Single-Trial {MEG} Data Can Be Denoised Through Cross-Subject Predictive Modeling

A pervasive challenge in brain imaging is the presence of noise that hinders investigation of underlying neural processes, with Magnetoencephalography (MEG) in particular having very low Signal-to-Noise Ratio (SNR). The established strategy to increase MEG's SNR involves averaging multiple repetitions of data corresponding to the same stimulus. However, repetition of stimulus can be undesirable, because underlying neural activity has been shown to change across trials, and repeating stimuli limits the breadth of the stimulus space experienced by subjects. In particular, the rising popularity of naturalistic studies with a single viewing of a movie or story necessitates the discovery of new approaches to increase SNR. We introduce a simple framework to reduce noise in single-trial MEG data by leveraging correlations in neural responses across subjects as they experience the same stimulus. We demonstrate its use in a naturalistic reading comprehension task with 8 subjects, with MEG data collected while they read the same story a single time. We find that our procedure results in data with reduced noise and allows for better discovery of neural phenomena. As proof-of-concept, we show that the N400m's correlation with word surprisal, an established finding in literature, is far more clearly observed in the denoised data than the original data. The denoised data also shows higher decoding and encoding accuracy than the original data, indicating that the neural signals associated with reading are either preserved or enhanced after the denoising procedure

Silent no more! The lived experiences of women with lichen sclerosis

Purpose: Lichen Sclerosis (LS) is an often unrecognized and misdiagnosed chronic inflammatory skin condition of the anogenital area that affects quality of life, bringing severe discomfort and distress to affected men, women, and children. The purpose of this qualitative study is to explore the lived experiences of women with LS. Data sources: Content analysis was conducted of data obtained from three public online forums/blogs used by women with LS. A total of 527 postings/entries were analyzed for patterns and themes by four researchers. Conclusions: Five core themes emerged as a result of this study, revealing feelings of frustration and despair stemming from healthcare providers' lack of knowledge in relation to Lichen Sclerosis, often leading to misdiagnosis, prolonged suffering, and an altered quality of life. Implications for practice: Knowledgeable healthcare providers and additional research into the cause, treatment, and cure of Lichen Sclerosis are needed. Advance‐practice nurses stand to play an important role in the areas of education, research, policy making, and clinical practice to advocate for and empower women with LS.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92447/1/j.1745-7599.2012.00715.x.pd

Want, need and habit as drivers of smoking behaviour: A preliminary analysis

BACKGROUND AND AIMS: Models of tobacco smoking behaviour propose that anticipated pleasure or satisfaction, the need to alleviate a nicotine-induced drive state and a stimulus-driven impulse potentially play an important role. This study aimed to provide a preliminary assessment of how far urges to smoke are reported by smokers and whether the strength of such urges prior to a quit attempt predicts short-term success at quitting. METHODS: In a prospective study, 566 smokers attending a treatment programme to help smokers quit completed a written questionnaire covering frequency of different types of urge to smoke (automatic impulse - 'automatic urges', anticipated pleasure - 'pleasure urges', and fulfilling a need - 'need urges'). They were asked to rate this for whichever of these urges was dominant for them. The questionnaire also assessed daily cigarette consumption, time to first cigarette of the day, age and gender. Carbon monoxide verified smoking status was recorded at 1 and 4weeks after the target quit date. FINDINGS: A total of 47.9% (271) of smokers reported that automatic urges were dominant, 21.7% (123) reported pleasure urges to be dominant, and 30.4% (172) reported need urges to be dominant. The strength of automatic urges predicted abstinence at both 1week (OR=0.74, p=0.005, 95%CI=0.60-0.92) and 4weeks (OR=0.73, p=0.008, 95%CI=0.59-0.92). Associations between other urge types and abstinence were not statistically significant. CONCLUSIONS: A substantial proportion of smokers attending a clinic for help with quitting report that their dominant urges to smoke occur without any anticipation of pleasure or relief and the strength of the automatic urges predicts failure to sustain abstinence following a quit attempt

Label-free characterization of biochemical changes within human cells under parasite attack using synchrotron based micro-FTIR

© 2019 The Royal Society of Chemistry. The protozoan Toxoplasma gondii is responsible for severe, potentially life-threatening, infection in immunocompromised individuals and when acquired during pregnancy. In the meantime, there is no available vaccine and the anti-T. gondii drug arsenal is limited. An important challenge to improve antiparasitic therapy is to understand chemical changes that occur during infection. Here, we used Fourier transform infrared spectroscopy (FTIR) to investigate the effect of T. gondii infection on the chemical composition of human brain microvascular endothelial cells (hBMECs) at 3, 6, 24 and 48 hours postinfection (hpi). Principal component analysis (PCA) showed that the best separation and largest difference between infected and uninfected hBMECs was detected at 24 hpi and within the 3400-2800 cm-1 region. At 48 hpi, although the difference between samples was obvious within the 3400-2800 cm-1 region, more differences were detected in the fingerprint region. These findings indicate that infected and control cells can be easily distinguished. Although differences between the spectra varied, the separation was most clear at 24 hpi. T. gondii increased signals for lipids (2853 cm-1) and nucleic acids (976 cm-1, 1097 cm-1 and 1245 cm-1), and decreased signals for proteins (3289 cm-1, 2963 cm-1, 2875 cm-1) in infected cells compared to controls. These results, supported by amino acid levels in culture media, and global metabolomic and gene expression analyses of hBMECs, suggest that T. gondii parasite exploits a wide range of host-derived chemical compounds and signaling pathways for its own survival and proliferation within host cells. Our data demonstrate that FTIR combined with chemometric analysis is a valuable approach to elucidate the temporal, infection-specific, chemical alterations in host cells at a single cell resolution

Chemotherapeutic response to cisplatin-like drugs in human breast cancer cells probed by vibrational microspectroscopy

Studies of drug-cell interactions in cancer model systems are essential in the preclinical stage of rational drug design, which relies on a thorough understanding of the mechanisms underlying cytotoxic activity and biological effects, at a molecular level. This study aimed at applying complementary vibrational spectroscopy methods to evaluate the cellular impact of two Pt(ii) and Pd(ii) dinuclear chelates with spermine (Pt2Spm and Pd2Spm), using cisplatin (cis-Pt(NH3)2Cl2) as a reference compound. Their effects on cellular metabolism were monitored in a human triple-negative metastatic breast cancer cell line (MDA-MB-231) by Raman and synchrotron-radiation infrared microspectroscopies, for different drug concentrations (2-8 μM) at 48 h exposure. Multivariate data analysis was applied (unsupervised PCA), unveiling drug- and concentration-dependent effects: apart from discrimination between control and drug-treated cells, a clear separation was obtained for the different agents studied - mononuclear vs. polynuclear, and Pt(ii) vs. Pd(ii). Spectral biomarkers of drug action were identified, as well as the cellular response to the chemotherapeutic insult. The main effect of the tested compounds was found to be on DNA, lipids and proteins, the Pd(ii) agent having a more significant impact on proteins while its Pt(ii) homologue affected the cellular lipid content at lower concentrations, which suggests the occurrence of distinct and unconventional pathways of cytotoxicity for these dinuclear polyamine complexes. Raman and FTIR microspectroscopies were confirmed as powerful non-invasive techniques to obtain unique spectral signatures of the biochemical impact and physiological reaction of cells to anticancer agents

Prospective randomized trial of iliohypogastric-ilioinguinal nerve block on post-operative morphine use after inpatient surgery of the female reproductive tract

<p>Abstract</p> <p>Objective</p> <p>To determine the impact of pre-operative and intra-operative ilioinguinal and iliohypogastric nerve block on post-operative analgesic utilization and length of stay (LOS).</p> <p>Methods</p> <p>We conducted a prospective randomized double-blind placebo controlled trial to assess effectiveness of ilioinguinal-iliohypogastric nerve block (IINB) on post-operative morphine consumption in female study patients (<it>n </it>= 60). Patients undergoing laparotomy via Pfannenstiel incision received injection of either 0.5% bupivacaine + 5 mcg/ml epinephrine for IINB (Group I, <it>n </it>= 28) or saline of equivalent volume given to the same site (Group II, <it>n </it>= 32). All injections were placed before the skin incision and after closure of rectus fascia via direct infiltration. Measured outcomes were post-operative morphine consumption (and associated side-effects), visual analogue pain scores, and hospital length of stay (LOS).</p> <p>Results</p> <p>No difference in morphine use was observed between the two groups (47.3 mg in Group I vs. 45.9 mg in Group II; <it>p </it>= 0.85). There was a trend toward lower pain scores after surgery in Group I, but this was not statistically significant. The mean time to initiate oral narcotics was also similar, 23.3 h in Group I and 22.8 h in Group II (<it>p </it>= 0.7). LOS was somewhat shorter in Group I compared to Group II, but this difference was not statistically significant (<it>p </it>= 0.8). Side-effects occurred with similar frequency in both study groups.</p> <p>Conclusion</p> <p>In this population of patients undergoing inpatient surgery of the female reproductive tract, utilization of post-operative narcotics was not significantly influenced by IINB. Pain scores and LOS were also apparently unaffected by IINB, indicating a need for additional properly controlled prospective studies to identify alternative methods to optimize post-surgical pain management and reduce LOS.</p