A combined cowhide/gelatine soft tissue simulant for ballistic studies.

The ballistic resistance of a combined soft tissue simulant was studied, consisting of gelatine as a simulant for human muscle tissue and tanned cowhide (leather) as a simulant for human skin. The simulant was manufactured by applying cowhide to liquid ballistic gelatine, as the gelatine solidified in its mould. Combining a skin and muscle tissue simulant in this adhered way opens the possibility to produce purpose-built proxies for human body parts in ballistic studies or for forensic shooting incident reconstructions. Ballistic resistance of adhered cowhide - (bonded) to solidifying ballistic gelatine - was compared to that of the same material applied on gelatine blocks in loose condition. Ballistic resistance of tanned cowhide was found to be more consistent in adhered condition. This enhanced consistency is a benefit, increasing reproducibility of results in ballistic studies. Additionally, two ways to assess ballistic resistance of a skin simulant were described and compared. Logistic regression, from a number of measured velocities and associated (non)perforations is recommended for testing ballistic resistance.

Preoperative PSMA-PET/CT as a predictor of biochemical persistence and early recurrence following radical prostatectomy with lymph node dissection.

BACKGROUND: This study aims to evaluate the predictive value of lymph nodes (LN) suspicious for metastases on preoperative prostate-specific membrane antigen (PSMA) PET/CT for biochemical persistence (BCP) and early biochemical recurrence (BCR) following robotic-assisted radical prostatectomy (RARP) with extended pelvic LN dissection (ePLND). METHODS: We evaluated 213 patients with intermediate and high-risk prostate cancer (PCa) who underwent clinical staging with preoperative 68Ga- or 18F-PSMA-PET/CT scan and subsequent RARP with ePLND. Patients were grouped as PSMA- or PSMA+ depending on their LN status on PSMA-PET/CT and subdivided according to histological LN status in pN0 or pN1. Diagnostic accuracy of PSMA-PET/CT for the detection of pN1 was evaluated. BCP was defined as a first postoperative serum PSA level ≥0.1 ng/mL 6-12 weeks following RP. Early BCR was defined as detectable PSA > 0.2 ng/mL within 12 months of follow-up. Univariable logistic regression analyses were used to evaluate the effect of PSMA+ on BCP and BCR. RESULTS: Forty patients (19%) were PSMA+. The overall incidence of pN1 was 23%. Sensitivity, specificity, PPV and NPV on a per patient level for the detection of pN1 was 29%, 84%, 35%, and 80% respectively. BCP was observed in 26 of 211 patients (12%) and early BCR in 23 of 110 patients (21%). The presence of PSMA+ was a significant predictor for BCP (OR 7.1, 2.9-17.1 95% CI) and BCR (OR 8.1, 2.9-22.6 95% CI). CONCLUSION: Preoperative PSMA-PET/CT may be a valuable tool for patient counseling for RARP and ePLND as it is a significant predictor for the risk of postoperative BCP and early BCR. We conclude that an ePLND should not be avoided in men with intermediate or high-risk PCa and preoperative negative PSMA-PET/CT, as 20% have microscopic LN metastasis.

Error estimation on extracorporeal trajectory determination from body scans.

This study explores the magnitude of two sources of error that are introduced when extracorporeal bullet trajectories are based on post-mortem computed tomography (PMCT) and/or surface scanning of a body. The first source of error is caused by an altered gravitational pull on soft tissue, which is introduced when a body is scanned in another position than it had when hit. The second source of error is introduced when scanned images are translated into a virtual representation of the victim's body. To study the combined magnitude of these errors, virtual shooting trajectories with known vertical angles through five "victims" (live test persons) were simulated. The positions of the simulated wounds on the bodies were marked, with the victims in upright positions. Next, the victims were scanned in supine position, using 3D surface scanning, similar to a body's position when scanned during a PMCT. Seven experts, used to working with 3D data, were asked to determine the bullet trajectories based on the virtual representations of the bodies. The errors between the known and determined trajectories were analysed and discussed. The results of this study give a feel for the magnitude of the introduced errors and can be used to reconstruct actual shooting incidents using PMCT data.

Pistol bullet deflection through soft tissue simulants.

Trajectory deflections of pistol bullets from four different firearms, fired through soft tissue simulants under two different incidence and exit angles were studied. The data from this study can be used in reconstructions of shooting incidents where human soft tissues (not bones) were perforated with pistol bullets and assumptions must be made about bullet deflection in order to correctly reconstruct trajectories. The results demonstrate that deflection was influenced by the length of the "wound channel" through the simulants. In short, deflection was small to virtually absent with 5 and 10cm channel lengths. With channel lengths of 15, 20 and 25cm, there was a clear increase in deflection and/or a more erratic deflection behaviour with most shots. The data also suggest an influence of the angle of incidence and/or exit on both the direction and the magnitude of the deflection.

The adaptation rate of a quantitative trait in an environmental gradient.

The spatial range of a species habitat is generally determined by the ability of the species to cope with biotic and abiotic variables that vary in space. Therefore, the species range is itself an evolvable property. Indeed, environmental gradients permit a mode of evolution in which range expansion and adaptation go hand in hand. This process can contribute to rapid evolution of drug resistant bacteria and viruses, because drug concentrations in humans and livestock treated with antibiotics are far from uniform. Here, we use a minimal stochastic model of discrete, interacting organisms evolving in continuous space to study how the rate of adaptation of a quantitative trait depends on the steepness of the gradient and various population parameters. We discuss analytical results for the mean-field limit as well as extensive stochastic simulations. These simulations were performed using an exact, event-driven simulation scheme that can deal with continuous time-, density- and coordinate-dependent reaction rates and could be used for a wide variety of stochastic systems. The results reveal two qualitative regimes. If the gradient is shallow, the rate of adaptation is limited by dispersion and increases linearly with the gradient slope. If the gradient is steep, the adaptation rate is limited by mutation. In this regime, the mean-field result is highly misleading: it predicts that the adaptation rate continues to increase with the gradient slope, whereas stochastic simulations show that it in fact decreases with the square root of the slope. This discrepancy underscores the importance of discreteness and stochasticity even at high population densities; mean-field results, including those routinely used in quantitative genetics, should be interpreted with care.

Can postmortem MRI be used to assess trajectories in gunshot victims?

PURPOSE: Multi-detector computed tomography (MDCT) has proven to be of value for the reconstruction of trajectories of projectiles and the assessment of the injuries in deceased gunshot victim. For the depiction of soft tissue injury, MRI is superior to MDCT and MRI may be of value to assess trajectories. In a clinical setting, there are guidelines for the application of MRI in patients with projectiles or projectile fragments and with precautions MRI is safe for these patients. However, this has not been studied for the postmortem application of MRI from a forensic point of view. SUBJECTS AND METHOD: To assess the behaviour of projectiles, two ferromagnetic and one non-ferromagnetic projectile were exposed to the magnetic field of a 1.5- and 3-T MRI. Projectiles were placed in six phantoms with the characteristics of human muscle tissue, with and without a simulated trajectory in the gel. Before and after exposure to the magnetic field, the gelatine phantoms were imaged with MDCT to assess the position of the projectiles. RESULTS: The ferromagnetic projectiles rotate to a position where their long axis is parallel to the z-axis of the magnetic field and five out of the six projectiles moved through, either through the simulated trajectory or through a new trajectory. This was observed in both the 1.5- and 3-T systems. CONCLUSION: Ferromagnetic projectiles can rotate and migrate in a gelatine phantom. It is very likely that these projectiles will also migrate in a human body in a MRI system. Therefore, from a forensic point of view, postmortem MR will make a reconstruction of the trajectories in the body and of the reconstruction of the incident as a whole less reliable.

Design and results of an exploratory double blind testing program in firearms examination.

In 2010, the Netherlands Forensic Institute (NFI) and the University of Amsterdam (UvA) started a series of tests for the NFI's Firearms Section. Ten cartridge case and bullet comparison tests were submitted by various external parties as regular cases and mixed in the flow of real cases. The results of the tests were evaluated with the VU University Amsterdam (VUA). A total of twenty-nine conclusions were drawn in the ten tests. For nineteen conclusions the submitted cartridge cases or bullets were either fired from the questioned firearm or from one and the same firearm, in tests where no firearm was submitted. For ten conclusions the submitted cartridge cases or bullets were either fired from another firearm than the submitted one or from several firearms, in tests where no firearm was submitted. In none of the conclusions misleading evidence was reported, in the sense that all conclusions supported the true hypothesis. This article discusses the design considerations of the program, contains details of the tests, and describes the various ways the test results were and could be analyzed.

A discussion on the usefulness of a shared European ballistic image database.

The introduction of electronic systems into the comparison of weapon marks in the mid 1990s caused a revolution in the discipline of "forensic ballistics". Most European states now use this technology to search their national open case files. Globalisation of crime and the loss of effective border controls have made the idea of a unified European ballistic system seem logical. The article critically considers the requirements and possible outcomes of such a system. Based on the experience of forensic practitioners it seems probable that a shared European electronic ballistic system will be of a very limited value at present. Further improvements of existing systems to reach compatibility are encouraged.

Increased oxytocin concentrations and prosocial feelings in humans after ecstasy (3,4-methylenedioxymethamphetamine) administration.

MDMA (3,4-methylenedioxymethamphetamine or "ecstasy") is a recreationally used drug with remarkable and characteristic prosocial effects. In spite of abundant attention in the scientific literature, the mechanism of its prosocial effects has not been elucidated in humans. Recently, research in animals has suggested that the neuropeptide oxytocin may induce these effects. In a double blind, randomized, crossover, and placebo-controlled study in 15 healthy volunteers we assessed blood oxytocin and MDMA concentrations and subjective prosocial effects after oral administration of 100 mg MDMA or placebo. MDMA induced a robust increase of blood oxytocin concentrations and an increase of subjective prosocial feelings. Within subjects, the variations in these feelings were significantly and positively correlated with variation in oxytocin levels, and the correlations between these feelings and oxytocin were significantly stronger than those between these feelings and blood MDMA levels. MDMA induces oxytocin release in humans, which may be involved in the characteristic prosocial effects of ecstasy.

Chemotherapy response evaluation with FDG-PET in patients with colorectal cancer.

BACKGROUND: The aim of this prospective study was to evaluate the value of F-18-fluorodeoxyglucose-positron emission tomography (FDG-PET) for early assessment of chemotherapy response in patients with advanced colorectal cancer. METHODS: Dynamic FDG-PET was carried out before and at 2 (n = 50) and 6 months (n = 19) after the start of treatment. Quantitative Patlak analysis [metabolic rate of glucose (MRGlu)] and a simplified method to measure glucose metabolism [standardized uptake value (SUV)] were evaluated. The predictive value of changes in glucose metabolism was assessed with Cox proportional regression analysis. Overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier estimates. RESULTS: There was an increase in the rates of death (P = 0.049 for DeltaMRGlu PET1-2; P = 0.017 for DeltaSUV PET1-2; P = 0.032 for DeltaMRGlu PET1-3; P = 0.048 for DeltaSUV PET1-3) and progression (P = 0.026 for DeltaMRGlu PET1-2; P = 0.035 for DeltaSUV PET1-2; P = 0.041 for DeltaMRGlu PET1-3; P = 0.081 for DeltaSUV PET1-3) associated with worse response as assessed by PET on Cox proportional regression analysis. The OS and PFS analysis showed a significant predictive value at broad ranges of DeltaMRGlu and DeltaSUV cut-off levels. CONCLUSION: The degree of chemotherapy-induced changes in tumor glucose metabolism is highly predictive for patient outcome. The use of FDG-PET for therapy monitoring seems clinically feasible since simplified methods (SUV) are sufficiently reliable.

Image matching algorithms for breech face marks and firing pins in a database of spent cartridge cases of firearms.

On the market several systems exist for collecting spent ammunition data for forensic investigation. These databases store images of cartridge cases and the marks on them. Image matching is used to create hit lists that show which marks on a cartridge case are most similar to another cartridge case. The research in this paper is focused on the different methods of feature selection and pattern recognition that can be used for optimizing the results of image matching. The images are acquired by side light images for the breech face marks and by ring light for the firing pin impression. For these images a standard way of digitizing the images used. For the side light images and ring light images this means that the user has to position the cartridge case in the same position according to a protocol. The positioning is important for the sidelight, since the image that is obtained of a striation mark depends heavily on the angle of incidence of the light. In practice, it appears that the user positions the cartridge case with +/-10 degrees accuracy. We tested our algorithms using 49 cartridge cases of 19 different firearms, where the examiner determined that they were shot with the same firearm. For testing, these images were mixed with a database consisting of approximately 4900 images that were available from the Drugfire database of different calibers.In cases where the registration and the light conditions among those matching pairs was good, a simple computation of the standard deviation of the subtracted gray levels, delivered the best-matched images. For images that were rotated and shifted, we have implemented a "brute force" way of registration. The images are translated and rotated until the minimum of the standard deviation of the difference is found. This method did not result in all relevant matches in the top position. This is caused by the effect that shadows and highlights are compared in intensity. Since the angle of incidence of the light will give a different intensity profile, this method is not optimal. For this reason a preprocessing of the images was required. It appeared that the third scale of the "à trous" wavelet transform gives the best results in combination with brute force. Matching the contents of the images is less sensitive to the variation of the lighting. The problem with the brute force method is however that the time for calculation for 49 cartridge cases to compare between them, takes over 1 month of computing time on a Pentium II-computer with 333MHz. For this reason a faster approach is implemented: correlation in log polar coordinates. This gave similar results as the brute force calculation, however it was computed in 24h for a complete database with 4900 images.A fast pre-selection method based on signatures is carried out that is based on the Kanade Lucas Tomasi (KLT) equation. The positions of the points computed with this method are compared. In this way, 11 of the 49 images were in the top position in combination with the third scale of the à trous equation. It depends however on the light conditions and the prominence of the marks if correct matches are found in the top ranked position. All images were retrieved in the top 5% of the database. This method takes only a few minutes for the complete database if, and can be optimized for comparison in seconds if the location of points are stored in files. For further improvement, it is useful to have the refinement in which the user selects the areas that are relevant on the cartridge case for their marks. This is necessary if this cartridge case is damaged and other marks that are not from the firearm appear on it.

Thiolated recombinant human tumor necrosis factor-alpha protects against Plasmodium berghei K173-induced experimental cerebral malaria in mice.

The introduction of reactive thiol groups in recombinant human tumor necrosis factor (TNF) alpha (rhTNF-alpha) by the reagent succinimidyl-S-acetylthioacetate resulted in the formation of a chemically stabilized rhTNF-alpha trimer (rhTNFalpha-AT; as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis). rhTNFalpha-AT showed a substantially enhanced protective efficacy against the development of experimental murine cerebral malaria (ECM) after intravenous injection compared to the protective efficacy of nonmodified rhTNF-alpha. Administration of thiolated rhTNF-alpha with protected thiol groups (rhTNFalpha-ATA; no stabilized trimers in vitro) exhibited the same protective efficacy against ECM, while in vitro bioactivity was reduced. Parasitemia was significantly suppressed in rhTNF-treated mice that were protected against ECM but not in treated mice that developed ECM. Protection against ECM was not related to increased concentrations in plasma of soluble TNF receptor 1 and 2 directly after injection or at the moment of development of ECM in nontreated mice. The results indicate that thiolation of rhTNF-alpha leads to the formation of stable trimers with increased potential in vivo.

A monoclonal antibody against tumour necrosis factor-alpha improves survival in experimental multiple organ dysfunction syndrome.

A single intraperitoneal administration of zymosan induces multiple organ dysfunction syndrome (MODS) in C57BL/6 mice. The authors investigated the effect of a monoclonal antibody V1q against murine tumour necrosis factor alpha (TNF-alpha) on the development of zymosan-induced MODS and on plasma concentrations and the production capacity of interleukin 6 (IL-6) by peritoneal cells. C57BL/6 mice received doses of V1q starting either simultaneously with administration of zymosan every four days, or from 4 or 8 days after administration of zymosan onwards. The animals were monitored for survival, condition, and body weight and temperature. Twelve days after zymosan all surviving animals were killed to obtain plasma, organs and peritoneal cells. Plasma concentrations of IL-6 and lipopolysaccharide-stimulated production of IL-6 by peritoneal cells were measured; organs were weighed as an indicator for organ damage and lung damage was assessed macroscopically. Survival improved when the animals were treated with V1q starting at either time point, and a subpopulation developed from the group receiving V1q from day 0 onwards that displayed improved body weight and temperature when compared to the animals receiving zymosan only. Also, the wet organ weights improved in this subgroup, indicating a beneficial effect of the monoclonal antibody. However, V1q administered could neither decrease the circulating IL-6 concentrations toward control values, nor did V1q treatment normalize IL-6 production capacity (stimulated or unstimulated). The development of zymosan-induced MODS can be attenuated by the monoclonal antibody V1q.

Origin of endotoxemia influences the metabolic response to endotoxin in dogs.

Different routes of endotoxin administration have been used to mimic inflammatory and metabolic responses observed during sepsis. Because the origin of endotoxemia may affect the reactions to endotoxin, we compared the induction of tumor necrosis factor (TNF), interleukin-6 (IL-6), hormones, and glucose production after endotoxin (1.0 microg/kg Escherichia coli 0111:B4) administration into a peripheral (n = 8) versus the portal (n = 8) vein in anesthetized dogs. Prior to endotoxin, a laparotomy was performed for cannulation of hepatic vessels. To evaluate the effects of surgery and anesthesia, we also studied the effects of peripheral endotoxin administration in six awake dogs. The rate of appearance of glucose was measured by primed continuous infusion of [6,6-2H2]glucose. In anesthetized dogs, arterial concentrations of TNF and IL-6 increased after endotoxin administration (P < 0.01 vs basal; NS between groups). Net hepatic TNF production was increased after endotoxin administration (peripheral vs portal endotoxin administration: 533 +/- 177 vs 2135 +/- 1127 ng/min, both P < 0.05 vs basal; NS between groups). Net hepatic IL-6 production was stimulated only after portal endotoxin delivery (from 86 +/- 129 to 4740 +/- 1899 ng/min, P < 0.05; NS between groups). Although there were no differences in neuroendocrine activation, portal endotoxin administration resulted in decreased glucose production compared with peripheral administration (13.6 +/- 0.9 vs 16.8 +/- 1.2 micromol/kg.min, P < 0. 05). In contrast to anesthetized dogs, endotoxin increased glucose production considerably in awake dogs from 13.8 +/- 1.2 to 24.2 +/- 3.2 micromol/kg.min (P < 0.05; P < 0.05 vs anesthetized dogs). The contribution of anesthesia and surgery increased the endotoxin-induced IL-6 response by approximately 350% compared with the effect of endotoxin in awake dogs (P < 0.01). In conclusion, there are no major differences in the responses to endotoxin between peripherally treated and portally treated dogs, except for differences in glucose production. Portal delivery compared with systemic delivery of endotoxin alters hepatic metabolism through nonendocrine mechanisms, reflected in decreased glucose production. The inflammatory, endocrine, and metabolic effects of endotoxin are altered by the combination of surgery and anesthesia.

The influence of absolute humidity on shear bond adhesion.

OBJECTIVES: The purpose of this study was to investigate the relationship between dentine shear bond strength, using data from experiments performed according to a standard protocol, and the absolute humidity for a new, fourth generation dentine adhesive system. METHODS: Results of seven recently performed adhesion experiments using the same protocol and product were analysed. Groups of 10 human molars were each bonded in a humidity chamber. The temperature and relative humidity conditions varied from 23 to 37 degrees C and 30 to 95%. After bonding of the composite resin a shear bond test at a crosshead speed of 2.0 mm/min was performed. RESULTS: The bond strength levels of the dentine adhesive system were influenced significantly by extreme temperature and humidity differences. Adhesion levels varied from 27.8 (SD 8.5) MPA to 12.8 (SD 1.4) MPA. Isobond strength curves are a good method to gain insight into the humidity sensitivity of adhesive systems. CONCLUSIONS: Results of in vitro adhesive bonding procedures for a dentine adhesive can be significantly influenced by the absolute humidity levels at which the procedures are performed. Consequently "Materials and Methods" sections of publications should refer to absolute humidity or temperature and relative humidity levels as a relevant parameter.

Antimalarial and toxic effects of the acyclic nucleoside phosphonate (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine in Plasmodium berghei-infected mice.

Plasmodium berghei-infected mice died with low levels of parasitemia after repeated intraperitoneal administration (five times at 15 mg kg of body weight-1 every other day) of the in vitro active antimalarial acyclic nucleoside phosphonate (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA]. Toxicological studies showed that the main cause of death resulted from (S)-HPMPA-induced nephrotoxicity. Although concomitant intraperitoneal administration of the tubular epithelium transport blocker probenecid prevented (S)-HPMPA-induced toxicity, mice eventually died with a high level of parasitemia, despite repeated administration of high doses of (S)-HPMPA. The short half-life of (S)-HPMPA in plasma combined with the insusceptibility of the nonreplicative stages of the parasite to (S)-HPMPA could explain this failure to eradicate all parasites. Indeed, a low but sustained (calculated) level of 200 nM (S)-HPMPA in plasma completely cured P. berghei-infected mice. However, these mice, which received a total dose of only 28 mg kg-1 administered via osmotic pumps for 7 days, died because of the toxicity of the drug. These findings indicate that nephrotoxicity hinders the use of (S)-HPMPA as a drug against blood stage parasites. An alternative application of (S)-HPMPA as a potent prophylactic drug is discussed.

Intraoral humidity during operative procedures.

Results of dentine adhesion studies are influenced by many factors such as intrinsic and extrinsic dentine wetness. Relative air humidity and temperature are extrinsic environmental factors whose influence on dentine bonding capability is not precisely known. It was the aim of this study to gain an understanding of these factors as present in the mouths of patients and as influenced by several variables. In six different experiments the influence of application of a rubber dam, high and low relative humidity in the dental surgery, nose and mouth breathing and tooth drying was investigated. The results show that without application of a rubber dam there was no statistically significant difference in temperature for the variables nose and mouth breathing and tooth drying (mean 27.7 +/- 1.5 degrees C). Only the difference in relative air humidity of the dental surgery was statistically significant. With the application of a rubber dam the relative air humidity and temperature were essentially the same as the dental surgery conditions. It is concluded that without rubber dam the intraoral environment in which bonding procedures are to be performed is comparable with a high humidity climate such as that of Central Africa or the South Pacific.

Loss of enamel due to etching with phosphoric or maleic acid.

In this study, the effect of enamel etching resulting in permanently lost enamel was investigated. Phosphoric acid and maleic acid were used as etchants. Also the etch duration was varied. The results of the study show that phosphoric acid removed significantly more enamel than maleic acid. The relationship found between the loss of enamel and the etch duration suggested that a diffusion controlled mechanism plays a role in the case of both acids. Morphological information obtained by scanning electron microscopy indicated that the surface structure resulting from etching with phosphoric acid and maleic acid is similar.