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Temporal-order judgment (TOJ) and duration perception are fundamental aspects of subjective time experience. Previous research indicates that both may involve the inferior parietal lobe (IPL), yet the two have been studied in different contexts. This study sought to determine whether the IPL causally contributes to the temporal stimulus encoding process in TOJ and duration perception. To this end, we utilized single-pulse transcranial magnetic stimulation (TMS) as both a task stimulus and a disruptive stimulant. We combined the two tasks into an adaptive staircase method and measured both discrimination thresholds and reaction times. In a 2 × 2 within-subjects design, 24 participants performed the two tasks over two separate days (left or right IPL). Discrimination thresholds during both tasks were significantly higher in right IPL than left IPL conditions, without significant reaction time differences between the conditions. We thus provide a shared neural substrate within the right IPL, which subserves both temporal-order judgment and duration perception by encoding temporal representations. Our novel use of single-pulse TMS would be useful for other TMS studies in terms of the ability to selectively disrupt the stimulus encoding process and experimental efficiency. more...

Evidence suggests that the cortico-striatal-thalamo-cortical circuitry plays an important role in schizophrenia pathophysiology. Cerebellar contribution from deep cerebellar nuclei to the circuitry has not yet been examined. The authors investigated resting-state functional connectivity (RSFC) of cerebellar output nuclei with striatal-thalamic-cortical regions in relation to white-matter integrity and regional gray-matter volumes in first-episode psychosis (FEP). more...

Background Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) are commonly used diagnostic modalities in biliary strictures. We compared the diagnostic yield of EUS and ERCP-based tissue sampling in intrinsic biliary strictures without extrinsic mass outside the bile duct. Methods A total of 85 patients who underwent ERCP and EUS for diagnosis of suspected biliary strictures confined to the bile duct were analyzed retrospectively at Samsung Medical Center, Seoul, Korea, between 2010 and 2018. Results Seventy-one patients were diagnosed with malignancy and 14 patients were diagnosed with benign strictures. EUS-based tissue sampling was more sensitive and accurate than ERCP-based tissue sampling (p = 0.038). The overall sensitivity and accuracy were 67.6% (95% confidence interval (CI) 56.1–77.3) and 72.9% (95% CI 62.7–81.2) for ERCP-based sampling, and 80.3% (95% CI 69.6–87.9) and 83.5% (95% CI 74.2–89.9) for EUS-based sampling, respectively. EUS-based sampling was superior to ERCP-based sampling in distal bile duct strictures (accuracy: 87.0% vs. 72.5%, p = 0.007), but not in perihilar strictures. In cases without intraductal mass, EUS-based tissue sampling was also superior to ERCP-based sampling (accuracy: 83.3% vs. 69.7%, p = 0.029), but not in cases with mass. Conclusion EUS-based tissue sampling was superior to ERCP-based method in intrinsic biliary stricture with no mass outside the bile duct, particularly in those without intraductal mass or those with strictures located in distal bile duct. Therefore, EUS-based sampling should be considered for making a pathological diagnosis of suspected distal bile duct strictures even in lesions without definite mass. more...

As there were few previous studies with a small number of subjects, the purpose of this was to evaluate the prognostic significance of 18F-FDG PET/CT in patients with distal bile duct cancer undergoing curative surgery. The study included 40 patients (M/F = 24:16; age 68.0 ± 8.0 years) who underwent preoperative 18F-FDG PET/CT followed by curative surgical resection. The participant’s age, sex, Eastern Cooperative Oncology Group performance-status score, baseline serum CA 19-9 level, stage, pathologic T and N stages, tumor size, tumor grade, tumor growth pattern, R0 resection, and adjuvant therapy were included as clinicopathological variables for predicting overall survival. The PET variables were maximum standardized uptake value (SUVmax), average SUV (SUVavg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the tumor. The Kaplan-Meyer method and Cox proportional hazards model were used for the survival analysis. A total of 15 of 40 patients (37.5%) died during the follow-up period. In univariate analysis, low SUVmax (≤ 2.7, p = 0.0005) and low SUVavg (≤ 2.6, p = 0.0034) were significant predictors of poor overall survival. In multivariate analyses, only low SUVmax (HR = 6.7016, 95% CI 1.9961–22.4993, p = 0.0047) was an independent prognostic factor associated with poor overall survival. The SUVmax of the primary tumor measured by 18F-FDG PET/CT was an independent significant prognostic factor for overall survival in patients with distal bile duct cancer. However, different results from a previous study warrant further large sample-sized study. more...

Background: Ampullary lesions are being detected with increased frequency with the growing use of esophagogastroduodenoscopy. However, it is uncertain how frequently endoscopists properly visualize the major papilla in routine clinical practice. This study was undertaken to determine the actual rate of observing the major papilla by endoscopists and if there is a room for improvement in visualizing the duodenal major papilla when performing esophagogastroduodenoscopy.Methods: This was a single-center, prospective, randomized study involving 3,088 consecutive patients referred for diagnostic esophagogastroduodenoscopy at tertiary-care referral center between September and November 2010. Six fellows-in-training in the study group attempted to visualize the major papilla up to three times, while six fellows-in-training in the control group performed endoscopy in a standard fashion.Results: The overall observation rate was significantly higher in study group (975 of 1070 [91.1%]) than in control group (624 of 1022 [61%], p more...

Accurate detection of genomic alterations using high-throughput sequencing is an essential component of precision cancer medicine. We characterize the variant allele fractions (VAFs) of somatic single nucleotide variants and indels across 5095 clinical samples profiled using a custom panel, CancerSCAN. Our results demonstrate that a significant fraction of clinically actionable variants have low VAFs, often due to low tumor purity and treatment-induced mutations. The percentages of mutations under 5% VAF across hotspots in EGFR, KRAS, PIK3CA, and BRAF are 16%, 11%, 12%, and 10%, respectively, with 24% for EGFR T790M and 17% for PIK3CA E545. For clinical relevance, we describe two patients for whom targeted therapy achieved remission despite low VAF mutations. We also characterize the read depths necessary to achieve sensitivity and specificity comparable to current laboratory assays. These results show that capturing low VAF mutations at hotspots by sufficient sequencing coverage and carefully tuned algorithms is imperative for a clinical assay., High-throughput sequencing is used to identify somatic variants in cancer patients. Here, the authors perform panel-based profiling of 5095 clinical samples and demonstrate that many clinically-actionable variants have low variant allele fractions, requiring assays with high detection sensitivity. more...

Sense of agency (SoA), the experience of being in control of our voluntary actions and their outcomes, is a key feature of normal human experience. Frontoparietal brain circuits associated with SoA undergo a major maturational process during adolescence. To examine whether this translates to neurodevelopmental changes in agency experience, we investigated two key neural processes associated with SoA, the activity that is leading to voluntary action (Readiness Potential) and the activity that is associated with the action outcome processing (attenuation of auditory N1 and P2 event related potentials, ERPs) in mid-adolescents (13-14), late-adolescents (18-20) and adults (25-28) while they perform an intentional binding task. In this task, participants pressed a button (action) that delivered a tone (outcome) after a small delay and reported the time of the tone using the Libet clock. This action-outcome condition alternated with a no-action condition where an identical tone was triggered by a computer. Mid-adolescents showed greater outcome binding, such that they perceived self-triggered tones as being temporally closer to their actions compared to adults. Suggesting greater agency experience over the outcomes of their voluntary actions during mid-adolescence. Consistent with this, greater levels of attenuated neural response to self-triggered auditory tones (specifically P2 attenuation) were found during mid-adolescence compared to older age groups. This enhanced attenuation decreased with age as observed in outcome binding. However, there were no age-related differences in the readiness potential leading to the voluntary action (button press) as well as in the N1 attenuation to the self-triggered tones. Notably, in mid-adolescents greater outcome binding scores were positively associated with greater P2 attenuation, and smaller negativity in the late readiness potential. These findings suggest that the greater experience of implicit agency observed during mid-adolescence may be mediated by a neural over-suppression of action outcomes (auditory P2 attenuation), and over-reliance on motor preparation (late readiness potential), which we found to become adult-like during late-adolescence. Implications for adolescent development and SoA related neurodevelopmental disorders are discussed. more...

Introduction: The fundamental role of the cerebellum in higher cognitive processing has recently been highlighted. However, inconsistent findings exist in schizophrenia with respect to the exact nature of cerebellar structural abnormalities and their associations with cognitive and clinical features. Materials and Methods: We undertook a detailed investigation of cerebellar lobular volumes in 40 patients with first-episode psychosis (FEP) and 40 healthy controls (HCs) using the spatially unbiased atlas template of the cerebellum (SUIT). We examined the functional significance of cerebellar structural abnormalities in relation to cognitive and clinical outcomes in patients. Results: We found that left cerebellar lobules VI and X volumes were lower in FEP patients, compared to HCs. Smaller left lobules VI and X volumes were associated with fewer number of categories completed on the Wisconsin Card Sorting Test (WCST) in patients. In addition, smaller left lobule X volume was related to performance delay on the Trail Making Test (TMT) Part B in patients. Conclusion: Our results demonstrate that cerebellar structural abnormalities are present at the early stage of schizophrenia. We suggest functional associations of cerebellar structural changes with non-verbal executive dysfunctions in FEP. more...

Increasing evidence indicates that multiple structures in the brain are associated with intelligence and cognitive function at the network level. The association between the grey matter (GM) structural network and intelligence and cognition is not well understood. We applied a multivariate approach to identify the pattern of GM and link the structural network to intelligence and cognitive functions. Structural magnetic resonance imaging was acquired from 92 healthy individuals. Source-based morphometry analysis was applied to the imaging data to extract GM structural covariance. We assessed the intelligence, verbal fluency, processing speed, and executive functioning of the participants and further investigated the correlations of the GM structural networks with intelligence and cognitive functions. Six GM structural networks were identified. The cerebello-parietal component and the frontal component were significantly associated with intelligence. The parietal and frontal regions were each distinctively associated with intelligence by maintaining structural networks with the cerebellum and the temporal region, respectively. The cerebellar component was associated with visuomotor ability. Our results support the parieto-frontal integration theory of intelligence by demonstrating how each core region for intelligence works in concert with other regions. In addition, we revealed how the cerebellum is associated with intelligence and cognitive functions. more...

Mismatch negativity (MMN) is thought to reflect preattentive, automatic auditory processing. Reduced MMN amplitude is among the most robust findings in schizophrenia research. MMN generators have been shown to be located in the temporal and frontal cortices, which are key areas in the pathophysiology of schizophrenia. This study investigated whether frontotemporal cortical thickness was associated with reduced MMN current source density (CSD) strength in patients with schizophrenia.Sixteen schizophrenia patients and 18 healthy controls (HCs) were examined using magnetoencephalography while they performed a passive auditory oddball paradigm. All participants underwent a T1 structural magnetic resonance imaging scan in a separate session. We evaluated MMN CSD and cortical thickness, and their associations, in the superior and transverse temporal gyri, as well as in the inferior and middle frontal gyri.Patients exhibited significantly reduced CSD strength in all temporal and frontal areas of interest relative to HCs. There was a positive correlation between CSD strength and cortical thickness in both temporal and frontal areas in HCs. However, schizophrenia patients showed negative correlations between CSD strength and cortical thickness in the bilateral inferior frontal gyri. Additionally, we found positive correlations between frontal cortical thickness and negative and total scores on the Positive and Negative Syndrome Scale (PANSS).Our findings provide evidence for deficient temporal and frontal MMN generators and a disruption of normal structure-function relationship in patients with schizophrenia. more...

Everolimus is a standard treatment option for advanced pancreatic neuroendocrine tumors (pNETs). This multicenter study evaluated the efficacy and safety of everolimus in low and intermediate grade advanced pNETs. Tumors were graded according to the World Health Organization 2010 classification system. Patients with low or intermediate grade pNETs who received everolimus as first- or second-line chemotherapy between 2002 and 2014 were included. A total of 40 patients with metastatic or recurrent pNETs were included in this study. The median age was 54.5 years (range 19–83 years). Twelve patients (30%) experienced recurrence. There were 11 patients (27.5%) with low grade pNETs and 29 (72.5%) with intermediate. Everolimus was administered as first-line therapy in 30 patients (75%) and as second-line therapy in 10 patients (25%). The median progression-free survival (PFS) of patients with low and intermediate grade pNETs was significantly different (median not reached vs. 11 months, P = 0.015). On multivariate analysis, tumor grade (intermediate grade; HR 6.52, 95% CI 1.31–32.27, P = 0.022) was the only independent prognostic factor for PFS in pNETs. The most common adverse events were stomatitis, skin rash, and anemia. World Health Organization 2010 grade is the most important determinant for PFS in patients undergoing everolimus treatment for pNETs with an acceptable incidence of adverse events. more...

Summary Background/goals Bile is normally sterile, but the presence of organisms in the bile does not necessarily imply an active infection. We wonder what the significance of bile culture results on antibiotics choice in cholangitis with negative blood culture. The aim of this study was to compare organisms cultured from bile with those from blood in bacteremic biliary tract infection and to evaluate factors associated with concordance between blood and bile isolates. Methods Between 2000 and 2010, 266 positive blood cultures with concomitant bile culture in bacteremic biliary tract infection were identified. Follow-up bile specimens obtained after negative conversion of blood culture and clinical recovery from acute infection were collected for supplementary analysis. Results Of the 266 events, 258 showed positive bile culture. Of the 258 bile samples, 80 yielded the same organisms with blood, 129 showed partial agreement and 49 yielded completely different organisms with blood. Only the number of organism was found to be independently associated with concordance. Of the 529 organisms isolated from bile, 227 were found in blood and gram-negative organisms showed higher rate of coincidence than gram-positive organisms. Of the 84 follow-up bile sample, 94% showed persistent positive culture and higher rate of antibiotics resistance than initial bile culture. Conclusions More than half of the organisms isolated from bile, especially gram-positive organisms, are not likely to be true pathogens. But single organism cultured from bile has clinical significance. Routine follow-up bile culture in patients showing clinical improvement is not necessary. more...

Background/Aims: Despite the common use of endoscopic ultrasound (EUS) for various gastrointestinal diseases in Asia, little is known about Asian endoscopists’ attitudes toward the practice. The aim of our study was to provide a profile of Korean endoscopists’ attitudes toward EUS use. Materials and Methods: Self-administered questionnaires were distributed to endoscopists who attended the 4 th EndoFest symposium of the Korean Society of Gastrointestinal Endoscopy on March 24, 2012. We evaluated opinions on the need for EUS for assessing gastrointestinal diseases and the perceived barriers to widespread EUS use. Results: Data from 214 (32.4%) responders were analyzed. Positive opinions (agree plus strongly agree) were given on the need for EUS in the evaluation of the following gastrointestinal diseases were: subepithelial tumor (94.9%), early esophageal cancer (88.8%), early gastric cancer (86%), pancreatic cancer (84.1%), early rectal cancer (83.6%), gallbladder polyp (73.4%), advanced esophageal cancer (47.7%), colon cancer (32.2%), advanced gastric cancer (31.8%), and advanced rectal cancer (28.5%). Significant differences were observed when they were asked about the need for EUS with respect to early versus advanced cancers of the esophagus, stomach, and rectum (all p more...

Background: Homelessness is associated with an increased incidence of mental illness and risk of self-harm, including suicide. Aims: To assess the prevalence of self-harm (including nonsuicidal self-injury and attempted suicide) among a UK sample of homeless adults and to compare demographic, clinical, and homeless-related variables to determine which are linked to self-harm in this population. Method: A sample of 80 homeless adults were interviewed regarding history of self-harm, mental health history, demographic, and homeless-related information. Results: Sixty-eight percent of the sample reported past acts of self-harm. Those with histories of self-harm started using significantly more substances since becoming homeless and were younger when they first became homeless. They were also significantly more likely to have a past psychiatric admission and thoughts of self-harm in the past year. Conclusion: Self-harm is common among homeless adults and linked to long-term and enduring social and mental health concerns. more...

Purpose:To investigate demographic, clinical and neuropsychological aspects of self-harm in schizophrenia and identify which are independently predictive of and therefore the most relevant to clinical intervention.Subjects and methods:Eighty-seven patients with schizophrenia were interviewed regarding substance misuse, depression, hopelessness, negative/positive symptoms and illness insight. Neuropsychological assessment included premorbid IQ, continuous performance test, cognitive-motor and trait impulsivity. A prospective three-month review of medical records was also undertaken.Results:Fifty-nine patients (68%) reported past self-harm (including attempted suicide). Those with past self-harm, compared to those without, were significantly more likely to report depression, hopelessness, impulsivity, a family history of self-harm, polysubstance abuse and had higher premorbid IQ. Logistic regression revealed that depression, higher premorbid IQ and polysubstance abuse were independently linked to self-harm. Five participants attempted self-harm during the 3-month prospective follow-up period. These all had a history of past self-harm and were significantly more likely to have been depressed at the initial interview than those who did not go on to self-harm.Discussion and conclusions:Independent predictors of self-harm in schizophrenia are premorbid IQ and polysubstance abuse. In addition, depression was both independently associated with past self-harm and predictive of self-harm in the follow-up period. more...

Background/Goals: The endoscopic treatment of ampullary adenomas is established; however, the false-negative rate of endoscopic biopsy for carcinoma is 20% to 30%, and it remains uncertain whether identifiable features predict malignancy. Our aim in this study was to evaluate the predictable factors of malignancy in ampullary adenomas on endoscopic biopsy. Study: Ninety-one subjects diagnosed with ampullary adenoma on endoscopic biopsy were confirmed after endoscopic or surgical resection of ampullary lesions between 1995 and 2011 respectively. Clinical, laboratory, radiologic, and endoscopic findings were compared between patients with adenoma and carcinoma after resection. We examined the predictors of malignancy in ampullary adenoma on endoscopic biopsy. Results: The malignancy rate in ampullary adenomas on endoscopic biopsy was 26.4%. Univariate analysis revealed that presence of symptoms, villous components, high-grade dysplasia (HGD), papilla enlargement on computed tomography, duct dilatation on radiologic imaging, bilirubin > 2mg/dL, aspartate aminotransferase > 40 IU/L, alanine aminotransferase > 40 IU/L, and alkaline phosphatase > 90U/L were associated with malignancy in patients over 65 years of age. HGD [odds ratio, 6.86 (95% confidence interval, 1.58-29.79)] and ductal dilatation [odds ratio, 11.12 (95% confidence interval, 2.27-54.37)] were independently associated with malignancy in multivariate analysis. The sensitivity and negative predictive value for >= 1 risk factors were 95.83% and 96.77%, respectively. The presence of 2 risk factors resulted in a high specificity (96%) and positive predictive value (84%) for malignancy. Conclusions: HGD and ductal dilatation are significant predictors of malignancy in ampullary adenomas. When these risk factors are present, precautions should be taken in the consideration of malignancy in patients with ampullary adenoma. more...

Background: A few studies have investigated resting-state functional connectivity (RSFC) between the cerebral cortex and cerebellar cortex in schizophrenia, but evidence on the contribution of cerebellar efferents to the striatum and cerebral cortex has been lacking. more...

This study assessed the clinicopathological features, therapeutic approaches, and prognosis of patients with biliary neuroendocrine neoplasm (NENs).Multicenter retrospective study of patients with biliary tract NENs in the gallbladder, the extrahepatic bile duct, or the ampulla of Vater between 2005 and 2014.Total of 43 patients were included in the study. The median age was 62 years (range: 29-84 years) and 58.1% of the patients were male. The tumors occurred in the gallbladder (n = 11), the extrahepatic bile duct (n = 5) or the ampulla of Vater (n = 27). The liver was the most common metastatic site. Based on the 2010 World Health Organization classification, more patients with gallbladder NENs (11/11 (100%)) had neuroendocrine carcinoma G3 than those with NENs in the ampulla of Vater (10/27 (37.1%)). The median progression free survival time (39.3 vs 5.1 months, p = 0.001) and median overall survival time (46.9 vs 7.9 months, p 0.001) were significantly longer in patients with ampulla of Vater NENs than gallbladder NENs. A 2010 World Health Organization classification of neuroendocrine carcinoma G3 was independently related to poor overall survival (hazard ratio (HR), 27.1; 95% confidence intervals (CI), 2.81-260.68; p = 0.004).The 2010 World Health Organization classification of neuroendocrine carcinoma G3 was the only factor related to poor prognosis in patients with biliary neuroendocrine neoplasms. more...

Adjustments to movement in response to changes in our surroundings are common in everyday behavior. Previous research has suggested that the left pre-motor cortex (PMC) is specialized for the temporal control of movement and may play a role in temporal error correction. The aim of this study was to determine the role of the left PMC in sensorimotor timing and error correction using theta burst transcranial magnetic stimulation (TBS). In Experiment 1, subjects performed a sensorimotor synchronization task (SMS) with the left and the right hand before and after either continuous or intermittent TBS (cTBS or iTBS). Timing accuracy was assessed during synchronized finger tapping with a regular auditory pacing stimulus. Responses following perceivable local timing shifts in the pacing stimulus (phase shifts) were used to measure error correction. Suppression of the left PMC using cTBS decreased timing accuracy because subjects tapped further away from the pacing tones and tapping variability increased. In addition, error correction responses returned to baseline tap–tone asynchrony levels faster following negative shifts and no overcorrection occurred following positive shifts after cTBS. However, facilitation of the left PMC using iTBS did not affect timing accuracy or error correction performance. Experiment 2 revealed that error correction performance may change with practice, independent of TBS. These findings provide evidence for a role of the left PMC in both sensorimotor timing and error correction in both hands. We propose that the left PMC may be involved in voluntarily controlled phase correction responses to perceivable timing shifts. more...

Gravitational forces may lead to local changes in subarachnoid cerebrospinal fluid (CSF) layer thickness, which has important implications for neurophysiological modulation and recording techniques. This study examines the effect of gravitational pull associated with different head positions on the distribution of subarachnoid CSF using structural magnetic resonance imaging. Images of seven subjects in three different positions (supine, left lateral and prone) were statistically compared. Results suggest that subarachnoid CSF volume decreases on the side of the head closest to the ground, due to downward brain movement with gravity. These findings warrant future research into currently unexplored gravitation-induced changes in regional subarachnoid CSF thickness. more...

Computational models have been be used to estimate the electric and magnetic fields induced by transcranial magnetic stimulation (TMS) and can provide valuable insights into the location and spatial distribution of TMS stimulation. However, there has been little translation of these findings into practical TMS research. This study uses the International 10-20 EEG electrode placement system to position a standard figure-of-eight TMS coil over 13 commonly adopted targets. Using a finite element method and an anatomically detailed and realistic head model, this study provides the first pictorial and numerical atlas of TMS-induced electric fields for a range of coil positions. The results highlight the importance of subject-specific gyral folding patterns and of local thickness of subarachnoid cerebrospinal fluid (CSF). Our modelling shows that high electric fields occur primarily on the peaks of those gyri which have only a thin layer of CSF above them. These findings have important implications for inter-individual generalizability of the TMS-induced electric field. We propose that, in order to determine with accuracy the site of stimulation for an individual subject, it is necessary to solve the electric field distribution using subject-specific anatomy obtained from a high-resolution imaging modality such as MRI. more...

Adaptation to delayed sensory feedback following an action produces a subjective time compression between the action and the feedback (temporal recalibration effect, TRE). TRE is important for sensory delay compensation to maintain a relationship between causally related events. It is unclear whether TRE is a sensory modality-specific phenomenon. In 3 experiments employing a sensorimotor synchronization task, we investigated this question using cathodal transcranial direct-current stimulation (tDCS). We found that cathodal tDCS over the visual cortex, and to a lesser extent over the auditory cortex, produced decreased visual TRE. However, both auditory and visual cortex tDCS did not produce any measurable effects on auditory TRE. Our study revealed different nature of TRE in auditory and visual domains. Visual-motor TRE, which is more variable than auditory TRE, is a sensory modality-specific phenomenon, modulated by the auditory cortex. The robustness of auditory-motor TRE, unaffected by tDCS, suggests the dominance of the auditory system in temporal processing, by providing a frame of reference in the realignment of sensorimotor timing signals. more...

Schizophrenia impairs both facial emotion processing and sustained attention. Through separate studies, it is known that the presence of a task-irrelevant facial stimulus disproportionately interferes with performance, whereas increasing the salience of task stimulus improves performance during a sustained attention task in patients with schizophrenia. We wished to investigate a potential interaction effect of background facial emotion expression (black and white happy faces vs. grey oval) and target stimulus salience (bright white vs. grey) using the Continuous Performance Test-Identical Pairs version (CPT-IP) in patients with schizophrenia. Thirty-six patients with schizophrenia and 28 healthy control subjects completed 4 different versions of the CPT-IP. We found that healthy controls exhibited higher signal detection sensitivity (d′) when salient target stimuli were presented on the facial background than when the same stimuli were presented on the grey-oval background. By contrast, patients were not affected by background stimuli when target number stimuli were salient. When target number stimuli were not salient, both patients and controls showed higher d′ in the grey-oval background condition compared with the facial background condition. This study highlight the significance of stimulus salience during CPT-IP in schizophrenia as background stimuli did not produce a differential effect on performance. Our results suggest that, in the situations where facial emotion stimuli are present, patients' sustained attention can be deteriorated and that the use of salient materials is important in improving performance in schizophrenia. more...

Many homeless people may have been exposed to events and situations that could potentially produce neuropsychological impairments. In the current study, 80 homeless participants underwent a battery of tests designed to 1) estimate long-standing established memory and intelligence, which was assumed to indicate prehomeless function and 2) measure current memory and intelligence function. Mental health screening and substance misuse data were also obtained. Results indicated that current memory and IQ were significantly lower than the estimated normal population means and also their prehomeless estimates. The memory score change was from 100.5 to 90.3 (p .001) and IQ change from 98.8 to 95.6 (p .038). The interaction between task type (memory or IQ) and measure (prehomeless or current) was also significant (p .003), signifying that there was a greater change in the domain of memory function than in IQ. Many participants reported substance misuse and clinically significant mental health concerns. We conclude that the homeless individuals in our sample appear to have suffered a reduction in cognitive function, which may have occurred either during homelessness or prior to it. more...

We systematically examined the impact of emotional stimuli on time perception in a temporal reproduction paradigm where participants reproduced the duration of a facial emotion stimulus using an oval-shape stimulus or vice versa. Experiment 1 asked participants to reproduce the duration of an angry face (or the oval) presented for 2,000 ms. Experiment 2 included a range of emotional expressions (happy, sad, angry, and neutral faces as well as the oval stimulus) presented for different durations (500, 1,500, and 2,000 ms). We found that participants over-reproduced the durations of happy and sad faces using the oval stimulus. By contrast, there was a trend of under-reproduction when the duration of the oval stimulus was reproduced using the angry face. We suggest that increased attention to a facial emotion produces the relativity of time perception. more...

Background/Aims: The aim of this study was to evaluate the usefulness of health screening for early detection and improved prognosis in pancreatic cancer. Methods: Between 1995 and 2008, 176,361 examinees visited the Health Promotion Center (HPC). Twenty patients diagnosed with pancreatic cancer were enrolled. During the same period, 40 patients were randomly selected from 2,202 patients diagnosed with pancreatic cancer at the Out Patient Clinic (OPC) for comparison. Results: Within the HPC group, 10 patients were initially suspected of having pancreatic cancer following abnormal ultrasonographic fi ndings, and 9 patients had suspected cases following the detection of elevated serum CA 19-9. The curative resection rate was higher in the HPC group than in the OPC group (p=0.011). The median survival was longer in the HPC group than in the OPC group (p=0.000). However, there was no significant difference in the 3-year survival rate between the two groups. Asymptomatic patients (n=6/20) in the HPC group showed better curative resection and survival rates than symptomatic patients. However, the difference was not statistically signifi cant. Conclusions: Health screening is somewhat helpful for improving the curative resection rate and median survival of patients with pancreatic cancer detected by screening tests. However, the benefi t of this method in improving long-term survival is limited by how early the cancer is detected. (Gut Liver 2011;5:194199) more...

Objectives. To describe levels of traumatic childhood events in a sample of homeless individuals and to assess the contribution of traumatic events to neurobehavioural traits (measured with the Frontal Systems Behaviour Scale, FrSBe) and general cognitive function (IQ). Design. A sample of 55 homeless adults was recruited from homeless services in the city of Sheffield, UK. All were interviewed to acquire substance misuse information, record experiences of childhood trauma, and assess cognitive and neurobehavioural traits. Methods. Experiences of abuse and neglect were assessed with the Childhood Trauma Questionnaire. Participants also completed the Wechsler Abbreviated Scale of Intelligence and the FrSBe, which was completed with respect to current behaviour and conduct prior to homelessness. Results. Around three-quarters of the sample scored in the clinically significant range for current neurobehavioural impairment. They also reported high levels of impairment when rating retrospectively for the period before they were homeless. The mean group IQ was below average at 88. Abuse or neglect during their upbringing was reported by 89% of the sample. Emotional abuse, emotional neglect, and physical neglect were all positively correlated with total FrSBe scores. Sexual abuse, emotional neglect, and physical neglect were all negatively correlated with IQ. The associations between trauma and IQ and neurobehavioural traits appear generally unrelated to the presence of substance misuse in the sample. Conclusion. Our homeless sample displayed relatively low IQ with high levels of neurobehavioural impairment. Our evidence suggests that these neuropsychological factors may, in part, constitute a long-term consequence of childhood trauma. more...

Introduction. Schizophrenia causes clinically conspicuous impairment of syntax and semantics as part of the disorganisation syndrome; however, little is known regarding its effect on the phonological stage of speech, where word meanings are resolved into speech imagery. Methods. We used a “tongue-twister” task to probe phonological speech production and its clinical associations in six schizophrenia patients and 16 controls. Results. Errors induced by phonological similarity were more common in the patients (p=.003), were positively associated with psychomotor poverty symptoms (p=.02) and negatively associated with reality distortion symptoms (p=.03). Conclusions. Our findings suggest that phonological speech production is markedly disrupted by schizophrenia. Further, this phonological abnormality is distinct from disorganisation syndrome. more...

Using the Zimbardo Time Perspective Inventory (ZTPI; P. G. Zimbardo & J. N. Boyd, 1999), the authors found that homeless people, in comparison with a control group, had a significantly more negative outlook concerning their past and present as evinced by high Past-Negative and Present-Fatalistic scores and low Past-Positive scores on the ZTPI. However, the homeless individuals were almost indistinguishable from control participants on measures of Present-Hedonism and Future thinking. The homeless individuals had significantly higher levels of depression, with 31 out of 50 (62%) reaching criteria for probable depression. However, this finding was unrelated to their atypical time perspective. There was no significant relation between substance misuse and time perspective. Despite their current difficulties, including depression and drug abuse, the homeless individuals maintained a propensity toward future thinking characterized by striving to achieve their goals. more...

Patients with schizophrenia have difficulty recognising the emotion that corresponds to a given facial expression. According to signal detection theory, two separate processes are involved in facial emotion perception: a sensory process (measured by sensitivity which is the ability to distinguish one facial emotion from another facial emotion) and a cognitive decision process (measured by response criterion which is the tendency to judge a facial emotion as a particular emotion). It is uncertain whether facial emotion recognition deficits in schizophrenia are primarily due to impaired sensitivity or response bias. In this study, we hypothesised that individuals with schizophrenia would have both diminished sensitivity and different response criteria in facial emotion recognition across different emotions compared with healthy controls. Twenty-five individuals with a DSM-IV diagnosis of schizophrenia were compared with age and IQ matched healthy controls. Participants performed a "yes-no" task by indicating whether the 88 Ekman faces shown briefly expressed one of the target emotions in three randomly ordered runs (happy, sad and fear). Sensitivity and response criteria for facial emotion recognition was calculated as d-prime and In(beta) respectively using signal detection theory. Patients with schizophrenia showed diminished sensitivity (d-prime) in recognising happy faces, but not faces that expressed fear or sadness. By contrast, patients exhibited a significantly less strict response criteria (In(beta)) in recognising fearful and sad faces. Our results suggest that patients with schizophrenia have a specific deficit in recognising happy faces, whereas they were more inclined to attribute any facial emotion as fearful or sad. more...

BackgroundThe ability to appreciate humour is essential to successful human interactions. In this study, we hypothesized that individuals with schizophrenia would have diminished ability to recognize and appreciate humour. The relationship between humour experience and clinical symptoms, cognitive and social functioning was examined.MethodThirty patients with a DSM-IV diagnosis of schizophrenia were compared with 30 age-, gender-, IQ- and ethnicity-matched healthy controls. Humour recognition was measured by identification of humorous moments in four silent slapstick comedy film clips and calculated as d-prime (d′) according to signal detection theory. Humour appreciation was measured by self-report mood state and funniness ratings. Patients were assessed for clinical symptoms, theory of mind ability, executive function [using the Wisconsin Card Sorting Test (WCST)] and social functioning [using the Life Skills Profile (LSP)].ResultsPatient and control groups did not differ in the funniness ratings they attributed to the video clips. Patients with schizophrenia had a lower d′ (humour) compared to the controls, after controlling for (1) the performance of a baseline recognition task with a non-humorous video clip and (2) severity of depressive symptoms. In patients, d′ (humour) had significant negative correlation with delusion and depression scores, the perseverative error score of the WCST and the total scores of the LSP.ConclusionsCompared with controls, patients with schizophrenia were less sensitive at detecting humour but similarly able to appreciate humour. The degree of humour recognition difficulty may be associated with the extent of executive dysfunction and thus contribute to the psychosocial impairment in patients with schizophrenia. more...

The Analogies Understanding Test (AUT) was developed as a brief cognitive screening task of executive problem solving. A few of the test items at the beginning are "facilitated" as a means of engaging patients. Individuals with schizophrenia and mild Alzheimer's Disease (AD) made significantly less correct responses than their control groups. The schizophrenia patients, but not AD patients, made significantly more perseverations than controls on the AUT. As expected, AUT performance in schizophrenia patients correlated with the Wisconsin Card Sorting test measures. Preliminary findings suggest that the AUT test may be useful as a measure of executive dysfunction in neuropsychiatric patients. more...

Cathepsin D (CatD) is a good candidate susceptibility marker for Alzheimer's disease (AD), since it was found to be involved in the processing of the amyloid precursor protein and the formation of the hyperphosphorylated tau. And recently, a CatD genetic polymorphism was found to be associated with the risk of Alzheimer's disease (AD) in a German population. However, the CatD T–AD association has not been replicated in a series of the successive independent studies in other races. Therefore, we determined CatD genotypes to examine the possible association of the CatD polymorphism with AD in Koreans. We failed to find significant association between the CatD T allele and AD. In addition, the CatD T–AD association was not significant regardless of the age at onset or the occurrence of the apolipoprotein ɛ4 allele. However, we cannot exclude the possible contribution of the CatD in the development of AD, since the power of the present study was not high enough because of low allelic frequency of the CatD T in Koreans and small sample size. In conclusion, the association between the CatD genetic polymorphism and AD was not found in Koreans, although it waits for further replication in an extended sample. more...

Background. A better understanding of the neural basis of social cognition including mindreading (or theory of mind) and empathy might help to explain some deficits in social functioning in people with schizophrenia. Our aim was to review neuroimaging and neuropsychological studies on social cognition, as they may shed light on the neural mechanisms of social cognition and its dysfunction in patients with schizophrenia.Method. A selective literature review was undertaken.Results. Neuroimaging and neuropsychological studies suggest convergence upon specific networks for mindreading and empathy (the temporal cortex, amygdala and the prefrontal cortex). The frontal lobe is likely to play a central role in enabling social cognition, but mindreading and empathic abilities may require relatively different weighting of subcomponents within the same frontal-temporal social cognition network.Conclusions. Disturbances in social cognition may represent an abnormal interaction between frontal lobe and its functionally connected cortical and subcortical areas. Future studies should seek to explore the heterogeneity of social dysfunction within schizophrenia. more...

We asked 24 schizophrenia patients and 24 healthy comparison subjects to complete a parametric working memory version of the continuous performance test. Patients exhibited a relatively rapid performance decline with increasing working memory demands. We suggest an interaction between sustained attention and working memory abnormalities in schizophrenia. more...

Self-harm, such as self-cutting, self-poisoning or jumping from height, regardless of intentions, is common among people with schizophrenia. We wished to investigate brain activations relating to self-harm, in order to test whether these activations could differentiate between schizophrenia patients with self-harm and those without. We used event-related functional MRI with a go/no-go response inhibition paradigm. Fourteen schizophrenia patients with a history of self-harm were compared with 14 schizophrenia patients without a history of self-harm and 17 healthy control participants. In addition, we used standard clinical measures and neuropsychological tests to assess risk factors associated with self-harm. The right dorsolateral prefrontal cortex (DLPFC) and the left posterior cingulate cortex differentiated all three groups; brain activation in these regions being greatest in the control group, and the self-harm patient group being greater than in the non-self-harm patient group. In the self-harm patient group, right DLPFC activity was positively correlated with severity of suicidal thinking. In addition, both patient groups showed less activation in the right orbitofrontal cortex, left ventral anterior cingulate cortex and right thalamus. This is the first study to report right DLPFC activation in association with self-harm and suicidal thinking in patients with schizophrenia. This area could be a target for future neuromodulation studies to treat suicidal thinking and self-harm behaviors in patients with schizophrenia. more...

BackgroundEvidence suggests that auditory hallucinations may result from abnormally enhanced auditory sensitivity.AimsTo investigate whether there is an auditory processing bias in healthy individuals who are prone to experiencing auditory hallucinations.MethodTwo hundred healthy volunteers performed a temporal order judgement task in which they determined whether an auditory or a visual stimulus came first under conditions of directed attention (‘attend-auditory’ and ‘attend-visual’ conditions). The Launay–Slade Hallucination Scale was used to divide the sample into high and low hallucination-proneness groups.ResultsThe high hallucination-proneness group exhibited a reduced sensitivity to auditory stimuli under the attend-auditory condition. By contrast, attention-directed visual sensitivity did not differ significantly between groups.ConclusionsHealthy individuals prone to hallucinatory experiences may possess a bias in attention towards internal auditory stimuli at the expense of external sounds. Interventions involving the redistribution of attentional resources would have therapeutic benefit in patients experiencing auditory hallucinations. more...

Objectives : Frontal and lateralized schizophrenia disturbances were examined in terms of arousal-modulated changes in 40 Hz Gamma activity. Methods : Forty patients with schizophrenia and 40 age- and gender-matched controls were studied in a conventional auditory ERP oddball paradigm. We investigated sub-averaged Gamma activity based upon a simultaneous measure of electrodemal skin conductance response (phasic arousal) to differentiate novelty (large responses) from routinization (small or no responses). Both early Gamma (Gamma 1) and later induced Gamma (Gamma 2) activities were examined. Results : Patients with schizophrenia (compared with controls) had significantly reduced Gamma 1 amplitude in the right hemisphere for novelty processing and delayed Gamma 2 latency in the left hemisphere for both novelty and routinization. Overall, reduced Gamma 1 amplitude in patients with schizophrenia was also evident. Conclusions : These findings indicate that the normal laterality of Gamma activity is specifically disturbed in schizophrenia in response to novel, but not routine (familiar) stimuli. The distinct pattern of findings suggests a dysregulation of activation across left and right hemispheres during initial attention and preparatory phases of information processing, in particular, in patients with schizophrenia. more...

There have been a number of studies on smooth pursuit eye movement (SPEM) dysfunction in schizophrenia. However, the association between SPEM dysfunction and particular clinical symptoms remains unclear. We examined SPEM dysfunction in relation to schizophrenic symptoms using both the positive/negative dichotomy and the three-syndrome model. Subjects included 78 patients with schizophrenia and 60 healthy control subjects. SPEM performance was indexed by root mean square error. Symptom profiles were assessed using the Positive and Negative Syndrome Scale (PANSS), and the three-primary syndromes were identified by factor analysis of PANSS ratings (Psychomotor poverty: deficit negative symptoms; Disorganization: defined primarily by thought disorder; and Reality distortion: hallucinations and delusions). Compared with controls, the schizophrenia group showed significant impairment in global SPEM function. The three-syndrome approach produced more specific findings than the dichotomous model. Of the three syndromes, only the Disorganization dimension showed a significant association with increased global SPEM dysfunction. The specificity of SPEM dysfunction to Disorganization was verified in comparisons among schizophrenia subgroups and the control group. By contrast, the general domains of positive and negative symptoms were both found to be modestly associated with SPEM dysfunction. The separation of positive and negative symptoms that contribute to Disorganization from those that define Reality Distortion and Psychomotor Poverty has revealed significant new associations between SPEM and schizophrenic symptoms. These findings are interpreted in light of the proposal that the Disorganization syndrome is the central form of pathology in schizophrenia. more...

Objective Our aim was to review smooth pursuit eye movement (SPEM) studies in schizophrenia and groups at high risk for schizophrenia, with a view to evaluating the utility of SPEM dysfunction as a biological marker of risk for schizophrenia. Method Smooth pursuit eye movement studies, related saccade function and the unresolved issues in this area of schizophrenia research were addressed. The different perspectives on the trait marker status of SPEM dysfunction, provided by both high-risk studies and related developmental research were considered. Attention was also given to the relationship between eye movement dysfunction and symptom profiles. Results Converging evidence points to the robust and specific nature of SPEM dysfunction in schizophrenia, and highlights the role of frontal lobe and a related network dysfunction. The vast majority of ‘high risk’ studies support the view that SPEM dysfunction is also genetically specific to schizophrenia, and is not simply due to the overt expression of this illness. Studies assessing SPEM in relation to symptomatology show an association with the Disorganisation syndrome in particular. Conclusions Evidence for the specificity of SPEM dysfunction to diagnosed schizophrenia, as well as to healthy individuals with a genetic vulnerability to schizophrenia, suggests that the SPEM task has efficacy as a test of gene carrier status in schizophrenia, and therefore as a trait marker of risk for schizophrenia. Future studies should seek to explore the relationships between SPEM and other eye movement dysfunctions (antisaccades, express saccades), in view of evidence that some of these dysfunctions also show specificity for schizophrenia. more...

The in-vitro activity of 12 antibacterial agents against 98 clinical isolates of Streptococcus pneumoniae, including 54 penicillin-resistant strains, was determined by a standardized broth microdilution method. CFC-222, vancomycin and imipenem were the most active agents, with an MIC90 of 0.5 mg/L for the test strains. CFC-222 was 16-fold more potent than ciprofloxacin and ofloxacin against all strains tested, including both penicillin-susceptible and -resistant strains. The anti-pneumococcal activity of fluoroquinolones was not affected by penicillin susceptibility. These results indicate that CFC-222 is potentially useful for treating infection caused by penicillin-resistant strains of S. pneumoniae. more...

Next-generation sequencing (NGS) that enables the analyses of massively parallel sequences of DNA can advance the understanding of the underlying molecular pathophysiologies of cancer. Such recent genomic analyses have revealed a complex mutational landscape in surgical specimens of PDAC. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is used in the diagnosis of pancreatic cancer. Several genomic analyses using EUS-FNA in PDAC have been undertaken in a small number of patients. This study evaluated the feasibility of targeted NGS of specimens obtained using EUS-FNA to clarify genetic markers associated with the prognosis of pancreatic cancer. One hundred sixty six patients who underwent EUS-FNA with pathologically confirmed PDAC were included. Genomic DNA was extracted and quality control metrics of DNA analytes were measured. The specimens that passed a quality control test (N = 101, 61%) underwent NGS using a customized cancer panel (CancerSCAN) enriched in the exons of 83 genes. Clinical prognostic factors associated with survival in PDAC were age, performance status, CA 19-9 level, curative resection, chemotherapy, tumor mass size, tumor location, stage and metastasis site in univariate analysis (P = 0.020, Citation Format: Joo Kyung Park, Kwang Hyuk Lee, Jong Kyun Lee, Kyu Taek Lee, Woong-Yang Park, Dae-Soon Son. Targeted sequencing from endoscopic ultrasound-guided fine needle aspirates of pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 96. more...

Background There is an established corpus of evidence linking substance abuse with neuropsychological impairment, particularly implicating frontal lobe functions. These could potentially be premorbid to, rather than consequences of, direct effects of substance abuse. Methods A matched pairs design was employed in which currently abstinent opiate abusers in treatment were matched to 22 healthy control individuals. These were compared for premorbid and current neurobehavioral abnormalities with the self-report Frontal Systems Behavior Scale (FrSBe). Estimated premorbid and current IQ scores were also ascertained. Results There was no difference between the groups regarding socioeconomic background. There was no evidence for an alteration in cognitive function as measured by current IQ associated with opiate abuse, nor evidence of premorbidly lower IQ. However, with the FrSBe, the opiate abusers reported overall higher levels of apathy. They also had raised FrSBe total scores, indicating the presence of neurobehavioral features associated with frontal lobe impairment. Furthermore, the opiate abusers reported higher levels of these neurobehavioral abnormalities compared to their matched controls, even in the period preceding substance abuse. Conclusions The results suggest that some substance abusing individuals in treatment demonstrate raised levels of neurobehavioral abnormalities, independently of general intellectual functioning. Furthermore, the results imply that these abnormalities may have already been present prior to the effects on the nervous system of substance abuse. more...