Human dental age estimation by calculation of pulp-tooth volume ratios yielded on clinically acquired cone beam computed tomography images of monoradicular teeth

Abstract: Secondary dentine is responsible for a decrease in the volume of the dental pulp cavity with aging. The aim of this study is to evaluate a human dental age estimation method based on the ratio between the volume of the pulp and the volume of its corresponding tooth, calculated on clinically taken cone beam computed tomography (CBCT) images from monoradicular teeth. On the 3D images of 111 clinically obtained CBCT images (Scanora^®3D dental cone beam unit) of 57 female and 54 male patients ranging in age between 10 and 65 years, the pulp–tooth volume ratio of 64 incisors, 32 canines, and 15 premolars was calculated with Simplant^® Pro software. A linear regression model was fit with age as dependent variable and ratio as predictor, allowing for interactions of specific gender or tooth type. The obtained pulp–tooth volume ratios were the strongest related to age on incisors.     

Psychopathic traits in Finnish homicide offenders with schizophrenia

There is a paucity of studies examining psychopathy in comparable samples of violent individuals with and without psychotic illness. The main goal of the study was to assess the prevalence and nature of psychopathic traits as measured by PCL-R among Finnish homicide offenders with schizophrenia. Further, the impact of co-morbid psychopathy on the homicidal incidents, as well as the associations of psychopathy and offender background factors, among offenders with schizophrenia was investigated.A retrospective study was performed using extensive forensic psychiatric evaluation reports and crime reports as sources of information. The sample consisted of 72 homicide offenders with schizophrenia and 72 controls without psychotic illness.Psychopathic features were prevalent among Finnish homicide offenders with schizophrenia, although for the most parts to a lesser extent compared to other homicide offenders. Like non-mentally ill psychopathic offenders, offenders with schizophrenia and many psychopathic traits are likely to present early starting problems in many areas of life and they also commit homicides that resemble other psychopathic offenders' in their choice of victims, intoxication and post-offense behavior.The observed prevalence of psychopathic traits highlights the importance of psychopathy assessment among violence-prone individuals with schizophrenia. In most respects, offenders with schizophrenia and high levels of psychopathic traits seem to be similar to psychopathic offenders without psychotic illness, which has implications for early intervention and management.     

License Compliance Issues For Biopharmaceuticals: Special Challenges For Negotiations Between Companies And Non-Profit Research Institutions

Biopharmaceuticals are therapeutic products based on biotechnology. They are manufactured by or from living organisms and are the most complex of all commercial medicines to develop, manufacture and qualify for regulatory approval. In recent years biopharmaceuticals have rapidly increased in number and importance with over 400() already marketed in the U.S. and European markets alone. Many companies throughout the world are now ramping up investments in biopharmaceutical R&D and expanding their portfolios through licensing of early-stage biotechnologies from universities and other non-profit research institutions, and there is an increasing number of license agreements for biopharmaceutical product development relative to traditional small molecule drug compounds. This trend will only continue as large numbers of biosimilars and biogenerics enter the market.A primary goal of technology transfer offices associated with publicly-funded, non-profit research institutions is to establish patent protection for inventions deemed to have commercial potential and license them for product development. Such licenses help stimulate economic development and job creation, bring a stream of royalty revenue to the institution and, hopefully, advance the public good or public health by bringing new and useful products to market. In the course of applying for such licenses, a commercial development plan is usually put forth by the license applicant. This plan indicates the path the applicant expects to follow to bring the licensed invention to market. In the case of small molecule drug compounds, there exists a widely-recognized series of clinical development steps, dictated by regulatory requirements, that must be met to bring a new drug to market, such as completion of preclinical toxicology, Phase 1, 2 and 3 testing and product approvals. These steps often become the milestone/benchmark schedule incorporated into license agreements which technology transfer offices use to monitor the licensee's diligence and progress; most exclusive licenses include a commercial development plan, with penalties, financial or even revocation of the license, if the plan is not followed, e.g., the license falls too far behind.This study examines whether developmental milestone schedules based on a small molecule drug development model are useful and realistic in setting expectations for biopharmaceutical product development. We reviewed the monitoring records of all exclusive Public Health Service (PHS) commercial development license agreements for small molecule drugs or therapeutics based on biotechnology (biopharmaceuticals) executed by the National Institutes of Health (NIH) Office of Technology Transfer (OTT) between 2003 and 2009. We found that most biopharmaceutical development license agreements required amending because developmental milestones in the negotiated schedule could not be met by the licensee. This was in stark contrast with license agreements for small molecule chemical compounds which rarely needed changes to their developmental milestone schedules. As commercial development licenses for biopharmaceuticals make up the vast majority of NIH's exclusive license agreements, there is clearly a need to: 1) more closely examine how these benchmark schedules are formed, 2) try to understand the particular risk factors contributing to benchmark schedule non-compliance, and 3) devise alternatives to the current license benchmark schedule structural model. Schedules that properly weigh the most relevant risk factors such as technology classification (e.g., vaccine vs recombinant antibody vs gene therapy), likelihood of unforeseen regulatory issues, and company size/structure may help assure compliance with original license benchmark schedules. This understanding, coupled with a modified approach to the license negotiation process that makes use of a clear and comprehensive term sheet to minimize ambiguities should result in a more realistic benchmark schedule.     

Under-recording of ethanol intoxication and poisoning in cause-of-death data: causes and consequences

In the present study we examined how consistently and completely the role of acute alcohol (ethanol) intake as a cause of death is reported on death certificates, how complete and specific the statistical recording of cause-of-death data on acute alcohol-induced deaths is, and how the information ultimately appears in the national mortality statistics. Data on all alcohol-positive deaths with blood alcohol concentration of ≥ 0.5‰ (g/kg) in Finland in 2005 (N = 2348) were reviewed. Overall, a concentration-dependent association was found between forensic-toxicologically determined blood alcohol concentrations and acute alcohol-specific cause-of-death diagnoses. Based on a medico-legal re-evaluation of death certificates, acute alcohol-specific causes were found to be underreported nationally at a rate of 8%. For accidental alcohol poisonings alone, the figure was about 1%. This underreporting was not corrected during recording of the cause-of-death data, though individual corrections and changes were observed. Especially, recording of multiple causes suffers from this underreporting of acute alcohol-specific causes. ICD-10 seems to do well in fulfilling the demands for a specific classification of uncomplicated alcohol poisoning. In combined alcohol-drug poisonings, however, ICD-10 shows a bias towards drugs over alcohol, even when alcohol has been specified and reported as the most toxic component by the medico-legal pathologist. Since the national statistics is based on the underlying causes, this state of affairs is likely to result in the underestimation of the role of acute alcohol intake as a cause of death. This observation of underreporting of acute alcohol-specific causes on death certificates should result in a harmonisation of education and principles and practices used in death certification. To increase the coverage and specificity of mortality statistics, based on the underlying causes of death, the coding of all components of alcohol-drug combinations and their classification according to the most important intoxicant or combination of intoxicants is recommended.     

Evaluation of vapor profiles of explosives over time using ATASS (Automated Training Aid Simulation using SPME)

Despite numerous instrumental achievements, canines are still considered the most effective field method for explosive detection. However, due to strict explosive regulations and safety requirements, it can be a challenge for agencies with "bomb dogs" to train using neat explosive materials. This establishes a need for non-explosive canine training aids with the same volatile component profiles as the explosives that they represent. In order to compare mimic materials to their explosive counterparts, a technique must be established that not only allows for identification of volatile compounds but also can monitor changes in the headspace profile over time with respect to time and temperature. The Automated Training Aid Simulation using SPME (or ATASS) was developed for that purpose. As described, ATASS was used to observe changes in the volatile profile of three explosives (Composition C-4, 2,4-dinitrotoluene (DNT), and triacetone triperoxide (TATP)) and respective prototype training materials (0.1% by mass C-4, 1% by mass 2,4-DNT, and 1% by mass TATP). Samples were prepared in vials and metal tins within a gallon (≈ 3785 mL) paint can to simulate common field techniques for canine training. Monitoring these materials in real time provides a better understanding of the major volatile components present and how the relative abundances of these components can change over time. The results presented indicate that ATASS successfully allows for a sufficient comparison between explosive and non-explosive training materials.     

Species identification of Papaver by metabolite profiling

This paper analyses and discusses arguments that emerge from a recent discussion about the proper assessment of the evidential value of correspondences observed between the characteristics of a crime stain and those of a sample from a suspect when (i) this latter individual is found as a result of a database search and (ii) remaining database members are excluded as potential sources (because of different analytical characteristics). Using a graphical probability approach (i.e., Bayesian networks), the paper here intends to clarify that there is no need to (i) introduce a correction factor equal to the size of the searched database (i.e., to reduce a likelihood ratio), nor to (ii) adopt a propositional level not directly related to the suspect matching the crime stain (i.e., a proposition of the kind 'some person in (outside) the database is the source of the crime stain' rather than 'the suspect (some other person) is the source of the crime stain'). The present research thus confirms existing literature on the topic that has repeatedly demonstrated that the latter two requirements (i) and (ii) should not be a cause of concern.     

LC-MS-MS analysis of buprenorphine and norbuprenorphine in whole blood from suspected drug users

A liquid chromatography tandem mass spectrometry method is described for the analysis of buprenorphine and norbuprenorphine in whole blood. Linearity was achieved between 0.2-5 ng/g for buprenorphine and 0.5-5 ng/g for norbuprenorphine. Stability studies on spiked whole blood and an authentic sample showed no degradation of buprenorphine- and norbuprenorphine-glucuronide to their respective aglycones. Buprenorphine and norbuprenorphine showed some degradation when stored at 4°C for three weeks, but was stable when stored at -20°C for 4 weeks. The method was applied to forensic cases of driving under the influence of drugs (DUID) and petty drug offences (PDO) during 2007-2009. Out of 2459 cases analyzed, 322 were positive for both buprenorphine and norbuprenorphine (13%), 219 for buprenorphine only (9%), and 12 for norbuprenorphine only (0.5%). The mean and median concentrations (N=322) were 1.7 and 1.0 ng/g, respectively, for buprenorphine and norbuprenorphine. The mean and median norbuprenorphine/buprenorphine ratios were 1.5 and 1.1, respectively. There was no significant difference in concentration ratios for DUID and PDO cases (p>0.05). We conclude that the described method for analysis of buprenorphine and norbuprenorphine in whole blood could be used to investigate use or misuse of buprenorphine but that many of the cases presented with very low concentrations of buprenorphine. We also conclude that analysis should be performed within two weeks unless samples are stored frozen prior to analysis.     

人格权与民法典——人格权的概念和范围

《法国民法典》中的人格权制度出现于二十世纪七十年代。本文作者介绍了《法国民法典》中现有的人格权家族,并构建了理想的人格权框架。作者认为,人格权是一项民事权利而不是一项基本权利,是一项法律赋予人的权利,而不是法律规定的制度。     

Spatially offset Raman spectroscopy (SORS) for the analysis and detection of packaged pharmaceuticals and concealed drugs

Spatially offset Raman spectroscopy (SORS) is a powerful new technique for the non-invasive detection and identification of concealed substances and drugs. Here, we demonstrate the SORS technique in several scenarios that are relevant to customs screening, postal screening, drug detection and forensics applications. The examples include analysis of a multi-layered postal package to identify a concealed substance; identification of an antibiotic capsule inside its plastic blister pack; analysis of an envelope containing a powder; and identification of a drug dissolved in a clear solvent, contained in a non-transparent plastic bottle. As well as providing practical examples of SORS, the results highlight several considerations regarding the use of SORS in the field, including the advantages of different analysis geometries and the ability to tailor instrument parameters and optics to suit different types of packages and samples. We also discuss the features and benefits of SORS in relation to existing Raman techniques, including confocal microscopy, wide area illumination and the conventional backscattered Raman spectroscopy. The results will contribute to the recognition of SORS as a promising method for the rapid, chemically specific analysis and detection of drugs and pharmaceuticals.