Heterotopic Heart Transplantation

The heterotopic heart transplant was pioneered by Christian Barnard in the late 1970s as a way to treat acute rejection in the pre-cyclosporine era. The technique was also used for the treatment of severe pulmonary hypertension, in patients unable to have an orthotopic heart transplant. Some surgeons have used the heterotopic heart transplant as a way to increase the donor heart pool around the world in more recent years. The heterotopic heart transplant is a good viable option for severe pulmonary hypertension patients, and, severe pulmonary vascular resistance patients, who would otherwise, not qualify for an orthotopic heart transplant. The outcomes for these recipients have been comparable to survival outcomes for similar orthotopic heart transplant recipients

Cardiac transplantation in patients over 50 years of age

Sixty-two patients underwent cardiac transplantation at the University of Arizona from March 1979 to March 1985. Thirteen patients (11 men and 2 women) were over 50 years of age at the time of transplantation and 49 were under the age of 50. The mean age (± SEM) of the patients over 50 was 53 ± 1 years. Eight of these patients were treated with conventional immunosuppressive therapy (azathioprine, prednisone and rabbit antithymocyte globulin) and Ave, beginning in January 1983, were treated with cyclosporine, prednisone and rabbit antithymocyte globulin.Early mortality (0 to 90 days) was 16% in the group over 50 versus 18% for those under 50. The late mortality (> 90 days) was 36 and 33%, respectively. In both groups, rejection and infection were the principal causes of death. The incidence of infection was 1.9 ± 0.5 episodes per patient in those patients over 50 and 1.9 ± 0.4 in those under 50. The incidence of rejection was 1.3 episodes per patient-year in patients over 50 and 1.7 episodes per patient-year in those under 50. Actuarial survival at 1 year was 72 ± 14% in the group over 50 and 66 ± 7% in the group under 50 years of age.These data indicate that the results of cardiac transplantation for patients over 50 do not differ significantly from those for patients under 50. Therefore, it is concluded that a rigidly defined age criterion for cardiac transplant recipients is not acceptable. Each potential recipient must be evaluated in terms of individual risk and benefit from the procedure

Singularities In Scalar-Tensor Cosmologies

In this article, we examine the possibility that there exist special scalar-tensor theories of gravity with completely nonsingular FRW solutions. Our investigation in fact shows that while most probes living in such a Universe never see the singularity, gravity waves always do. This is because they couple to both the metric and the scalar field, in a way which effectively forces them to move along null geodesics of the Einstein conformal frame. Since the metric of the Einstein conformal frame is always singular for configurations where matter satisfies the energy conditions, the gravity wave world lines are past inextendable beyond the Einstein frame singularity, and hence the geometry is still incomplete, and thus singular. We conclude that the singularity cannot be entirely removed, but only be made invisible to most, but not all, probes in the theory.Comment: 23 pages, latex, no figure

Anomaly Mediation and Cosmology

We consider an extension of the MSSM wherein anomaly mediation is the source of supersymmetry breaking, and the tachyonic slepton problem is solved by a gauged U(1) symmetry, which is broken at high energies in a manner preserving supersymmetry, thereby also facilitating the see-saw mechanism for neutrino masses and a natural source for the Higgs mu-term. We show that these favourable outcomes can occur both in the presence and the absence of a large Fayet-Iliopoulos (FI) D-term associated with the new U(1). We explore the cosmological consequences of the model, showing that it naturally produces a period of hybrid inflation, terminating in the production of cosmic strings. In spite of the presence of a U(1) (even with an FI term), inflation is effected by the F-term, with a D-flat tree potential (the FI term, if present, being cancelled by non-zero squark and slepton fields). Calculating the 1-loop corrections to the inflaton potential, we estimate the constraints on the parameters of the model from Cosmic Microwave Background data. We will see that a consequence of these constraints is that the Higgs mu-term necessarily small. We briefly discuss the mechanisms for baryogenesis via conventional leptogenesis, the out-of-equilibrium production of neutrinos from the cosmic strings, or the Affleck-Dine mechanism. Cosmic string decays also boost the relic density of dark matter above the low value normally obtained in AMSB scenarios.Comment: 34 pages. Revised to incorporate discussion of the case when the Fayet-Ilipoulos term is absen

Goldstone inflation

Identifying the inflaton with a pseudo-Goldstone boson explains the flatness of its potential. Successful Goldstone Inflation should also be robust against UV corrections, such as from quantum gravity: in the language of the effective field theory this implies that all scales are sub-Planckian. In this paper we present scenarios which realise both requirements by examining the structure of Goldstone potentials arising from Coleman-Weinberg contributions. We focus on single-field models, for which we notice that both bosonic and fermionic contributions are required and that spinorial fermion representations can generate the right potential shape. We then evaluate the constraints on non-Gaussianity from higher-derivative interactions, finding that axiomatic constraints on Goldstone boson scattering prevail over the current CMB measurements. The fit to CMB data can be connected to the UV completions for Goldstone Inflation, finding relations in the spectrum of new resonances. Finally, we show how hybrid inflation can be realised in the same context, where both the inflaton and the waterfall fields share a common origin as Goldstones

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Skipping of Exons by Premature Termination of Transcription and Alternative Splicing within Intron-5 of the Sheep SCF Gene: A Novel Splice Variant

Stem cell factor (SCF) is a growth factor, essential for haemopoiesis, mast cell development and melanogenesis. In the hematopoietic microenvironment (HM), SCF is produced either as a membrane-bound (−) or soluble (+) forms. Skin expression of SCF stimulates melanocyte migration, proliferation, differentiation, and survival. We report for the first time, a novel mRNA splice variant of SCF from the skin of white merino sheep via cloning and sequencing. Reverse transcriptase (RT)-PCR and molecular prediction revealed two different cDNA products of SCF. Full-length cDNA libraries were enriched by the method of rapid amplification of cDNA ends (RACE-PCR). Nucleotide sequencing and molecular prediction revealed that the primary 1519 base pair (bp) cDNA encodes a precursor protein of 274 amino acids (aa), commonly known as ‘soluble’ isoform. In contrast, the shorter (835 and/or 725 bp) cDNA was found to be a ‘novel’ mRNA splice variant. It contains an open reading frame (ORF) corresponding to a truncated protein of 181 aa (vs 245 aa) with an unique C-terminus lacking the primary proteolytic segment (28 aa) right after the D175G site which is necessary to produce ‘soluble’ form of SCF. This alternative splice (AS) variant was explained by the complete nucleotide sequencing of splice junction covering exon 5-intron (5)-exon 6 (948 bp) with a premature termination codon (PTC) whereby exons 6 to 9/10 are skipped (Cassette Exon, CE 6–9/10). We also demonstrated that the Northern blot analysis at transcript level is mediated via an intron-5 splicing event. Our data refine the structure of SCF gene; clarify the presence (+) and/or absence (−) of primary proteolytic-cleavage site specific SCF splice variants. This work provides a basis for understanding the functional role and regulation of SCF in hair follicle melanogenesis in sheep beyond what was known in mice, humans and other mammals

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes