Buckling and friction-based linear motion clutch with application to medical devices

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2008.Includes bibliographical references (p. 158).Improperly inserted and positioned needles and catheters often require repeated attempts at correct placement causing injury to adjacent structures or infusions into inappropriate spaces. Existing catheter insertion methods do not uniformly provide needle tip location feedback, nor prevent the needle from going beyond the target space. This research achieved the development of design methods and analysis tools that can be used to create a new catheter insertion device. This device can advance a needle through firm tissue but automatically stop advancing it upon entrance into a target space. Prototypes of the device were tested on raw chicken breast, the best of which had about a 50% success rate. Tests performed on deceased pigs showed the device advanced well through muscle but not the peritoneum. The system studied consisted of a flexible filament (OD ~0.9 mm) passing through a tube (ID ~1.2 mm) with both straight and curved sections. Initially it was believed that the capstan equation would provide a good model for the system in tension and compression. Though the capstan equation proved valid for the system under tension, models from drill strings used in the petroleum industry provided an accurate model for the system in compression. Based on the geometry of the tube, this model accurately predicts the compressive force in the filament and when the filament locks-up inside the tube (needle). An alternate method to measure the tube geometry using a flatbed scanner was developed and studied. This method was found to provide excellent accuracy and repeatability for measuring tubes, and has shown potential as a measurement method for many other applications.by Erik K. Bassett.S.M

Gas Transfer in Cellularized Collagen-Membrane Gas Exchange Devices

Chronic lower respiratory disease is highly prevalent in the United States, and there remains a need for alternatives to lung transplant for patients who progress to end-stage lung disease. Portable or implantable gas oxygenators based on microfluidic technologies can address this need, provided they operate both efficiently and biocompatibly. Incorporating biomimetic materials into such devices can help replicate native gas exchange function and additionally support cellular components. In this work, we have developed microfluidic devices that enable blood gas exchange across ultra-thin collagen membranes (as thin as 2 μm). Endothelial, stromal, and parenchymal cells readily adhere to these membranes, and long-term culture with cellular components results in remodeling, reflected by reduced membrane thickness. Functionally, acellular collagen-membrane lung devices can mediate effective gas exchange up to ~288 mL/min/m[superscript 2] of oxygen and ~685 mL/min/m[superscript 2] of carbon dioxide, approaching the gas exchange efficiency noted in the native lung. Testing several configurations of lung devices to explore various physical parameters of the device design, we concluded that thinner membranes and longer gas exchange distances result in improved hemoglobin saturation and increases in pO[subscript 2]. However, in the design space tested, these effects are relatively small compared to the improvement in overall oxygen and carbon dioxide transfer by increasing the blood flow rate. Finally, devices cultured with endothelial and parenchymal cells achieved similar gas exchange rates compared with acellular devices. Biomimetic blood oxygenator design opens the possibility of creating portable or implantable microfluidic devices that achieve efficient gas transfer while also maintaining physiologic conditions.National Institute of General Medical Sciences (U.S.) (MSTP T32GM007753

Rapid Prototyping of Flexible Structures for Tissue Engineered Ear Reconstruction

The tissue engineered ear has been an iconic symbol of the field since 1991, when the report of an engineered ear in a mouse model was first published A tissue engineered ear has an inherent advantage over conventional approaches because the structure is derived from the patient's own cartilage. In this approach, autologous auricular chondrocytes are harvested from the patient and grown within an ear-shaped scaffold. However, as the scaffold degrades or remodels, the ear-shaped structure undergoes significant distortion, resulting in a skewed ear shape that is smaller and often unrecognizable In order to maintain the desired ear geometry, a composite scaffold concept was developed Methods Several functional requirements for the manufacturing process were identified. First, the wire framework must be created with arbitrary three dimensional (3D) control, and with a diameter significantly smaller than the thickness of normal ear cartilage, which is about 2 mm. The bending stiffness must be sufficiently high so that shape is maintained during neocartilage maturation and sufficiently low such that flexibility of the overall structure is not impaired. The material must be approved for clinical use, and must not cause an inflammatory reaction. Finally, the manufacturing process must be capable of producing single, custom parts without significant cost burden. Plastic surgeons identified titanium and stainless steel as preferred materials due to their long history of success in medical implants Three manufacturing processes were identified that are capable of producing arbitrary shapes with the listed metals: wire bending, direct metal laser sintering (DMLS) Results Ear frameworks produced using DMLS and EBM technology are shown in Interpretation Ear frameworks produced using DMLS and EBM technology are shown i

Secular trends: a ten-year comparison of the amount and type of physical activity and inactivity of random samples of adolescents in the Czech Republic

BACKGROUND: An optimal level of physical activity (PA) in adolescence influences the level of PA in adulthood. Although PA declines with age have been demonstrated repeatedly, few studies have been carried out on secular trends. The present study assessed levels, types and secular trends of PA and sedentary behaviour of a sample of adolescents in the Czech Republic. METHODS: The study comprised two cross-sectional cohorts of adolescents ten years apart. The analysis compared data collected through a week-long monitoring of adolescents' PA in 1998-2000 and 2008-2010. Adolescents wore either Yamax SW-701 or Omron HJ-105 pedometer continuously for 7 days (at least 10 hours per day) excluding sleeping, hygiene and bathing. They also recorded their number of steps per day, the type and duration of PA and sedentary behaviour (in minutes) on record sheets. In total, 902 adolescents (410 boys; 492 girls) aged 14-18 were eligible for analysis. RESULTS: Overweight and obesity in Czech adolescents participating in this study increased from 5.5% (older cohort, 1998-2000) to 10.4% (younger cohort, 2008-2010). There were no inter-cohort significant changes in the total amount of sedentary behaviour in boys. However in girls, on weekdays, there was a significant increase in the total duration of sedentary behaviour of the younger cohort (2008-2010) compared with the older one (1998-2000). Studying and screen time (television and computer) were among the main sedentary behaviours in Czech adolescents. The types of sedentary behaviour also changed: watching TV (1998-2000) was replaced by time spent on computers (2008-2010).The Czech health-related criterion (achieving 11,000 steps per day) decreased only in boys from 68% (1998-2000) to 55% (2008-2010). Across both genders, 55%-75% of Czech adolescents met the health-related criterion of recommended steps per day, however less participants in the younger cohort (2008-2010) met this criterion than in the older cohort (1998-2000) ten years ago. Adolescents' PA levels for the monitored periods of 1998-2000 and 2008-2010 suggest a secular decrease in the weekly number of steps achieved by adolescent boys and girls. CONCLUSION: In the younger cohort (2008-2010), every tenth adolescent was either overweight or obese; roughly twice the rate when compared to the older cohort (1998-2000). Sedentary behaviour seems relatively stable across the two cohorts as the increased time that the younger cohort (2008-2010) spent on computers is compensated with an equally decreased time spent watching TV or studying. Across both cohorts about half to three quarters of the adolescents met the health-related criterion for achieved number of steps. The findings show a secular decrease in PA amongst adolescents. The significant interaction effects (cohort × age; and cohort × gender) that this study found suggested that secular trends in PA differ by age and gender

Exponential growth, high prevalence of SARS-CoV-2, and vaccine effectiveness associated with the Delta variant

SARS-CoV-2 infections were rising during early summer 2021 in many countries associated with the Delta variant. We assessed RT-PCR swab-positivity in the REal-time Assessment of Community Transmission-1 (REACT-1) study in England. We observed sustained exponential growth with average doubling time (June-July 2021) of 25 days driven by complete replacement of Alpha variant by Delta, and by high prevalence at younger less-vaccinated ages. Unvaccinated people were three times more likely than double-vaccinated people to test positive. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination

Genomic assessment of quarantine measures to prevent SARS-CoV-2 importation and transmission

Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness of travellers being required to quarantine for 14-days on return to England in Summer 2020. We identified 4,207 travel-related SARS-CoV-2 cases and their contacts, and identified 827 associated SARS-CoV-2 genomes. Overall, quarantine was associated with a lower rate of contacts, and the impact of quarantine was greatest in the 16–20 age-group. 186 SARS-CoV-2 genomes were sufficiently unique to identify travel-related clusters. Fewer genomically-linked cases were observed for index cases who returned from countries with quarantine requirement compared to countries with no quarantine requirement. This difference was explained by fewer importation events per identified genome for these cases, as opposed to fewer onward contacts per case. Overall, our study demonstrates that a 14-day quarantine period reduces, but does not completely eliminate, the onward transmission of imported cases, mainly by dissuading travel to countries with a quarantine requirement

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

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

Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study

Background The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. Methods We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates. Findings From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Interpretation The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. Funding Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society

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