Commercializing discontinuous innovations: bridging the gap from discontinuous innovation project to operations

Since 1995, a multidisciplinary team of researchers has deployed case study methodology to follow the progress of 12 discontinuous innovation projects in ten large R&D-intensive firms. The study has illuminated the challenges of managing the surprisingly difficult transition from R&D project to an operating unit in the eight of the 12 projects that reached transition. A substantial "readiness gap" existed between the project teams and the receiving business units. The challenges have been captured in the form of ten critical questions that must be addressed before a project can be successfully transitioned. Based on an analysis of transition practices, the authors identify seven propositions for improving the effectiveness of transition management suggesting the potential usefulness of the following managerial approaches: (1) conducting a transition readiness assessment; (2) assembling a transition team; (3) establishing an oversight board; (4) developing a transition plan; (5) providing transition funding from corporate sources; (6) laying the groundwork for a big market; and (7) engaging senior management champions.     

Purification by reflux electrophoresis of whey proteins and of a recombinant protein expressed in Dictyostelium discoideum

Protein purification that combines the use of molecular mass exclusion membranes with electrophoresis is particularly powerful as it uses properties inherent to both techniques. The use of membranes allows efficient processing and is easily scaled up, while electrophoresis permits high resolution separation under mild conditions. The Gradiflow apparatus combines these two technologies as it uses polyacrylamide membranes to influence electrokinetic separations. The reflux electrophoresis process consists of a series of cycles incorporating a forward phase and a reverse phase. The forward phase involves collection of a target protein that passes through a separation membrane before trailing proteins in the same solution. The forward phase is repeated following clearance of the membrane in the reverse phase by reversing the current. We have devised a strategy to establish optimal reflux separation parameters, where membranes are chosen for a particular operating range and protein transfer is monitored at different pH values. In addition, forward and reverse phase times are determined during this process. Two examples of the reflux method are described. In the first case, we described the purification strategy for proteins from a complex mixture which contains proteins of higher electrophoretic mobility than the target protein. This is a two-step procedure, where first proteins of higher mobility than the target protein are removed from the solution by a series of reflux cycles, so that the target protein remains as the leading fraction. In the second step the target protein is collected, as it has become the leading fraction of the remaining proteins. In the second example we report the development of a reflux strategy which allowed a rapid one-step preparative purification of a recombinant protein, expressed in Dictyostelium discoideum. These strategies demonstrate that the Gradiflow is amenable to a wide range of applications, as the protein of interest is not necessarily required to be the leading fraction in solution.     

Bacteremia and sepsis

Recent evolution in the thinking of sepsis syndrome has provided a framework on which new clinical and basic research can be built. The separation of the inciting event and the cascade of subsequent physiologic changes has profound effects on how sepsis is thought of and ultimately how it will be treated. Early identification and treatment of infections and identifying patients at risk, to prevent SIRS, is the current role of Eps. Resuscitation of severe sepsis is more complex than other forms of shock and may require extensive resources if rapid admission or transfer to an intensive care unit is not available. As in many instances, the EP must be knowledgeable and skilled in the early identification and initial management of these patients until the definitive care can be provided. Modulation of the inflammatory response appears to be a prime prospect, but its practicality remains to be proved. Research and future roles of EPs include defining the population of ED patients at risk for SIRS and use of mediators of the inflammatory response. Emergency medicine is positioned in a critical point in the care of these patients.     

Serotonin function and treatment response to clozapine in schizophrenic patients

OBJECTIVE: Clozapine is the only compound proven to be effective in the 20% of schizophrenic patients refractory to treatment with conventional neuroleptics. Although its mechanism of action has not been elucidated, clozapine appears, in contrast to most conventional neuroleptics, to be a potent serotonin (5-HT) antagonist. This study hypothesized that 5-HT function is increased in patients who benefit from clozapine treatment relative to patients who fail to improve on it. METHOD: The 5-HT receptor agonist m-chlorophenylpiperazine (MCPP) was used as a probe to examine 5-HT function. MCPP (0.35 mg/kg p.o.) was administered in a placebo-controlled design after a 3-week drug-free period to 19 schizophrenic patients. ACTH, prolactin, body temperature, behavior, and MCPP blood level were measured. Patients were then treated with a conventional neuroleptic, and, having failed to respond to it, were treated with clozapine for 5 weeks (up to 600 mg/day). RESULTS: Patients who responded to clozapine had significantly higher ACTH responses to MCPP during the drug-free state than the patients who failed to benefit from clozapine. Moreover, the degree of improvement with clozapine, particularly the improvement in psychotic symptoms, was strongly correlated with the magnitude of MCPP-induced ACTH release. Other MCPP-induced responses and MCPP blood level were similar for the two groups and did not correlate with the degree of symptomatic improvement with clozapine. CONCLUSIONS: Results of this study suggest that MCPP-induced ACTH release, and by inference 5-HT receptor function, may be increased in patients who benefit from treatment with clozapine relative to patients who fail to improve on this drug.     

Merkel cell tumor of the head and neck. Five new cases with literature review

Merkel cell carcinoma (MCC) of the skin is an uncommon, but highly aggressive neoplasm with a marked propensity for local and distant metastasis. Despite the fact that more than half of the 600 cases of MCC reported in the literature involved primary sites in the head and neck, MCC has rarely been discussed in otolaryngology publications. We present five new cases of MCC of the head and neck and summarize 89 additional cases from the literature in which detailed treatment and survival data were given. Our findings again emphasize the difficulty in making the initial histopathologic diagnosis of MCC and demonstrate the necessity of early diagnosis and multimodality treatment.     

The role of laparoscopy in the management of suspected pancreatic and periampullary malignancies

Laparoscopic evaluation of patients with suspected periampullary malignancies has been utilized more frequently in recent years. Its exact role with regard to staging and surgical bypass for palliation have yet to be clearly defined. To better define the role of laparoscopy in the evaluation and palliation of periampullary malignancy, a retrospective review of the Duke experience was carried out. Fifty-three patients with suspected pancreatic or periampullary malignancies were referred for surgical evaluation at Duke University Medical Center between 1993 and 1995. All patients underwent CT scanning and lesions were classified as resectable or unresectable based on previously established criteria. Patients either underwent laparoscopic evaluation (n = 30; 11 with laparoscopic palliation) or proceeded directly to celiotomy (n = 23). Charts were reviewed for postoperative course including complications, length of stay, and hospital costs. Although laparoscopy had a sensitivity of 93.3% for metastatic disease, CT scans accurately staged 86.8% of patients missing only one patient with peritoneal/hepatic disease. Based on these results, laparoscopy may not be beneficial for every patient with a suspected pancreatic malignancy. Retrospectively an attempt was made to determine which patients benefited from laparoscopy and which patients are best served by proceeding directly to open exploration. From these data we devised an algorithm that outlines an efficient and cost-effective approach for this patient population.     

In vivo delivery of interleukin-4 by a recombinant vaccinia virus prevents tumor development in mice

To study the immunotherapeutic potential of interleukin-4 (IL-4) delivered in vivo via a recombinant vaccinia virus, a thymidine kinase-negative (TK-) vaccinia virus that expressed the murine IL-4 gene (VV1/IL-4) was constructed. When mice were inoculated with 10(7) plaque-forming units (pfu) of VV1/IL-4 subcutaneously (s.c.), 10(5) pfu/cm2 were found in skin, and smaller numbers in liver and kidney between 1 and 7 days after infection; few viral pfu were found in spleen and lung, or in any organ after intravenous infection. This suggested that recombinant vaccinia viruses might be most efficient at delivery of cytokine genes to the skin. Because IL-4 has recently been found to have potent anti-tumor activity, the effect of recombinant virus infection on the development of s.c. tumors was studied. A single s.c. inoculation with VV1/IL-4 delayed the development of NCTC 2472 tumors, but when VV1/IL-4 was inoculated s.c. weekly for 8 weeks, tumor development was completely prevented in 93% of mice. Similarly, the development of M-3 melanoma tumors was also prevented by weekly s.c. inoculations of VV1/IL-4. About 40% of mice treated with control VV2/beta gal by the same regimen also failed to develop tumors. Weekly virus treatment did not prevent NCTC 2472 tumor development in athymic nu/nu mice, suggesting that mature T cells are required for expression of VV1/IL-4 induced antitumor activity. Thus, recombinant vaccinia viruses may be especially well suited for convenient therapeutic delivery of immunomodulator genes to skin-related sites.     

A randomized community trial to increase mammography utilization among low-income women living in public housing

BACKGROUND: A randomized trial was conducted to evaluate the impact of a community-based intervention on mammography use among low-income women living in public housing. METHODS: All 41 public housing high-rise buildings were randomized to treatment and delayed treatment (control) conditions. After a cross-sectional baseline survey, an intervention called Friend to Friend was conducted in the treatment buildings by American Cancer Society and building resident volunteers. The intervention consisted of a health professional talk, small group discussions, and an opportunity to request assistance in obtaining a mammogram or mammogram reminder. A second cross-sectional survey was conducted to measure differences in screening rates between the study groups. RESULTS: Participation in the intervention averaged 27%. The study groups were equivalent at baseline. At follow-up, the proportion of women age 50-79 years who reported mammography screening in the previous 15 months was significantly higher in the treatment group (64%) than in the control group (52%). Breast cancer knowledge, attitudes, and beliefs did not differ between groups. CONCLUSIONS: These findings suggest that a multidimensional intervention which reaches women within their social environment and uses community volunteers can increase mammography utilization among women in public housing.