High-density microfibers as a deep brain bidirectional optical interface

Optical interrogation and manipulation of neural dynamics is a cornerstone of systems neuroscience. Genetic targeting enable delivering fluorescent indicators and opsins to specific neural subpopulations. Optic probes can fluorescently sense and convey calcium, voltage, and neurotransmitter dynamics. This optical toolkit enables recording and perturbing cellular-resolution activity in thousands of neurons across a field of view. Yet these techniques are limited by the light scattering properties of tissues. The cutting edge of microscopy, three-photon imaging, can record from intact tissues at depths up to 1 mm, but requires head-fixed experimental paradigms. To access deeper layers and non-cortical structures, researchers rely on optical implants, such as GRIN lenses or prisms, or the removal of superficial tissue. In this thesis, we introduce a novel implant for interfacing with deep brain regions constructed from bundles of hundreds or thousands of dissociated, small diameter (<8 µm) optical fibers. During insertion into the tissue, the fibers move independently, splaying through the target region. Each fiber achieves near total internal reflection, acting as a bidirectional optical interface with a small region of tissue near the fiber aperture. The small diameter and flexibility of the fibers minimize tissue response, preserving local connectivity and circuit dynamics. Histology and immunohistochemistry from implants into zebra finch basal ganglia (depth 2.9 mm) show the splaying of the fibers and the presence of NeuN-stained cells in close proximity to the fiber tips. By modeling the optical properties of the fibers and tissue, we simulate the interface properties of a bundle of fibers. Overlap in the sensitivity between nearby fibers allows application of blind source separation to extract individual neural traces. We describe a nonnegative independent component analysis algorithm especially suited to the interface. Finally, experimental data from implants in transgenic mice yield proof of principle recordings during both cortical spreading depolarization and forepaw stimulation. Collectively, the data presented here paint a compelling picture of splaying microfibers as a deep brain interface capable of sampling or perturbing neural activity at hundreds or thousands of points throughout a 3D volume of tissue while eliciting less response than existing optical implants

An abridged enterprise assessment model to promote consistent reassessment : model development, assessment process and results analysis

Thesis (S.M. in Technology and Policy)--Massachusetts Institute of Technology, Engineering Systems Division, Technology and Policy Program, 2011.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student submitted PDF version of thesis.Includes bibliographical references (p. 136-140).Enterprise assessment is increasingly important, both as a cross-time and cross-industry measurement and as a guiding force in enterprise transformation. Assessments provide crucial information about strengths, areas for improvement and potential investment strategies for achieving performance benefits. As performance is being recognized as a complex and multifaceted construct, assessment tools seek to incorporate and reflect a holistic measurement of performance across multiple dimensions such as stakeholder value, leadership, culture and quality. The Lean Enterprise Self-Assessment Tool (LESAT) is one such enterprise assessment tool that closely ties into a clearly defined enterprise transformation framework and roadmap. Ideal use of assessment involves regular reassessment of 54 practices and continual feedback, but due to the resource and time commitment required to perform assessment, this iterative process is deprioritized. In order to facilitate and promote regular reassessment, we demonstrate a methodology for creating an abridged assessment tool. By creating a predictive model based on the unidemnsionality of LESAT, a small selection of highly indicative practices is used to predict the remaining practices. Based on these predictions, respondents assess follow-up practices selected to target high-priority areas for improvement. Using this approach, we are able to create an abridged LESAT that assesses six of the original 54 practices for the predictive model and an additional twelve dynamically selected practices to target high-priority areas. Based on training data and novel testing data (271 respondents from 24 companies), we validate the accuracy of the predictive model and show that high-priority areas are correctly identified over 90% of the time. The abridged LESAT shows promise as a way to reassess, with significantly lower time and resource commitment normally required. We review the practical applications of the abridged LESAT and present a revised recommended process for assessment and for evaluation of results. The revised process seeks to articulate how the new assessment tool can be practically applied in the context of an ongoing enterprise transformation.by L. Nathan Perkins.S.M.in Technology and Polic

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Technologies of contraception and abortion

Soon to turn 60, the oral contraceptive pill still dominates histories of technology in the ‘sexual revolution’ and after. ‘The pill’ was revolutionary for many, though by no means all, women in the west, but there have always been alternatives, and looking globally yields a different picture. The condom, intrauterine device (IUD), surgical sterilization (male and female) and abortion were all transformed in the twentieth century, some more than once. Today, female sterilization (tubal ligation) and IUDs are the world's most commonly used technologies of contraception. The pill is in third place, followed closely by the condom. Long-acting hormonal injections are most frequently used in parts of Africa, male sterilization by vasectomy is unusually prevalent in Britain, and about one in five pregnancies worldwide ends in induced abortion. Though contraceptive use has generally increased in recent decades, the disparity between rich and poor countries is striking: the former tend to use condoms and pills, the latter sterilization and IUDs. Contraception, a term dating from the late nineteenth century and since then often conflated with abortion, has existed in many forms, and techniques have changed and proliferated over time. Diverse local cultures have embraced new technologies while maintaining older practices. Focusing on Britain and the United States, with excursions to India, China and France, this chapter shows how the patterns observed today were established and stabilized, often despite persistent criticism and reform efforts. By examining past innovation, and the distribution and use of a variety of tools and techniques, it reconsiders some widely held assumptions about what counts as revolutionary and for whom. Analytically, it takes up and reflects on one of the main issues raised by feminists and social historians: the agency of users as patients and consumers faced with choice and coercion. By examining practices of contraception alongside those of abortion, it revisits the knotty question of technology in the sexual revolution and the related themes of medical, legal, religious and political forms of control

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Rapid corneal nerve fiber loss: A marker of diabetic neuropathy onset and progression

OBJECTIVE Corneal nerve fiber length (CNFL) represents a biomarker for diabetic distal symmetric polyneuropathy (DSP). We aimed to determine the reference distribution of annual CNFL change, the prevalence of abnormal change in diabetes, and its associated clinical variables. RESEARCH DESIGN AND METHODS We examined 590 participants with diabetes (399 with type 1 diabetes [T1D] and 191 with type 2 diabetes [T2D]) and 204 control patients without diabetes with at least 1 year of follow-up and classified them according to rapid corneal nerve fiber loss (RCNFL) if CNFL change was below the 5th percentile of the control patients without diabetes. RESULTS Control patients without diabetes were 37.9 6 19.8 years old, had median follow-up of three visits over 3.0 years, and mean annual change in CNFL was 20.1% (90% CI 25.9% to 5.0%). RCNFL was defined by values exceeding the 5th percentile of 6% loss. Participants with T1D were 39.9 6 18.7 years old, had median follow-up of three visits over 4.4 years, and mean annual change in CNFL was 20.8% (90% CI 214.0% to 9.9%). Participants with T2D were 60.4 6 8.2 years old, had median follow-up of three visits over 5.3 years, and mean annual change in CNFL was 20.2% (90% CI 214.1% to 14.3%). RCNFL prevalence was 17% overall and was similar by diabetes type (64 T1D [16.0%], 37 T2D [19.4%], P 5 0.31). RNCFL was more common in those with baseline DSP (47% vs. 30% in those without baseline DSP, P 5 0.001), which was associated with lower peroneal conduction velocity but not with baseline HbA1c or its change over follow-up. CONCLUSIONS An abnormally rapid loss of CNFL of 6% per year or more occurs in 17% of diabetes patients. RCNFL may identify patients at highest risk for the development and progression of DSP.</p