The possibility to predict biologic behaviour and outcome by mean

The possibility to predict biologic behaviour and outcome by means of molecular biology techniques applied to the EUS-FNA cell sample has also been described. This approach allows to limit the number of false positive findings of the morphologic EUS test alone, which may be due to intra- or peri-pancreatic lymph nodes or splenosis nodules. A methylene blue tattoo can be made with EUS-guided injection on a small NET of the pancreas in order to facilitate intraoperative Inhibitors,research,lifescience,medical localization. Both linear and radial new generation electronic EUS scopes enable application of pulsed colour and power Doppler functions, more recently associated

with the use of ultrasound contrast media. These techniques can help in localization

and differential diagnosis of small hypervascular pancreatic nodules (89). A look in the near future IntraDuctal UltraSound (IDUS) and 3-Dimensional Inhibitors,research,lifescience,medical IDUS will perhaps add something to the already high performances of EUS in diagnosis and staging of biliary and pancreatic diseases (90). A new frontier in diagnosis and therapy could be opened by a new technique, named Endoscopic Ultrasound Retrograde CholangioPancreatography (EURCP) (91), that with some needed technological advances will allow us to put together in the same instrument the diagnostic accuracy of EUS and EUS-FNA with the therapeutic possibilities of ERCP and EUS. With such Inhibitors,research,lifescience,medical an instrument in experienced hands we can predict that the benefits to the patients and the health care system will be substantial. Today EUS is following the same way as endoscopy, i.e., to cross the bridge between a mere diagnostic technique and a therapeutic modality. In this view Inhibitors,research,lifescience,medical EUS can guide or better will guide in the near future a number of therapeutic procedures, such as ablative techniques (92,93), injection therapies (94,95), creation of digestive anastomoses (96,97). Regrettably these

new techniques have progressed very slowly till now for several reasons (small number of operative endosonographers, Inhibitors,research,lifescience,medical very little incentive by manufacturers to put substantial resources Dipeptidyl peptidase into EUS and accessories Everolimus mouse development because the market is too small, the competition of CT, MRI and vascular interventional radiology). Conclusions To date the most accurate imaging techniques for the pancreas remain CE MDHCT and EUS. They provide the most cost-effective and accurate modalities for diagnosis and staging of most cases of pancreatic diseases. CE spiral CT or better MDHCT must today be the initial study of choice in patients with suspected PC. It has replaced digital subtraction angiography for evaluation of vascular infiltration and has similar or higher accuracy than EUS in assessing locoregional extension and vascular involvement. EUS has the highest accuracy in detecting small lesions, in assessing tumor size and lymph nodes involvement.

For example, despite proven benefit in metastatic colon cancer (1

For example, despite proven benefit in metastatic colon cancer (12), irinotecan has not shown benefit

in the adjuvant setting. While signals of activity were seen in one trial, overall there were no statistically significant differences in DFS or OS with the addition of irinotecan to 5-FU/leucovorin in the adjuvant setting (13-15). This finding gave an early indication that the mechanism of chemotherapy action might be different in the setting of macrometastatic versus micrometastatic disease, a theme that Inhibitors,research,lifescience,medical has pervaded the testing of biologic agents in adjuvant colon cancer as well. Biologic agents in colon cancer Anti-VEGF therapy Vascular endothelial growth factor (VEGF) regulates angiogenesis both in health and disease, and contributes to angiogenesis in malignancy (16). For this reason, bevacizumab Inhibitors,research,lifescience,medical (Avastin®), a humanized monoclonal antibody to circulating vascular endothelial growth factor A (VEGF-A) was developed. Preclinical studies have shown multiple mechanisms of action for bevacizumab including inhibition of angiogenesis (17) by pruning of existing vessels and normalization of aberrant

vessels which is thought to improve delivery of concurrently administered chemotherapy (18). Notably, however, bevacizumab is thought to be cytostatic rather than cytotoxic, which may explain its success only in combination with cytotoxic Inhibitors,research,lifescience,medical chemotherapy, rather than as monotherapy (17). Of note, however, the majority of pre-clinical work with bevacizumab has been in models of metastatic disease and the importance of these mechanisms of action are less clear in the adjuvant setting. Clinically, in 2004, bevacizumab received Food and Drug Administration (FDA) approval Inhibitors,research,lifescience,medical for use as first line therapy in metastatic colorectal cancer based on studies Protein Tyrosine Kinase inhibitor showing improved response rate (RR), progression free survival (PFS), and OS when bevacizumab was added to 5-FU

containing regimens (19). Soon thereafter, approval for use in the 2nd line metastatic setting was granted, again based on studies indicating improved OS in combination with 5-FU containing regimens (20). Inhibitors,research,lifescience,medical In 2013, bevacizumab received an additional indication for continuation therapy at progression of metastatic disease based on data showing improved OS with ongoing bevacizumab use after progression also when the chemotherapy backbone was changed (21). In 2012, two additional anti-VEGF agents received FDA approval for use in metastatic colorectal cancer. Ziv-aflibercept (Zaltrap®) is a recombinant fusion protein with VEGF binding regions that function as decoy receptors binding intra- and extra-vascular VEGF-A such that they cannot bind to their usual receptors. The VELOUR trial showed improved OS with FOLIFRI plus ziv-aflibercept versus FOLFIFI plus placebo in metastatic colorectal cancer that progressed following an oxaliplatin-containing regimen (22). Regorafenib (Stivarga®) is an oral tyrosine kinase inhibitor that inhibits VEGF receptors 1 and 3.

By scanning each color separately, differential gene expression c

By scanning each color separately, differential gene expression can be assessed in an internally controlled manner. This method of gene expression analysis is a convenient way to compare the efficacy and side effects of drug candidates: cultured cells or animals are treated with several drug candidates that, share a common mechanism. A comparison of gene expression changes often reveals changes that Inhibitors,research,lifescience,medical are mechanism-related and are shared by such compounds, as well as changes that are

peculiar to one compound and suggest, that the compound has side effects. Such analyses can help clarify the therapeutic mechanism of action of drugs. Oligonucleotide arrays, upon which sets of oligonucleotides represent different alleles of an SNP, are used for the analysis of DNA variation. Inhibitors,research,lifescience,medical In this way, thousands of SNPs can be read out automatically and rapidly63,64 By applying whole-genome SNP LD mapping to patients during phase 2 clinical trials of a drug, it may be possible to select multiple small regions from the whole-genome Inhibitors,research,lifescience,medical SNP map where SNPs are in LD and associated with efficacy and common adverse

event, phenotypes. Selecting only these small regions of SNP LD into abbreviated SNP LD profiles will enable more rapid and inexpensive screening of patients who are likely to experience efficacy or ADRs in response to that drug.65 Thus, whereas the phase 2 SNP scan might, genotype up to 200 000 SNPs for each patient,66 the critical data, used for identifying markers for efficacy for subsequent, phase 3 clinical trials may use only several hundred SNPs from Inhibitors,research,lifescience,medical multiple small regions in LD associated with efficacy or ADRs. The cost of chips as a platform for drug response

profiling is likely to be reduced when analyses of hundreds of thousands of patients are performed once the medicine is marketed. In fact, each chip could contain a panel of abbreviated SNP LD profiles for several drugs with the same clinical indications, Inhibitors,research,lifescience,medical so that the most appropriate medicine with that indication for that patient can be determined from Digestive enzyme a single blood sample. Competition in the biotechnology sector to develop industrial genotyping capacity has reduced the retail price of genotyping some SNPs from US1 to US0.10 per SNP within 1 year,12 and the prediction is a continued decrease in price to less than US$0.01. There are ongoing technological developments, eg, the extraction of DNA from a few cells, from a buccal swab, and for the amplification of human DNA and RNA, in order to produce sufficient, quantities from minute samples (eg, GenomiPhi®, Amersham). This will circumvent, the need for a blood sample and make individual sampling even easier. One can predict that, in the future, metabolic screens of genetic variants will be standardized so that automated read-outs of each person’s predicted response to each medicine can be BLU9931 in vivo generated.

Dimension 5 – family size was protective of depressive symptoms

Dimension 5 – family size was protective of depressive symptoms. The variable maternal expectation had a long Linsitinib datasheet vector in the biplots indicating that it accounted for a large amount of variance. It did not, however, load onto one of the five dimensions. Consequently, we elected to include maternal expectation in the regression studies. Maternal expectation was strongly predictive of EPDS >12 (OR 2.77; CI 95%: 2.55–3.01). Inhibitors,research,lifescience,medical Table 2 Univariate and multivariate logistic regression on EPDS >12 In the multivariate model social exclusion, infant behavior, migrant isolation, and maternal expectation

remain significant. Family size (dimension 5) is no longer significant when controlling Inhibitors,research,lifescience,medical for the other dimensions and maternal expectation (Table 2). For the multivariate model, the Hosmer and Lemeshow Test was not significant (χ2 = 11.1, df 8, P = 0.169) indicating that the data fit the model well. The model was able to correctly classify 100% of EPDS >12 for an overall success rate of 92.4%. The Hosmer and Lemeshow Test for a model with dimension 5 – family size removed indicated a poorer fit. Discussion Inhibitors,research,lifescience,medical In our survey of mothers

of infants born in South West Sydney from 2002 to 2003, we identified a five-dimension solution using nonlinear PCA for ordinal, nominal, and dichotomous items. The solution accounted for 51% of the variance among the items studied. The five dimensions identified may represent important underlying latent variables that have causal relationships with maternal depressive symptoms. In addition to the five identified dimensions, the variable maternal expectation was identified as contributing significantly to total variance. Maternal

expectation did not cluster with one of the five identified dimensions Inhibitors,research,lifescience,medical and has therefore been analyzed separately. The first identified dimension, maternal responsiveness Inhibitors,research,lifescience,medical included the three variables, enjoys contact with the child, comforts the child, and responds to the child. Interestingly, the vectors for this dimension were perpendicular to other vectors indicating that this dimension is uncorrelated to the other variables in the data set. Poor maternal responsiveness to the infant is recognized as an important outcome of maternal depressive symptoms. The third identified dimension was infant behavior, which included: baby not unless content, -trouble sleeping, -demanding, -difficult feeder, and -difficult to comfort. Maternal depression has been shown to have an impact on infant behavior and attachment. Where a mother is depressed, the effects on her infant have been shown to be mediated by her “attachment state of mind” (McMahon et al. 2006). There has been less research on the impact of infant temperament on maternal stress and depression. Beck in her systematic review found that infant temperament was moderately related to postpartum depression (Beck 2001).

However, in clinical practice monitoring for antipsychotic side e

However, in clinical Compound C practice monitoring for antipsychotic side effects is often haphazard. A UK national audit of nearly 6000 patients prescribed depot antipsychotic medication in 2008 showed that 35% had no documented assessment of side effects in the

previous 12 months. The proportion declined during a postaudit improvement programme but was still 18% in a repeat audit in 2011 [Barnes and Paton, 2012]. Some rating scales are designed to assess specific Inhibitors,research,lifescience,medical antipsychotic side effects, for example, the Simpson Angus rating Scale (SAS) assesses parkinsonism [Simpson and Angus, 1970], the Barnes Akathisia Scale (BAS) evaluates akathisia Inhibitors,research,lifescience,medical [Barnes, 1989] and the Abnormal Involuntary Movement Scale (AIMS) assesses tardive dyskinesia [Guy et al. 1976]. Other rating scales assess a range of side effects. For example, the Glasgow Antipsychotics Side-Effect Scale (GASS) covers 22 items (Waddell and Taylor, 2008), the Udvalg for Kliniske Undersøgelser (UKU) [Lingjaerde et al. 1987] evaluates 48 possible side effects, the Liverpool University Neuroleptic Side-Effect Rating Scale (LUNSERS) includes 41 items, plus 10 ‘red herring’ items [Day

et al. 1995] and the Systematic Assessment For Treatment Emergent Events (SAFTEE) has over 70 event terms [Levine and Schooler, 1986]. Some scales Inhibitors,research,lifescience,medical are clinician-completed and some are patient-completed. Among current scales, the Inhibitors,research,lifescience,medical GASS is one of the most practical for clinical use (Waddell and Taylor, 2008). It is patient-completed, relatively

short (21 items for men and women), global in its coverage, and rates both the frequency and distress of each item. Many of the other scales are impractical for use in routine clinical practice. Among the general scales, the UKU and SAFTEE are time-consuming and require the clinician to conduct a semi-structured interview Inhibitors,research,lifescience,medical (a patient-completed version of the UKU is available) [Lindström et al. 2001]. The LUNSERS, although patient-rated, is cumbersome. The movement-specific scales, including the AIMS, SAS and BAS, are primarily research tools to characterize in detail a narrow range of side effects. The purpose of this paper is to describe the development for of a short, easy-to-use checklist that could be used in routine clinical practice to screen for a range of common antipsychotic side effects. We emphasize that it is not primarily a research tool, but rather a clinical checklist to identify symptomatic side effects and facilitate subsequent clinician–patient discussion. If it is conducted together with a physical examination and biochemical blood tests, then it can form part of a more comprehensive assessment of potential antipsychotic side effects.

This property leads to more complete spectral analyses and increa

This property leads to more complete spectral analyses and increases the speed at which acoustic windows are found (Moehring and Spencer 2002; Tsivgoulis et al. 2008). This is based on the fact that the average age of our patients was slightly higher than of those evaluated by Marinoni (58.0 ± 20.7 vs. 55.2 ± 16.1) and there was a higher percentage of females in our study. The times used in our evaluations were also shorter than those of other studies (Marinoni et al. 1997). Our #selleck chemicals keyword# TCD studies were more thorough compared to other experiments (Halsey 1990; Itoh et al. 1993), although

the suboptimal TWs could have been caused by the absence of the ACA, PCA, and/or the TICA. All of these elements may have biased our results toward a higher proportion of inadequate TWs;

in fact, there Inhibitors,research,lifescience,medical was a 10–12% proportion of suboptimal TWs in our study. For the transforaminal window, our proportion of suboptimal windows was similar to that reported by Marinoni et al. (1997), whose Inhibitors,research,lifescience,medical rate of 9.0% compares with our rate of 12.6%; these results were not affected by mechanical ventilation. We found a high success rate for TCD in the transorbital window that is probably explained by the absence of bone between the probe and the artery, which is a situation that results in the ultrasound Inhibitors,research,lifescience,medical being neither absorbed nor scattered (Ackerman et al. 1982). The rate of successful TW insonation decreases in females and with advancing age in all population groups (Halsey 1990; Itoh et al. 1993; Marinoni et al. 1997), and the latter factor was the most relevant for our population. This result is in contrast to that reported by Wijnhoud for a European (mostly Caucasian) population, in which gender was the

most important Inhibitors,research,lifescience,medical variable (Wijnhoud et al. 2008). Age clearly affects the detection of ideal TWs in a more dramatic way in females. Women 80 years or older had optimal windows in only 46.1% of the cases, compared with a rate of 72.7% in males from the same age group. This difference is explained by females having thicker temporal bones and more temporal bone inhomogeneity. The latter factor is related to osteoporosis and poorer arterial detection on TCD Ketanserin (Kwon et al. 2006); some of these anatomical characteristics are shared with African Americans (Halsey 1990). An important finding of our study was that having ideal TWs is dependent only on the patient characteristics and not on environmental elements, the location of the examination, the time of the day, the use of mechanical ventilation, among other factors. This finding is evident because the difference in the time required for our TCD examinations in different settings did not influence the likelihood of having ideal TWs.

A second class of drugs with hallucinogenic properties often refe

A second class of drugs with hallucinogenic properties often referred to as psychedelic or dissociative anesthetics includes arykyclohexy lamines, whose

most important representatives are PCP and ketamine. These agents primarily act as antagonists of the vV-mcthyl-D-aspartate (NMDA) subtype of the glutamate receptor. Finally, a third Inhibitors,research,lifescience,medical class of drugs, the so-called “entactogens,” produce psychedelic-like effects, but virtually no hallucinations. They arc closely related structurally to hallucinogenic phenylethylamines and stimulant amphetamines and include phenyttsopropy lamines, such as 3,4-methylenedioxymethamphetaminc (MDMA), 3,4-methylenedioxyethylamphctamine (MDE), and related compounds. Figure 1. Chemical structures of some important representatives of hallucinogens. Baf-A1 Classic serotonergic hallucinogens include indolamines, such as the semisynthetic lysergic acid diethylamide (LSD) and psilocybin/psilocin (the active principle of the sacred Aztec … This review summarizes Inhibitors,research,lifescience,medical recent experiments to elucidate

the neurobiological basis of the psychological effects of psilocybin, ketamine, and MDMA, each representing one of the three classes of psychedelics. Functional brain imaging with positron emission Inhibitors,research,lifescience,medical tomography (PET) was used Inhibitors,research,lifescience,medical to identify the brain regions or functional interactions among the neurotransmitter systems involved in the action of these drugs. Furthermore, receptor mechanisms of hallucinogenic and related drugs have been investigated by exploring the effects of specific receptor antagonists on drug-induced psychological alterations and information-processing functions, such as sensorimotor gating as indexed by prepulse inhibition (PPI)

of the startle reflex. The premise of the present review is that many Inhibitors,research,lifescience,medical of the shared psychedelic effects of serotonergic hallucinogens and NMDA antagonists can be understood as an effect downstream of a common neurotransmitter system or final pathway. First, both serotonergic hallucinogens and NMDA antagonists produce sufficient overlapping psychologial Adenylyl cyclase alterations despite different primary modes of action. Second, there is converging evidence from brain imaging, behavioral, and electrophysiological studies that both serotonergic hallucinogens and NMDA antagonists disrupt information processing within corticostriato-thalamic pathways implicated in the pathogenesis of psychotic disorders. Since entactogens such as MD.M.A are expected to produce only mild psychedelic symptoms, it will be of interest to know to what extent MDMA-induced neurobiological alterations differ from those seen in the states induced by hallucinogens and NMDA antagonists.

Pre-publication history The pre-publication history for this pape

Pre-publication history The pre-publication history for this paper can be accessed here: Acknowledgements We would like to thank Anders and Linnea Holmén #Selleck R428 randurls[1|1|,|CHEM1|]# for help with follow-up forms. We would like to thank the FoU department at Halmstad Regional Hospital for support during this work. This study was funded with non-commercial (Swedish State) funds via the Scientific Committee (Vetenskapsrådet) at the Halmstad Regional Hospital and Region Skåne, Sweden. The funding bodies had no input on any aspects of the final

In November 2008, a surgical team from the Red Cross Hospital Beverwijk, the Netherlands, was deployed in Afghanistan Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical for three months to attend in the army hospital of Kandahar. During their stay, four incidents of armored personnel carriers encountering an improvised explosive device were assessed. In each incident, two soldiers were involved, whose injuries were strikingly similar. Case presentation The described cases comprise paired thoracic vertebral fractures, radial neck fractures, calcaneal fractures and talar fractures. Moreover, the different types of blast injury

are mentioned and related to the injuries described in our series. Acknowledging the different Inhibitors,research,lifescience,medical blast mechanisms is important for understanding possible injury patterns. Conclusion From this case series, as well as the existing literature on injury patterns caused by blast injuries, it seems appropriate to pay extra attention to bodily areas that were injured in other occupants of the same vehicle. Obviously, the additional surveillance for specific injuries should be complementary Inhibitors,research,lifescience,medical to the regular trauma work-up (e.g., ATLS). Keywords: Improvised explosive devices, Identical injuries, Blast injury Background In November 2008, a surgical team from The Red Cross Hospital Beverwijk, the Netherlands, went to Afghanistan to attend in the army hospital of Kandahar Air

Field (KAF). During the three-month stay, several armored personnel carriers, type MRAP, encountered improvised explosive devices (IEDs). IEDs are homemade explosives that are often used by insurgents and terrorists in Inhibitors,research,lifescience,medical the Middle East. In Iraq, in 2005, 10,000 attacks were reported. From June 2003 to January 2008, IEDs caused over 1,500 fatalities. IEDs are similar to mines and are often activated by the victim Thymidine kinase himself. Often, IEDs incorporate metal fragments and/or animal fecal excrements [1-4]. IEDs contributed to the majority of injuries in casualties in the British Military Field Hospital, Shaibah, Iraq in 2006 [5]. Upon the victims’ arrival in the hospital, after triage, resuscitation and stabilization, it became clear that the occupants in each vehicle had sustained strikingly similar injuries. In this report we will describe the four cases and the trauma mechanisms. To comprehend the trauma mechanisms, it is important to be well aware of the different types of blast trauma and their impact.

56 We are cautiously hopeful that in the current decade much prog

56 We are cautiously hopeful that in the current decade much progress will be achieved in developing and implementing pharmacogenomics as a translational clinical tool to improve the outcomes and reduce the risks of antidepressant treatment. Furthermore, novel and robust pharmacogenomic findings would represent the next logical therapeutic

targets for drug development in depression. As examples, recent work by our group has #Ipatasertib keyword# identified phosphodiesterases (PDE11A) and inflammatory mediators (PSMB4, TBX21, and STAT3) as potential novel antidepressant targets.3,54 This way, pharmacogenomics will not only identify predictors of response to existing treatments, it will also have the potential to lead to conceptually novel treatments.
Major Depressive Disorder (MDD) is Inhibitors,research,lifescience,medical typically considered a mental illness, yet pathology associated with MDD is evident in cells and organs throughout the body. For example, MDD is associated with an increased risk of developing atherosclerosis, heart disease, hypertension, stroke, cognitive decline, and

dementia (including Alzheimer’s disease), osteoporosis, immune impairments (eg, Inhibitors,research,lifescience,medical “immunosenescence”), obesity, metabolic syndrome, insulin resistance, and type 2 diabetes,1-4 and individuals who are afflicted both by MDD and one of these diseases have a poorer prognosis than individuals afflicted by either

alone.3 Inhibitors,research,lifescience,medical This increased risk of serious medical diseases is not fully explained by lifestyle choices such as diet, exercise, and smoking, and the reasons for the heightened risk remain unknown.4 Moreover, many of the medical comorbidities seen in MDD Inhibitors,research,lifescience,medical are diseases more commonly seen with advanced age, and MDD has even been characterized as a disease of “accelerated aging.”1,5,6 In this review article, we explore certain biological mediators that are dysregulated in MDD and that may contribute to the depressed state itself, to the comorbid medical conditions, and to “accelerated aging.” Discovering novel pathological mediators in MDD could help identify new targets for treating depression and its comorbid crotamiton medical conditions and could help reclassify MDD as a multisystem disorder rather than one confined to the brain. Theoretical model We propose a model of MDD comprised of certain pathogenic processes that are interlinked and often recursive, that occur in the brain and in the periphery, and that can culminate in cellular damage, cellular aging, and disease.6-10 This model is presented schematically in Figure 1 and is briefly described in this introduction; the individual moderators and mediators are described in greater detail in the remainder of this article.

The alertness score was nonsignificantly decreased (F [1, 24]=3 3

The alertness score was nonsignificantly decreased (F [1, 24]=3.35, P<0.079) (Figure 3). For CTD,10 Four-way ANOVA (two group factors and, for each condition, type of score and left/right stimulus placement.) showed impaired attentional disengagement, with greater attentional cost, in patients versus controls (F [1, 24]=6.76, P<0.016) (Figure 4). However, no right/left asymmetry was observed. Figure 3. Choice reaction time (CRT) alertness scores (difference between the Inhibitors,research,lifescience,medical “with-warning” and “no-warning” conditions), showing nonsignificant decrease in patients with 0.5 s preparation time versus controls (F [1 , 24]=3.35, ... Figure 4. Different

types of cued target detection (CTD) tasks under nogap (overlap) conditions showing greater attentional cost Inhibitors,research,lifescience,medical (difference between double and no-cue conditions) in patients versus controls (F [1 , 24]=6.76, P=0.01) (as also under gap conditions). … Study 2: attention disengagement in untreated schizophrenics The aim of the second study was to determine whether the changes in attentional cost observed in patients on second-generation antipsychotics were also found in untreated patients. Inhibitors,research,lifescience,medical Subsidiary aims were to determine whether acute decompensation caused changes in alertness and processing speed, and whether these changes had any clinical correlates.

Twelve untreated patients were matched to 12 healthy subjects for age (patients: 27 [6.9] years; controls: 24.6 [3.5] years), years of education, and intelligence quotient (10) “(patients: 98 [20]; controls: 108 [15]). PANSS positive subscores were 20 (7); negative subscores: 22 (4), disorganization Inhibitors,research,lifescience,medical subscore: 1 1 (4); total subscore: 85 (9); mean Andreasen thought-language-communication (TLC) disorganization scale11: 9 (9); age of onset: 22 (7) years;

disease duration: 4 (2) years. Results For CRT, The Mann-Whitney test showed significantly longer RT values in patients at. both preparation times with or without, the warning signal. For CTD, RT values were significantly longer Inhibitors,research,lifescience,medical in patients under both gap and no-gap conditions (P=0.06 overall). Although there was a gap effect, in both patients and controls (mean gap/nogap difference between the found two populations: 31 ms), the gap alertness score was virtually zero in patients as opposed to substantial in controls (Figure 5). Figure 5. Cued target detection (CTD) task showing virtually zero alertness score (difference between double and no-cue conditions) under gap conditions in patients versus controls. Clinical correlates There was no correlation with positive or negative symptoms. However, there was a very close correlation between the PANSS disorganization subscore and the effect of the 0.5-s CRT signal (r=-0.81; P<0.01; Figure 6.). There were also correlations between the PANSS disorganization subscore and attentional benefit, in the no-gap CTD (r=0.71; P<0.05) and validity score (r=-0.71; P<0.05), and between the TLC disorganization score and attentional benefit. (r=-0.62; P<0.05).