Mobilizing the Temporary Organization: The Governance Roles of Selection and Pricing

Many marketing transactions between buyers and suppliers involve short-term collaborations or so-called temporary organizations. Such organizations have considerable value-creation potential but also face challenges, as evidenced by their mixed performance records. One particular challenge involves relationship governance, and in this respect, temporary organizations represent a conundrum: On the one hand, they pose significant governance problems due to the need to manage numerous independent specialists under time constraints. On the other hand, temporary organizations lack the inherent governance properties of other organizational forms such as permanent organizations. The authors conduct an empirical study of 429 business-to-business construction projects designed to answer two specific questions: First, how are particular selection and pricing strategies deployed in response to monitoring and coordination problems? Second, does the joint alignment between the two mechanisms and their respective attributes help mitigate cost overruns? The authors follow a formal hypothesis test with a series of in-depth interviews to explore and to gain insight into the validity of the key constructs, explanatory mechanisms, and outcomes. Managerially, the authors answer the long-standing question of how to mobilize a temporary organization. Theoretically, they develop an augmented “discriminating alignment” heuristic for relationship management involving multiple governance mechanisms and attributes.acceptedVersio

Comparative Genomics of Bordetella pertussis Reveals Progressive Gene Loss in Finnish Strains

BACKGROUND: Bordetella pertussis is a gram-negative bacterium that infects the human respiratory tract and causes pertussis or whooping cough. The disease has resurged in many countries including Finland where the whole-cell pertussis vaccine has been used for more than 50 years. Antigenic divergence has been observed between vaccine strains and clinical isolates in Finland. To better understand genome evolution in B. pertussis circulating in the immunized population, we developed an oligonucleotide-based microarray for comparative genomic analysis of Finnish strains isolated during the period of 50 years. METHODOLOGY/PRINCIPAL FINDINGS: The microarray consisted of 3,582 oligonucleotides (70-mer) and covered 94% of 3,816 ORFs of Tohama I, the strain of which the genome has been sequenced. Twenty isolates from 1953 to 2004 were studied together with two Finnish vaccine strains and two international reference strains. The isolates were selected according to their characteristics, e.g. the year and place of isolation and pulsed-field gel electrophoresis profiles. Genomic DNA of the tested strains, along with reference DNA of Tohama I strain, was labelled and hybridized. The absence of genes as established with microarrays, was confirmed by PCR. Compared with the Tohama I strain, Finnish isolates lost 7 (8.6 kb) to 49 (55.3 kb) genes, clustered in one to four distinct loci. The number of lost genes increased with time, and one third of lost genes had functions related to inorganic ion transport and metabolism, or energy production and conversion. All four loci of lost genes were flanked by the insertion sequence element IS481. CONCLUSION/SIGNIFICANCE: Our results showed that the progressive gene loss occurred in Finnish B. pertussis strains isolated during a period of 50 years and confirmed that B. pertussis is dynamic and is continuously evolving, suggesting that the bacterium may use gene loss as one strategy to adapt to highly immunized populations

A Protocol of Process Evaluations of Interventions for the Prevention of Type 2 Diabetes in Women With Gestational Diabetes Mellitus: A Systematic Review

Background Process evaluations of randomised controlled trials (RCTs) can provide insight and inform us on the intervention implementation, the causal mechanisms and the contextual factors. This will inform about interventions’ success or failure due to their implementation or the interventions themselves. We aim to consolidate the methodology from previous process evaluations of complex interventions upon their findings on facilitators and barriers to address the prevention of type 2 diabetes mellitus among women with gestational diabetes mellitus (GDM). Methods Comprehensive search will be conducted on electronic databases and reference lists of recent reviews for RCTs of complex interventions which address process evaluations of diabetes prevention intervention (DPI) for women with GDM in healthcare settings. There is no restriction on the language of the papers and year of publication until December 2020. Data from each study will be extracted by two reviewers independently using standardised forms. Data extracted include descriptive items on the study design and the outcomes of process evaluations from the three dimensions: (1) implementation; (2) mechanism of impact and (3) context. The quality of the studies will be assessed using mixed methods appraisal tool which is designed for the appraisal of mixed studies in systematic reviews. A narrative and framework analysis of the findings will be presented to inform the contents of a new DPI for women with GDM. Discussion The findings from this process evaluation findings are valuable in determining whether a complex intervention should be scaled up or modified for other contexts in future plan. It will give deeper understanding of potential challenges and solutions to aid in the implementation of effective DPIs for GDM in Malaysia

Differential Expression of Type III Effector BteA Protein Due to IS481 Insertion in Bordetella pertussis

BACKGROUND: Bordetella pertussis is the primary etiologic agent of the disease pertussis. Universal immunization programs have contributed to a significant reduction in morbidity and mortality of pertussis; however, incidence of the disease, especially in adolescents and adults, has increased in several countries despite high vaccination coverage. During the last three decades, strains of Bordetella pertussis in circulation have shifted from the vaccine-type to the nonvaccine-type in many countries. A comparative proteomic analysis of the strains was performed to identify protein(s) involved in the type shift. METHODOLOGY/PRINCIPAL FINDING: Proteomic analysis identified one differentially expressed protein in the B. pertussis strains: the type III cytotoxic effector protein BteA, which is responsible for host cell death in Bordetella bronchiseptica infections. Immunoblot analysis confirmed the prominent expression of BteA protein in the nonvaccine-type strains but not in the vaccine-type strains. Sequence analysis of the vaccine-type strains revealed an IS481 insertion in the 5' untranslated region of bteA, -136 bp upstream of the bteA start codon. A high level of bteA transcripts from the IS481 promoter was detected in the vaccine-type strains, indicating that the transcript might be an untranslatable form. Furthermore, BteA mutant studies demonstrated that BteA expression in the vaccine-type strains is down-regulated by the IS481 insertion. CONCLUSION/SIGNIFICANCE: The cytotoxic effector BteA protein is expressed at higher levels in B. pertussis nonvaccine-type strains than in vaccine-type strains. This type-dependent expression is due to an insertion of IS481 in B. pertussis clinical strains, suggesting that augmented expression of BteA protein might play a key role in the type shift of B. pertussis

Multicentre phase II study of gemcitabine and cisplatin in malignant pleural mesothelioma

Malignant pleural mesothelioma is a notoriously chemoresistant tumour. However, a recent single institution study showed an impressive activity of gemcitabine and cisplatin. Our aim is to investigate the efficacy and toxicity of a gemcitabine and cisplatin combination in selected and chemo-naive patients with histologically proven malignant pleural mesothelioma. Method: Gemcitabine 1250 mg m−2 was administered on day 1 and day 8 and cisplatin 80 mg m−2 was administered on day 1 in a 3-week cycle with a maximum of six cycles. Response and toxicity evaluations were performed according to WHO and NCIC-CTC criteria. Pathology and radiology were centrally reviewed. Results show that in 25 evaluable patients, four PR were observed (ORR 16%, 95% CI 1–31%). Responses of seven patients were unevaluable. No unexpected toxicity occurred. Time to progression was 6 months (5–7 months) with a median survival from registration of 9.6 months (95% CI 8–12 months). In conclusion this trial excludes with 90% power a response rate of greater than 30% in patients with malignant pleural mesothelioma using a combination of gemcitabine and cisplatin at the proposed dose and schedule

Genomic Content of Bordetella pertussis Clinical Isolates Circulating in Areas of Intensive Children Vaccination

BACKGROUND: The objective of the study was to analyse the evolution of Bordetella pertussis population and the influence of herd immunity in different areas of the world where newborns and infants are highly vaccinated. METHODOLOGY: The analysis was performed using DNA microarray on 15 isolates, PCR on 111 isolates as well as GS-FLX sequencing technology on 3 isolates and the B. pertussis reference strain, Tohama I. PRINCIPAL FINDINGS: Our analyses demonstrate that the current circulating isolates are continuing to lose genetic material as compared to isolates circulating during the pre-vaccine era whatever the area of the world considered. The lost genetic material does not seem to be important for virulence. Our study confirms that the use of whole cell vaccines has led to the control of isolates that were similar to vaccine strains. GS-FLX sequencing technology shows that current isolates did not acquire any additional material when compared with vaccine strains or with isolates of the pre-vaccine era and that the sequenced strain Tohama I is not representative of the isolates. Furthermore, this technology allowed us to observe that the number of Insertion Sequence elements contained in the genome of the isolates is temporally increasing or varying between isolates. CONCLUSIONS: B. pertussis adaptation to humans is still in progress by losing genetic material via Insertion Sequence elements. Furthermore, recent isolates did not acquire any additional material when compared with vaccine strains or with isolates of the pre-vaccine era. Herd immunity, following intensive vaccination of infants and children with whole cell vaccines, has controlled isolates similar to the vaccine strains without modifying significantly the virulence of the isolates. With the replacement of whole cell vaccines by subunit vaccines, containing only few bacterial antigens targeting the virulence of the bacterium, one could hypothesize the circulation of isolates expressing less or modified vaccine antigens

Pertussis resurgence in Toronto, Canada: a population-based study including test-incidence feedback modeling

<p>Abstract</p> <p>Background</p> <p>Pertussis continues to challenge medical professionals; recently described increases in incidence may be due to age-cohort effects, vaccine effectiveness, or changes in testing patterns. Toronto, Canada has recently experienced increases in pertussis incidence, and provides an ideal jurisdiction for evaluating pertussis epidemiology due to centralized testing. We evaluated pertussis trends in Toronto using all available specimen data, which allowed us to control for changing testing patterns and practices.</p> <p>Methods</p> <p>Data included all pertussis culture and PCR test records for Greater Toronto from 1993 to 2007. We estimated incidence trends using Poisson regression models; complex relationships between disease incidence and test submission were explored with vector autoregressive models.</p> <p>Results</p> <p>From 1993 to 2007, 26988 specimens were submitted for testing; 2545 (9.4%) were positive. Pertussis incidence was 2 per 100,000 from 1993 to 2004 and increased to 10 per 100,000 from 2005-2007, with a concomitant 6-fold surge in test specimen submissions after the introduction of a new, more sensitive PCR assay. The relative change in incidence was less marked after adjustment for testing volumes. Bidirectional feedbacks between test positivity and test submissions were identified.</p> <p>Conclusions</p> <p>Toronto's recent surge in pertussis reflects a true increase in local disease activity; the apparent size of the outbreak has likely been magnified by increasing use of pertussis testing by clinicians, and by improved test sensitivity since 2005. These findings may be applicable to changes in pertussis epidemiology that have been noted elsewhere in North America.</p

Addressing preference heterogeneity in public health policy by combining Cluster Analysis and Multi-Criteria Decision Analysis: Proof of Method.

The use of subgroups based on biological-clinical and socio-demographic variables to deal with population heterogeneity is well-established in public policy. The use of subgroups based on preferences is rare, except when religion based, and controversial. If it were decided to treat subgroup preferences as valid determinants of public policy, a transparent analytical procedure is needed. In this proof of method study we show how public preferences could be incorporated into policy decisions in a way that respects both the multi-criterial nature of those decisions, and the heterogeneity of the population in relation to the importance assigned to relevant criteria. It involves combining Cluster Analysis (CA), to generate the subgroup sets of preferences, with Multi-Criteria Decision Analysis (MCDA), to provide the policy framework into which the clustered preferences are entered. We employ three techniques of CA to demonstrate that not only do different techniques produce different clusters, but that choosing among techniques (as well as developing the MCDA structure) is an important task to be undertaken in implementing the approach outlined in any specific policy context. Data for the illustrative, not substantive, application are from a Randomized Controlled Trial of online decision aids for Australian men aged 40-69 years considering Prostate-specific Antigen testing for prostate cancer. We show that such analyses can provide policy-makers with insights into the criterion-specific needs of different subgroups. Implementing CA and MCDA in combination to assist in the development of policies on important health and community issues such as drug coverage, reimbursement, and screening programs, poses major challenges -conceptual, methodological, ethical-political, and practical - but most are exposed by the techniques, not created by them