398 research outputs found
Complementarity Among Vertical Integration Decisions: Evidence from Automobile Product Development
This paper examines complementarity among vertical integration decisions in automobile product development. Though most research assumes that contracting choices are independent of each other, contracting complementarity arises when the returns to a single vertical integration decision are increasing in the level of vertical integration associated with other contracting choices. First, effective coordination may depend on the level of (non-contractible) effort on the part of each agent; contracting complementarity results if coordination efforts are interdependent and vertical integration facilitates a higher level of non-contractible effort. Second, effective coordination may require the disclosure of proprietary trade secrets, and the potential for expropriation by external suppliers may induce complementarity among vertical integration choices. We provide evidence for complementarity in product development contracting by taking advantage of a detailed dataset that includes the level of vertical integration and the contracting environment for individual automobile systems in the luxury automobile segment. Using an instrumental variables framework that distinguishes complementarity from unobserved firm-level factors, the evidence is consistent with the hypothesis that contracting complementarity is an important driver of vertical integration choices. The findings suggest that contracting complementarity may be particularly important when coordination is important to achieve but difficult to monitor.
On the Grouping of Tasks into Firms: Make-or-Buy with Interdependent Parts
We study the division of labor within production systems and look for the optimal grouping of tasks into firms. Using a unique dataset on the global automobile industry, we present evidence consistent with the prediction that pairs of tasks requiring more frequent mutual adaptation are more likely to be performed by the same firm. By taking account of interdependencies between tasks, our econometric approach generalizes standard make-or-buy analysis and yields improvements in predictive accuracy
Culture Clash: The Corporate Socialization Process Meets Non-Congruent Organization Subcultures
The literature on organization socialization suggests characteristics
associated with strong organization culture. Key among these is a socialization
process that emphasizes well-defined roles, rules, routines, and values;
reinforcement with intrinsic and extrinsic reward systems; and conditioning
experiences. That literature also suggests that an organization exhibiting a
strong culture and socialization process will likely elicit participant behavior that
is highly congruent with the espoused values and objectives stated by the
organization.
This paper uses a case study of General Motors' Saturn Corporation to
suggest an enrichment of this theory. We argue that Saturn fulfills all the
requirements of a strong culture and socialization process yet we find patterns of
behavior seemingly at odds with the espoused values and objectives articulated
in the environment. Co-existing with and within the strong corporate culture at
Saturn, we found work group subcultures whose socialization processes can be
just as strong as those at the corporate level but whose values suggest individual
behaviors that conflict with those espoused at the corporate level.
These observations lead us to suggest a model of culture-influenced
behavior that explicitly addresses the existence of distinct subgroup cultures.
Interestingly, the workgroup subcultures that generated behaviors at odds with
the outcomes desired at the corporate level were encouraged by exactly those
reward systems designed by Saturn to reinforce the espoused values of
consensus decision-making at the workgroup level. Such observations
underscore the complexity and subtlety involved in designing coherent
organization-wide cultures and reinforcing mechanisms.MIT's International
Motor Vehicle Program and Project Delta at the Sloan School of Management
Fitting Teams to the Task: Product Development Vs. Operations Improvement at Saturn and Nummi
In the automotive industry, Saturn and NUMMI are often touted as
exemplars of successful implementation of manufacturing employee
involvement. Building on data and extended on-site interviews, this paper
explores the differences between the approaches taken at each plant and the
relationship between worker involvement and plant performance. Based on this
comparison, we offer a model to assess the fit between employee involvement
activity emphasis (product development vs. operations improvement) and
timescale of the involvement process.MIT's International
Motor Vehicle Program and Project Delta at the Sloan School of Management
Bone Involvement in Hyperphosphatemic Familial Tumoral Calcinosis: A New Phenotypic Presentation
Mutations in FGF23, KL, and GALNT3 have been identified as the cause for the development of hyperphosphatemic familial tumoral calcinosis (HFTC). Patients with HFTC typically present in childhood or adolescence with periarticular soft tissue deposits that eventually progress to disrupt normal joint articulation. Mutations in the GALNT3 gene were shown to account for the hyperphosphatemic state in both HFTC and hyperostosis-hyperphosphatemia syndrome (HHS), the latter characterized by bone involvement. We present the case of a patient of a Druze ethnic origin with known HFTC that presented to our department with the first documented case of pathologic fracture occurring secondary to the disease. Our report introduces this new phenotypic presentation, suggests a potential role for prophylactic bone screening, and highlights the need for preconception genetic screening in selected populations
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A Randomized, Controlled, Phase 2 Study of Maralixibat in the Treatment of Itching Associated With Primary Biliary Cholangitis.
Primary biliary cholangitis (PBC) is typically associated with elevated serum bile acid levels and pruritus, but pruritus is often refractory to treatment with existing therapies. This phase 2 study assessed the efficacy and safety of maralixibat, a selective, ileal, apical, sodium-dependent, bile acid transporter inhibitor, in adults with PBC and pruritus. Adults with PBC and pruritus who had received ursodeoxycholic acid (UDCA) for ≥6 months or were intolerant to UDCA were randomized 2:1 to maralixibat (10 or 20 mg/day) or placebo for 13 weeks in combination with UDCA (when tolerated). The primary outcome was change in Adult Itch Reported Outcome (ItchRO™) average weekly sum score (0, no itching; 70, maximum itching) from baseline to week 13/early termination (ET). The study enrolled 66 patients (maralixibat [both doses combined], n = 42; placebo, n = 24). Mean ItchRO™ weekly sum scores decreased from baseline to week 13/ET with maralixibat (-26.5; 95% confidence interval [CI], -31.8, -21.2) and placebo (-23.4; 95% CI, -30.3, -16.4). The difference between groups was not significant (P = 0.48). In the maralixibat and placebo groups, adverse events (AEs) were reported in 97.6% and 70.8% of patients, respectively. Gastrointestinal disorders were the most frequently reported AEs (maralixibat, 78.6%; placebo, 50.0%). Conclusion: Reductions in pruritus did not differ significantly between maralixibat and placebo. However, a large placebo effect may have confounded assessment of pruritus. Lessons learned from this rigorously designed and executed trial are indispensable for understanding how to approach trials assessing pruritus as the primary endpoint and the therapeutic window of bile acid uptake inhibition as a therapeutic strategy in PBC
A Phase 1a/1b Clinical Trial Design to Assess Safety, Acceptability, Pharmacokinetics and Tolerability of Intranasal Q-Griffithsin for COVID-19 Prophylaxis
Background: The COVID-19 pandemic remains an ongoing threat to global public health. Q-Griffithsin (Q-GRFT) is a lectin that has demonstrated potent broad-spectrum inhibitory activity in preclinical studies in models of Nipah virus and the beta coronaviruses SARS-CoV, MERS-CoV, and SARS-CoV-2.
Methods: Here, we propose a clinical trial design to test the safety, pharmacokinetics (PK), and tolerability of intranasally administered Q-GRFT for the prevention of SARS-CoV-2 infection as a prophylaxis strategy. The initial Phase 1a study will assess the safety and PK of a single dose of intranasally administered Q-GRFT. If found safe, the safety, PK, and tolerability of multiple doses of intranasal Q-GRFT will be assessed in a Phase 1b study. Group 1 participants will receive 3 mg of intranasal Q-GRFT (200 μL/nostril) once daily for 7 days. If this dose is tolerated, participants will be enrolled in Group 2 to receive 3 mg twice daily for 7 days. Secondary endpoints of the study will be user perceptions, acceptability, and the impact of product use on participants’ olfactory sensation and quality of life.
Discussion: Results from this study will support further development of Q-GRFT as a prophylactic against respiratory viral infections in future clinical trials
BurkDiff: A Real-Time PCR Allelic Discrimination Assay for Burkholderia Pseudomallei and B. mallei
A real-time PCR assay, BurkDiff, was designed to target a unique conserved region in the B. pseudomallei and B. mallei genomes containing a SNP that differentiates the two species. Sensitivity and specificity were assessed by screening BurkDiff across 469 isolates of B. pseudomallei, 49 isolates of B. mallei, and 390 isolates of clinically relevant non-target species. Concordance of results with traditional speciation methods and no cross-reactivity to non-target species show BurkDiff is a robust, highly validated assay for the detection and differentiation of B. pseudomallei and B. mallei
Performance of swabs, lavage, and diluents to quantify biomarkers of female genital tract soluble mucosal mediators
Background: Measurement of immune mediators and antimicrobial activity in female genital tract secretions may provide biomarkers predictive of risk for HIV-1 acquisition and surrogate markers of microbicide safety. However, optimal methods for sample collection do not exist. This study compared collection methods. Methods: Secretions were collected from 48 women (24 with bacterial vaginosis [BV]) using vaginal and endocervical Dacron and flocked swabs. Cervicovaginal lavage (CVL) was collected with 10 mL of Normosol-R (n = 20), saline (n = 14), or water (n = 14). The concentration of gluconate in Normosol-R CVL was determined to estimate the dilution factor. Cytokine and antimicrobial mediators were measured by Luminex or ELISA and corrected for protein content. Endogenous anti-HIV-1 and anti-E. coli activity were measured by TZM-bl assay or E. coli growth. Results: Higher concentrations of protein were recovered by CVL, despite a 10-fold dilution of secretions, as compared to swab eluents. After protein correction, endocervical swabs recovered the highest mediator levels regardless of BV status. Endocervical and vaginal flocked swabs recovered significantly higher levels of anti-HIV-1 and anti-E. coli activity than Dacron swabs (P<0.001). BV had a significant effect on CVL mediator recovery. Normosol-R tended to recover higher levels of most mediators among women with BV, whereas saline or water tended to recover higher levels among women without BV. Saline recovered the highest levels of anti-HIV-1 activity regardless of BV status. Conclusions: Endocervical swabs and CVL collected with saline provide the best recovery of most mediators and would be the optimal sampling method(s) for clinical trials. © 2011 Dezzutti et al
Diversity of 16S-23S rDNA Internal Transcribed Spacer (ITS) Reveals Phylogenetic Relationships in Burkholderia pseudomallei and Its Near-Neighbors
Length polymorphisms within the 16S-23S ribosomal DNA internal transcribed spacer (ITS) have been described as stable genetic markers for studying bacterial phylogenetics. In this study, we used these genetic markers to investigate phylogenetic relationships in Burkholderia pseudomallei and its near-relative species. B. pseudomallei is known as one of the most genetically recombined bacterial species. In silico analysis of multiple B. pseudomallei genomes revealed approximately four homologous rRNA operons and ITS length polymorphisms therein. We characterized ITS distribution using PCR and analyzed via a high-throughput capillary electrophoresis in 1,191 B. pseudomallei strains. Three major ITS types were identified, two of which were commonly found in most B. pseudomallei strains from the endemic areas, whereas the third one was significantly correlated with worldwide sporadic strains. Interestingly, mixtures of the two common ITS types were observed within the same strains, and at a greater incidence in Thailand than Australia suggesting that genetic recombination causes the ITS variation within species, with greater recombination frequency in Thailand. In addition, the B. mallei ITS type was common to B. pseudomallei, providing further support that B. mallei is a clone of B. pseudomallei. Other B. pseudomallei near-neighbors possessed unique and monomorphic ITS types. Our data shed light on evolutionary patterns of B. pseudomallei and its near relative species
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