GMP-grade human neural progenitors delivered subretinally protect vision in rat model of retinal degeneration and survive in minipigs.

BACKGROUND: Stem cell products are increasingly entering early stage clinical trials for treating retinal degeneration. The field is learning from experience about comparability of cells proposed for preclinical and clinical use. Without this, preclinical data supporting translation to a clinical study might not adequately reflect the performance of subsequent clinical-grade cells in patients. METHODS: Research-grade human neural progenitor cells (hNPC) and clinical-grade hNPC (termed CNS10-NPC) were injected into the subretinal space of the Royal College of Surgeons (RCS) rat, a rodent model of retinal degeneration such as retinitis pigmentosa. An investigational new drug (IND)-enabling study with CNS10-NPC was performed in the same rodent model. Finally, surgical methodology for subretinal cell delivery in the clinic was optimized in a large animal model with Yucatan minipigs. RESULTS: Both research-grade hNPC and clinical-grade hNPC can survive and provide functional and morphological protection in a dose-dependent fashion in RCS rats and the optimal cell dose was defined and used in IND-enabling studies. Grafted CNS10-NPC migrated from the injection site without differentiation into retinal cell phenotypes. Additionally, CNS10-NPC showed long-term survival, safety and efficacy in a good laboratory practice (GLP) toxicity and tumorigenicity study, with no observed cell overgrowth even at the maximum deliverable dose. Finally, using a large animal model with the Yucatan minipig, which has an eye size comparable to the human, we optimized the surgical methodology for subretinal cell delivery in the clinic. CONCLUSIONS: These extensive studies supported an approved IND and the translation of CNS10-NPC to an ongoing Phase 1/2a clinical trial (NCT04284293) for the treatment of retinitis pigmentosa.

Impact of Nonadherence to NCCN Adjuvant Radiotherapy Initiation Guidelines in Head and Neck Squamous Cell Carcinoma in an Underserved Urban Population.

BACKGROUND: Nonadherence to NCCN Guidelines during time from surgery to postoperative radiotherapy (S-PORT) can alter survival outcomes in head and neck squamous cell carcinomna (HNSCC). There is a need to validate this impact in an underserved urban population and to understand risk factors and reasons for delay. We sought to investigate the impact of delayed PORT with outcomes of overall survival (OS) in HNSCC, to analyze predictive factors of delayed PORT, and to identify reasons for delay. METHODS: We conducted a retrospective cohort study in an urban, community-based academic center. A total of 184 patients with primary HNSCC were identified through the Montefiore Medical Center cancer registry who had been treated between March 1, 2005, and March 8, 2017, and met the inclusion and exclusion criteria. The primary exposure was S-PORT. OS, recurrence, and risk factors and reasons for treatment delay were the main outcomes and measures. RESULTS: Among 184 patients with HNSCC treated with PORT, the median S-PORT was 48.5 days (interquartile range, 41-67 days). The S-PORT threshold that optimally differentiated worse OS outcomes was >50 days (46.7% of our cohort; n=86). Independent of other relevant factors, patients with HNSCC and S-PORT >50 days had worse OS (hazard ratio, 2.30; 95% CI, 1.34-3.95) and greater recurrence (odds ratio, 3.51; 95% CI, 1.31-9.39). Predictors of delayed S-PORT included being underweight or obese, prolonged postoperative length of stay, and age >70 years. The most frequent reasons for PORT delay were complications related to surgery (22.09%), unrelated medical comorbidities (18.60%), and nonadherence/missed appointments (6.98%). CONCLUSIONS: Delayed PORT beyond 50 days after surgery was associated with decreased OS and greater recurrence. Identification of predictive factors and reasons for treatment delay helps to target at-risk patients and facilitates interventions in underserved populations.

Complement C3 Inhibitor Pegcetacoplan for Geographic Atrophy Secondary to Age-Related Macular Degeneration: A Randomized Phase 2 Trial.

PURPOSE: Geographic atrophy (GA), a late stage of age-related macular degeneration (AMD), is a major cause of blindness. Even while central visual acuity remains relatively well preserved, GA often causes considerable compromise of visual function and quality of life. No treatment currently exists. We evaluated the safety and efficacy of pegcetacoplan, a complement C3 inhibitor, for treatment of GA. DESIGN: Prospective, multicenter, randomized, sham-controlled phase 2 study. PARTICIPANTS: Two hundred forty-six patients with GA. METHODS: Patients with GA were assigned randomly in a 2:2:1:1 ratio to receive intravitreal injections of 15 mg pegcetacoplan monthly or every other month (EOM) or sham intravitreal injections monthly or EOM for 12 months with follow-up at months 15 and 18. Area and growth of GA were measured using fundus autofluorescence imaging. MAIN OUTCOME MEASURES: The primary efficacy end point was mean change in square root GA lesion area from baseline to month 12. Secondary outcome measures included mean change from baseline in GA lesion area without the square root transformation, distance of GA lesion from the fovea, best-corrected visual acuity (BCVA), low-luminance BCVA, and low-luminance visual acuity deficit. The primary safety end point was the number and severity of treatment-emergent adverse events. RESULTS: In patients receiving pegcetacoplan monthly or EOM, the GA growth rate was reduced by 29% (95% confidence interval [CI], 9-49; P = 0.008) and 20% (95% CI, 0-40; P = 0.067) compared with the sham treatment group. Post hoc analysis showed that the effect was greater in the second 6 months of treatment, with observed reductions of 45% (P = 0.0004) and 33% (P = 0.009) for pegcetacoplan monthly and EOM, respectively. Two cases of culture-positive endophthalmitis and 1 case of culture-negative endophthalmitis occurred in the pegcetacoplan monthly group. New-onset investigator-determined exudative AMD was reported more frequently in pegcetacoplan-treated eyes (18/86 eyes [20.9%] and 7/79 eyes [8.9%] in monthly and EOM groups, respectively) than in sham-treated eyes (1/81 eyes [1.2%]). CONCLUSIONS: Local C3 inhibition with pegcetacoplan resulted in statistically significant reductions in the growth of GA compared with sham treatment. Phase 3 studies will define the efficacy and safety profile further.

The Valuation of Rhytidectomy in Different Economic Markets.

This study demonstrates that the trend of how rhytidectomy is valued can be used to determine not only the pricing of this good but also how receptive developing economic markets are to the export of cosmetic facial plastic surgery. This study seeks to analyze and compare the value of rhytidectomy in an established market and an emerging market. A cross-sectional survey was administered through public online forums to 162 casual observers in the United States and 74 casual observers in India. Participants were shown pre- and postoperative photos of 10 patients who underwent cosmetic rhinoplasty and 2 patients who did not undergo surgery. Observers were asked to quantify the perceived change in attractiveness, change in age, and willingness to pay (WTP). There is a similar nonlinear trend between WTP and change in attractiveness in both the United States and India. Baseline values of rhytidectomy in the United States and India have a similar ratio of 2.122 compared with the ratio between both countries in the 2018 Big Mac index. The comparison of the trend in WTP in the United States and India shows that facial cosmetic surgery functions as a luxury good in both an established market and an emerging market. Our model successfully approximates the relationship between each country's purchasing power parity. Since the market behavior of rhytidectomy can be predicted based on purchasing power parity, there may be an untapped market for facial cosmetic surgery among populations with growing economies.

Accelerated detection of viral particles by combining AC electric field effects and micro-Raman spectroscopy.

A detection method that combines electric field-assisted virus capture on antibody-decorated surfaces with the "fingerprinting" capabilities of micro-Raman spectroscopy is demonstrated for the case of M13 virus in water. The proof-of-principle surface mapping of model bioparticles (protein coated polystyrene spheres) captured by an AC electric field between planar microelectrodes is presented with a methodology for analyzing the resulting spectra by comparing relative peak intensities. The same principle is applied to dielectrophoretically captured M13 phage particles whose presence is indirectly confirmed with micro-Raman spectroscopy using NeutrAvidin-Cy3 as a labeling molecule. It is concluded that the combination of electrokinetically driven virus sampling and micro-Raman based signal transduction provides a promising approach for time-efficient and in situ detection of viruses.

Augmented Virtual Examination for Cosmetic and Functional Rhinoplasty.

Background: Few studies have critically evaluated the quality of data obtained during telemedical evaluations of patients with nasal complaints. Objective: To compare the quality of data provided by remote endoscopic and external nasal examination with those by in-person evaluations for rhinoplasty and functional nasal surgery, measured by detectability of anatomic features, and to assess associated patient experience measured by reported ease, discomfort, and likelihood of peer recommendation. Materials and Methods: Twenty healthy subjects performed a nasal self-examination using an endoscope and webcam under remote videoconferencing service (VCS) guidance. They subsequently underwent in-person examination and were surveyed about their experience. Inter-rater reliability was calculated using kappa coefficients. Detectability of anatomic features by in-person versus virtual examination was compared using Wilcoxon and chi-square tests. Results: Median subject age was 27.5 years (range 23-77). Kappa coefficients were 0.78 for in-person and 0.66 for virtual evaluations. Only the internal nasal valve and inferior turbinate were better visualized in person. There were no differences between detectability of external features on in-person versus virtual examinations. Subjects' average likelihood of recommending this technology (1-10) was 8.65 (SD 1.4). Conclusions: Intranasal examination by physician-guided remote endoscopy and webcam-based facial analysis demonstrate nasal anatomy comparable with in-person evaluation and anterior rhinoscopy.

Outcomes of Gender-Affirming Voice and Communication Modification Training for Non-binary Individuals: A Case Series.

OBJECTIVES: There is currently no research reporting solely on outcomes of voice and communication modification training (VCMT) in individuals who identify as non-binary and genderqueer (NBGQ) in the English literature. This study aimed to describe the objective and subjective impact of VCMT on the voice of NBGQ individuals undergoing a 12-week gender-affirming VCMT program. METHODS: A retrospective consecutive case series of NBGQ individuals enrolled in a VCMT program was performed. Demographics, Transgender Self-Evaluation Questionnaire (TSEQ), fundamental frequency (F0), and frequency range were collected before and after the program. RESULTS: Four NBGQ individuals enrolled between January 2019 and June 2021; the mean age was 27.0 years. While all four participants represented in this case series showed improvement in at least one of their initial goals, only one improved both their F0 and TSEQ scores; the other three participants had mixed results. CONCLUSION: NBGQ individuals experienced improvements in self-reported outcomes and changes in acoustic measures after completing VCMT in our case series. Individuals experienced significant improvement in subjective outcomes despite small changes in acoustic measures, and vice versa. More research is needed to better understand the voice and communication needs of NBGQ individuals, along with their outcomes with VCMT. LEVEL OF EVIDENCE: Level 4.

Differential effects of exposure to toxic or nontoxic mold spores on brain inflammation and Morris water maze performance.

People who live or work in moldy buildings often complain of "brain fog" that interferes with cognitive performance. Until recently, there was no published research on the effects of controlled exposure to mold stimuli on cognitive function or an obvious mechanism of action, fueling controversy over these claims. The constellation of health problems reported by mold-exposed individuals (respiratory issues, fatigue, pain, anxiety, depression, and cognitive deficits) correspond to those caused by innate immune activation following exposure to bacterial or viral stimuli. To determine if mold-induced innate immune activation might cause cognitive issues, we quantified the effects of both toxic and nontoxic mold on brain immune activation and spatial memory in the Morris water maze. We intranasally administered either 1) intact, toxic Stachybotrys chartarum spores; 2) ethanol-extracted, nontoxic Stachybotrys chartarum spores; or 3) control saline vehicle to mice. Inhalation of nontoxic spores caused significant deficits in the test of long-term memory of platform location, while not affecting short-term memory. Inhalation of toxic spores increased motivation to reach the platform. Interestingly, in both groups of mold-exposed males, numbers of interleukin-1ß-immunoreactive cells in many areas of the hippocampus significantly correlated with latency to find the platform, path length, and swimming speed during training, but not during testing for long-term memory. These data add to our prior evidence that mold inhalation can interfere with cognitive processing in different ways depending on the task, and that brain inflammation is significantly correlated with changes in behavior.

Conceptualizing a tool to optimize therapy based on dynamic heterogeneity.

Complex biological systems often display a randomness paralleled in processes studied in fundamental physics. This simple stochasticity emerges owing to the complexity of the system and underlies a fundamental aspect of biology called phenotypic stochasticity. Ongoing stochastic fluctuations in phenotype at the single-unit level can contribute to two emergent population phenotypes. Phenotypic stochasticity not only generates heterogeneity within a cell population, but also allows reversible transitions back and forth between multiple states. This phenotypic interconversion tends to restore a population to a previous composition after that population has been depleted of specific members. We call this tendency homeostatic heterogeneity. These concepts of dynamic heterogeneity can be applied to populations composed of molecules, cells, individuals, etc. Here we discuss the concept that phenotypic stochasticity both underlies the generation of heterogeneity within a cell population and can be used to control population composition, contributing, in particular, to both the ongoing emergence of drug resistance and an opportunity for depleting drug-resistant cells. Using notions of both 'large' and 'small' numbers of biomolecular components, we rationalize our use of Markov processes to model the generation and eradication of drug-resistant cells. Using these insights, we have developed a graphical tool, called a metronomogram, that we propose will allow us to optimize dosing frequencies and total course durations for clinical benefit.

Generalized principles of stochasticity can be used to control dynamic heterogeneity.

It is increasingly appreciated that phenotypic stochasticity plays fundamental roles in biological systems at the cellular level and that a variety of mechanisms generates phenotypic interconversion over a broad range of time scales. The ensuing dynamic heterogeneity can be used to understand biological and clinical processes involving diverse phenotypes in different cell populations. The same principles can be applied, not only to populations composed of cells, but also to populations composed of molecules, tissues, and multicellular organisms. Stochastic units generating dynamic heterogeneity can be integrated across various length scales. We propose that a graphical tool we have developed, called a metronomogram, will allow us to identify factors that suitably influence the restoration of homeostatic heterogeneity so as to modulate the consequences of dynamic heterogeneity for desired outcomes.

Pegcetacoplan treatment for geographic atrophy due to age-related macular degeneration: a plain language summary of the FILLY study.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of a publication about the FILLY study, which was published in Ophthalmology in 2020. The FILLY study looked at an investigational medicine called pegcetacoplan as a possible treatment for geographic atrophy. Geographic atrophy, also known as GA, is the late stage of an eye disease called dry age-related macular degeneration, also known as dry AMD. In people with GA, lesions form on a part of the back of the eye called the retina. GA lesions are patches of thin retina. Growth of GA lesions ultimately causes blindness, which cannot be reversed. There is currently no approved treatment for GA. Pegcetacoplan, also called APL-2, could be a possible treatment for GA. Pegcetacoplan is an investigational medicine, which means it has not yet been approved. It is currently being studied in clinical studies to see how well it works. WHAT HAPPENED IN THE FILLY STUDY?: The FILLY study included participants with GA and tested how well pegcetacoplan worked compared to a sham injection (an injection that looks like the study treatment but does not have any medicine in it). The study also looked at how safe it was in adults with GA. WHAT WERE THE RESULTS?: The main questions the researchers wanted to answer were: Did pegcetacoplan slow the growth of the study participants' GA lesions? ○Yes. Overall, the researchers found that pegcetacoplan did slow the growth of the study participants' GA lesions. Did pegcetacoplan change the participants' vision? ○No. Overall, the researchers found that pegcetacoplan did not change the participants' vision. What medical problems happened after the participants received pegcetacoplan? ○The researchers kept track of any serious medical problems that happened during the study, also called serious adverse events. They also kept track of other medical problems that happened, or got worse, only at some point after the participants received the study treatment. These are called treatment emergent adverse events, also known as TEAEs. The serious adverse events and TEAEs that the participants had are described later in this summary. WHAT DO THE RESULTS OF THE STUDY MEAN?: Overall, results from this study showed that participants who received pegcetacoplan had slower growth of GA lesions than participants who received the sham injection. After the participants had stopped receiving pegcetacaoplan, the effect of the treatment seemed to be reduced. Pegcetacoplan did not change how well the participants could see during their vision tests in this trial. ClinicalTrials.gov NCT number: NCT02503332.

What's in a Name? A Cost-Effectiveness Analysis of the Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features' Nomenclature Revision.

Background: The noninvasive subtype of encapsulated follicular variant of papillary thyroid carcinoma (eFVPTC) has been reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in 2016 to reflect the indolent behavior and favorable prognosis of this type of tumor. This terminology change has also de-escalated its management approach from cancer treatment to a more conservative treatment strategy befitting a benign thyroid neoplasm. Objective: To characterize the reduced health care costs and improved quality of life (QOL) from management of NIFTP as a nonmalignant tumor compared with the previous management as eFVPTC. Methods: A cost-effectiveness analysis was performed by creating Markov models to simulate two management strategies for NIFTP: (i) de-escalated management of the tumor as NIFTP involving lobectomy with reduced follow-up, (ii) management of the tumor as eFVPTC involving completion thyroidectomy/radioactive iodine ablation for some patients, and follow-up recommended for carcinoma. The model was simulated for 5 and 20 years following diagnosis of NIFTP. Aggregate costs and quality-life years were measured. One-way sensitivity analysis was performed for all variables. Results: Over a five-year simulation period, de-escalated management of NIFTP had a total cost of $12,380.99 per patient while the more aggressive management of the tumor as eFVPTC had a total cost of $16,264.03 per patient (saving $3883.05 over five years). Management of NIFTP provided 5.00 quality-adjusted life years, whereas management as eFVPTC provided 4.97 quality-adjusted life years. Sensitivity analyses showed that management of NIFTP always resulted in lower costs and greater quality-adjusted life years (QALYs) over the sensitivity ranges for individual variables. De-escalated management for NIFTP is expected to produce ∼$6-42 million in cost savings over a five-year period for these patients, and incremental 54-370 QALYs of increased utility in the United States. Conclusion: The degree of cost savings and improved patient utility of de-escalated NIFTP management compared with traditional management was estimated to be $3883.05 and 0.03 QALYs per patient. We demonstrate that these findings persisted in sensitivity analysis to account for variability in recurrence rate, surveillance approaches, and other model inputs. These findings allow for greater understanding of the economic and QOL impact of the NIFTP reclassification.

Anomalous spatial redistribution of competing bacteria under starvation conditions.

Bacterial cells evolved under prolonged stress often have a growth advantage in stationary phase (GASP); we expect GASP cells to maintain a proliferative state and dominate wild-type cells during starvation, especially when nutrients are limited and the medium has been conditioned. However, when we compete GASP mutants against wild-type cells in a chain of microfluidic microhabitat patches (MHPs) with alternating nutrient-rich and nutrient-limited regions, we observe the reverse effect: wild-type cells achieve maximum relative density under nutrient-limited conditions, while GASP cells dominate nutrient-rich regions. We explain this surprising observation in terms of ideal free distributions, where we show that wild-type cells maximize their fitness at high cell density by redistributing themselves to sparsely populated MHPs. At the microscopic level, we describe how biofilm formation also contributes to the population redistribution. We conclude by discussing the implications of these results for social interactions of more complex organisms.

The Goldilocks principle and antibiotic resistance in bacteria.

We have designed and fabricated a microecology to mimic a naturally occurring bacterial culture, which includes the stress gradient, metapopulation, and cellular motility. In this microecology, we show that it is possible to fix the resistance to the mutagenic antibiotic Ciprofloxacin in wild-type Escherichia coli within 10 h. We found the evolution of resistance is further accelerated in microecology if bacteria have already acquired the phenotype of growth advantage at the stationary phase (GASP).

Computation of mutual fitness by competing bacteria.

Competing populations in shared spaces with nonrenewable resources do not necessarily wage a battle for dominance at the cost of extinction of the less-fit strain if there are fitness advantages to the presence of the other strain. We report on the use of nanofabricated habitat landscapes to study the population dynamics of competing wild type and a growth advantage in stationary phase (GASP) mutant strains of Escherichia coli in a sealed and heterogeneous nutrient environment. Although GASP mutants are competitors with wild-type bacteria, we find that the 2 strains cooperate to maximize fitness (long-term total productivity) via spatial segregation: despite their very close genomic kinship, wild-type populations associate with wild-type populations and GASP populations with GASP populations. Thus, wild-type and GASP strains avoid each other locally, yet fitness is enhanced for both strains globally. This computation of fitness enhancement emerges from the local interaction among cells but maximizes global densities. At present we do not understand how fluctuations in both spatial and temporal dimensions lead to the emergent computation and how multilevel aggregates produce this collective adaptation.

An introduction to micro-ecology patches.

Bacterial systems offer excellent tests of how well the general theoretical predictions of ecology dynamics do or do not in fact conform to reality. We believe that the basic rules that govern the cohabitation of competing species for limited resources are the same from bacteria to man, we just don't know the rules, and that fundamental studies of the games bacteria play will give fundamental insight into the vastly more complex systems we hope to attack later. In this tutorial review we discuss how simplified micro-ecologies constructed using tools of micro and nanofabrication techniques offer some idea of how physical principles and analysis can address the issue of complex ecology dynamics.

Tracheotomy Outcomes in 64 Ventilated COVID-19 Patients at a High-Volume Center in Bronx, NY.

OBJECTIVES/HYPOTHESIS: The COVID-19 pandemic has resulted in a dramatic increase in the number of patients requiring prolonged mechanical ventilation. Few studies have reported COVID-19 specific tracheotomy outcomes, and the optimal timing and patient selection criteria for tracheotomy remains undetermined. We delineate our outcomes for tracheotomies performed on COVID-19 patients during the peak of the pandemic at a major epicenter in the United States. METHODS: This is a retrospective observational cohort study. Mortality, ventilation liberation rate, complication rate, and decannulation rate were analyzed. RESULTS: Sixty-four patients with COVID-19 underwent tracheotomy between April 1, 2020 and May 19, 2020 at two tertiary care hospitals in Bronx, New York. The average duration of intubation prior to tracheotomy was 20 days ((interquartile range [IQR] 16.5-26.0). The mortality rate was 33% (n = 21), the ventilation liberation rate was 47% (n = 30), the decannulation rate was 28% (n = 18), and the complication rate was 19% (n = 12). Tracheotomies performed by Otolaryngology were associated with significantly improved survival (P < .05) with 60% of patients alive at the conclusion of the study compared to 9%, 12%, and 19% of patients undergoing tracheotomy performed by Critical Care, General Surgery, and Pulmonology, respectively. CONCLUSIONS: So far, this is the second largest study describing tracheotomy outcomes in COVID-19 patients in the United States. Our early outcomes demonstrate successful ventilation liberation and decannulation in COVID-19 patients. Further inquiry is necessary to determine the optimal timing and identification of patient risk factors predictive of improved survival in COVID-19 patients undergoing tracheotomy. LEVEL OF EVIDENCE: 4-retrospective cohort study Laryngoscope, 131:E1797-E1804, 2021.

Impact of COVID-19 on Endoscopy Training: Perspectives from a Global Survey of Program Directors and Endoscopy Trainers.

BACKGROUND/AIMS: The coronavirus disease of 2019 (COVID-19) pandemic has impacted the training of medical trainees internationally. The aim of this study was to assess the global impact of COVID-19 on endoscopy training from the perspective of endoscopy trainers and to identify strategies implemented to mitigate the impact on trainee education. METHODS: Teaching faculty of gastroenterology (GI) training programs globally were invited to complete a 36-question web-based survey to report the characteristics of their training programs and the impact of COVID-19 on various aspects of endoscopy training, including what factors decisions were based on. RESULTS: The survey response rate was 52.6% (305 out of 580 individuals); 92.8% reported a negative impact on endoscopy training, with suspension of elective procedures (77.1%) being the most detrimental factor. Geographic variations were noted, with European programs reporting the lowest percentage of trainee participation in procedures. A higher proportion of trainees in the Americas were allowed to continue performing procedures, and trainers from the Americas reported receiving the greatest support for endoscopy teaching. CONCLUSION: This study demonstrated that the COVID-19 pandemic has had a significant negative impact on GI endoscopy training internationally, as reported by endoscopy trainers. Focus-optimizing endoscopy training and assessment of competencies are necessary to ensure adequate endoscopy training.

A microfluidic device for continuous cancer cell culture and passage with hydrodynamic forces.

We demonstrate a novel and robust microfluidic chip with combined functions of continuous culture and output of PC-3 prostate cancer cells. With digital controls, polydimethylsiloxane (PDMS) flexible diaphragms are able to apply hydrodynamic shear forces on cultures, detaching a fraction of attached cancer cells from the surface for output while leaving others for reuse in subsequent cultures. The fractions of detached cells and remaining cells can be precisely controlled. The system has not only the advantages of small size, high cell culture efficiency, and digital control, but also of simple fabrication at low cost, easy operation and robust performance. The chip performs 9 passages during 30 days of continuous culture and shows promise as a durable design suitable for long-term cell output.

Collective escape of chemotactic swimmers through microscopic ratchets.

We report on the emergence of spontaneously forming migrating bands of E. coli bacteria inside a microchannel containing microstructured ratchets. We show that a collection of bacteria is able to migrate against the funnel-shaped barriers by creating and maintaining a chemoattractant gradient. A transition between pure rectification and chemotaxis-driven collective motion is predicted from theoretical models, and is observed experimentally as the initial inoculation density is varied.