Pseudomonas aeruginosa bacteremia in patients undergoing liver transplantation: An emerging problem

In our institution, Pseudomonas aeruginosa bacteremia appeared to occur with increasing frequency in patients undergoing liver transplantation. We thus conducted a prospective study to define risk factors and outcome in these patients. Over a 19-month period 6% of liver transplants were followed by Pseudomonas bacteremia. The mean age was 46 years (range, 24 to 67 years). The interval between transplantation and onset of bacteremia was 3 to 372 days (mean, 80). The incidence of Pseudomonas bacteremia in liver transplants was three times that of other transplants (heart, lung, kidney). Ninety one percent of infections were nosocomial. Polymicrobial bacteremia occurred in 30% of episodes. The portal of entry was respiratory in 30%, abdominal in 35%, and biliary in 13%. Four patients had recurrent Pseudomonas bacteremia: liver abscess (1), biliary obstruction (2), subhepatic abscess (1). Survival at 14 days was 70%. Survival rates were significantly lower for patients with hypotension, on mechanical ventilators, and increasing severity of illness (p < 0.05). Survival was higher when bacteremia occurred within the first 30 days after transplantation compared to after 30 days. A large number (43.4%) of Pseudomonas bacteremias occurred after transplant surgery or biliary tract manipulation, while the patient was receiving a prophylactic regimen of cefotaxime and ampicillin. P. aeruginosa is an important pathogen in the liver transplant recipient; prevention may be possible for a subgroup of patients with the use of prophylactic antibiotics with activity against P. aeruginosa

What makes a crystal supersolid ?

For nearly half a century the supersolid phase of matter has remained mysterious, not only eluding experimental observation, but also generating a great deal of controversy among theorists. Recent discovery of what is interpreted as a non-classical moment of inertia at low temperature in solid He-4 has elicited much excitement as a possible first observation of a supersolid phase. In the two years following the discovery, however, more puzzles than answers have been provided to the fundamental issue of whether the supersolid phase exists, in helium or any other naturally occurring condensed matter system. Presently, there is no established theoretical framework to understand the body of experimental data on He-4. Different microscopic mechanisms that have been suggested to underlie superfluidity in a perfect quantum crystal do not seem viable for \he4, for which a wealth of experimental and theoretical evidence points to an insulating crystalline ground state. This perspective addresses some of the outstanding problems with the interpretation of recent experimental observations of the apparent superfluid response in He-4 (seen now by several groups) and discusses various scenarios alternative to the homogeneous supersolid phase, such as superfluidity induced by extended defects of the crystalline structure which include grain boundaries, dislocations, anisotropic stresses, etc. Can a metastable superfluid "glassy" phase exist, and can it be relevant to some of the experimental observations ? One of the most interesting and unsolved fundamental questions is what interatomic potentials, given the freedom to design one, can support an ideal supersolid phase in continuous space, and can they be found in Nature.Comment: Perspective to appear in Advances in Physics, 25 pages, 7 figure

Decreased incidence of viral infections in liver transplant recipients - Possible effects of FK506?

Cytomegalovirus (CMV) is a major infectious complication of organ transplantation and its incidence is influenced by the type and intensity of immunosuppressive therapy employed. Using a new immunosuppressive agent FK506, CMV infection was observed in 30% and CMV disease in 15% of the 26 liver transplant recipients. Delayed onset of CMV disease was noted; the mean time to the occurrence of CMV disease being 137 days posttransplantation. No graft loss or mortality could be attributed to CMV infection. Mucocutaneous herpes simplex virus (HSV) infections were encountered in 19% of the patients, while no disease could be attributed to varicella zoster virus or Epstein-Barr virus (EBV). The contribution of FK506 to a decrease in viral morbidity and associated mortality bears further investigation. © 1994 Plenum Publishing Corporation

A high incidence of native portal vein thrombosis in veterans undergoing liver transplantation

The incidence of native portal vein thrombosis (PVT) in liver transplant recipients has been reported to range from 2.1 to 13.8%. We have identified an inordinately high incidence of PVT in a consecutive series of U.S. veterans receiving liver transplants. Between October 1989 and February 1994, 88 consecutive U.S. veterans received 99 orthotopic liver transplants under primary Tacrolimus (Prograf, formerly FK506) based immunosuppression. A number of clinical features were examined in an effort to identify risk factors for PVT and outcome was compared to patients without PVT. Native PVT was present in 23/88 (26%) patients. All of these patients were male U.S. veterans with a mean age of 47 years. When compared to the 65 patients without PVT, we found no significant difference with respect to underlying liver disease, age, Childs-Pugh score (mean = 12), UNOS status as defined prior to April 1995 (95% UNOS 3 or 4), previous abdominal surgery, or liver volume. Median blood loss for patients with PVT (21 units of packed red blood cells) was greater than for those without PVT (14 units, P = 0.04). Portal thrombectomy was performed in 11 patients, 11 patients required mesoportal jump grafts, and 1 patient had an interposition graft. Standard veno-venous bypass was used in 10 patients with single bypass utilized for the remainder. Actuarial patient survival for all patients at 1, 2, and 4 years was 88, 85, and 79%, respectively. There was no significant difference in patients with or without PVT. Patients with PVT had poorer graft survival than patients without PVT (86% vs 65%, 1 year; 81% vs 65%, 2 years; 81% vs 61%, 4 years; P = 0.03); however, this was not related to technical problems with the portal venous inflow. PVT occurred in 26% of U.S. veterans undergoing liver transplantation. These patients bad significantly higher operative blood loss and poorer graft survival. The high incidence of postnecrotic cirrhosis in a predominantly male group of patients with advanced disease, as is evident by the high mean Childs-Pugh score and UNOS status, perhaps accounts for our observations

The cost of vaginal birth at home, in a birth centre or in a hospital setting in New South Wales: A micro-costing study

© 2019 Australian College of Midwives Background: Women want greater choice of place of birth in New South Wales, Australia. It is perceived to be more costly to health services for women with a healthy pregnancy to give birth at home or in a birth centre. It is not known how much it costs the health service to provide care for women planning to give birth in these settings. Aim: The aim of this study was to determine the direct cost of giving birth vaginally at home, in a birth centre or in a hospital for women at low risk of complications, in New South Wales. Methods: A micro-costing design was used. Observational (time and motion) and resource use data collection was undertaken to identify the staff time and resources required to provide care in a public hospital, birth centre or at home for women with a healthy pregnancy. Findings: The median cost of providing care for women who plan to give birth at home, in a birth centre and in a hospital were similar (AUD $2150.07,$2100.59 and $2097.30 respectively). Midwifery time was the largest contributor to the cost of birth at home, and overhead costs accounted for over half of the total cost of BC and hospital birth. The cost of consumables was low in all three settings. Conclusion: In this study, we have found there is little difference in the cost to the health service when a woman has an uncomplicated vaginal birth at home, in a birth centre or in a hospital setting

Mapping the trajectories for women and their babies from births planned at home, in a birth centre or in a hospital in New South Wales, Australia, between 2000 and 2012

© 2019 The Author(s). Background: In New South Wales (NSW) Australia, women at low risk of complications can choose from three birth settings: home, birth centre and hospital. Between 2000 and 2012, around 6.4% of pregnant women planned to give birth in a birth centre (6%) or at home (0.4%) and 93.6% of women planned to birth in a hospital. A proportion of the woman in the home and birth centre groups transferred to hospital. However, their pathways or trajectories are largely unknown. Aim: The aim was to map the trajectories and interventions experienced by women and their babies from births planned at home, in a birth centre or in a hospital over a 13-year period in NSW. Methods: Using population-based linked datasets from NSW, women at low risk of complications, with singleton pregnancies, gestation 37-41 completed weeks and spontaneous onset of labour were included. We used a decision tree framework to depict the trajectories of these women and estimate the probabilities of the following: giving birth in their planned setting; being transferred; requiring interventions and neonatal admission to higher level hospital care. The trajectories were analysed by parity. Results: Over a 13-year period, 23% of nulliparous and 0.8% of multiparous women planning a home birth were transferred to hospital. In the birth centre group, 34% of nulliparae and 12% of multiparas were transferred to a hospital. Normal vaginal birth rates were higher in multiparous women compared to nulliparous women in all settings. Neonatal admission to SCN/NICU was highest in the planned hospital group for nulliparous women (10.1%), 7.1% for nulliparous women planning a birth centre birth and 5.1% of nulliparous women planning a homebirth. Multiparas had lower admissions to SCN/NICU for all thee settings (hospital 6.3%, BC 3.6%, home 1.6%, respectively). Conclusions: Women who plan to give birth at home or in a birth centre have high rates of vaginal birth, even when transferred to hospital. Evidence on the trajectories of women who choose to give birth at home or in birth centres will assist the planning, costing and expansion of models of care in NSW

Modelling the cost of place of birth: a pathway analysis

Background In New South Wales (NSW), Australia there are three settings available for women at low risk of complications to give birth: home, birth centre and hospital. Between 2000 and 2012, 93.6% of babies were planned to be born in hospital, 6.0% in a birth centre and 0.4% at home. Availability of alternative birth settings is limited and the cost of providing birth at home or in a birth centre from the perspective of the health system is unknown. Objectives The objective of this study was to model the cost of the trajectories of women who planned to give birth at home, in a birth centre or in a hospital from the public sector perspective. Methods This was a population-based study using linked datasets from NSW, Australia. Women included met the following selection criteria: 37-41 completed weeks of pregnancy, spontaneous onset of labour, and singleton pregnancy at low risk of complications. We used a decision tree framework to depict the trajectories of these women and Australian Refined-Diagnosis Related Groups (AR-DRGs) were applied to each trajectory to estimate the cost of birth. A scenario analysis was undertaken to model the cost for 30 000 women in one year. Findings 496 387 women were included in the dataset. Twelve potential outcome pathways were identified and each pathway was costed using AR-DRGs. An overall cost was also calculated by place of birth: $AUD4802 for homebirth,$AUD4979 for a birth centre birth and $AUD5463 for a hospital birth. Conclusion The findings from this study provides some clarity into the financial saving of offering more options to women seeking an alternative to giving birth in hospital. Given the relatively lower rates of complex intervention and neonatal outcomes associated with women at low risk of complications, we can assume the cost of providing them with homebirth and birth centre options could be cost-effective

Phylogeny of Prokaryotes and Chloroplasts Revealed by a Simple Composition Approach on All Protein Sequences from Complete Genomes Without Sequence Alignment

The complete genomes of living organisms have provided much information on their phylogenetic relationships. Similarly, the complete genomes of chloroplasts have helped to resolve the evolution of this organelle in photosynthetic eukaryotes. In this paper we propose an alternative method of phylogenetic analysis using compositional statistics for all protein sequences from complete genomes. This new method is conceptually simpler than and computationally as fast as the one proposed by Qi et al. (2004b) and Chu et al. (2004). The same data sets used in Qi et al. (2004b) and Chu et al. (2004) are analyzed using the new method. Our distance-based phylogenic tree of the 109 prokaryotes and eukaryotes agrees with the biologists tree of life based on 16S rRNA comparison in a predominant majority of basic branching and most lower taxa. Our phylogenetic analysis also shows that the chloroplast genomes are separated to two major clades corresponding to chlorophytes s.l. and rhodophytes s.l. The interrelationships among the chloroplasts are largely in agreement with the current understanding on chloroplast evolution

Fully-automated μMRI morphometric phenotyping of the Tc1 mouse model of Down Syndrome

We describe a fully automated pipeline for the morphometric phenotyping of mouse brains from μMRI data, and show its application to the Tc1 mouse model of Down syndrome, to identify new morphological phenotypes in the brain of this first transchromosomic animal carrying human chromosome 21. We incorporate an accessible approach for simultaneously scanning multiple ex vivo brains, requiring only a 3D-printed brain holder, and novel image processing steps for their separation and orientation. We employ clinically established multi-atlas techniques-superior to single-atlas methods-together with publicly-available atlas databases for automatic skull-stripping and tissue segmentation, providing high-quality, subject-specific tissue maps. We follow these steps with group-wise registration, structural parcellation and both Voxel- and Tensor-Based Morphometry-advantageous for their ability to highlight morphological differences without the laborious delineation of regions of interest. We show the application of freely available open-source software developed for clinical MRI analysis to mouse brain data: NiftySeg for segmentation and NiftyReg for registration, and discuss atlases and parameters suitable for the preclinical paradigm. We used this pipeline to compare 29 Tc1 brains with 26 wild-type littermate controls, imaged ex vivo at 9.4T. We show an unexpected increase in Tc1 total intracranial volume and, controlling for this, local volume and grey matter density reductions in the Tc1 brain compared to the wild-types, most prominently in the cerebellum, in agreement with human DS and previous histological findings

Outer mitochondrial membrane localization of apoptosis-inducing factor: mechanistic implications for release

Poly(ADP-ribose) polymerase-1-dependent cell death (known as parthanatos) plays a pivotal role in many clinically important events including ischaemia/reperfusion injury and glutamate excitotoxicity. A recent study by us has shown that uncleaved AIF (apoptosis-inducing factor), but not calpain-hydrolysed truncated-AIF, was rapidly released from the mitochondria during parthanatos, implicating a second pool of AIF that might be present in brain mitochondria contributing to the rapid release. In the present study, a novel AIF pool is revealed in brain mitochondria by multiple biochemical analyses. Approx. 30% of AIF loosely associates with the outer mitochondrial membrane on the cytosolic side, in addition to its main localization in the mitochondrial intermembrane space attached to the inner membrane. Immunogold electron microscopic analysis of mouse brain further supports AIF association with the outer, as well as the inner, mitochondrial membrane in vivo. In line with these observations, approx. 20% of uncleaved AIF rapidly translocates to the nucleus and functionally causes neuronal death upon NMDA (N-methyl-d-aspartate) treatment. In the present study we show for the first time a second pool of AIF in brain mitochondria and demonstrate that this pool does not require cleavage and that it contributes to the rapid release of AIF. Moreover, these results suggest that this outer mitochondrial pool of AIF is sufficient to cause cell death during parthanatos. Interfering with the release of this outer mitochondrial pool of AIF during cell injury paradigms that use parthanatos hold particular promise for novel therapies to treat neurological disorders