A Systematic Review of Cases of Meningitis in the Absence of Cerebrospinal Fluid Pleocytosis on Lumbar Puncture

Background: Definitive diagnosis of meningitis is made by analysis of cerebrospinal fluid (CSF) culture or polymerase chain reaction (PCR) obtained from a lumbar puncture (LP), which may take days. A timelier diagnostic clue of meningitis is pleocytosis on CSF analysis. However, meningitis may occur in the absence of pleocytosis on CSF. Areas of Uncertainty: A diagnosis of meningitis seems less likely without pleocytosis on CSF, leading clinicians to prematurely exclude this. Further, there is little available literature on the subject.Methods: Ovid/Medline and Google Scholar search was conducted for cases of CSF culture-confirmed meningitis with lack of pleocytosis. Inclusion criterion was reported cases of CSF culture-positive or PCR positive meningitis in the absence of pleocytosis on LP. Exclusion criteria were pleocytosis on CSF, cases in which CSF cultures/PCR were not performed, and articles that did not include CSF laboratory values.Results: A total of 124 cases from 51 articles were included. Causative organisms were primarily bacterial (99 cases). Outcome was reported in 86 cases, 27 of which died and 59 survived. Mortality in viral, fungal and bacterial organisms was 0, 56 and 31%, respectively. The overall percentage of positive initial CSF PCR/culture for viral, fungal and bacterial organisms was 100, 89 and 82%, respectively. Blood cultures were performed in 79 of the 124 cases, 56 (71%) of which ultimately cultured the causative organism. In addition to bacteremia, concomitant sources of infection occurred in 17 cases.Conclusions: Meningitis in the absence of pleocytosis on CSF is rare. If this occurs, causative organism is likely bacterial. We recommend ordering blood cultures as an adjunct, and, if clinically relevant, concomitant sources of infection should be sought. If meningitis is suspected, empiric antibiotics/antifungals should be administered regardless of initial WBC count on lumbar puncture

Using the Internet to improve university education

Up to this point, university education has largely remained unaffected by the developments of novel approaches to web-based learning. The paper presents a principled approach to the design of problem-oriented, web-based learning at the university level. The principles include providing authentic contexts with multimedia, supporting collaborative knowledge construction, making thinking visible with dynamic visualisation, quick access to content resources via information and communication technologies, and flexible support by tele-tutoring. These principles are used in the MUNICS learning environment, which is designed to support students of computer science to apply their factual knowledge from the lectures to complex real-world problems. For example, students may model the knowledge management in an educational organisation with a graphical simulation tool. Some more general findings from a formative evaluation study with the MUNICS prototype are reported and discussed. For example, the students' ignorance of the additional content resources is discussed in the light of the well-known finding of insufficient use of help systems in software applications

Effective interaction between a colloid and a soft interface near criticality

Within mean-field theory we determine the universal scaling function for the effective force acting on a single colloid located near the interface between two coexisting liquid phases of a binary liquid mixture close to its critical consolute point. This is the first study of critical Casimir forces emerging from the confinement of a fluctuating medium by at least one soft interface, instead by rigid walls only as studied previously. For this specific system, our semi-analytical calculation illustrates that knowledge of the colloid-induced, deformed shape of the interface allows one to accurately describe the effective interaction potential between the colloid and the interface. Moreover, our analysis demonstrates that the critical Casimir force involving a deformable interface is accurately described by a universal scaling function, the shape of which differs from that one for rigid walls.Comment: 19 pages, 11 figure

Adverse Effects of Trichothiodystrophy DNA Repair and Transcription Gene Abnormalities on Human Fetal Development

The effects of DNA repair and transcription genes in human prenatal life have never been studied. Trichothiodystrophy (TTD) is a rare (affected frequency of 10^-6^) recessive disorder caused by mutations in genes involved in the nucleotide excision repair (NER) pathway and in transcription. Based on our clinical observations, we conducted a genetic epidemiologic study to investigate gestational outcomes associated with TTD. We compared pregnancies resulting in TTD-affected offspring (N=24) with respect to abnormalities in their antenatal and neonatal periods to pregnancies resulting in their unaffected siblings (N=18), accounting for correlation, and to population reference values. Significantly higher incidence of several severe gestational complications was noted in TTD-affected pregnancies. Gestational complications were noted in nearly all pregnancies resulting in TTD-affected offspring with _XPD_ and _TTDN1_, but not _TTD-A_, gene mutations. Abnormal placental development may explain the constellation of observed complications; therefore, we hypothesize that some TTD genes play an important role in normal placental and fetal development. We investigated this hypothesis by analyzing the expression patterns of TTD genes. Expression of _TTDA_ was strongly negatively correlated (r=-0.7,P<0.0001) with gestational age, while _XPD, XPB_ and _TTDN1_ were consistently expressed from 14 to 40 weeks gestation. *Conclusion:* Our results indicate an important role for _XPD, XPB_ and _TTDN1_ gene products during normal human placental and fetal development

Replication and exploratory analysis of 24 candidate risk polymorphisms for neural tube defects.

BackgroundNeural tube defects (NTDs), which are among the most common congenital malformations, are influenced by environmental and genetic factors. Low maternal folate is the strongest known contributing factor, making variants in genes in the folate metabolic pathway attractive candidates for NTD risk. Multiple studies have identified nominally significant allelic associations with NTDs. We tested whether associations detected in a large Irish cohort could be replicated in an independent population.MethodsReplication tests of 24 nominally significant NTD associations were performed in racially/ethnically matched populations. Family-based tests of fifteen nominally significant single nucleotide polymorphisms (SNPs) were repeated in a cohort of NTD trios (530 cases and their parents) from the United Kingdom, and case-control tests of nine nominally significant SNPs were repeated in a cohort (190 cases, 941 controls) from New York State (NYS). Secondary hypotheses involved evaluating the latter set of nine SNPs for NTD association using alternate case-control models and NTD groupings in white, African American and Hispanic cohorts from NYS.ResultsOf the 24 SNPs tested for replication, ADA rs452159 and MTR rs10925260 were significantly associated with isolated NTDs. Of the secondary tests performed, ARID1A rs11247593 was associated with NTDs in whites, and ALDH1A2 rs7169289 was associated with isolated NTDs in African Americans.ConclusionsWe report a number of associations between SNP genotypes and neural tube defects. These associations were nominally significant before correction for multiple hypothesis testing. These corrections are highly conservative for association studies of untested hypotheses, and may be too conservative for replication studies. We therefore believe the true effect of these four nominally significant SNPs on NTD risk will be more definitively determined by further study in other populations, and eventual meta-analysis

Reconstruction and measurement of (100) MeV energy electromagnetic activity from π0 arrow γγ decays in the MicroBooNE LArTPC

We present results on the reconstruction of electromagnetic (EM) activity from photons produced in charged current νμ interactions with final state π0s. We employ a fully-automated reconstruction chain capable of identifying EM showers of (100) MeV energy, relying on a combination of traditional reconstruction techniques together with novel machine-learning approaches. These studies demonstrate good energy resolution, and good agreement between data and simulation, relying on the reconstructed invariant π0 mass and other photon distributions for validation. The reconstruction techniques developed are applied to a selection of νμ + Ar → μ + π0 + X candidate events to demonstrate the potential for calorimetric separation of photons from electrons and reconstruction of π0 kinematics

Ionization Electron Signal Processing in Single Phase LArTPCs II. Data/Simulation Comparison and Performance in MicroBooNE

The single-phase liquid argon time projection chamber (LArTPC) provides a large amount of detailed information in the form of fine-grained drifted ionization charge from particle traces. To fully utilize this information, the deposited charge must be accurately extracted from the raw digitized waveforms via a robust signal processing chain. Enabled by the ultra-low noise levels associated with cryogenic electronics in the MicroBooNE detector, the precise extraction of ionization charge from the induction wire planes in a single-phase LArTPC is qualitatively demonstrated on MicroBooNE data with event display images, and quantitatively demonstrated via waveform-level and track-level metrics. Improved performance of induction plane calorimetry is demonstrated through the agreement of extracted ionization charge measurements across different wire planes for various event topologies. In addition to the comprehensive waveform-level comparison of data and simulation, a calibration of the cryogenic electronics response is presented and solutions to various MicroBooNE-specific TPC issues are discussed. This work presents an important improvement in LArTPC signal processing, the foundation of reconstruction and therefore physics analyses in MicroBooNE.Comment: 54 pages, 36 figures; the first part of this work can be found at arXiv:1802.0870