We report here the long‐term results of HLA‐mismatched kidney transplantation without maintenance immunosuppression (IS) in 10 subjects following combined kidney and bone marrow transplantation. All ...subjects were treated with nonmyeloablative conditioning and an 8‐ to 14‐month course of calcineurin inhibitor with or without rituximab. All 10 subjects developed transient chimerism, and in seven of these, IS was successfully discontinued for 4 or more years. Currently, four subjects remain IS free for periods of 4.5–11.4 years, while three required reinstitution of IS after 5–8 years due to recurrence of original disease or chronic antibody‐mediated rejection. Of the 10 renal allografts, three failed due to thrombotic microangiopathy or rejection. When compared with 21 immunologically similar living donor kidney recipients treated with conventional IS, the long‐term IS‐free survivors developed significantly fewer posttransplant complications. Although most recipients treated with none or two doses of rituximab developed donor‐specific antibody (DSA), no DSA was detected in recipients treated with four doses of rituximab. Although further revisions of the current conditioning regimen are planned in order to improve consistency of the results, this study shows that long‐term stable kidney allograft survival without maintenance IS can be achieved following transient mixed chimerism induction.
The authors evaluate the long‐term results of HLA‐mismatched kidney transplantation without maintenance immunosuppression in 10 subjects following combined kidney and bone marrow transplantation in comparison with 21 immunologically similar living donor kidney recipients who were treated with conventional immunosuppression.
Recently, polymerization-induced self-assembly (PISA) has become widely recognized as a robust and efficient route to produce block copolymer nanoparticles of controlled size, morphology, and surface ...chemistry. Several reviews of this field have been published since 2012, but a substantial number of new papers have been published in the last three years. In this Perspective, we provide a critical appraisal of the various advantages offered by this approach, while also pointing out some of its current drawbacks. Promising future research directions as well as remaining technical challenges and unresolved problems are briefly highlighted.
It remains an enigma whether gestational hypertension (GH) and pre-eclampsia (PE) are distinct entities or different spectrum of the same disease. We aimed to compare the risk factors and outcomes ...between GH and PE.
A total of 7,633 pregnant women recruited between 12 and 20 weeks of gestation in the Ottawa and Kingston Birth Cohort from 2002 to 2009 were included in the analysis. Cox proportional hazards model was used to identify and compare the risk factors for GH and PE by treating gestational age at delivery as the survival time. Logistic regression model was used to compare outcome. Subgroup analysis was performed for early- and late-onset PE.
GH and PE shared most risk factors including overweight and obesity, nulliparity, PE history, type 1 and 2 diabetes, and twin birth. Effect size of PE history (RR = 14.1 for GH vs. RR = 6.4 for PE) and twin birth (RR = 4.8 for GH vs. RR = 10.3 for PE) showed substantial difference. Risk factors modified gestational age at delivery in patients with GH and PE in similar pattern. Subgroup analysis showed that early- and late-onset PE shared some risk factors with different effect sizes, whereas folic acid supplementation showed protective effect for early-onset PE only. PE was strongly associated with several adverse outcomes including cesarean section, placental abruption, small for gestational age, preterm birth, and 5 min Apgar score < 7, whereas GH was associated with increased risk of preterm birth only.
GH and PE shared common risk factors. Differences in effect sizes of risk factors and outcomes indicate that the conditions may have different pathophysiology and mechanism.
This paper proposes a simple model for the 19th century eruption of Eta Carinae that consists of two components: (1) a strong wind (
yr−1; v
∞ = 200 km s−1), blowing for 30 yr, followed by (2) a 1050 ...erg explosion (10 M; 750-1000 km s−1) occurring in 1844. The ensuing collision between the fast ejecta and the dense circumstellar material (CSM) causes an increase in brightness observed at the end of 1844, followed by a sustained high-luminosity phase lasting for 10-15 yr that provides a close match to the observed historical light curve. The emergent luminosity is powered by converting kinetic energy to radiation through CSM interaction, analogous to the process occurring in more luminous Type IIn supernovae, except with ∼10 times lower explosion energy and at slower speeds (causing a longer duration and lower emergent luminosity). We demonstrate that such an explosive event not only provides a natural explanation for the light-curve evolution, but also accounts for a number of puzzling attributes of the highly scrutinized Homunculus, including: (1) rough equipartition of total radiated and kinetic energy in the event, (2) the double-shell structure of the Homunculus, with a thin massive outer shell (corresponding to the coasting cold dense shell) and a thicker inner layer (between the cold dense shell and the reverse shock), (3) the apparent single age and Hubble-like flow of the Homunculus resulting from the thin swept-up shell, (4) the complex mottled appearance of the polar lobes in Hubble Space Telescope images, arising naturally from Raleigh-Taylor or Vishniac instabilities at the contact discontinuity of the shock, (5) efficient and rapid dust formation, which has been observed in the post-shock zones of Type IIn supernovae, and (6) the fast (3000-5000 km s−1) material outside the Homunculus, arising from the acceleration of the forward shock upon exiting the dense CSM. In principle, the bipolar shape could be explained borrowing from earlier studies of interacting winds, except that here the requisite pre-existing 'torus' may be provided by periastron collisions occurring around the same time, and the CSM interaction occurs over only 10 yr, producing a thin shell with the resulting structures then frozen-in to a homologously expanding bipolar nebula. This self-consistent picture has a number of implications for other eruptive transients, many of which may also be powered by CSM interaction. A key remaining unknown is the ultimate source of the 1050 erg of energy required in the explosion.
Corporate social responsibility (CSR) is not a new idea. However, CSR has never been more prominent on the corporate agenda than it is today. This article examines the pressures for increased ...corporate attention to CSR and whether this attention is warranted and likely to be sustained. It differentiates between the business case for CSR and the normative case and concludes that often there may be a compelling business case for making a substantial commitment to CSR, but an individual firm must assess the extent to which the general business case for CSR applies to its specific circumstances. For some firms, CSR may be a major influence on corporate strategy. Companies making a substantial commitment to CSR—because of a business or a normative case—are likely to find that this involves major challenges with respect to the formulation and implementation of CSR strategy, not least because of the uncertainties inevitably associated with determining a firm's societal obligations.
Chronic pulmonary aspergillosis (CPA) is a condition caused by the ubiquitous fungus Aspergillus fumigatus in non-immunocompromised individuals. Numerous underlying conditions have been associated ...with CPA. Details of the underlying conditions of 126 CPA patients attending our tertiary referral clinic from all over the UK were extracted from the clinical notes, and the distribution of these underlying conditions was analysed. For those with several underlying pulmonary conditions, one was nominated as the primary condition. Many patients presented with multiple underlying conditions, and a total of 232 underlying conditions were identified for the 126 patients. Previous classical tuberculosis and non-tuberculous mycobacterial infection were the most common primary underlying conditions (15.3% and 14.9%, respectively). Others included allergic bronchopulmonary aspergillosis (ABPA), chronic obstructive pulmonary condition (COPD) and/or emphysema, pneumothorax and prior treated lung cancer. Some conditions were found more often as one of multiple underlying conditions, while others were found only as secondary underlying conditions. Tuberculosis, non-tuberculous mycobacterial infection and ABPA remain the predominant risk factors for development of CPA, with COPD, prior pneumothorax or treated lung cancer also relatively common among our referrals. Many patients have multiple underlying pulmonary conditions. CPA should be considered when upper lobe cavitary or fibrotic disease and systemic symptoms are present in those with lung disease.
The epilepsies are a heterogeneous group of disorders characterized by the propensity to experience spontaneous recurrent seizures. Epilepsies can be genetic or acquired, and the underlying ...mechanisms of seizure initiation, seizure propagation, and comorbid conditions are incompletely understood. Metabolic changes including the production of reactive species are known to result from prolonged seizures and may also contribute to epilepsy development. In this review, we focus on the evidence that metabolic and redox disruption is both cause and consequence of epileptic seizures. Additionally, we discuss the promise of targeting redox processes as a therapeutic option in epilepsy.
This paper examines the shareholder primacy norm (SPN) as a widely acknowledged impediment to corporate social responsibility and explores the role of business schools in promoting the SPN but also ...potentially as an avenue for change by addressing misconceptions about shareholder primacy and the purpose of business. We start by explaining the SPN and then review its status under US and UK laws and show that it is not a likely legal requirement, at least under the guise of shareholder value maximization. This is in contrast to the common assertion that managers are legally constrained from addressing CSR issues if doing so is inconsistent with the economic interests of shareholders. Nonetheless, while the SPN might be muted as a legal norm, we show that it is certainly evident as a social norm among managers and in business schools—reflective, in part, of the sole voting rights of shareholders on corporate boards and of the dominance of shareholder theory—and justifiably so in the view of many managers and business academics. We argue that this view is misguided, not least when associated with claims of a purported legally enforceable requirement to maximize shareholder value. We propose two ways by which the influence of the SPN among managers might be attenuated: extending fiduciary duties of executives to non-shareholder stakeholders and changes in business school teaching such that it covers a plurality of conceptions of the purpose of the corporation.
We experimentally investigate the nature of 2D phase transitions in a quasi-2D granular fluid. Using a surface decorated with periodically spaced dimples we observe interfacial tension between ...coexisting granular liquid and crystal phases. Measurements of the orientational and translational order parameters and associated susceptibilities indicate that the surface topography alters the order of the phase transition from a two-step continuous one to a first-order liquid-solid one. The interplay of boundary inelasticity and geometry, either order promoting or inhibiting, controls whether it is the granular crystal or the granular fluid which makes contact with the edge. This order induced wetting has important consequences, determining how coexisting phases separate spatially.
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