Fundamental modes of swimming correspond to fundamental modes of shape: engineering I-, U-, and S-shaped swimmers

Hydrogels have received increased attention due to their biocompatible material properties, adjustable porosity, ease of functionalization, tuneable shape, and Young's moduli. Initial work has recognized the potential that conferring out‐of‐equilibrium properties to these on the microscale holds and envisions a broad range of biomedical applications. Herein, a simple strategy to integrate multiple swimming modes into catalase‐propelled hydrogel bodies, produced via stop‐flow lithography (SFL), is presented and the different dynamics that result from bubble expulsion are studied. It is found that for “Saturn” filaments, with active poles and an inert midpiece, the fundamental swimming modes correspond to the first three fundamental shape modes that can be obtained by buckling elastic filaments, namely, I, U, and S‐shapes

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Topological analysis to enhance the understanding of transdisciplinary engineering

In engineering, the design of a product relies heavily on a design specification; a co-creation of customer and engineer which captures the requirements. Subjectivity is intrinsic to this process. Whilst engineers typically have a high appreciation of the technical aspects of design, the detailed knowledge of environmental and socioeconomic (ESE) implications are often held elsewhere. As such, efficient and effective design is critically dependent on the processes underpinning knowledge transfer. However, the information interfaces between engineering and the requirements of our swiftly changing civilisation remain indirect and suboptimal, and the unintended consequences of design choices are becoming increasingly serious.Transdisciplinary engineering bridges knowledge boundaries interfacing with engineering (e.g. social science). This paper explores whether topology (a branch of pure mathematics) presents an opportunity to analyse the complex interdependency of transdisciplinary engineering information. Topology and geometry describe the structure of objects such as connectedness or the number of holes and have recently provided a suite of powerful and robust tools for analysing high-dimensional data sets. However, the real-world implementation of the term topology is still evolving. Interviews with engineering organisations, revealed that topology is almost exclusively interpreted as ‘Topology Optimisation’ in the context of advanced design and manufacturing. To date, mathematical processes for critically and systematically examining the topology of systems have not been transferred through to the engineering industry. This paper compares how topology is interpreted by the engineering industry, compared to academic literature, and reflects on the opportunities of applying the mathematical theory of topological analysis to transdisciplinary engineering data

Topological analysis to enhance the understanding of transdisciplinary engineering

In engineering, the design of a product relies heavily on a design specification; a co-creation of customer and engineer which captures the requirements. Subjectivity is intrinsic to this process. Whilst engineers typically have a high appreciation of the technical aspects of design, the detailed knowledge of environmental and socioeconomic (ESE) implications are often held elsewhere. As such, efficient and effective design is critically dependent on the processes underpinning knowledge transfer. However, the information interfaces between engineering and the requirements of our swiftly changing civilisation remain indirect and suboptimal, and the unintended consequences of design choices are becoming increasingly serious.Transdisciplinary engineering bridges knowledge boundaries interfacing with engineering (e.g. social science). This paper explores whether topology (a branch of pure mathematics) presents an opportunity to analyse the complex interdependency of transdisciplinary engineering information. Topology and geometry describe the structure of objects such as connectedness or the number of holes and have recently provided a suite of powerful and robust tools for analysing high-dimensional data sets. However, the real-world implementation of the term topology is still evolving. Interviews with engineering organisations, revealed that topology is almost exclusively interpreted as ‘Topology Optimisation’ in the context of advanced design and manufacturing. To date, mathematical processes for critically and systematically examining the topology of systems have not been transferred through to the engineering industry. This paper compares how topology is interpreted by the engineering industry, compared to academic literature, and reflects on the opportunities of applying the mathematical theory of topological analysis to transdisciplinary engineering data

The role of the double-layer potential in regularised stokeslet models of self-propulsion

The method of regularised stokeslets is widely used to model microscale biological propulsion. The method is usually implemented with only the single-layer potential, the double-layer potential being neglected, despite this formulation often not being justified a priori due to nonrigid surface deformation. We describe a meshless approach enabling the inclusion of the double layer which is applied to several Stokes flow problems in which neglect of the double layer is not strictly valid: the drag on a spherical droplet with partial-slip boundary condition, swimming velocity and rate of working of a force-free spherical squirmer, and trajectory, swimmer-generated flow and rate of working of undulatory swimmers of varying slenderness. The resistance problem is solved accurately with modest discretisation on a notebook computer with the inclusion of the double layer ranging from no-slip to free-slip limits; the neglect of the double-layer potential results in up to 24% error, confirming the importance of the double layer in applications such as nanofluidics, in which partial slip may occur. The squirming swimmer problem is also solved for both velocity and rate of working to within a small percent error when the double-layer potential is included, but the error in the rate of working is above 250% when the double layer is neglected. The undulating swimmer problem by contrast produces a very similar value of the velocity and rate of working for both slender and nonslender swimmers, whether or not the double layer is included, which may be due to the deformation’s ‘locally rigid body’ nature, providing empirical evidence that its neglect may be reasonable in many problems of interest. The inclusion of the double layer enables us to confirm robustly that slenderness provides major advantages in efficient motility despite minimal qualitative changes to the flow field and force distribution