Fungal infections of the central nervous system: A review of fungal pathogens and treatment

Multiple factors influence the outcome of fungal infection of the central nervous system (CNS). The host and the pathogen in concert with drug delivery across the blood-brain barrier and drug activity are key factors in outcome. Drug costs can be prohibitively expensive. Drug toxicity with standard antifungal agents such as amphotericin B (infusion rate toxicity) can be reduced using simple techniques such as slower infusion and appropriate saline loading. Continuous infusion can allow relatively large doses of amphotericin B (up to 2 mg/kg/day, remaining below 0.08 mg/kg/hour) to be given with toxicity profiles comparable to expensive lipid formulations of amphotericin B. Dedicated peripherally inserted central catheters can remain in situ for weeks to months and are safe and relatively inexpensive. Correction of metabolic pathology in the case of mucormycosis and resolution of neutropenia are essential to effective treatment of filamentous fungal infections such as Mucor, Aspergillus and Scedosporium. The pharmacology and pharmacokinetics of the current major antifungal agents used to treat fungal infections of the CNS are reviewed. Tables that provide information about achievable CNS drug levels, antifungal susceptibilities and the likelihood of intrinsic drug resistance of significant fungal pathogens have been included to help the clinician with therapy. Treatment recommendations for Cryptococcal and Candida meningitis and for rhinocerebral infection with Mucor and Aspergillus have been included

Australian SMEs waste to landfill

Landfill waste has a negative impact on the environment and small and medium sized enterprises (SMEs) are believed to be significant contributors. There is little government or scholarly research, however, quantifying the collective volume of waste SMEs send to landfill. Where studies do exist they measure total volumes (landfill and recycling combined) and/or do not distinguish between specific waste streams (e.g. wood) and subcategories (e.g. dust). This paper contributes to knowledge by giving insight into the collective volume of waste of 404 SMEs, reconceptualising SME waste into subcategories and by measuring landfill volumes. It presents findings from these 404 Australian SMEs which found that, in descending order, cardboard, paper, plastic wrap, wood dust and particleboard were the subcategories these SMEs sent to landfill in the greatest volumes. It also argues that this reconceptualisation, and associated data collection protocols, have the potential to enable scholars and policy makers to determine the waste subcategories to which SMEs contribute most, formulate targeted interventions and research or evaluate environmental outcomes. © 2014 © 2014 Environment Institute of Australia and New Zealand Inc

Analytic perturbation theory in QCD and Schwinger's connection between the beta-function and the spectral density

We argue that a technique called analytic perturbation theory leads to a well-defined method for analytically continuing the running coupling constant from the spacelike to the timelike region, which allows us to give a self-consistent definition of the running coupling constant for timelike momentum. The corresponding $\beta$-function is proportional to the spectral density, which confirms a hypothesis due to Schwinger.Comment: 11 pages, 2 figure

The Accelerated Kepler Problem

The accelerated Kepler problem is obtained by adding a constant acceleration to the classical two-body Kepler problem. This setting models the dynamics of a jet-sustaining accretion disk and its content of forming planets as the disk loses linear momentum through the asymmetric jet-counterjet system it powers. The dynamics of the accelerated Kepler problem is analyzed using physical as well as parabolic coordinates. The latter naturally separate the problem's Hamiltonian into two unidimensional Hamiltonians. In particular, we identify the origin of the secular resonance in the accelerated Kepler problem and determine analytically the radius of stability boundary of initially circular orbits that are of particular interest to the problem of radial migration in binary systems as well as to the truncation of accretion disks through stellar jet acceleration.Comment: 16 pages, 9 figures, in press at Celestial Mechanics and Dynamical Astronom

Dirac Cat States in Relativistic Landau Levels

We show that a relativistic version of Schrodinger cat states, here called Dirac cat states, can be built in relativistic Landau levels when an external magnetic field couples to a relativistic spin 1/2 charged particle. Under suitable initial conditions, the associated Dirac equation produces unitarily Dirac cat states involving the orbital quanta of the particle in a well defined mesoscopic regime. We demonstrate that the proposed Dirac cat states have a purely relativistic origin and cease to exist in the non-relativistic limit. In this manner, we expect to open relativistic quantum mechanics to the rich structures of quantum optics and quantum information.Comment: Revtex4, color figures, submitted for publicatio

Hip contact forces in asymptomatic total hip replacement patients differ from normal healthy individuals: implications for preclinical testing

BACKGROUND Preclinical durability testing of hip replacement implants is standardised by ISO-14242-1 (2002) which is based on historical inverse dynamics analysis using data obtained from a small sample of normal healthy individuals. It has not been established whether loading cycles derived from normal healthy individuals are representative of loading cycles occurring in patients following total hip replacement. METHODS Hip joint kinematics and hip contact forces derived from multibody modelling of forces during normal walking were obtained for 15 asymptomatic total hip replacement patients and compared to 38 normal healthy individuals and to the ISO standard for pre-clinical testing. FINDINGS Hip kinematics in the total hip replacement patients were comparable to the ISO data and the hip contact force in the normal healthy group was also comparable to the ISO cycles. Hip contact forces derived from the asymptomatic total hip replacement patients were comparable for the first part of the stance period but exhibited 30% lower peak loads at toe-off. INTERPRETATION Although the ISO standard provides a representative kinematic cycle, the findings call into question whether the hip joint contact forces in the ISO standard are representative of those occurring in the joint following total hip replacement

Australian SMEs: Waste sent to landfill

Landfill waste has a negative impact on the environment and Small and Medium Enterprises (SMEs) are believed to be significant contributors. There is little government or scholarly research, however, quantifying the collective volume of waste SMEs send to landfill. The limited studies instead measure total volumes (landfill and recycling combined) and/or do not distinguish between specific waste streams (e.g. wood) and subcategories (e.g. dust). This paper contributes to knowledge by reconceptualising SME waste into subcategories and by measuring landfill volumes. It presents findings from 404 Australian SMEs which found that, in descending order, cardboard, paper, plastic wrap, wood dust and particleboard were the subcategories these SMEs sent to landfill in the greatest volumes. It also argues that this reconceptualisation and associated data collection protocols have the potential to enable scholars and policymakers to determine the waste subcategories to which SMEs contribute most, formulate targeted interventions and research/evaluate environmental outcomes

Unilateral total hip replacement patients with symptomatic leg length inequality have abnormal hip biomechanics during walking

BACKGROUND Symptomatic leg length inequality accounts for 8.7% of total hip replacement related claims made against the UK National Health Service Litigation authority. It has not been established whether symptomatic leg length inequality patients following total hip replacement have abnormal hip kinetics during gait. METHODS Hip kinetics in 15 unilateral total hip replacement patients with symptomatic leg length inequality during gait was determined through multibody dynamics and compared to 15 native hip healthy controls and 15 'successful' asymptomatic unilateral total hip replacement patients. FINDING More significant differences from normal were found in symptomatic leg length inequality patients than in asymptomatic total hip replacement patients. The leg length inequality patients had altered functions defined by lower gait velocity, reduced stride length, reduced ground reaction force, decreased hip range of motion, reduced hip moment and less dynamic hip force with a 24% lower heel-strike peak, 66% higher mid-stance trough and 37% lower toe-off peak. Greater asymmetry in hip contact force was also observed in leg length inequality patients. INTERPRETATION These gait adaptions may affect the function of the implant and other healthy joints in symptomatic leg length inequality patients. This study provides important information for the musculoskeletal function and rehabilitation of symptomatic leg length inequality patients

In silico karyotyping of chromosomally polymorphic malaria mosquitoes in the Anopheles gambiae complex

Chromosomal inversion polymorphisms play an important role in adaptation to environmental heterogeneities. For mosquito species in the Anopheles gambiae complex that are significant vectors of human malaria, paracentric inversion polymorphisms are abundant and are associated with ecologically and epidemiologically important phenotypes. Improved understanding of these traits relies on determining mosquito karyotype, which currently depends upon laborious cytogenetic methods whose application is limited both by the requirement for specialized expertise and for properly preserved adult females at specific gonotrophic stages. To overcome this limitation, we developed sets of tag single nucleotide polymorphisms (SNPs) inside inversions whose biallelic genotype is strongly correlated with inversion genotype. We leveraged 1,347 fully sequenced An. gambiae and Anopheles coluzzii genomes in the Ag1000G database of natural variation. Beginning with principal components analysis (PCA) of population samples, applied to windows of the genome containing individual chromosomal rearrangements, we classified samples into three inversion genotypes, distinguishing homozygous inverted and homozygous uninverted groups by inclusion of the small subset of specimens in Ag1000G that are associated with cytogenetic metadata. We then assessed the correlation between candidate tag SNP genotypes and PCA-based inversion genotypes in our training sets, selecting those candidates with >80% agreement. Our initial tests both in held-back validation samples from Ag1000G and in data independent of Ag1000G suggest that when used for in silico inversion genotyping of sequenced mosquitoes, these tags perform better than traditional cytogenetics, even for specimens where only a small subset of the tag SNPs can be successfully ascertained