7-[125I]iodoclonazepam: purification by high-performance liquid chromatography for use in a very sensitive benzodiazepine radioimmunoassay of broad specificity

The purification of 7-[125I]iodoclonazepam by high-performance liquid chromatography (HPLC) for use in a very sensitive benzodiazepine radioimmunoassay is described. A silica column is used with a non-aqueous eluent and sequential ultra-violet and gamma-ray detection. A commercially available antiserum is used at a dilution of 1:1000. Blood samples are diluted 10-fold with buffer before analysis and only 25 microliters of diluted sample are required per assay tube. Benzodiazepines, but not the radiolabel, appear to be bound by blood proteins in competition with the antiserum and so, if undiluted blood is assayed, erroneously low results are obtained. The minimal sample requirement and the high sensitivity of the assay described here largely avoid this problem while maintaining acceptable detection limits. For diazepam, the detection limit is 2.5 ng/ml in blood or urine (after correction for the initial 10-fold dilution) and therapeutic or sub-therapeutic levels of many other benzodiazepines can be detected. In practice, the assay is reliable, simple to perform and extremely economical.     

Illuminating the benefits and limitations of forensic light sources

Forensic light sources, such as a Crime-lite, are used in forensic laboratories and by police staff in the examination for, and detection of, biological material. Whilst the benefits of using forensic light sources are relatively well understood, their limitations are less-so. This report details the outcome of studies, validation and review by three forensic laboratories, as well as three case examples, to highlight both the strengths and weaknesses of the tested forensic light sources and to demonstrate that, whilst a useful preliminary screening tool, they should not be used in isolation without subsequent presumptive chemical testing. False positives and negatives are common, and the background substrate and specific biological material present can have a significant effect on the outcome of examination when using a forensic light source.     

The FAA's postmortem forensic toxicology self-evaluated proficiency test program: the first seven years

Existing proficiency-testing (PT) programs do not address the complexity of postmortem forensic toxicology. These programs do not include decomposed samples and solid tissues. Therefore, the Federal Aviation Administration in July 1991 started such a needed PT program. This program is used to: (i) professionally develop and maintain technical currency on a voluntary, interlaboratory, and self-evaluation basis, and (ii) quantifiably assess methods in the absence and presence of interfering substances. There are currently about 30 laboratories in the program. Functioning under various governmental/non-governmental agencies and academic institutions, these laboratories represent a broad cross-section of the country. PT samples are distributed quarterly, and result summaries are sent to the participants, while maintaining their anonymity. Since the inception of the program, 28 PT samples encompassing whole blood, plasma, urine, kidney, or liver, with (or without) drugs, metabolites, and common chemicals (nicotine, caffeine, beta-phenylethylamine, etc.) have been analyzed by the participants. Analytical findings were generally consistent with the anticipated values, but they were dependent on the nature and conditions of the specimens and types of the added analytes. Some incidences of false positives of concern were noted, as well. This PT program is one of the few programs recommended by the American Board of Forensic Toxicology in which laboratories may participate for their accreditation by the Board. It is anticipated that this PT program will continue to play a critical part in supporting the quality assurance/quality control (QA/QC) component of forensic toxicology, thereby enhancing operational performance.     

Evaluating the sensitivity,stability, and cross-reactivity of commercial fentanyl immunoassay test strips

Illicit fentanyl has flooded the United States' drug market, increasing the risk of overdose and poisonings throughout the general population and accidental exposure among law enforcement officers confiscating the increasing number of seizures. Fentanyl test strips (FTS) are used to obtain presumptive information about the presence of fentanyl in a suspected sample. However, their adoption by law enforcement personnel and seized-drug analysts has been limited because most products are advertised for urine testing, not for assays using water solutions. This study presents an evaluation of four commercial FTS: Rapid Response from BTNX, Inc.; T-Dip Fentanyl (FTY) Urine Dip Cards obtained from Amazon.com ; Premier BioDip FYL10 from Premier Biotech Inc.; and MobileDetect Fentanyl strips from DetectaChem, Inc. Performance characteristics curves were used to compare the products' sensitivity, showing that all can reliably detect fentanyl in aqueous solutions at concentrations below 1 μg/mL, with some of the tests able to reliably detect the drug at 200 ng/mL. A stability study demonstrates the performance of all four FTS brands was only slightly affected after 30 days of storage at two extreme environmental conditions. Fentanyl-related substances are also evaluated using the Rapid Response FTS, which showed high cross-reactivity with para-fluorofentanyl and acetylfentanyl, but lower with ortho-chlorofentanyl, carfentanil, and 4-ANPP. Users should be aware that FTS may give false-negative results even when potentially dangerous levels of carfentanil are present. When testing other common drugs, adulterants, and diluents frequently encountered in seized tablets, concentration-dependent results were obtained and multiple instances of false positives were recorded.     

The consequences of error: Recidivism prediction and civil-libertarian ratios

The utility of recidivistic prediction is limited by the false positive problem: predictions of failure (recidivism) that do not occur. False negatives (predicted successes but observed failures) are also worrisome, and together both types of error can be formally evaluated by what Blumstein, Farrington, and Moitra call the civil-libertarian ratio: the ratio of the subjective cost of a false positive to a false negative. Choice of a recidivistic criterion and selection of a proportion of offenders for criminal justice intervention have implications for the evaluation of the disutility or subjective cost associated with various civil-libertarian ratios. Logistic regression models of four recidivistic criteria are evaluated to demonstrate how base rate (observed failure rate) and selection ratio (proportion selected to fail) affect the disutility associated with a range of civil-libertarian ratios. Use of civil-libertarian ratios by criminal justice policy makers is demonstrated. Predictive utility is relatively difficult to achieve for rare recidivistic events if the decisions involve severe deprivation of liberty (incarceration decisions). Predictive utility is easier to achieve for more common forms of recidivism or in decision contexts where there is less concern for false positives, such as for “intermediate sanctions.”     

Pitfalls in the diagnosis of drug smuggler's abdomen

Narcotics "body packing" can be detected in abdominal X-rays by the ring shadow caused by air trapped in the packs. In a series of 82 cases admitted for abdominal X-ray in Helsinki, Finland, in 1982 through 1988, we encountered 9 (11.0%) true positives, 3 (3.6%) false positives, and 1 (1.2%) false negative. The false positives were due to the constipation often associated with the narcotics abuse. The false negative X-ray diagnosis was attributable to an inexperienced radiologist. False negatives may also be associated with packets containing marijuana, packs with few wrappings, aluminum-foil coated packs, and machine-packed narcotics. Searching for trapped air in radiographs, repeated X-raying by an experienced radiologist, use of computed tomography, or combined urinary drug screening may be applied to diminish false findings and to avoid unnecessary arrest for the purpose of fecal screening over several days.     

Validation of an ELISA-based screening assay for the detection of amphetamine, MDMA and MDA in blood and oral fluid

The use of amphetamine and 'ecstasy' (MDMA) has increased exponentially in many European countries since the late nineties, leading to a rapid growth in the number of clinical and forensic analyses. Therefore, a rapid screening procedure for these substances in biological specimens has become an important part of routine toxicological analysis in forensic laboratories. The objective of this study was to evaluate the Cozart amphetamine enzyme-linked immunosorbent assay (ELISA) for the screening of plasma samples and oral fluid samples (collected with the Intercept device). Authentic plasma samples from drivers (n=360) were screened, using an 1:5-fold dilution. True positive, true negative, false positive and false negative results were determined relative to the in-house routine GC-MS analysis. Samples consisted of 144 amphetamine-only positives, 141MDMA/MDA-only positives, and 74 negatives when using the limit of quantitation as the cut-off level for confirmation (10 ng/mL). Using these results, receiver operating characteristic (ROC) curves were generated and optimal cut-off values for the screening assay were calculated. Analysis showed that the ELISA is able to predict the presence of either amphetamine or *MDMA/MDA (*MDMA as its metabolite MDA) in plasma samples with 98.3% sensitivity and 100% specificity at a cut-off value of 66.5 ng/mL d-amphetamine equivalents. A similar analysis was conducted on 216 oral fluid specimens collected from a controlled double blind study. Subjects received placebo or a high (100 mg) or low (75 mg) dose of MDMA. Oral fluid samples were collected at 1.5 and 5.5h after administration. Combined results of the analysis of the high and low dose oral fluid samples indicated a screening cut-off of 51 ng/mL d-amphetamine equivalents with both a sensitivity and specificity of 98.6% (using a LC-MS/MS confirmation cut-off of 10 ng/mL). In conclusion, these data indicate that the Cozart AMP EIA plates constitute a fast and accurate screening technique for the identification of amphetamine and MDMA/MDA positive plasma samples and oral fluid specimens (collected with Intercept. It should be emphasized that method validation should be performed for each type of biological matrix.     

Using Gas Chromatography with Ion Mobility Spectrometry to Resolve Explosive Compounds in the Presence of Interferents*

Abstract: Ion mobility spectrometry (IMS) is a valued field detection technology because of its speed and high sensitivity, but IMS cannot easily resolve analytes of interest within mixtures. Coupling gas chromatography (GC) to IMS adds a separation capability to resolve complex matrices. A GC‐IONSCAN^® operated in IMS and GC/IMS modes was evaluated with combinations of five explosives and four interferents. In 100 explosive/interferent combinations, IMS yielded 21 false positives while GC/IMS substantially reduced the occurrence of false positives to one. In addition, the results indicate that through redesign or modification of the preconcentrator there would be significant advantages to using GC/IMS, such as enhancement of the linear dynamic range (LDR) in some situations. By balancing sensitivity with LDR, GC/IMS could prove to be a very advantageous tool when addressing real world complex mixture situations.     

Hair analysis by immunological methods from the beginning to 2000

Immunoassays for hair testing must satisfy three requirements: (1) They must have cross-reactivity with parent drug and lipophilic metabolites actually found in hair (2) they must not experience interference from the dissolved hair matrix and (3) they must be titered for cutoffs appropriate to the drug concentrations found in hair. Because the analytes found in hair after drug use are generally the parent drug or its lipophilic metabolites, immunoassays developed and intended for urine testing are not suitable for hair. Immunoassays whose antibodies are bound to a solid support, such as coated-tube radioimmunoassay or coated-plate ELISA tests, experience less matrix interference than those which use other means of separation of bound and free fractions. Homogenous assays are not suitable for hair testing because the hair matrix frequently interferes in the detection of the signal. Historically radioimmunoassays for drugs of abuse were first used for detecting drugs in hair. Currently ELISAs and coated-plate 96 well microplate EIAs are employed for screening hair digests or extracts for drugs. The optimum cutoffs for immunoassays for drugs in hair should be chosen based on the analyte concentration which produces the fewest false positive or false negative results when applied to tests of hair from known users and non-users of drugs. A hair immunoassay test at these cutoffs should have a sensitivity and specificity of better than 90%. The predictive value of the test will depend on the prevalence of drug use in the tested population. Cutoffs or decision thresholds for immunoassays used for screening for drugs should not be at the limit of detection of the assay because that produces a very large incidence of false positives. Because immunoassays are ligand-binding assays, they have a short range of linearity with low precision at both ends of the range. In the future, immunoassays will continue to be used for screening hair and other matrices for drugs of abuse because they provide rapid, inexpensive automated procedures for separating negative specimens from those which are suspected of containing drugs. For forensic purposes, all positive results must be confirmed by an independent analysis using a procedure based on a different property of the analyte. An immunoassay test should not be confirmed by a second immunoassay test but by a chromatographic test performed on a different dissolved or extracted aliquot of the original specimen.     

虚报公司资本与虚假出资行为本不应去罪化

虚报公司资本与虚假出资行为在此次《公司法》修改后依然会存在,而且可能更加泛滥。"两虚"行为是具有可谴责性的不道德行为;侵害登记机关的管理秩序,威胁公司债权人权益、交易安全,社会危害性不容小视。尽管理论上对于"两虚"行为的处罚规定存在质疑,但这些质疑尚不足以推翻一种已运行近二十年并且具有一定的理论和实践基础的制度。此次公司法修改并未就有关争议给出确定性结论。我们在解决争议前本不应让虚报公司资本与虚假出资行为去罪化。     

The detection and separation of antiparkinson preparations in cadaveric material by gas-liquid chromatography

Method of gas-chromatographic detection of anti-parkinsonism substances (amedine, amysile, dinesine, midantane, tropazine and cyclodole) isolated from the cadaveric material is suggested. Conditions for separation of anti-parkinsonism substances when they are all present in the cadaveric material are developed.     

Observations on the specificity of breath-alcohol analyzers used for clinical and medicolegal purposes

This paper deals with the application of three kinds of breath-alcohol analyzer for clinical and medicolegal purposes. The limited specificity for analyzing ethanol in expired breath has given misleading information with potential serious consequences. Three different methods of alcohol analysis are reported: semiconductor sensing (Alcotest 7310), electrochemical fuel cell (Alcolmeter SM-1), and infrared (IR) absorptiometry (IR Intoximeter 3000). Methanol could not be distinguished from ethanol with any of these breath-test instruments. When nonspecific techniques of ethanol analysis are used, the results must be considered with caution when interfering substances expelled in breath cannot be excluded.     

Fourier transform infrared analyses of some particulate drug mixtures using a diamond anvil cell with a beam condenser and an infrared microscope.

Although the diamond anvil cell (DAC) has been used in many forensic science laboratories for the analysis of trace evidence, few applications of this technique for the analysis of controlled substances have been reported. This may be due to both an unfamiliarity on the part of forensic drug chemists with this accessory and the nature and quality of spectra that result from use of a DAC on a dispersive instrument. Along with low energy throughput, which results in relatively high noise levels, strong broad diamond absorptions occur. With the use of a Fourier transform infrared instrument, these do not present a problem and nanogram quantities of materials can be analyzed when the DAC is used with an infrared microscope. Since single crystals can be sampled with the DAC, simple physical separations (involving particle-picking) can be used in certain cases to isolate drugs from particulate mixtures for infrared analysis. This method is especially useful for some "difficult" mixtures and residues, and several examples of such analyses involving samples of forensic science interest are presented.     

毒物分析在侦查破案中的应用

毒物分析主要研究涉及法律问题的生物检材或其他检材中毒物的分离与鉴定,能查明中毒原因,澄清案件性质,在死因鉴定中是不可或缺的关键环节。近年来,随着毒物检验鉴定技术的不断发展,毒物分析技术手段已在侦查破案中发挥着越来越重要的作用。本文报道了两起中毒死亡的案例,通过运用气相色谱-质谱联用技术,在关键检材中分别检出特丁硫磷和一氧化碳目标物质,后结合现场勘查等材料成功侦破,还原了案件真实面目,突显了毒物分析技术在服务和支撑实战中发挥的决定性作用。     

Medical Malpractice Appeals in a Civil Law System: Do Administrative and Civil Courts Award Noneconomic Damages Differently?

How do courts award noneconomic damages? Does it matter if the state is the defendant? This article addresses these questions in the context of medical malpractice appeals to the Spanish Supreme Court. Moreover, this study provides the first empirical analysis of the quantification of noneconomic damages in medical malpractice cases in administrative courts, where the state is the defendant, and in civil courts. This separation of jurisdictions is a common feature in civil law tradition countries. Yet, critics of this separation in general, and specialized courts in particular, argue that parties might be subject to different treatments and that similar cases might reach different outcomes, namely in terms of the quantification of damages. A consistent result of this paper is that no significant differences between noneconomic damages in civil and administrative appeals were found. The separation of jurisdictions does not necessarily imply that courts reach different outcomes, even when the state is the defendant. Citizens should not refrain from bringing their claims forward against the state, a more powerful party. In the current era of increasing juridification and judicialization of modern life (Ginsburg 2009; Hirschl 2006; Hirschl 2011), it is crucial for society that citizens and other parties litigating with the state are not disadvantageously treated.     

Experimental results on data analysis algorithms for extracting and interpreting edge feature data for duct tape and textile physical fit examinations

A physical fit is an important observation that can result from the forensic analysis of trace evidence as it conveys a high degree of association between two items. However, physical fit examinations can be time-consuming, and potential bias from analysts may affect judgment. To overcome these shortcomings, a data analysis algorithm using mutual information and a decision tree has been developed to support practitioners in interpreting the evidence. We created these tools using data obtained from physical fit examinations of duct tape and textiles analyzed in previous studies, along with the reasoning behind the analysts' decisions. The relative feature importance is described by material type, enhancing the knowledge base in this field. Compared with the human analysis, the algorithms provided accuracies above 90%, with an improved rate of true positives for most duct tape subsets. Conversely, false positives were observed in high-quality scissor cut (HQ-HT-S) duct tape and textiles. As such, it is advised to use these algorithms in tandem with human analysis. Furthermore, the study evaluated the accuracy of physical fits when only partial sample lengths are available. The results of this investigation indicated that acceptable accuracies for correctly identifying true fits and non-fits occurred when at least 35% of a sample length was present. However, lower accuracies were observed for samples prone to stretching or distortion. Therefore, the models described here can provide a valuable supplementary tool but should not be the sole means of evaluating samples.     

The spatial distribution of zinc and cobalt in single human head hairs.

The concentration patterns of indigenous zinc and of zinc and cobalt absorbed from radiotracer solutions have been measured via flameless AA and radioactivity assay, respectively, in individual human head hairs. Patterns for indigenous zinc were found to be relatively flat and featureless. Patterns for absorbed zinc (like those for indigenous and absorbed copper in the same subjects) showed increasing concentrations with increasing distance from the root, plus zones of locally increased concentrations at positions different from those for zones of increased copper concentrations. In bleached hair, indigenous zinc concentrations were decreased, and absorbed zinc and cobalt concentrations were increased compared to values in normal hair. The data for absorbed zinc and cobalt were interpreted in terms of a variable concentration of metal-binding sites in the hair structure, coupled with an increased porosity induced by hair bleaching. The flat patterns for the indigenous zinc content were interpreted as indicating the importance of dietary zinc and incorporation via the follicle, and the unimportance of external contamination as the source of this zinc. The forensic implications of the data have been discussed.     

The Waning of Legality in the Concept of Policy Implementation

The study of "implementation" has become a favorite subject of policy sciences in recent years. In part, this interest has been stimulated by the disappointments of the "great society program" in the United States in the sixties where goals formulated at the program level very often were not implemented. In the context of European constitutional thinking, the topic gains an ideological-critical emphasis. For those who believe in the reality of normative theories of separation of powers, it comes as a surprise that though political goals may be determined at the policy-formulation level, it is at the implementation stage where decisionmakers have a full range of possibilities to fulfill or to displace such goals. Concepts similar to "policy" and "implementation" (which are untranslatable in German legal language) have nevertheless been implicit in theories claiming a tendency to replace "conditional," compliance-oriented laws with goal-oriented legislation. To the degree that executive agencies become less strictly bound by precise legal rules and more by goal-oriented policy programs, they seem to lose legal legitimacy. This has to be replaced by increasing responsiveness at the implementation phase, which can be enhanced institutionally through participation, or what we might call the "democratic legitimacy of implementation."     

Shame,anger, and conflict: Case study of emotional violence

This paper proposes a new theory and method for understanding emotional violence: conflict results from threats to the social bond. Protracted conflict may be a result of social-emotional separation and unacknowledged shame. A single case is used to analyze the dynamics of marital conflict. Discourse is analyzed during an actual quarrel; sequences of emotion are traced prior to moments of escalation. The results indicate that not only did anger occur during conflict, but also it was preceded by unacknowledged shame. Sequences within and between spouses alternated from emotional separation and shame, to anger, to disrespect, to further separation and shame, and so on. Interaction in this couple was marked by alienation rather than solidarity.     

The false claims act and the eroding scienter in healthcare fraud litigation

This article addresses the federal government's expansive methods in tackling healthcare fraud, particularly in misapplying the False Claims Act. Although tasked with the obligation to curtail the fraudulent submission of Medicare & Medicaid claims, the U.S. government must rein in the current trend to utilize the False Claims Act against smaller medical providers. As the Act's original focus has ebbed in significance, the government has increasingly applied the False Claims Act to circumstances that do not evince actual fraud. In doing so, federal courts have effectively eroded the statute's critical scienter requirement. The federal common-law doctrines of "payment by mistake" and "unjust enrichment" adequately address the payment of non-fraudulent, albeit false, Medicare & Medicaid claims. Yet the federal government pursues these appropriate remedies only rarely and in the alternative, essentially when the government fails under the False Claims Act. Thus, this article argues for reform, calling for a clearer delineation between remedial and punitive measures. In cases involving smaller medical providers, courts should strictly limit the False Claims Act to those instances where fraud is clearly manifest.