Genomic reconstruction of the SARS-CoV-2 epidemic in England.

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021.

How do you implement value-based care methodologies in dentistry with existing dental organizational paradigms?

The U.S. healthcare sector is a paradox - achieving comparatively poor population health outcomes despite outspending the world - and the current paradigm is a dichotomy - pursuing value definition consisting of quality, outcome, and cost, but failing to act in aligned and informed manner. In 2018, U.S. dental spending was $136 billion, accounting for 3.7 percent of total healthcare spending, a relatively nominal amount when considering oral diseases are among the most prevalent and have serious health and economic burdens, greatly reducing quality of life for those affected. Consistent and growing evidence shows that primary care-oriented systems achieve better health outcomes, more health equity, and lower costs; however, to date, there is little means to structuralize the role of oral health and quantify the value provided. To understand the reasons behind the abstract nature of value-based care requires an in-depth understanding of the drivers impeding the transition to a value based oral health system of care. One large clinically integrated network will provide detail of their experience.

Computer Modeling of Clot Retrieval-Circle of Willis.

Endovascular clot retrieval, often referred to as mechanical thrombectomy, has transformed the treatment of patients with ischemic stroke based on an underlying large cerebral vessel occlusion, ranging from the extracranial internal carotid artery (ICA) to the M1 (proximal) segment of the middle cerebral artery (MCA). The aim of this study was to evaluate the effect of a progressive occlusion of the extracranial portion of the ICA on the cerebral blood flow either with a conventional guiding catheter or a balloon-guiding catheter, which enables the operator to completely occlude the parent artery by inflating the balloon around the tip of this type of guiding catheter. We evaluated the impact of flow reduction in the ICA in the setting of ipsilateral MCA occlusion given the different configurations of the circle of Willis (CoW). The computer model of cerebral arteries was based on anatomical works by Rhoton (1) and van der Eecken (2). The interactive experimental results are available on the web at https://gntem3.shinyapps.io/ecrsim. In the setting of left MCA occlusion, compensation from the anterior and posterior communicating artery preserved the flow in the left anterior cerebral artery (ACA) but not the left MCA branches. Under selected CoW configurations, such as classic, missing Acom, or missing A1 segment of the ACA and concurrent right ICA occlusion, there was a progressive decrease of flow in the left ACA to a minimum of 78% when the simulated catheter fully occluded the left ICA. Flow collapsed (<10%) in the left ACA and MCA branches under CoW configurations, such as bilateral fetal PCA. In summary, compensatory flow collapsed under certain clot retrieval scenarios and unusual configurations of CoW.

Combining Information from Crosslinks and Monolinks in the Modeling of Protein Structures.

Monolinks are produced in a chemical crosslinking mass spectrometry experiment and are more abundant than crosslinks. They convey residue exposure information, but so far have not been used in the modeling of protein structures. Here, we present the Monolink Depth Score (MoDS), for assessing structural models based on the depth of monolinked residues, corresponding to their distance to the nearest bulk water. Using simulated and reprocessed experimental data from the Proteomic Identification Database, we compare the performance of MoDS to MNXL, our previously developed score for assessing models based on crosslinking data. Our results show that MoDS can be used to effectively score models based on monolinks, and that a crosslink/monolink combined score (XLMO) leads to overall higher performance. The work strongly supports the use of monolink data in the context of integrative structure determination. We also present XLM-Tools, a program to assist in this effort, available at: https://github.com/Topf-Lab/XLM-Tools.

Investigating mixing and emptying for aqueous liquid content from the stomach using a coupled biomechanical-SPH model.

The stomach is a critical organ for food digestion but it is not well understood how it operates, either when healthy or when dysfunction occurs. Stomach function depends on the timing and amplitude of wall contractions, the fill level and the type of gastric content. Using a coupled biomechanical-Smoothed Particle Hydrodynamics (B-SPH) model, we investigate how gastric discharge is affected by the contraction behaviour of the stomach wall and the viscosity of the content. The results of the model provide new insights into how the content viscosity and the number of compression waves down the length of the stomach affect the mixing within and the discharge rate of the content exiting from the stomach to the duodenum. This investigation shows that the B-SPH model is capable of simulating complicated stomach behaviour. The rate of gastric emptying is found to increase with a smaller period in between contractile waves and to have a nonlinear relationship with content viscosity. Increased resistance to flow into the duodenum is also shown to reduce the rate of emptying. The degree of gastric mixing is found to be insensitive to changes in the period between contractile waves for fluid with a viscosity of water but to be substantially affected by the viscosity of the gastric content.

Surgery for the fractured clavicle: factors predicting nonunion.

BACKGROUND: This study identifies the reasons for failure after plate osteosynthesis of midshaft clavicle fractures, complication rates, and time to radiographic union. METHODS: A retrospective review of 84 consecutive patients who had undergone surgical fixation for a midshaft clavicle fracture was performed. RESULTS: There were 82 patients who were included for analysis and operated on by 11 different surgeons using a mixture of locking (63%) and nonlocking (37%) plates. The rate of osteosynthesis failure was 12.2%. A logistical regression analysis found that failure of osteosynthesis had no relationship to type of plate used (P = .82), gender (P = .42), number of proximal (P = .96) or distal (P = .63) screws to the fracture, or length of plate (P = .42). Smoking was found to be the only risk factor (P = .02) that increased failure rates after midshaft clavicle osteosynthesis. CONCLUSION: Smoking was the only identifiable risk factor to increase failure rates in clavicle osteosynthesis. Preoperative counseling can identify those at increased risk of implant failure and can help improve clinical results by implementing a smoking cessation plan.

Computer modeling of anterior circulation stroke: proof of concept in cerebrovascular occlusion.

BACKGROUND: Current literature emphasizes the role of the Circle of Willis (CoW) in salvaging ischemic brain tissue but not that of leptomeningeal anastomoses (LA). We developed a computational model of the cerebral circulation to (1) evaluate the roles of the CoW and LA in restoring flow to the superficial compartment of the middle cerebral artery (MCA) territory and (2) estimate the size of the LA required to maintain flow above the critical ischemic threshold (>30% of baseline) under simulated occlusion. METHODS: Cerebral vasculature was modeled as a network of junctions connected by cylindrical pipes. The experiments included occlusion of successive distal branches of the intracranial arteries while the diameters of LA were varied. RESULTS: The model showed that the region of reduced flow became progressively smaller as the site of occlusion was moved from the large proximal to the smaller distal arteries. There was no improvement in flow in the MCA territory when the diameters of the inter-territorial LA were varied from 0.0625 to 0.5 mm while keeping the intra-territorial LA constant. By contrast, the diameter of the inter-territorial LA needed to be >1.0 mm in order to provide adequate (>30%) flow to selected arteries in the occluded MCA territory. CONCLUSION: The CoW and inter-territorial LA together play important supportive roles in intracranial artery occlusion. Computational modeling provides the ability to experimentally investigate the effect of arterial occlusion on CoW and LA function.

Challenges in computational modelling of food breakdown and flavour release.

A dynamic, three dimensional (3D) computational model that predicts the breakdown of food and the release of tastants and aromas could enhance the understanding of how food is perceived during consumption. This model could also shorten the development process of new foods because many virtual foods could be assessed, and discarded if unsuitable, before any physical prototyping is required. The construction and testing of a complete 3D model of mastication presents many challenges including an accurate representation of: the anatomical movements of the oral cavity (including the teeth, tongue, cheeks and palates), the breakdown behaviour of the food, the interactions between comminuted food and saliva as the bolus is formed, the release and transport of taste and aromas and how these physical and chemical processes are perceived by a person. These challenges are discussed in reference to previous experimental and simulation work and using results of new applications of a coupled biomechanical-smoothed particle hydrodynamics (B-SPH) model. The B-SPH model is demonstrated to simulate several complicated aspects of mastication including: (1) the sensitivity of particle size to changes in the movements of the jaw and tongue; (2) large strain behaviour of food due to softening by heating; (3) interactions between solid and liquid food components; (3) the release of tastants into the saliva; and (4) the transport of tastants to the taste buds. These applications show the possibilities of a model to viably simulate mastication, but highlight the many modelling and experimental challenges that remain.

Carotid artery anatomy and geometry as risk factors for carotid atherosclerotic disease.

BACKGROUND AND PURPOSE: Traditional vascular risk factors do not completely explain the asymmetry, racial, and sex differences in carotid artery disease. Carotid anatomy and geometry may play a role in the pathogenesis of internal carotid artery (ICA) stenosis, but their effects are unknown. We hypothesized that carotid artery anatomy and geometry would be independently associated with ICA stenosis. METHOD: This is a retrospective study of patients with CT angiography at Monash Medical Centre, 2006 to 2007. Carotid arteries were segmented using semiautomated methods to estimate measures of carotid anatomy and geometry. Measurements of carotid artery geometry were performed according to the recent article by Thomas and colleagues. ICA stenosis was dichotomized as <30% or ≥ 30% stenosis. Cluster logistic regression was used to examine the associations of anatomy and geometry with stenosis accounting for the paired arteries within subjects, adjusting for age, sex, and vascular risk factors. RESULTS: Mean age of the sample (n=178) was 68.4 years (SD, 14 years). The following were independently associated with ICA stenosis: ICA radius at the bifurcation (OR, 0.20; 95% CI, 0.14-0.29), ICA angle (OR, 1.05 per degree increment; 95% CI, 1.04-1.07), age (OR, 1.05 per year increment; 95% CI, 1.03-1.07), male sex (OR, 1.72; 95% CI, 1.08-2.8), and ever-smoker (OR, 1.85; 95% CI, 1.15-2.96). CONCLUSIONS: Carotid anatomy and geometry may enhance the risk of stenosis independent of traditional vascular risk factors and may be of help in very early identification of patients at high risk of developing carotid artery atherosclerosis for aggressive intervention.

Does the principle of minimum work apply at the carotid bifurcation: a retrospective cohort study.

BACKGROUND: There is recent interest in the role of carotid bifurcation anatomy, geometry and hemodynamic factors in the pathogenesis of carotid artery atherosclerosis. Certain anatomical and geometric configurations at the carotid bifurcation have been linked to disturbed flow. It has been proposed that vascular dimensions are selected to minimize energy required to maintain blood flow, and that this occurs when an exponent of 3 relates the radii of parent and daughter arteries. We evaluate whether the dimensions of bifurcation of the extracranial carotid artery follow this principle of minimum work. METHODS: This study involved subjects who had computed tomographic angiography (CTA) at our institution between 2006 and 2007. Radii of the common, internal and external carotid arteries were determined. The exponent was determined for individual bifurcations using numerical methods and for the sample using nonlinear regression. RESULTS: Mean age for 45 participants was 56.9 ± 16.5 years with 26 males. Prevalence of vascular risk factors was: hypertension--48%, smoking--23%, diabetes--16.7%, hyperlipidemia--51%, ischemic heart disease--18.7%.The value of the exponent ranged from 1.3 to 1.6, depending on estimation methodology. CONCLUSIONS: The principle of minimum work (defined by an exponent of 3) may not apply at the carotid bifurcation. Additional factors may play a role in the relationship between the radii of the parent and daughter vessels.