The organization of research corporations and researcher ability

This paper analyzes the formation of Research Corporations as an alternative governance structure for performing R&D compared to pursuing in-house R&D projects. Research Corporations are privatefor-profit research centers that bring together several firms with similar research goals. In a Research Corporation formal authority over the choice of projects is jointly exercised by the top management of the member firms. A private for-profit organization cannot commit not to interfere with the project choice of the researchers. However, increasing the number of member firms of the Research Corporation reduces the incentive of member firms to meddle with the research projects of researchers because exercising formal authority over the choice of research projects is a public good. The Research Corporation thus offers researchers greater autonomy than a single firm pursuing an identical research program in its in-house R&D department. This attracts higher ability researchers to the Research Corporation compared to the internal R&D department. The paper uses the theoretical model to analyze the organization of the Microelectronics and Computer Technology Corporation (MCC). The facts of this case confirm the existence of a tension between control over the choice of research projects and the ability of researchers that the organization is able to attract or hold onto.

The co-evolution of social institutions, demography, and large-scale human cooperation.

Human cooperation is typically coordinated by institutions, which determine the outcome structure of the social interactions individuals engage in. Explaining the Neolithic transition from small- to large-scale societies involves understanding how these institutions co-evolve with demography. We study this using a demographically explicit model of institution formation in a patch-structured population. Each patch supports both social and asocial niches. Social individuals create an institution, at a cost to themselves, by negotiating how much of the costly public good provided by cooperators is invested into sanctioning defectors. The remainder of their public good is invested in technology that increases carrying capacity, such as irrigation systems. We show that social individuals can invade a population of asocials, and form institutions that support high levels of cooperation. We then demonstrate conditions where the co-evolution of cooperation, institutions, and demographic carrying capacity creates a transition from small- to large-scale social groups.

Risk factor profile and management of cerebrovascular patients in the REACH Registry.

BACKGROUND: Cerebrovascular disease (CVD) is a global public health problem. CVD patients are at high risk of recurrent stroke and other atherothrombotic events. Prevalence of risk factors, comorbidities, utilization of secondary prevention therapies and adherence to guidelines all influence the recurrent event rate. We assessed these factors in 18,992 CVD patients within a worldwide registry of stable outpatients. METHODS: The Reduction of Atherothrombosis for Continued Health Registry recruited >68,000 outpatients (44 countries). The subjects were mainly recruited by general practitioners (44%) and internists (29%) if they had symptomatic CVD, coronary artery disease, peripheral arterial disease (PAD) and/or >or=3 atherothrombotic risk factors. RESULTS: The 18,992 CVD patients suffered a stroke (53.7%), transient ischemic attack (TIA) (27.7%) or both (18.5%); 40% had symptomatic atherothrombotic disease in >or=1 additional vascular beds: 36% coronary artery disease; 10% PAD and 6% both. The prevalence of risk factors at baseline was higher in the TIA subgroup than in the stroke group: treated hypertension (83.5/82.0%; p = 0.02), body mass index >or=30 (26.7/20.8%; p < 0.0001), hypercholesterolemia (65.1/52.1%; p < 0.0001), atrial fibrillation (14.7/11.9%; p < 0.0001) and carotid artery disease (42.3/29.7%; p < 0.0001). CVD patients received antiplatelet agents (81.7%), oral anticoagulants (17.3%), lipid-lowering agents (61.2%) and antihypertensives (87.9%), but guideline treatment targets were frequently not achieved (54.5% had elevated blood pressure at baseline, while 4.5% had untreated diabetes). CONCLUSIONS: A high percentage of CVD patients have additional atherothrombotic disease manifestations. The risk profile puts CVD patients, especially the TIA subgroup, at high risk for future atherothrombotic events. Undertreatment is common worldwide and adherence to guidelines needs to be enforced.

Endogenous growth with capital in R&D production functions

[eng] In this paper we claim that capital is as important in the production of ideas as in the production of final goods. Hence, we introduce capital in the production of knowledge and discuss the associated problems arising from the public good nature of knowledge. We show that although population growth can affect economic growth, it is not necessary for growth to arise. We derive both the social planner and the decentralized economy growth rates and show the optimal subsidy that decentralizes it. We also show numerically that the effects of population growth on the market growth rate, the optimal growth rate and the optimal subsidy are small. Besides, we find that physical capital is more important for the production of knowledge than for the production of goods.

Endogenous growth with capital in R&D production functions

[eng] In this paper we claim that capital is as important in the production of ideas as in the production of final goods. Hence, we introduce capital in the production of knowledge and discuss the associated problems arising from the public good nature of knowledge. We show that although population growth can affect economic growth, it is not necessary for growth to arise. We derive both the social planner and the decentralized economy growth rates and show the optimal subsidy that decentralizes it. We also show numerically that the effects of population growth on the market growth rate, the optimal growth rate and the optimal subsidy are small. Besides, we find that physical capital is more important for the production of knowledge than for the production of goods.

Identification of novel HIV restriction factors

To efficiently replicate within mammalian cells, viruses have to manoeuvre through complex host mechanisms, hijacking a network of host proteins to achieve successful propagation. To prevent this invasion, cells have evolved over time to efficiently block the incursing pathogen by direct or indirect targeting. Human immunodeficiency virus (HIV) is a retrovirus of major global public health issue. In the last decade, extensive focus on innate immune proteins has been given, and particularly restriction factors, proteins inhibiting HIV replication by affecting various stages of the viral cycle. Because of the importance of developing new HIV therapies that are associated with reduced side effects and resistances, there is an urge to understand the antiviral response against HIV. Using common features of known restriction factors as a signature to identify new anti-HIV factors, candidates were identified. Particularly multiple members of the apolipoproteins L (APOL) family were found. Cotransfection experiments confirmed very potent inhibitory effects on HIV-1 expression. Further characterization of APOL6, the best candidate, was carried out. APOL6 was not able to inhibit HIV specifically but rather inhibited any gene-encoded DNA that was cotransfected and therefore APOL6 does not classify as a bona fide restriction factor. In addition, we were able to map the activity of APOL6 to the MAD domain and mainly to residue 174. We also found that other members of the family identified in the screen, APOL1 and 3, could have similar mechanism of action as APOL6. Finally, although the complete mechanism of action of APOL6 has yet to be elucidated, it might be blocked during transfections, potentially improving transfection of primary cells. -- Pour se répliquer efficacement dans les cellules de mammifères, les virus doivent manoeuvrer à travers des mécanismes cellulaires complexes et détourner un réseau de protéines de l'hôte. Pour empêcher cette invasion, les gènes de l'hôte ont évolué dans le temps pour cibler efficacement, directement ou indirectement, l'agent pathogène. Le virus de l'immunodéficience humaine (VIH) est un rétrovirus de problème majeur de santé publique mondiale, mais le faible risque de transmission du virus pourrait être expliqué par la présence d'un système antiviral de l'hôte qui, en cas d'échec, conduit à une infection productive. Durant la dernière décennie, il y a eu un intérêt spécial porté sur les protéines immunitaires innées appelé facteurs de restriction présentant des effets inhibiteurs puissants sur la réplication du VIH en affectant différentes étapes du cycle viral. En raison de l'importance de la recherche de nouvelles thérapies anti-VIH associées à des effets secondaires et des résistances réduites comparé aux traitements actuels, il existe un besoin de comprendre la réponse antivirale innée contre le VIH. Basé sur des caractéristiques communes des facteurs de restriction connus, nous avons proposé d'identifier de nouveaux facteurs anti-VIH. Nous avons trouvé une famille de protéines, les apolipoprotéines L (APOL) montrant les effets inhibiteurs très puissants contre l'expression du VIH-1 dans des expériences de co-transfection. Nous avons décidé d'approfondir le rôle de ces protéines dans l'immunité innée et de se concentrer sur le meilleur candidat APOL6. Nous avons en outre établi qu'APOL6 n'a pas d'activité anti-virale spécifique et donc pas classé comme un facteur de bonne foi de restriction. Par ailleurs, APOL6 est capable d'inhiber fortement l'expression de tout Plasmide cotransfecté. En outre, nous avons été en mesure de cartographier l'activité d'APOL6 au domaine MAD et principalement au résidu 174. Nous avons également constaté que d'autres membres de la famille identifiés dans l'étude, APOL1 et 3, pourraient avoir le même mécanisme d'action qu'APOL6. Enfin, bien que le mécanisme d'action complet d'APOL6 reste à être élucidé, il pourrait être d'une importance biotechnologique car il pourrait potentiellement faciliter la transfection de cellules primaires après l'inhibition d'APOL6.

Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data.

BACKGROUND: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). METHODS: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. RESULTS: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 °C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). CONCLUSIONS: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.

Analysis of fracture healing in osteopenic bone caused by disuse: experimental study

Osteoporosis has become a serious global public health issue. Hence, osteoporotic fracture healing has been investigated in several previous studies because there is still controversy over the effect osteoporosis has on the healing process. The current study aimed to analyze two different periods of bone healing in normal and osteopenic rats. Sixty, 7-week-old female Wistar rats were randomly divided into four groups: unrestricted and immobilized for 2 weeks after osteotomy (OU2), suspended and immobilized for 2 weeks after osteotomy (OS2), unrestricted and immobilized for 6 weeks after osteotomy (OU6), and suspended and immobilized for 6 weeks after osteotomy (OS6). Osteotomy was performed in the middle third of the right tibia 21 days after tail suspension, when the osteopenic condition was already set. The fractured limb was then immobilized by orthosis. Tibias were collected 2 and 6 weeks after osteotomy, and were analyzed by bone densitometry, mechanical testing, and histomorphometry. Bone mineral density values from bony calluses were significantly lower in the 2-week post-osteotomy groups compared with the 6-week post-osteotomy groups (multivariate general linear model analysis, P<0.000). Similarly, the mechanical properties showed that animals had stronger bones 6 weeks after osteotomy compared with 2 weeks after osteotomy (multivariate general linear model analysis, P<0.000). Histomorphometry indicated gradual bone healing. Results showed that osteopenia did not influence the bone healing process, and that time was an independent determinant factor regardless of whether the fracture was osteopenic. This suggests that the body is able to compensate for the negative effects of suspension.

The Military Monitor and American Register- 31 August 1812

The Military Monitor was a weekly periodical that was published every Monday. The first issue was printed for August 17, 1812 and is believed to have ceased in 1814, as the last issue located was April 2, 1814. The periodical was suspended with the November 23, 1812 issue and resumed with the December 14, 1812 issue. The quote at the top of the first page is "The public good our end". The periodical's various authors included: Desnoues, Joseph, 1794?-1837. O'Connor, Thomas, 1770-1855. Hardcastle, John, 1778?-1835. Van Pelt, Peter, 1779?-1843. Wall, Stephen. Van Riper, Nicholas. Other authors are believed to be the American Antiquarian Society. Proprietors: T. O'Connor and S. Wall, 1812; T. O'Connor, 1812- . Printers: Hardcastle and Van Pelt, for T. O'Connor and S. Wall, Sept. 14-Oct. 5, 1812; J. Desnoues, Oct. 12, 1812- ; N. Van Riper, Nov. 6, 1813- . This issue was included in a bound volume of the Military Monitor and American Register. Other Dates included are: 1812 October 12 1812 October 19 1812 November 23 1812 December 14 1812 December 21 1813 January 11 1813 February 1 1813 March 29 1813 April 5 1813 April 12 1813 April 26 1813 May 31

The Military Monitor and American Register- 14 December 1812

The Military Monitor was a weekly periodical that was published every Monday. The first issue was printed for August 17, 1812 and is believed to have ceased in 1814, as the last issue located was April 2, 1814. The periodical was suspended with the November 23, 1812 issue and resumed with the December 14, 1812 issue. The quote at the top of the first page is "The public good our end". The periodical's various authors included: Desnoues, Joseph, 1794?-1837. O'Connor, Thomas, 1770-1855. Hardcastle, John, 1778?-1835. Van Pelt, Peter, 1779?-1843. Wall, Stephen. Van Riper, Nicholas. Other authors are believed to be the American Antiquarian Society. Proprietors: T. O'Connor and S. Wall, 1812; T. O'Connor, 1812- . Printers: Hardcastle and Van Pelt, for T. O'Connor and S. Wall, Sept. 14-Oct. 5, 1812; J. Desnoues, Oct. 12, 1812- ; N. Van Riper, Nov. 6, 1813- . This issue was included in a bound volume of the Military Monitor and American Register. Other Dates included are: 1812 August 31 1812 October 12 1812 October 19 1812 November 23 1812 December 21 1813 January 11 1813 February 1 1813 March 29 1813 April 5 1813 April 12 1813 April 26 1813 May 31

The Military Monitor and American Register- 21 December 1812

The Military Monitor was a weekly periodical that was published every Monday. The first issue was printed for August 17, 1812 and is believed to have ceased in 1814, as the last issue located was April 2, 1814. The periodical was suspended with the November 23, 1812 issue and resumed with the December 14, 1812 issue. The quote at the top of the first page is "The public good our end". The periodical's various authors included: Desnoues, Joseph, 1794?-1837. O'Connor, Thomas, 1770-1855. Hardcastle, John, 1778?-1835. Van Pelt, Peter, 1779?-1843. Wall, Stephen. Van Riper, Nicholas. Other authors are believed to be the American Antiquarian Society. Proprietors: T. O'Connor and S. Wall, 1812; T. O'Connor, 1812- . Printers: Hardcastle and Van Pelt, for T. O'Connor and S. Wall, Sept. 14-Oct. 5, 1812; J. Desnoues, Oct. 12, 1812- ; N. Van Riper, Nov. 6, 1813- . This issue was included in a bound volume of the Military Monitor and American Register. Other Dates included are: 1812 August 31 1812 December 14 1812 November 23 1812 October 12 1812 October 19 1813 April 5 1813 April 12 1813 April 26 1813 February 1 1813 January 11 1813 March 29

The Military Monitor and American Register- 23 November 1812

The Military Monitor was a weekly periodical that was published every Monday. The first issue was printed for August 17, 1812 and is believed to have ceased in 1814, as the last issue located was April 2, 1814. The periodical was suspended with the November 23, 1812 issue and resumed with the December 14, 1812 issue. The quote at the top of the first page is "The public good our end". The periodical's various authors included: Desnoues, Joseph, 1794?-1837. O'Connor, Thomas, 1770-1855. Hardcastle, John, 1778?-1835. Van Pelt, Peter, 1779?-1843. Wall, Stephen. Van Riper, Nicholas. Other authors are believed to be the American Antiquarian Society. Proprietors: T. O'Connor and S. Wall, 1812; T. O'Connor, 1812- . Printers: Hardcastle and Van Pelt, for T. O'Connor and S. Wall, Sept. 14-Oct. 5, 1812; J. Desnoues, Oct. 12, 1812- ; N. Van Riper, Nov. 6, 1813- . This issue was included in a bound volume of the Military Monitor and American Register. Other Dates included are: 1812 August 31 1812 October 12 1812 October 19 1812 December 14 1812 December 21 1813 January 11 1813 February 1 1813 March 29 1813 April 5 1813 April 12 1813 April 26 1813 May 31

The Military Monitor and American Register- 12 October 1812

The Military Monitor was a weekly periodical that was published every Monday. The first issue was printed for August 17, 1812 and is believed to have ceased in 1814, as the last issue located was April 2, 1814. The periodical was suspended with the November 23, 1812 issue and resumed with the December 14, 1812 issue. The quote at the top of the first page is "The public good our end". The periodical's various authors included: Desnoues, Joseph, 1794?-1837. O'Connor, Thomas, 1770-1855. Hardcastle, John, 1778?-1835. Van Pelt, Peter, 1779?-1843. Wall, Stephen. Van Riper, Nicholas. Other authors are believed to be the American Antiquarian Society. Proprietors: T. O'Connor and S. Wall, 1812; T. O'Connor, 1812- . Printers: Hardcastle and Van Pelt, for T. O'Connor and S. Wall, Sept. 14-Oct. 5, 1812; J. Desnoues, Oct. 12, 1812- ; N. Van Riper, Nov. 6, 1813- . This issue was included in a bound volume of the Military Monitor and American Register. Other Dates included are: 1812 August 31 1812 October 19 1812 November 23 1812 December 14 1812 December 21 1813 January 11 1813 February 1 1813 March 29 1813 April 5 1813 April 12 1813 April 26 1813 May 31

The Military Monitor and American Register- 19 October 1812

The Military Monitor was a weekly periodical that was published every Monday. The first issue was printed for August 17, 1812 and is believed to have ceased in 1814, as the last issue located was April 2, 1814. The periodical was suspended with the November 23, 1812 issue and resumed with the December 14, 1812 issue. The quote at the top of the first page is "The public good our end". The periodical's various authors included: Desnoues, Joseph, 1794?-1837. O'Connor, Thomas, 1770-1855. Hardcastle, John, 1778?-1835. Van Pelt, Peter, 1779?-1843. Wall, Stephen. Van Riper, Nicholas. Other authors are believed to be the American Antiquarian Society. Proprietors: T. O'Connor and S. Wall, 1812; T. O'Connor, 1812- . Printers: Hardcastle and Van Pelt, for T. O'Connor and S. Wall, Sept. 14-Oct. 5, 1812; J. Desnoues, Oct. 12, 1812- ; N. Van Riper, Nov. 6, 1813- . This issue was included in a bound volume of the Military Monitor and American Register. Other Dates included are: 1812 August 31 1812 October 12 1812 November 23 1812 December 14 1812 December 21 1813 January 11 1813 February 1 1813 March 29 1813 April 5 1813 April 12 1813 April 26

The Military Monitor and American Register- 5 April 1813

The Military Monitor was a weekly periodical that was published every Monday. The first issue was printed for August 17, 1812 and is believed to have ceased in 1814, as the last issue located was April 2, 1814. The periodical was suspended with the November 23, 1812 issue and resumed with the December 14, 1812 issue. The quote at the top of the first page is "The public good our end". The periodical's various authors included: Desnoues, Joseph, 1794?-1837. O'Connor, Thomas, 1770-1855. Hardcastle, John, 1778?-1835. Van Pelt, Peter, 1779?-1843. Wall, Stephen. Van Riper, Nicholas. Other authors are believed to be the American Antiquarian Society. Proprietors: T. O'Connor and S. Wall, 1812; T. O'Connor, 1812- . Printers: Hardcastle and Van Pelt, for T. O'Connor and S. Wall, Sept. 14-Oct. 5, 1812; J. Desnoues, Oct. 12, 1812- ; N. Van Riper, Nov. 6, 1813- . This issue was included in a bound volume of the Military Monitor and American Register. Other Dates included are: 1812 August 31 1812 October 12 1812 October 19 1812 November 23 1812 December 14 1812 December 21 1813 January 11 1813 February 1 1813 March 29 1813 April 12 1813 April 26 1813 May 31