The Role of Topology and Topological Changes in the Mechanical Properties of Epithelia

Epithelia, quasi-two-dimensional sheets of cells, are important in molding organs into their correct final shape and size during animal development. Epithelia are active materials that are capable of both generating and reacting to mechanical forces, in a manner that depends on the organization of their cells. Cells in an epithelium may divide, exchange neighbors, or otherwise remodel their packing topology, thereby creating a complex feedback loop between tissue topology and mechanical forces. A full theory of the interplay between mechanical forces and cellular arrangement has not yet been developed. Here we work towards developing such a theory using a vertex model framework, which represents complex biological processes as an active network of cell-cell interactions. We consider several specific problems: We carefully derive the forces acting on vertices, places where three or more cells meet, with special attention to fourfold vertices. This work results in a mathematical proof of the criterion for stabilizing fourfold vertices, which places theoretical limits on the types of tissues that can support stable fourfold vertices. Continuous supra-cellular actomyosin cables are capable of generating large forces to either resist external stress or drive cell motion. These cables have been extensively studied in isolation, but there has been little work on the effect of multiple parallel cables on tissue mechanics. Here we show that these cables prevent cells from becoming elongated or misshapen under large stress anisotropies and can only arise in certain favorable topologies. We develop two measures of the favorability of a disordered packing to forming cables, a quality we call cableness, and show that passive cell flow reduces cableness whereas oriented cell divisions increase cableness. A large anisotropic stress is applied to the Drosophila pupal notum for a few hours during its development, at which time it develops internal apical actomyosin fibers. We present a toy model incorporating these fibers into the network of cell-cell interactions, based on the assumption that these fibers form in order to resist the applied stress, and validate predictions of the model against experimental data. We also summarize the computational methods that are the foundation of our scientific results. We present the design philosophy for our highly modular vertex model, as well as the algorithms we developed to correctly implement T1 transitions. We also discuss our use of automated image analysis techniques in the context of fluorescent imaging, including both morphological operations and machine learning algorithms.PHDPhysicsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/149932/1/maspenc_1.pd

Sphere-Graph: A Compact 3D Topological Map for Robotic Navigation and Segmentation of Complex Environments

Topological maps are a common framework for enabling autonomous robotic navigation. To be effective for robotic exploration the maps must be able to be generated quickly and compact enough to store on lightweight hardware. Here we propose a novel 3D topological map called Sphere-Graph which has adaptive edge lengths, can be quickly generated, and can be used to semantically identify hallways and rooms to produce a compact representation of complex environments. We give examples of the Sphere-Graph representation of large 3D urban and cave environments

Abnormal rib count in scoliosis surgery: impact on the reporting of spinal fusion levels

Purpose Variation in rib numbering has been noted in adolescent idiopathic scoliosis (AIS), but its effect on the reporting of fusion levels has not been studied. We hypothesized that vertebral numbering variations can lead to differing documentation of fusion levels. Methods: We examined the radiographs of 161 surgical AIS patients and 179 control patients without scoliosis. For AIS patients, the operative report of fusion levels was compared to conventional vertebral labeling from the first thoracic level and proceeding caudal. We defined normal counts as 12 thoracic (rib-bearing) and five lumbar (non-rib-bearing) vertebrae. We compared our counts with data from 181 anatomic specimens. Results: Among AIS patients, 22 (14 %) had an abnormal number of ribs and 29 (18 %) had either abnormal rib or lumbar count. In 12/29 (41 %) patients, the operative report differed from conventional labeling by one level, versus 3/132 (2 %) patients with normal numbering (p < 0.001). However, there were no cases seen of wrong fusion levels based on curve pattern. Among controls, 11 % had abnormal rib count (p = 0.41) compared to the rate in AIS. Anatomic specimen data did not differ in abnormal rib count (p = 1.0) or thoracolumbar pattern (p = 0.59). Conclusions: The rate of numerical variations in the thoracolumbar vertebrae of AIS patients is equivalent to that in the general population. When variations in rib count are present, differences in numbering levels can occur. In the treatment of scoliosis, no wrong fusion levels were noted. However, for both scoliosis patients and the general population, we suggest adherence to conventional labeling to enhance clarity

NHS orthodontic services in Wales: orthodontic workforce distribution and primary care commissioned activity in 2021

Objectives 1) To ascertain the volume of primary care orthodontic activity commissioned within Wales and compare this to the 12-year-old population; and 2) To ascertain the orthodontic workforce undertaking NHS orthodontic provision within Wales and their distribution. Methods Information was gathered between September and November 2021 from multiple sources within Wales, including: Freedom of Information requests; Welsh Government statistics; orthodontic professional networks; orthodontic provider websites; health boards (HBs); and directors of primary care/contracting/commissioning. Results The HBs had varying levels of orthodontic need and commissioned activity with a significant amount of cross border activity in South Wales. Overall, it indicated that Wales was only commissioning orthodontic activity to meet 76% of the annual orthodontic need. Overall, 97.9% of commissioned primary care orthodontic activity was being used to provide treatment for 9,500 patients per year. Furthermore, 112 GDC-registered clinicians provide NHS orthodontic care within Wales - 52 orthodontic specialists; 32 orthodontic therapists; 24 DwSIs; and 4 orthodontic trainees (StR 1-3). NHS orthodontic care is provided at 47 sites within Wales - 32 sites in the GDS/Specialist Practice, 6 sites within the CDS and 9 secondary care settings. Conclusions NHS commissioned primary care orthodontic activity within Wales is 76% of the potential orthodontic annual need. Primary care orthodontic services are efficient with 97.9% of commissioned activity being used to provide treatment. In total, 112 GDC-registered clinicians provide NHS orthodontic care across 47 sites within Wales, with 29.5% of clinicians working at multiple sites. The distribution of the orthodontic providers is predominately in areas of high population density, resulting in some rural communities being a significant distance from any orthodontic provider

Endovascular strategy or open repair for ruptured abdominal aortic aneurysm: one-year outcomes from the IMPROVE randomized trial.

AIMS: To report the longer term outcomes following either a strategy of endovascular repair first or open repair of ruptured abdominal aortic aneurysm, which are necessary for both patient and clinical decision-making. METHODS AND RESULTS: This pragmatic multicentre (29 UK and 1 Canada) trial randomized 613 patients with a clinical diagnosis of ruptured aneurysm; 316 to an endovascular first strategy (if aortic morphology is suitable, open repair if not) and 297 to open repair. The principal 1-year outcome was mortality; secondary outcomes were re-interventions, hospital discharge, health-related quality-of-life (QoL) (EQ-5D), costs, Quality-Adjusted-Life-Years (QALYs), and cost-effectiveness [incremental net benefit (INB)]. At 1 year, all-cause mortality was 41.1% for the endovascular strategy group and 45.1% for the open repair group, odds ratio 0.85 [95% confidence interval (CI) 0.62, 1.17], P = 0.325, with similar re-intervention rates in each group. The endovascular strategy group and open repair groups had average total hospital stays of 17 and 26 days, respectively, P < 0.001. Patients surviving rupture had higher average EQ-5D utility scores in the endovascular strategy vs. open repair groups, mean differences 0.087 (95% CI 0.017, 0.158), 0.068 (95% CI -0.004, 0.140) at 3 and 12 months, respectively. There were indications that QALYs were higher and costs lower for the endovascular first strategy, combining to give an INB of £3877 (95% CI £253, £7408) or €4356 (95% CI €284, €8323). CONCLUSION: An endovascular first strategy for management of ruptured aneurysms does not offer a survival benefit over 1 year but offers patients faster discharge with better QoL and is cost-effective. CLINICAL TRIAL REGISTRATION: ISRCTN 48334791

The effect of aortic morphology on peri-operative mortality of ruptured abdominal aortic aneurysm

Aims To investigate whether aneurysm shape and extent, which indicate whether a patient with ruptured abdominal aortic aneurysm (rAAA) is eligible for endovascular repair (EVAR), influence the outcome of both EVAR and open surgical repair. Methods and results The influence of six morphological parameters (maximum aortic diameter, aneurysm neck diameter, length and conicality, proximal neck angle, and maximum common iliac diameter) on mortality and reinterventions within 30 days was investigated in rAAA patients randomized before morphological assessment in the Immediate Management of the Patient with Rupture: Open Versus Endovascular strategies (IMPROVE) trial. Patients with a proven diagnosis of rAAA, who underwent repair and had their admission computerized tomography scan submitted to the core laboratory, were included. Among 458 patients (364 men, mean age 76 years), who had either EVAR (n = 177) or open repair (n = 281) started, there were 155 deaths and 88 re-interventions within 30 days of randomization analysed according to a pre-specified plan. The mean maximum aortic diameter was 8.6 cm. There were no substantial correlations between the six morphological variables. Aneurysm neck length was shorter in those undergoing open repair (vs. EVAR). Aneurysm neck length (mean 23.3, SD 16.1 mm) was inversely associated with mortality for open repair and overall: adjusted OR 0.72 (95% CI 0.57, 0.92) for each 16 mm (SD) increase in length. There were no convincing associations of morphological parameters with reinterventions. Conclusion Short aneurysm necks adversely influence mortality after open repair of rAAA and preclude conventional EVAR. This may help explain why observational studies, but not randomized trials, have shown an early survival benefit for EVAR. Clinical trial registration: ISRCTN 48334791