Biostatistics Faculty and NIH Awards at U.S. Medical Schools

<div><p>Statistical principles and methods are critical to the success of biomedical and translational research. However, it is difficult to track and evaluate the monetary value of a biostatistician to a medical school (SoM). Limited published data on this topic are available, especially comparing across SoMs. Using National Institutes of Health (NIH) awards and American Association of Medical Colleges (AAMC) faculty counts data (2010–2013), together with online information on biostatistics faculty from 119 institutions across the country, we demonstrated that the number of biostatistics faculty was significantly positively associated with the amount of NIH awards, both as a school total and on a per faculty basis, across various sizes of U.S. SoMs. Biostatisticians, as a profession, should be proactive in communicating and advocating the value of their work and their unique contribution to the long-term success of a biomedical research enterprise. Supplementary materials for this article are available online.</p></div

High-Efficiency BODIPY-Based Organic Photovoltaics

A benzannulated boron dipyrromethene (BODIPY, bDIP) molecule exhibiting strong absorption at 640 nm was synthesized. The organic dye was used in an organic solar cell as the electron donor with C₆₀ as the acceptor. The BODIPY dye demonstrated the best performance in lamellar architecture (indium tin oxide (ITO)/bDIP/C₆₀/bathocuproine/Al), giving power conversion efficiency up to 4.5% with short-circuit current (<i>J</i>_SC) of 8.7 mA/cm² and an open-circuit voltage (<i>V</i>_OC) of 0.81 V. Neutron reflectivity experiments were performed on the bilayer film to investigate the thickness dependence of <i>J</i>_SC. A 13 nm mixed layer was found to be present at the donor/acceptor interface in the bilayer device, formed when the C₆₀ was deposited onto a room temperature bDIP film. Planar-mixed heterojunction devices were fabricated to understand the extent of spontaneous mixing between the donor and acceptor materials. The native mixed region in the bilayer device was shown to most resemble 1:3 bDIP:C₆₀ layer in the structure: (ITO/bDIP/bDIP:C₆₀ blend/C₆₀/bathocuproine/Al)

SCCA expression correlates to high grade breast cancer in the CDP progression TMA.

<p>The three CDP progression TMA case sets (designated as Case Sets 3, 5, and 7 by CDP) were probed for SCCA expression and scored. The grading information was provided by CDP in 291 accountable samples.</p

SCCA expression correlates to a decreased overall survival and recurrence-free survival.

<p>IHC was performed using the SCCA antibody FL-390 on the CDP prognostic TMAs. Kaplan-Meier survival curves for all patients (A–B) and only Grade II and Grade III patients (C–D) with SCCA-positive and negative tumors were compared for overall survival (A&C) and recurrence-free survival (B&D).</p

SCCA expression correlates to advanced stage breast carcinomas.

<p>The Stage I, Stage II, and Stage III prognostic TMAs were obtained from CDP. IHC was against SCCA. The tissue was scored and the SCCA-positive cases are shown in parentheses against the number of cases for each stage. Note that all of the normal tissue were SCCA-negative, whereas 14 out of 573 (2.4%) Stage I, 12 out of the 391 (3.1%) Stage II, and 15 out of 174 (8.6%) Stage III cases were SCCA-positive.</p

SCCA expression correlates to high grade breast carcinoma in the CDP prognostic TMA.

<p>The Stage I (Case Sets 9–13), Stage II (Case Sets 14–17), and Stage III (Case Sets 18–19) prognostic TMAs were obtained from CDP, containing 598, 411, and 184 tissue specimens, respectively. IHC was performed against SCCA. The tissue was scored and the SCCA-positive cases are shown in parentheses against the number of cases in each grade. Note that all of the normal tissue were SCCA-negative, whereas 1 out of 294 Grade I, 11 out of the 534 Grade II, and 29 out of 310 Grade III cases were SCCA-positive.</p

SCCA expression correlates to high grade breast carcinomas.

<p>The cumulative results of the SCCA positivity against the breast carcinoma grading from the CDP progression and prognostic TMAs are shown. SCCA is negative in the 124 normal or non-neoplastic cases of breast tissue. SCCA is positive in 1 of the 330 (0.3%) Grade I cases, 16 of the 638 (2.5%) Grade II cases, and in 37 of the 392 (9.4%) Grade III cases.</p

Validation of SCCA antibodies.

<p>293T cells were transfected with either vector alone, Flag-SCCA1, or Flag-SCCA2 plasmids. (A) Cells were subjected to immunoblot analysis using three SCCA antibodies: FL-390 for SCCA1/2, 8H11 for SCCA1, and 10C12 for SCCA2, as well as Flag antibody and β-tubulin antibody. (B) Cells were fixed and embedded in paraffin. IHC was performed with FL-390 and 10C12 antibodies. (C) IHC was performed on normal human tissue using the antibody Clone FL-390. Scale bars  = 50 µm.</p

Elevated SCCA expression is found in human breast cancer cell lines and human breast cancer carcinomas, but not in normal breast epithelium.

<p>(A) A panel of human cancer cells was probed for SCCA expression by immunoblotting. Five out of the six breast cancer cell lines (denoted with an asterisk) were positive for SCCA expression. (B) IHC analysis was performed on an array of breast carcinomas and normal breast tissue obtained from CHTN, using antibody FL-390. Representative images of normal breast tissue and sections with Grade III invasive ductal carcinoma are shown. (C) IHC staining was performed on the NCI CDP breast cancer progression and the prognostic TMAs using antibody FL-390. SCCA staining was scored on a tiered-scale (0–3). A representative panel is shown. Scale bars  = 50 µm.</p

The Antibody Response of Pregnant Cameroonian Women to VAR2CSA ID1-ID2a, a Small Recombinant Protein Containing the CSA-Binding Site

<div><p>In pregnant women, <i>Plasmodium falciparum</i>-infected erythrocytes expressing the VAR2CSA antigen bind to chondroitin sulfate A in the placenta causing placental malaria. The binding site of VAR2CSA is present in the ID1-ID2a region. This study sought to determine if pregnant Cameroonian women naturally acquire antibodies to ID1-ID2a and if antibodies to ID1-ID2a correlate with absence of placental malaria at delivery. Antibody levels to full-length VAR2CSA and ID1-ID2a were measured in plasma samples from 745 pregnant Cameroonian women, 144 Cameroonian men, and 66 US subjects. IgM levels and IgG avidity to ID1-ID2a were also determined. As expected, antibodies to ID1-ID2a were absent in US controls. Although pregnant Cameroonian women developed increasing levels of antibodies to full-length VAR2CSA during pregnancy, no increase in either IgM or IgG to ID1-ID2a was observed. Surprisingly, no differences in antibody levels to ID1-ID2a were detected between Cameroonian men and pregnant women. For example, in rural settings only 8–9% of males had antibodies to full-length VAR2CSA, but 90–96% had antibodies to ID1-ID2a. In addition, no significant difference in the avidity of IgG to ID1-ID2a was found between pregnant women and Cameroonian men, and no correlation between antibody levels at delivery and absence of placental malaria was found. Thus, the response to ID1-ID2a was not pregnancy specific, but predominantly against cross-reactivity epitopes, which may have been induced by other PfEMP1 antigens, malarial antigens, or microbes. Currently, ID1-ID2a is a leading vaccine candidate, since it binds to the CSA with the same affinity as the full-length molecule and elicits binding-inhibitory antibodies in animals. Further studies are needed to determine if the presence of naturally acquired cross-reactive antibodies in women living in malaria endemic countries will alter the response to ID1-ID2a following vaccination with ID1-ID2a.</p></div