INTEGRATION OF MULTIFOCAL MULTIPHOTON MICROSCOPE (MMM) AND SECOND HARMONIC GENERATION MICROSCOPE (SHG) FOR 3D HIGHRESOLUTION IMAGING IN LIVER FIBROSIS

Ph.DDOCTOR OF PHILOSOPH

Effects of High-Frequency Transcranial Magnetic Stimulation for Cognitive Deficit in Schizophrenia: A Meta-Analysis

Objective: Repetitive transcranial magnetic stimulation (rTMS) has been applied to dorsolateral prefrontal cortex (DLPFC) to improve cognitive function of patients with schizophrenia (SZs). The aim of this meta-analysis was to evaluate whether a high-frequency rTMS course could enhance cognitive function in SZs.Methods: Studies published in PubMed, Cochrane Library, Embase, ScienceDirect, and Web of science were searched until April 2018. The search terms included: “repetitive transcranial magnetic stimulation” or “Rtms,” “SZ,” or “schizophrenia,” and “neuro-cognition” or “neurocognitive performance” or “cognitive effects” or “cognitive” or “cognition” or “working memory” or “executive function” or “language function” or “processing speed,” After screening the literatures according to inclusion and exclusion criteria, extracting data, and evaluating the methodological quality of the included studies, a meta-analysis was performed using RevMan 5.3 software (The Cochrane Collaboration, USA).Results: A total of 9 studies on cognitive dysfunction of SZs were included and involved 351 patients. A significant efficacy of high-frequency rTMS on working memory in SZs was found compared to sham stimulation [p = 0.009, standardized mean difference (SMD) = 0.34]. Specifically, rTMS treatment positioned on the left DLPFC, with a total pluses <30,000 was more significantly more effective in improving the working memory (SMD = 0.33, p = 0.03). No improvement was found in other cognitive domains such as executive function, attention, processing speed, and language function. For the follow-up observations, high-frequency rTMS had long-lasting sustained effects on working memory (SMD = 0.45, p = 0.01) and language function (SMD = 0.77, p = 0.02) in SZs.Conclusions: High-frequency rTMS over the left DLPFC with a total pulses <30,000 stimulation could significantly improve working memory in SZs for an extended period of time

Reassignment of Scattered Emission Photons in Multifocal Multiphoton Microscopy

Multifocal multiphoton microscopy (MMM) achieves fast imaging by simultaneously scanning multiple foci across different regions of specimen. The use of imaging detectors in MMM, such as CCD or CMOS, results in degradation of image signal-to-noise-ratio (SNR) due to the scattering of emitted photons. SNR can be partly recovered using multianode photomultiplier tubes (MAPMT). In this design, however, emission photons scattered to neighbor anodes are encoded by the foci scan location resulting in ghost images. The crosstalk between different anodes is currently measured a priori, which is cumbersome as it depends specimen properties. Here, we present the photon reassignment method for MMM, established based on the maximum likelihood (ML) estimation, for quantification of crosstalk between the anodes of MAPMT without a priori measurement. The method provides the reassignment of the photons generated by the ghost images to the original spatial location thus increases the SNR of the final reconstructed image.RO1 EY017656Singapore-MIT Alliance for Research and TechnologyNIH P41EB0158715 R01 NS0513204R44EB012415NSF CBET-0939511MIT Skoltech InitiativeDavid H. Koch Institute for Integrative Cancer Research at MI

Experimenting Liver Fibrosis Diagnostic by Two Photon Excitation Microscopy and Bag-of-Features Image Classification

The accurate staging of liver fibrosis is of paramount importance to determine the state of disease progression, therapy responses, and to optimize disease treatment strategies. Non-linear optical microscopy techniques such as two-photon excitation fluorescence (TPEF) and second harmonic generation (SHG) can image the endogenous signals of tissue structures and can be used for fibrosis assessment on non-stained tissue samples. While image analysis of collagen in SHG images was consistently addressed until now, cellular and tissue information included in TPEF images, such as inflammatory and hepatic cell damage, equally important as collagen deposition imaged by SHG, remain poorly exploited to date. We address this situation by experimenting liver fibrosis quantification and scoring using a combined approach based on TPEF liver surface imaging on a Thioacetamide-induced rat model and a gradient based Bag-of-Features (BoF) image classification strategy. We report the assessed performance results and discuss the influence of specific BoF parameters to the performance of the fibrosis scoring framework.Romania. Executive Agency for Higher Education, Research, Development and Innovation Funding (research grant PN-II-PT-PCCA-2011-3.2-1162)Rectors' Conference of the Swiss Universities (SCIEX NMS-CH research fellowship nr. 12.135)Singapore. Agency for Science, Technology and Research (R-185-000-182-592)Singapore. Biomedical Research CouncilInstitute of Bioengineering and Nanotechnology (Singapore)Singapore-MIT Alliance (Computational and Systems Biology Flagship Project funding (C-382-641-001-091))Singapore-MIT Alliance for Research and Technology (SMART BioSyM and Mechanobiology Institute of Singapore (R-714-001-003-271)

Antidepressant Effects of Repetitive Transcranial Magnetic Stimulation Over Prefrontal Cortex of Parkinson's Disease Patients With Depression: A Meta-Analysis

Objective: The purpose of this meta-analysis was to investigate the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex (PFC) of patients with Parkinson's disease (PD) and to determine the optimal rTMS parameters, such as the intensity, frequency and the delivered pattern of rTMS stimulation.Methods: EMBASE, PubMed, Web of Science, MEDLINE, and Cochrane data bases were researched for papers published before March 12, 2018. Studies investigating the anti-depression effects of rTMS over PFC in patients with PD were considered. The main outcomes of pre- and post-rTMS treatment as well as score changes were all extracted. The mean effect size was estimated by calculating the standardized mean difference (SMD) with 95% confidence interval (CI) by using fixed or random effect models as appropriate.Results: Nine studies containing 137 PD patients with depression were included. The pooled results showed significant pre-post anti-depressive effects of rTMS over PFC in PD patients with depression (SMD = −0.80, P < 0.00001). The subgroup analyses of stimulation intensity, frequencies, and models also revealed significant effects (Intensities: 90% RMT: SMD = −1.16, P = 0.0006; >100% RMT: SMD = −0.82, P < 0.0001. Frequencies: < 1.0 Hz: SMD = −0.83, P = 0.03; 5.0 Hz: SMD = −1.10, P < 0.0001; ≥10.0 Hz: SMD = −0.55, P = 0.02. Models: Continuous: SMD = −0.79, P < 0.0001; Discontinuous: SMD = −0.84, P = 0.02). But the results of the studies with place-controlled designs were not significant (Overall: SMD = −0.27, P = 0.54. Intensities: 90% RMT: SMD = 0.27, P = 0.68; 100% RMT: SMD = −0.32, P = 0.33. Frequencies: 5.0 Hz: SMD = −0.87, P = 0.10; ≥10.0 Hz: SMD = 0.27, P = 0.66. Models: Continuous: SMD = −0.28, P = 0.68; Discontinuous: SMD = −0.32, P = 0.33). The greater effect sizes of rTMS with 90% RMT, 5.0 Hz in discontinuous days can be observed rather than the other parameters in both kinds of analyses across study design.Conclusions: rTMS may have a significant positive pre-post anti-depressive effect over PFC on patients with depression, especially by using 5.0 Hz frequency with 90% RMT intensity in discontinuous days, which may produce better effects than other parameters. The real effect, though, was not different from that of the placebo. Future studies with larger sample sizes and high-quality studies are needed to further corroborate our results and to identify the optimal rTMS protocols

Active Surveillance of Carbapenemase-Producing Organisms (CPO) Colonization With Xpert Carba-R Assay Plus Positive Patient Isolation Proves to Be Effective in CPO Containment

Background: Rapid screening of patients for colonization with carbapenemase-producing organisms (CPO), coupled with implementation of infection prevention strategies, has the potential to contain the spread of CPO.Methods: We first evaluated the performance of Xpert Carba-R assay (in comparison with other phenotypic methods) for carbapenemase detection using clinical isolates, and then used it to determine the intestinal CPO colonization in hospitalized patients. We then assessed the effectiveness of patient isolation in controlling the spread of CPO in a medical intensive care unit.Results: The Xpert Carba-R assay required the least processing time to reveal results and showed a 94.5% sensitivity and specificity in carbapenemase detection, except for IMP-8 (n = 4). During a 6-month study period, 134 patients in one ward were studied for CPO colonization and infection. Fifteen patients (11.2%) were colonized by CPO as detected by Xpert Carba-R assay, including three NDM, three IMP, and nine KPC possessing strains. The overall colonization and CPO infection rates were both 11.2% each. Isolation of patients with CPO led to a reduction in both colonization (from 28.6 to 5.6%) and infection rates (from 35.7 to 2.8%) during the study period (p < 0.05).Conclusion: Active surveillance of CPO utilizing the Xpert Carba-R assay supplemented with immediate patient isolation, proved to be an effective strategy to limit the spread of CPO in a health care setting

Pre‐symptomatic transmission of novel coronavirus in community settings

We used contact tracing to document how COVID‐19 was transmitted across 5 generations involving 10 cases, starting with an individual who became ill on January 27. We calculated the incubation period of the cases as the interval between infection and development of symptoms. The median incubation period was 6.0 days (interquartile range, 3.5‐9.5 days). The last two generations were infected in public places, 3 and 4 days prior to the onset of illness in their infectors. Both had certain underlying conditions and comorbidity. Further identification of how individuals transmit prior to being symptomatic will have important consequences.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163478/2/irv12773.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163478/1/irv12773_am.pd

Plasmon-driven nanowire actuators for on-chip manipulation.

Funder: National Natural Science Foundation of China (11674230); Shanghai Rising-Star Program (18QA1403200)Chemically synthesized metal nanowires are promising building blocks for next-generation photonic integrated circuits, but technological implementation in monolithic integration will be severely hampered by the lack of controllable and precise manipulation approaches, due to the strong adhesion of nanowires to substrates in non-liquid environments. Here, we demonstrate this obstacle can be removed by our proposed earthworm-like peristaltic crawling motion mechanism, based on the synergistic expansion, friction, and contraction in plasmon-driven metal nanowires in non-liquid environments. The evanescently excited surface plasmon greatly enhances the heating effect in metal nanowires, thereby generating surface acoustic waves to drive the nanowires crawling along silica microfibres. Advantages include sub-nanometer positioning accuracy, low actuation power, and self-parallel parking. We further demonstrate on-chip manipulations including transporting, positioning, orientation, and sorting, with on-situ operation, high selectivity, and great versatility. Our work paves the way to realize full co-integration of various functionalized photonic components on single chips