Phase II study of Vigil® DNA engineered immunotherapy as maintenance in advanced stage ovarian cancer.

OBJECTIVES: The majority of women with Stage III/IV ovarian cancer who achieve clinical complete response with frontline standard of care will relapse within 2years. Vigil immunotherapy, a GMCSF/bi-shRNA furin DNA engineered autologous tumor cell (EATC) product, demonstrated safety and induction of circulating activated T-cells against autologous tumor in Phase I trial Senzer et al. (2012, 2013) . Our objectives for this study include evaluation of safety, immune response and recurrence free survival (RFS). METHODS: This is a Phase II crossover trial of Vigil (1.0×107 cells/intradermal injection/month for 4 to 12 doses) in Stage III/IV ovarian cancer patients achieving cCR (normal imaging, CA-125≤35units/ml, physical exam, and no symptoms suggestive of the presence of active disease) following primary surgical debulking and carboplatin/paclitaxel adjuvant or neoadjuvant chemotherapy. Patients received Vigil or standard of care during the maintenance period. RESULTS: Forty-two patients were entered into trial, 31 received Vigil and 11 received standard of care. No≥Grade 3 toxicity related to product was observed. A marked induction of circulating activated T-cell population was observed against individual, pre-processed autologous tumor in the Vigil arm as compared to pre-Vigil baseline using IFNγ ELISPOT response (30/31 negative ELISPOT pre Vigil to 31/31 positive ELISPOT post Vigil, median 134 spots). Moreover, in correlation with ELISPOT response, RFS from time of procurement was improved (mean 826days/median 604days in the Vigil arm from mean 481days/median 377days in the control arm, p=0.033). CONCLUSION: In conjunction with the demonstrated safety, the high rate of induction of T-cell activation and correlation with improvement in RFS justify further Phase II/III assessment of Vigil.

Allometric scaling of strength scores in NCAA division I-A football athletes.

This study examined population-specific allometric exponents to control for the effect of body mass (BM) on bench press, clean, and squat strength measures among Division I-A collegiate football athletes. One repetition maximum data were obtained from a university pre-season football strength assessment (bench press, n = 207; clean, n = 88; and squat n = 86) and categorized into 3 groups by positions (line, linebacker, and skill). Regression diagnostics and correlations of scaled strength data to BM were used to assess the efficacy of the allometric scaling model and contrasted with that of ratio scaling and theoretically based allometric exponents of 0.67 and 0.33. The log-linear regression models yielded the following exponents (b): b = 0.559, 0.287, and 0.496 for bench press, clean, and squat, respectively. Correlations between bench press, clean, and squat to BM were r = -0.024, -0.047, and -0.018, respectively, suggesting that the derived allometric exponents were effective in partialling out the effect of BM on these lifts and removing between-group differences. Conversely, unscaled, ratio-scaled, and allometrically scaled (b = 0.67 or 0.33) data resulted in significant differences between groups. It is suggested that the exponents derived in the present study be used for allometrically scaling strength measures in National Collegiate Athletic Association Division I-A football athletes. Use of the normative percentile rank scores provide coaches and trainers with a valid means of judging the effectiveness of their training programs by allowing comparisons between individuals without the confounding influence of BM.

The Acute and Chronic Cognitive Effects of a Sage Extract: A Randomized, Placebo Controlled Study in Healthy Humans.

The sage (Salvia) plant contains a host of terpenes and phenolics which interact with mechanisms pertinent to brain function and improve aspects of cognitive performance. However, previous studies in humans have looked at these phytochemicals in isolation and following acute consumption only. A preclinical in vivo study in rodents, however, has demonstrated improved cognitive outcomes following 2-week consumption of CogniviaTM, a proprietary extract of both Salvia officinalis polyphenols and Salvia lavandulaefolia terpenoids, suggesting that a combination of phytochemicals from sage might be more efficacious over a longer period of time. The current study investigated the impact of this sage combination on cognitive functions in humans with acute and chronic outcomes. Participants (n = 94, 25 M, 69 F, 30-60 years old) took part in this randomised, double-blind, placebo-controlled, parallel groups design where a comprehensive array of cognitions were assessed 120- and 240-min post-dose acutely and following 29-day supplementation with either 600 mg of the sage combination or placebo. A consistent, significant benefit of the sage combination was observed throughout working memory and accuracy task outcome measures (specifically on the Corsi Blocks, Numeric Working Memory, and Name to Face Recall tasks) both acutely (i.e., changes within day 1 and day 29) and chronically (i.e., changes between day 1 to day 29). These results fall slightly outside of those reported previously with single Salvia administration, and therefore, a follow-up study with the single and combined extracts is required to confirm how these effects differ within the same cohort.

Recurrent phyllodes tumor of the vulva: a case report with review of diagnostic criteria and differential diagnosis.

Phyllodes tumor of the vulva is extremely rare with only 6 cases reported in the literature. We report a case of recurrent phyllodes tumor of the vulva in a 39-year-old woman. The tumor showed biphasic morphology with a typical leaf-like pattern and a cellular stroma with rare mitosis. Expression of estrogen receptors, progesterone receptors mammoglobin, and BRST-2 was shown in the epithelial component. Review of literature with emphasis on diagnostic features and differential diagnosis are discussed.

A short self-report measure of problems with executive function suitable for administration via the Internet.

This article describes a short self-report measure of problems with executive function designed for use in Internet-mediated research. In Study 1, participants completed the online measure (Webexec) using a browser but under laboratory conditions. They also completed a paper self-report measure of executive problems (the Dysexecutive Questionnaire; DEX) and three objective tasks involving executive function: reverse digit span, semantic fluency (unconstrained), and semantic fluency (constrained). Webexec scores correlated positively with the DEX and negatively with the three executive tasks. Further evidence of construct validity came from Study 2, in which Webexec scores correlated positively with both use of cannabis and prospective memory problems reported in an online drug questionnaire. Webexec thus appears suitable for online research with normal populations.

Subjective ratings of prospective memory deficits in chronic alcohol users.

Previous research showing everyday memory is impaired by heavy alcohol use may have underestimated the cognitive impairment of heavy users because drinkers consuming over the recommended limits for safe drinking have often been treated as a homogeneous group, often with a low threshold for inclusion. The current study investigated whether the reported linear relationship applies to participants consuming alcohol significantly above recommended limits. The everyday memory of 80 participants (43 men; modal age, 31-35 years) was investigated using the Prospective Memory Questionnaire. Participants also detailed their average weekly intake of alcohol and other substances. Current heavy users of alcohol (who consumed on average over 25 units per week) reported more memory problems than low (1-9 units per week) or medium users (10-25 units per week). Participants undergoing counselling for alcohol use reported more deficits than low or medium drinkers, but fewer than current heavy drinkers. Possible reasons for this were discussed. Strengths and limitations of subjective approaches to memory assessment were discussed as well as suggestions for future research.

Sensitivity to Experiencing Alcohol Hangovers: Reconsideration of the 0.11% Blood Alcohol Concentration (BAC) Threshold for Having a Hangover.

The 2010 Alcohol Hangover Research Group consensus paper defined a cutoff blood alcohol concentration (BAC) of 0.11% as a toxicological threshold indicating that sufficient alcohol had been consumed to develop a hangover. The cutoff was based on previous research and applied mostly in studies comprising student samples. Previously, we showed that sensitivity to hangovers depends on (estimated) BAC during acute intoxication, with a greater percentage of drinkers reporting hangovers at higher BAC levels. However, a substantial number of participants also reported hangovers at comparatively lower BAC levels. This calls the suitability of the 0.11% threshold into question. Recent research has shown that subjective intoxication, i.e., the level of severity of reported drunkenness, and not BAC, is the most important determinant of hangover severity. Non-student samples often have a much lower alcohol intake compared to student samples, and overall BACs often remain below 0.11%. Despite these lower BACs, many non-student participants report having a hangover, especially when their subjective intoxication levels are high. This may be the case when alcohol consumption on the drinking occasion that results in a hangover significantly exceeds their "normal" drinking level, irrespective of whether they meet the 0.11% threshold in any of these conditions. Whereas consumers may have relative tolerance to the adverse effects at their "regular" drinking level, considerably higher alcohol intake-irrespective of the absolute amount-may consequentially result in a next-day hangover. Taken together, these findings suggest that the 0.11% threshold value as a criterion for having a hangover should be abandoned.

Objectively assessed prospective memory failures and diurnal cortisol secretion in caregivers of children with ASD.

Caregivers of children with autism spectrum disorder (ASD) self-report more prospective memory (PM) failures compared with controls. Subjective and objective measures of PM, however, tend to be poorly correlated. This study therefore explored the cognitive impact of caring for a child with ASD using the Cambridge Prospective Memory Test (CAMPROMPT), a more objective, performance-based assessment of PM failures. Whether atypical cortisol secretion patterns might mediate caregivers' compromised cognition was also explored. A sample of n = 23 caregivers of children with ASD and n = 11 parent controls completed time- and event-cued PM tasks with CAMPROMPT. Diurnal cortisol indices, the cortisol-awakening response, diurnal cortisol slope, and mean diurnal output were estimated from saliva samples on multiple days. Results indicated objectively assessed event- but not time-cued PM failures were greater in caregivers compared with controls. Variations in cortisol secretion patterns, however, did not mediate the group effect. In conclusion, caring for a child with ASD was associated with greater deficits in event-cued PM. Future studies might examine the influence of caregivers' event-cued PM failures on quality of provided care. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Alcohol Hangover Has Detrimental Impact Upon Both Executive Function and Prospective Memory.

The alcohol hangover (AH) is a state of general malaise following an evening of heavy episodic drinking when the blood alcohol concentration of the person reaches/approaches zero. The aim of the current study was to investigate what impact the AH has upon both executive function (EF) and prospective memory (PM). Previous research has shown that the AH has a detrimental effect upon cognitive abilities, including attention, working memory, and PM. The current study focused upon what impact AH might have upon both EF and related PM in the same cohort, both of which underpin everyday remembering. The current study compared an AH group (AHG) with a non-hangover group (NHG) on both EF and PM measures. Forty-one participants aged 18-29 years were tested; 19 comprised the AHG and 22 of whom made up the NHG (individuals who reported no heavy drinking the day before and did not report any significant hangover symptoms). A Verbal Fluency task measured EF and the Prospective Remembering Video Procedure measured PM. The Acute Hangover Rating Scale measured AH symptoms and severity, and a Digital Breath Analyzer Test measured their blood alcohol concentration (BAC). A Recreational Drug Use Questionnaire measured alcohol and other drug use. Anyone reporting having used an illicit substance across their lifetime (e.g., cannabis, ecstasy) or who smoked heavily were omitted from the study. Two univariate analyses of covariance compared the AHG and NHG groups on Verbal Fluency and Prospective Remembering Video Task scores (controlling for age, total alcohol units consumed per week, and the number of years spent drinking). The AHG recalled significantly fewer items on the Verbal Fluency task [F (1, 36) = 7.42, p < 0.01] and on the Prospective Remembering Video Task NHG [F (1, 36) = 14.9, p < 0.001] when compared with the NHG. Overall, it appeared that a state of AH significantly impaired both EF and PM. Given the importance of EF and PM to everyday remembering, these findings may have farther-reaching implications.

A review of the literature on the cognitive effects of alcohol hangover.

AIMS: Alcohol misuse is a prime social and health problem in the UK. This paper presents a critical review of literature on the performance effects in the morning after binge drinking - during the alcohol hangover. Several pathophysiological changes that both follow and outlast acute intoxication may give rise to alcohol hangover effects. We have identified 27 English language peer-reviewed studies that investigate aspects of psychological performance during alcohol hangover following controlled alcohol ingestion. However, the majority of studies had basic methodological shortcomings. Of eight laboratory studies rigorous enough to warrant serious attention, only two showed effects. We interpret these largely negative findings as evidence of an insensitivity that is intrinsic to laboratory-based studies of performance under the influence of alcohol. Several studies have investigated the cognitive consequences of hangover subsequent to naturalistic consumption, where participants have chosen what and where to drink. Although these studies have tended to show effects, participants were always informed at the outset that hangover effects were to be assessed, and participants knew which was the hangover condition. Under these circumstances expectancy effects have possibly contaminated the results significantly. Therefore, naturalistic alcohol consumption studies (and laboratory studies that did not employ a placebo) can be considered as being suggestive of hangover effects, but should not be interpreted as providing definitive evidence of such effects. In conclusion, although there is empirical evidence showing impaired performance as a result of the alcohol hangover, future studies should confirm these findings and overcome the shortcomings of previous research.

A State of Alcohol Hangover Impedes Everyday Prospective Memory.

The aim of the current study was to investigate what impact a state of alcohol hangover (AH) has upon everyday prospective memory (PM; memory for future events/intentions). Previous research has shown that the AH has a detrimental effect upon cognitive abilities, including memory and attentional deficits. No published research articles to date have focused upon what impact AH might have upon everyday memory, of which PM is a good example. The current study compared an AH group (AHG) with a non-hangover group (NHG) on PM. Since other drug use, anxiety and depression can affect PM independent of the AH, these covariates were controlled for in the study. Fifty-eight young adults studying at university participated in this between-subjects design study-25 in the AHG and 33 in the NHG. The Prospective Remembering Video Procedure (PRVP) measured PM. The Acute Hangover Rating Scale confirmed a state of AH and a Digital Breath Analyzer Test measured their BAC. The Hospital Anxiety and Depression Scale gauged levels of anxiety and depression and a Recreational Drug Use Questionnaire (RDUQ) measured alcohol and other drug use. Anyone who reported having used an illicit substance (e.g., cannabis, ecstasy) or who smoked, were excluded from the study. After controlling for age, alcohol units per week, years spent drinking alcohol, anxiety and depression scores, a one-way analysis of covariance (ANCOVA) revealed that the AHG (mean = 5.16) recalled significantly fewer items on the PRVP than the NHG (mean = 7.51)-F (1,52) = 5.69, p < 0.05. Overall, it appeared that a state of AH significantly impaired PM, which was not attributable to age, alcohol use, or anxiety or depression indices. Given the importance of PM to everyday activities, such as remembering to keep appointments or to take an important medication on time, this finding may have farther-reaching implications. These findings should also be used to educate young adults and health professionals dealing with the consequences with regards the dangers of alcohol misuse.

Short-term prospective memory deficits in chronic back pain patients.

OBJECTIVE: Chronic pain, particularly low back pain, is widespread. Although a great deal is known about the impact that this has on quality of life and physical activity, relatively little has been established regarding the more cognitive effects of pain. This study aims to find out whether individuals with chronic pain experience memory deficits in prospective memory (PM), the process of remembering to do things at some future point in time. Examples of PM include remembering to keep an appointment, such as a visit to a clinic, or to perform a particular task, such as paying a bill on time. METHODS: The PM of 50 participants with chronic pain was compared with 50 pain-free participants. Each participant completed the Prospective Memory Questionnaire, which assesses three aspects of prospective memory (short-term habitual, long-term episodic, and internally cued), and records the use of strategies to aid remembering. RESULTS: In comparison to those not in pain, participants with chronic pain had significantly impaired short-term prospective memory, an effect which was evident even after co-varying use of analgesics and other drugs. CONCLUSIONS: These findings provide new insights into prospective memory dysfunction in people with chronic pain. Possible mechanisms for this dysfunction are discussed and suggestions for future research given.

Sex differences in the Poggendorff illusion: identifying the locus of the effect.

Extensive research has identified individual differences associated with sex in a range of visual task performances, including susceptibility to visual illusions. The aim of this study was to identify the locus of sex differences within the context of the Poggendorf illusion. 79 women and 79 men participated within a mixed factorial design. Analyses indicated that sex differences were only present in the stimulus context with the full inducing element present. This finding replicates recent research and provides qualifying evidence as to the locus of the effect. The findings are discussed within the functional framework of perceptual processes involved in extrapolating 3-dimensional characteristics from 2-dimensional visual stimuli.

The Synergistic Impact of Excessive Alcohol Drinking and Cigarette Smoking upon Prospective Memory.

The independent use of excessive amounts of alcohol or persistent cigarette smoking have been found to have a deleterious impact upon Prospective Memory (PM: remembering future intentions and activities), although to date, the effect of their concurrent use upon PM is yet to be explored. The present study investigated the impact of the concurrent use of drinking excessive amounts of alcohol and smoking cigarettes (a "Polydrug" group) in comparison to the combined effect of the single use of these substances upon PM. The study adopted a single factorial independent groups design. The Cambridge Prospective Memory Test (CAMPROMPT) is a test of both time-based and event-based PM and was used here to measure PM. The CAMPROMPT was administered to 125 adults; an excessive alcohol user group (n = 40), a group of smokers who drink very little alcohol (n = 20), a combined user group (the "Polydrug" group) who drink excessively and smoke cigarettes (n = 40) and a non-drinker/low alcohol consumption control group (n = 25). The main findings revealed that the Polydrug users recalled significantly fewer time-based PM tasks than both excessive alcohol users p < 0.001 and smokers p = 0.013. Polydrug users (mean = 11.47) also remembered significantly fewer event-based PM tasks than excessive alcohol users p < 0.001 and smokers p = 0.013. With regards to the main aim of the study, the polydrug users exhibited significantly greater impaired time-based PM than the combined effect of single excessive alcohol users and cigarette smokers p = 0.033. However, no difference was observed between polydrug users and the combined effect of single excessive alcohol users and cigarette smokers in event-based PM p = 0.757. These results provide evidence that concurrent (polydrug) use of these two substances has a synergistic effect in terms of deficits upon time-based PM. The observation that combined excessive drinking and cigarette smoking leads to a greater impairment in time-based PM may be of paramount importance, given the key role PM plays in everyday independent living.

Subjective ratings of prospective memory deficits in MDMA ('ecstasy') users.

Chronic use of MDMA (3,4-methylenedioxymethamphetamine), or 'ecstasy', is associated with significant cognitive impairments, particularly in laboratory and field tests of memory for previously encoded material. Less is known about the effects of a history of MDMA use on aspects of everyday cognitive functioning-of which prospective memory (typically characterised as 'remembering to do something at some future point') is an important aspect. Self-ratings of prospective memory among 30 regular ecstasy users (taking the drug 10 or more times per month) and 31 ecstasy-free controls were compared. Each participant completed the Prospective Memory Questionnaire, which measures self-rated error frequencies relating to three aspects of prospective memory (short-term habitual, long-term episodic and internally cued); the scale also records the use of strategies to aid remembering. Compared with non-users, ecstasy users reported significantly more self-rated errors in prospective memory, an effect which was evident after co-varying levels of other drug use. There were no significant differences in the use of strategies to aid memory. These findings provide new insights into prospective memory dysfunction in recreational drug users. Prospective memory deficits may be related to the reported serotonergic and frontal lobe deficits in chronic MDMA users. It is necessary to use more objective tasks to assess putative prospective memory deficits in ecstasy users. Copyright 2001 John Wiley & Sons, Ltd.

Increased intensity of Ecstasy and polydrug usage in the more experienced recreational Ecstasy/MDMA users: a WWW study.

Recreational Ecstasy/MDMA (3,4-methylenedioxymethamphetamine) users often take a variety of psychoactive drugs, but there is little empirical data on how these drug consumption patterns change with greater experience of Ecstasy. The aim of this study was to compare the polydrug usage patterns reported by non-Ecstasy users, novice Ecstasy users, moderate Ecstasy users, and heavy Ecstasy users. In a WWW study of 763 unpaid volunteers, 481 had never taken Ecstasy, whereas 282 reported they had taken it. The Ecstasy users comprised 109 novice users (1-9 occasions), 136 moderate Ecstasy users (10-99 occasions), and 36 heavy Ecstasy users (+100 occasions). Each participant also reported their experience with a range of other psychoactive drugs. The Ecstasy users reported significantly greater psychoactive drug usage than the non-Ecstasy users. The novice, moderate, and heavy Ecstasy users also differed significantly from each other in the use of cocaine, amphetamine, LSD, and psilocybin mushrooms, but not of alcohol, cannabis, or cigarettes/nicotine. Experienced Ecstasy users also took significantly more MDMA tablets on each occasion, and reported a higher maximum weekly intake. The increased use of Ecstasy is associated with more intensive patterns of Ecstasy/MDMA intake, and the greater use of illicit CNS stimulants and hallucinogens, but not of alcohol, nicotine, or cannabis. These results are discussed in the context of cross-tolerance and drug predisposition/preference.

Exposure to second-hand smoke damages everyday prospective memory.

AIMS: Prospective memory (PM: remembering future intentions and activities) is critical to everyday remembering. This study compared a group of never-smokers who reported regular exposure to second-hand smoke (the SHS group) with a group of current smokers (the CS group) and a group of never-smokers who reported never having been exposed to SHS (the non-SHS group) on objective PM. DESIGN: An existing groups design was employed to compare the SHS, CS and non-SHS groups. PARTICIPANTS AND SETTING: Twenty-four SHS, 27 CS and 28 non-SHS were tested on objective PM. All participants were university undergraduates aged between 18-30 years. All participants were tested individually in a laboratory setting. MEASUREMENTS: The Cambridge Prospective Memory Test (CAMPROMPT) was used to assess objective PM. Age, other drug use, mood and IQ were also measured as covariates in the study. FINDINGS: The non-SHS group recalled significantly more time-based PM tasks than the SHS group (means = 16.3 versus 13.7, P < 0.001) and significantly more than the CS group (CS mean = 11.6, P < 0.001); and the SHS group recalled significantly more time-based tasks than the CS group (P < 0.002). The non-SHS group recalled significantly more event-based PM tasks than the CS group (means = 15.2 versus 11.3, P < 0.002) with no significant difference between the non-SHS group and SHS group (SHS mean = 14.3, P = 0.234); and the SHS group recalled significantly more event-based tasks than the CS group (P < 0.001). CONCLUSION: Non-smokers exposed to second-hand smoke may suffer impairment in time-based prospective memory.

Everyday prospective memory and executive function deficits associated with exposure to second-hand smoke.

This study explored whether exposure to second-hand smoke (SHS) has a detrimental impact upon everyday memory in two groups of non-smokers; one which reported regular exposure to SHS and one that reported never having been exposed to SHS. Thirty-four non-smokers who reported having been regularly exposed to SHS (SHS group) and 34 non-smokers who reported never having been exposed to SHS (non-SHS group) were compared on self-reports of prospective memory (PM: remembering future intentions and/or activities) and executive function (EF: those processes involved in attention, multitasking and decision-making). The Prospective and Retrospective Memory Questionnaire (PRMQ) assessed everyday PM lapses; the Executive Function Questionnaire (EFQ) assessed self-reported problems in EF; a drug-use questionnaire and a mood questionnaire were also administered. Two univariate ANCOVAs were applied to the PM and EF data, controlling for between-group differences in age, weekly alcohol use, anxiety and depression scores, and self-reported retrospective memory scores. The SHS group reported significantly more lapses on the PRMQ and more deficits on the EFQ than the non-SHS group. These findings provide new insights into PM and EF deficits associated with prolonged exposure to SHS in a group of non-smokers. Possible explanations and suggestions for future research are also considered.

Time based prospective memory deficits associated with binge drinking: evidence from the Cambridge Prospective Memory Test (CAMPROMPT).

AIMS: To examine whether 'binge drinking' (BD) in young adults adversely affects prospective memory (PM). BD was defined as males drinking 8/more units and females 6/more units on at least one session per-week. BDs and non-binge drinkers (NBDs) were compared on self-reported and objective PM. DESIGN: An existing-groups design compared BDs with NBDs as the independent factor. Scores on the PM and retrospective memory (RM) subscales of the Prospective and Retrospective Memory Questionnaire (PRMQ) and scores on the Cambridge Prospective Memory Task (CAMPROMPT) were the dependent factors. Age, total years spent drinking, time since last drink consumed (hours), mood, strategy-use and pre-morbid IQ were measured as covariates. SETTING: Each participant was tested in a laboratory setting. PARTICIPANTS: An opportunity sample of 28 BDs and 28 NBDs were compared. MEASUREMENTS: Self-reported PM and RM lapses were measured using the PRMQ and the CAMPROMPT measured objective PM. Drug use was assessed using a Recreational Drug Use Questionnaire. The Hospital Anxiety and Depression Scale measured mood. The strategy-scale from the Prospective Memory Questionnaire measured strategy use. The National Adult Reading Test measured pre-morbid IQ. FINDINGS: BDs and NBDs did not differ in terms of gender makeup and a series of ANCOVAs (controlling for the covariates) revealed no significant between-groups differences on self-reported PM/RM lapses; but BDs exhibited reduced function on time-based PM, but not event-based PM, when compared with NBDs. CONCLUSIONS: BDs exhibit selective impairments on time-based PM; this deficit is a new finding in terms of the neuropsychological sequelae associated with BD.