Determining the location and distribution of cockpit and aircrew-related equipment within the wid... more Determining the location and distribution of cockpit and aircrew-related equipment within the wider debris field of a military aircraft crash site is an essential first step in planning and executing the recovery of missing aircrew members presumed still to be on the site. Understanding the spatial relationship of these materials improves the likelihood of finding and recovering the remains of the aircrew during the excavation of an aircraft crash site. Since the greater portion of these unaccounted for crewmembers were involved in aircraft with single-seat cockpits or cockpits with two or three seats in tandem, pre-analysis of the debris pattern may be more-or-less straightforward. Larger, multiple-personnel aircraft, on the other hand, create a potentially more complex analytical situation given the aircrew's greater freedom of movement within the aircraft. Nevertheless, the same fundamental principles apply and, indeed, have been successfully so for some time in the civilian arena. But older aircraft crash sites, i.e., those dating to World War II, Korea, or the Vietnam conflict, have been and still are undergoing taphonomic processes that progressively alter these relationships. The following will illustrate that exchange of information between the anthropologist/archaeologist and the life-support analyst is required to maximize the effectiveness of field recovery and demonstrates the relationship between the recovery of life-support equipment and human remains and the effect that aircraft type has on this relationship.
This report describes the genetic identification of James ''Earthquake McGoon'' McGovern, a WWII ... more This report describes the genetic identification of James ''Earthquake McGoon'' McGovern, a WWII fighter ace who perished in Laos while providing supplies to French troops during the French Indochina war. Because reference samples were unavailable for all of the potential casualties, testing of the entire mitochondrial genome, autosomal STRs and Y-chromosomal STRs was performed to increase the genetic information available for analysis. Kinship analyses performed on the evidentiary data and numerous indirect family references for McGovern excluded other possible casualties and definitively established McGovern's identity. This particular case demonstrates the practical utility of novel research technologies and aggressive genetic typing protocols in the identification of aged, degraded remains.
See the Editorial Commentary by Cornely and Vehreschild on pages 735-6.) Background. Although new... more See the Editorial Commentary by Cornely and Vehreschild on pages 735-6.) Background. Although newer studies have evaluated risk factors for recurrent Clostridium difficile infection (CDI), the vast majority did not measure important biomarkers such as endogenous anti-toxin A and anti-toxin B antibody levels. Methods. Data from the placebo group of a phase 2 trial testing monoclonal antibodies to C. difficile toxins A and B for preventing CDI recurrence (rCDI) were analyzed to assess risk factors associated with rCDI. Patients with symptomatic CDI taking metronidazole or vancomycin were enrolled. The primary outcome was rCDI within 84 days of treatment start. Univariate and multivariate logistic regression was used to examine associations between potential risk factors and rCDI. At baseline, demographic and clinical characteristics were recorded; endogenous antibody levels were assessed using 2 enzyme-linked immunosorbent assays. Results. A predictor of recurrence was age ≥65 years, and an antibody-mediated immune response to toxin B appears to be protective against rCDI. Conclusions. Our findings demonstrate the importance of clinical as well as immunological risk factors in rCDI and provide more robust evidence for the protective effects of antibody to toxin B in the prevention of rCDI. Clinical Trials Registration. NCT00350298.
Background New therapies are needed to manage the increasing incidence, severity, and high rate o... more Background New therapies are needed to manage the increasing incidence, severity, and high rate of recurrence of Clostridium difficile infection. Methods We performed a randomized, double-blind, placebo-controlled study of two neutralizing, fully human monoclonal antibodies against C. difficile toxins A (CDA1) and B (CDB1). The antibodies were administered together as a single infusion, each at a dose of 10 mg per kilogram of body weight, in patients with symptomatic C. difficile infection who were receiving either metronidazole or vancomycin. The primary outcome was laboratory-documented recurrence of infection during the 84 days after the administration of monoclonal antibodies or placebo. Results Among the 200 patients who were enrolled (101 in the antibody group and 99 in the placebo group), the rate of recurrence of C. difficile infection was lower among patients treated with monoclonal antibodies (7% vs. 25%; 95% confidence interval, 7 to 29; P<0.001). The recurrence rates among patients with the epidemic BI/NAP1/027 strain were 8% for the antibody group and 32% for the placebo group (P = 0.06); among patients with more than one previous episode of C. difficile infection, recurrence rates were 7% and 38%, respectively (P = 0.006). The mean duration of the initial hospitalization for inpatients did not differ significantly between the antibody and placebo groups (9.5 and 9.4 days, respectively). At least one serious adverse event was reported by 18 patients in the antibody group and by 28 patients in the placebo group (P = 0.09). Conclusions The addition of monoclonal antibodies against C. difficile toxins to antibiotic agents significantly reduced the recurrence of C. difficile infection. (ClinicalTrials.gov number, NCT00350298.
Mitochondrial DNA (mtDNA) single nucleotide polymorphisms (SNPs) in an 11-plex assay were typed i... more Mitochondrial DNA (mtDNA) single nucleotide polymorphisms (SNPs) in an 11-plex assay were typed in three missing person cases involving highly degraded human remains. Unlike the traditional forensic approach to analyzing mtDNA which focuses on sequencing portions of the noncoding Control Region, this assay targets discriminatory SNPs that reside principally in the coding region. In two of the cases, the SNP typing successfully excluded one of two reference families that could not be excluded on the basis of mtDNA hypervariable region sequencing alone, and resulted in the final resolution of both decades-old cases. In a third case, SNP typing confirmed the sorting and reassociation of multiple commingled skeletal elements. The application of a specific mtDNA SNP assay in these cases demonstrates its utility in distinguishing samples when the most common Caucasian hypervariable region type is encountered in forensic casework.
Low copy number (LCN) STR typing was successfully applied to four interesting cases during develo... more Low copy number (LCN) STR typing was successfully applied to four interesting cases during developmental validation of the approach for degraded skeletal remains. Specific questions were addressed in each case, with the acquisition of STR data largely serving as additional confirmatory or investigatory information in any specific situation, and not necessarily providing the definitive evidence to establish identity. The cases involve missing U.S. service members from World War I, World War II, and the Vietnam War. The variety of these cases, in terms of the questions addressed, the age of the remains, and the type of reference material available for comparison, demonstrates the broad utility of LCN STR typing in the identification of degraded skeletal remains from missing persons.
Rapid allograft infection complicates liver transplantation (LT) in patients with hepatitis C vir... more Rapid allograft infection complicates liver transplantation (LT) in patients with hepatitis C virus (HCV). Pegylated interferon-α and ribavirin therapy after LT has significant toxicity and limited efficacy. The effect of a human monoclonal antibody targeting the HCV E2 glycoprotein (MBL-HCV1) on viral clearance was examined in a randomized, double-blind, placebo-controlled pilot study in patients infected with HCV genotype 1a undergoing LT. Subjects received 11 infusions of 50 mg/kg MBL-HCV1 (n=6) or placebo (n=5) intravenously with three infusions on day of transplant, a single infusion on days 1 through 7 and one infusion on day 14 after LT. MBL-HCV1 was well-tolerated and reduced viral load for a period ranging from 7 to 28 days. Median change
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Sep 30, 2016
Although newer studies have evaluated risk factors for recurrent Clostridium difficile infection... more Although newer studies have evaluated risk factors for recurrent Clostridium difficile infection (CDI), the vast majority did not measure important biomarkers such as endogenous anti-toxin A and anti-toxin B antibody levels. Data from the placebo group of a phase 2 trial testing monoclonal antibodies to C. difficile toxins A and B for preventing CDI recurrence (rCDI) were analyzed to assess risk factors associated with rCDI. Patients with symptomatic CDI taking metronidazole or vancomycin were enrolled. The primary outcome was rCDI within 84 days of treatment start. Univariate and multivariate logistic regression was used to examine associations between potential risk factors and rCDI. At baseline, demographic and clinical characteristics were recorded; endogenous antibody levels were assessed using 2 enzyme-linked immunosorbent assays. A predictor of recurrence was age ≥65 years, and an antibody-mediated immune response to toxin B appears to be protective against rCDI. Our find...
Prompt administration of anti-toxin reduces mortality following Corynebacterium diphtheriae infec... more Prompt administration of anti-toxin reduces mortality following Corynebacterium diphtheriae infection. Current treatment relies upon equine diphtheria anti-toxin (DAT), with a 10% risk of serum sickness and rarely anaphylaxis. The global DAT supply is extremely limited; most manufacturers have ceased production. S315 is a neutralizing human IgG1 monoclonal antibody to diphtheria toxin that may provide a safe and effective alternative to equine DAT and address critical supply issues. To guide dose selection for IND-enabling pharmacology and toxicology studies, we dose-ranged S315 and DAT in a guinea pig model of diphtheria intoxication based on the NIH Minimum Requirements potency assay. Animals received a single injection of antibody premixed with toxin, were monitored for 30 days, and assigned a numeric score for clinical signs of disease. Animals receiving ≥ 27.5 µg of S315 or ≥ 1.75 IU of DAT survived whereas animals receiving ≤ 22.5 µg of S315 or ≤ 1.25 IU of DAT died, yielding ...
Kruuk sees otters existing 'at the edge of a precipice': they live in a relatively uncommon, line... more Kruuk sees otters existing 'at the edge of a precipice': they live in a relatively uncommon, linear habitat, where they must cover great distances to satisfy their needs. They specialize in prey that are difficult to capture and young animals require considerable time to acquire the necessary skills, Foraging in cold water is so energetically expensive that large quantities of prey must be captured in a short time. Finally, toxic sub stances are more likely to accumulate in aquatic habitats than elsewhere. As a consequence, he feels that otter populations are highly vulnerable and that it is likely that 'only a small increase in a pollutant, a decrease in prey population, a severe winter or a drought may have effects much more dramatic than for many other similar-sized species'. I found this book fascinating. Although no doubt biased because of my own interest in otters, 1 recommend it to anyone interested in carnivore ecology and conservation.
Rapid allograft infection complicates liver transplantation (LT) in patients with hepatitis C vir... more Rapid allograft infection complicates liver transplantation (LT) in patients with hepatitis C virus (HCV). Pegylated interferon-α and ribavirin therapy after LT has significant toxicity and limited efficacy. The effect of a human monoclonal antibody targeting the HCV E2 glycoprotein (MBL-HCV1) on viral clearance was examined in a randomized, double-blind, placebo-controlled pilot study in patients infected with HCV genotype 1a undergoing LT. Subjects received 11 infusions of 50 mg/kg MBL-HCV1 (n=6) or placebo (n=5) intravenously with three infusions on day of transplant, a single infusion on days 1 through 7 and one infusion on day 14 after LT. MBL-HCV1 was well-tolerated and reduced viral load for a period ranging from 7 to 28 days. Median change
23 THE APPLICATION OF MTDNA SNPS TO FORENSIC CASEWORK Rebecca S. Just, Michael D. Coble, Mark D. ... more 23 THE APPLICATION OF MTDNA SNPS TO FORENSIC CASEWORK Rebecca S. Just, Michael D. Coble, Mark D. Leney, Suzanne M. Barritt and Thomas J. Parsons Armed Forces DNA Identification Laboratory, Armed Forces Institute of Pathology, AFIP Annex, 1413 Research Blvd., Rockville, MD 20850, USA Joint POW/MIA Accounting Command – Central Identification Laboratory, 310 Worchester Ave. Bldg. 45, Hickam AFB, HI 96853, USA Massachusetts Biologic Laboratories, University of Massachusetts Medical School, Jamaica Plain, MA 02310, USA Scientific Advisor, The National League of Families of American Prisoners and Missing in Southeast Asia,1005 Glebe Road, Suite 170 Arlington, VA 22201 International Commission on Missing Persons, Alipasina 45 A, 71000, Sarajevo, Bosnia The Armed Forces DNA Identification Laboratory (AFDIL) routinely uses mitochondrial DNA (mtDNA) sequence data for sample sorting and individuation in Vietnam, Korea, and WWII-era cases where the DNA is expected to be highly degraded. mtDNA, ...
Determining the location and distribution of cockpit and aircrew-related equipment within the wid... more Determining the location and distribution of cockpit and aircrew-related equipment within the wider debris field of a military aircraft crash site is an essential first step in planning and executing the recovery of missing aircrew members presumed still to be on the site. Understanding the spatial relationship of these materials improves the likelihood of finding and recovering the remains of the aircrew during the excavation of an aircraft crash site. Since the greater portion of these unaccounted for crewmembers were involved in aircraft with single-seat cockpits or cockpits with two or three seats in tandem, pre-analysis of the debris pattern may be more-or-less straightforward. Larger, multiple-personnel aircraft, on the other hand, create a potentially more complex analytical situation given the aircrew&amp;amp;amp;amp;#39;s greater freedom of movement within the aircraft. Nevertheless, the same fundamental principles apply and, indeed, have been successfully so for some time in the civilian arena. But older aircraft crash sites, i.e., those dating to World War II, Korea, or the Vietnam conflict, have been and still are undergoing taphonomic processes that progressively alter these relationships. The following will illustrate that exchange of information between the anthropologist/archaeologist and the life-support analyst is required to maximize the effectiveness of field recovery and demonstrates the relationship between the recovery of life-support equipment and human remains and the effect that aircraft type has on this relationship.
This report describes the genetic identification of James ''Earthquake McGoon'' McGovern, a WWII ... more This report describes the genetic identification of James ''Earthquake McGoon'' McGovern, a WWII fighter ace who perished in Laos while providing supplies to French troops during the French Indochina war. Because reference samples were unavailable for all of the potential casualties, testing of the entire mitochondrial genome, autosomal STRs and Y-chromosomal STRs was performed to increase the genetic information available for analysis. Kinship analyses performed on the evidentiary data and numerous indirect family references for McGovern excluded other possible casualties and definitively established McGovern's identity. This particular case demonstrates the practical utility of novel research technologies and aggressive genetic typing protocols in the identification of aged, degraded remains.
See the Editorial Commentary by Cornely and Vehreschild on pages 735-6.) Background. Although new... more See the Editorial Commentary by Cornely and Vehreschild on pages 735-6.) Background. Although newer studies have evaluated risk factors for recurrent Clostridium difficile infection (CDI), the vast majority did not measure important biomarkers such as endogenous anti-toxin A and anti-toxin B antibody levels. Methods. Data from the placebo group of a phase 2 trial testing monoclonal antibodies to C. difficile toxins A and B for preventing CDI recurrence (rCDI) were analyzed to assess risk factors associated with rCDI. Patients with symptomatic CDI taking metronidazole or vancomycin were enrolled. The primary outcome was rCDI within 84 days of treatment start. Univariate and multivariate logistic regression was used to examine associations between potential risk factors and rCDI. At baseline, demographic and clinical characteristics were recorded; endogenous antibody levels were assessed using 2 enzyme-linked immunosorbent assays. Results. A predictor of recurrence was age ≥65 years, and an antibody-mediated immune response to toxin B appears to be protective against rCDI. Conclusions. Our findings demonstrate the importance of clinical as well as immunological risk factors in rCDI and provide more robust evidence for the protective effects of antibody to toxin B in the prevention of rCDI. Clinical Trials Registration. NCT00350298.
Background New therapies are needed to manage the increasing incidence, severity, and high rate o... more Background New therapies are needed to manage the increasing incidence, severity, and high rate of recurrence of Clostridium difficile infection. Methods We performed a randomized, double-blind, placebo-controlled study of two neutralizing, fully human monoclonal antibodies against C. difficile toxins A (CDA1) and B (CDB1). The antibodies were administered together as a single infusion, each at a dose of 10 mg per kilogram of body weight, in patients with symptomatic C. difficile infection who were receiving either metronidazole or vancomycin. The primary outcome was laboratory-documented recurrence of infection during the 84 days after the administration of monoclonal antibodies or placebo. Results Among the 200 patients who were enrolled (101 in the antibody group and 99 in the placebo group), the rate of recurrence of C. difficile infection was lower among patients treated with monoclonal antibodies (7% vs. 25%; 95% confidence interval, 7 to 29; P<0.001). The recurrence rates among patients with the epidemic BI/NAP1/027 strain were 8% for the antibody group and 32% for the placebo group (P = 0.06); among patients with more than one previous episode of C. difficile infection, recurrence rates were 7% and 38%, respectively (P = 0.006). The mean duration of the initial hospitalization for inpatients did not differ significantly between the antibody and placebo groups (9.5 and 9.4 days, respectively). At least one serious adverse event was reported by 18 patients in the antibody group and by 28 patients in the placebo group (P = 0.09). Conclusions The addition of monoclonal antibodies against C. difficile toxins to antibiotic agents significantly reduced the recurrence of C. difficile infection. (ClinicalTrials.gov number, NCT00350298.
Mitochondrial DNA (mtDNA) single nucleotide polymorphisms (SNPs) in an 11-plex assay were typed i... more Mitochondrial DNA (mtDNA) single nucleotide polymorphisms (SNPs) in an 11-plex assay were typed in three missing person cases involving highly degraded human remains. Unlike the traditional forensic approach to analyzing mtDNA which focuses on sequencing portions of the noncoding Control Region, this assay targets discriminatory SNPs that reside principally in the coding region. In two of the cases, the SNP typing successfully excluded one of two reference families that could not be excluded on the basis of mtDNA hypervariable region sequencing alone, and resulted in the final resolution of both decades-old cases. In a third case, SNP typing confirmed the sorting and reassociation of multiple commingled skeletal elements. The application of a specific mtDNA SNP assay in these cases demonstrates its utility in distinguishing samples when the most common Caucasian hypervariable region type is encountered in forensic casework.
Low copy number (LCN) STR typing was successfully applied to four interesting cases during develo... more Low copy number (LCN) STR typing was successfully applied to four interesting cases during developmental validation of the approach for degraded skeletal remains. Specific questions were addressed in each case, with the acquisition of STR data largely serving as additional confirmatory or investigatory information in any specific situation, and not necessarily providing the definitive evidence to establish identity. The cases involve missing U.S. service members from World War I, World War II, and the Vietnam War. The variety of these cases, in terms of the questions addressed, the age of the remains, and the type of reference material available for comparison, demonstrates the broad utility of LCN STR typing in the identification of degraded skeletal remains from missing persons.
Rapid allograft infection complicates liver transplantation (LT) in patients with hepatitis C vir... more Rapid allograft infection complicates liver transplantation (LT) in patients with hepatitis C virus (HCV). Pegylated interferon-α and ribavirin therapy after LT has significant toxicity and limited efficacy. The effect of a human monoclonal antibody targeting the HCV E2 glycoprotein (MBL-HCV1) on viral clearance was examined in a randomized, double-blind, placebo-controlled pilot study in patients infected with HCV genotype 1a undergoing LT. Subjects received 11 infusions of 50 mg/kg MBL-HCV1 (n=6) or placebo (n=5) intravenously with three infusions on day of transplant, a single infusion on days 1 through 7 and one infusion on day 14 after LT. MBL-HCV1 was well-tolerated and reduced viral load for a period ranging from 7 to 28 days. Median change
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Sep 30, 2016
Although newer studies have evaluated risk factors for recurrent Clostridium difficile infection... more Although newer studies have evaluated risk factors for recurrent Clostridium difficile infection (CDI), the vast majority did not measure important biomarkers such as endogenous anti-toxin A and anti-toxin B antibody levels. Data from the placebo group of a phase 2 trial testing monoclonal antibodies to C. difficile toxins A and B for preventing CDI recurrence (rCDI) were analyzed to assess risk factors associated with rCDI. Patients with symptomatic CDI taking metronidazole or vancomycin were enrolled. The primary outcome was rCDI within 84 days of treatment start. Univariate and multivariate logistic regression was used to examine associations between potential risk factors and rCDI. At baseline, demographic and clinical characteristics were recorded; endogenous antibody levels were assessed using 2 enzyme-linked immunosorbent assays. A predictor of recurrence was age ≥65 years, and an antibody-mediated immune response to toxin B appears to be protective against rCDI. Our find...
Prompt administration of anti-toxin reduces mortality following Corynebacterium diphtheriae infec... more Prompt administration of anti-toxin reduces mortality following Corynebacterium diphtheriae infection. Current treatment relies upon equine diphtheria anti-toxin (DAT), with a 10% risk of serum sickness and rarely anaphylaxis. The global DAT supply is extremely limited; most manufacturers have ceased production. S315 is a neutralizing human IgG1 monoclonal antibody to diphtheria toxin that may provide a safe and effective alternative to equine DAT and address critical supply issues. To guide dose selection for IND-enabling pharmacology and toxicology studies, we dose-ranged S315 and DAT in a guinea pig model of diphtheria intoxication based on the NIH Minimum Requirements potency assay. Animals received a single injection of antibody premixed with toxin, were monitored for 30 days, and assigned a numeric score for clinical signs of disease. Animals receiving ≥ 27.5 µg of S315 or ≥ 1.75 IU of DAT survived whereas animals receiving ≤ 22.5 µg of S315 or ≤ 1.25 IU of DAT died, yielding ...
Kruuk sees otters existing 'at the edge of a precipice': they live in a relatively uncommon, line... more Kruuk sees otters existing 'at the edge of a precipice': they live in a relatively uncommon, linear habitat, where they must cover great distances to satisfy their needs. They specialize in prey that are difficult to capture and young animals require considerable time to acquire the necessary skills, Foraging in cold water is so energetically expensive that large quantities of prey must be captured in a short time. Finally, toxic sub stances are more likely to accumulate in aquatic habitats than elsewhere. As a consequence, he feels that otter populations are highly vulnerable and that it is likely that 'only a small increase in a pollutant, a decrease in prey population, a severe winter or a drought may have effects much more dramatic than for many other similar-sized species'. I found this book fascinating. Although no doubt biased because of my own interest in otters, 1 recommend it to anyone interested in carnivore ecology and conservation.
Rapid allograft infection complicates liver transplantation (LT) in patients with hepatitis C vir... more Rapid allograft infection complicates liver transplantation (LT) in patients with hepatitis C virus (HCV). Pegylated interferon-α and ribavirin therapy after LT has significant toxicity and limited efficacy. The effect of a human monoclonal antibody targeting the HCV E2 glycoprotein (MBL-HCV1) on viral clearance was examined in a randomized, double-blind, placebo-controlled pilot study in patients infected with HCV genotype 1a undergoing LT. Subjects received 11 infusions of 50 mg/kg MBL-HCV1 (n=6) or placebo (n=5) intravenously with three infusions on day of transplant, a single infusion on days 1 through 7 and one infusion on day 14 after LT. MBL-HCV1 was well-tolerated and reduced viral load for a period ranging from 7 to 28 days. Median change
23 THE APPLICATION OF MTDNA SNPS TO FORENSIC CASEWORK Rebecca S. Just, Michael D. Coble, Mark D. ... more 23 THE APPLICATION OF MTDNA SNPS TO FORENSIC CASEWORK Rebecca S. Just, Michael D. Coble, Mark D. Leney, Suzanne M. Barritt and Thomas J. Parsons Armed Forces DNA Identification Laboratory, Armed Forces Institute of Pathology, AFIP Annex, 1413 Research Blvd., Rockville, MD 20850, USA Joint POW/MIA Accounting Command – Central Identification Laboratory, 310 Worchester Ave. Bldg. 45, Hickam AFB, HI 96853, USA Massachusetts Biologic Laboratories, University of Massachusetts Medical School, Jamaica Plain, MA 02310, USA Scientific Advisor, The National League of Families of American Prisoners and Missing in Southeast Asia,1005 Glebe Road, Suite 170 Arlington, VA 22201 International Commission on Missing Persons, Alipasina 45 A, 71000, Sarajevo, Bosnia The Armed Forces DNA Identification Laboratory (AFDIL) routinely uses mitochondrial DNA (mtDNA) sequence data for sample sorting and individuation in Vietnam, Korea, and WWII-era cases where the DNA is expected to be highly degraded. mtDNA, ...
Uploads
Papers by Mark Leney