Diagnostic challenges of central nervous system infection: extensive multiplex panels versus stepwise guided approach.

BACKGROUND: Cerebrospinal fluid (CSF) testing is a key component for the diagnosis of central nervous system (CNS) infections. Current meningitis and encephalitis management guidelines agree on the need for CSF molecular testing in combination with other direct and indirect biological testing, both in CSF and blood. Multiplex molecular tests have been developed to reduce turnaround times and facilitate the diagnostic approach. OBJECTIVES: We aim to discuss the role of multiplex molecular panels in the management of CNS infections. SOURCES: The MEDLINE database and the grey literature have been searched for relevant articles. CONTENT: New molecular multiplex panels are being developed to simultaneously detect a large array of neuropathogens in CSF. Although one of these assays has been US Food and Drug Administration-approved, extensive analytical and clinical validation is still missing, and suboptimal performance related issues have been raised. Its use has been associated with decreased costs, reduced length of hospital stay and reduced antiviral therapy administration in retrospective, industry-sponsored studies. The pros and cons of this multiplex syndromic approach are discussed in this narrative review. IMPLICATIONS: Molecular multiplex CNS infection diagnosis panels have been developed and present several attractive features, including ease of use and low turnaround time. However, suboptimal analytical performances render these tests difficult to use without additional confirmatory tests. Such panels are not comprehensive nor adapted to all situations, depending on the epidemiological or clinical context. Overall, available data in the literature currently do not support the use of a multiplex PCR panel in clinical routine as a 'stand-alone' molecular assay. Except in restricted laboratory capacity settings where such easy-to-use multiplex panels offer the diagnostic means that would otherwise not be available, the stepwise testing approach remains a more rational option. Serological testing both in blood and CSF should not be neglected, but it represents essential complementary tools regarding some neuropathogens.

Controllable Non-Markovianity for a Spin Qubit in Diamond.

We present a flexible scheme to realize non-Markovian dynamics of an electronic spin qubit, using a nitrogen-vacancy center in diamond where the inherent nitrogen spin serves as a regulator of the dynamics. By changing the population of the nitrogen spin, we show that we can smoothly tune the non-Markovianity of the electron spin's dynamics. Furthermore, we examine the decoherence dynamics induced by the spin bath to exclude other sources of non-Markovianity. The amount of collected measurement data is kept at a minimum by employing Bayesian data analysis. This allows for a precise quantification of the parameters involved in the description of the dynamics and a prediction of so far unobserved data points.

[Ebola: the unexpected emerging disease]. / Ebola: le point au crépuscule d'une épidémie inattendue.

In one year, Ebola virus disease has already been responsible of around 10000 deaths. 24 patients have been medically evacuated in different University Hospitals in Europe or in the United States. One medical doctor, infected during a humanitarian mission in the field has been treated in Geneva at the end of 2014. This review aims to summarize the epidemiology of the current outbreak, to describe the main virological and clinical characteristics of Ebola virus disease, and to address the most important experimental treatments available. Although the number of cases has fallen the last two months, the outbreak is not over. A safe and proctective vaccine is still needed in the race to fight this emerging viral disease.

Development of an evaluation function for eye-hand coordination robotic therapy.

This paper is the continuation of a work presented at ICORR 07, in which we discussed the possibility of improving eye-hand coordination in children diagnosed with this problem, using a robotic mapping from a haptic user interface to a virtual environment. Our goal is to develop, implement and refine a system that will assess and improve the eye-hand coordination and grip strength in children diagnosed with poor graphomotor skills. A detailed analysis of patters (e.g., labyrinths, letters and angles) was conducted in order to select three very distinguishable levels of difficulty that could be included in the system, and which would yield the greatest benefit in terms of assessment of coordination and strength issues as well as in training. Support algorithms (position, force, velocity, inertia and viscosity) were also developed and incorporated into the tasks in order to introduce general computer assistance to the mapping of the user's movements to the computer screen without overriding the user's commands to the robotic device. In order to evaluate performance (given by %accuracy and time) of the executed tasks, a sophisticated evaluation function was designed based on image analysis and edge detection algorithms. This paper presents the development of the haptic tasks, the various assistance algorithms, the description of the evaluation function and the results of a study implemented at the Motor Development Clinic at Cal Poly Pomona. The results (Accuracy and Time) of this function are currently being used as inputs to an Intelligent Decision Support System (described in), which in turn, suggests the next task to be executed by the subject based on his/her performance.

[Acute colonic pseudoobstruction following fixation of a pertrochanteric fracture]. / Akute intestinale Kolonpseudoobstruktion 2 Tage nach Versorgung einer pertrochantären Femurfraktur.

Acute colonic pseudoobstruction, following traumatic injuries, is a rare diagnosis. Nevertheless it is life threatening, if it is not recognized and treated promptly. We report one case of this so-called Ogilvie's syndrome, which followed fixation of a trochanteric fracture by intramedullary nailing within 2 days. Due to massive acute colonic distension, the patient suffered from respiratory failure. We excluded other intestinal diseases by CT scanning. After conservative colonic decompression, he recovered after 2 days in the intensive care unit. We describe a variable treatment depending on the severity of the colonic atony. Knowledge of Ogilvie's syndrome, or acute colonic pseudoobstruction, is a must for trauma surgeons, since it can occur within a few hours and can lead to dramatic situations.

Measurement of the beta-nu correlation using magneto-optically trapped 21Na.

The beta-neutrino correlation coefficient, a(betanu), in 21Na is inferred from detecting the beta(+) and low-energy recoil daughter nucleus. 21Na is produced at the 88-Inch Cyclotron at Lawrence Berkeley National Laboratory and 800 000 atoms are maintained in a magneto-optical trap. From the measured time of flight of recoil ions in the presence of a drift electric field, we find a(betanu)=0.5243+/-0.0091. There may be a dependence on the trapped atom population. This and other systematic uncertainties are discussed.

Search for CPT-odd decays of positronium.

We have limited a CPT-violating correlation in annihilations of polarized ortho-positronium. We searched for an asymmetry in the triple correlation s-->.(k-->(1)xk-->(2)), where k-->(1) and k-->(2) are the two largest photon momenta, and s--> is the spin of the positronium. Using the Gammasphere array of Compton-suppressed high-purity germanium detectors, we detected 2.65x10(7) events of ortho-Ps annihilation. The amplitude of a CPT-violating asymmetry in the data set is found to be 0.0026+/-0.0031, a factor of 6 smaller than previous experiments.

Lack of association between schizophrenia and the phospholipase-A(2) genes cPLA2 and sPLA2.

The well-established role of genetic factors in the etiology of schizophrenia together with reports of allelic association with cPLA2, a phospholipase-A(2) gene, a reported increase of phospholipase-A(2) activity, and the phospholipase-A(2) hypothesis of Horrobin et al. [1995: Med Hypotheses 45:605-613] strongly support cPLA2 (PLA2G4A) and sPLA2 (PLA2G1B) as candidate genes for schizophrenia. In search for allelic association between these phospholipase-A(2) genes and schizophrenia, two samples of Chinese and European origins, in total 328 unrelated schizophrenic patients and their parents, were investigated using Falk and Rubinstein's haplotype relative risk method. Both genes showed marginally significant evidence for association in the total sample (P

No association between dopamine D2 receptor gene (DRD2) and human intelligence.

Significantly diminished intellectual functioning, as indicated by appropriately administered IQ tests with scores below 70, is a frequent mental handicap leading to severe social disadvantages and serves as a paradigm for molecular genetic research of complex disorders and traits due to its multitude of known and unknown, genetic as well as environmental causes. Since the number of confounding variables is expected to be considerably reduced in the normal population at the opposite ends of the IQ distribution, we employed a contrast of extremes approach by comparing adults of high (N = 71) and average IQ (N = 78) in association studies to search for genes involved in the multigenic forms of familial mental retardation. The dopamine D2 receptor gene (DRD2) was chosen as a candidate gene for general cognitive ability (g) since it has been found to be associated with visuospatial ability which in turn is highly correlated with g. Confirming two similar studies in children, however, no significant differences were obtained. Given three negative studies, the DRD2 gene is unlikely to pay a major role in g.

The influence of previous experience on predictive motor control.

Anticipating the consequences of our motor commands is a fundamental component of sensorimotor control. For example, when one hand pulls on an object held in the other, the restraining hand generates an anticipatory increase in grip force thereby preventing the object from slipping. To investigate how such anticipation is learned subjects held an object, whose properties were under computer control, between their hands. This allowed instant changes in the behaviour of the manipulated object on a trial by trial basis. The extent of grip force modulation seen in one hand, when the other pulled on the object was found to depend in a systematic way on the object's properties experienced over at least the previous three trials.

Propagation of action potentials in dendrites depends on dendritic morphology.

Action potential propagation links information processing in different regions of the dendritic tree. To examine the contribution of dendritic morphology to the efficacy of propagation, simulations were performed in detailed reconstructions of eight different neuronal types. With identical complements of voltage-gated channels, different dendritic morphologies exhibit distinct patterns of propagation. Remarkably, the range of backpropagation efficacies observed experimentally can be reproduced by the variations in dendritic morphology alone. Dendritic geometry also determines the extent to which modulation of channel densities can affect propagation. Thus in Purkinje cells and dopamine neurons, backpropagation is relatively insensitive to changes in channel densities, whereas in pyramidal cells, backpropagation can be modulated over a wide range. We also demonstrate that forward propagation of dendritically initiated action potentials is influenced by morphology in a similar manner. We show that these functional consequences of the differences in dendritic geometries can be explained quantitatively using simple anatomical measures of dendritic branching patterns, which are captured in a reduced model of dendritic geometry. These findings indicate that differences in dendritic geometry act in concert with differences in voltage-gated channel density and kinetics to generate the diversity in dendritic action potential propagation observed between neurons. They also suggest that changes in dendritic geometry during development and plasticity will critically affect propagation. By determining the spatial pattern of action potential signaling, dendritic morphology thus helps to define the size and interdependence of functional compartments in the neuron.

The validity of the ICD-10 classification of recurrent affective disorders: do endogenous and psychogenic depressions form a homogeneous diagnostic group?

Fifty-five hospital-treated patients with the ICD-10 diagnosis of 'recurrent depressive episode(s)' were classified according to the Newcastle Depressive Diagnostic Scale as having either psychogenic (n = 25) or endogenous (n = 30) depression and interviewed using several inventories on personality and psychopathology (Composite International Diagnostic Interview, Symptom Check List, Inventory of Interpersonal Problems, IIP, NEO Five-Factor Personality Inventory, Social Adjustment Scale, Questionnaire of the Motivation to Seek Psychotherapy). Except for the IIP, individual subscales disclosed significant differences between the two groups. In light of these results, the grouping of these two disorders into one diagnostic group in the ICD-10 is critically discussed.

The CNS updates its context estimate in the absence of feedback.

Human motor behaviour is remarkably accurate and appropriate even though our bodies and the objects we interact with change over time. To achieve such performance the motor system has to tailor the motor commands to the current context, that is the properties of objects in the world and the prevailing environmental conditions. The current context can be estimated by integrating two sources of information, sensory feedback and knowledge about how the context is likely to have changed from the previous estimate. Here we show that in the absence of sensory feedback about the context the second process is able to extrapolate the likely evolution of the context without requiring awareness that the context is changing.

Context estimation for sensorimotor control.

Human motor behavior is remarkably accurate and appropriate even though the properties of our own bodies as well as the objects we interact with vary over time. To adjust appropriately, the motor system has to estimate the context, that is the properties of objects in the world and the prevailing environmental conditions. Here we show that to determine the current context the CNS uses information from both prior knowledge of how the context might evolve over time and from the comparison of predicted and actual sensory feedback. We show that these two sources of information may be modeled within the CNS and combined to derive an accurate estimate of the context which adjusts motor command selection. This provides a novel probabilistic framework for sensorimotor control.

Reliability and stability of contingent negative variation.

Reliability parameters of a test indicate the stability (and quality) of the test itself. Reliability coefficients greater than 0.70 suggest an attribute as being sufficiently stable over time to be characterized as a trait. Reliability parameters of contingent negative variation (CNV) amplitudes in 27 healthy individuals were determined using a test-retest design. CNV was recorded at Cz, with an interstimulus interval of 3 s, on 2 separate occasions: initial session and 10 days later. Correlation coefficients between the 2 recording sessions were 0.675 for the total-CNV (tCNV), 0.855 for the early component (iCNV), 0.631 for the late component (lCNV), and 0.420 for the post-imperative negative variation (PINV). Statistical retest parameters for Spearman Brown were 0.806 for tCNV, 0.922 for iCNV, 0.774 for lCNV, and 0.655 for PINV. The iCNV, more than the other parameters, remained stable over the period of 10 days. It is suggested that the described standardized CNV recording procedure ensures reproducible and stable results in healthy subjects.

Motivation to seek psychotherapy in patients with recurrent depressive disorder.

Fifty-five hospital-treated patients with the ICD-10 diagnosis of recurrent depressive episode(s) were classified according to the Newcastle Depressive Diagnostic Scale as having either psychogenic (n = 25) or endogenous (n = 30) depression and interviewed using the Composite International Diagnostic Interview and the Questionnaire for Assessment of Motivation to Seek Psychotherapy. The two groups were found to differ significantly from one another in two Motivation to Seek Psychotherapy subscales ("layman's etiology" and "general expectations from therapy"). The motivation to seek psychotherapy was greater in patients with psychogenic depression than in patients with endogenous depression. Nonetheless, psychotherapy is indispensable in treating endogenous depression, especially for patients under situational stress or at risk of suicide.

Regulation of synaptic transmission in the mossy fibre-granule cell pathway of rat cerebellum by metabotropic glutamate receptors.

The role of metabotropic glutamate receptors (mGluRs) in the mossy fibre-granule cell pathway in rat cerebellum was studied using slice preparations and electrophysiological techniques. Application of the group I selective agonist (S)-3,5-dihydroxyphenylglycine (DHPG) evoked, in a concentration-dependent manner (EC50 = 33 microM), a depolarising/hyperpolarising complex response from granule cells which was preferentially inhibited by the group I selective antagonist (S)-4-carboxyphenylglycine (4CPG). The group III selective agonist L-amino-4-phosphonobutyrate (AP4) evoked a hyperpolarising response (EC50 = 10 microM) which was inhibited by the group II/III selective antagonist (S)-alpha-methyl-4-phosphonophenylglycine (MPPG). The group II agonist (2S,2'R,3'R)-2-(2',3'-dicarboxylcyclopropyl)glycine (DCG-IV) elicited no measurable voltage change. The amplitude of the synaptically-mediated mossy fibre response in granule cells was unaffected during application of AP4, was reduced by DHPG and was enhanced by DCG-IV (EC50 = 80 nM). These effects were inhibited by the group selective antagonists 4CPG and (2S,1'S,2'S,3'R)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine (PCCG-4), respectively. Further investigation using patch-clamp recording revealed that DCG-IV potently inhibited spontaneous GABAergic currents. We conclude that group I and III (but not group II) mGluRs are functionally expressed by granule cells, whereas unexpectedly group II or III mGluRs do not appear to be present presynaptically on mossy fibre terminals. Group II mGluRs are located on Golgi cell terminals; when activated these receptors cause disinhibition, a function which may be important for gating information transfer from the mossy fibres to the granule cells.

Vascular dementia versus dementia of Alzheimer's type: do they have differential effects on caregivers' burden?

OBJECTIVES: We investigated homecare patients with dementia of Alzheimer's type (DAT; n = 36) or vascular dementia (VD; n = 36) and their care-providing relatives regarding clinical and psychosocial variables to determine whether DAT and VD impose different burdens on caregivers. METHOD: All patients were diagnosed according to ICD-10 criteria. The diagnoses were confirmed by internal medical, clinical-neurological, and psychiatric parameters. The severity of the dementias was graded according to the Global Deterioration Scale (GDS). Caregiving relatives responded to the Behavioral Pathology in Alzheimer's Disease Rating Scale (BAD), the Blessed Dementia Scale (BDS), and the Screen for Caregiver Burden (SCB). RESULTS: Analyses revealed that caregivers' burden (SCB), disease symptoms and personality changes of patients (BAD), and the patients' inability to cope with everyday tasks (BDS) were sharply higher for DAT than for VD patients in the group with severe dementia. Concerning patients with mild or moderately severe disease, scores in the DAT group were similar or lower than those in the VD group. CONCLUSION: In early stages, VD patients impose a greater burden on relatives than do patients with DAT. In severe stages this relationship undergoes a reversal, with relatives of DAT patients experiencing the burden more adversely than those of VD patients. The differences in the onset and course characteristics, as well as the specific differences between these two types of dementia with respect to caregiver burden factors, call for their diagnostic separation and the development of specific homecare support systems for family caregivers.