Hamster-to-rat heart and liver xenotransplantation with FK506 plus antiproliferative drugs

Heterotopic hamster hearts transplanted to unmodified LEW rats underwent humoral rejection in 3 days. Survival was prolonged to a median of 4 days with 2 mg/kg/day FK506. As monotherapy, 15 mg/kg/day cyclophosphamide greatly prolonged graft survival-far more than could be accomplished with RS-61443, brequinar (BQR), mizoribine, methotrexate, or deoxyspergualin. However, when FK506 treatment, which was ineffective alone, was combined with a short induction course (14 or 30 days) of subtherapeutic BQR, RS-61443, or cyclophosphamide, routine survival of heart xenografts was possible for as long as the daily FK506 was continued. In addition, a single large dose of 80 mg/kg cyclophosphamide 10 days preoperatively allowed routine cardiac xenograft survival under FK506. The ability of these antimetabolites to unmask the therapeutic potential of FK506 correlated, although imperfectly, with the prevention of rises of preformed heterospecific cytotoxic antibodies immediately postoperatively. As an adjunct to FK506, azathioprine was of marginal value, whereas mizoribine, methotrexate, and deoxyspergualin (DSPG) were of intermediate efficacy. After orthotopic hepatic xenotransplantation, the perioperative survival of the liver with its well-known resistance to antibodies was less dependent than the heart on the antimetabolite component of the combined drug therapy, but the unsatisfactory results with monotherapy of FK506, BQR, RS-61443, or cyclophosphamide were changed to routine success by combining continuous FK506 with a short course of any of the other drugs. Thus, by breaking down the antibody barrier to xenotransplantation with these so-called antiproliferative drugs, it has been possible with FK506 to transplant heart and liver xenografts with consistent long-term survival of healthy recipients

The stransverse mass, MT2, in special cases

This document describes some special cases in which the stransverse mass, MT2, may be calculated by non-iterative algorithms. The most notable special case is that in which the visible particles and the hypothesised invisible particles are massless -- a situation relevant to its current usage in the Large Hadron Collider as a discovery variable, and a situation for which no analytic answer was previously known. We also derive an expression for MT2 in another set of new (though arguably less interesting) special cases in which the missing transverse momentum must point parallel or anti parallel to the visible momentum sum. In addition, we find new derivations for already known MT2 solutions in a manner that maintains manifest contralinear boost invariance throughout, providing new insights into old results. Along the way, we stumble across some unexpected results and make conjectures relating to geometric forms of M_eff and H_T and their relationship to MT2.Comment: 11 pages, no figures. v2 corrects minor typos. v3 corrects an incorrect statement in footnote 8 and inserts a missing term in eq (3.9). v4 and v5 correct minor typos spotted by reader

Severe loss-of-function mutations in the adrenocorticotropin receptor (ACTHR, MC2R) can be found in patients diagnosed with salt-losing adrenal hypoplasia

Objective: Familial glucocorticoid deficiency type I (FGD1) is a rare form of primary adrenal insufficiency resulting from recessive mutations in the ACTH receptor (MC2R, MC2R). Individuals with this condition typically present in infancy or childhood with signs and symptoms of cortisol insufficiency, but disturbances in the renin-angiotensin system, aldosterone synthesis or sodium homeostasis are not a well-documented association of FGD1. As ACTH stimulation has been shown to stimulate aldosterone release in normal controls, and other causes of hyponatraemia can occur in children with cortisol deficiency, we investigated whether MC2R changes might be identified in children with primary adrenal failure who were being treated for mineralocorticoid insufficiency. Design: Mutational analysis of MC2R by direct sequencing. Patients: Children (n = 22) who had been diagnosed with salt-losing forms of adrenal hypoplasia (19 isolated cases, 3 familial), and who were negative for mutations in DAX1 (NR0B1) and SF1 (NR5A1). Results: MC2R mutations were found in three individuals or kindred (I: homozygous S74I; II: novel compound heterozygous R146H/560delT; III: novel homozygous 579-581delTGT). These changes represent severely disruptive loss-of-function mutations in this G-protein coupled receptor, including the first reported homozygous frameshift mutation. The apparent disturbances in sodium homeostasis were mild, manifest at times of stress (e.g. infection, salt-restriction, heat), and likely resolved with time. Conclusions: MC2R mutations should be considered in children who have primary adrenal failure with apparent mild disturbances in renin-sodium homeostasis. These children may have been misdiagnosed as having salt-losing adrenal hypoplasia. Making this diagnosis has important implications for treatment, counselling and long-term prognosi

Heparin and air filters reduce embolic events caused by intra-arterial cerebral angiography - A prospective, randomized trial

Background-Intra-arterial cerebral angiography is associated with a low risk for neurological complications, but clinically silent ischemic events after angiography have been seen in a substantial number of patients.Methods and Results-In a prospective study, diffusion-weighted magnetic resonance imaging (DW-MRI) before and after intra-arterial cerebral angiography and transcranial Doppler sonography during angiography were used to evaluate the frequency of cerebral embolism. One hundred fifty diagnostic cerebral angiographies were randomized into 50 procedures, each using conventional angiographic technique, or systemic heparin treatment throughout the procedure, or air filters between the catheter and both the contrast medium syringe and the catheter flushing. There was no neurological complication during or after angiography. Overall, DW-MRI revealed 26 new ischemic lesions in 17 patients (11%). In the control group, 11 patients showed a total of 18 lesions. In the heparin group, 3 patients showed a total of 4 lesions. In the air filter group, 3 patients exhibited a total of 4 lesions. The reduced incidence of ischemic events in the heparin and air filter groups compared with the control group was significantly different (P=0.002). Transcranial Doppler sonography demonstrated a large number of microembolic signals that was significantly lower in the air filter group compared with the heparin and control groups (P=0.01), which did not differ from each other.Conclusions-Air filters and heparin both reduce the incidence of silent ischemic events detected by DW-MRI after intra-arterial cerebral angiography and can potentially lower clinically overt ischemic complications. This may apply to any intra-arterial angiographic procedure

Graphs Identified by Logics with Counting

We classify graphs and, more generally, finite relational structures that are identified by C2, that is, two-variable first-order logic with counting. Using this classification, we show that it can be decided in almost linear time whether a structure is identified by C2. Our classification implies that for every graph identified by this logic, all vertex-colored versions of it are also identified. A similar statement is true for finite relational structures. We provide constructions that solve the inversion problem for finite structures in linear time. This problem has previously been shown to be polynomial time solvable by Martin Otto. For graphs, we conclude that every C2-equivalence class contains a graph whose orbits are exactly the classes of the C2-partition of its vertex set and which has a single automorphism witnessing this fact. For general k, we show that such statements are not true by providing examples of graphs of size linear in k which are identified by C3 but for which the orbit partition is strictly finer than the Ck-partition. We also provide identified graphs which have vertex-colored versions that are not identified by Ck.Comment: 33 pages, 8 Figure

The Kato square root problem on vector bundles with generalised bounded geometry

We consider smooth, complete Riemannian manifolds which are exponentially locally doubling. Under a uniform Ricci curvature bound and a uniform lower bound on injectivity radius, we prove a Kato square root estimate for certain coercive operators over the bundle of finite rank tensors. These results are obtained as a special case of similar estimates on smooth vector bundles satisfying a criterion which we call generalised bounded geometry. We prove this by establishing quadratic estimates for perturbations of Dirac type operators on such bundles under an appropriate set of assumptions.Comment: Slight technical modification of the notion of "GBG constant section" on page 7, and a few technical modifications to Proposition 8.4, 8.6, 8.

Achievement Goal

Achievement goals are self-regulatory commitments that provide direction to individuals as they interpret and respond to competence-relevant situations. Four types of achievement goals have been the primary focus of the literature: Masteryapproach goals (master a task; improve over time), performance-approach goals (outperform others), mastery-avoidance goals (not fall short of mastering a task; not decline over time), and performance-avoidance goals (not be outperformed by others)