Antibiotic research and development: business as usual?

This article contends that poor economic incentives are an important reason for the lack of new drugs and explains how the DRIVE-AB intends to change the landscape by harnessing the expertise, motivation and diversity of its partner

The profitability-risk tradeoff of just-in-time manufacturing technologies

Qualitative survey studies and a recent quantitative study by Callen et al. (2000) indicate that JIT manufacturing is more profitable than conventional non-JIT manufacturing. This study tests the hypothesis that the excess profitability of JIT manufacturing just compensates for the additional operational risks of JIT technology relative to conventional manufacturing. An often-suggested alternative hypothesis is that JIT manufacturing dominates conventional manufacturing in reducing costs and increasing revenues and that risk is not an issue. The multivariate results unambiguously reject the hypothesis that excess JIT profits are compensation for additional risk. We find that profitability is inversely related to risk, especially for JIT plants. We also find that the JIT plants in our sample are more profitable than non-JIT plants even after adjusting for risk, consistent with the dominance argument. Copyright © 2003 John Wiley & Sons, Ltd.

Circulating T-Cell Subsets, Monocytes, and Natural Killer Cells in Peripartum Cardiomyopathy: Results From the Multicenter IPAC Study

•Immune cell subsets were examined in healthy postpartum and peripartum cardiomyopathy (PPCM) women.•In the early postpartum, PPCM women had lower NK and higher CD3+CD4–CD8–CD38+ T cell levels.•Levels largely normalized by 6 months postpartum. The aim of this work was to evaluate the hypothesis that the distribution of circulating immune cell subsets, or their activation state, is significantly different between peripartum cardiomyopathy (PPCM) and healthy postpartum (HP) women. PPCM is a major cause of maternal morbidity and mortality, and an immune-mediated etiology has been hypothesized. Cellular immunity, altered in pregnancy and the peripartum period, has been proposed to play a role in PPCM pathogenesis. The Investigation of Pregnancy-Associated Cardiomyopathy (IPAC) study enrolled 100 women presenting with a left ventricular ejection fraction of <0.45 within 2 months of delivery. Peripheral T-cell subsets, natural killer (NK) cells, and cellular activation markers were assessed by flow cytometry in PPCM women early (<6 wk), 2 months, and 6 months postpartum and compared with those of HP women and women with non–pregnancy-associated recent-onset cardiomyopathy (ROCM). Entry NK cell levels (CD3–CD56+CD16+; reported as % of CD3– cells) were significantly (P < .0003) reduced in PPCM (6.6 ± 4.9% of CD3– cells) compared to HP (11.9 ± 5%). Of T-cell subtypes, CD3+CD4–CD8–CD38+ cells differed significantly (P < .004) between PPCM (24.5 ± 12.5% of CD3+CD4–CD8– cells) and HP (12.5 ± 6.4%). PPCM patients demonstrated a rapid recovery of NK and CD3+CD4–CD8–CD38+ cell levels. However, black women had a delayed recovery of NK cells. A similar reduction of NK cells was observed in women with ROCM. Compared with HP control women, early postpartum PPCM women show significantly reduced NK cells, and higher CD3+CD4–CD8–CD38+ cells, which both normalize over time postpartum. The mechanistic role of NK cells and “double negative” (CD4–CD8–) T regulatory cells in PPCM requires further investigation