A calibration friendly approach to identify drugs of abuse mixtures with a portable near-infrared analyzer

Both the increasing number and diversity of illicit-drug seizures complicate forensic drug identification. Traditionally, colorimetric tests are performed on-site, followed by transport to a laboratory for confirmatory analysis. Higher caseloads increase laboratory workload and associated transport and chain-of-evidence assurance performed by police officers. Colorimetric tests are specific only for a small set of drugs. The rise of new psychoactive substances therefore introduces risks for erroneous results. Near-infrared (NIR)-based analyzers may overcome these encumbrances by their compound-specific spectral selectivity and broad applicability. This work introduces a portable NIR analyzer that combines a broad wavelength range (1300–2600 nm) with a chemometric model developed specifically for forensic samples. The application requires only a limited set of reference spectra for time-efficient model training. This calibration-light approach thus eliminates the need of extensive training sets including mixtures. Performance was demonstrated with 520 casework samples resulting in a 99.6% true negative and 97.6% true positive rate for cocaine. Similar results were obtained for MDMA, methamphetamine, ketamine, and heroin. Additionally, 236 samples were analyzed by scanning directly through their plastic packaging. Also here, a >97% true positive rate was obtained. This allows for non-invasive, operator-safe chemical identification of potentially potent drugs of abuse. Our results demonstrate the applicability for multiple drug-related substances. Ideally, the combination of this NIR approach with other portable techniques, such as Raman and IR spectroscopy and electrochemical tests, may eventually eliminate the need for subsequent laboratory analysis; therefore, saving tremendous resources in the overall forensic process of confirmatory illicit drug identification.     

Rationing and the Role of the Emergency Department as Society''s Safety Net

Emergency medicine has an integral role in the establishment of universal access to health care for all persons living in the United States. Currently, emergency departments provide the only unfunded mandate available to millions of American residents who otherwise have no access to health care coverage. Any effort to establish universal care must accept health care rationing as a basic principle, and establish a minimum standard of benefits to which all human beings are entitled in this country. People and employers should be allowed to purchase additional care based on their willingness and ability to pay, but under no circumstances should anyone be denied a basic package of health care benefits. Emergency care must be part of those basic benefits. Emergency medicine charges should be structured so that they are not unduly onerous to society, and should reflect true expenses, including marginal costs for nonurgent care. Emergency physicians (EPs) and hospital administrations should recognize their critical role in serving society in roles that are not strictly medical, and allocate resources to benefit the general population in the greatest way. This role will be expanded to include preventive care, to provide for basic pharmacologic coverage as needed, and to provide necessary immunizations when traditional primary care has failed. We have a moral obligation to recognize that resources are limited and to allocate them so as to benefit the greatest number of patients in the greatest way. As members of the medical profession best equipped to assume such a task, it is incumbent upon EPs to act as advocates to the public to enable us to fulfill this mission.     

Evaluation of the wash resistance of three types of manufactured insecticidal nets in comparison to conventionally treated nets

The present study evaluated the efficacy and wash resistance of several commercial deltamethrin-treated nets (PermaNet™, from factory (PN-F) and market (PN-M), Yorkool (Y) and AZ net) that were claimed by the manufacturers to be Long-Lasting Insecticide Treated Nets (LLITNs), compared to ITNs conventionally treated with deltamethrin (23-27 mg/m², using one K-O Tab^® tablet (KO) per net). Montpellier washing technique was used for washing the pieces of the nets. Insecticidal activity was assessed on dried pieces of nets after 0, 2, 5, 8, 11, 15, 18 and 21 washes, using two types of bioassay (mean median knock down times and mortality 24 h after a 3-min exposure) and reared female Anopheles stephensi. To evaluate the effect of heat on diffusion of insecticide from inside of the nets to the surface of them, some Permanet nets were heated. For all the types of nets tested the median knock down time (MKDT) increased approximately linearly with number of washes. The slopes of the lines (increase of MKDT per wash) were low with the PN-F and PN-M, intermediate with Y and equally high with KO and AZ. No significant differences can be claimed with the 3-min exposure tests. The slopes of the regression lines did not differ significantly between the heated and unheated samples. It is concluded that diffusion at ambient temperature is fast enough to rapidly compensate for the loss of insecticide on the surface with no need to artificially stimulate diffusion by heating.     

真皮下血管网皮瓣早期修复手部电击伤创面

目的评价真皮下血管网皮瓣早期修复手部电击伤创面的临床疗效。方法自1995年4月～2000年4月,25例电击伤病人行早期清创后真皮下血管网皮瓣修复,并于术后6～18个月随访20例。结果25个皮瓣全部成活,皮瓣面积3cm×8cm～11cm×14cm,长宽比为1∶1～5∶1。平均断蒂时间13天。术后6～18个月随访见皮瓣色泽和谐,质地柔软,厚薄相称,外形良好。功能恢复总主动活动度达优良者占60%。神经功能恢复优良者占70%。结论早期真皮下血管网皮瓣手部电击伤可防止创面感染而继发的神经肌腱坏死,避免严重伤残,缩短疗程,免除二次去脂等手术。认为真皮下血管网皮瓣是早期修复手部电击伤创面理想的手术方法。     

When the Safety Net Is Unsafe Real-time Assessment of the Overcrowded Emergency Department

Although much work has been done evaluating causes for increased demand for emergency department (ED) services, few ways are available to help determine that an individual ED is overcrowded. Four calculations are proposed using real-time data for accurately diagnosing an ED with potential for failing both as a safety net and as a source for quality health care. The bed ratio (BR) accounts for the number of patients in relation to the available treatment spaces. The BR is obtained by adding the current number of ED patients to the predicted arrivals minus the predicted departures and dividing the result by the total number of treatment spaces. The acuity ratio (AR) measures the relative burden of illness in the ED. The AR is the average triage category of all patients in the ED. The provider ratio (PR) determines the volume of patients that can be evaluated and treated by the physician providers. The PR is found by dividing the arrivals per hour by the sum of the average patients per hour usually disposed for each provider on duty. From these ratios, the demand value (DV) is calculated, which gives an overall measure of current demand. The DV is found by taking the sum of the BR and PR and multiplying by the AR. A DV of more than 7 should initiate a specific assessment of the individual ratios in order to accurately diagnose the problem and institute action. Based on the values, predetermined processes can be instituted to help remedy the overcrowded situation. Trended over time, the ratios can provide the data needed for better resource assessment, planning, and allocation.     

Hepatic balances of glucose and insulin in response to physiological increments of endogenous insulin during glucose infusions in dogs.

Hepatic glucose uptake was measured in dogs in relation to physiological increments of plasma insulin levels under steady state conditions. Endogenous insulin secretion was stimulated by the infusion of small glucose loads, achieving normoglycaemia or mild hyperglycaemia. The measurement of hepatic arterial and portal venous blood flows allowed calculation of the relationships between net hepatic balances of insulin and glucose, the magnitude of insulin extraction by the liver and the hepatic sensitivity to physiological levels of insulin. During normoglycaemia, small glucose loads (2 and 4.5 mg/min. kg) reduced hepatic glucose output without a concomitant increase of the estimated total glucose utilization. No changes in arterial or hepatic venous plasma insulin levels occurred. Portal venous plasma insulin alone rose under the influence of the glucose stimulus. In the presence of hyperglycaemia, the liver further reduced its glucose output. Infusions of 11.3 mg/min. kg glucose resulted in reversal of hepatic glucose output to a net uptake of glucose. However, due to the large amounts of insulin emerging from the liver, peripheral tissue glucose utilization was significantly increased. A strong inverse correlation existed between arterial glucose concentration and hepatic glucose output as well as between portal venous plasma insulin level and hepatic glucose output. The net hepatic balance of insulin was promptly raised in response to the glucose perfusions, even when normoglycaemia was maintained. A highly significant, inverse correlation was demonstrated between net hepatic balance of insulin (i.e. net uptake of insulin by the liver) and hepatic glucose output. Hepatic insulin extraction ratio and hepatic plasma insulin clearance increased during glucose administration but no evident relationship to portal venous plasma insulin levels was found. These data suggest that insulin rather than glucose is the primary agent responsible for the reversal of the hepatic gradient of glucose in vivo.     

Deep Learning to Estimate Biological Age From Chest Radiographs

ObjectivesThe goal of this study was to assess whether a deep learning estimate of age from a chest radiograph image (CXR-Age) can predict longevity beyond chronological age.BackgroundChronological age is an imperfect measure of longevity. Biological age, a measure of overall health, may improve personalized care. This paper proposes a new way to estimate biological age using a convolutional neural network that takes as input a CXR image and outputs a chest x-ray age (in years) as a measure of long-term mortality risk.MethodsCXR-Age was developed using CXR from 116,035 individuals and validated in 2 held-out testing sets: 1) 75% of the CXR arm of PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) (N = 40,967); and 2) the CXR arm of NLST (National Lung Screening Trial) (N = 5,414). CXR-Age was compared to chronological age and a multivariable regression model of chronological age, risk factors, and radiograph findings to predict all-cause and cardiovascular mortality with a maximum 23 years and 13 years of follow-up, respectively. The primary outcome was observed mortality; results are provided for the testing datasets only.ResultsIn the PLCO testing dataset, a 5-year increase in CXR-Age carried a higher risk of all-cause mortality than a 5-year increase in chronological age (CXR-Age hazard ratio [HR]: 2.26 [95% confidence interval (CI): 2.24 to 2.29] vs. chronological age HR: 1.77 [95% CI: 1.75 to 1.78]; p < 0.001). A similar pattern was found for cardiovascular mortality (CXR-Age cause-specific HR: 2.45 per 5 years [95% CI: 2.34 to 2.56] vs. chronological age HR: 1.82 per 5 years [95% CI: 1.74 to 1.90]). Similar results were seen for both outcomes in the NLST external testing dataset. Adding CXR-Age to the multivariable model resulted in significant improvements for predicting both outcomes in both testing datasets (p < 0.001 for all comparisons).ConclusionsBased on a CXR image, CXR-Age predicted long-term all-cause and cardiovascular mortality.     

Cell‐specific and developmental expression of lectican‐cleaving proteases in mouse hippocampus and neocortex

Mounting evidence has demonstrated that a specialized extracellular matrix exists in the mammalian brain and that this glycoprotein‐rich matrix contributes to many aspects of brain development and function. The most prominent supramolecular assemblies of these extracellular matrix glycoproteins are perineuronal nets, specialized lattice‐like structures that surround the cell bodies and proximal neurites of select classes of interneurons. Perineuronal nets are composed of lecticans, a family of chondroitin sulfate proteoglycans that includes aggrecan, brevican, neurocan, and versican. These lattice‐like structures emerge late in postnatal brain development, coinciding with the ending of critical periods of brain development. Despite our knowledge of the presence of lecticans in perineuronal nets and their importance in regulating synaptic plasticity, we know little about the development or distribution of the extracellular proteases that are responsible for their cleavage and turnover. A subset of a large family of extracellular proteases (called a disintegrin and metalloproteinase with thrombospondin motifs [ADAMTS]) is responsible for endogenously cleaving lecticans. We therefore explored the expression pattern of two aggrecan‐degrading ADAMTS family members, ADAMTS15 and ADAMTS4, in the hippocampus and neocortex. Here, we show that both lectican‐degrading metalloproteases are present in these brain regions and that each exhibits a distinct temporal and spatial expression pattern. Adamts15 mRNA is expressed exclusively by parvalbumin‐expressing interneurons during synaptogenesis, whereas Adamts4 mRNA is exclusively generated by telencephalic oligodendrocytes during myelination. Thus, ADAMTS15 and ADAMTS4 not only exhibit unique cellular expression patterns but their developmental upregulation by these cell types coincides with critical aspects of neural development. J. Comp. Neurol. 523:629–648, 2015. © 2014 Wiley Periodicals, Inc.