A guide to formulating fairness in an optimization model.

Optimization models typically seek to maximize overall benefit or minimize total cost. Yet fairness is an important element of many practical decisions, and it is much less obvious how to express it mathematically. We provide a critical survey of various schemes that have been proposed for formulating ethics-related criteria, including those that integrate efficiency and fairness concerns. The survey covers inequality measures, Rawlsian maximin and leximax criteria, convex combinations of fairness and efficiency, alpha fairness and proportional fairness (also known as the Nash bargaining solution), Kalai-Smorodinsky bargaining, and recently proposed utility-threshold and fairness-threshold schemes for combining utilitarian with maximin or leximax criteria. The paper also examines group parity metrics that are popular in machine learning. We present what appears to be the best practical approach to formulating each criterion in a linear, nonlinear, or mixed integer programming model. We also survey axiomatic and bargaining derivations of fairness criteria from the social choice literature while taking into account interpersonal comparability of utilities. Finally, we cite relevant philosophical and ethical literature where appropriate.

[11C]PBR28 MR-PET imaging reveals lower regional brain expression of translocator protein (TSPO) in young adult males with autism spectrum disorder.

Mechanisms of neuroimmune and mitochondrial dysfunction have been repeatedly implicated in autism spectrum disorder (ASD). To examine these mechanisms in ASD individuals, we measured the in vivo expression of the 18 kDa translocator protein (TSPO), an activated glial marker expressed on mitochondrial membranes. Participants underwent scanning on a simultaneous magnetic resonance-positron emission tomography (MR-PET) scanner with the second-generation TSPO radiotracer [11C]PBR28. By comparing TSPO in 15 young adult males with ASD with 18 age- and sex-matched controls, we showed that individuals with ASD exhibited lower regional TSPO expression in several brain regions, including the bilateral insular cortex, bilateral precuneus/posterior cingulate cortex, and bilateral temporal, angular, and supramarginal gyri, which have previously been implicated in autism in functional MR imaging studies. No brain region exhibited higher regional TSPO expression in the ASD group compared with the control group. A subset of participants underwent a second MR-PET scan after a median interscan interval of 3.6 months, and we determined that TSPO expression over this period of time was stable and replicable. Furthermore, voxelwise analysis confirmed lower regional TSPO expression in ASD at this later time point. Lower TSPO expression in ASD could reflect abnormalities in neuroimmune processes or mitochondrial dysfunction.

The neuroinflammatory component of negative affect in patients with chronic pain.

Negative affect (NA) is a significant cause of disability for chronic pain patients. While little is known about the mechanism underlying pain-comorbid NA, previous studies have implicated neuroinflammation in the pathophysiology of both depression and chronic pain. Here, we tested the hypothesis that NA in pain patients is linked to elevations in the brain levels of the glial marker 18 kDa translocator protein (TSPO), and changes in functional connectivity. 25 cLBP patients (42.4 ± 13 years old; 13F, 12M) with chronic low back pain (cLBP) and 27 healthy control subjects (48.9 ± 13 years old; 14F, 13M) received an integrated (i.e., simultaneous) positron emission tomography (PET)/magnetic resonance imaging (MRI) brain scan with the second-generation TSPO ligand [11C]PBR28. The relationship between [11C]PBR28 signal and NA was assessed first with regression analyses against Beck Depression Inventory (BDI) scores in patients, and then by comparing cLBP patients with little-to-no, or mild-to-moderate depression against healthy controls. Further, the relationship between PET signal, BDI and frontolimbic functional connectivity was evaluated in patients with mediation models. PET signal was positively associated with BDI scores in patients, and significantly elevated in patients with mild-to-moderate (but not low) depression compared with controls, in anterior middle and pregenual anterior cingulate cortices (aMCC, pgACC). In the pgACC, PET signal was also associated with this region's functional connectivity to the dorsolateral PFC (pgACC-dlPFC), and mediated of the association between pgACC-dlPFC connectivity and BDI. These observations support a role for glial activation in pain-comorbid NA, identifying in neuroinflammation a potential therapeutic target for this condition.

Imaging HDACs In Vivo: Cross-Validation of the [11C]Martinostat Radioligand in the Pig Brain.

PURPOSE: With the emerging knowledge about the impact of epigenetic alterations on behavior and brain disorders, the ability to measure epigenetic alterations in brain tissue in vivo has become critically important. We present the first in vivo/in vitro cross-validation of the novel positron emission tomography (PET) radioligand [11C]Martinostat in the pig brain with regard to its ability to measure histone deacetylase 1-3 (HDAC1-3) levels in vivo. PROCEDURES: Nine female Danish landrace pigs underwent 121-min dynamic PET scans with [11C]Martinostat. We quantified [11C]Martinostat uptake using both a simple ratio method and kinetic models with arterial input function. By the end of the scan, the animals were euthanized and the brains were extracted. We measured HDAC1-3 protein levels in frontal cortex, cerebellum vermis, and hippocampus and compared the protein levels and regional outcome values to the [11C]Martinostat PET quantification. RESULTS: [11C]Martinostat distributed widely across brain regions, with the highest uptake in the cerebellum vermis and the lowest in the olfactory bulbs. Based on the Akaike information criterion, the quantification was most reliably performed by Ichise MA1 kinetic modeling, but since the radioligand displayed very slow kinetics, we also calculated standard uptake value (SUV) ratios which correlated well with VT. The western blots revealed higher brain tissue protein levels of HDAC1/2 compared to HDAC3, and HDAC1 and HDAC2 levels were highly correlated in all three investigated brain regions. The in vivo SUV ratio measure correlated well with the in vitro HDAC1-3 levels, whereas no correlation was found between VT values and HDAC levels. CONCLUSIONS: We found good correlation between in vivo measured SUV ratios and in vitro measures of HDAC 1-3 proteins, supporting that [11C]Martinostat provides a good in vivo measure of the cerebral HDAC1-3 protein levels.

A Protocol for Sedation Free MRI and PET Imaging in Adults with Autism Spectrum Disorder.

Imaging technologies such as positron emission tomography (PET) and magnetic resonance imaging (MRI) present unparalleled opportunities to investigate the neural basis of autism spectrum disorder (ASD). However, challenges such as deficits in social interaction, anxiety around new experiences, impaired language abilities, and hypersensitivity to sensory stimuli make participating in neuroimaging studies challenging for individuals with ASD. In this commentary, we describe the existent training protocols for preparing individuals with ASD for PET/MRI scans and our own experience developing a training protocol to facilitate the inclusion of low-functioning adults with ASD in PET-MRI studies. We hope to raise awareness of the need for more information exchange between research groups about lessons learned in this context in order to include the entire disease spectrum in neuroimaging studies.

Magnetic resonance elastography identifies fibrosis in adults with alpha-1 antitrypsin deficiency liver disease: a prospective study.

BACKGROUND: Limited data exist on the clinical presentation and non-invasive detection of liver fibrosis in adults with homozygous Z genotype alpha-1 antitrypsin (AAT) deficiency. AIMS: To compare demographic, biochemical, histological and imaging data of AAT deficient patients to normal-control and biopsy-proven non-alcoholic fatty liver disease (NAFLD) patients, and to assess the diagnostic accuracy of magnetic resonance elastography (MRE) in detecting fibrosis in AAT deficiency. METHODS: Study includes 33 participants, 11 per group, who underwent clinical research evaluation, liver biopsy (AAT and NAFLD groups), and MRE. Histological fibrosis was quantified using a modified Ishak 6-point scale and liver stiffness by MRE. Diagnostic performance of MRE in detecting fibrosis was assessed by receiver operating characteristic (ROC) analysis. RESULTS: Mean (±s.d.) of age and BMI of normal-control, AAT and NAFLD groups was 57 (±19), 57 (±18), and 57 (±13) years, and 22.7 (±2.5), 24.8 (±4.0) and 31.0 (±5.1) kg/m(2) respectively. Serum ALT [mean ± s.d.] was similar within normal-control [16.4 ± 4.0] and AAT groups [23.5 ± 10.8], but was significantly lower in AAT than NAFLD even after adjustment for stage of fibrosis (P < 0.05, P = 0.0172). For fibrosis detection, MRE-estimated stiffness had an area under the ROC curve of 0.90 (P < 0.0001); an MRE threshold of ≥3.0 kPa provided 88.9% accuracy, with 80% sensitivity and 100% specificity to detect presence of any fibrosis (stage ≥1). CONCLUSIONS: This pilot prospective study suggests magnetic resonance elastography may be accurate for identifying fibrosis in patients with alpha-1 antitrypsin deficiency. Larger validation studies are warranted.

Non-invasive screening of diabetics in primary care for NAFLD and advanced fibrosis by MRI and MRE.

BACKGROUND: Current guidelines do not recommend screening for non-alcoholic fatty liver disease (NAFLD) or advanced fibrosis. Patients with type 2 diabetes mellitus (T2DM) are known to be at increased risk for NAFLD and advanced fibrosis. AIM: To assess the feasibility in diabetics in a primary care setting of screening for NAFLD and advanced fibrosis, by using non-invasive magnetic resonance imaging (MRI) to estimate the hepatic proton density fat fraction (MRI-PDFF) and magnetic resonance elastography (MRE) to estimate hepatic stiffness. METHODS: We performed a cross-sectional analysis of a prospective study that included 100 (53% men) consecutively enrolled diabetics who did not have any other aetiology of liver disease. All patients underwent a standardised research visit, laboratory tests, MRI-PDFF, and MRE. RESULTS: Mean (±s.d.) age and body mass index (BMI) was 59.7 (±11.2) years and 30.8 (±6.5) kg/m(2) , respectively. The prevalence of NAFLD (defined as MRI-PDFF ≥5%) and advanced fibrosis (defined as MRE ≥3.6 kPa) was 65% and 7.1%, respectively. One patient with advanced fibrosis had definite hepatocellular carcinoma. When compared to those without NAFLD, patients with NAFLD were younger (P = 0.028) and had higher mean BMI (P = 0.0008), waist circumference (P < 0.0001) and prevalence of metabolic syndrome (84.6% vs. 40.0%, P < 0.0001). Only 26% of those with NAFLD had elevated alanine aminotransferase. CONCLUSIONS: This proof-of-concept study demonstrates that T2DM has significant rates of both NAFLD and advanced fibrosis. Concomitant screening for NAFLD and advanced fibrosis by using MRI-proton density fat fraction and magnetic resonance elastography in T2DM is feasible and may be considered after validation in a larger cohort.

Psychomotor impairment detection via finger interactions with a computer keyboard during natural typing.

Modern digital devices and appliances are capable of monitoring the timing of button presses, or finger interactions in general, with a sub-millisecond accuracy. However, the massive amount of high resolution temporal information that these devices could collect is currently being discarded. Multiple studies have shown that the act of pressing a button triggers well defined brain areas which are known to be affected by motor-compromised conditions. In this study, we demonstrate that the daily interaction with a computer keyboard can be employed as means to observe and potentially quantify psychomotor impairment. We induced a psychomotor impairment via a sleep inertia paradigm in 14 healthy subjects, which is detected by our classifier with an Area Under the ROC Curve (AUC) of 0.93/0.91. The detection relies on novel features derived from key-hold times acquired on standard computer keyboards during an uncontrolled typing task. These features correlate with the progression to psychomotor impairment (p < 0.001) regardless of the content and language of the text typed, and perform consistently with different keyboards. The ability to acquire longitudinal measurements of subtle motor changes from a digital device without altering its functionality may allow for early screening and follow-up of motor-compromised neurodegenerative conditions, psychological disorders or intoxication at a negligible cost in the general population.

PET imaging demonstrates histone deacetylase target engagement and clarifies brain penetrance of known and novel small molecule inhibitors in rat.

Histone deacetylase (HDAC) enzymes have been demonstrated as critical components in maintaining chromatin homeostasis, CNS development, and normal brain function. Evidence in mouse models links HDAC expression to learning, memory, and mood-related behaviors; small molecule HDAC inhibitor tool compounds have been used to demonstrate the importance of specific HDAC subtypes in modulating CNS-disease-related behaviors in rodents. So far, no direct evidence exists to understand the quantitative changes in HDAC target engagement that are necessary to alter biochemistry and behavior in a living animal. Understanding the relationship between target engagement and in vivo effect is essential in refining new ways to alleviate disease. We describe here, using positron emission tomography (PET) imaging of rat brain, the in vivo target engagement of a subset of class I/IIb HDAC enzymes implicated in CNS-disease (HDAC subtypes 1, 2, 3, and 6). We found marked differences in the brain penetrance of tool compounds from the hydroxamate and benzamide HDAC inhibitor classes and resolved a novel, highly brain penetrant benzamide, CN147, chronic treatment with which resulted in an antidepressant-like effect in a rat behavioral test. Our work highlights a new translational path for understanding the molecular and behavioral consequences of HDAC target engagement.

Visualizing epigenetics: current advances and advantages in HDAC PET imaging techniques.

Abnormal gene regulation as a consequence of flawed epigenetic mechanisms may be central to the initiation and persistence of many human diseases. However, the association of epigenetic dysfunction with disease and the development of therapeutic agents for treatment are slow. Developing new methodologies used to visualize chromatin-modifying enzymes and their function in the human brain would be valuable for the diagnosis of brain disorders and drug discovery. We provide an overview of current invasive and noninvasive techniques for measuring expression and functions of chromatin-modifying enzymes in the brain, emphasizing tools applicable to histone deacetylase (HDAC) enzymes as a leading example. The majority of current techniques are invasive and difficult to translate to what is happening within a human brain in vivo. However, recent progress in molecular imaging provides new, noninvasive ways to visualize epigenetics in the human brain. Neuroimaging tool development presents a unique set of challenges in order to identify and validate CNS radiotracers for HDACs and other histone-modifying enzymes. We summarize advances in the effort to image HDACs and HDAC inhibitory effects in the brain using positron emission tomography (PET) and highlight generalizable techniques that can be adapted to investigate other specific components of epigenetic machinery. Translational tools like neuroimaging by PET and magnetic resonance imaging provide the best way to link our current understanding of epigenetic changes with in vivo function in normal and diseased brains. These tools will be a critical addition to ex vivo methods to evaluate - and intervene - in CNS dysfunction.

In vivo imaging of adult human hippocampal neurogenesis: progress, pitfalls and promise.

New neurons are produced within the hippocampus of the mammalian brain throughout life. Evidence from animal studies has suggested that the function of these adult-born neurons is linked to cognition and emotion. Until we are able to detect and measure levels of adult neurogenesis in living human brains-a formidable challenge for now-we cannot establish its functional importance in human health, disease and new treatment development. Current non-invasive neuroimaging modalities can provide live snapshots of the brain's structure, chemistry, activity and connectivity. This review explores whether existing macroscopic imaging methods can be used to understand the microscopic dynamics of adult hippocampal neurogenesis in living individuals. We discuss recent studies that have found correlations between neuroimaging measures of human hippocampal biology and levels of pro- or anti-neurogenic stimuli, weigh whether these correlations reflect changes in adult neurogenesis, detail the conceptual and technical limitations of these studies and elaborate on what will be needed to validate in vivo neuroimaging measures of adult neurogenesis for future investigations.

Noninvasive determination of 2-[18F]-fluoroisonicotinic acid hydrazide pharmacokinetics by positron emission tomography in Mycobacterium tuberculosis-infected mice.

Tuberculosis (TB) is a global pandemic requiring sustained therapy to facilitate curing and to prevent the emergence of drug resistance. There are few adequate tools to evaluate drug dynamics within infected tissues in vivo. In this report, we evaluated a fluorinated analog of isoniazid (INH), 2-[(18)F]fluoroisonicotinic acid hydrazide (2-[(18)F]-INH), as a probe for imaging Mycobacterium tuberculosis-infected mice by dynamic positron emission tomography (PET). We developed a tail vein catheter system to safely deliver drugs to M. tuberculosis aerosol-infected mice inside sealed biocontainment devices. Imaging was rapid and noninvasive, and it could simultaneously visualize multiple tissues. Dynamic PET imaging demonstrated that 2-[(18)F]-INH was extensively distributed and rapidly accumulated at the sites of infection, including necrotic pulmonary TB lesions. Compared to uninfected animals, M. tuberculosis-infected mice had a significantly higher PET signal within the lungs (P < 0.05) despite similar PET activity in the liver (P > 0.85), suggesting that 2-[(18)F]-INH accumulated at the site of the pulmonary infection. Furthermore, our data indicated that similar to INH, 2-[(18)F]-INH required specific activation and accumulated within the bacterium. Pathogen-specific metabolism makes positron-emitting INH analogs attractive candidates for development into imaging probes with the potential to both detect bacteria and yield pharmacokinetic data in situ. Since PET imaging is currently used clinically, this approach could be translated from preclinical studies to use in humans.

Bitter taster status predicts susceptibility to vection-induced motion sickness and nausea.

BACKGROUND: Sensitivity to bitter taste and susceptibility to nausea are both protective mechanisms that guard against toxin ingestion, and both these traits vary within and between populations. Thus, we postulated that they may have co-evolved, such that they are associated. METHODS: Bitter taster status was determined in 40 subjects (13 men, 27 women) by measuring the differential perceived taste intensity between salt and n-propylthiouracil using a labeled magnitude scale; susceptibility to vection-induced motion sickness and nausea was assessed using an optokinetic drum, a validated multi-symptom scoring scale, and electrogastrography. KEY RESULTS: Taster status distribution was 25% non-tasters (NT), 40% tasters (T), and 35% supertasters (ST). Gender had no impact on this distribution, but females had a higher mean maximum symptom score than males (12.4 ± 1.4 vs 7.3 ± 2.0). Non-tasters displayed a faster and larger increase in mean symptom scores, had a higher percentage of subjects with high maximum symptom scores, and had a higher mean maximum score than T or ST, (14.8 ± 2.6 vs 7.1 ± 1.8, vs 9.8 ± 2.0). Taster status did not affect the gastric myoelectric frequency response to vection. CONCLUSIONS & INFERENCES: Non-tasters are more susceptible to vection-induced motion sickness and nausea than T or ST, suggesting these two traits may have co-evolved in a reciprocal manner: in environments where the NT trait conferred an evolutionary advantage by enabling intake of fruits and vegetables containing bitter, yet beneficial, phytonutrients, increased nausea susceptibility may have arisen to maintain protection against ingested toxins.

Preliminary report on a catalyst derived from induced cells of Rhodococcus rhodochrous strain DAP 96253 that delays the ripening of selected climacteric fruit: bananas, avocados, and peaches.

Despite the use of refrigeration, improved packaging, adsorbents, and ethylene receptor blockers, on average, nearly 40% of all fruits and vegetables harvested in the US are not consumed. Many plant products, especially fruit, continue to ripen after harvesting, and as they do so, become increasingly susceptible to mechanical injury, resulting in increased rot. Other plant products during transportation and storage are susceptible to chill injury (CI). There is a real need for products that can delay ripening or mitigate the effects of CI, yet still permit full ripeness and quality to be achieved. Preliminary results are discussed where catalyst derived from cells of Rhodococcus rhodochrous DAP 96253, grown under conditions that induced high levels of nitrile hydratase, were able to extend the ripening and thus the shelf-life of selected climacteric fruits (banana, avocado, and peach). A catalyst, when placed in proximity to, but not touching, the test fruit delayed the ripening but did not alter the final ripeness of the fruit tested. Organoleptic evaluations conducted with control peaches and with peaches exposed to, but not in contact with, the catalyst showed that the catalyst-treated peaches achieved full, natural levels of ripeness with respect to aroma, flavor, sweetness, and juice content. Furthermore, the results of delayed ripening were achieved at ambient temperatures (without the need for refrigeration).

The European Multiple System Atrophy-Study Group (EMSA-SG).

Introduction. The European Multiple System Atrophy-Study Group (EMSA-SG) is an academic network comprising 23 centers across Europe and Israel that has constituted itself already in January 1999. This international forum of established experts under the guidance of the University Hospital of Innsbruck as coordinating center is supported by the 5th framework program of the European Union since March 2001 (QLK6-CT-2000-00661). Objectives. Primary goals of the network include (1) a central Registry for European multiple system atrophy (MSA) patients, (2) a decentralized DNA Bank, (3) the development and validation of the novel Unified MSA Rating Scale (UMSARS), (4) the conduction of a Natural History Study (NHS), and (5) the planning or implementation of interventional therapeutic trials. Methods. The EMSA-SG Registry is a computerized data bank localized at the coordinating centre in Innsbruck collecting diagnostic and therapeutic data of MSA patients. Blood samples of patients and controls are recruited into the DNA Bank. The UMSARS is a novel specific rating instrument that has been developed and validated by the EMSA-SG. The NHS comprises assessments of basic anthropometric data as well as a range of scales including the UMSARS, Unified Parkinson's Disease Rating Scale (UPDRS), measures of global disability, Red Flag list, MMSE (Mini Mental State Examination), quality of live measures, i.e. EuroQoL 5D (EQ-5D) and Medical Outcome Study Short Form (SF-36) as well as the Beck Depression Inventory (BDI). In a subgroup of patients dysautonomic features are recorded in detail using the Queen Square Cardiovascular Autonomic Function Test Battery, the Composite Autonomic Symptom Scale (COMPASS) and measurements of residual urinary volume. Most of these measures are repeated at 6-monthly follow up visits for a total study period of 24 months. Surrogate markers of the disease progression are identified by the EMSA-SG using magnetic resonance and diffusion weighted imaging (MRI and DWI, respectively). Results. 412 patients have been recruited into the Registry so far. Probable MSA-P was the most common diagnosis (49% of cases). 507 patients donated DNA for research. 131 patients have been recruited into the NHS. There was a rapid deterioration of the motor disorder (in particular akinesia) by 26.1% of the UMSARS II, and - to a lesser degree - of activities of daily living by 16.8% of the UMSARS I in relation to the respective baseline scores. Motor progression was associated with low motor or global disability as well as low akinesia or cerebellar subscores at baseline. Mental function did not deteriorate during this short follow up period. Conclusion. For the first time, prospective data concerning disease progression are available. Such data about the natural history and prognosis of MSA as well as surrogate markers of disease process allow planning and implementation of multi-centre phase II/III neuroprotective intervention trials within the next years more effectively. Indeed, a trial on growth hormone in MSA has just been completed, and another on minocycline will be completed by the end of this year.

Gaseous emissions from burning diesel, crude and prime bleachable summer yellow cottonseed oil in a burner for drying seedcotton.

Cottonseed oil has been used as a fuel source either as a blend with diesel in varying proportions or undiluted (100%) in numerous studies evaluating its potential use in internal combustion engines. However, limited research is available on the use of cottonseed oil as a fuel source in a multi-fueled burner similar to those used by cottonseed oil mills and cotton gins in their drying operations. The purpose of this study was to evaluate emissions from five fuel oil treatments while firing a multi-fueled burner in a setup similar to those used for drying operations of both cottonseed oil mills and cotton gins. For each treatment, gaseous emissions were measured while firing the burner at three fuel flow rates. The five fuel oil treatments evaluated were: (1) No. 2 diesel at 28.3 degrees C, (2) prime bleachable summer yellow (PBSY) cottonseed oil at 28.3 degrees C (PBSY-28), (3) crude cottonseed oil at 28.3 degrees C (Crude-28), (4) PBSY at 60 degrees C (PBSY-60), and (5) crude at 60 degrees C (Crude-60). Results indicate that PBSY treatments had the lowest overall emissions of all treatments. The other treatments varied in emission rates based on treatment and fuel flow rate. Preheating the oil to 60 degrees C resulted in higher NO(x) emissions but displayed varying results in regards to CO. The CO emissions for the crude treatments were relatively unaffected by the 60 degrees C preheat temperature whereas the preheated PBSY treatments demonstrated lower CO emissions. Overall, both cottonseed oils performed well in the multi-fueled burner and displayed a promising potential as an alternative fuel source for cottonseed oil mills and cotton gins in their drying operations.

Diagnostic utility of cerebrospinal fluid studies in patients with clinically suspected tuberculous meningitis.

OBJECTIVE: To compare yields of cerebrospinal fluid (CSF) studies in the diagnosis of tuberculosis meningitis (TBM). DESIGN: Prospective laboratory study, Kenyatta National Hospital, Kenya. STUDY POPULATION: Consecutive patients with 1) headache, neck stiffness and altered consciousness for more than 14 days, 2) above features plus evidence of tuberculosis elsewhere in the body, and 3) on standard antimeningitic drugs for one week without response, were included. Those with contraindications to lumbar puncture, confirmed causes of meningitis (except TB) and on anti-tuberculosis treatment were excluded. METHODS: CSF cell counts, glucose and protein were assayed. CSF was stained on ZN, cultured on LJ and BACTEC and subjected to PCR and LCR for Mycobacterium tuberculosis DNA sequences. Positive tests for M. tuberculosis were classified as definite and the rest as probable TBM. RESULTS: Fifty-eight patients with a mean age of 33.0 years were recruited. Mean CSF cell count was 71/microl and CSF lymphocyte count up 67%. Mean CFS protein and glucose were 2.10 g/l and 2.05 mmol/l, respectively. BACTEC was positive in 20 cases, LJ 12, LCR eight, and PCR and ZN one each. Twenty-six patients had definite and 32 probable TBM. Patients with definite TBM had significantly higher CSF protein, lower CSF glucose, higher CSF cell count and lower CSF lymphocytes. CONCLUSION: TBM can be confirmed in half of clinically suspected cases. More sensitive tests for confirmation of TBM are required.

Effects of symbiosis with Frankia and arbuscular mycorrhizal fungus on the natural abundance of 15N in four species of Casuarina.

The effect of interactions between Casuarina species, Frankia strains and AMF on nitrogen isotope fractionation within the plant were determined under conditions where changes in source nitrogen were minimized by growing plants in mineral nitrogen-deficient conditions and without added organic N. Casuarina cunninghamiana, C. equisetifolia, C. glauca, and C. junghuniana were inoculated singly with three Frankia strains or were dual inoculated with Frankia and Glomus fasciculatum. The %N and delta 15N of separated parts of plants inoculated with the three Frankia strains or with Frankia + Glomus were not significantly different within Casuarina species. However, the slow-growing C. junghuniana differed in several variables from the other three species. There was a highly significant, linear relationship between the natural logarithms of cladode N content and delta 15N of plants of the four Casuarina species when inoculated with Frankia or with Frankia + Glomus, showing that nitrogen supply and the correlated variable, plant growth rate, were major determinants of delta 15N. Provision of small quantities of (NH4)2SO4 or KNO3 increased several-fold the growth of three of the Casuarina species when inoculated with Frankia alone or with Frankia + Glomus. Within species, mycorrhizal and non-mycorrhizal plants receiving supplementary soluble phosphate were of similar dry weights at harvest. delta 15N values for cladodes of C. cunninghamiana, C. equisetifolia and C. glauca were similar, but values for the poor growing C. junghuniana were more variable and, with the exception of plants receiving KNO3, were lower than those of the other three species. Reduced growth due to suboptimal availability of N or P had a major influence on delta 15N and, in these conditions where plants could not access significant amounts of organic N, outweighed any effects on cladode delta 15N of colonization by Glomus. delta 15N values of nodules were higher than other parts of Frankia or Frankia + Glomus inoculated Casuarinas, conceivably due to retention in nodules of fixed N, with delta 15N close to zero.

Efficacy of prophylaxis against thromboembolism with intermittent pneumatic compression after primary and revision total hip arthroplasty.

BACKGROUND: Thromboembolism is a common and important complication after total hip arthroplasty. A variety of pharmacological and mechanical measures have been proposed for prophylaxis. The purpose of the present study was to evaluate the efficacy of intermittent pneumatic compression as prophylaxis against thromboembolism following total hip arthroplasty. METHODS: The prospective study involved a consecutive series of 425 patients in whom a total of 502 (324 primary and 178 revision) total hip arthroplasties had been performed by two surgeons. The patients were managed intraoperatively and postoperatively with use of thigh-high elastic compression stockings and thigh-high intermittent pneumatic compression sleeves. Experienced vascular technologists performed venous duplex ultrasonography on both lower extremities of all patients at a mean of six days (range, two to fifteen days) postoperatively. All patients were followed for at least one year in order to detect late thromboembolism. RESULTS: An asymptomatic deep-vein thrombosis was noted on the scans made after twenty-three (4.6 percent) of the 502 procedures. Nineteen (3.8 percent) of the arthroplasties were followed by the development of a proximal thrombosis and four (0.8 percent), a distal thrombosis. Nineteen of the thromboses were ipsilateral (eighteen were proximal and one, distal), and four were contralateral (one was proximal and three, distal). No symptomatic deep-vein thrombosis developed in the hospital. In addition, three (two proximal and one distal) symptomatic ipsilateral deep-vein thromboses (a prevalence of 0.6 percent) developed three to twenty-three weeks after postoperative scans revealed negative findings and the patients were discharged from the hospital. Three symptomatic pulmonary embolisms (a prevalence of 0.6 percent) were confirmed by ventilation-perfusion scanning while the patients were in the hospital. There were no symptomatic pulmonary embolisms after discharge, and there were no fatal pulmonary embolisms. With the numbers available, we were unable to detect an association between deep-vein thrombosis and age (p = 0.76), gender (p = 0.13), body-mass index (p = 0.12), type of arthroplasty (primary or revision) (p = 0.12), operative approach (p = 0.37), duration of the operation (p = 0.21), type of anesthesia (general or regional) (p = 0.51), units of blood transfused (autologous, p = 0.79; homologous, p = 0.57), blood type (p = 0.18), or the presence of a so-called classic risk factor for the development of thrombosis (p = 0.22). Five arthroplasties (1.0 percent) were followed by the development of a wound hematoma, but only one hematoma necessitated operative drainage. CONCLUSIONS: The use of intraoperative and postoperative thigh-high intermittent pneumatic compression, combined with duplex ultrasonography performed by experienced vascular technologists, is effective for prophylaxis against thromboembolism after both primary and revision total hip arthroplasties. The low prevalence of deep-vein thrombosis (4.6 percent) and symptomatic pulmonary embolism (0.6 percent) is comparable with that associated with pharmacological prophylaxis.

Isolation of the 3-phosphoglycerate kinase gene of the arbuscular mycorrhizal fungus Glomus mosseae (Nicol. & Gerd.) Gerdemann & Trappe.

The 3-phosphoglycerate kinase (PGK) gene of the arbuscular mycorrhizal fungus Glomus mosseae has been isolated by differential RNA display (DD). Experimentally, the technique of DD was utilized to simultaneously compare the mRNA transcript populations from Lycopersicon esculentum root systems colonized by the arbuscular mycorrhizal fungus G. mosseae and non-mycorrhizal plants. A differentially expressed band was isolated and cloned from mycorrhizal tissue. The isolated DD fragment was screened and sequenced. A reverse transcription-PCR (RT-PCR) technique detected transcripts in germinated spores and G. mosseae-colonized root systems but not in uncolonised root systems. The full-length cDNA was isolated by RACE and corresponded to the 3-phosphoglycerate kinase gene of G. mosseae. The cDNA encodes a polypeptide of 416 amino acids, with a predicted molecular weight of 44 764 Da. The PGK proteins shows high homology to those PGKs of other fungi and the phylogenetic relationship among 14 isolated fungal PGK sequences is illustrated.