur even when the intervals and the visual configurations in a sequence were drastically changed so that participants did not notice that the required sequences of responses were identical. In the experiment, two (or three) sequential button presses comprised a "set," and nine (or six) consecutive sets comprised a "hyperset." In the first session, participants learned either a 2 × 9 or 3 × 6 hyperset by trial and error until they completed it 20 times without error. In the second block, the 2 × 9 (3 × 6) hyperset was changed into the 3 × 6 (2 × 9) hyperset, resulting in different visual configurations and intervals between stimuli and responses. Participants were assigned into two groups: the Identical and Random groups. In the Identical group, the sequence (i.e., the buttons to be pressed) in the second block was identical to that in the first block. In the Random group, a new hyperset was learned. Even in the Identical group, no participants noticed that the sequences were identical. Nevertheless, a significant transfer of performance occurred. However, in the subsequent experiment that did not require explicit trial-and-error learning in the first session, implicit transfer in the second session did not occur. These results indicate that learning with explicit elaboration strengthens the implicit representation of the sequence order as a whole; this might occur independently of the intervals between elements and enable implicit transfer.

How many categories are there in crossmodal correspondences? A study based on exploratory factor analysis.

Humans naturally associate stimulus features of one sensory modality with those of other modalities, such as associating bright light with high-pitched tones. This phenomenon is called crossmodal correspondence and is found between various stimulus features, and has been suggested to be categorized into several types. However, it is not yet clear whether there are differences in the underlying mechanism between the different kinds of correspondences. This study used exploratory factor analysis to address this question. Through an online experiment platform, we asked Japanese adult participants (Experiment 1: N = 178, Experiment 2: N = 160) to rate the degree of correspondence between two auditory and five visual features. The results of two experiments revealed that two factors underlie the subjective judgments of the audiovisual crossmodal correspondences: One factor was composed of correspondences whose auditory and visual features can be expressed in common Japanese terms, such as the loudness-size and pitch-vertical position correspondences, and another factor was composed of correspondences whose features have no linguistic similarities, such as pitch-brightness and pitch-shape correspondences. These results confirm that there are at least two types of crossmodal correspondences that are likely to differ in terms of language mediation.

Current status of long-term follow-up system for women with a history of hypertensive disorders of pregnancy: the HDP-PPAP study (HDP-Postpartum in Aomori prefecture study).

OBJECTIVE: Women with a history of hypertensive disorders of pregnancy (HDP), especially those with gestational hypertension and preeclampsia, are more likely to develop hypertension, cerebrovascular disease, ischemic heart disease, diabetes mellitus, dyslipidemia, and chronic kidney disease later in life. However, the risk of lifestyle-related diseases in the immediate postpartum period among Japanese women with preexisting HDP is unclear, and a follow-up system for women with preexisting HDP has not been established in Japan. The purpose of this study was to examine the risk factors for lifestyle-related diseases in Japanese women in the immediate postpartum period and the usefulness of HDP follow-up outpatient clinics based on the situation of the HDP follow-up outpatient clinic at our hospital. METHOD: We included 155 women with a history of HDP who visited our outpatient clinic between April 2014 and February 2020. We examined the reasons for dropout during the follow-up period. We also examined the number of new cases of lifestyle-related diseases and compared Body Mass Index(BMI), blood pressure values, and blood and urine test results at 1 and 3 years postpartum in 92 women who had been continuously followed for more than 3 years postpartum. RESULTS: The average age of our patient cohort was 34.8 ± 4.5 years. A total of 155 women with previous HDP were continuously followed for more than 1 year, of whom 23 had new pregnancies, and eight had recurrent HDP (recurrence rate 34.8%). Of the 132 patients who were not newly pregnant, 28 dropped out during follow-up, the most common reason being that the patient did not show up. The patients in this study developed hypertension, diabetes mellitus, and dyslipidemia within a short period. Both systolic and diastolic blood pressures were at normal high levels at 1-year postpartum, and BMI significantly increased at 3 years postpartum. Blood tests revealed significant deterioration in creatinine (Cre), estimated glomerular filtration rate (eGFR), and γ-glutamyl transpeptidase (γGTP) levels. CONCLUSION: In this study, women with preexisting HDP were found to have developed hypertension, diabetes, and dyslipidemia several years postpartum. We also found a significant increase in BMI and worsening of Cre, eGFR, and γGTP levels at 1 and 3 years postpartum. Although the 3-year follow-up rate at our hospital was relatively good (78.8%), some women discontinued follow-up due to self-interruption or relocation, suggesting the need to establish a nationwide follow-up system.

Association between the Change in Blood Pressure during Normotensive Pregnancy and the Development of Hypertension in Later Life.

Introduction: Women who experience maternal complications, including pre-eclampsia, have a higher risk of cardiovascular disease development. Although the mechanism remains unclear, there is a hypothesis that pregnancy would be a stress test for cardiovascular disease. This study aimed to investigate whether changes in blood pressure during pregnancy would be associated with developing hypertension, which is a main risk of cardiovascular disease. Methods: We conducted a retrospective study by collecting Maternity Health Record Books from 735 middle-aged women. Of these, 520 women were selected based on our criteria. 138 were defined as the hypertensive group according to the criteria of receiving antihypertensive medications or blood pressures of >140/90 mmHg at the survey. The rest 382 were defined as the normotensive group. We compared the blood pressures of the hypertensive group with those of the normotensive group during pregnancy and postpartum. Then, 520 women were divided into quartiles (Q1-Q4) according to their blood pressures during pregnancy. After the changes in blood pressure for each gestational month relative to nonpregnant measurements were calculated, the changes in blood pressure were compared among the four groups. Additionally, the rate of developing hypertension was evaluated among the four groups. Results: The average age of the participants was 54.8 years (range: 40-85 years) at the time of the study and 25.9 years (range: 18-44 years) at delivery. There were significant differences in blood pressure during pregnancy between the hypertensive group and the normotensive group. Meanwhile, these two groups did not indicate any differences in blood pressure in postpartum. Higher mean blood pressure during pregnancy was associated with smaller changes in blood pressure during pregnancy. The rate of development of hypertension in each group of systolic blood pressure was 15.9% (Q1), 24.6% (Q2), 29.7% (Q3), and 29.7% (Q4). The rate of development of hypertension in each group of diastolic blood pressure (DBP) was 18.8% (Q1), 24.6% (Q2), 22.5% (Q3), and 34.1% (Q4). Conclusions: Changes in blood pressure during pregnancy are small in women who have a higher risk of hypertension. Levels of blood pressure during pregnancy may be reflected in individual stiffness of blood vessels by the burden of pregnancy. If so, levels of blood pressure would be used to facilitate highly cost-effective screening and interventions for women with a high risk of cardiovascular diseases.

Chorioamnionitis and maternal sepsis caused by AmpC ß-lactamase-producing Escherichia coli infection: A case report.

INTRODUCTION: Multidrug resistant bacteria have increasingly become a concern regarding infection treatment. The clinical course of chorioamnionitis (CAM) caused by multidrug-resistant bacteria is not well understood. PRESENTATION OF CASE: We report a case of CAM caused by AmpC-type ß-lactamase (AmpC)-producing Escherichia coli (E. coli), a multidrug-resistant bacterium. A 35-year-old primipara was hospitalized with preterm membrane rupture at 36 weeks of gestation and was started on oral ampicillin. On the fourth day after admission, the patient was diagnosed with CAM owing to high fever development and uterine tenderness; therefore, an emergency cesarean section was performed. AmpC-producing E. coli were detected in blood and amniotic fluid cultures. Post-operation, the patient received treatment for septic shock and was discharged on the 15th post-operative day. DISCUSSION: The patient initially had no symptoms of infection but later experienced fever and uterine pain. She underwent an emergency cesarean section, and both mother and baby were successfully treated with broad-spectrum antibiotics. CAM associated with multidrug-resistant bacteria is more challenging to manage compared to infections in other parts of the body, as it occurs in unique environments such as the uterus, during pregnancy, and in the presence of compromised immunity. CONCLUSION: The development of new diagnostic criteria and effective biomarkers is needed to improve early detection, and adherence to standard precautions can help prevent the acquisition of multidrug-resistant bacteria in healthcare settings.

High doses of intravenous immunoglobulin stimulate regulatory T cell and suppress natural killer cell in women with recurrent pregnancy loss.

The aim was to evaluate whether natural killer (NK) cells and regulatory T (Treg) cells were involved in mechanisms underlying beneficial effects of a high dose of intravenous immunoglobulin (IVIG) on recurrent pregnancy losses (RPL) of unexplained etiology. In a double-blind, randomized, placebo-controlled trial of IVIG (400 mg/kg, for 5 days in 4-6 weeks of gestation) in women with RPL, blood samples were collected pre-infusion, one week after infusion (1 w), and eight weeks of gestation/when miscarried (8 w). Levels of NK and Treg cells in peripheral blood were compared between women with IVIG (n = 50) and placebo (n = 49), and between women with IVIG who gave live birth (n = 29) and those who had miscarriage with normal chromosome (n = 12). Effector Treg cell percentages in IVIG group at 1 w (mean 1.43 % vs. 1.03 %) and at 8 w (1.91 % vs. 1.18 %) were higher than those in placebo group (p < 0.01). Total Treg cell percentages in IVIG group at 1 w (4.75 % vs. 4.08 %) and at 8 w (5.55 % vs. 4.47 %) were higher than those in placebo group (p < 0.05). In women with live birth, total Treg cell percentages increased at 8 w (5.52 %, p < 0.001) compared with pre-infusion (4.54 %) and 1 w (4.47 %), while NK cell activity decreased at 1 w (20.18 %, p < 0.001) compared with pre-infusion (26.59 %). IVIG increased Treg cell percentages and suppressed NK cell activity very early in pregnancy, and these were associated with subsequent live birth. Stimulation of Treg cells and suppression of NK cell activity very early in pregnancy may be a mechanism of pharmacological effects of high dose IVIG.

Defining PET standardized uptake value threshold for tumor delineation with metastatic lymph nodes in head and neck cancer.

OBJECTIVE: Hot spots of F-18 fluorodeoxyglucose positron emission tomograms are variable in size according to window settings of standardized uptake values. The purpose of this study was to determine the standardized uptake value threshold that represents the target volume. METHODS: Sixty-three patients who underwent fluorodeoxyglucose positron emission tomographic computed tomography and were diagnosed as having head and neck cancer with cervical lymphadenopathy were studied. The horizontal and vertical diameters of metastatic lymph nodes (LN-CT) were measured at the center of computed tomographic images. Of the corresponding nodes, the maximal standardized uptake value (SUVmax) and standardized uptake value profiles along the central horizontal and vertical axes were calculated on positron emission tomographic images (LN-PET). On the standardized uptake value profiles, the standardized uptake value levels (SUVeq) where the size of LN-PET was equivalent to the diameters of LN-CT were obtained. The regression formula between SUVeq and SUVmax was obtained. The regression formula of SUVeq was validated in subsequent 30 positron emission tomographic computed tomography studies. RESULTS: The mean horizontal and vertical diameters of LN-CT were 14.9 and 16.4 mm, respectively. SUVmax ranged from 1.88 to 9.07, and SUVeq was between 1.16 and 6.42. The regression formula between SUVeq and SUVmax was as follows: SUVeq = 1.21 + 0.34 × SUVmax (coefficient of correlation: R = 0.69). The validation study resulted in a good correlation between the volume of lymph nodes on computed tomography and positron emission tomographic computed tomography (R(2) = 0.93). CONCLUSIONS: The formula with a relatively high coefficient of correlation is considered to indicate that SUVeq is not constant, but is a complex of an absolute standardized uptake value and is proportional to SUVmax.

Memory decay enhances central bias in time perception.

Temporal expectations are essential for appropriately interacting with the environment, but they can be biased. This tendency, called central bias, places higher weights on expected rather than actual duration distributions when perceiving incoming sensory stimuli. In particular, the central bias is strengthened in order to decrease total response error when incoming sensory stimuli are unclear. In the present study, we investigated whether the central bias was enhanced via memory decay. For this, we used a delayed reproduction task, manipulating retention periods by introducing delays between the sample interval and the reproduction phase (0.4, 2, 4 s in Experiment 1; 0.4, 2, 8 s in Experiments 2 and 3). Through three experiments, we found the gradual strengthening of the central bias as a function of the retention period (i.e., short-term memory decay). This suggests that the integration of temporal expectation, generated from past trials and stored sensory stimuli, in a current trial occurs in the reproduction phase in the delayed reproduction task.

Motor engagement enhances incidental memory for task-irrelevant items.

Actions shape what we see and memorize. A previous study suggested the interaction between motor and memory systems by showing that memory encoding for task-irrelevant items was enhanced when presented with motor-response cues. However, in the studies on the attentional boost effect, it has been revealed that detection of the target stimulus can lead to memory enhancement without requiring overt action. Thus, the direct link between the action and memory remains unclear. To exclude the effect of the target detection process as a potential confounder, this study assessed the benefit of action for memory by separating items from the response cue in time. In our pre-registered online experiment (N = 142), participants responded to visual Go cues by pressing a key (i.e., motor task) or counting (i.e., motor-neutral cognitive task) while ignoring No-go cues. In each trial, two task-irrelevant images were sequentially presented after the cue disappearance. After encoding the Go/No-go tasks, participants performed a surprise recognition memory test for those images. Importantly, we quantified the impact of overt execution of the action by comparing memories with and without motor response and the impact of covert motor processes (e.g., preparation and planning of action) by comparing memory between the motor and cognitive tasks. The results showed no memory differences between Go and No-go trials in the motor task. This means that the execution itself was not critical for memory enhancement. However, the memory performance in the motor No-go trials was higher than that in the cognitive No-go trials, only for the items presented away from the cues in time. Therefore, engaging the motor task itself could increase incidental memory for the task-irrelevant items compared to a passive viewing situation. We added empirical evidence on the online interaction between action and memory encoding. These memory advantages could be especially brought in action preparation and planning. We believe this fact may expand our present understanding of everyday memory, such as active learning.

Perceptual inference, accuracy, and precision in temporal reproduction in schizophrenia.

Accumulating evidence suggests that deficits in perceptual inference account for symptoms of schizophrenia. One manifestation of perceptual inference is the central bias, i.e., the tendency to put emphasis on prior experiences over actual events in perceiving incoming sensory stimuli. Using an interval reproduction task, this study aimed to determine whether patients with schizophrenia show a stronger central bias than participants without schizophrenia. In the interval reproduction task, participants were shown a cross on a screen. The cross was replaced with a Gaussian patch for a predetermined time interval, and participants were required to reproduce the interval duration by pressing and releasing the space key. We manipulated the uncertainty of prior information using different interval distributions. We found no difference in the influence of prior information on interval reproduction between patients and controls. However, patients with SZ showed a stronger central bias than healthy participants in the intermediate interval range (approximately 450 ms to 900 ms). It is possible that the patients in SZ have non-uniform deficits associated with interval range or uncertainty of prior information in perceptual inference. Further, the severity of avolition and alogia was correlated with the strength of central bias in SZ. This study provides some insights into the mechanisms underlying the association between schizophrenic symptoms and perceptual inference.

A multicenter prospective study of home blood pressure measurement (HBPM) during pregnancy in Japanese women.

In the near future, hypertensive disorders of pregnancy (HDP) have been diagnosed by home blood pressure monitoring (HBPM) instead of clinic BP monitoring. A multicenter study of HBPM was performed in pregnant Japanese women in the non-high risk group for HDP. Participants were women (n = 218), uncomplicated pregnancy who self-measured and recorded their HBP daily. Twelve women developed HDP. HBP was appropriate (100 mmHg in systole and 63 mmHg in diastole), bottoming out at 17 to 21 weeks of gestation. It increased after 24 weeks of gestation and returned to non-pregnant levels by 4 weeks of postpartum. The upper limit of normal HBP was defined as the mean value +3 SD for systolic and mean +2 SD for diastolic with reference to the criteria for non-pregnant women. Using the polynomial equation, the hypertensive cut-off of systolic HBP was 125 mmHg at 15 weeks and 132 mmHg at 30 weeks of gestation, while it for diastolic HBP was 79 mmHg at 15 weeks and 81 mmHg at 30 weeks of gestation. Systolic HBP in women who developed HDP was higher after 24 weeks of gestation, and diastolic HBP was higher during most of the pregnancy compared to normal pregnancy. When the variability of individual HBP in women developed HDP compared to normal pregnant women was examined using the coefficient of variation (CV), the CV was lower in HDP before the onset of HDP. HBPM can be used not only for HDP determination, but also for early detection of HDP.

Intravenous immunoglobulin treatment in women with four or more recurrent pregnancy losses: A double-blind, randomised, placebo-controlled trial.

Background: There is no effective treatment for women with unexplained recurrent pregnancy loss (RPL). We aimed to investigate whether treatment with a high dose of intravenous immunoglobulin (IVIG) in early pregnancy can improve pregnancy outcomes in women with unexplained RPL. Methods: In a double-blind, randomised, placebo-controlled trial, women with primary RPL of unexplained aetiology received 400 mg/kg of IVIG daily or placebo for five consecutive days starting at 4-6 weeks of gestation. They had experienced four or more miscarriages except biochemical pregnancy loss and at least one miscarriage of normal chromosome karyotype. The primary outcome was ongoing pregnancy rate at 22 weeks of gestation, and the live birth rate was the secondary outcome. We analysed all women receiving the study drug (intention-to-treat, ITT) and women except those who miscarried due to fetal chromosome abnormality (modified-ITT). This study is registered with ClinicalTrials.gov number, NCT02184741. Findings: From June 3, 2014 to Jan 29, 2020, 102 women were randomly assigned to receive IVIG (n = 53) or placebo (n = 49). Three women were excluded; therefore 50 women received IVIG and 49 women received placebo in the ITT population. The ongoing pregnancy rate at 22 weeks of gestation (31/50 [62·0%] vs. 17/49 [34·7%]; odds ratio [OR] 3·07, 95% CI 1·35-6·97; p = 0·009) and the live birth rate (29/50 [58·0%] vs. 17/49 [34·7%]; OR 2·60, 95% CI 1·15-5·86; p = 0·03) in the IVIG group were higher than those in the placebo group in the ITT population. The ongoing pregnancy rate at 22 weeks of gestation (OR 6·27, 95% CI 2·21-17·78; p < 0·001) and the live birth rate (OR 4·85, 95% CI 1·74-13·49; p = 0·003) significantly increased in women who received IVIG at 4-5 weeks of gestation as compared with placebo, but these increases were not evident in women who received IVIG at 6 weeks of gestation. Four newborns in the IVIG group and none in the placebo group had congenital anomalies (p = 0·28). Interpretation: A high dose of IVIG in very early pregnancy improved pregnancy outcome in women with four or more RPLs of unexplained aetiology. Funding: The Japan Blood Products Organization.

Sense of agency with illusory visual events.

Sense of agency (SoA) is the subjective feeling of being in control of one's own actions and that one's action causes changes in external circumstances. In the present study, we investigated how percepts influenced a production of SoA when effect-related signals were illusory. For this purpose, we adopted the cross-modal double-flash illusion (DFI). In DFI, when two brief auditory stimuli (i.e., beeps) are presented in quick succession and accompanied by a single visual flash, observers tend to report two visual flashes. In the experiments, we let participants press a given button once or twice. Three stimulus conditions were used: one beep sound (inducer) with a single flash (effect; 1B1F), two beeps with two flashes (2B2F), and two beeps with one flash (DFI condition). Then, participants reported how much they thought they had caused the events (i.e., visual flashes) by their actions. Through the series of experiments, we found even illusory visual events enhanced SoA in the DFI condition. However, SoA in the DFI condition was smaller than that in the 2B2F condition. These results indicate that both the congruency between action and apparent stimulus as well as the stimulus property modulate SoA. (PsycInfo Database Record (c) 2021 APA, all rights reserved).