Accurate prediction of saw blade thicknesses from false start measurements.

BACKGROUND: False start analysis is the examination of incomplete saw marks created on bone in an effort to establish information on the saw that created them. The present study aims to use quantitative data from micro-CT cross-sections to predict the thickness of the saw blade used to create the mark. Random forest statistical models are utilised for prediction to present a methodology that is useful to both forensic researchers and practitioners. METHOD: 340 false starts were created on 32 fleshed cadaveric leg bones by 38 saws of various classes. False starts were micro-CT scanned and seven measurements taken digitally. A regression random forest model was produced from the measurement data of all saws to predict the saw blade thickness from false starts with an unknown class. A further model was created, consisting of three random forests, to predict the saw blade thickness when the class of the saw is known. The predictive capability of the models was tested using a second sample of data, consisting of measurements taken from a further 17 false starts created randomly selected saws from the 38 in the experiment. RESULTS: Random forest models were able to accurately predict up to 100% of saw blade thicknesses for both samples of false starts. CONCLUSION: This study demonstrates the applicability of random forest statistical regression models for reliable prediction of saw blade thicknesses from false start data. The methodology proposed enables prediction of saw blade thickness from empirical data and offers a significant step towards reduced subjectivity and database formation in false start analysis. Application of this methodology to false start analysis, with a more complete database, will allow complementary results to current analysis techniques to provide more information on the saw used in dismemberment casework.

Creating a legacy for future generations.

Creating a legacy is an important aspect of professional development. The Fellows of the American Association of Nurse Practitioners legacy award was established to honor nurse practitioners who have led the way throughout their lifetime. Their stories provide a road map for nurse practitioners to continue to lead the way into the future.

Micro-CT for saw mark analysis on human bone.

In toolmark analysis, microscopy techniques, such as micro-CT, are used to visualise and measure toolmarks left on bones by a tool. In dismemberment cases, properties such as the width of the saw mark can provide cues to which tool was used by the culprit. The aim of the current study was to establish whether; (i) micro-CT is an appropriate imaging technique for saw mark analysis, (ii) toolmarks statistically differ when created with different tools, (iii) toolmark width can predict tool blade width, and (iv) toolmarks differ if created under different methodological conditions. Across two experiments, 270 saw marks were created using eight tools with either a controlled or free saw action on either fleshed or defleshed human long bone. Toolmarks were micro-CT scanned and seven toolmark properties were categorised or measured by two independent raters. The current study found that; (i) micro-CT was found to be a powerful and reliable imaging method for the visualisation and measurement of saw mark properties, (ii) toolmark properties differed significantly within and between various methodological conditions (p<.001) when created by eight different tools, (iii) a regression model developed using toolmark widths from Experiment 2 overall predicted 94% of tool widths in Experiment 1, and iv) methodological factors such as tissue presence and saw action significantly and inconsistently influenced toolmark properties for different tools. The study further validates the use of mirco-CT for saw mark analysis and demonstrates the potential of using toolmark properties to determine the tool used in cases of dismemberment. Given the effects that methodological factors such as tissue presence can have on toolmark properties, future studies should use experimental set ups with fleshed human tissue and use a free saw action.

An evidence based method to calculate pedestrian crossing speeds in vehicle collisions (PCSC).

Pedestrian accident reconstruction is necessary to establish cause of death, i.e. establishing vehicle collision speed as well as circumstances leading to the pedestrian being impacted and determining culpability of those involved for subsequent court enquiry. Understanding the complexity of the pedestrian attitude during an accident investigation is necessary to ascertain the causes leading to the tragedy. A generic new method, named Pedestrian Crossing Speed Calculator (PCSC), based on vector algebra, is proposed to compute the pedestrian crossing speed at the moment of impact. PCSC uses vehicle damage and pedestrian anthropometric dimensions to establish a combination of head projection angles against the windscreen; this angle is then compared against the combined velocities angle created from the vehicle and the pedestrian crossing speed at the time of impact. This method has been verified using one accident fatality case in which the exact vehicle and pedestrian crossing speeds were known from Police forensic video analysis. PCSC was then applied on two other accident scenarios and correctly corroborated with the witness statements regarding the pedestrians crossing behaviours. The implications of PCSC could be significant once fully validated against further future accident data, as this method is reversible, allowing the computation of vehicle impact velocity from pedestrian crossing speed as well as verifying witness accounts.

The cutting edge - Micro-CT for quantitative toolmark analysis of sharp force trauma to bone.

Toolmark analysis involves examining marks created on an object to identify the likely tool responsible for creating those marks (e.g., a knife). Although a potentially powerful forensic tool, knife mark analysis is still in its infancy and the validation of imaging techniques as well as quantitative approaches is ongoing. This study builds on previous work by simulating real-world stabbings experimentally and statistically exploring quantitative toolmark properties, such as cut mark angle captured by micro-CT imaging, to predict the knife responsible. In Experiment 1 a mechanical stab rig and two knives were used to create 14 knife cut marks on dry pig ribs. The toolmarks were laser and micro-CT scanned to allow for quantitative measurements of numerous toolmark properties. The findings from Experiment 1 demonstrated that both knives produced statistically different cut mark widths, wall angle and shapes. Experiment 2 examined knife marks created on fleshed pig torsos with conditions designed to better simulate real-world stabbings. Eight knives were used to generate 64 incision cut marks that were also micro-CT scanned. Statistical exploration of these cut marks suggested that knife type, serrated or plain, can be predicted from cut mark width and wall angle. Preliminary results suggest that knives type can be predicted from cut mark width, and that knife edge thickness correlates with cut mark width. An additional 16 cut marks walls were imaged for striation marks using scanning electron microscopy with results suggesting that this approach might not be useful for knife mark analysis. Results also indicated that observer judgements of cut mark shape were more consistent when rated from micro-CT images than light microscopy images. The potential to combine micro-CT data, medical grade CT data and photographs to develop highly realistic virtual models for visualisation and 3D printing is also demonstrated. This is the first study to statistically explore simulated real-world knife marks imaged by micro-CT to demonstrate the potential of quantitative approaches in knife mark analysis. Findings and methods presented in this study are relevant to both forensic toolmark researchers as well as practitioners. Limitations of the experimental methodologies and imaging techniques are discussed, and further work is recommended.

Complementing anatomy education using three-dimensional anatomy mobile software applications on tablet computers.

Anatomy has traditionally been a cornerstone of medical education, which has been taught via dissection and didactic lectures. The rising prevalence of mobile tablet technology means medical software applications ("apps") play an increasingly important role in medical education. The applications highlighted in this article will aid anatomical educators to identify which are the most useful in clinical, academic, and educational environments. These have been systematically identified by downloading all applications with keywords related to anatomy and then carrying out qualitative assessment. Novel anatomy applications from developers such as Visible Body, 3D4Medical, and Pocket Anatomy allow students to visualize and manipulate complex anatomical structures using detailed 3D models. They often contain additional content including clinical correlations and a range of media from instructional videos to interactive quiz functions. The strength of tablet technology lies in its ability to consolidate and present anatomical information to the user in the most appropriate manner for their learning style. The only question mark remains over the level of detail and accuracy of these applications. Innovative medical educators who embrace tablet technology will find that anatomy applications serve as a useful learning tool when used in conjunction with existing teaching setups.

Warfarin dosing after bariatric surgery: a retrospective study of 10 patients previously stable on chronic warfarin therapy.

Many changes associated with bariatric surgery have the potential to affect warfarin dosing; yet current literature includes little data describing this phenomenon. Investigating this relationship may allow for determination of post-bariatric surgery warfarin dosing using stable pre-operative dosing levels. A retrospective chart review was completed for 10 patients stabilized on chronic warfarin therapy who underwent bariatric surgery. Data collection consisted of the following: warfarin requirement in mg/week, time in target range (TTR), creatinine, liver function, diarrhoea, medication changes, diet, and signs of bleeding and/or thrombosis. Three study patients underwent laparoscopic adjustable gastric banding procedures and seven patients underwent Roux-en-Y gastric bypass. The average (standard deviation) weekly warfarin dose required in the immediate post-operative interval was 64% (25%) of baseline dosing, corresponding to a TTR of 48%. At 6 months, patients required 85% (19%) of baseline weekly dosing, with TTR of 53.4%. At 1 year, dosing was 90% (16%) of baseline with TTR of 63.5%. Patients underwent medication changes as well as transient bouts of diarrhoea. Two patients suffered unspecified haemorrhages of the gastrointestinal tract (international normalized ratio [INR] = 2.3 and 9.8). This patient set demonstrated an initial drop in warfarin requirement, followed by escalating dosing trends that became more predictable as patients were farther out from procedure.

Effects of flavocoxid, a dual inhibitor of COX and 5-lipoxygenase enzymes, on benign prostatic hyperplasia.

BACKGROUND AND PURPOSE: Inflammation plays a key role in the development of benign prostatic hyperplasia (BPH). Eicosanoids derived from the COX and 5-lipoxygenase (5-LOX) pathways are elevated in the enlarging prostate. Flavocoxid is a novel flavonoid-based 'dual inhibitor' of the COX and 5-LOX enzymes. This study evaluated the effects of flavocoxid in experimental BPH. EXPERIMENTAL APPROACH: Rats were treated daily with testosterone propionate (3 mg·kg(-1) s.c.) or its vehicle for 14 days to induce BPH. Animals receiving testosterone were randomized to receive vehicle (1 mL·kg(-1) , i.p.) or flavocoxid (20 mg·kg(-1) , i.p.) for 14 days. Histological changes, eicosanoid content and mRNA and protein levels for apoptosis-related proteins and growth factors were assayed in prostate tissue. The effects of flavocoxid were also tested on human prostate carcinoma PC3 cells. KEY RESULTS: Flavocoxid reduced prostate weight and hyperplasia, blunted inducible expression of COX-2 and 5-LOX as well as the increased production of PGE(2) and leukotriene B(4) (LTB(4) ), enhanced pro-apoptotic Bax and caspase-9 and decreased the anti-apoptotic Bcl-2 mRNA. Flavocoxid also reduced EGF and VEGF expression. In PC3 cells, flavocoxid stimulated apoptosis and inhibited growth factor expression. Flavocoxid-mediated induction of apoptosis was inhibited by the pan-caspase inhibitor, Z-VAD-FMK, in PC3 cells, suggesting an essential role of caspases in flavocoxid-mediated apoptosis during prostatic growth. CONCLUSION AND IMPLICATIONS: Our results show that a 'dual inhibitor' of the COX and 5-LOX enzymes, such as flavocoxid, might represent a rational approach to reduce BPH through modulation of eicosanoid production and a caspase-induced apoptotic mechanism.

Genistein aglycone effect on bone loss is not enhanced by supplemental calcium and vitamin D3: a dose ranging experimental study.

Genistein aglycone (GEN) has a favorable effect on bone loss. We investigated the effects of GEN alone or in combination with supplemental calcium and vitamin D(3) in an animal model of bone loss to evaluate if there was additional benefit. Ovariectomized (OVX) and SHAM-OVX rats were used. OVX were divided into 12 groups and randomized to receive: GEN at 27, 54, 200, 500 or 1000 mg (human equivalent dose (HED)/day/ip injection alone or with calcium carbonate (Ca) (360 mg/kg/day/gavages) and vitamin D(3) (D(3)) (50 IU/kg/day/gavages) or Ca/D(3) without GEN or untreated for 6 weeks. SHAM-OVX were randomized into 7 groups and treated with: Ca and D(3) alone or in combination with GEN (same doses as OVX), or left untreated. Bone mineral density (BMD), bone-alkaline phosphatase (b-ALP), collagen C-telopeptides (CTX), osteoprotegerin (OPG) and soluble receptor activator of NFκB ligand (sRANKL) were assessed. Femurs were excised and tested for breaking strength and histology. Uterine weight was analyzed to assess GEN's estrogenic effects on the SHAM-OVX. The most effective dose of GEN, independent of Ca/D(3) supplementation, was 54 mg/day. Higher doses yielded no further improvement in bone biomarkers, histology or strength. Only 1000 mg/day HED of genistein produced statistically significant changes in uterine weight of the SHAM-OVX. This study suggests that 54 mg/day of GEN is the threshold dose for efficacy. In addition, supplemental calcium and vitamin D(3), beyond normal dietary intake do not enhance the effects of genistein on improving measures of bone loss. This observation has implications regarding the use of calcium and vitamin D(3) supplementation.

Application of biomarkers in the development of drugs intended for the treatment of osteoarthritis.

OBJECTIVE: Osteoarthritis (OA) is a chronic and slowly progressive disease for which biomarkers may be able to provide a more rapid indication of therapeutic responses to therapy than is currently available; this could accelerate and facilitate OA drug discovery and development programs. The goal of this document is to provide a summary and guide to the application of in vitro (biochemical and other soluble) biomarkers in the development of drugs for OA and to outline and stimulate a research agenda that will further this goal. METHODS: The Biomarkers Working Group representing experts in the field of OA biomarker research from both academia and industry developed this consensus document between 2007 and 2009 at the behest of the Osteoarthritis Research Society International Federal Drug Administration initiative (OARSI FDA initiative). RESULTS: This document summarizes definitions and classification systems for biomarkers, the current outcome measures used in OA clinical trials, applications and potential utility of biomarkers for development of OA therapeutics, the current state of qualification of OA-related biomarkers, pathways for biomarker qualification, critical needs to advance the use of biomarkers for drug development, recommendations regarding practices and clinical trials, and a research agenda to advance the science of OA-related biomarkers. CONCLUSIONS: Although many OA-related biomarkers are currently available they exist in various states of qualification and validation. The biomarkers that are likely to have the earliest beneficial impact on clinical trials fall into two general categories, those that will allow targeting of subjects most likely to either respond and/or progress (prognostic value) within a reasonable and manageable time frame for a clinical study (for instance within 1-2 years for an OA trial), and those that provide early feedback for preclinical decision-making and for trial organizers that a drug is having the desired biochemical effect. As in vitro biomarkers are increasingly investigated in the context of specific drug treatments, advances in the field can be expected that will lead to rapid expansion of the list of available biomarkers with increasing understanding of the molecular processes that they represent.

Efficacy of genistein aglycone on some cardiovascular risk factors and homocysteine levels: A follow-up study.

BACKGROUND AND AIM: Recent evidence suggests that genistein aglycone may act beneficially on surrogate cardiovascular risk markers in postmenopausal women. We assessed the effects of genistein aglycone on some cardiovascular risk factors and homocysteine levels after 3-years of continued therapy in a cohort of osteopenic, postmenopausal women. METHODS AND RESULTS: The parent study was a randomized, double-blind, placebo-controlled trial involving 389 postmenopausal women with low bone mass for 24 months. Subsequently, a subcohort (138 patients) continued therapy for an additional year. Participants received 54mg of genistein aglycone (n=71) or placebo (n=67), daily. Both arms received calcium and vitamin D(3) in therapeutic doses. Moreover, 4 weeks before randomization procedures and during our follow-up study, all patients received dietary instructions in an isocaloric fat-restricted diet. Blood lipid profiles, fasting glucose and insulin, insulin resistance (HOMA-IR), fibrinogen, osteoprotegerin (OPG) and homocysteine at baseline and after 24 and 36 months of treatment were measured. Compared to placebo, genistein significantly decreased fasting glucose and insulin, HOMA-IR, fibrinogen and homocysteine after 24 and 36 months of treatment. By contrast, isoflavone administration did not affect high-density lipoprotein cholesterol and triglycerides though serum OPG was higher in the genistein recipients. There were no differences in adverse events or discomfort between groups. Results on routine biochemical, liver function, and hematologic testing did not change over time in placebo or genistein group. CONCLUSIONS: After 3-years of treatment, genistein aglycone plus calcium, vitamin D(3) and a healthy diet showed positive effects on some cardiovascular risk factors and homocysteine levels in a cohort of postmenopausal women with low bone mass.

Flavocoxid, a dual inhibitor of cyclooxygenase and 5-lipoxygenase, blunts pro-inflammatory phenotype activation in endotoxin-stimulated macrophages.

BACKGROUND AND PURPOSE: The flavonoids, baicalin and catechin, from Scutellaria baicalensis and Acacia catechu, respectively, have been used for various clinical applications. Flavocoxid is a mixed extract containing baicalin and catechin, and acts as a dual inhibitor of cyclooxygenase (COX) and 5-lipoxygenase (LOX) enzymes. The anti-inflammatory activity, measured by protein and gene expression of inflammatory markers, of flavocoxid in rat peritoneal macrophages stimulated with Salmonella enteritidis lipopolysaccharide (LPS) was investigated. EXPERIMENTAL APPROACH: LPS-stimulated (1 microg.mL(-1)) peritoneal rat macrophages were co-incubated with different concentrations of flavocoxid (32-128 microg.mL(-1)) or RPMI medium for different incubation times. Inducible COX-2, 5-LOX, inducible nitric oxide synthase (iNOS) and inhibitory protein kappaB-alpha (IkappaB-alpha) levels were evaluated by Western blot analysis. Nuclear factor kappaB (NF-kappaB) binding activity was investigated by electrophoretic mobility shift assay. Tumour necrosis factor-alpha (TNF-alpha) gene and protein expression were measured by real-time polymerase chain reaction and enzyme-linked immunosorbent assay respectively. Finally, malondialdehyde (MDA) and nitrite levels in macrophage supernatants were evaluated. KEY RESULTS: LPS stimulation induced a pro-inflammatory phenotype in rat peritoneal macrophages. Flavocoxid (128 microg.mL(-1)) significantly inhibited COX-2 (LPS = 18 +/- 2.1; flavocoxid = 3.8 +/- 0.9 integrated intensity), 5-LOX (LPS = 20 +/- 3.8; flavocoxid = 3.1 +/- 0.8 integrated intensity) and iNOS expression (LPS = 15 +/- 1.1; flavocoxid = 4.1 +/- 0.4 integrated intensity), but did not modify COX-1 expression. PGE(2) and LTB(4) levels in culture supernatants were consequently decreased. Flavocoxid also prevented the loss of IkappaB-alpha protein (LPS = 1.9 +/- 0.2; flavocoxid = 7.2 +/- 1.6 integrated intensity), blunted increased NF-kappaB binding activity (LPS = 9.2 +/- 2; flavocoxid = 2.4 +/- 0.7 integrated intensity) and the enhanced TNF-alpha mRNA levels (LPS = 8 +/- 0.9; flavocoxid = 1.9 +/- 0.8 n-fold/beta-actin) induced by LPS. Finally, flavocoxid decreased MDA, TNF and nitrite levels from LPS-stimulated macrophages. CONCLUSION AND IMPLICATIONS: Flavocoxid might be useful as a potential anti-inflammatory agent, acting at the level of gene and protein expression.

Genistein aglycone reverses glucocorticoid-induced osteoporosis and increases bone breaking strength in rats: a comparative study with alendronate.

BACKGROUND AND PURPOSE: Glucocorticoid-induced osteoporosis (GIO) is the leading cause of secondary osteoporosis. Clinical evidence suggests a role for genistein aglycone in the treatment of post-menopausal osteopenia although proof of efficacy in comparison with currently available treatments is still lacking. To clarify this issue, we investigated the effects of genistein on bone compared with alendronate in experimental GIO. EXPERIMENTAL APPROACH: A total of 28 female Sprague-Dawley rats were used. GIO was induced by daily injections of methylprednisolone (MP; 30 mg x kg(-1) s.c.) for 60 days. Sham GIO animals (Sham-MP) were injected daily with the MP vehicle. At the end of the osteoporosis development period, MP rats were randomized to receive: vehicle (n= 7), genistein aglycone (5 mg x kg(-1) s.c.; n= 7) or alendronate (0.03 mg x kg(-1) s.c.; n= 7). Treatment lasted 60 days. Sham-MP animals were treated with vehicle for an additional 60 days. At the beginning and at the end of treatments, animals were examined for bone mineral density and bone mineral content. Bone-alkaline phosphatase and carboxy-terminal collagen cross links were determined; femurs were removed and tested for breaking strength and histology. KEY RESULTS: Genistein aglycone showed a greater increase in bone mineral density, bone mineral content and in breaking strength than alendronate and significantly increased bone-alkaline phosphatase (bone formation marker), reduced carboxy-terminal collagen cross links (bone resorption marker), compared with alendronate. Both treatments improved bone histology and the histological score. CONCLUSION AND IMPLICATIONS: The results strongly suggest that the genistein aglycone might be an alternative therapy for the management of secondary osteoporosis.

Effects of genistein aglycone in osteoporotic, ovariectomized rats: a comparison with alendronate, raloxifene and oestradiol.

BACKGROUND AND PURPOSE: Genistein aglycone positively affects bone loss in postmenopausal women, but bone quality data are still lacking. To clarify this, we investigated the effects of genistein compared with alendronate, raloxifene and oestradiol in an animal model of established osteoporosis. EXPERIMENTAL APPROACH: Six months after ovariectomy, 96 ovariectomized (OVX) rats were divided into 8 equal groups, randomized to treatments (genistein aglycone (1 and 10 mg kg(-1) s.c.); alendronate (0.003 and 0.03 mg kg(-1) s.c.); raloxifene hydrochloride (0.05 and 0.5 mg kg(-1) s.c.); 17-alpha-ethinyl oestradiol (0.003 and 0.03 mg kg(-1) s.c.)) for 12 weeks. Untreated OVX (n=12) and sham OVX (n=12) were used as controls. At the beginning and end of treatment, bone mineral density (BMD) and bone mineral content (BMC) were assessed. At the end of the experiment, calcium, phosphorus, bone-alkaline phosphatase (b-ALP), collagen C-telopeptide (CTX), osteoprotegerin (OPG) and soluble receptor activator of nuclear factor-kappaB ligand (sRANKL) were assayed. Femurs were removed and tested for breaking strength and histology. KEY RESULTS: Genistein (10 mg kg(-1)) showed a greater increase in both BMD (P<0.0001 vs OVX) and BMC than all the other treatments. Moreover, genistein significantly increased breaking strength, bone quality, b-ALP (P<0.0001 vs OVX) and OPG, and reduced CTX and sRANKL compared with the other treatments at all dose levels. CONCLUSIONS AND IMPLICATIONS: The results strongly suggest that the genistein aglycone might be a new therapy for the management of postmenopausal osteoporosis in humans.

A medicinal extract of Scutellaria baicalensis and Acacia catechu acts as a dual inhibitor of cyclooxygenase and 5-lipoxygenase to reduce inflammation.

A mixed extract containing two naturally occurring flavonoids, baicalin from Scutellaria baicalensis and catechin from Acacia catechu, was tested for cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) inhibition via enzyme, cellular, and in vivo models. The 50% inhibitory concentration for inhibition of both ovine COX-1 and COX-2 peroxidase enzyme activities was 15 microg/mL, while the mixed extract showed a value for potato 5-LOX enzyme activity of 25 microg/mL. Prostaglandin E2 generation was inhibited by the mixed extract in human osteosarcoma cells expressing COX-2, while leukotriene production was inhibited in both human cell lines, immortalized THP-1 monocyte and HT-29 colorectal adenocarcinoma. In an arachidonic acid-induced mouse ear swelling model, the extract decreased edema in a dose-dependent manner. When arachidonic acid was injected directly into the intra-articular space of mouse ankle joints, the mixed extract abated the swelling and restored function in a rotary drum walking model. These results suggest that this natural, flavonoid mixture acts via "dual inhibition" of COX and LOX enzymes to reduce production of pro-inflammatory eicosanoids and attenuate edema in an in vivo model of inflammation.

Transarterial chemoembolisation for advanced hepatocellular carcinoma: results from a North American cancer centre.

AIMS: In Asian countries, transarterial chemoembolisation (TACE) has long been used for palliation of unresectable hepatocellular carcinoma (HCC) without strong evidence of improved survival or quality of life. In 2002, a survival benefi of TACE was shown in two randomised controlled trials in Europe and Hong Kong. The effectiveness of interventions fo HCC is influenced by geographical factors related to diverse patient characteristics and protocols. Therefore, the validation of TACE as palliative modality for unresectable HCC requires confirmation in diverse patient populations. The aim of the present study was to assess the effectiveness of TACE for HCC in a North American population. MATERIALS AND METHODS: This was a single centre prospective cohort study. Child-Pugh A cirrhosis or better patients wit unresectable HCC and without radiological evidence of metastatic disease or segmental portal vein thrombosis wer assessed between November 2001 and May 2004. Of 54 patients who satisfied the inclusion criteria, 47 underwent 80 TACE sessions. Chemoembolisation was carried out using selective hepatic artery injection of 75 mg/m(2) doxorubicin and lipiodol followed by an injection of embolic particles when necessary. Repeat treatments were carried out at 2-3 month intervals for recurrent disease. The primary outcome was overall survival; secondary outcomes were morbidity and tumour response. RESULTS: The survival probabilities at 1, 2 and 3 years were 76.6, 55.5 and 50%, respectively. At 6 months after the first intervention, 31% of patients had a partial response and 60% had stable disease by RECIST criteria. Minor adverse events occurred after 39% of TACEs and major adverse events after 20% of sessions, including two treatment-related deaths (4% of patients). One patient had complete cancer remission after undergoing three TACE treatments. Further progression of tumour growth was prevented in 91% of tumours at the 6 month point after the first TACE. At 3 months, serum levels of the tumour marker alpha-feto protein were significantly reduced in patients with elevated levels before TACE. CONCLUSIONS: The survival probabilities at 1 and 2 years after TACE were comparable with results in randomised studies from Europe and Asia. Most patients tolerated TACE well, but clinicians need to be aware that moderately severe sideeffects require close monitoring and prompt intervention.

A shot through the window.

At issue in this case was whether an unusual window defect seen in two of the crime scene photographs was due to a bullet and if so, if that same bullet fatally wounded the victim. The window appeared to have been cracked prior to the apparent shot through it. A .22 bullet recovered from autopsy, when examined only by light microscopy, failed to show associated glass fragments. A previously cracked test window was shot a number of times with .22 caliber bullets near the cracks in an effort to simulate the window defect seen in the crime scene photographs. Several of the defects produced by the test window shots appeared similar to the crime scene window defect. The .22 bullet taken from the victim and several of the test bullets (collected by a cotton box) were examined by scanning electron microscopy/energy dispersive X-ray spectroscopy. The test bullets showed glass particles on and embedded in their surfaces. Particles of similar size and composition were found embedded in the surface of the bullet from the victim. The bullet likely struck the window prior to hitting the victim. It was apparent by the morphology of some of the mushroomed test .22 bullets that they hit the window crack. These bullets showed that the glass on one side of a crack often fails before the other side during the strike. Aggregations of powdered glass on many of the mushroomed surfaces of the .22 bullets suggest that as the bullet mushrooms during impact on the window surface, the glass in contact with the bullet powderizes and coats the mushroomed surface of the bullet with a layer of fine glass particles.

The first mail bomb?

A news item in the newspaper, the Evening Star, for the Country, October 18, 1833, probably is the first report of a mail bomb in the United States. It is also likely to be the first defusing of a mail bomb. The device appeared to be extraordinarily sophisticated and would have likely worked had it not been for suspicions of the recipient of the bomb.