Analytical examination of animal remains from Borneo:the painting of bone and shell

Examination of a selection of shell and bone from archaeological assemblages excavated at Niah Cave and Gua Sireh, both of which are located in Sarawak, Borneo, has revealed the deliberate application of coloured material to one or more surfaces. Small fragments of the surface colourant were analysed using a variety of techniques, including microscopy, energy dispersive microwave analysis and infra-red spectrophotometry. These procedures established that, although red in colour, the applied coating in each instance was not red iron oxide. It is suggested that, based on the chemical components present, this coating was a tree resin or a similar organic substance. The paper further reports the presence of enhanced chloride values in the colourant recovered from the ancient human cranial fragment tested. It is suggested that elevated concentrations of this trace element may indicate that the site, the human remains or ingredients within the colourant were once in close proximity to the sea. (C) 2010 Elsevier Ltd. All rights reserved.

The emergence of bone technologies at the end of the pleistocene in Southeast Asia:Regional and evolutionary implications

For many decades Palaeolithic research viewed the development of early modern human behaviour as largely one of progress down a path towards the modernity of the present. The European Palaeolithic sequence the most extensively studied was for a long time the yard-stick against which records from other regions were judged. Recent work undertaken in Africa and increasingly Asia, however, now suggests that the European evidence may tell a story that is more parochial and less universal than previously thought. While tracking developments at the large scale (the grand narrative) remains important, there is growing appreciation that to achieve a comprehensive understanding of human behavioural evolution requires an archaeologically regional perspective to balance this. One of the apparent markers of human modernity that has been sought in the global Palaeolithic record, prompted by finds in the European sequence, is innovation in bonebased technologies. As one step in the process of re-evaluating and contextualizing such innovations, in this article we explore the role of prehistoric bone technologies within the Southeast Asian sequence, where they have at least comparable antiquity to Europe and other parts of Asia. We observe a shift in the technological usage of bone from a minor component to a medium of choice during the second half of the Last Termination and into the Holocene. We suggest that this is consistent with it becoming a focus of the kinds of inventive behaviour demanded of foraging communities as they adapted to the far-reaching environmental and demographic changes that were reshaping this region at that time. This record represents one small element of a much wider, much longerterm adaptive process, which we would argue is not confined to the earliest instances of a particular technology or behaviour, but which forms part of an on-going story of our behavioural evolution. © 2012 The McDonald Institute for Archaeological Research.

Bone tool analysis

This article examines the osseous technologies that can be created from animal skeletons. 'Tool' status is accorded to a skeletal element or fragment that has been modified subsequent to its isolation from the carcass. Such anthropic adaptation may be deliberate (e.g., through manufacture) and/or appear as a result of utilization, and is granted in instances where these details cannot otherwise be ascribed to alternative nonanthropic causes. Implements can display a combination of traces from both human and natural sources and as such the study of them involves both zooarchaeological (i.e., via animal ecology, hunting, and butchery) and technological analysis.... As an exemplar of this, the following discussion will present some of the similarities and differences that exist between osseous and lithic raw materials and tool-blank production, and will situate both in an operational sequence of animal procurement and processing. It will then give an account of principal manufacturing techniques, methods for establishing tool function, and the phenomenon of 'pseudo tools'. © 2008 Copyright © 2008 Elsevier Inc.

The early exploitation of Southeast Asian mangroves:Bone technology from caves and open sites

This paper focuses on the contribution that the study of bone technology is making to the understanding of early tropical subsistence in Southeast Asia. Newly completed research suggests that during the period from the terminal Pleistocene to mid Holocene, bone tools may have featured prominently in coastal subsistence. There are indications that this technology may have had a particular association with hunting and gathering in the mangrove forests that proliferated along many coasts during this period. The study of these tools thus represents a rare chance to examine prehistoric extractive technologies, which are generally agreed to have been predominantly made on organic, nonpreserving media. The evidence presented also suggests that prehistoric foragers from this region possessed a good working understanding of the mechanical properties of bone and used bone implements where conditions and needs suited the parameters of this material. © 2005 by the University of Hawai'i Press.

Urban high-density construction sites and their surrounding community:issues encountered and strategiesadopted by contractors

Inner city developments are a common feature within many urban environments. Where these construction sites are not managed effectively, they can negatively impact their surrounding community. The aim of this paper is to identify and document, in an urban context, the numerous issues encounter and subsequent strategies adopted by on-site contractors and local people, in the mitigation of factors which negatively impact their surrounding community. The objectives in achieving this aim are to identify what effect, if any, an urban construction site has on its surrounding environment, the issues and resulting strategies adopted by contractors on the factors identified, and also what measures are put in place to minimise such disturbances to the local community. In order to meet the requirements, a mixed methodology is adopted culminating in a literature review, case study analysis, contractor and community interviews, concluding in the development of two specific questions for both perspectives in question. The data is assessed using severity indices based on mean testing in the development of key findings. The results indicate that the main forms of disturbance to the local community from an urban development include noise, dust and traffic congestion. With respect to a contractor on-site, the key issues include damaging surrounding buildings, noise control and off-site parking. The resulting strategies identified in the mitigation of such issues include the implementation of noise and dust containment measures and minimising disruption to local infrastructure. It is envisaged that the results of this study will provide contractors operating in such environments, with the required information which can assist in minimising disruption and therefore, avoiding disputes with the local community members. By consulting with and surveying those most affected, this research will illustrate to on-site management, the difficulties faced by those who accommodate such developments within their living environment.

Marine Collagen Reinforcement of Calcium Phosphate Bone Cements: A Biological Assessment

Induction of in vivo responses by implanted biomaterials is of great interest in the medical device field. Calcium phosphate bone cements (CPCs) can potentially promote natural bone remodelling and ingrowth in vivo and, as such are becoming more common place in a range of orthopaedic procedures. However, concerns remain regarding their mechanical and handling properties. Compressive modulus and fracture toughness of CPCs can be improved, without compromising injectability and setting time, through the incorporation of bovine collagen fibres1. Incorporation of marine derived collagen fibres has also yielded similar improvements2. It is hypothesised that, due to its role in bone formation and function, that incorporation of collagen in CPCs will also result in biological benefits.
The biological properties of α-TCP-CPC were largely unchanged by the incorporation of marine derived collagen. However, as a result of significant improvements to the mechanical properties, its incorporation may still result in a suitable alternative to some commercially available bone cements.

(223)Ra and other bone-targeting radiopharmaceuticals-the translation of radiation biology into clinical practice

Osseous metastases are a source of significant morbidity for patients with a variety of cancers. Radiotherapy is well established as an effective means of palliating symptoms associated with such metastases. The role of external beam radiotherapy is limited where sites of metastases are numerous and widespread. Low linear energy transfer (LET) radionuclides have been utilized to allow targeted delivery of radiotherapy to disparate sites of disease, with evidence of palliative benefit. More recently, the bone targeting, high LET radionuclide (223)Ra has been shown to not only have a palliative effect but also a survival prolonging effect in metastatic, castration-resistant prostate cancer with bone metastases. This article reviews the different radionuclide-based approaches for targeting bone metastases, with an emphasis on (223)Ra, and key elements of the underlying radiobiology of these that will impact their clinical effectiveness. Consideration is given to the remaining unknowns of both the basic radiobiological and applied clinical effects of (223)Ra as targets for future research.

Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial

BACKGROUND: Bone metastases frequently cause skeletal events in patients with metastatic castration-resistant prostate cancer. Radium-223 dichloride (radium-223) selectively targets bone metastases with high-energy, short-range α-particles. We assessed the effect of radium-223 compared with placebo in patients with castration-resistant prostate cancer and bone metastases.

METHODS: In this phase 3, double-blind, randomised ALSYMPCA trial, we enrolled patients who had symptomatic castration-resistant prostate cancer with two or more bone metastases and no known visceral metastases, who were receiving best standard of care, and had previously either received or were unsuitable for docetaxel. Patients were stratified by previous docetaxel use, baseline total alkaline phosphatase level, and current bisphosphonate use, then randomly assigned (2:1) to receive either six intravenous injections of radium-223 (50 kBq/kg) or matching placebo; one injection was given every 4 weeks. Randomisation was done with an interactive voice response system, taking into account trial stratification factors. Participants and investigators were masked to treatment assignment. The primary endpoint was overall survival, which has been reported previously. Here we report on time to first symptomatic skeletal event, defined as the use of external beam radiation to relieve bone pain, or occurrence of a new symptomatic pathological fracture (vertebral or non-verterbal), or occurence of spinal cord compression, or tumour-related orthopeadic surgical intervention. All events were required to be clinically apparent and were not assessed by periodic radiological review. Statistical analyses of symptomatic skeletal events were based on the intention-to-treat population. The study has been completed and is registered with ClinicalTrials.gov, number NCT00699751.

FINDINGS: Between June 12, 2008, and Feb 1, 2011, 921 patients were enrolled, of whom 614 (67%) were randomly assigned to receive radium-223 and 307 (33%) placebo. Symptomatic skeletal events occurred in 202 (33%) of 614 patients in the radium-223 group and 116 (38%) of 307 patients in the placebo group. Time to first symptomatic skeletal event was longer with radium-223 than with placebo (median 15·6 months [95% CI 13·5-18·0] vs 9·8 months [7·3-23·7]; hazard ratio [HR]=0·66, 95% CI 0·52-0·83; p=0·00037). The risks of external beam radiation therapy for bone pain (HR 0·67, 95% CI 0·53-0·85) and spinal cord compression (HR=0·52, 95% CI 0·29-0·93) were reduced with radium-233 compared with placebo. Radium-223 treatment did not seem to significantly reduce the risk of symptomatic pathological bone fracture (HR 0·62, 95% CI 0·35-1·09), or the need for tumour-related orthopaedic surgical intervention (HR 0·72, 95% CI 0·28-1·82).

INTERPRETATION: Radium-223 should be considered as a treatment option for patients with castration-resistant prostate cancer and symptomatic bone metastases.

FUNDING: Algeta and Bayer HealthCare Pharmaceuticals.

The influence of cyclosporin alone, or cyclosporin and methotrexate, on the incidence of mixed haematopoietic chimaerism following allogeneic sibling bone marrow transplantation for severe aplastic anaemia

We previously reported a randomized trial comparing Cyclosporin-A (CsA) and short-term methotrexate versus CsA alone for graft-versus-host disease (GvHD) prophylaxis in 71 patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) from a human leucocyte antigen-identical sibling for severe aplastic anaemia (SAA). We found a better survival in the group receiving the two-drug prophylaxis regimen with no significant difference in the probability of developing GvHD between the two groups. The present study details chimaeric analysis and its influence on survival and GvHD occurrence in 45 of the original 71 patients in whom serial samples were available. Analysis was carried out in a blinded prospective manner. Seventy-two per cent achieved complete donor chimaerism (DC), 11% stable mixed chimaerism (SMC) and 17% progressive mixed chimaerism (PMC). The overall 5-year survival probability was 82% (+/-11%) with a significant survival advantage (P = 0.0009) in DC or SMC compared to those with PMC. Chronic GvHD was more frequent in DC patients, whereas no patient with SMC developed chronic GvHD. Graft failure occurred in 50% of the PMC group. This study demonstrates the relevance of chimaerism analysis in patients receiving HSCT for SAA and confirms the occurrence of mixed chimaerism in a significant proportion of recipients.

Characterization of NKR+ T-cell subsets in human bone marrow:implications for immunosurveillance of neoplasia

In addition to hematopoietic progenitors, human bone marrow contains mature T/NK lymphocytes. Valpha24Vbeta11 NKT-cells, a subset of NK receptor+ (NKR+) T-cells in humans, are rare in bone marrow, suggesting the presence of other NKR+ T-cells which may contribute to tumor surveillance. NKR+/- T-cells were examined in blood (PB), and bone marrow from donors (DM) and patients with active hematopoietic malignancy (PM), or in remission (PR). T-cells in PR & PM were enriched for CD56+ and CD57+ subsets, compared to DM. All marrow NKR+/- T-cell subsets were more activated than PB. PM and, surprisingly, PR marrow contained more activated cells than DM. CD8+ cells were significantly increased in all patient marrows and there was evidence of the formation of an effector/memory pool in malignant marrow. These data suggest that NKR+ T-cell enrichment in human bone marrow that has been exposed to neoplastic transformation is compatible with a role in localized tumor surveillance/eradication.

Leukaemic transformation of donor cells in a patient receiving a second allogeneic bone marrow transplant for severe aplastic anaemia

Allogeneic blood or bone marrow transplantation is a successful treatment for leukaemia and severe aplastic anaemia (SAA). Graft rejection following transplantation for leukaemia is a rare event but leukaemic relapse may occur at varying rates, depending upon the stage of leukaemia at which the transplant was undertaken and the type of leukaemia. Relapse is generally assumed to occur in residual host cells, which are refractory to, or escape from the myeloablative conditioning therapy. Rare cases have been described, however, in which the leukaemia recurs in cells of donor origin. Lack of a successful outcome of blood or bone marrow transplantation for severe aplastic anaemia (SAA), however, is due to late graft rejection or graft-versus-host disease. Leukaemia in cells of donor origin has rarely been reported in patients following allogeneic bone marrow transplantation for SAA. This report describes leukaemic transformation in donor cells following a second allogeneic BMT for severe aplastic anaemia. PCR of short tandem repeats in bone marrow aspirates and in colonies derived from BFUE and CFU-GM indicated the donor origin of leukaemia. Donor leukaemia is a rare event following transplantation for severe aplastic anaemia but may represent the persistence or perturbation of a stromal defect in these patients inducing leukaemic change in donor haemopoietic stem cells.