Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-15 (of 15 Records) |
Query Trace: Dwivedi M[original query] |
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Signatures of somatic mutations and gene expression from p16INK4A positive head and neck squamous cell carcinomas (HNSCC).
Saba NF , Dinasarapu AR , Magliocca KR , Dwivedi B , Seby S , Qin ZS , Patel M , Griffith CC , Wang X , El-Deiry M , Steuer CE , Kowalski J , Shin DM , Zwick ME , Chen ZG . PLoS One 2020 15 (9) e0238497 ![]() Human papilloma virus (HPV) causes a subset of head and neck squamous cell carcinomas (HNSCC) of the oropharynx. We combined targeted DNA- and genome-wide RNA-sequencing to identify genetic variants and gene expression signatures respectively from patients with HNSCC including oropharyngeal squamous cell carcinomas (OPSCC). DNA and RNA were purified from 35- formalin fixed and paraffin embedded (FFPE) HNSCC tumor samples. Immuno-histochemical evaluation of tumors was performed to determine the expression levels of p16INK4A and classified tumor samples either p16+ or p16-. Using ClearSeq Comprehensive Cancer panel, we examined the distribution of somatic mutations. Somatic single-nucleotide variants (SNV) were called using GATK-Mutect2 ("tumor-only" mode) approach. Using RNA-seq, we identified a catalog of 1,044 and 8 genes as significantly expressed between p16+ and p16-, respectively at FDR 0.05 (5%) and 0.1 (10%). The clinicopathological characteristics of the patients including anatomical site, smoking and survival were analyzed when comparing p16+ and p16- tumors. The majority of tumors (65%) were p16+. Population sequence variant databases, including gnomAD, ExAC, COSMIC and dbSNP, were used to identify the mutational landscape of somatic sequence variants within sequenced genes. Hierarchical clustering of The Cancer Genome Atlas (TCGA) samples based on HPV-status was observed using differentially expressed genes. Using RNA-seq in parallel with targeted DNA-seq, we identified mutational and gene expression signatures characteristic of p16+ and p16- HNSCC. Our gene signatures are consistent with previously published data including TCGA and support the need to further explore the biologic relevance of these alterations in HNSCC. |
Impact of enzymatic hydrolysis on the quantification of total urinary concentrations of chemical biomarkers
Dwivedi P , Zhou X , Powell TG , Calafat AM , Ye X . Chemosphere 2018 199 256-262 Human exposure to consumer and personal care products chemicals such as phenols, including parabens and other antimicrobial agents, can be assessed through biomonitoring by quantifying urinary concentrations of the parent chemical or its metabolites, often after hydrolysis of phase II conjugates. Developing suitable analytical methods for the concurrent quantification of multiple exposure biomarkers is challenging because optimal conditions for the hydrolysis of such conjugates (e.g., O-glucuronides, N-glucuronides, sulfates) may differ depending on the biomarker. We evaluated the effectiveness of seven commercial hydrolytic enzymes to simultaneously hydrolyze N-glucuronides (using the antibacterial triclocarban as example compound) and other conjugates (using select phenols and parabens as examples) by using on-line solid phase extraction-high performance liquid chromatography-isotope dilution-tandem mass spectrometry. Incubation (30min, 55 degrees C) with a genetically engineered beta-glucuronidase (IMCS, >/=15 units/muL urine) hydrolyzed N-glucuronide triclocarban, but did not fully hydrolyze the conjugates of phenols and parabens. By contrast, incubation (4h, 37 degrees C) with solid beta-glucuronidase (Helix pomatia, Type H-1, >/=30 units/muL urine) or liquid beta-glucuronidase/arylsulfatase (Helix pomatia, 30 units/muL urine [i.e., 30 muL/100muL urine]) in the presence of 100muL methanol for 100muL urine completely hydrolyzed N-glucuronide triclocarban and the conjugates of several phenols and parabens, without cleaving the ester bond of the parabens to form p-hydroxybenzoic acid. These results highlight the relevance of method validation procedures that include optimizing the hydrolysis of phase II urinary conjugates (e.g., enzyme type and amount used, reaction time, temperature) to quantify accurately and concurrently multiple exposure biomarkers for biomonitoring purposes. |
Prevalence of substandard and falsified artemisinin-based combination antimalarial medicines on Bioko Island, Equatorial Guinea
Kaur H , Allan EL , Mamadu I , Hall Z , Green MD , Swamidos I , Dwivedi P , Culzoni MJ , Fernandez FM , Garcia G , Hergott D , Monti F . BMJ Glob Health 2017 2 (4) e000409 INTRODUCTION: Poor-quality artemisinin-containing antimalarials (ACAs), including falsified and substandard formulations, pose serious health concerns in malaria endemic countries. They can harm patients, contribute to the rise in drug resistance and increase the public's mistrust of health systems. Systematic assessment of drug quality is needed to gain knowledge on the prevalence of the problem, to provide Ministries of Health with evidence on which local regulators can take action. METHODS: We used three sampling approaches to purchase 677 ACAs from 278 outlets on Bioko Island, Equatorial Guinea as follows: convenience survey using mystery client (n=16 outlets, 31 samples), full island-wide survey using mystery client (n=174 outlets, 368 samples) and randomised survey using an overt sampling approach (n=88 outlets, 278 samples). The stated active pharmaceutical ingredients (SAPIs) were assessed using high-performance liquid chromatography and confirmed by mass spectrometry at three independent laboratories. RESULTS: Content analysis showed 91.0% of ACAs were of acceptable quality, 1.6% were substandard and 7.4% falsified. No degraded medicines were detected. The prevalence of medicines without the SAPIs was higher for ACAs purchased in the convenience survey compared with the estimates obtained using the full island-wide survey-mystery client and randomised-overt sampling approaches. Comparable results were obtained for full island survey-mystery client and randomised overt. However, the availability of purchased artesunate monotherapies differed substantially according to the sampling approach used (convenience, 45.2%; full island-wide survey-mystery client, 32.6%; random-overt sampling approach, 21.9%). Of concern is that 37.1% (n=62) of these were falsified. CONCLUSION: Falsified ACAs were found on Bioko Island, with the prevalence ranging between 6.1% and 16.1%, depending on the sampling method used. These findings underscore the vital need for national authorities to track the scale of ineffective medicines that jeopardise treatment of life-threatening diseases and value of a representative sampling approach to obtain/measure the true prevalence of poor-quality medicines. |
Association of acute toxic encephalopathy with litchi consumption in an outbreak in Muzaffarpur, India, 2014: a case-control study
Shrivastava A , Kumar A , Thomas JD , Laserson KF , Bhushan G , Carter MD , Chhabra M , Mittal V , Khare S , Sejvar JJ , Dwivedi M , Isenberg SL , Johnson R , Pirkle JL , Sharer JD , Hall PL , Yadav R , Velayudhan A , Papanna M , Singh P , Somashekar D , Pradhan A , Goel K , Pandey R , Kumar M , Kumar S , Chakrabarti A , Sivaperumal P , Kumar AR , Schier JG , Chang A , Graham LA , Mathews TP , Johnson D , Valentin L , Caldwell KL , Jarrett JM , Harden LA , Takeoka GR , Tong S , Queen K , Paden C , Whitney A , Haberling DL , Singh R , Singh RS , Earhart KC , Dhariwal AC , Chauhan LS , Venkatesh S , Srikantiah P . Lancet Glob Health 2017 5 (4) e458-e466 BACKGROUND: Outbreaks of unexplained illness frequently remain under-investigated. In India, outbreaks of an acute neurological illness with high mortality among children occur annually in Muzaffarpur, the country's largest litchi cultivation region. In 2014, we aimed to investigate the cause and risk factors for this illness. METHODS: In this hospital-based surveillance and nested age-matched case-control study, we did laboratory investigations to assess potential infectious and non-infectious causes of this acute neurological illness. Cases were children aged 15 years or younger who were admitted to two hospitals in Muzaffarpur with new-onset seizures or altered sensorium. Age-matched controls were residents of Muzaffarpur who were admitted to the same two hospitals for a non-neurologic illness within seven days of the date of admission of the case. Clinical specimens (blood, cerebrospinal fluid, and urine) and environmental specimens (litchis) were tested for evidence of infectious pathogens, pesticides, toxic metals, and other non-infectious causes, including presence of hypoglycin A or methylenecyclopropylglycine (MCPG), naturally-occurring fruit-based toxins that cause hypoglycaemia and metabolic derangement. Matched and unmatched (controlling for age) bivariate analyses were done and risk factors for illness were expressed as matched odds ratios and odds ratios (unmatched analyses). FINDINGS: Between May 26, and July 17, 2014, 390 patients meeting the case definition were admitted to the two referral hospitals in Muzaffarpur, of whom 122 (31%) died. On admission, 204 (62%) of 327 had blood glucose concentration of 70 mg/dL or less. 104 cases were compared with 104 age-matched hospital controls. Litchi consumption (matched odds ratio [mOR] 9.6 [95% CI 3.6 - 24]) and absence of an evening meal (2.2 [1.2-4.3]) in the 24 h preceding illness onset were associated with illness. The absence of an evening meal significantly modified the effect of eating litchis on illness (odds ratio [OR] 7.8 [95% CI 3.3-18.8], without evening meal; OR 3.6 [1.1-11.1] with an evening meal). Tests for infectious agents and pesticides were negative. Metabolites of hypoglycin A, MCPG, or both were detected in 48 [66%] of 73 urine specimens from case-patients and none from 15 controls; 72 (90%) of 80 case-patient specimens had abnormal plasma acylcarnitine profiles, consistent with severe disruption of fatty acid metabolism. In 36 litchi arils tested from Muzaffarpur, hypoglycin A concentrations ranged from 12.4 mug/g to 152.0 mug/g and MCPG ranged from 44.9 mug/g to 220.0 mug/g. INTERPRETATION: Our investigation suggests an outbreak of acute encephalopathy in Muzaffarpur associated with both hypoglycin A and MCPG toxicity. To prevent illness and reduce mortality in the region, we recommended minimising litchi consumption, ensuring receipt of an evening meal and implementing rapid glucose correction for suspected illness. A comprehensive investigative approach in Muzaffarpur led to timely public health recommendations, underscoring the importance of using systematic methods in other unexplained illness outbreaks. FUNDING: US Centers for Disease Control and Prevention. |
Urinary concentrations of the antibacterial agent triclocarban in United States residents: 2013-2014 National Health and Nutrition Examination Survey
Ye X , Wong LY , Dwivedi P , Zhou X , Jia T , Calafat AM . Environ Sci Technol 2016 50 (24) 13548-13554 Triclocarban is widely used as an antibacterial agent in personal care products, and the potential for human exposure exists. We present here the first nationally representative assessment of exposure to triclocarban among Americans ≥6 years of age who participated in the 2013-2014 National Health and Nutrition Examination Survey. We detected triclocarban at concentrations above 0.1 mug/L in 36.9% of 2686 urine samples examined. Triclocarban was detected more frequently in adolescents and adults than in children, and in non-Hispanic black compared to other ethnic groups. In univariate analysis, log-creatinine, sex, age, race, and body surface area (BSA) were significantly associated with the likelihood of having triclocarban concentrations above the 95th percentile. In multiple regression models, persons with BSA at or above the median (≥1.86 m2) were 2.43 times more likely than others, and non-Hispanic black and non-Hispanic white were 3.71 times and 2.23 times more likely than "all Hispanic," respectively, to have urinary concentrations above the 95th percentile. We found no correlations between urinary concentrations of triclocarban and triclosan, another commonly used antibacterial agent. Observed differences among demographic groups examined may reflect differences in physiological factors (i.e., BSA) as well as use of personal care products containing triclocarban. |
Gene integrated set profile analysis: a context-based approach for inferring biological endpoints.
Kowalski J , Dwivedi B , Newman S , Switchenko JM , Pauly R , Gutman DA , Arora J , Gandhi K , Ainslie K , Doho G , Qin Z , Moreno CS , Rossi MR , Vertino PM , Lonial S , Bernal-Mizrachi L , Boise LH . Nucleic Acids Res 2016 44 (7) e69 ![]() The identification of genes with specific patterns of change (e.g. down-regulated and methylated) as phenotype drivers or samples with similar profiles for a given gene set as drivers of clinical outcome, requires the integration of several genomic data types for which an 'integrate by intersection' (IBI) approach is often applied. In this approach, results from separate analyses of each data type are intersected, which has the limitation of a smaller intersection with more data types. We introduce a new method, GISPA (Gene Integrated Set Profile Analysis) for integrated genomic analysis and its variation, SISPA (Sample Integrated Set Profile Analysis) for defining respective genes and samples with the context of similar, a priori specified molecular profiles. With GISPA, the user defines a molecular profile that is compared among several classes and obtains ranked gene sets that satisfy the profile as drivers of each class. With SISPA, the user defines a gene set that satisfies a profile and obtains sample groups of profile activity. Our results from applying GISPA to human multiple myeloma (MM) cell lines contained genes of known profiles and importance, along with several novel targets, and their further SISPA application to MM coMMpass trial data showed clinical relevance. |
Quality of Artemisinin-Containing Antimalarials in Tanzania's Private Sector--Results from a Nationally Representative Outlet Survey
ACT Consortium Drug Quality Project Team and the IMPACT2 Study Team , Swamidoss I , Green MD , Dwivedi P , Kachur SP . Am J Trop Med Hyg 2015 92 75-86 Ensuring that artemisinin-containing antimalarials (ACAs) are of good quality is a key component of effective malaria treatment. There are concerns that a high proportion of ACAs are falsified or substandard, though estimates are rarely based on representative data. During a nationally representative survey in Tanzania, ACAs were purchased from private retail drug outlets, and the active pharmaceutical ingredient (API) was measured. All 1,737 ACAs contained the labeled artemisinin derivative, with 4.1% being outside the 85-115% artemisinin API range defined as acceptable quality. World Health Organization (WHO) prequalified drugs had 0.1 times the odds of being poor quality compared with non-prequalified ACAs for the artemisinin component. When partner components of combination therapies were also considered, 12.1% were outside the acceptable API range, and WHO prequalified ACAs had 0.04 times the odds of being poor quality. Although the prevalence of poor quality ACAs was lower than reported elsewhere, the minority of samples found to be substandard is a cause for concern. Improvements in quality could be achieved by increasing the predominance of WHO prequalified products in the market. Continued monitoring of quality standards is essential. |
Electrothermal vaporization sample introduction for spaceflight water quality monitoring via gas chromatography-differential mobility spectrometry
Wallace WT , Gazda DB , Limero TF , Minton JM , Macatangay AV , Dwivedi P , Fernandez FM . Anal Chem 2015 87 (12) 5981-8 In the history of manned spaceflight, environmental monitoring has relied heavily on archival sampling. However, with the construction of the International Space Station (ISS) and the subsequent extension in mission duration up to one year, an enhanced, real-time method for environmental monitoring is necessary. The station air is currently monitored for trace volatile organic compounds (VOCs) using gas chromatography-differential mobility spectrometry (GC-DMS) via the Air Quality Monitor (AQM), while water is analyzed to measure total organic carbon and biocide concentrations using the Total Organic Carbon Analyzer (TOCA) and the Colorimetric Water Quality Monitoring Kit (CWQMK), respectively. As mission scenarios extend beyond low Earth orbit, a convergence in analytical instrumentation to analyze both air and water samples is highly desirable. Since the AQM currently provides quantitative, compound-specific information for air samples and many of the targets in air are also common to water, this platform is a logical starting point for developing a multimatrix monitor. Here, we report on the interfacing of an electrothermal vaporization (ETV) sample introduction unit with a ground-based AQM for monitoring target analytes in water. The results show that each of the compounds tested from water have similar GC-DMS parameters as the compounds tested in air. Moreover, the ETV enabled AQM detection of dimethlsilanediol (DMSD), a compound whose analysis had proven challenging using other sample introduction methods. Analysis of authentic ISS water samples using the ETV-AQM showed that DMSD could be successfully quantified, while the concentrations obtained for the other compounds also agreed well with laboratory results. |
Quality of artemisinin-based combination formulations for malaria treatment: prevalence and risk factors for poor quality medicines in public facilities and private sector drug outlets in Enugu, Nigeria
Kaur H , Allan EL , Mamadu I , Hall Z , Ibe O , El Sherbiny M , Wyk AV , Yeung S , Swamidoss I , Green MD , Dwivedi P , Culzoni MJ , Clarke S , Schellenberg D , Fernandez FM , Onwujekwe O . PLoS One 2015 10 (5) e0125577 BACKGROUND: Artemisinin-based combination therapies are recommended by the World Health Organisation (WHO) as first-line treatment for Plasmodium falciparum malaria, yet medication must be of good quality for efficacious treatment. A recent meta-analysis reported 35% (796/2,296) of antimalarial drug samples from 21 Sub-Saharan African countries, purchased from outlets predominantly using convenience sampling, failed chemical content analysis. We used three sampling strategies to purchase artemisinin-containing antimalarials (ACAs) in Enugu metropolis, Nigeria, and compared the resulting quality estimates. METHODS: ACAs were purchased using three sampling approaches - convenience, mystery clients and overt, within a defined area and sampling frame in Enugu metropolis. The active pharmaceutical ingredients were assessed using high-performance liquid chromatography and confirmed by mass spectrometry at three independent laboratories. Results were expressed as percentage of APIs stated on the packaging and used to categorise each sample as acceptable quality, substandard, degraded, or falsified. RESULTS: Content analysis of 3024 samples purchased from 421 outlets using convenience (n=200), mystery (n=1,919) and overt (n=905) approaches, showed overall 90.8% ACAs to be of acceptable quality, 6.8% substandard, 1.3% degraded and 1.2% falsified. Convenience sampling yielded a significantly higher prevalence of poor quality ACAs, but was not evident by the mystery and overt sampling strategies both of which yielded results that were comparable between each other. Artesunate (n=135; 4 falsified) and dihydroartemisinin (n=14) monotherapy tablets, not recommended by WHO, were also identified. CONCLUSION: Randomised sampling identified fewer falsified ACAs than previously reported by convenience approaches. Our findings emphasise the need for specific consideration to be given to sampling frame and sampling approach if representative information on drug quality is to be obtained. |
Quality of antimalarials at the epicenter of antimalarial drug resistance: results from an overt and mystery client survey in Cambodia
Yeung S , Lawford HL , Tabernero P , Nguon C , van Wyk A , Malik N , DeSousa M , Rada O , Boravann M , Dwivedi P , Hostetler DM , Swamidoss I , Green MD , Fernandez FM , Kaur H . Am J Trop Med Hyg 2015 92 39-50 Widespread availability of monotherapies and falsified antimalarials is thought to have contributed to the historical development of multidrug-resistant malaria in Cambodia. This study aimed to document the quality of artemisinin-containing antimalarials (ACAs) and to compare two methods of collecting antimalarials from drug outlets: through open surveyors and mystery clients (MCs). Few oral artemisinin-based monotherapies and no suspected falsified medicines were found. All 291 samples contained the stated active pharmaceutical ingredient (API) of which 69% were considered good quality by chemical analysis. Overall, medicine quality did not differ by collection method, although open surveyors were less likely to obtain oral artemisinin-based monotherapies than MCs. The results are an encouraging indication of the positive impact of the country's efforts to tackle falsified antimalarials and artemisinin-based monotherapies. However, poor-quality medicines remain an ongoing challenge that demands sustained political will and investment of human and financial resources. |
A repeat random survey of the prevalence of falsified and substandard antimalarials in the Lao PDR: a change for the better
Tabernero P , Mayxay M , Culzoni MJ , Dwivedi P , Swamidoss I , Allan EL , Khanthavong M , Phonlavong C , Vilayhong C , Yeuchaixiong S , Sichanh C , Sengaloundeth S , Kaur H , Fernandez FM , Green MD , Newton PN . Am J Trop Med Hyg 2015 92 95-104 In 2003, a stratified random sample survey was conducted in the Lao People's Democratic Republic (Laos) to study the availability and quality of antimalarials in the private sector. In 2012, this survey was repeated to allow a statistically valid analysis of change through time. The counterfeit detection device 3 (CD-3) was used to assess packaging quality in the field. The availability of oral artesunate monotherapies had significantly decreased from 22.9% (22) of 96 outlets in southern Laos in 2003 to 4.8% (7) of 144 outlets in 2012 (P < 0.0001). All the samples collected in 2012 survey contained the correct active pharmaceutical ingredients (APIs) in contrast to the 21 (84%) falsified artesunate samples found in the 2003 survey. Although none of the medicines found in 2012 survey had evidence for falsification, 25.4% (37) of the samples were outside the 90-110% pharmacopeial limits of the label claim, suggesting that they were substandard or degraded. Results obtained from this survey show that patients are still exposed to poorly manufactured drugs or to ineffective medicines such as chloroquine. The quality of artemisinin-based combination therapies (ACTs) used in Laos needs to be monitored; since falsified ACTs would have devastating consequences in public health. |
Outbreaks of unexplained neurologic illness - Muzaffarpur, India, 2013-2014
Shrivastava A , Srikantiah P , Kumar A , Bhushan G , Goel K , Kumar S , Kumar T , Mohankumar R , Pandey R , Pathan P , Pappanna M , Pasi A , Pradhan A , Singh P , Somashekar D , Velayudhan A , Yadav R , Chhabra M , Mittal V , Khare S , Sejvar JJ , Dwivedi M , Laserson K , Earhart KC , Sivaperumal P , Kumar AR , Chakrabarti A , Thomas J , Schier J , Singh R , Singh RS , Dhariwal AC , Chauhan LS . MMWR Morb Mortal Wkly Rep 2015 64 (3) 49-53 Outbreaks of an unexplained acute neurologic illness affecting young children and associated with high case-fatality rates have been reported in the Muzaffarpur district of Bihar state in India since 1995. The outbreaks generally peak in June and decline weeks later with the onset of monsoon rains. There have been multiple epidemiologic and laboratory investigations of this syndrome, leading to a wide spectrum of proposed causes for the illness, including infectious encephalitis and exposure to pesticides. An association between illness and litchi fruit has been postulated because Muzaffarpur is a litchi fruit-producing region. To better characterize clinical and epidemiologic features of the illness that might suggest its cause and how it can be prevented, the Indian National Centre for Disease Control (NCDC) and CDC investigated outbreaks in 2013 and 2014. Clinical and laboratory findings in 2013 suggested a noninflammatory encephalopathy, possibly caused by a toxin. A common laboratory finding was low blood glucose (<70 mg/dL) on admission, a finding associated with a poorer outcome; 44% of all cases were fatal. An ongoing 2014 investigation has found no evidence of any infectious etiology and supports the possibility that exposure to a toxin might be the cause. The outbreak period coincides with the month-long litchi harvesting season in Muzaffarpur. Although a specific etiology has not yet been determined, the 2014 investigation has identified the illness as a hypoglycemic encephalopathy and confirmed the importance of ongoing laboratory evaluation of environmental toxins to identify a potential causative agent, including markers for methylenecyclopropylglycine (MCPG), a compound found in litchi seeds known to cause hypoglycemia in animal studies. Current public health recommendations are focused on reducing mortality by urging affected families to seek prompt medical care, and ensuring rapid assessment and correction of hypoglycemia in ill children. |
Characteristics of patients who died from traumatic brain injury in two rural hospital emergency departments in Maharashtra, India, 2007-2009
Agrawal A , Coronado VG , Bell JM , Baisakhiya N , Kakani A , Galwankar S , Dwivedi S . Int J Crit Illn Inj Sci 2014 4 (4) 293-7 INTRODUCTION: Trauma is one of the leading causes of morbidity and mortality in the world and in India. OBJECTIVE: To describe 1) selected epidemiological and clinical characteristics of persons with traumatic brain injury (TBI) who died within 24 h after admission to the emergency departments (EDs) of two medical facilities in rural India and 2) the methods used to transport these patients from the locale of the injury incident to the study sites. MATERIALS AND METHODS: Medical records of all injured patients regardless of age or sex who died within 24 h after admission to both EDs during January 31, 2007 through December 31, 2009 were reviewed and abstracted. Demographic variables and information on prehospital care, time and mechanism of injury, mode of transport to EDs, and primary hospital resuscitation were abstracted and analyzed. RESULTS: Of the 113 injured patients in this study, 42 had TBI and died within 24 h of ED admission. All of these TBI patients were transported to the ED by relatives or bystanders in non-ambulance vehicles. Most of the patients with TBI (78.5%) were 21-50-years-old; and overall 90.0% were males. Persons working near or along busy roads struck by vehicles accounted for 80.9% of all TBI cases. Severe TBIs were present in 97.6% of the patients; of these, 92.8% had a Glasgow Coma Scale (GCS) score of 3 on arrival. Other concurrent injuries included superficial lacerations (85.7%), facial injuries (57.1%), and upper (35.7%) and lower (30.9%) extremity fractures. Common lesions recognized on computed tomography (CT) scan were acute subdural hematoma (21.4%), subarachnoid hemorrhage with diffuse cerebral edema (16.6%), and skull base fracture with diffuse cerebral edema (14.2%); in 21.4% of cases, the CT scan were reported normal. CONCLUSION: Most of the TBI patients who died within 24 h after admission to EDs in this study were not transported to EDs in emergency medical vehicles; most were of working age (ages 20-50 years); were male; and were day laborers working on busy interstate roads where they were hit by vehicles. |
Desorption atmospheric pressure photoionization and direct analysis in real time coupled with travelling wave ion mobility mass spectrometry
Rasanen RM , Dwivedi P , Fernandez FM , Kauppila TJ . Rapid Commun Mass Spectrom 2014 28 (21) 2325-36 RATIONALE: Ambient mass spectrometry (MS) is a tool for screening analytes directly from sample surfaces. However, background impurities may complicate the spectra and therefore fast separation techniques are needed. Here, we demonstrate the use of travelling wave ion mobility spectrometry in a comparative study of two ambient MS techniques. METHODS: Desorption atmospheric pressure photoionization (DAPPI) and direct analysis in real time (DART) were coupled with travelling wave ion mobility mass spectrometry (TWIM-MS) for highly selective surface analysis. The ionization efficiencies of DAPPI and DART were compared. Test compounds were: bisphenol A, benzo[a]pyrene, ranitidine, cortisol and alpha-tocopherol. DAPPI-MS and DART-TWIM-MS were also applied to the analysis of chloroquine from dried blood spots, and alpha-tocopherol from almond surface, and DAPPI-TWIM-MS was applied to analysis of pharmaceuticals and multivitamin tablets. RESULTS: DAPPI was approximately 100 times more sensitive than DART for bisphenol A and 10-20 times more sensitive for the other compounds. The limits of detection were between 30-290 and 330-8200 fmol for DAPPI and DART, respectively. Also, from the authentic samples, DAPPI ionized chloroquine and alpha-tocopherol more efficiently than DART. The mobility separation enabled the detection of species with low signal intensities, e.g. thiamine and cholecalciferol, in the DAPPI-TWIM-MS analysis of multivitamin tablets. CONCLUSIONS: DAPPI ionized the studied compounds of interest more efficiently than DART. For both DAPPI and DART, the mobility separation prior to MS analysis reduced the amount of chemical noise in the mass spectrum and significantly increased the signal-to-noise ratio for the analytes. |
Falsified medicines in Africa: all talk, no action
Newton PN , Tabernero P , Dwivedi P , Culzoni MJ , Monge ME , Swamidoss I , Mildenhall D , Green MD , Jähnke R , de Oliveira MDS , Simao J , White NJ , Fernández FM . Lancet Glob Health 2014 2 (9) e509-10 Poor-quality medicines and medical products, both substandard and falsified, cause avoidable morbidity, mortality, drug resistance, and loss of faith in health systems, especially in low-income and middle-income countries.1, 2, 3 We report the analysis of two falsified medicines from Angola and discuss what lessons such a discovery could hold. | The tablets were seized at Luanda docks in June, 2012, after failing Minilab testing.4, 5 The seized shipment was enormous (1·4 million packets), and hidden in loudspeakers in a container from China.4 One sample was labelled as an adult course of the vital antimalarial drug artemether-lumefantrine, and as being manufactured by “Novartis Pharmaceutical Corporation”; it also bore an Affordable Medicines Facility—malaria logo (figure). Another sample was labelled as the broad-spectrum anthelmintic mebendazole, and as being manufactured by “Janssen-Cilag SpA”. |
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