A Review of Validation Methods for the Intracranial Response of FEHM to Blunt Impacts

The following is a review of the processes currently employed when validating the intracranial response of Finite Element Head Models (FEHM) against blunt impacts. The authors aim to collate existing validation tools, their applications and findings on their effectiveness to aid researchers in the validation of future FEHM and potential efforts in improving procedures. In this vain, publications providing experimental data on the intracranial pressure, relative brain displacement and brain strain responses to impacts in human subjects are surveyed and key data are summarised. This includes cases that have previously been used in FEHM validation and alternatives with similar potential uses. The processes employed to replicate impact conditions and the resulting head motion are reviewed, as are the analytical techniques used to judge the validity of the models. Finally, publications exploring the validation process and factors affecting it are critically discussed. Reviewing FEHM validation in this way highlights the lack of a single best practice, or an obvious solution to create one using the tools currently available. There is clear scope to improve the validation process of FEHM, and the data available to achieve this. By collecting information from existing publications, it is hoped this review can help guide such developments and provide a point of reference for researchers looking to validate or investigate FEHM in the future, enabling them to make informed choices about the simulation of impacts, how they are generated numerically and the factors considered during output assessment, whilst being aware of potential limitations in the process

From hormone replacement therapy to regenerative scaffolds:A review of current and novel primary hypothyroidism therapeutics

Primary hypothyroidism severely impacts the quality of life of patients through a decrease in the production of the thyroid hormones T3 and T4, leading to symptoms affecting cardiovascular, neurological, cognitive, and metabolic function. The incidence rate of primary hypothyroidism is expected to increase in the near future, partially due to increasing survival of patients that have undergone radiotherapy for head and neck cancer, which induces this disease in over half of those treated. The current standard of care encompasses thyroid hormone replacement therapy, traditionally in the form of synthetic T4. However, there is mounting evidence that this is unable to restore thyroid hormone signaling in all tissues due to often persistent symptoms. Additional complications are also present in the form of dosage difficulties, extensive drug interactions and poor patience compliance. The alternative therapeutic approach employed in the past is combination therapy, which consists of administration of both T3 and T4, either synthetic or in the form of desiccated thyroid extract. Here, issues are present regarding the lack of regulation concerning formulation and lack of data regarding safety and efficacy of these treatment methods. Tissue engineering and regenerative medicine have been applied in conjunction with each other to restore function of various tissues. Recently, these techniques have been adapted for thyroid tissue, primarily through the fabrication of regenerative scaffolds. Those currently under investigation are composed of either biopolymers or native decellularized extracellular matrix (dECM) in conjunction with either primary thyrocytes or stem cells which have undergone directed thyroid differentiation. Multiple of these scaffolds have successfully restored an athyroid phenotype in vivo. However, further work is needed until clinical translation can be achieved. This is proposed in the form of exploration and combination of materials used to fabricate these scaffolds, the addition of peptides which can aid restoration of tissue homeostasis and additional in vivo experimentation providing data on safety and efficacy of these implants