Delayed self-regulation and time-dependent chemical drive leads to novel states in epigenetic landscapes.

The epigenetic pathway of a cell as it differentiates from a stem cell state to a mature lineage-committed one has been historically understood in terms of Waddington's landscape, consisting of hills and valleys. The smooth top and valley-strewn bottom of the hill represent their undifferentiated and differentiated states, respectively. Although mathematical ideas rooted in nonlinear dynamics and bifurcation theory have been used to quantify this picture, the importance of time delays arising from multistep chemical reactions or cellular shape transformations have been ignored so far. We argue that this feature is crucial in understanding cell differentiation and explore the role of time delay in a model of a single-gene regulatory circuit. We show that the interplay of time-dependent drive and delay introduces a new regime where the system shows sustained oscillations between the two admissible steady states. We interpret these results in the light of recent perplexing experiments on inducing the pluripotent state in mouse somatic cells. We also comment on how such an oscillatory state can provide a framework for understanding more general feedback circuits in cell development.

An approach to designing viable and sustainable telehealth services.

Telehealth can be viewed as an intervention in the established and stable clinician-patient system with outcomes that are not always predictable. The success of a new telehealth service depends far more on changing the clinicians and patient's expectations and patterns of behaviour than on technology. Success in telehealth projects is critically dependent on understanding how the new telehealth offering changes the distinct value proposition for each of the parties - clinicians, patients and administrators. As with any intervention, design is the key to ensuring more predictable outcomes. An approach to the design of telehealth services is described that takes a holistic view of telehealth by acknowledging the multiple and interdependent dimensions of telehealth services (clinical process change, clinical risk and governance, adoption and change management, clinician and patient experience, operational sustainability, support, and least of all, technology). The approach draws on current themes in design including 'design thinking' and service design.

The comminuted midshaft clavicle fracture: a biomechanical evaluation of plating methods.

BACKGROUND: The optimal plate location and fixation method for midshaft fractures of the clavicle remains undetermined. The objective of this study was to develop a realistic biomechanical model with which to compare superior with inferior-medial plate placement, and the failure resistance of locked and against non-locked constructs. METHODS: We estimated implant loads for operated patients in early rehabilitation utilising 3-D mathematical model of the shoulder. During simulation of upper limb motion associated with eating, the fracture opened in an inferior and frontal direction. The peak X, Y, and Z loads from the simulation were reproduced using a materials testing machine. A one centimetre transverse osteectomy was created at the midshaft of forty composite clavicles. Each specimen was then fixed with either (1) non-locked superior plating (n=10), (2) locked superior plating (n=10), (3) non-locked inferior-medial plating (n=10), or (4) locked inferior-medial plating (n=10). Specimens were loaded at 20 N/s in four-point bending for 50 cycles to the peak X, Y, Z moment obtained from the computational model (-3.50, 2.46, and -1.00 N m), then loaded to failure at 20 N/s. FINDINGS: Inferior-medial unlocked plates were significantly stiffer than superior locked plates (P=0.046). INTERPRETATION: Operative fixation of midshaft clavicle fractures is controversial, though becoming more widely accepted. Few biomechanical data are available to assist surgical decision-making. Inferior plates may be better equipped to resist the in vivo loads experienced by the clavicle during early rehabilitation after internal fixation, particularly during the shoulder flexion motions associated with eating.

Removal of the well-fixed hip resurfacing acetabular component: a simple, bone preserving technique.

Removal of the acetabular component of a hip resurfacing prosthesis is occasionally necessary for infection, malposition, metal sensitivity, wear, or as a necessary part of a femoral revision. Extraction of a well-fixed acetabular component can be technically demanding as it is often extremely well integrated into host bone and can result in catastrophic bone loss or fracture. We present an undescribed, simple technique that enables use of the Explant system (Zimmer, Warsaw, Ind) to remove the component with minimal bone loss and reduce fracture risk. Bone stock is therefore preserved for subsequent cup reimplantation.