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Combinatorial auctions are auctions in which bids can be submitted on sets of items, rather than just on individual items. These auctions are generally beneficial to both auctioneers and bidders, as they allow bidders to express their synergies for sets of items. In recent years, we have seen the advent of combinatorial auctions as well as the emergence of online market platforms with competing auctioneers. However, combinatorial auctions have largely been absent from these platforms. Our article provides an explanation for this absence by demonstrating that competition between auctioneers can reduce the attractiveness of offering combinatorial auctions. Specifically, we show that auctioneers can limit competitive pressure between themselves by allowing bids only on specific packages, where these packages differ between auctioneers. This results in market segmentation, which increases bidder competition, and consequently increases auctioneer revenues. These findings have implications for market design. In particular they imply that, for an online market platform having multiple sellers offering auctions to the same set of buyers, it might not be advantageous to offer combinatorial auctions as a design option to the competing sellers. We investigate whether revenue-maximizing auctioneers selling heterogeneous items will allow for combinatorial bidding in the presence of auctioneer competition. We compare the choice of auction format by two competing auctioneers with that of a single auctioneer. Bidders are heterogeneous in their demands, with some having synergies for items. We find that, even if a single auctioneer offers a combinatorial auction, competing auctioneers in a comparable setting will not. Instead, the competing auctioneers will segment the market by restricting allowable package bids in order to increase competition between bidders. This shows that it might not be advantageous for an online market platform to offer combinatorial auctions as a design option to competing auctioneers. History: This paper has been accepted for the Information Systems Research Special Section on Market Design and Analytics. Funding: Financial support from the Deutsche Forschungsgemeinschaft [Grants KI 1915/1-1 and OT 487/2-1] is gratefully acknowledged by T. Kittsteiner and M. Ott. Supplemental Material: The online appendix is available at https://doi.org/10.1287/isre.2021.1018. [ABSTRACT FROM AUTHOR]

Gene-modified autologous hematopoietic stem cells (HSC) can provide ample clinical benefits to subjects suffering from X-linked chronic granulomatous disease (X-CGD), a rare inherited immunodeficiency characterized by recurrent, often life-threatening bacterial and fungal infections. Here we report on the molecular and cellular events observed in two young adults with X-CGD treated by gene therapy in 2004. After the initial resolution of bacterial and fungal infections, both subjects showed silencing of transgene expression due to methylation of the viral promoter, and myelodysplasia with monosomy 7 as a result of insertional activation of ecotropic viral integration site 1 (EVI1). One subject died from overwhelming sepsis 27 months after gene therapy, whereas a second subject underwent an allogeneic HSC transplantation. Our data show that forced overexpression of EVI1 in human cells disrupts normal centrosome duplication, linking EVI1 activation to the development of genomic instability, monosomy 7 and clonal progression toward myelodysplasia., Treatment of primary immunodeficiencies with gene-modified autologous stem cells may offer considerable benefits over allogeneic cell transplantation, particularly when human leukocyte antigen (HLA)-matched donors are not available. Phase 1/2 clinical [...]

Gene transfer into hematopoietic stem cells has been used successfully for correcting lymphoid but not myeloid immunodeficiencies. Here we report on two adults who received gene therapy after nonmyeloablative bone marrow conditioning for the treatment of X-linked chronic granulomatous disease (X-CGD), a primary immunodeficiency caused by a defect in the oxidative antimicrobial activity of phagocytes resulting from mutations in gp91[sup.phox]. We detected substantial gene transfer in both individuals' neutrophils that lead to a large number of functionally corrected phagocytes and notable clinical improvement. Large-scale retroviral integration site-distribution analysis showed activating insertions in MDS1-EVI1, PRDM16 or SETBP1 that had influenced regulation of long-term hematopoiesis by expanding gene-corrected myelopoiesis three- to four-fold in both individuals. Although insertional influences have probably reinforced the therapeutic efficacy in this trial, our results suggest that gene therapy in combination with bone marrow conditioning can be successfully used to treat inherited diseases affecting the myeloid compartment such as CGD., Author(s): Marion G Ott [1, 16]; Manfred Schmidt [2, 3, 4, 16]; Kerstin Schwarzwaelder [3, 4, 5, 16]; Stefan Stein [6, 16]; Ulrich Siler [7, 16]; Ulrike Koehl [8]; Hanno [...]

Research suggests the relationship between time pressure and software quality to be more complex than presumed. While software developers can adjust their output to improve observed performance at the expense of software quality, the latter has been found to increase with time pressure in case of work-pace dependent incentives. An untested, but widely disseminated game-theoretical model seeks to resolve this contradiction and hypothesizes that high rates of time pressure avoid so-called 'shortcuts', which occur in the form of imperfections induced by developers to meet unrealistically tight deadlines. We conduct two laboratory experiments to empirically test this model for the first time. Our results corroborate the model with regard to its suggestion that shortcuts can be reduced if developers perceive unrealistic deadlines as ever-present. However, we also show that the actual critical probability of unrealistic deadlines–the point at which shortcut taking is drastically reduced–is above the theoretical one. Although final conclusions on the impact of time pressure on software quality remain to be drawn, our results suggest that–considering the contingencies of our study–time pressure helps in striving for quality in software projects. [ABSTRACT FROM AUTHOR]

Copyright of Journal for Sociology of Education & Socialization / Zeitschrift für Soziologie der Erziehung & Sozialisation is the property of Julius Beltz GmbH & Co. KG Beltz Juventa and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal for Sociology of Education & Socialization / Zeitschrift für Soziologie der Erziehung & Sozialisation is the property of Julius Beltz GmbH & Co. KG Beltz Juventa and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This article deals with discourses of breastfeeding in routine paediatric check ups. The authors reconstruct how breastfeeding discourses are invoked during check ups and how breastfeeding norms can be established. It is shown that the divergent invocations of breastfeeding-discourses during check ups entail an unintended dynamic for check ups in practice. The face-to-face interaction within the institutional setting enforces specific position in relation to the breastfeeding discourses from all participants. [ABSTRACT FROM AUTHOR]

Balancing power markets involve complex procurement auction mechanisms that are challenging both to design for auctioneers and to take part in for suppliers. Recent empirical work indicates that auction results from Austria and Germany do not match game‐theoretic predictions. Instead, suppliers adjust their bids to previous auctions results and do not reveal their actual costs within their bids. Therefore, this work focuses on bidding strategies of suppliers in the Austrian and German automatically‐activated Frequency Restoration Reserve auctions. First, the operating principle of the auctions is analyzed and the cost and profit structures are illustrated. Then, a theoretic approach for the derivation of optimal bidding strategies is presented, that allows the integration of price expectations based on historical market data. We validate our approach by a numerical application of the bidder's calculus. Finally, our theoretic results are confronted with Austrian and German auction outcomes. We find evidence that the identified bidding strategies are applied by the suppliers. This article is categorized under:Energy Systems Analysis > Economics and PolicyEnergy Infrastructure > Economics and PolicyEnergy Policy and Planning > Economics and PolicyConcentrating Solar Power > Economics and Policy Graphical representation of the bidder's calculus for different price scenarios in Austrian and German balancing power auctions. [ABSTRACT FROM AUTHOR]

An abstract of the article "Correction of Chronic Granulomatous Disease by Gene Therapy," by Manuel Grez, Marion G. Ott, Stefan Stein, Ulrich Siler, Ulrike Koehl, Hana Kunkel, Andrea Schilz, Klaus Kuehlcke, Dieter Hoelzer and Reinhard Seger is presented.

An abstract of the article "Chronic Granulomatous Disease Gene Therapy Functionally Corrects the Phenotype of Polymorphonuclear Leukocytes (PMN)," by Ulrich Siler, Marion G. Ott, Stefan Stein, Elke Karaus, Maja Rutishauser, Corinne Wenk, Dieter Hoelzer, Manuel Grez and Reinhard Seger is presented.

An abstract of the article "Stable Polyclonal Hematopoietic Repopulation after Successful Clinical Gene Therapy of Chronic Granulomatous Disease (CGD)," by Manfred Schmidt and colleagues is presented.

Gene transfer into hematopoietic stem cells has been successfully used to correct immunodeficiencies affecting the lymphoid compartment. However, similar results have not been reported for diseases affecting myeloid cells, mainly due to low engraftment levels of gene-modified cells observed in unconditioned patients. Here we review the developments leading to a gene therapy approach for the treatment of Chronic Granulomatous Disease (CGD), a primary life threatening immunodeficiency caused by a defect in the oxidative antimicrobial activity of phagocytes. Although the disease can be cured by bone marrow transplantation, this treatment is only available to patients with HLA-identical sibling or matched unrelated donors. One therapeutic option for patients without suitable donor is the genetic modification of autologous hematopoietic stem cells. Although early attempts to correct CGD by gene therapy were unsuccessful, these studies demonstrated the safety and limitations of gene transfer into hematopoietic stem cells (HSC) of CGD patients using retroviral vectors. The recent development of advanced gene transduction protocols together with improved retroviral vectors, combined with low intensity chemotherapy conditioning, allowed partial correction of the granulocytic function with a significant clinical benefit in treated patients. These results may have important implications for future applications of gene therapy in myeloid disorders and inherited diseases using hematopoietic stem cells.

Chronic granuloniatous disease (CGD) is a rare inherited imnunodeficiency characterized by recurrent, often life threatening bacterial and fungal infections due to a functional defect in the microbial-killing activity of phagocytic neutrophils. If regular care and conventional therapy fail, tile disease can be cured by bone marrow transplantation. This treatment is, however, only available to patients with human leukocyte antigen-identical sibling or matched unrelated donors. One therapeutic option for patients lacking suitable donors is the genetic modification of autologous hematopoietic stem cells. This review discusses the developments that have led to the realization of a successful gene therapy protocol for the correction of CGD.

As a single-gene defect in phagocytes, the X-linked form of chronic granulomatous disease (X-CGD) is a disorder potentially amenable to gene therapy by transfer of a functional copy of the gp91(phox) gene into hematopoietic stem cells (HSC). Although antimicrobial agents and interferon-gamma (IFN-gamma) have significantly improved its prognosis, CGD is still associated with high morbidity and mortality. The disease can be cured by bone marrow transplantation (BMT); however, BMT in CGD has been associated with unacceptably high rates of morbidity, mortality, and graft failure, except in very selected cases in which an HLA-identical donor is available. Prerequisites for a clinical gene therapy of CGD are an efficient mobilization of peripheral blood stem cells (PBSC) as well as the preservation of their viability and hematopoietic potential following transduction and ex vivo culture. We show that (i) mobilization and collection of CD34(+) cells after a 4-week IFN-gamma-free period by G-CSF results in sufficient numbers of cells for transplantation; (ii) the quality of collected stem cells is not altered in comparison to cells obtained from healthy volunteers as assessed by long-term culture initiating cells (LTC-IC) and progenitor cell expansion; (iii) retroviral transfer of the gp91(phox) gene under defined, serum-free conditions leads to high and stable reconstitution of the respiratory burst activity in X-CGD neutrophils derived from transduced CD34(+) progenitor and LTC-IC. Withdrawal of IFN-gamma in CGD patients may improve mobilization of CD34(+) stem cells by G-CSF. The gene transfer conditions established here are applicable to a clinical approach for gene therapy of X-CGD.