"Almost-stable" matchings in the Hospitals / Residents problem with Couples

The Hospitals / Residents problem with Couples (hrc) models the allocation of intending junior doctors to hospitals where couples are allowed to submit joint preference lists over pairs of (typically geographically close) hospitals. It is known that a stable matching need not exist, so we consider min bp hrc, the problem of finding a matching that admits the minimum number of blocking pairs (i.e., is “as stable as possible”). We show that this problem is NP-hard and difficult to approximate even in the highly restricted case that each couple finds only one hospital pair acceptable. However if we further assume that the preference list of each single resident and hospital is of length at most 2, we give a polynomial-time algorithm for this case. We then present the first Integer Programming (IP) and Constraint Programming (CP) models for min bp hrc. Finally, we discuss an empirical evaluation of these models applied to randomly-generated instances of min bp hrc. We find that on average, the CP model is about 1.15 times faster than the IP model, and when presolving is applied to the CP model, it is on average 8.14 times faster. We further observe that the number of blocking pairs admitted by a solution is very small, i.e., usually at most 1, and never more than 2, for the (28,000) instances considered

Access and non–access site bleeding after percutaneous coronary intervention and risk of subsequent mortality and major adverse cardiovascular events:Systematic review and meta-analysis

Background: The prognostic impact of site-specific major bleeding complications after percutaneous coronary intervention (PCI) has yielded conflicting data. The aim of this study is to provide an overview of site-specific major bleeding events in contemporary PCI and study their impact on mortality and major adverse cardiovascular event outcomes. Methods and Results: We conducted a meta-analysis of PCI studies that evaluated site-specific periprocedural bleeding complications and their impact on major adverse cardiovascular events and mortality outcomes. A systematic search of MEDLINE and Embase was conducted to identify relevant studies and random effects meta-analysis was used to estimate the risk of adverse outcomes with site-specific bleeding complications. Twenty-five relevant studies including 2 400 645 patients that underwent PCI were identified. Both non–access site (risk ratio [RR], 4.06; 95% confidence interval [CI], 3.21–5.14) and access site (RR, 1.71; 95% CI, 1.37–2.13) related bleeding complications were independently associated with an increased risk of periprocedural mortality. The prognostic impact of non–access site–related bleeding events on mortality related to the source of anatomic bleeding, for example, gastrointestinal RR, 2.78; 95% CI, 1.25 to 6.18; retroperitoneal RR, 5.87; 95% CI, 1.63 to 21.12; and intracranial RR, 22.71; 95% CI, 12.53 to 41.15. Conclusions: The prognostic impact of bleeding complications after PCI varies according to anatomic source and severity. Non–access site-related bleeding complications have a similar prevalence to those from the access site but are associated with a significantly worse prognosis partly related to the severity of the bleed. Clinicians should minimize the risk of major bleeding complications during PCI through judicious use of bleeding avoidance strategies irrespective of the access site used

Foreign investment in Scotland

A significant feature of the UK economy throughout the post-war period has been the growth in direct foreign investment in manufacturing industries. For the host nation the main benefits are employment creation, income generation and import reduction or export expansion. Scotland has been particularly successful in attracting the lion's inward investment for example in the period 1945- 1965 a total of 108,500 jobs were created by foreign firms setting up manufacturing units in the despite its size, obtained 46,221 (42.6%), whereas the second most SE England, gained only 16,926 (15.6%). The reasons for this success have been attributed primarily to a combination of the availability of labour in Scotland, the financial inducements offered by central government as part of regional policy and, the undoubted attraction of the environment, notably of course golf courses, for foreign businessmen. This brief paper explores the nature of Scotland's direct foreign investment and the reasons for its success

Knowledge-based design of bimodular and trimodular polyketide synthases based on domain and module swaps: a route to simple statin analogues

AbstractBackground: Polyketides are structurally diverse natural products that have a range of medically useful activities. Nonaromatic bacterial polyketides are synthesised on modular polyketide synthase (PKS) multienzymes, in which each cycle of chain extension requires a different ‘module’ of enzymatic activities. Attempts to design and construct modular PKSs that synthesise specified novel polyketides provide a particularly stringent test of our understanding of PKS structure and function.Results: We have constructed bimodular and trimodular PKSs based on DEBS1-TE, a derivative of the erythromycin PKS that contains only modules 1 and 2 and a thioesterase (TE), by substituting multiple domains with appropriate counterparts derived from the rapamycin PKS. Hybrid PKSs were obtained that synthesised the predicted target triketide lactones, which are simple analogues of cholesterol-lowering statins. In constructing intermodular fusions, whether between modules in the same or in different proteins, it was found advantageous to preserve intact the acyl carrier protein-ketosynthase (ACP-KS) didomain that spans the junction between successive modules.Conclusions: Relatively simple considerations govern the construction of functional hybrid PKSs. Fusion sites should be chosen either in the surface-accessible linker regions between enzymatic domains, as previously revealed, or just inside the conserved margins of domains. The interaction of an ACP domain with the adjacent KS domain, whether on the same polyketide or not, is of particular importance, both through conservation of appropriate protein-protein interactions, and through optimising molecular recognition of the altered polyketide chain in the key transfer of the acyl chain from the ACP of one module to the KS of the downstream module

Cumulative mutagenesis of the basic residues in the 201-218 region of insulin-like growth factor (IGF)-binding protein-5 results in progressive loss of both IGF-I binding and inhibition of IGF-I biological action

We have reported previously that mutation of two conserved nonbasic amino acids (G203 and Q209) within the highly basic 201–218 region in the C-terminal domain of IGF-binding protein-5 (IGFBP-5) decreases binding to IGFs. This study reveals that cumulative mutagenesis of the 10 basic residues in this region, to create the C-Term series of mutants, ultimately results in a 15-fold decrease in the affinity for IGF-I and a major loss in heparin binding. We examined the ability of mutants to inhibit IGF-mediated survival of MCF-7 cells and were able to demonstrate that this depended not only upon the affinity for IGF-I, but also the kinetics of this interaction, because IGFBP-5 mutants with similar affinity constants (KD) values, but with different association (Ka) and dissociation (Kd) rate values, had markedly different inhibitory properties. In contrast, the affinity for IGF-I provided no predictive value in terms of the ability of these mutants to enhance IGF action when bound to the substratum. Instead, these C-Term mutants appeared to enhance the actions of IGF-I by a combination of increased dissociation of IGF-IGFBP complexes from the substratum, together with dissociation of IGF-I from IGFBP-5 bound to the substratum. These effects of the IGFBPs were dependent upon binding to IGF-I, because a non-IGF binding mutant (N-Term) was unable to inhibit or enhance the actions of IGF-I. These results emphasize the importance of the kinetics of association/dissociation in determining the enhancing or inhibiting effects of IGFBP-5 and demonstrate the ability to generate an IGFBP-5 mutant with exclusively IGF-enhancing activity

The role of the chemical composition of monetite on the synthesis and properties of α-tricalcium phosphate

Peer reviewedPublisher PD

The Scottish economy [October 1979]

The previous two issues of this Commentary have both indicated that the Scottish economy has been performing poorly since the mid 1970's. This is true in both an absolute and a relative sense. Manufacturing production only increased by 1.2% between 1976 and 1978 and, after dropping below 1975 levels in the first quarter of 1979, is unlikely to show any substantial improvement for the year as a whole. In an international context the 1975-1978 performance can best be described as appalling. Over the same period industrial production in Eire grew by 28%, in Japan and the US by 23% and in West Germany and France by 15%. Inertia in developing new markets and lack of competitiveness in existing markets both contributed substantially to the virtual stagnation of Scottish output. Because the problems are so diverse, so too must be the solutions