Arterial Mycotic Aneurysm and Rupture: A Potentially Fatal Complication of Pancreas Transplantation in Diabetes Mellitus

• Mycotic aneurysm at the site of a Carrel patch arterial anastomosis occurred in four patients who had undergone whole pancreas transplantation 2.5 to 14.5 months previously. In all patients, the graft had been removed, leaving the Carrel patch on the iliac artery. The aneurysms ruptured into the intestine or the extraperitoneal space. The ruptures were sudden and life-threatening in three of four cases. This diagnosis must be suspected in patients with a history of pancreas transplantation in the immediate or distant past if they present with unexplained hypotension, cardiac arrest, or gastrointestinal tract bleeding. © 1989, American Medical Association. All rights reserved

Theory Morphisms in Church's Type Theory with Quotation and Evaluation

${\rm CTT}_{\rm qe}$ is a version of Church's type theory with global quotation and evaluation operators that is engineered to reason about the interplay of syntax and semantics and to formalize syntax-based mathematical algorithms. ${\rm CTT}_{\rm uqe}$ is a variant of ${\rm CTT}_{\rm qe}$ that admits undefined expressions, partial functions, and multiple base types of individuals. It is better suited than ${\rm CTT}_{\rm qe}$ as a logic for building networks of theories connected by theory morphisms. This paper presents the syntax and semantics of ${\rm CTT}_{\rm uqe}$, defines a notion of a theory morphism from one ${\rm CTT}_{\rm uqe}$ theory to another, and gives two simple examples that illustrate the use of theory morphisms in ${\rm CTT}_{\rm uqe}$.Comment: 17 page

A randomized clinical trial of methylnaltrexone for the treatment of opioid induced constipation & gastrointestinal stasis in intensive care patients; results from the MOTION trial

PurposeConstipation can be a significant problem in critically unwell patients, associated with detrimental outcomes. Opioids are thought to contribute to the mechanism of bowel dysfunction. We tested if methylnaltrexone, a pure peripheral mu-opioid receptor antagonist, could reverse opioid induced constipationMethodsThe MOTION trial is a multi-centre, double blind, randomised placebo controlled trial to investigate whether methylnaltrexone alleviatesopioid induced constipation (OIC) in critical care patients. Eligibility criteria included adult ICU patients who were mechanically ventilated, receiving opioids and were constipated (had not opened bowels for a minimum 48 hours) despite prior administration of regular laxatives as per local bowel management protocol. The primary outcome was time to significant rescue-free laxation. Secondary outcomes included gastric residual volume, tolerance of enteral feeds, requirement for rescue laxatives, requirement for prokinetics, average number of bowel movements per day,escalation of opioid dose due to antagonism/reversal of analgesia, incidence of ventilator-associated pneumonia, incidence of diarrhoea and Clostridium difficileinfection and finally 28 day, ICU and hospital mortality.ResultsA total of 84 patients were enrolled and randomized (41 to methylnaltrexone and 43 to placebo). The baseline demographic characteristics of the two groups were generally well balanced. There was no significant differencein time to rescue-free laxation between the groups (Hazard ratio 1.42, 95%CI 0.82-2.46, p=0.22). There were no significant differencesin the majority of secondary outcomes, particularly days 1-3. However, during days 4-28, there were fewer median number of bowel movements per day in the methylnaltrexone group, (p=0.01) and a greater incidence of diarrhoea in the placebo group (p=0.02). There was a marked difference in mortality between the groups, with ten deaths in the methylnaltrexone group and two in the placebo group during days 4-28. (p=0.007).ConclusionWe found no evidence to support the addition of methylnaltrexone to regular laxatives for the treatment of opioidinduced constipation in critically ill patients, however the confidence interval was wide and a clinically important difference cannot be excluded

The Itinerary of Autophagosomes: From Peripheral Formation to Kiss-and-Run Fusion with Lysosomes

Macroautophagy, a constitutive process in higher eukaryotic cells, mediates degradation of many long-lived proteins and organelles. The actual events occurring during the process in the dynamic system of a living cell have never been thoroughly investigated. We aimed to develop a live-cell assay in which to follow the complete itinerary of an autophagosome. Our experiments show that autophagosomes are formed randomly in peripheral regions of the cell. They then move bidirectionally along microtubules, accumulating at the microtubule-organizing centre, in a similar way to lysosomes. Their centripetal movement is dependent on the motor protein dynein and is important for their fusion with lysosomes. Initially, autophagosomes dock on to lysosomes, independent of lysosomal acidification. Two kinds of fusion then occur: complete fusions, creating a hybrid organelle, or more often kiss-and-run fusions, i.e. transfer of some content while still maintaining two separate vesicles. Surprisingly, the autophagolysosomal compartment seems to be more long lived than expected. Our study documents many aspects of autophagosome behaviour, adding to our understanding of the mechanism and control of autophagy. Indeed, although the formation of autophagosomes is completely different from any other vesicular structures, their later itinerary appears to be very similar to those of other trafficking pathways

Hepatitis C prevalence in Denmark -an estimate based on multiple national registers

Background: A national survey for chronic hepatitis C has not been performed in Denmark and the prevalence is unknown. Our aim was to estimate the prevalence of chronic hepatitis C from public registers and the proportion of these patients who received specialized healthcare. Methods: Patients with a diagnosis of chronic hepatitis C were identified from four national registers: a laboratory register, the Hospital Discharge Register, a clinical database of chronic viral hepatitis and the Register of Communicable Diseases. The total population diagnosed with hepatitis C was estimated by capture-recapture analysis. The population with undiagnosed hepatitis C was derived from the national register of drug users by comparing diagnosed and tested persons. Results: A total of 6,935 patients diagnosed with chronic hepatitis C were identified in the four registers and the estimated population diagnosed with the disease was 9,166 persons (95% C.I. interval 8,973 – 9,877), corresponding to 0.21% (95% CI 0.21%-0.23%) of the Danish population over 15years of age. The prevalence was highest among persons 40–49years old (0.39%) and males (0.28%). It was estimated that 40% of the diagnosed patients lived in the capital region, and 33.5% had attended specialised healthcare. It was estimated that 46% of hepatitis C patients had not been diagnosed and the total population with chronic hepatitis C in Denmark was 16,888 (95% C.I. 16,474-18,287), corresponding to 0.38% (95% CI 0.37-0.42) of the population over 15years of age. Conclusions: The estimated prevalence of chronic hepatitis C in Denmark was 0.38%. Less than half of the patients with chronic hepatitis C in Denmark have been identified and among these patients, one in three has attended specialised care

In vitro culture with gemcitabine augments death receptor and NKG2D ligand expression on tumour cells

Much effort has been made to try to understand the relationship between chemotherapeutic treatment of cancer and the immune system. Whereas much of that focus has been on the direct effect of chemotherapy drugs on immune cells and the release of antigens and danger signals by malignant cells killed by chemotherapy, the effect of chemotherapy on cells surviving treatment has often been overlooked. In the present study, tumour cell lines: A549 (lung), HCT116 (colon) and MCF-7 (breast), were treated with various concentrations of the chemotherapeutic drugs cyclophosphamide, gemcitabine (GEM) and oxaliplatin (OXP) for 24 hours in vitro. In line with other reports, GEM and OXP upregulated expression of the death receptor CD95 (fas) on live cells even at sub-cytotoxic concentrations. Further investigation revealed that the increase in CD95 in response to GEM sensitised the cells to fas ligand treatment, was associated with increased phosphorylation of stress activated protein kinase/c-Jun N-terminal kinase and that other death receptors and activatory immune receptors were co-ordinately upregulated with CD95 in certain cell lines. The upregulation of death receptors and NKG2D ligands together on cells after chemotherapy suggest that although the cells have survived preliminary treatment with chemotherapy they may now be more susceptible to immune cell-mediated challenge. This re-enforces the idea that chemotherapy-immunotherapy combinations may be useful clinically and has implications for the make-up and scheduling of such treatments

The Higher-Order Prover Leo-II.

Leo-II is an automated theorem prover for classical higher-order logic. The prover has pioneered cooperative higher-order-first-order proof automation, it has influenced the development of the TPTP THF infrastructure for higher-order logic, and it has been applied in a wide array of problems. Leo-II may also be called in proof assistants as an external aid tool to save user effort. For this it is crucial that Leo-II returns proof information in a standardised syntax, so that these proofs can eventually be transformed and verified within proof assistants. Recent progress in this direction is reported for the Isabelle/HOL system.The Leo-II project has been supported by the following grants: EPSRC grant EP/D070511/1 and DFG grants BE/2501 6-1, 8-1 and 9-1.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s10817-015-9348-y

Direct photon production with effective field theory

The production of hard photons in hadronic collisions is studied using Soft-Collinear Effective Theory (SCET). This is the first application of SCET to a physical, observable cross section involving energetic partons in more than two directions. A factorization formula is derived which involves a non-trivial interplay of the angular dependence in the hard and soft functions, both quark and gluon jet functions, and multiple partonic channels. The relevant hard, jet and soft functions are computed to one loop and their anomalous dimensions are determined to three loops. The final resummed inclusive direct photon distribution is valid to next-to-next-to-leading logarithmic order (NNLL), one order beyond previous work. The result is improved by including non-logarithmic terms and photon isolation cuts through matching, and compared to Tevatron data and to fixed order results at the Tevatron and the LHC. The resummed cross section has a significantly smaller theoretical uncertainty than the next-to-leading fixed-order result, particularly at high transverse momentum.Comment: 42 pages, 9 figures; v2: references added, minor changes; v3: typos; v4: typos, corrections in (16), (47), (72