A survey of case studies on the use of forensic three-dimensional printing in England and Wales

3D printing has rapidly developed and been applied in forensic science due to its use in creating demonstrations for courts of law. Much of the literature on this specific topic has focused on the use of 3D printed models in academia, the potential influence on a jury, and its use as a long-term documentation process, but with few actual forensic case examples. This paper offers an insight into the development of 3D printing in forensic practice and how 3D printing is currently being used in the criminal justice system in England and Wales.

A series of case reports were gathered from multiple police forces and forensic practitioners in the UK to identify how 3D printing was being used. These discussions established who was requesting 3D printed exhibits, what type of technologies were being utilised, what type of exhibits were being printed, and resulting feedback for the use of 3D printed material within a criminal case. As a result, this research demonstrates the current use of 3D printing in England and Wales, discussing the associated cases that have been known to incorporate 3D prints. Likewise, this work explores the limitations that have been encountered by forensic practitioners and identifies a series of research questions that should be considered in future investigations.

     

Effects of nabumetone,celecoxib, and ibuprofen on blood pressure control in hypertensive patients on angiotensin converting enzyme inhibitors

Nonsteroidal anti-inflammatory drugs interfere with certain antihypertensive therapies. In a double-blind study, 385 hypertensive patients stabilized on an angiotensin converting enzyme inhibitor were treated with nabumetone, celecoxib, ibuprofen, or placebo for 4 weeks. Ibuprofen caused significantly greater increases in systolic (P < .001) and diastolic (P < .01) blood pressures (BPs) compared to placebo, but not nabumetone or celecoxib. The proportion of patients with systolic BP increases of clinical concern at end point was significantly higher (P < .001) for the ibuprofen group (16.7%; 15 of 90), but not for the nabumetone group (5.5%; 5 of 91) or the celecoxib group (4.6%; 4 of 87) compared to the placebo group (1.1%; 1 of 91).     

Age-dependent neurological phenotypes in a mouse model of PRRT2-related diseases

Paroxysmal kinesigenic dyskinesia is an episodic movement disorder caused by dominant mutations in the proline-rich transmembrane protein PRRT2, with onset in childhood and typically with improvement or resolution by middle age. Mutations in the same gene may also cause benign infantile seizures, which begin in the first year of life and typically remit by the age of 2 years. Many details of PRRT2 function at the synapse, and the effects of mutations on neuronal excitability in the pathophysiology of epilepsy and dyskinesia, have emerged through the work of several groups over the last decade. However, the age dependence of the phenotypes has not been explored in detail in transgenic models. Here, we report our findings in heterozygous and homozygous Prrt2 knockout mice that recapitulate the age dependence of dyskinesia seen in the human disease. We show that Prrt2 deletion reduces the levels of synaptic proteins in a dose-dependent manner that is most pronounced at postnatal day 5 (P5), attenuates at P60, and disappears by P180. In a test for foot slippage while crossing a balance beam, transient loss of coordination was most pronounced at P60 and less prominent at age extremes. Slower traverse time was noted in homozygous knockout mice only, consistent with the ataxia seen in rare individuals with biallelic loss of function mutations in Prrt2. We thus identify three age-dependent phenotypic windows in the mouse model, which recapitulate the pattern seen in humans with PRRT2-related diseases.

     

An alternative extrinsic pathway of human blood coagulation

To study the interrelationships of the major human coagulation pathways, factor X activation in normal and various deficient human plasmas was evaluated when clotting was triggered by dilute rabbit or human thromboplastin. Various dilutions of thromboplastin were added to plasma samples containing 3H-labeled factor X, and the time course of factor X activation was determined. At a 1/250 dilution of rabbit brain thromboplastin the rate of factor X activation in factor VIII or factor IX deficient plasma was only 10% of the activation rate seen for normal or factor XI deficient plasma. Reconstitution of the deficient plasmas with factors VIII or IX, respectively, restored normal factor X activation. Similar results were obtained when various dilutions of human thromboplastin replaced the rabbit thromboplastin. From these experiments, it is inferred that normal activation of factor X in plasma due to dilute thromboplastin requires factors VII, IX and VIII. An alternative extrinsic pathway that involves factors VII, IX, and VIII may be a major physiologic extrinsic pathway, and this pathway may help to explain the clinical observations of bleeding diatheses in patients deficient in factors IX or VIII.     

Clinical features and outcome of T-cell acute lymphoblastic leukemia in childhood with respect to alterations at the TAL1 locus: a Pediatric Oncology Group study

Alteration of the TAL1 locus is the most common nonrandom genetic defect in childhood T-cell acute lymphoblastic leukemia (T-ALL). To determine if rearrangements of the TAL1 proto-oncogene confer a distinct leukemic phenotype, we studied leukemic peripheral blood or bone marrow samples from 182 children with newly diagnosed T-ALL enrolled on Pediatric Oncology Group treatment protocols. Forty-eight (26%) of the samples had a local rearrangement of the TAL1 locus. Demographic and clinical features were compared for patient subgroups with and without TAL1 rearrangements. The only clinical correlates that were significantly associated with TAL1 gene rearrangements were higher white blood cell count (P = .017) and higher hemoglobin (P = .007) at diagnosis. Immunophenotypically, samples with altered TAL1 were more likely to be CD2+ (P = .001) and lack CD10 (cALLa) expression (P = .007) than those without the rearrangement. There was a trend toward improved event-free survival (EFS) in patients with TAL1 rearrangements (4-year EFS was 44% +/- 7% for patients without the rearrangements v 59% +/- 11% for those with rearrangements), but the difference was not significant (P = .34). The role of TAL1 in leukemogenesis has yet to be clearly defined, and the prognostic significance of TAL1 gene rearrangements in T-ALL deserves further study.     

From the Cover: A global carbon and nitrogen isotope perspective on modern and ancient human diet

Stable carbon and nitrogen isotope analyses are widely used to infer diet and mobility in ancient and modern human populations, potentially providing a means to situate humans in global food webs. We collated 13,666 globally distributed analyses of ancient and modern human collagen and keratin samples. We converted all data to a common “Modern Diet Equivalent” reference frame to enable direct comparison among modern human diets, human diets prior to the advent of industrial agriculture, and the natural environment. This approach reveals a broad diet prior to industrialized agriculture and continued in modern subsistence populations, consistent with the human ability to consume opportunistically as extreme omnivores within complex natural food webs and across multiple trophic levels in every terrestrial and many marine ecosystems on the planet. In stark contrast, isotope dietary breadth across modern nonsubsistence populations has compressed by two-thirds as a result of the rise of industrialized agriculture and animal husbandry practices and the globalization of food distribution networks.

Homo sapiens are the most widely distributed terrestrial mammal on the planet. Over the course of the Holocene, modern human range has extended to all continents, to the farthest islands of every ocean, and above the polar circles. The ability to rapidly adapt to newly encountered environments via technological and cultural innovation, that manifested ultimately in changes to our own genome, enabled this breath-taking range of expansion (1). Our capacity for successful innovation is tightly coupled to our ability to consume as “extreme opportunistic omnivores,” that is, across multiple trophic levels, from the base of a food web to filling the niche of apex predator (2–4). The development of agriculture, animal husbandry, urbanized societies, and commercial trade progressively allowed us to engage in niche construction of increasing complexity and extent (5, 6). As we permanently extended our range to above the Antarctic Circle in the 20th century, we progressively extended our capacity for advanced ecosystem engineering, thereby achieving a high degree of control over the production and distribution of our food supply across the globe (6, 7).The archaeological record documents our expansion into new habitats, our technological and social innovations, changing cultural practices, and the food that sustained us (8). While the physical remains of our diets, such as bones and charred plant remains, provide direct evidence of diet, not all foodstuffs are well-preserved. Moreover, such direct evidence does not indicate the proportion of different components that were consumed. A challenge in recreating past dietary components lies in accounting for taphonomic processes that may impact different dietary items at different rates, leading to underrepresentation of some important taxa (2). In contrast, the stable carbon and nitrogen isotope composition of human tissue (mostly collagen and keratin) has been investigated over the last several decades as a proxy for the proportions of different potential dietary components enabling an accounting for taphonomy (9). Carbon isotope composition (δ¹³C value) provides an indication of relative contributions of aquatic and/or terrestrial sources of carbon in the diet. Nitrogen isotope composition (δ¹⁵N value) is used to draw inferences regarding both the protein source and trophic level of an individual in the months or years before their death (10).To date, studies involving patterns in the stable isotope composition of ancient human remains (mostly bone collagen that can be well-preserved) have tended to focus on regional-scale variations during the Holocene, with the intent of determining wholesale changes in subsistence strategies (e.g., agriculture and pastoralism) and changing technological innovation, as well as social practices and structures (11–13). Although interpretation can sometimes be straightforward when observed differences are large, smaller differences are complicated by the complexities associated with disentangling the ecosystem processes driving C and N isotope fractionation within the food webs supporting human diet (13, 14).A parallel body of research has been conducted on the stable isotope composition of the tissues of contemporary humans (15–18). This research has mostly focused on noninvasive nail and hair keratin to examine the physiological processes in the human body, to deduce the recent movements of individuals (19), or to identify locations for repatriation of human remains (20). Substantial effort has been directed toward developing a spatial understanding of the controls on the stable isotope composition of modern human tissues, mostly as a consequence of the potential forensic application of this type of research (18, 21).Archaeological and modern stable isotope results on human tissues are not readily comparable for multiple reasons (Materials and Methods), hence there has been no attempt to interrogate the full record of dietary breadth and change for a globally distributed, omnivorous species, from the prehistoric to recent times. To address this gap, we collated isotope compositions of collagen as well as hair and nail keratin from three worldwide populations: modern urban (dates AD 1910 to 2020; Materials and Methods), modern subsistence (dates AD 1910 to 2020), and material dating to before the manufacture of industrial fertilizer (before AD 1910; pre-Haber–Bosch; hereafter, PHB). We calibrated all isotope compositions to their modern diet equivalent in order to directly compare modern and PHB distributions on a common scale. We show that the industrialized food system is vastly compressed in niche space and vastly less resilient compared with modern subsistence and PHB diets that are underpinned by complex food webs.We systematically collated (n = 6,879) globally distributed analyses of PHB archaeological bone collagen (pre-1910), with the majority of the data derived from samples of mid-Holocene or later age. We further collated analyses from studies of modern (post-1910) hair and nail keratin from populations of subsistence foragers, fishers, agriculturalists and pastoralists (n = 1,167), and urban populations (n = 5,610). In order to compare populations, we adjusted all measured values onto a common frame of reference; this being the equivalent δ¹³C and δ¹⁵N values of hair keratin in 2010 or modern keratin equivalent. We then used the accepted fractionations between human hair keratin and diet to calculate the modern diet equivalent (δ¹³C_MDE value) and (δ¹⁵N_MDE) values for all samples in 2010 (Materials and Methods).This approach has the advantage of allowing direct comparison of all results against the framework of our much more detailed contemporary understanding of stable isotope systematics in the modern biosphere. Exploiting this link between PHB and modern samples requires the assumption that the environmental conditions that drive the food webs that humans rely upon, wherever they are, have remained stable and that the past can be mapped onto the present. While there have been changes in climate and environment during the Holocene, these have been relatively muted, with most larger-scale landscape change resulting from human intervention beginning at varying times across the world in the Holocene and accelerating rapidly with the rise of industrial agriculture in the 20th Century (22).