Making sense: dopamine activates conscious self-monitoring through medial prefrontal cortex

When experiences become meaningful to the self, they are linked to synchronous activity in a paralimbic network of self-awareness and dopaminergic activity. This network includes medial prefrontal and medial parietal/posterior cingulate cortices, where transcranial magnetic stimulation may transiently impair self-awareness. Conversely, we hypothesize that dopaminergic stimulation may improve self-awareness and metacognition (i.e., the ability of the brain to consciously monitor its own cognitive processes). Here, we demonstrate improved noetic (conscious) metacognition by oral administration of 100 mg dopamine in minimal self-awareness. In a separate experiment with extended self-awareness dopamine improved the retrieval accuracy of memories of self-judgment (autonoetic, i.e., explicitly self-conscious) metacognition. Concomitantly, magnetoencephalography (MEG) showed increased amplitudes of oscillations (power) preferentially in the medial prefrontal cortex. Given that electromagnetic activity in this region is instrumental in self-awareness, this explains the specific effect of dopamine on explicit self-awareness and autonoetic metacognition

On-scalp MEG sensor localization using magnetic dipole-like coils: A method for highly accurate co-registration

Source modelling in magnetoencephalography (MEG) requires precise co-registration of the sensor array and the anatomical structure of the measured individual\u27s head. In conventional MEG, the positions and orientations of the sensors relative to each other are fixed and known beforehand, requiring only localization of the head relative to the sensor array. Since the sensors in on-scalp MEG are positioned on the scalp, locations of the individual sensors depend on the subject\u27s head shape and size. The positions and orientations of on-scalp sensors must therefore be measured a every recording. This can be achieved by inverting conventional head localization, localizing the sensors relative to the head - rather than the other way around. In this study we present a practical method for localizing sensors using magnetic dipole-like coils attached to the subject\u27s head. We implement and evaluate the method in a set of on-scalp MEG recordings using a 7-channel on-scalp MEG system based on high critical temperature superconducting quantum interference devices (high-T-c SQUIDs). The method allows individually localizing the sensor positions, orientations, and responsivities with high accuracy using only a short averaging time (<= 2 mm, < 3 degrees and < 3%, respectively, with 1-s averaging), enabling continuous sensor localization. Calibrating and jointly localizing the sensor array can further improve the accuracy of position and orientation (< 1 mm and < 1 degrees, respectively, with 1-s coil recordings). We demonstrate source localization of on-scalp recorded somatosensory evoked activity based on coregistration with our method. Equivalent current dipole fits of the evoked responses corresponded well (within 4.2 mm) with those based on a commercial, whole-head MEG system

Detection of interictal epileptiform discharges: A comparison of on-scalp MEG and conventional MEG measurements

Objective: Conventional MEG provides an unsurpassed ability to, non-invasively, detect epileptic activity. However, highly resolved information on small neuronal populations required in epilepsy diagnostics is lost and can be detected only intracranially. Next-generation on-scalp magnetencephalography (MEG) sensors aim to retrieve information unavailable to conventional non-invasive brain imaging techniques. To evaluate the benefits of on-scalp MEG in epilepsy, we performed the first-ever such measurement on an epilepsy patient. Methods: Conducted as a benchmarking study focusing on interictal epileptiform discharge (IED) detectability, an on-scalp high-temperature superconducting quantum interference device magnetometer (high-Tc SQUID) system was compared to a conventional, low-temperature SQUID system. Coregistration of electroencephalopraphy (EEG) was performed. A novel machine learning-based IED-detection algorithm was developed to aid identification of on-scalp MEG unique IEDs. Results: Conventional MEG contained 24 IEDs. On-scalp MEG revealed 47 IEDs (16 co-registered by EEG, 31 unique to the on-scalp MEG recording). Conclusion: Our results indicate that on-scalp MEG might capture IEDs not seen by other non-invasive modalities. Significance: On-scalp MEG has the potential of improving non-invasive epilepsy evaluation. (C) 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table

Dysregulation of the transcription factors SOX4, CBFB and SMARCC1 correlates with outcome of colorectal cancer

The aim of this study was to identify deregulated transcription factors (TFs) in colorectal cancer (CRC) and to evaluate their relation with the recurrence of stage II CRC and overall survival. Microarray-based transcript profiles of 20 normal mucosas and 424 CRC samples were used to identify 51 TFs displaying differential transcript levels between normal mucosa and CRC. For a subset of these we provide in vitro evidence that deregulation of the Wnt signalling pathway can lead to the alterations observed in tissues. Furthermore, in two independent cohorts of microsatellite-stable stage II cancers we found that high SOX4 transcript levels correlated with recurrence (HR 2.7; 95% CI, 1.2–6.0; P=0.01). Analyses of ∼1000 stage I–III adenocarcinomas, by immunohistochemistry, revealed that patients with tumours displaying high levels of CBFB and SMARCC1 proteins had a significantly better overall survival rate (P=0.0001 and P=0.0275, respectively) than patients with low levels. Multivariate analyses revealed that a high CBFB protein level was an independent predictor of survival. In conclusion, several of the identified TFs seem to be involved in the progression of CRC

Risk of surgical site infection and efficacy of antibiotic prophylaxis: a cohort study of appendectomy patients in Thailand

BACKGROUND: No data currently exist about use of antibiotics to prevent surgical site infections (SSI) among patients undergoing appendectomy in Thailand. We therefore examined risk factors, use, and efficacy of prophylactic antibiotics for surgical site infection SSI among patients with uncomplicated open appendectomy. METHODS: From July 1, 2003 to June 30, 2004 we conducted a prospective cohort study in eight hospitals in Thailand. We used the National Nosocomial Infection Surveillance (NNIS) system criteria to identify SSI associated with appendectomy. We used logistic regression analysis to obtain relative risk estimates for predictors of SSI. RESULTS: Among 2139 appendectomy patients, we identified 26 SSIs, yielding a SSI rate of 1.2 infections/100 operations. Ninety-two percent of all patients (95% CI, 91.0–93.3) received antibiotic prophylaxis. Metronidazole and gentamicin were the two most common antibiotic agents, with a combined single dose administered in 39% of cases. In 54% of cases, antibiotic prophylaxis was administered for one day. We found that a prolonged duration of operation was significantly associated with an increased SSI risk. Antibiotic prophylaxis was significantly associated with a decreased risk of SSI regardless of whether the antibiotic was administered preoperatively or intraoperatively. Compared with no antibiotic prophylaxis, SSI relative risks for combined single-dose of metronidazole and gentamicin, one-day prophylaxis, and multiple-day antibiotic prophylaxis were 0.28 (0.09–0.90), 0.30 (0.11–0.88) and 0.32 (0.10–0.98), respectively. CONCLUSION: Single-dose combination of metronidazole and gentamicin seems sufficient to reduce SSIs in uncomplicated appendicitis patients despite whether the antibiotic was administered preoperatively or intraoperatively

The Complete Genome Sequence of Escherichia coli EC958: A High Quality Reference Sequence for the Globally Disseminated Multidrug Resistant E. coli O25b:H4-ST131 Clone

Escherichia coli ST131 is now recognised as a leading contributor to urinary tract and bloodstream infections in both community and clinical settings. Here we present the complete, annotated genome of E. coli EC958, which was isolated from the urine of a patient presenting with a urinary tract infection in the Northwest region of England and represents the most well characterised ST131 strain. Sequencing was carried out using the Pacific Biosciences platform, which provided sufficient depth and read-length to produce a complete genome without the need for other technologies. The discovery of spurious contigs within the assembly that correspond to site-specific inversions in the tail fibre regions of prophages demonstrates the potential for this technology to reveal dynamic evolutionary mechanisms. E. coli EC958 belongs to the major subgroup of ST131 strains that produce the CTX-M-15 extended spectrum β-lactamase, are fluoroquinolone resistant and encode the fimH30 type 1 fimbrial adhesin. This subgroup includes the Indian strain NA114 and the North American strain JJ1886. A comparison of the genomes of EC958, JJ1886 and NA114 revealed that differences in the arrangement of genomic islands, prophages and other repetitive elements in the NA114 genome are not biologically relevant and are due to misassembly. The availability of a high quality uropathogenic E. coli ST131 genome provides a reference for understanding this multidrug resistant pathogen and will facilitate novel functional, comparative and clinical studies of the E. coli ST131 clonal lineage

Optimization of a Morphing Wing Based on Coupled Aerodynamic and Structural Constraints

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77091/1/AIAA-39016-101.pd

Identification, characterisation and expression analysis of natural killer receptor genes in Chlamydia pecorum infected koalas (Phascolarctos cinereus)

BACKGROUND: Koalas (Phascolarctos cinereus), an iconic Australian marsupial, are being heavily impacted by the spread of Chlamydia pecorum, an obligate intracellular bacterial pathogen. Koalas vary in their response to this pathogen, with some showing no symptoms, while others suffer severe symptoms leading to infertility, blindness or death. Little is known about the pathology of this disease and the immune response against it in this host. Studies have demonstrated that natural killer (NK) cells, key components of the innate immune system, are involved in the immune response to chlamydial infections in humans. These cells can directly lyse cells infected by intracellular pathogens and their ability to recognise these infected cells is mediated through NK receptors on their surface. These are encoded in two regions of the genome, the leukocyte receptor complex (LRC) and the natural killer complex (NKC). These two families evolve rapidly and different repertoires of genes, which have evolved by gene duplication, are seen in different species. METHODS: In this study we aimed to characterise genes belonging to the NK receptor clusters in the koala by searching available koala transcriptomes using a combination of search methods. We developed a qPCR assay to quantify relative expression of four genes, two encoded within the NK receptor cluster (CLEC1B, CLEC4E) and two known to play a role in NK response to Chalmydia in humans (NCR3, PRF1). RESULTS: We found that the NK receptor repertoire of the koala closely resembles that of the Tasmanian devil, with minimal genes in the NKC, but with lineage specific expansions in the LRC. Additional genes important for NK cell activity, NCR3 and PRF1, were also identified and characterised. In a preliminary study to investigate whether these genes are involved in the koala immune response to infection by its chlamydial pathogen, C. pecorum, we investigated the expression of four genes in koalas with active chlamydia infection, those with past infection and those without infection using qPCR. This analysis revealed that one of these four, CLEC4E, may be upregulated in response to chlamydia infection. CONCLUSION: We have characterised genes of the NKC and LRC in koalas and have discovered evidence that one of these genes may be upregulated in koalas with chlamydia, suggesting that these receptors may play a role in the immune response of koalas to chlamydia infection

Factors Associated with Influenza Vaccination of Hospitalized Elderly Patients in Spain

Vaccination of the elderly is an important factor in limiting the impact of influenza in the community. The aim of this study was to investigate the factors associated with influenza vaccination coverage in hospitalized patients aged ≥ 65 years hospitalized due to causes unrelated to influenza in Spain. We carried out a cross-sectional study. Bivariate analysis was performed comparing vaccinated and unvaccinated patients, taking in to account sociodemographic variables and medical risk conditions. Multivariate analysis was performed using multilevel regression models. We included 1038 patients: 602 (58%) had received the influenza vaccine in the 2013-14 season. Three or more general practitioner visits (OR = 1.61; 95% CI 1.19-2.18); influenza vaccination in any of the 3 previous seasons (OR = 13.57; 95% CI 9.45-19.48); and 23-valent pneumococcal polysaccharide vaccination (OR = 1.97; 95% CI 1.38-2.80) were associated with receiving the influenza vaccine. Vaccination coverage of hospitalized elderly people is low in Spain and some predisposing characteristics influence vaccination coverage. Healthcare workers should take these characteristics into account and be encouraged to proactively propose influenza vaccination to all patients aged ≥ 65 year