Effortful retrieval of semantic memories induces forgetting of related negative and neutral episodic memories.

Retrieval-induced forgetting (RIF) experiments show that the act of retrieving some recently encoded items from a given conceptual category leads to greater forgetting of competing items from that same category. However, RIF studies using emotional stimuli have produced mixed results, perhaps due to the reinstatement of arousal or negative affect during retrieval practice. To induce forgetting of negative episodic memories more indirectly, we examined if retrieving neutral semantic memories leads to RIF of related negative memories.

Emotional arousal lingers in time to bind discrete episodes in memory.

Temporal stability and change in neutral contexts can transform continuous experiences into distinct and memorable events. However, less is known about how shifting emotional states influence these memory processes, despite ample evidence that emotion impacts non-temporal aspects of memory. Here, we examined if emotional stimuli influence temporal memory for recent event sequences.

Dynamic emotional states shape the episodic structure of memory.

Human emotions fluctuate over time. However, it is unclear how these shifting emotional states influence the organization of episodic memory. Here, we examine how emotion dynamics transform experiences into memorable events.

Does social rigidity predict cognitive rigidity? Profiles of socio-cognitive polarization.

Recent research has proposed a relationship between rigid political ideologies and underlying 'cognitive styles'. However, there remain discrepancies in how both social and cognitive rigidity are defined and measured. Problem-solving, or the ability to generate novel ideas by exploring unusual reasoning paths and challenging rigid perspectives around us, is often used to operationalize cognitive flexibility.

Counterconditioning reduces contextual renewal in a novel context but not in the acquisition context.

As extinction is a context-dependent form of learning, conditioned responses tend to return when the conditioned stimulus (CS) is encountered outside the extinction context, known as contextual renewal. Counterconditioning is a technique that may lead to a more persistent reduction of the conditioned response. However, the effects of aversive-to-appetitive counterconditioning on contextual renewal in rodent studies are mixed.

Neural reinstatement reveals divided organization of fear and extinction memories in the human brain.

Neurobiological research in rodents has revealed that competing experiences of fear and extinction are stored as distinct memory traces in the brain. This divided organization is adaptive for mitigating overgeneralization of fear to related stimuli that are learned to be safe while also maintaining threat associations for unsafe stimuli. The mechanisms involved in organizing these competing memories in the human brain remain unclear.

Generalization of conditioned fear along a dimension of increasing positive valence.

The amount of fear evoked by potential threats is oftentimes proportional to the overlap in shared features with known threats. An adaptive learning system should therefore extract relevant features from threat stimuli to successfully detect other novel threats in the environment. But what if the most relevant feature of a threat stimulus is emotionally positive? Here, we used Pavlovian fear conditioning to ask whether people extract positive emotional features of a fear conditioned stimulus (CS) to selectively generalize to other stimuli that contain positive features.

Contextual reinstatement promotes extinction generalization in healthy adults but not PTSD.

For episodic memories, reinstating the mental context of a past experience improves retrieval of memories formed during that experience. Does context reinstatement serve a similar role for implicit, associative memories such as fear and extinction? Here, we used a fear extinction paradigm to investigate whether the retrieval of extinction (safety) memories is associated with reactivation of the mental context from extinction memory formation. In a two-day Pavlovian conditioning, extinction, and renewal protocol, we collected functional MRI data while healthy adults and adults with PTSD symptoms learned that conditioned stimuli (CSs) signaled threat through association with an electrical shock.

Threat-induced modulation of hippocampal and striatal memory systems during navigation of a virtual environment.

The brain is composed of multiple memory systems that mediate distinct types of navigation. The hippocampus is important for encoding and retrieving allocentric spatial cognitive maps, while the dorsal striatum mediates procedural memories based on stimulus-response (S-R) associations. These memory systems are differentially affected by emotional arousal.

Context conditioning in humans using commercially available immersive Virtual Reality.

Despite a wealth of knowledge on how humans and nonhuman animals learn to associate meaningful events with cues in the environment, far less is known about how humans learn to associate these events with the environment itself. Progress on understanding spatiotemporal contextual processes in humans has been slow in large measure by the methodological constraint of generating and manipulating immersive spatial environments in well-controlled laboratory settings. Fortunately, immersive Virtual Reality (iVR) technology has improved appreciably and affords a relatively straightforward methodology to investigate the role of context on learning, memory, and emotion while maintaining experimental control.

A phase II study of high dose tamoxifen and weekly cisplatin in patients with metastatic melanoma.

We have previously demonstrated that the combination of tamoxifen and cisplatin has activity in patients with metastatic melanoma. In vitro studies have demonstrated that tamoxifen and cisplatin exhibit cytotoxic synergy in human melanoma cells and that this interaction is dependent on a tamoxifen effect. The mechanism of this effect is currently under investigation in in vitro studies.

Equity in access to exercise tolerance testing, coronary angiography, and coronary artery bypass grafting by age, sex and clinical indications.

Objectives: To assess whether patients with heart disease in a single UK hospital have equitable access to exercise testing, coronary angiography, and coronary artery bypass graft surgery (CABG).

Method: Retrospective analysis of patients' medical case notes (n = 1790), tracking each case back 12 months and forward 12 months from the patient's date of entry to the study.

Setting: Single UK district hospital in the Thames Region.

The effect of tamoxifen and cisplatin on the disease-free and overall survival of patients with high risk malignant melanoma.

The adjuvant treatment of high-risk malignant melanoma remains problematic. Previously we reported moderate success in the treatment of metastatic disease using tamoxifen, cisplatin, dacarbazine and carmustine. Based upon data that suggested tamoxifen and cisplatin were the active agents in this regimen, we initiated a phase II trial of this combination in the adjuvant setting.

Evaluation of outreach clinics held by specialists in general practice in England.

Objectives: To measure the processes of care, health benefits and costs of outreach clinics held by hospital specialists in primary care settings.

Design: The study was designed as a case-referent (comparative) study in which the features of 19 outreach clinics (cases) were compared with matched outpatient clinics (controls). The measuring instruments were self administered questionnaires.

A phase I and pharmacokinetic study of high dose tamoxifen and weekly cisplatin in patients with metastatic melanoma.

Background: The authors have previously demonstrated that tamoxifen (TAM) is synergistic with cisplatin (DDP) in patients with metastatic melanoma. In vitro studies have demonstrated that TAM/DDP synergy is dependent on a TAM effect that is currently under investigation. In an attempt to improve the complete response rate of this regimen, the authors initiated a Phase I trial to determine the maximum tolerated dose (MTD) of TAM that could be safely administered with weekly DDP.

A phase II trial of intraperitoneal high-dose carboplatin and etoposide with granulocyte macrophage-colony stimulating factor support in patients with ovarian carcinoma.

Based upon results obtained in a Phase I study, we conducted a Phase II trial of high-dose CBDCA and etoposide administered via the intraperitoneal (IP) route in patients with ovarian cancer. CBDCA at a dose of 600 mg/m2 and etoposide at a dose of 400 mg/m2 were administered rapidly into the peritoneal cavity. The total dose of each agent was calculated and given daily over 3 days in amounts equal to one-third of the total dose.

A phase I trial of intraperitoneal carboplatin and etoposide with granulocyte macrophage colony stimulating factor support in patients with intraabdominal malignancies.

Background: Although somewhat controversial, there are data to suggest that patients with ovarian cancer may experience a survival advantage if the dose intensity of platinum-containing regimens can be maximized. Administration of chemotherapeutic agents via the intraperitoneal route offers the opportunity to increase dose intensity of several chemotherapeutic agents.

Methods: The authors conducted a Phase I trial of intraperitoneal carboplatin and etoposide in combination with granulocyte macrophage colony stimulating factor (GM-CSF) in an attempt to determine the maximum tolerated dose of carboplatin.

Tamoxifen: is it useful in the treatment of patients with metastatic melanoma?

Purpose: We have attempted to review the data regarding the activity of tamoxifen (TAM) to clarify the role of this agent in the treatment of metastatic melanoma.

Methods: Using the Melvyl Medline system, we identified recent reports describing the results of clinical trials that used TAM either as a single agent or in combination with other cytotoxic agents. Additionally, we reviewed the abstracts from the 29th Annual Meeting of the American Society of Clinical Oncology held in May 1993.