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Timothy Brown

Publications and source records attributed to Timothy Brown.

10 recordsLinked to original sources

Transiting extrasolar planetary candidates in the Galactic bulge.

More than 200 extrasolar planets have been discovered around relatively nearby stars, primarily through the Doppler line shifts owing to reflex motions of their host stars, and more recently through transits of some planets across the faces of the host stars. The detection of planets with the shortest known periods, 1.2-2.5 days, has mainly resulted from transit surveys which have generally targeted stars more massive than 0.75 M(o), where M(o) is the mass of the Sun. Here we report the results from a planetary transit search performed in a rich stellar field towards the Galactic bulge. We discovered 16 candidates with orbital periods between 0.4 and 4.2 days, five of which orbit stars of masses in the range 0.44-0.75 M(o). In two cases, radial-velocity measurements support the planetary nature of the companions. Five candidates have orbital periods below 1.0 day, constituting a new class of ultra-short-period planets, which occur only around stars of less than 0.88 M(o). This indicates that those orbiting very close to more-luminous stars might be evaporatively destroyed or that jovian planets around stars of lower mass might migrate to smaller radii.

Journal Article↗

Mycobacterium tuberculosis and rifampin resistance, United Kingdom.

The United Kingdom Health Protection Agency Mycobacterium Reference Unit offers a national "Fastrack" molecular service for detecting Mycobacterium tuberculosis complex (MTBC) and rifampin resistance by using the INNO-LiPA Rif.TB assay. We analyzed the service in a routine, nontrial context of 1,997 primary clinical specimens, including 658 nonrespiratory specimens. The overall adjusted concordance, sensitivity, specificity, positive predictive value, and negative predictive value for detecting MTBC were 91.2%, 85.2%, 96.2%, 95.7%, and 86.7%, respectively (unadjusted, 86.7%, 85.2%, 88.2%, 86.9%, and 86.7%), when false-positive samples from patients (n = 83) with a known microbiologic diagnosis of MTBC or patients receiving current or recent antituberculous treatment were excluded. The parameters for detecting rifampin resistance were 99.1%, 95.0%, 99.6%, 92.7%, and 99.7%, respectively. The assay enabled earlier diagnosis of MTBC and rifampin resistance (15.2 days) compared with culture-based techniques (30.7 days).

Antibiotics, Antitubercular↗

Differentiation of tuberculosis strains in a population with mainly Beijing-family strains.

A high prevalence of tuberculosis (TB) isolates that are genetically homogenous and from the Beijing family has been reported in Russia. To map TB transmission caused by these strains, new genotyping systems are needed. Mycobacterial interspersed repetitive units (MIRUs) offer the possibility of rapid PCR-based typing with comparable discrimination to IS6110 restriction fragment length polymorphism techniques. Spoligotyping and detection of IS6110 insertion in the dnaA-dnaN region were used to identify Beijing strains in 187 Mycobacterium tuberculosis isolates from Samara, Russia. The Beijing isolates were analyzed by using 12-MIRU and 3-exact tandem repeats (ETR) loci and by an expanded set of 10 additional variable number tandem repeats loci. The expanded set of 25 MIRUs provided better discrimination than the original set of 15 (Hunter-Gaston diversity index 0.870 vs. 0.625). Loci MIRU 26, 1982, and 3232 were the most polymorphic in Beijing isolates.

Adult↗

Regionally specific disturbance of dorsolateral prefrontal-hippocampal functional connectivity in schizophrenia.

BACKGROUND: Two brain regions often implicated in schizophrenia are the dorsolateral prefrontal cortex (DLPFC) and the hippocampal formation (HF). It has been hypothesized that the pathophysiology of the disorder might involve an alteration of functional interactions between medial temporal and prefrontal areas. METHODS: We used neuroimaging data acquired during a working memory challenge and a sensorimotor control task in 22 medication-free schizophrenic patients and 22 performance-, age-, and sex-matched healthy subjects to investigate "functional connectivity" between HF and DLPFC in schizophrenia. The HF blood flow, measured with positron emission tomography, was assessed within a probabilistic template. Brain areas whose activity was positively or negatively coupled to HF were identified using voxelwise analysis of covariance throughout the entire brain and analyzed using a random effects model. RESULTS: During working memory, patients showed reduced activation of the right DLPFC and left cerebellum. In both groups, inverse correlations were observed between the HF and the contralateral DLPFC and inferior parietal lobule. While these did not differ between diagnostic groups during the control task, the working memory challenge revealed a specific abnormality in DLPFC-HF functional connectivity-while the right DLPFC was significantly coupled to the left HF in both groups during the control task, this correlation was not seen in healthy subjects during working memory but persisted undiminished in patients, resulting in a significant task-by-group interaction. CONCLUSIONS: Our results suggest a regionally specific alteration of HF-DLPFC functional connectivity in schizophrenia that manifests as an unmodulated persistence of an HF-DLPFC linkage during working memory activation. Thus, a mechanism by which HF dysfunction may manifest in schizophrenia is by inappropriate reciprocal modulatory interaction with the DLPFC.

Adult↗

Can 15-locus mycobacterial interspersed repetitive unit-variable-number tandem repeat analysis provide insight into the evolution of Mycobacterium tuberculosis?

The phylogeny and evolution of the bacterium Mycobacterium tuberculosis is still poorly understood despite the application of a variety of molecular techniques. We analyzed 469 M. tuberculosis and 49 Mycobacterium bovis isolates to evaluate if the mycobacterial interspersed repetitive units-variable-number tandem repeats (MIRU-VNTR) commonly used for epidemiological studies can define the phylogeny of the M. tuberculosis complex. This population was characterized by previously identified silent single-nucleotide polymorphisms (sSNPs) or by a macroarray based on these sSNPs that was developed in this study. MIRU-VNTR phylogenetic codes capable of differentiating between phylogenetic lineages were identified. Overall, there was 90.9% concordance between the lineages of isolates as defined by the MIRU-VNTR and sSNP analyses. The MIRU-VNTR phylogenetic code was unique to M. bovis and was not observed in any M. tuberculosis isolates. The codes were able to differentiate between different M. tuberculosis strain families such as Beijing, Delhi, and East African-Indian. Discrepant isolates with similar but not identical MIRU-VNTR codes often displayed a stepwise trend suggestive of bidirectional evolution. A lineage-specific panel of MIRU-VNTR can be used to subdivide each lineage for epidemiological purposes. MIRU-VNTR is a valuable tool for phylogenetic studies and could define an evolutionarily uncharacterized population of M. tuberculosis complex organisms.

Base Sequence↗

Audiotactile temporal order judgments.

We report a series of three experiments in which participants made unspeeded 'Which modality came first?' temporal order judgments (TOJs) to pairs of auditory and tactile stimuli presented at varying stimulus onset asynchronies (SOAs) using the method of constant stimuli. The stimuli were presented from either the same or different locations in order to explore the potential effect of redundant spatial information on audiotactile temporal perception. In Experiment 1, the auditory and tactile stimuli had to be separated by nearly 80 ms for inexperienced participants to be able to judge their temporal order accurately (i.e., for the just noticeable difference (JND) to be achieved), no matter whether the stimuli were presented from the same or different spatial positions. More experienced psychophysical observers (Experiment 2) also failed to show any effect of relative spatial position on audiotactile TOJ performance, despite having much lower JNDs (40 ms) overall. A similar pattern of results was found in Experiment 3 when silent electrocutaneous stimulation was used rather than vibrotactile stimulation. Thus, relative spatial position seems to be a less important factor in determining performance for audiotactile TOJ than for other modality pairings (e.g., audiovisual and visuotactile).

Acoustic Stimulation↗

Soft tissue perineuriomas in children: report of three cases and review of the literature [corrected].

Perineuriomas (PN) are uncommon, slowly growing, usually benign tumors composed of well-differentiated perineural cells. Two variants are recognized: intraneural perineuriomas and soft tissue perineurioma, which includes a sclerosing subset of tumors. They are usually reported in the adult population. We present three cases of soft tissue perineuriomas in children. One was located in the deep soft tissue of the retroperitoneum in a 14-year-old girl, the second one in the left thumb of a 14-year-old boy, and the third one in the index finger of a 16-year-old boy. This report, which describes the clinicopathologic, immunohistochemical, and ultrastructural features of these tumors, should alert pathologists to the occurrence of perineuriomas in children. A review of the English language literature on perineuriomas in children is also included.

Adolescent↗

Rifampin- and multidrug-resistant tuberculosis in Russian civilians and prison inmates: dominance of the beijing strain family.

Consecutive patient cultures (140) of Mycobacteriium tuberculosis were collected from five Russian civilian and prison tuberculosis laboratories and analyzed for rifampin (rpoB) and isoniazid resistance (inhA, katG, ahpC); transmission of Beijing family isolates; and the importance of prison and previous therapy in drug resistance. Rifampin, isoniazid, and multidrug resistance occurred in 58.2%, 51.6%, and 44.7% of cultures, respectively; 80% of prison cultures were rifampin resistant. Spoligotyping and variable number tandem repeat (VNTR) fingerprinting divided the isolates into 43 groups. Spoligotyping demonstrated that a high proportion (68.1%) of patients were infected with Beijing family strains and that most (69.1%) were rifampin resistant; the highest proportion (81.6%) occurred in prison. One VNTR subgroup (42435) comprised 68 (72.3%) of the Beijing isolates with a small number of IS6110 types; 50 (73.5%) were rifampin resistant. Rifampin-resistant Beijing isolates are dominant within the patient population, especially among prisoners, and threaten treatment programs.

Antitubercular Agents↗

Recent advances in the treatment of L-DOPA-induced dyskinesia.

Parkinson's disease (PD) is a degenerative movement disorder resulting from the loss of dopaminergic neurons in the substantia nigra pars compacta. The most widely used treatment for PD is administration of the dopamine precursor L-DOPA, although this eventually results in uncontrolled involuntary movements (dyskinesia) that can be more debilitating than the underlying disease itself. The causes of L-DOPA-induced dyskinesia are unclear, but probably involve non-physiological pulsatile stimulation of dopamine receptors or non-physiological dopamine release (eg, from serotonergic nerve terminals) in the striatum. In any case, this signaling leads to an imbalance in the activity of two basal ganglia pathways, the 'direct' and 'indirect' striatal output pathways, that are characterized by distinct neurochemical architectures. The wide range of neurotransmitter and neuromodulatory receptors present on these two striatal output pathways offers a huge range of potential therapeutic targets. Two main strategies for the treatment of dyskinesia exist: the use of drugs that can be given as an adjunct to L-DOPA, reducing the occurrence of dyskinesia without impairing its antiparkinsonian effect, or therapies with equal antiparkinsonian action as L-DOPA that do not elicit dyskinesia. Novel treatments for dyskinesia in clinical/preclinical development include A(2alpha) receptor antagonists, alpha(2) adrenoceptor antagonists, mu-opioid receptor antagonists and subtype-selective NMDA antagonists. Future research strategies are likely to focus on the molecular mechanisms underlying the emergence of dyskinesia and may lead to the development of agents that can prevent or reverse the cellular changes underlying this phenomenon.

Journal Article↗