Immunization of Healthy Adult Subjects in the United States with Inactivated Mycobacterium vaccae Administered in a Three-Dose Series

Abstract Background Carbapenem-resistant Acinetobacter baumannii infections are defined by the WHO as a critical threat. IV minocycline is approved in the United States for treatment of Acinetobacter infections at doses up to 200 mg BID. This study investigated safety and PK of single and multiple doses of IV minocycline, including doses higher than approved in the United States. Methods This was a randomized, double blind, placebo-controlled, SAD/MAD study of 6 doses (100–600 mg) of IV minocycline. Healthy adult subjects received a single dose of minocycline or placebo on Day 1, and 15 doses BID starting on Day 4. Safety was assessed throughout the study. Serial blood and urine samples were collected for PK assessment. Results Sixty-nine healthy subjects were randomized, 49 were included in the PK analysis. No serious adverse events (AEs) occurred; 55 subjects (79.9%) reported study drug-related AEs; dizziness 40 (58.0%) and nausea 34 (49.3%) were the most common. All related AEs were mild except for seven subjects with moderate nausea and/or dizziness. Dosing in the 400 mg cohort was discontinued due to AEs, therefore MAD escalation was stopped. Subsequent cohorts were escalated for SAD and loading dose only. Conclusion Single IV doses of minocycline up to 600 mg were tolerated reasonably well, but the maximum tolerated multi-dose was 300 mg BID. Most common AEs were mild nausea and dizziness with evidence of increasing incidence but not increasing severity with increasing dose. Exposure increased in a dose proportional fashion with exception of the 500 mg dose. The dosage regimen selected for further studies will be a 600 mg loading dose followed by 300 mg BID. Disclosures O. A. Cornely, Innovative Medicines Initiative Joint Undertaking: Grant Investigator, Grant recipient. A. MacGowan, Merck: Commercial grant, Research support; Paratek: Commercial grant, Research support; VenatoRx: Commercial grant, Research support; Bayer: Commercial grant, Research support; Achaogen: Commercial grant, Research support; AiCuris: Collaborator and Commercial grant, Grant recipient and Research support; Polyphor: Commercial grant, Research support; Pfizer: Commercial grant, Research support; Roche: Commercial grant, Research support; Melinta: Industrial partner, Research support; MedImmune (AZ): Industrial partner (IMI), Research support; NIHR England: Grant Investigator, Grant recipient; MRC (UK): Grant Investigator, Grant recipient; Innovate UK: Grant Investigator, Grant recipient. Newton Fund (FCO): Grant Investigator, Grant recipient. S. K. Cammarata, Melinta Therapeutics, Inc.: Employee, Salary. K. Fusaro, Melinta Therapeutics: Employee, Salary. J. S. Loutit, The Medicines Company: Employee and Shareholder, Salary

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Comparison of the Gut Microbiotas of Healthy Adult Twins Living in South Korea and the United States

Applied and Environmental Microbiology ◽

10.1128/aem.05490-11 ◽

2011 ◽

Vol 77 (20) ◽

pp. 7433-7437 ◽

Cited By ~ 52

Author(s):

Sunghee Lee ◽

Joohon Sung ◽

JungEun Lee ◽

GwangPyo Ko

Keyword(s):

United States ◽

Environmental Factors ◽

Gut Microbiota ◽

South Korea ◽

Regional Differences ◽

Healthy Adult ◽

The United States ◽

Phenotypic Variations ◽

Adult Twins

ABSTRACTWe compared the composition of the fecal microbiotas of Korean and U.S. adult twins. Our data indicated that the gut microbiota shows some signature of biogeography, potentially mediated by differences in diet and/or other environmental factors; however, these regional differences may be masked by other phenotypic variations, such as obesity.

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Party Strength in the United States: Some Corrections

The Journal of Politics ◽

10.1017/s0022381600041591 ◽

1975 ◽

Vol 37 (2) ◽

pp. 641-642 ◽

Cited By ~ 1

Author(s):

Paul T. David

Keyword(s):

United States ◽

The United States ◽

Party Strength

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Correlative microscopy in distrubuted (client/server) computing environments: tools for catalyzing the rapid dissemination of information about the cell biology of the human prostate

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100139780 ◽

1995 ◽

Vol 53 ◽

pp. 682-683

Author(s):

A. Hakam ◽

J.T. Gau ◽

M.L. Grove ◽

B.A. Evans ◽

M. Shuman ◽

...

Keyword(s):

United States ◽

Cell Biology ◽

Tissue Bank ◽

The United States ◽

Prostate Adenocarcinoma ◽

Correlative Microscopy ◽

Client Server ◽

Critical Elements ◽

Transplant Organ

Prostate adenocarcinoma is the most common malignant tumor of men in the United States and is the third leading cause of death in men. Despite attempts at early detection, there will be 244,000 new cases and 44,000 deaths from the disease in the United States in 1995. Therapeutic progress against this disease is hindered by an incomplete understanding of prostate epithelial cell biology, the availability of human tissues for in vitro experimentation, slow dissemination of information between prostate cancer research teams and the increasing pressure to “ stretch” research dollars at the same time staff reductions are occurring.To meet these challenges, we have used the correlative microscopy (CM) and client/server (C/S) computing to increase productivity while decreasing costs. Critical elements of our program are as follows:1) Establishing the Western Pennsylvania Genitourinary (GU) Tissue Bank which includes >100 prostates from patients with prostate adenocarcinoma as well as >20 normal prostates from transplant organ donors.

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Digital image acquisition, processing, and analysis in a polymer microscopy laboratory

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100170001 ◽

1994 ◽

Vol 52 ◽

pp. 454-455

Author(s):

Vinod K. Berry ◽

Xiao Zhang

Keyword(s):

United States ◽

Image Analysis ◽

Digital Image ◽

Image Acquisition ◽

Image Transmission ◽

The United States ◽

Quantitative Image Analysis ◽

Quantitative Image

In recent years it became apparent that we needed to improve productivity and efficiency in the Microscopy Laboratories in GE Plastics. It was realized that digital image acquisition, archiving, processing, analysis, and transmission over a network would be the best way to achieve this goal. Also, the capabilities of quantitative image analysis, image transmission etc. available with this approach would help us to increase our efficiency. Although the advantages of digital image acquisition, processing, archiving, etc. have been described and are being practiced in many SEM, laboratories, they have not been generally applied in microscopy laboratories (TEM, Optical, SEM and others) and impact on increased productivity has not been yet exploited as well.In order to attain our objective we have acquired a SEMICAPS imaging workstation for each of the GE Plastic sites in the United States. We have integrated the workstation with the microscopes and their peripherals as shown in Figure 1.

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Silence of the Land: On the Historical Irrelevance of Territory to Congressional Districting and Political Representation in the United States

Studies in American Political Development ◽

10.1017/s0898588x01010045 ◽

2001 ◽

Vol 15 (01) ◽

pp. 53-87 ◽

Cited By ~ 2

Author(s):

Andrew Rehfeld

Keyword(s):

United States ◽

House Of Representatives ◽

Political Representation ◽

The United States ◽

Representative Government ◽

Congressional District ◽

Congressional Districts ◽

Communities Of Interest

Every ten years, the United States “constructs” itself politically. On a decennial basis, U.S. Congressional districts are quite literally drawn, physically constructing political representation in the House of Representatives on the basis of where one lives. Why does the United States do it this way? What justifies domicile as the sole criteria of constituency construction? These are the questions raised in this article. Contrary to many contemporary understandings of representation at the founding, I argue that there were no principled reasons for using domicile as the method of organizing for political representation. Even in 1787, the Congressional district was expected to be far too large to map onto existing communities of interest. Instead, territory should be understood as forming a habit of mind for the founders, even while it was necessary to achieve other democratic aims of representative government.

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