Spaced training facilitates long-term retention of place navigation in adult but not in adolescent rats

Young and adult Long Evans rats were tested in the water maze according to two different procedures: half of the subjects were given one session of four trials a day for 6 days, whereas the other subjects had the same amount of training massed in 1 day. For both conditions, a 14-day retention interval was then introduced to test long-term memory. This was followed by a four-trial reversal session. All groups showed a significant learning curve, but escape latencies were shorter for the adult than for the young rats, without differential effect of the training procedure. A first probe trial (PT1) confirmed similar accurate short-term retention in all the groups. But unimpaired long-term memory was only seen in the adult rats trained with the spaced procedure. The young rats trained over 1 day also showed some retention of the platform location after 14 days, but not the other two groups. Reversal acquisition of the new platform location was rapid in the four groups. These results indicate that although accurate short-term spatial memory in the water maze is seen after a 1-day massed training in both age groups, unimpaired long-term retention is only observed in adult rats trained with 24-h inter-session intervals.

Test of four colon cancer risk-scores in formalin fixed paraffin embedded microarray gene expression data.

BACKGROUND: Prognosis prediction for resected primary colon cancer is based on the T-stage Node Metastasis (TNM) staging system. We investigated if four well-documented gene expression risk scores can improve patient stratification. METHODS: Microarray-based versions of risk-scores were applied to a large independent cohort of 688 stage II/III tumors from the PETACC-3 trial. Prognostic value for relapse-free survival (RFS), survival after relapse (SAR), and overall survival (OS) was assessed by regression analysis. To assess improvement over a reference, prognostic model was assessed with the area under curve (AUC) of receiver operating characteristic (ROC) curves. All statistical tests were two-sided, except the AUC increase. RESULTS: All four risk scores (RSs) showed a statistically significant association (single-test, P < .0167) with OS or RFS in univariate models, but with HRs below 1.38 per interquartile range. Three scores were predictors of shorter RFS, one of shorter SAR. Each RS could only marginally improve an RFS or OS model with the known factors T-stage, N-stage, and microsatellite instability (MSI) status (AUC gains < 0.025 units). The pairwise interscore discordance was never high (maximal Spearman correlation = 0.563) A combined score showed a trend to higher prognostic value and higher AUC increase for OS (HR = 1.74, 95% confidence interval [CI] = 1.44 to 2.10, P < .001, AUC from 0.6918 to 0.7321) and RFS (HR = 1.56, 95% CI = 1.33 to 1.84, P < .001, AUC from 0.6723 to 0.6945) than any single score. CONCLUSIONS: The four tested gene expression-based risk scores provide prognostic information but contribute only marginally to improving models based on established risk factors. A combination of the risk scores might provide more robust information. Predictors of RFS and SAR might need to be different.

HIERFSTAT, a package for R to compute and test hierarchical F-statistics

The package HIERFSTAT for the statistical software R, created by the R Development Core Team, allows the estimate of hierarchical F-statistics from a hierarchy with any numbers of levels. In addition, it allows testing the statistical significance of population differentiation for these different levels, using a generalized likelihood-ratio test. The package HIERFSTAT is available at http://www.unil.ch/popgen/softwares/hierfstat.htm.

Altered vision during motion: an unusual symptom of cerebellar dysfunction, quantifiable by a simple clinical test.

PURPOSE: To report a series of patients with cerebellar dysfunction and altered vision during motion, and to quantify their visual impairment in motion with a simple clinical test. METHODS: Twenty consecutive patients suffering from cerebellar dysfunction and altered vision during motion were examined between 1994 and 2007. A control group consisted of 20 age- and sex-matched healthy people. All patients had a full neuro-ophthalmic examination. Near visual acuity (NVA) was measured at rest (static NVA) and during chair rotation (dynamic NVA). Distance visual acuity (DVA) was measured at rest (static DVA) and during rotation of the patient's head (dynamic DVA). RESULTS: Only four of the 20 patients reported altered vision during motion spontaneously. The remaining 16 patients admitted this unusual visual disturbance only when asked specifically. All patients exhibited abnormal eye movements, including saccadic smooth pursuit (20/20), dysmetric saccades (15/20), nystagmus (19/20) and impaired suppression of vestibulo-ocular reflex (VOR) (20/20). During rotation of the examination chair (dynamic NVA), the drop in NVA averaged 5.6 lines (range 1-10 lines). During rotation of the patient's head (dynamic DVA), the drop in DVA averaged only 2.5 lines (range 0-10 lines). For the control group, there was no significant drop in NVA under dynamic conditions. CONCLUSION: Patients with cerebellar dysfunction rarely complain spontaneously of altered vision during motion. However, specific questioning may bring up this unusual symptom. The use of a simple clinical test, consisting of NVA measurement during rotation of the examination chair (dynamic NVA), allows practitioners to quantify the level of visual impairment in patients presenting altered VOR modulation.

Intrahippocampal cholinergic grafts in aged rats compensate impairments in a radial maze and in a place learning task

Age-related cognitive impairments were studied in rats kept in semi-enriched conditions during their whole life, and tested during ontogeny and adult life in various classical spatial tasks. In addition, the effect of intrahippocampal grafts of fetal septal-diagonal band tissue, rich in cholinergic neurons, was studied in some of these subjects. The rats received bilateral cell suspensions when aged 23-24 months. Starting 4 weeks after grafting, they were trained during 5 weeks in an 8-arm maze made of connected plexiglass tunnels. No age-related impairment was detected during the first eight trials, when the maze shape was that of a classical radial maze in which the rats had already been trained when young. The older rats were impaired when the task was made more difficult by rendering two arms parallel to each other. They developed an important neglect of one of the parallel tunnels resulting in a high amount of errors before completion of the task. In addition, the old rats developed a systematic response pattern of visits to adjacent arms in a sequence, which was not observed in the younger subjects. None of these behaviours were observed in the old rats with a septal transplant. Sixteen weeks after grafting, another experiment was conducted in a homing hole board task. Rats were allowed to escape from a large circular arena through one hole out of many, and to reach home via a flexible tube under the table. The escape hole was at a fixed position according to distant room cues, and olfactory cues were made irrelevant by rotating the table between the trials. An additional cue was placed on the escape position. No age-related difference in escape was observed during training. During a probe trial with no hole connected and no proximal cue present, the old untreated rats were less clearly focussed on the training sector than were either the younger or the grafted old subjects. Taken together, these experiments indicate that enriched housing conditions and spatial training during adult life do not protect against all age-related deterioration in spatial ability. However, it might be that the considerable improvement observed in the grafted subjects results from an interaction between the graft treatment and the housing conditions.

A new blood-based screening test for colorectal cancer: a pilot study

Background: Colorectal cancer (CRC) can be cured when diagnosed in its early or precancerous (adenoma) stages. Mostly due to poor compliance towards invasive screening procedures, detection rates for adenoma and early CRCs are still low. Available non-invasive screening tests have unfortunately low sensitivity and specificity performances. Therefore, there is a large unmet need calling for a cost-effective, reliable and non-invasive test to screen for early neoplastic and pre-neoplastic lesions. Objective: To develop a routine screening test based on a nucleic acids multi-gene assay performed on peripheral blood mononuclear cells (PBMCs) that can detect early CRCs and adenomas. Methods: 116 patients (mean age: 55 years; range: 18 to 74 years; female/male ration 0.98) were included in this pilot, nonblinded, colonoscopy-controlled study. Colonoscopy revealed 21 patients with CRC, 30 patients with adenoma bigger than 1 cm, 24 patients with inflammatory bowel disease (IBD) and 41 patients had no neoplastic or inflammatory lesions. Blood samples were taken from each patient the day of the colonoscopy and PBMCs were purified. Total RNA was extracted following standard procedures. Multiplex RT-qPCR was applied on 92 different candidate biomarkers. Different univariate and multivariate statistical methods were applied on these candidates, and among them, 57 biomarkers with significant p values (<0.01, Wilcoxon test) were selected, including ADAMTS1, MMP9, CXCL10, CXCR4, VEGFA and CDH1. Two distinct biomarker signatures are used to separate patients without neoplastic lesion from those with cancer (named COLOX 1 test), respectively from those with adenoma (named COLOX 2 test). Result: COLOX 1 and 2 tests have successfully separated patients without neoplastic lesion from those with CRC (sensitivity 70%, specificity 90%, AUC 0.88), respectively from those with adenoma bigger than 1cm (sensitivity 61%, specificity 80%, AUC 0.80). 6/24 patients in the IBD group have a positive COLOX 1 test. Conclusion: These two COLOX tests demonstrated an acceptable sensitivity and a high specificity to detect the presence of CRCs and adenomas bigger than 1 cm. The false positives COLOX 1 test in IBD patients could possibly be due to the chronic inflammatory state. A prospective, multicenter, pivotal study is underway in order to confirm these promising results in a larger cohort.

Elevated inflammatory markers combined with positive pneumococcal urinary antigen are a good predictor of pneumococcal community-acquired pneumonia in children.

BACKGROUND: Our objective was to evaluate procalcitonin (PCT) and C-reactive protein (CRP) as predictors of a pneumococcal etiology in community-acquired pneumonia (CAP) in hospitalized children. METHODS: Children requiring hospitalization for CAP were prospectively enrolled. The following indices were determined: antibodies against pneumococcal surface proteins (anti-PLY, pneumococcal histidine triad D, pneumococcal histidine triad E, LytB and pneumococcal choline-binding protein A), viral serology, nasopharyngeal cultures and polymerase chain reaction for 13 respiratory viruses, blood pneumococcal polymerase chain reaction, pneumococcal urinary antigen, PCT and CRP. Presumed pneumococcal CAP (P-CAP) was defined as a positive blood culture or polymerase chain reaction for Streptococcus pneumoniae or as a pneumococcal surface protein seroresponse (≥2-fold increase). RESULTS: Seventy-five patients were included from which 37 (49%) met the criteria of P-CAP. Elevated PCT and CRP values were strongly associated with P-CAP with odds ratios of 23 (95% confidence interval: 5-117) for PCT and 19 (95% confidence interval: 5-75) for CRP in multivariate analysis. The sensitivity was 94.4% for PCT (cutoff: 1.5 ng/mL) and 91.9% for CRP (cutoff: 100 mg/L). A value≤0.5 ng/mL of PCT ruled out P-CAP in >90% of cases (negative likelihood ratio: 0.08). Conversely, a PCT value≥1.5 ng/mL associated with a positive pneumococcal urinary antigen had a diagnostic probability for P-CAP of almost 80% (positive likelihood ratio: 4.59). CONCLUSIONS: PCT and CRP are reliable predictors of P-CAP. Low cutoff values of PCT allow identification of children at low risk of P-CAP. The association of elevated PCT or CRP with a positive pneumococcal urinary antigen is a strong predictor of P-CAP.

The trail making test as a screening instrument for driving performance in older drivers; a translational research.

BACKGROUND: In many countries, primary care physicians determine whether or not older drivers are fit to drive. Little, however, is known regarding the effects of cognitive decline on driving performance and the means to detect it. This study explores to what extent the trail making test (TMT) can provide indications to clinicians about their older patients' on-road driving performance in the context of cognitive decline. METHODS: This translational study was nested within a cohort study and an exploratory psychophysics study. The target population of interest was constituted of older drivers in the absence of important cognitive or physical disorders. We therefore recruited and tested 404 home-dwelling drivers, aged 70 years or more and in possession of valid drivers' licenses, who volunteered to participate in a driving refresher course. Forty-five drivers also agreed to undergo further testing at our lab. On-road driving performance was evaluated by instructors during a 45 minute validated open-road circuit. Drivers were classified as either being excellent, good, moderate, or poor depending on their score on a standardized evaluation of on-road driving performance. RESULTS: The area under the receiver operator curve for detecting poorly performing drivers was 0.668 (CI95% 0.558 to 0.778) for the TMT-A, and 0.662 (CI95% 0.542 to 0.783) for the TMT-B. TMT was related to contrast sensitivity, motion direction, orientation discrimination, working memory, verbal fluency, and literacy. Older patients with a TMT-A ≥ 54 seconds or a TMT-B ≥ 150 seconds have a threefold (CI95% 1.3 to 7.0) increased risk of performing poorly during the on-road evaluation. TMT had a sensitivity of 63.6%, a specificity of 64.9%, a positive predictive value of 9.5%, and a negative predictive value of 96.9%. CONCLUSION: In screening settings, the TMT would have clinicians uselessly consider driving cessation in nine drivers out of ten. Given the important negative impact this could have on older drivers, this study confirms the TMT not to be specific enough for clinicians to justify driving cessation without complementary investigations on driving behaviors.

Dealing with clients' diversity in test situations: Client categorisations in psychologists' accounts of their practices

Reducing a test administration to standardised procedures reflects the test designers' standpoint. However, from the practitioners' standpoint, each client is unique. How do psychologists deal with both standardised test administration and clients' diversity? To answer this question, we interviewed 17 psychologists working in three public services for children and adolescents about their assessment practices. We analysed the numerous "client categorisations" they produced in their accounts. We found that they had shared perceptions about their clients' diversity, and reported various non-standard practices that complemented standardised test administration, but also differed from them or were even forbidden. They seem to experience a dilemma between: (a) prescribed and situated practices; (b) scientific and situated reliability; (c) commutative and distributive justice. For practitioners, dealing with clients' diversity this is a practical problem, halfway between a problem-solving task and a moral dilemma.

Comparison of C-reactive protein and white blood cell count with differential in neonates at risk for septicaemia.

We prospectively compared the diagnostic value of C-reactive protein (CRP) and white blood cell counts for detection of neonatal septicaemia. Sensitivity and specifity in receiver operating characteristics, and positive and negative predictive value of CRP and white blood cell count were compared in 195 critically ill preterm and term newborns clinically suspected of infection. Blood cultures were positive in 33 cases. During the first 3 days after birth CRP elevation (sensitivity 75%, specifity 86%), leukopenia (67%/90%), neutropenia (78%/80%) and immature to total neutrophil count (I/T) ratio (78%/73%) were good diagnostic parameters, as opposed to band forms with absolute count (84%/66%) or percentage (79%/71%), thrombocytopenia (65%/57%) and toxic granulations (44%/94%). Beyond 3 days of age elevated CRP (88%/87%) was the best parameter. Increased total (84%/66%) or percentage band count (79%/71%) were also useful. Leukocytosis (74%/56%), increased neutrophils (67%/65%), I/T ratio (79%/47%), thrombocytopenia (65%/57%) and toxic granulations had a low specifity. The positive predictive value of CRP was 32% before and 37% after 3 days of age, that of leukopenia was 37% in the first 3 days. CONCLUSION: During the first 3 days of life CRP, leukopenia and neutropenia were comparably good tests while after 3 days of life CRP was the best single test in early detection of neonatal septicaemia. Serial CRP estimations confirm the diagnosis, monitor the course of infection and the efficacy of antibiotic treatment.

Passive knee-extension test to measure hamstring tightness: influence of gravity correction

CONTEXT: A passive knee-extension test has been shown to be a reliable method of assessing hamstring tightness, but this method does not take into account the potential effect of gravity on the tested leg. OBJECTIVE: To compare an original passive knee-extension test with 2 adapted methods including gravity's effect on the lower leg. DESIGN: Repeated measures. SETTING: Laboratory. PARTICIPANTS: 20 young track and field athletes (16.6 ± 1.6 y, 177.6 ± 9.2 cm, 75.9 ± 24.8 kg). INTERVENTION: Each subject was tested in a randomized order with 3 different methods: In the original one (M1), passive knee angle was measured with a standard force of 68.7 N (7 kg) applied proximal to the lateral malleolus. The second (M2) and third (M3) methods took into account the relative lower-leg weight (measured respectively by handheld dynamometer and anthropometrical table) to individualize the force applied to assess passive knee angle. MAIN OUTCOME MEASURES: Passive knee angles measured with video-analysis software. RESULTS: No difference in mean individualized applied force was found between M2 and M3, so the authors assessed passive knee angle only with M2. The mean knee angle was different between M1 and M2 (68.8 ± 12.4 vs 73.1 ± 10.6, P < .001). Knee angles in M1 and M2 were correlated (r = .93, P < .001). CONCLUSIONS: Differences in knee angle were found between the original passive knee-extension test and a method with gravity correction. M2 is an improved version of the original method (M1) since it minimizes the effect of gravity. Therefore, we recommend using it rather than M1.

Elevated serum uric acid is associated with high circulating inflammatory cytokines in the population-based Colaus study.

BACKGROUND: The relation of serum uric acid (SUA) with systemic inflammation has been little explored in humans and results have been inconsistent. We analyzed the association between SUA and circulating levels of interleukin-6 (IL-6), interleukin-1beta (IL-1beta), tumor necrosis factor- alpha (TNF-alpha) and C-reactive protein (CRP). METHODS AND FINDINGS: This cross-sectional population-based study conducted in Lausanne, Switzerland, included 6085 participants aged 35 to 75 years. SUA was measured using uricase-PAP method. Plasma TNF-alpha, IL-1beta and IL-6 were measured by a multiplexed particle-based flow cytometric assay and hs-CRP by an immunometric assay. The median levels of SUA, IL-6, TNF-alpha, CRP and IL-1beta were 355 micromol/L, 1.46 pg/mL, 3.04 pg/mL, 1.2 mg/L and 0.34 pg/mL in men and 262 micromol/L, 1.21 pg/mL, 2.74 pg/mL, 1.3 mg/L and 0.45 pg/mL in women, respectively. SUA correlated positively with IL-6, TNF-alpha and CRP and negatively with IL-1beta (Spearman r: 0.04, 0.07, 0.20 and 0.05 in men, and 0.09, 0.13, 0.30 and 0.07 in women, respectively, P<0.05). In multivariable analyses, SUA was associated positively with CRP (beta coefficient +/- SE = 0.35+/-0.02, P<0.001), TNF-alpha (0.08+/-0.02, P<0.001) and IL-6 (0.10+/-0.03, P<0.001), and negatively with IL-1beta (-0.07+/-0.03, P = 0.027). Upon further adjustment for body mass index, these associations were substantially attenuated. CONCLUSIONS: SUA was associated positively with IL-6, CRP and TNF-alpha and negatively with IL-1beta, particularly in women. These results suggest that uric acid contributes to systemic inflammation in humans and are in line with experimental data showing that uric acid triggers sterile inflammation.

How to screen for problematic cannabis use in population surveys: an evaluation of the Cannabis Use Disorders Identification Test (CUDIT) in a Swiss sample of adolescents and young adults.

BACKGROUND/AIMS: Cannabis use is a growing challenge for public health, calling for adequate instruments to identify problematic consumption patterns. The Cannabis Use Disorders Identification Test (CUDIT) is a 10-item questionnaire used for screening cannabis abuse and dependency. The present study evaluated that screening instrument. METHODS: In a representative population sample of 5,025 Swiss adolescents and young adults, 593 current cannabis users replied to the CUDIT. Internal consistency was examined by means of Cronbach's alpha and confirmatory factor analysis. In addition, the CUDIT was compared to accepted concepts of problematic cannabis use (e.g. using cannabis and driving). ROC analyses were used to test the CUDIT's discriminative ability and to determine an appropriate cut-off. RESULTS: Two items ('injuries' and 'hours being stoned') had loadings below 0.5 on the unidimensional construct and correlated lower than 0.4 with the total CUDIT score. All concepts of problematic cannabis use were related to CUDIT scores. An ideal cut-off between six and eight points was found. CONCLUSIONS: Although the CUDIT seems to be a promising instrument to identify problematic cannabis use, there is a need to revise some of its items.

Does Direct Democracy Matters for Political Parties : An Empirical Test in the Swiss Cantons

According to most political scientists and commentators, direct democracy seems to weaken political parties. Our empirical analysis in the 26 Swiss cantons shows that this thesis in its general form cannot be maintained. Political parties in cantons with extensive use of referendums and initiatives are not in all respects weaker than parties in cantons with little use of direct democratic means of participation. On the contrary, direct democracy goes together with more professional and formalized party organizations. Use of direct democracy is associated with more fragmented and volatile party systems, and with greater support for small parties, but causal interpretations of these relationships are difficult.

Inferring transport characteristics in a fractured rock aquifer by combining single-hole ground-penetrating radar reflection monitoring and tracer test data

Investigations of solute transport in fractured rock aquifers often rely on tracer test data acquired at a limited number of observation points. Such data do not, by themselves, allow detailed assessments of the spreading of the injected tracer plume. To better understand the transport behavior in a granitic aquifer, we combine tracer test data with single-hole ground-penetrating radar (GPR) reflection monitoring data. Five successful tracer tests were performed under various experimental conditions between two boreholes 6 m apart. For each experiment, saline tracer was injected into a previously identified packed-off transmissive fracture while repeatedly acquiring single-hole GPR reflection profiles together with electrical conductivity logs in the pumping borehole. By analyzing depth-migrated GPR difference images together with tracer breakthrough curves and associated simplified flow and transport modeling, we estimate (1) the number, the connectivity, and the geometry of fractures that contribute to tracer transport, (2) the velocity and the mass of tracer that was carried along each flow path, and (3) the effective transport parameters of the identified flow paths. We find a qualitative agreement when comparing the time evolution of GPR reflectivity strengths at strategic locations in the formation with those arising from simulated transport. The discrepancies are on the same order as those between observed and simulated breakthrough curves at the outflow locations. The rather subtle and repeatable GPR signals provide useful and complementary information to tracer test data acquired at the outflow locations and may help us to characterize transport phenomena in fractured rock aquifers.