Radiological imaging of melanoma: a review to guide clinical practice in New Zealand.

The aim of this review is to propose guidelines for initial radiological staging and the follow-up imaging regime for melanoma. This will provide consistency in the access and delivery of quality melanoma care. Radiological imaging plays an important role in assessing the extent of disease, guiding individual treatment and evaluating treatment response. However, there exists limited literature addressing the optimal radiological staging and surveillance imaging regimes for melanoma. The lack of consensus on imaging for melanoma can generate inconsistency in the standard of skin cancer care provided. This review considers the appropriate imaging techniques for both initial melanoma staging and follow-up specifically in the New Zealand clinical environment. The recommendations in this article are based on evaluation of the currently available literature and consensus of feedback from consultation with a working group of New Zealand clinicians involved in providing care to patients with melanoma. The proposed guidelines are considered the standard of care, but regional practice may differ based on access to imaging technology, cost limitations and the clinical experience of healthcare professionals.

An Assessment of the Skeletal Fracture Patterns Resulting from Fatal High (˃3 m) Free Falls.

The injury patterns resulting from fatal high (˃3 m) free falls have previously been documented in clinical and medico-legal contexts; however, details relating specifically to the skeletal blunt force trauma (BFT) have been limited. This study aimed to augment what is known of the skeletal fracture patterns resulting from fatal high free falls. Skeletal trauma was analyzed from full-body postmortem computed tomography scans of 95 individuals who died following a high free fall. Fracture patterns were documented using the five general anatomical regions, axial and appendicular regions, and postcranial unilateral and bilateral regions. Patterns were analyzed in the context of the extrinsic and intrinsic variables that may influence fractures using multiple logistic regression. Fracture patterns involved all aspects of the skeleton, with 98.9% exhibiting polytrauma, and were influenced primarily by the height fallen, manner of death, and landing surface. This improved understanding of fracture patterns will augment anthropological interpretations of the mechanism of BFT in cases of suspected high falls.

An Anthropological Examination of the Types of Skeletal Fractures Resulting from Fatal High (˃3 m) Free Falls.

Fatal falls from heights (˃3 m) often result in blunt force trauma (BFT) to the skeleton. The fracture patterns that result from this BFT mechanism are well understood in forensic anthropology and forensic pathology; however, details of the specific types of fractures that result remain poorly documented. The aim of this study was to provide a detailed examination of the types of fractures that may result from fatal high falls. Fractures were recorded from 95 full-body postmortem computed tomography scans of individuals known to have died from a high fall. Trauma was then analyzed taking into account the extrinsic and intrinsic variables known to influence a fall using multiple logistic regression. A total of 339 types of fractures were classified, of which 16 were significantly associated with this BFT mechanism. Classified fracture types will augment anthropological interpretations of the circumstances of death from BFT in cases of suspected high falls.

Fatal falls involving stairs: an anthropological analysis of skeletal trauma.

The skeletal blunt force trauma resulting from fatal falls involving stairs is complex. There are countless ways an individual may fall when stairs are involved, and thus a variety of ways the skeleton may fracture. Therefore anecdotally, it may be said that there is no specific skeletal trauma characteristic of this fall type. In order to scientifically investigate this anecdotal understanding, this study provides a detailed investigation of the skeletal fracture patterns and morphologies resulting from fatal falls involving stairs. Skeletal trauma was analyzed using the full-body postmortem computed tomography scans of 57 individuals who died from a fall involving stairs. Trauma was examined in the context of the variables that potentially influence how an individual falls (i.e. sex, age, body mass index, number of stairs involved, psychoactive drugs, pre-existing conditions, landing surface and manner of the fall) using logistic regression. Skeletal trauma primarily occurred in the axial skeleton. An analysis of fracture patterns showed the cranial base was less likely to fracture in younger individuals and the cervical vertebrae were more likely to fracture in falls that involved more than half a flight of stairs. A total of 56 fracture morphologies were identified. Of these, diastatic fractures were less likely to occur in older individuals. Findings indicate that there are skeletal fracture patterns and morphologies characteristic of a fatal fall involving stairs.

Skeletal Trauma Resulting From Fatal Low (≤3 m) Free Falls: An Analysis of Fracture Patterns and Morphologies.

The skeletal trauma resulting from fatal low (≤3 m) free falls is poorly researched and understood by forensic practitioners. The aim of this study was to identify the types of skeletal trauma resulting from low falls through investigating fracture patterns and morphologies. Skeletal trauma was analyzed using full-body postmortem computed tomography scans of 145 individuals who died from a low free fall. Trauma was then contextualized to the variables that influence how a person falls using multiple logistic regression. Results showed fracture patterning primarily involved the axial skeleton and that there were a number of patterns significantly associated with the height fallen, pre-existing health conditions, and age. Analysis of fracture morphologies showed 108 possible fracture types, six of which were significantly associated with the height fallen. Understanding the skeletal trauma characteristic of low free falls will further inform anthropological interpretations of trauma in cases where a fall may be considered the possible mechanism.

Multistep Reaction Based De Novo Drug Design: Generating Synthetically Feasible Design Ideas.

We describe a "multistep reaction driven" evolutionary algorithm approach to de novo molecular design. Structures generated by the approach include a proposed synthesis path intended to aid the chemist in assessing the synthetic feasibility of the ideas that are generated. The methodology is independent of how the design ideas are scored, allowing multicriteria drug design to address multiple issues including activity at one or more pharmacological targets, selectivity, physical and ADME properties, and off target liabilities; the methods are compatible with common computer-aided drug discovery "scoring" methodologies such as 2D- and 3D-ligand similarity, docking, desirability functions based on physiochemical properties, and/or predictions from 2D/3D QSAR or machine learning models and combinations thereof to be used to guide design. We have performed experiments to assess the extent to which known drug space can be covered by our approach. Using a library of 88 generic reactions and a database of ∼20 000 reactants, we find that our methods can identify "close" analogs for ∼50% of the known small molecule drugs with molecular weight less than 300. To assess the quality of the in silico generated synthetic pathways, synthesis chemists were asked to rate the viability of synthesis pathways: both "real" and in silico generated. In silico reaction schemes generated by our methods were rated as very plausible with scores similar to known literature synthesis schemes.