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Summary Memory and perception have long been considered separate cognitive processes, and amnesia resulting from medial temporal lobe (MTL) damage is thought to reflect damage to a dedicated memory system. Recent work has questioned these views, suggesting that amnesia can result from impoverished perceptual representations in the MTL, causing an increased susceptibility to interference. Using a perceptual matching task for which fMRI implicated a specific MTL structure, the perirhinal cortex, we show that amnesics with MTL damage including the perirhinal cortex, but not those with damage limited to the hippocampus, were vulnerable to object-based perceptual interference. Importantly, when we controlled such interference, their performance recovered to normal levels. These findings challenge prevailing conceptions of amnesia, suggesting that effects of damage to specific MTL regions are better understood not in terms of damage to a dedicated declarative memory system, but in terms of impoverished representations of the stimuli those regions maintain., Highlights ► Perception can be impaired in amnesia resulting from perirhinal cortex (PRC) damage ► Reducing object perceptual interference can rescue PRC-damaged amnesics' performance ► Memory loss after PRC damage can reflect heightened susceptibility to interference ► Impoverished object representations may contribute to amnesia, Barense and colleagues demonstrate that perceptual deficits in amnesic patients with medial temporal lobe damage can be rescued by reducing interference from visually similar stimuli. These findings challenge current views on amnesia and the neural basis of memory.

There has been considerable debate surrounding the functions of the medial temporal lobe (MTL). Although this region has been traditionally thought to subserve long-term declarative memory only, recent evidence suggests a role in short-term working memory and even higher order perception. To investigate this issue, functional neuroimaging was used to investigate the involvement of the MTL in spatial scene perception and working memory. Healthy participants were scanned during a working memory task incorporating two factors of working memory (high vs. low demand) and spatial processing (complex vs. simple). It was found that an increase in spatial processing demand produced significantly greater activity in the posterior hippocampus and parahippocampal cortex irrespective of whether working memory demand was high or low. In contrast, there was no region within the MTL that increased significantly in activity during both the complex and the simple spatial processing conditions when working memory demand was increased. There was, however, a significant interaction effect between spatial processing and working memory in the right posterior hippocampus and parahippocampal cortex bilaterally: An increase in working memory demand produced a significant increase in activity in these areas during the complex, but not simple, spatial processing conditions. These findings suggest that although there may be a role for the MTL in both stimulus processing and working memory, increasing the latter does not necessarily increase posterior MTL involvement. We suggest that these structures may play a critical role in processing complex spatial representations, which, in turn, may form the basis of short- and long-term mnemonic processes.

Infancy is a vulnerable age group for anemia throughout the world. However, community-based screening for infantile anemia is seldom reported. This study determined the prevalence of anemia among infants in an Okinawan village from 2003 to 2008, in relation to secondary prevention of the condition. The prevalence among infants aged 3–5, 6–12 and 16–23 months was 12.3%, 15.8%, and 4.2%, respectively, based on cross-sectional surveys (n=3070), and was 11.0%, 17.2%, and 3.9% according to another retrospective cohort study (n=511). The relatively low prevalence of anemia at early childhood suggested that previous detection and treatment through early and late infantile screening had been successful.

The idea that the medial temporal lobe (MTL), traditionally viewed as an exclusive memory system, may also subserve higher-order perception has been debated fiercely. To support this suggestion, monkey and human lesion studies have demonstrated that perirhinal cortex damage impairs complex object discrimination. The interpretation of these findings has, however, been disputed because these impairments may reflect a primary deficit in MTL-mediated working memory processes or, in the case of human patients, undetected damage to visual processing regions beyond the MTL. To address these issues, this study investigated object perception in two human amnesic patients who were chosen on the basis of their lesion locations and suitability for detailed neuroimaging investigation. A neuropsychological task with minimal working memory demands was administered in which participants assessed the structural coherency of single novel objects. Critically, only the patient with perirhinal atrophy was impaired. Moreover, volumetric and functional neuroimaging data demonstrated that this deficit cannot be attributed to the dysfunction of visual cortical areas. Additional analyses of eye-movement patterns during the perceptual task revealed an inability of this patient to detect structural incoherency consistently. This study uses a combination of techniques to provide strong evidence that the perirhinal cortex subserves perception and suggests that the MTL perceptual-mnemonic debate cannot be dismissed on the basis of anatomy or a working memory impairment.

Cashdollar and colleagues (1) describe a powerful combination of behavioral and magnetoencephalography data from healthy participants and patients with bilateral hippocampal sclerosis to support a role for the hippocampus in the active maintenance of configural-relational (C-R) information. This study reveals the importance of hippocampal-dependent theta synchronization of temporal and occipital regions in humans to C-R working memory, and how such coordination may contribute to the integration of visual information represented throughout the rostral-caudal extent of the ventral visual processing stream. These findings, therefore, add to a growing body of literature arguing for an involvement of the hippocampus in both long- and short-term relational memory.

The medial temporal lobe (MTL), a set of heavily interconnected structures including the hippocampus and underlying entorhinal, perirhinal and parahippocampal cortex, is traditionally believed to be part of a unitary system dedicated to declarative memory. Recent studies, however, demonstrated perceptual impairments in amnesic individuals with MTL damage, with hippocampal lesions causing scene discrimination deficits, and perirhinal lesions causing object and face discrimination deficits. The degree of impairment on these tasks was influenced by the need to process complex conjunctions of features: discriminations requiring the integration of multiple visual features caused deficits, whereas discriminations that could be solved on the basis of a single feature did not. Here, we address these issues with functional neuroimaging in healthy participants as they performed a version of the oddity discrimination task used previously in patients. Three different types of stimuli (faces, scenes, novel objects) were presented from either identical or different viewpoints. Consistent with studies in patients, we observed increased perirhinal activity when participants distinguished between faces and objects presented from different, compared to identical, viewpoints. The posterior hippocampus, by contrast, showed an effect of viewpoint for both faces and scenes. These findings provide convergent evidence that the MTL is involved in processes beyond longterm declarative memory and suggest a critical role for these structures in integrating complex features of faces, objects, and scenes into viewinvariant, abstract representations.

Background: To ascertain the relationship between habitual physical activity and the risk of ischemic stroke among the Chinese population. Methods: A case-control study was conducted in Foshan, Guangdong Province, during 2007–2008. Information on physical activity exposure and lifestyle characteristics was obtained from 374 incident ischemic stroke patients and 464 hospital-based controls (mean age 66 years) using a validated and reliable questionnaire. Logistic regression analyses were performed to assess the association between physical activity levels and the ischemic stroke risk. Results: The control subjects reported significantly longer duration of strenuous sports and moderate activity in recent daily life than the stroke patients. Increased engagements in such leisure time activities were associated with reduced risks of ischemic stroke after adjustment for confounding factors. A significant inverse dose-response relationship was also found for total physical activity exposure, with an adjusted odds ratio of 0.25 (95% confidence interval = 0.14–0.45) for older adults engaged in 22 or more metabolic equivalent task hours per week relative to those engaged in less than 10 metabolic equivalent task hours per week. Conclusions: The study provided evidence of an inverse association between habitual physical activity and the risk of ischemic stroke, which is important for the promotion and encouragement of leisure time exercise activities among elderly Chinese adults.

Background: Experimental studies have suggested that soybean products may protect against ischemic stroke, but only limited epidemiological evidence is available. Objective: Our aim was to investigate the relationship between soy food consumption and the risk of ischemic stroke among the Chinese population. Methods: A case-control study was conducted in southern China during 2007–2008. Soy food consumption, dietary intake and lifestyle information were obtained from 374 incident ischemic stroke patients and 464 hospital-based controls. Logistic regression analyses were performed to assess the association between soy food intake and the ischemic stroke risk. Results: The mean weekly soy food intake was significantly lower (p = 0.001) among cases (89.9, SD = 239.3 g) than control subjects (267.7, SD = 426.1 g). Increased consumptions of dried soybean, tofu, soymilk and total soy foods were associated with reduced risks of ischemic stroke after adjusting for confounding factors. The corresponding adjusted odds ratios for the highest versus lowest level (Conclusion: The results provided evidence of inverse association between habitual soy food consumption and the risk of ischemic stroke for Chinese adults.

Background: Respiratory infections are common in acute stroke. Previous studies have found dysphagia is associated with respiratory infections. Of interest is whether patients who are ‘Nil by Mouth’ (NBM) and tube fed have higher risk of developing infections due to aspiration of bacteria-laden saliva or refluxed material than stroke patients who are fed orally. Methods: Prospective cohort of 330 ischemic stroke survivors were followed for 30 days and infections recorded. Results: 115 infections were treated with antibiotics; these included 51 respiratory infections. Incidence of infection in NBM tube-fed stroke patients (n = 74) was 69%, with 30 respiratory infections occurring in 74 patients who received enteral feeding after stroke. Logistic regression analysis showed tube feeding during admission was a significant risk for respiratory infection. We also saw a significant time-to-event effect with 73% (22/30) respiratory infections in tube-fed survivors diagnosed on days 2–4 after stroke, and 76% (39/51) of infections in all tube-fed survivors occurring by day 7 after stroke. Relevance to a theory of critical period of susceptibility to infection in acute stroke is discussed. Conclusions: NBM tube-fed survivors were unlikely to have aspirated anything other than saliva/secretions or reflux, yet experienced significantly higher rates of respiratory infections than survivors fed orally. Stringent oral care and measures to prevent reflux are potentially modifiable aspects of stroke management.

Impairments in visual discrimination beyond long-term declarative memory have been found in amnesic individuals, with hippocampal lesions resulting in deficits in scene discrimination and perirhinal cortex damage affecting object discrimination. To complement these findings, the present functional magnetic resonance imaging study found that in healthy participants oddity judgment for novel trial-unique scenes, compared with face or size oddity, was associated with increased posterior hippocampus and parahippocampal cortex activity. In contrast, perirhinal and anterior hippocampus activity was observed during unfamiliar trial-unique face oddity judgment, when contrasted with scene or size oddity tasks. Activity in all of these regions decreased as the stimuli were repeated across trials, reflecting the participants' increasing familiarity with the stimuli. This change was significant in all areas, with the exception of the perirhinal cortex, right anterior hippocampus, and to a lesser extent the left anterior hippocampus during face oddity judgment. One possibility is that the activity in these regions may not reflect entirely episodic memory encoding but, in part, processes beyond the mnemonic domain. Thus, the perirhinal cortex, and possibly anterior hippocampus, may play a more generic role in the discrimination and processing of objects.

Recent findings from animal and human studies of memory have challenged existing accounts of the role of the medial temporal lobe (MTL) in human long-term declarative memory. These studies indicate that the MTL is not exclusively specialized for declarative long-term memory, with evidence of impairments in short-term memory and perceptual discrimination in patients with progressive and nonprogressive MTL damage. These deficits have been elicited by the increased use of paradigms developed from the animal literature which have highlighted two key factors that seem to differentially influence performance after MTL lesions: (a) whether participants are asked to perceive and remember scenes vs. objects/faces; and (b) the use of simple or complex feature ambiguous stimuli. Functional neuroimaging in healthy participants using similar paradigms has provided convergent evidence for these neuropsychological studies, revealing differential activation of two distinct networks involving different MTL regions during face and scene processing. These results are discussed with respect to existing models of the role of human MTL regions in long-term memory.

A prominent and long-standing view of human long-term memory is that structures within the medial temporal lobe (MTL) work together to support the acquisition of memory for facts and events. In contrast to this view, recent studies in rats and non-human primates suggest dissociations in function between regions comprising the MTL. Evidence in support of such specialisation in humans, however, has been inconclusive, leading some researchers to propose that human MTL functions as a unitary system uniquely specialised for the acquisition and storage of long-term memory. This paper reviews some of the key studies from the animal and human literature that support an account of functional differentiation and discusses the different theoretical positions that have emerged from their findings. A series of recent experiments in humans designed to determine whether there is functional homogeneity in MTL regions across species are also reviewed and an alternative account of human memory - in which long-term memory is dependent upon representations distributed throughout the human brain rather than one specialised system - is proposed. © 2008 Psychology Press.

Background/Aim: Stroke is a leading cause of mortality and morbidity in China. Accurate diagnosis of stroke type requires advanced imaging techniques. However, CT scan and MRI were not widely used in China until the middle 1990s. We estimate the stroke incidence based on stroke hospitalizations in Shunde District, Foshan, south China. Methods: Stroke hospitalization rates were calculated for different age strata using the number of cases observed and the population size of Shunde in 2005 and 2006. Results: The age-adjusted hospitalization rates (per 100,000 person-years) for all strokes were 57.4 overall, 65.1 for males and 50.0 for females, standardized according to Segi’s world population. Conclusion: The stroke incidence appeared to be lower in Shunde than those reported for other parts of China.

Previous fMRI studies have demonstrated preferential involvement of the perirhinal cortex and hippocampus in tasks of object and spatial memory, respectively. Here we investigated whether similar activity would also be present when object and spatial discrimination was assessed in the absence of explicit declarative memory demands. On each trial in the scanner, participants were presented simultaneously with two arrays of objects and were asked to indicate whether both arrays were identical, differed with respect to the identity of one object or differed with respect to the spatial arrangement of the objects. It was found that the detection of an object identity change was associated with significant right perirhinal cortex activity. We suggest that this perirhinal activity indicates a role of this structure in processes beyond declarative memory, for example, short-term visual working memory or higher order perception. Significantly greater hippocampal activity was not, however, observed during the spatial arrangement condition, perhaps due to the relatively low spatial processing demands of this task.

Investigations of memory in rats and nonhuman primates have demonstrated functional specialization within the medial temporal lobe (MTL), a set of heavily interconnected structures including the hippocampal formation and underlying entorhinal, perirhinal, and parahippocampal cortices. Most studies in humans, however, especially in patients with brain damage, suggest that the human MTL is a unitary memory system supporting all types of declarative memory, our conscious memory for facts and events. To resolve this discrepancy, amnesic patients with either selective hippocampal damage or more extensive MTL damage were tested on variations of an object discrimination task adapted from the nonhuman primate literature. Although both groups were equally impaired on standard recall-based memory tasks, they exhibited different profiles of performance on the object discrimination test, arguing against a unitary view of MTL function. Cases with selective hippocampal damage performed normally, whereas individuals with broader MTL lesions were impaired. Furthermore, deficits in this latter group were related not to the number of discriminations to be learned and remembered, but to the degree of “feature ambiguity,” a property of visual discriminations that can emerge when features are part of both rewarded and unrewarded stimuli. These findings resolve contradictions between published studies in humans and animals and introduce a new way of characterizing the impairments that arise after damage to the MTL.

Evidence for an association between indicators of adiposity and survival after ovarian cancer has been inconsistent. A prospective cohort study was conducted in China to examine the relationship between ovarian cancer survival and body mass index (BMI). From the 214 patients recruited in 1999 to 2000 with histopathologically confirmed invasive epithelial ovarian cancer, 207 patients or their close relatives (96.7% of cases) were traced and followed to 2003. Deaths were recorded and Cox proportional hazards regression was used to obtain hazard ratios (HR) and 95% confidence intervals (95% CI) from multivariate models. Reduced survival was observed among patients with BMI ≥ 25 kg/m2 at 5 years before diagnosis (P = 0.001). There were 98 (59.8%) of 164 patients with BMI

The medial temporal lobe (MTL) has been considered traditionally to subserve declarative memory processes only. Recent studies in nonhuman primates suggest, however, that the MTL may also be critical to higher order perceptual processes, with the hippocampus and perirhinal cortex being involved in scene and object perception, respectively. The current article reviews the human neuropsychological literature to determine whether there is any evidence to suggest that these same views may apply to the human MTL. Although the majority of existing studies report intact perception following MTL damage in human amnesics, there have been recent studies that suggest that when scene and object perception are assessed systematically, signifi-cant impairments in perception become apparent. These findings have important implications for current mnemonic theories of human MTL function and our understanding of human amnesia as a result of MTL lesions.

Although monkey lesion studies involving the prefrontal cortex commonly report working memory deficits, and neuroimaging studies consistently show prefrontal involvement in such tasks, patients with damage to this region commonly fail to show any working memory impairment. Such a discrepancy may be due to insensitive testing measures for patients, as well as small, yet critical differences between working memory tasks in imaging and patient studies. The current study utilised a more sensitive measure of spatial working memory spans, based either on structured or unstructured spatial arrays. A PET study in normal subjects confirmed that both variants did indeed activate prefrontal cortex. The same tasks were given to frontal lobe patients and closely matched controls. Patients with large frontal lesions were significantly impaired on this task, with those patients with damage to the right dorsolateral prefrontal cortex appearing particularly impaired. This result demonstrates that prefrontal cortex is necessary for normal working memory, even in simple tasks, such as spatial span. It is suggested, however, that the patient deficit reflects strategic or goal-based dysfunction, rather than storage limitations.

Recent animal studies suggest that the medial temporal lobe (MTL), which is thought to subserve memory exclusively, may support non-mnemonic perceptual processes, with the hippocampus and perirhinal cortex contributing to spatial and object perception, respectively. There is, however, no support for this view in humans, with human MTL lesions causing prominent memory deficits in the context of apparently normal perception. We assessed visual discrimination in amnesic cases to reveal that while selective hippocampal damaged patients could discriminate faces, objects, abstract art and colour, they were significantly poorer in discriminating spatial scenes. By contrast, patients with MTL damage, including perirhinal cortex, were significantly impaired in discriminating scenes, faces, and to a lesser extent objects, with relatively intact discrimination of art and colour. These novel observations imply that the human MTL subserves both perceptual and mnemonic functions, with the hippocampus and perirhinal cortex playing distinct roles in spatial and object discrimination, respectively.

A novel, neuropsychologically informed paradigm (extended retrieval of events in response to a cue word) was used to investigate the neural basis of autobiographical and semantic memory. Contrasting retrieval of autobiographical memories with retrieval of semantic facts (ABM — SEM) in 24 subjects across three PET studies revealed bilateral involvement of the middle temporal gyrus (BA 21) and medial frontal cortex (BA 9/10). The opposite contrast, SEM — ABM, resulted in increased regional cerebral blood flow in left posterior temporal regions (BA 37) and left prefrontal cortex (BA 45/46). Laterality maps suggest that the bilateral pattern seen in our studies, but not often in other neuroimaging investigations, reflects the use of a task stressing retrieval of specific personal events. Further comparisons revealed that the activation in the right anterior temporal lobe during autobiographical recall was virtually identical to that seen during retrieval of information about famous people or events in contrast with retrieval of general semantic facts. These findings suggest that the retrieval of an autobiographical event requires participation from conceptual knowledge, and that this type of knowledge is bilaterally distributed in the temporal lobes.

One problem in studying the neural basis of semantic memory using functional neuroimaging is that it is often difficult to disentangle activation associated with semantic memory retrieval from that associated with episodic memory encoding and retrieval. To address this issue, a novel homophone task was used in which subjects were PET scanned whilst learning a series of real words (e.g., prey). In a subsequent scan, the subjects were presented with homophone pairs (e.g., prey vs pray) and were required to choose the one that had been shown previously. In two corresponding baseline tasks, the subjects were scanned whilst learning and recognizing pronounceable nonwords. Thus, while all of these tasks recruited either episodic memory encoding or retrieval processes, only the homophone tasks involved semantic memory retrieval. A conjunction analysis designed to isolate activation associated with semantic memory retrieval, revealed changes in several left lateral frontal regions (BA 9/10, 9/45), the left middle temporal cortex (BA 21), and in the left inferior temporoparietal cortex (BA 39). In contrast, a conjunction analysis designed to isolate activation associated with episodic memory encoding, revealed significant changes in the left hippocampus, as well as in the frontopolar cortex (BA 10) bilaterally, the left inferior parietal cortex (BA 40), and the left superior temporal gyrus (BA 22, 28). The present results clarify and extend recent attempts to understand the neural basis of semantic memory retrieval, by actively controlling for the confounding effects of episodic memory encoding and retrieval processes.

Recently, there has been considerable debate regarding the involvement of the left and right prefrontal cortices in the encoding and retrieval of episodic memory. In a previous PET study, we found that the use of easily verbalisable material may lead to activation predominantly in the left lateral frontal cortex whilst the use of non-easily verbalisable material may lead to activation predominantly in the right lateral frontal cortex, in both cases irrespective of encoding and retrieval processes. In order to replicate and extend these findings, the same task was modified for use with fMRI. Six healthy volunteers were scanned while encoding and then recalling stimuli that either emphasised visual or verbal processes. It was found that, in comparison to a baseline condition, the encoding of visual stimuli led to a bilateral activation of the prefrontal cortex whilst the encoding of verbal stimuli led to a preferential activation of the left prefrontal cortex. An effect of stimulus type was less evident during retrieval, with both visual and verbal stimuli leading to bilateral prefrontal cortex activation. Overall, encoding and retrieval activated similar regions of the prefrontal cortex suggesting that these areas mediate processes that are fundamental to both aspects of memory. To extend these findings further, the tasks used in the fMRI study were used to assess a group of patients with unilateral frontal lesions and a group of healthy control volunteers. The patients were significantly impaired compared to the healthy volunteers, although no significant differences were found in performance between the right- and left-sided lesioned patients. This result suggests that the memory-related asymmetries observed during functional neuroimaging studies may not be critical for task performance.

135 Background: Active surveillance (AS) has emerged as a viable option for many men with early stage prostate cancer (PC). This approach of careful monitoring with prostate-specific antigen (PSA) level, digital rectal examination, and prostate biopsy may allow men to avoid or delay the potentially debilitating side effects of such aggressive treatments as surgery or radiation; however, AS may create uncertainty and anxiety for men with PC. We examined the associations between illness uncertainty and anxiety and general and PC-specific quality of life (QOL) of 191 men with favorable-risk PC participating in the AS program at MD Anderson Cancer Center. Methods: Men completed measures of uncertainty (Mishel Uncertainty in Illness Scale), anxiety (State-Trait Anxiety Inventory), and general (SF-12, Physical Health [PCS] and Mental Health Component Score [MCS]) and disease-specific (Expanded Prostate Index Composite [EPIC]) QOL questionnaires upon study entry and every 6 months. These results are through a 2.5 year follow-up. Results: Men were primarily (86%) white and an average age of 67.2 (SD=8.9). Average baseline PSA was 3.3 ng/mL (SD=1.6), 98% had a Gleason score of 6, and 85% had cT1c disease. Both general and PC-specific QOL were relatively unchanged across the 2.5 year study period, except for statistically significant declines in the EPIC Sexual score (p

22 Background: Prostate cancer (PC) screening is controversial and a better assessment of individualized PC risk is needed. Several single nucleotide polymorphisms (SNPs) conferring a cumulative risk of PC have been identified. We have explored the potential role of genetic markers for targeted screening in a population with increased risk of PC due to family history (FH). Methods: PROFILE was developed as a pilot study to determine the feasibility of targeted PC screening using prostatic biopsy (PB) and its association with specific genetic profiles in men with FH. We also evaluated the role of PSA and Diffusion Weighted MRI (DW-MRI) as screening tools. One hundred sixteen men age 40 to 69 with FH of PC were enrolled between October 2009 and December 2012. Cumulative SNP risk scores were calculated by summing 59 risk alleles for each locus using the weighted effect (log-additive model). DW-MRI was performed in 50 patients. Participants were asked to undergo a 10 core PB regardless of baseline PSA. Results: Median age 53 (40 to 69) and median PSA was 1.15. One hundred and two men accepted to undergo a PB as primary PC screening. Twenty-three tumours were found (22.5% of biopsies) as well as seven men diagnosed with atypical small acinar proliferation (ASAP) (6.8%) and eight men with high-grade prostatic intraepithelial neoplasia (HG-PIN) (7.8%). In total 37.1% received an abnormal result. Out of the diagnosed PC 41% were intermediate or high risk and requiring treatment, which compares with 24% in general population screening. The predictive performance of DW-MRI, PSA, genetic model and genetic model plus PSA measured by AUC were: 0.85, 0.73, 0.57 and 0.74, respectively. The genetic model performed best in men with a normal PSA of

This chapter describes the design, theoretical rationale, and validation of the Cambridge Neuropsychological Test Automated Battery (CANTAB). The utility of the battery for functional neuroimaging studies is examined, based on its links with animal neuropsychological research, its decomposition of complex tests of cognition into their constituent parts, and its validation in patient groups with defined brain lesions. The CANTAB has now been used quite extensively in the testing of patients with Alzheimer's disease and other forms of dementia. Two CANTAB tests specifically target spatial working memory functions, the spatial span and the self-ordered spatial working memory tasks. Both have been used in the context of positron emission tomography (PET) scanning to resolve a number of theoretical issues concerning the organization of working memory within the frontal lobe. In the CANTAB, short-term visual recognition memory is assessed using the delayed-matching-to-sample (DMTS) task.

e12554 Background: Hodgkin Lymphoma (HL) is an uncommon lymphoid malignancy with an estimated 9,060 new cases and 1,170 patients dying of disease each year in the US. High dose chemotherapy followed by autologous stem cell transplant (ASCT) is standard treatment for relapsed or refractory HL. Patients who do not respond to or relapse after ASCT have a short survival and are candidates for investigational agents. In the absence of published studies, the primary objective of this study was to estimate the percent and number of patients with HL who relapsed after ASCT. Methods: Number of ASCT performed for HL patients and relapse rate reported in the literature was used to estimate number of HL patients who relapsed after ASCT. Number of ASCT in US with HL was extracted from 2008-2010 CIBMTR (Center for International Blood and Marrow Transplant Research) data assuming a stable number for 2010-2012. A literature review (1993-2012) using EMBASE identified relapse rate after ASCT in HL. A model was built using relapse rates at 12, 24, 36, 48 and 60 months. If there was no relapse rate at a time point, it was estimated by dividing nearest data point following relapse rate by period length. Rate differences at 12 and 24 months were used to estimate relapse rate for 2ndyear. Same methods were used to calculate other year rates. Results: An estimated 791 patients underwent ASCT for HL in 2012 based on prior years data. Three clinical trials and 9 epidemiological studies providing post-ASCT relapse rate were identified from the literature review. Relapse rates over 5 years and number of patients with relapsed HL after ASCT were estimated to be 44.7% and 352 patients, respectively, in 2012. Conclusions: : In the absence of published literature, a model was built to estimate the number of HL patients who relapsed after ASCT suggesting a high rate at 44.7% over 5 years. Because not all US centers participate in the CIBMTR registry, these numbers are likely to be conservative and actual rate may be higher. Clinical trials targeting this relatively small patient population with clear unmet medical need require collaborative efforts to enroll patients and more research to understand factors for patients relapsing post-ASCT.

5054 Background: Prostate cancer (PC) screening is controversial and better approaches are needed, including a better assessment of individualized PC risk. Several studies have identified a number of common single nucleotide polymorphisms (SNPs) that confer a cumulative risk of PC. We have explored the potential role of genetic markers in identifying men who should be selectively targeted for screening in a population with increased risk of PC due to family history (FH) of the disease. Methods: PROFILE has been developed as a pilot study. The primary aim is to determine the feasibility of targeted PC screening using prostatic biopsy (PB) and its association with specific genetic profiles in men with FH. Secondary aims are to evaluate the role of PSA and Diffusion Weighted MRI (DW-MRI) as screening tools in this population. From December 2010 men aged 40-69 with FH of PC were invited into the study until 100 men were enrolled. Blood samples were provided for PSA and DNA extraction. The cumulative SNP risk scores for each patient were calculated by summing 59 risk alleles for each locus using the weighted effect as estimated in previous studies (log-additive model). DW-MRI was performed in 50 patients. All participants were asked to undergo a 10 core PB regardless of baseline PSA. Those who declined PB have been excluded from this analysis. Data on side effects and cancer worry were also collected. Results: 35% of invited men entered the study. Median age was 53 yrs (40-69) and median PSA was 1.15. Ninety men accepted to undergo a PB as primary PC screening. Twenty-two tumours were found and 45% of them were clinically significant [Median age 64yrs (47-69), median PSA 5.4 (0.91-9.3)]. The predictive performance of DW-MRI, PSA, genetic model and genetic model plus PSA measured by AUC were: 0.85, 0.73, 0.57 and 0.74, respectively. The genetic model performed better in men with PSA

243 Background: Endorectal balloons (ERB) are routinely used in proton radiation for prostate cancer (PCa). The dosimetric implications, however, in conjunction with scanning proton beam therapy (SPT) have not been studied. We sought to describe dose-volume values with the use of an ERB vs no ERB for SPT for PCa. Methods: We analyzed 10 patients with localized PCa. Each patient underwent two CT simulations, one with a water-filled ERB (50-60 ml) and one with no ERB. For 8 patients, the prostate and proximal 1 cm of the seminal vesicles was the clinical target volume (CTV), with the prostate only as CTV for 2 patients. We defined 3 structures: rectum (R), anterior rectal wall (ARW) as a 3 mm rim of the anterior half of the rectum, and AR-CTV as the ARW only on slices with a contoured CTV. SPT plans were created in both cases for each patient, with the creation of a scanning target volume (STV), which expanded the CTV by 6 mm in all dimensions except 4 mm posteriorly and 12 mm laterally. Two opposed lateral beams were used to plan to the STV. Total dose was 78 Co-60 Gy equivalent in 39 fractions, to cover 95% of the STV. RBE was 1.1. We compared the dose-volume values for the R, ARW, and AR-CTV between the two arms. Results: The ERB significantly increased the R volume for all cases (61 ± 11 ml vs 105 ± 10 ml (p

176 Background: Independently, dose-escalated external beam radiation therapy (DE-EBRT) and short-term androgen deprivation therapy (ADT) improve outcomes for men with intermediate-risk prostate cancer; however, the incremental benefit of adding short-term ADT to DE-EBRT is uncertain. The aim of this study was to determine the effect of adding ADT to DE-EBRT and to identify men most likely to benefit from ADT. Methods: We reviewed the medical records of 636 men treated for intermediate-risk prostate cancer with DE-EBRT (>75 Gy) from 1995 to 2009. The adult comorbidity evaluation-27 index categorized severity of comorbidity. Recursive partitioning analysis defined unfavorable disease. Kaplan-Meier and log-rank tests compared failure-free survival (FFS) with and without ADT. Results: Median age was 70 years (interquartile range [IQR] 65–74). Overall, 45% received DE-EBRT alone and 55% DE-EBRT with ADT (median 6 months, IQR 6-8). Median follow up was 4.3 years. On Cox-proportional hazard regression analysis that adjusted for differences in comorbidities and tumor characteristics, administration of ADT improved FFS (adjusted hazard ratio 0.36, 95% confidence interval 0.18–0.72; p=0.004). Recursive partitioning analysis of men without ADT classified Gleason 4+3=7 or ≥ 50% positive cores as unfavorable disease (5-year FFS 96.3% favorable vs. 81.6% unfavorable; p Conclusions: The addition of ADT to DE-EBRT improves FFS for men with unfavorable intermediate-risk prostate cancer (Gleason 4+3=7 or ≥ 50% positive cores) especially those with no or minimal comorbidity. Men with favorable intermediate-risk disease or with moderate to severe comorbidity may not benefit from the addition of ADT to DE-EBRT.

Recent functional-neuroimaging studies have provided a wealth of new information suggesting that regions of the prefrontal cortex play a role in episodic memory encoding and retrieval. This review seeks to evaluate the results of these studies in the context of one general model that has proposed that the left prefrontal cortex is preferentially involved in episodic memory encoding, whereas the right prefrontal cortex is preferentially involved in episodic memory retrieval, irrespective of the type (e.g., modality) of information being remembered. The origins of this framework are considered in some detail and then all relevant functional-neuroimaging studies are critically reviewed. The results of this review fail to provide support for the functional-asymmetry model, suggesting instead that episodic memory encoding and retrieval may actually involve similar regions of the lateral prefrontal cortex when all factors relating to the type of stimulus material (i.e., modality), are appropriately controlled.

Background: The CanRisk Tool (https://canrisk.org) is the next-generation web interface for the latest version of the BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) state-of-the-art risk model and a forthcoming ovarian cancer risk model. Methods: The tool captures information on family history, rare pathogenic variants in cancer susceptibility genes, polygenic risk scores, lifestyle/hormonal/clinical features, and imaging risk factors to predict breast and ovarian cancer risks and estimate the probabilities of carrying pathogenic variants in certain genes. It was implemented using modern web frameworks, technologies, and web services to make it extensible and increase accessibility to researchers and third-party applications. The design of the graphical user interface was informed by feedback from health care professionals and a formal evaluation. Results: This freely accessible tool was designed to be user friendly for clinicians and to boost acceptability in clinical settings. The tool incorporates a novel graphical pedigree builder to facilitate collection of the family history data required by risk calculations. Conclusions: The CanRisk Tool provides health care professionals and researchers with a user-friendly interface to carry out multifactorial breast and ovarian cancer risk predictions. It is the first freely accessible cancer risk prediction program to carry the CE marking. Impact: There have been over 3,100 account registrations, and 98,000 breast and ovarian cancer risk calculations have been run within the first 9 months of the CanRisk Tool launch.

Is human semantic knowledge neurally organised according to either category (e.g. living vs non-living) or attribute type (e.g. perceptual vs non-perceptual information)? Normal subjects were scanned using PET during a novel semantic production task, in which they generated either perceptual or non-perceptual information in response to names of living or non-living concepts. Analyses of blood flow in the temporal lobes revealed no significant differences associated with responses to living vs non-living concepts. Comparisons between retrieval of perceptual vs non-perceptual information, however, revealed significantly greater blood flow in left posterior inferior temporal cortex and right fusiform cortex associated with perceptual information and in left middle temporal cortex with non-perceptual information. These findings support a primarily attribute-based neural organisation of semantic knowledge.