LRRK2 G2019S and I2020T mutations are not common in Alzheimer's disease and vascular dementia.
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Aged↗
Biomedical subjects
G Ho
Publications and source records attributed to G Ho.
Solutions to a combined problem of excessive hydrogen sulfide in biogas and struvite scaling.
The Woodman Point Wastewater Treatment Plant (WWTP) in Western Australia has experienced two separate problems causing avoidable maintenance costs: the build-up of massive struvite (MgNH4PO4. 6H2O) scaling downstream of the anaerobic digester and the formation of hydrogen sulfide (H2S) levels in the digester gas to levels that compromised gas engine operation and caused high operating costs on the gas scrubber. As both problems hang together with a chemical imbalance in the anaerobic digester, we decided to investigate whether both problems could be (feasibly and economically) addressed by a common solution (such as dosing of iron solutions to precipitate both sulfide and phosphate), or by using separate approaches. Laboratory results showed that, the hydrogen sulfide emission in digesters could be effectively and economically controlled by the addition of iron dosing. Slightly higher than the theoretical value of 1.5 mol of FeCl3 was required to precipitate 1 mol of dissolved sulfide inside the digester. Due to the high concentration of PO4(3-) in the digested sludge liquor, significantly higher iron is required for struvite precipitation. Iron dosing did not appear an economic solution for struvite control via iron phosphate formation. By taking advantage of the natural tendency of struvite formation in the digester liquid, it is possible to reduce the risk of struvite precipitation in and around the sludge-dewatering centrifuge by increasing the pH to precipitate struvite out before passing through the centrifuge. However, as the Mg2+/PO4(3-) molar ratio in digested sludge was low, by increasing the pH alone (using NaOH) the precipitation of PO4(3-) was limited by the amount of cations (Ca2+ and Mg2+) available in the sludge. Although this would reduce struvite precipitation in the centrifuge, it could not significantly reduce PO4(3-) recycling back to the plant. For long-term operation, maximum PO4(3-) reduction should be the ultimate aim to minimise PO4(3-) accumulation in the plant. Magnesium hydroxide liquid (MHL) was found to be the most cost-effective chemical to achieve this goal. It enhanced struvite precipitation from both, digested sludge and centrate to the point where more than 95% PO4(3-) reduction in the digested sludge was achieved.
Bacteria, Anaerobic↗
Technology for sustainability: the role of onsite, small and community scale technology.
An overview of available onsite, small and community scale wastewater treatment technology shows that it is diverse compared to current technology for centralised collection and treatment of wastewater. An analysis of the onsite, small and community scale technology for achieving sustainability shows that it more conducive to achieving sustainability than the centralised technology. It is likely, however, that its application is in remote and rural areas, where the technology should be improved and integrated with other technology sectors (energy, food production) for improved sustainability. Opportunities exist in new urban developments to achieve similar outcomes, but concerted efforts are required to demonstrate or showcase sustainability benefits in real situations. A huge potential also exists for the use of onsite, small and community scale technology in developing countries for achieving the same sustainability outcomes. It is likely to succeed if the technology is modified to be of lower cost but based on the same science, and that research, development and demonstrations in developed countries are shown to be successful.
Conservation of Natural Resources↗
Emerging approaches to integrated urban water management: cluster scale application.
Integrated Urban Water Management (IUWM) seeks to extend Water Sensitive Urban Design to a total water cycle approach that includes reuse of wastewaters. This paper investigates the appropriateness of environmental technologies for application at a cluster scale in IUWM. Many environmental technologies are economically or physically unsuited to use on a municipal or unit scale. Cluster scale is a middle ground that will allow such environmental technologies to achieve full potential. The concept of cluster scale and the application of environmental technologies at this scale are discussed along with some examples of suitable technologies.
Cities↗
Small scale sanitation technologies.
Small scale systems can improve the sustainability of sanitation systems as they more easily close the water and nutrient loops. They also provide alternate solutions to centrally managed large scale infrastructures. Appropriate sanitation provision can improve the lives of people with inadequate sanitation through health benefits, reuse products as well as reduce ecological impacts. In the literature there seems to be no compilation of a wide range of available onsite sanitation systems around the world that encompasses black and greywater treatment plus stand-alone dry and urine separation toilet systems. Seventy technologies have been identified and classified according to the different waste source streams. Sub-classification based on major treatment methods included aerobic digestion, composting and vermicomposting, anaerobic digestion, sand/soil/peat filtration and constructed wetlands. Potential users or suppliers of sanitation systems can choose from wide range of technologies available and examine the different treatment principles used in the technologies. Sanitation systems need to be selected according to the local social, economic and environmental conditions and should aim to be sustainable.
Biodegradation, Environmental↗
Subsurface flow reedbeds using alternative media for the treatment of domestic greywater in Monteverde, Costa Rica, Central America.
This paper describes the performance of reedbeds using plastic (PET) bottle segments as an alternative low-cost media for the treatment of domestic greywater in Monteverde, Costa Rica, Central America. Twelve reedbeds consisting of four sets of triplicates were monitored through wet and dry seasons in order to determine the effect of media type (PET versus crushed rock) and the effect of plants. In both seasons, performance of the planted reedbeds with PET media, for BOD and fecal coliform removal, was either comparable to, or better than, that of the crushed rock systems. The planted PET reedbeds achieved fecal coliform removal rates > 99.9% in all cases equating to reductions of between 3 and nearly 5 log, with an average BOD outflow of 12.9 mg/L over both seasons. The hydraulic loading rate varied between 1.33 and 2.67 cm/day and hydraulic retention times (HRT) ranged from 3.5 to 7.5 days. The six reedbeds planted with Coix lacryma-jobi proved to be significantly more effective in pathogen removal and BOD reduction than the unplanted reedbeds. The planted PET reedbeds also increased their biomass by twice that of the planted crushed rock reedbeds during the study period. The majority of this increase was shown to be due to root growth. This paper discusses the implications of the above results for developing countries and identifies potential areas for further research.
Biomass↗
Hydrogen sulphide production tests and the detection of groundwater faecal contamination by septic seepage.
The 'H2S test' is being advanced for microbiological water quality testing where conventional coliform based methods are impractical or too expensive. It involves ambient temperature incubation of water samples with nutrient formulated to generate hydrogen sulphide when 'faecal' bacteria are present. Recently a WHO review identified several concerns including the limited number of comparative studies, formulation variability, and false positives and negatives. In response we have compared the H2S test's ability to detect and quantify faecal contamination in an aquifer impacted by septic tank leachfields with measurements obtained concurrently using conventional bacterial indicators, coliphages, faecal sterol biomarkers, Cryptosporidium and Giardia. Like these other analytes, H2S testing detected a contamination gradient ranging from high (septic liquid) to moderate (exfiltration zones), to background (e.g. domestic bores), corresponding to indicator removal + dilution by factors > 10(6). Presence/absence tests could not distinguish between heavily and slightly contaminated waters, whereas multi-tube testing (e.g. 10 x 10 mL arrays) did. It was concluded that while the WHO review concerns are justified, the H2S test performance shows promise in sanitary survey work, can be improved by employing an mpn approach and has potential to aid in the protection of source water and identifying contaminated groundwater.
Environmental Monitoring↗
A multicenter, randomized, placebo controlled, multiple-dose, safety and pharmacokinetic study of AIT-082 (Neotrofin) in mild Alzheimer's disease patients.
A phase 1, randomized, double-blind, placebo-controlled, dose escalation study of the purine derivative, AIT-082 (Neotrofin, NeoTherapeutics) was conducted in mild Alzheimer's disease (AD) patients to evaluate multiple-dose safety, tolerability, and pharmacokinetics. Possible short-term effects of AIT-082 on cognition and memory were preliminarily investigated. AIT-082 is currently being developed as a potential treatment for Alzheimer's disease and other neurological disorders. Pre-clinical studies indicate that AIT-082 has memory enhancing properties, stimulates neuritogenesis and the production of neurotrophic factors. Patients received an oral dose of AIT-082 or placebo daily for one week. Thirty-six AD patients were divided into three dose cohorts; each dose cohort consisted of twelve patients with 8 patients randomized to AIT-082 and 4 to placebo. The 3 doses of AIT-082 evaluated in this study were 100 mg/day, 500 mg/day, and 2,000 mg/day. There were no serious adverse events at any dose and the drug was well tolerated without significant side effects. AIT-082 was orally and rapidly absorbed, resulting in peak serum concentrations within 2 hours with an elimination half-life of approximately 20 hours. Higher doses resulted in corresponding increases in peak concentrations and areas under the curve (AUC). There was an approximate 2-fold accumulation in AIT-082 with daily dosing (as reflected by the AUC) at steady state. There were no significant differences by treatment arm on the clinical or neuropsychological evaluations. AIT-082 was rapidly absorbed by the oral route with a half-life suitable for dosing once or twice daily. No problems with tolerability or safety were found. AIT-082 appears suitable for testing in larger clinical trials for the treatment of AD and other neurologic disorders.
Administration, Oral↗
Adoptive cellular immunotherapy for non-small cell lung cancer: a pilot study.
BACKGROUND: Priming with autologous tumor vaccine followed by ex vivo expansion of activated T cells is a feasible experimental strategy. This paper describes the application of this cellular therapy to treat patients with late-stage non-small-cell lung cancer (NSCLC). METHODS: Twenty-one patients with Stages III and IV NSCLC were treated. Tumor samples were obtained surgically (five patients) or by using aco-axial biopsy needle (16 patients). Each course of vaccination consisted of irradiated tumor cells, mixed with GM-CSF and injected intradermally on Day 1, followed by GM-CSF only on Days 2- 5. The course was repeated 10-14 days later. Lymphocytes were collected 10-14 day after the second course and ex vivo expanded using IL-2 and anti-CD3 Ab. The expansion products were then re-infused into the patients. RESULTS: Twelve out of 16 biopsies resulted in optimal cell numbers for vaccine preparation. Nineteen out of 21 patients achieved a delayed type hypersensitivity (DTH response after two courses of vaccination. In 18/21 patients, the ex vivo expansion products contained > 1.6 x 10(10) cells. Subset analysis showed 77.0-97.2% T cells with a CD4:CD8 ratio of 0.65-4.0; natural killer cells were 2.0-18.6%. There were no significant toxicities. The median survival of all 21 patients was 18.6 months, with a 1-year survival of 51.6%. CONCLUSION: Autologous tumor cell-vaccination may be combined with ex vivo expansion of lymphocytes as adoptive cellular immunotherapy for advanced NSCLC. Overall survival in this cohort of poor prognosis patients compared favorably with results reported in the literature.
Carcinoma, Non-Small-Cell Lung↗
Small water and wastewater systems: pathways to sustainable development?
Globally we are faced with billions of people without access to safe water and adequate sanitation. These are generally located in developing communities. Even in developed communities the current large scale systems for supplying water, collecting wastewater and treating it are not environmentally sustainable, because it is difficult to close the cycle of water and nutrients. This paper discusses the advantages of small scale water and wastewater systems in overcoming the difficulties in providing water and wastewater systems in developing communities and in achieving sustainability in both developed and developing communities. Particular attention is given to technology and technology choice, even though technology alone does not provide the complete answer. Disadvantages of small scale systems and how they may be overcome are discussed.
Conservation of Natural Resources↗
Co-treatment of septage in a municipal sewage treatment pond system.
This paper deals with the characteristics and treatment options of septage. The objective of the paper is to evaluate the effects of co-treatment of 50 MLD of septage in a sewage treatment pond system. The treatment efficiency of the pond system for BOD5 and Fecal Coliform (FC) has been estimated using a first order kinetics model. The model has predicted that the treatment pond system has a maximum capacity of 8.5 MLD and will have a reserve of 28.3% of its total capacity even after the proposed addition of 50 MLD of septage. Separation of oil and grease from septage prior to discharge into the pond system is recommended.
Oxygen↗
Increased metallothionein in mouse liver, kidneys, and duodenum during lactation.
Lactation-induced increases in cadmium absorption and retention have been demonstrated in mid-lactating mice, but no systematic measurements of endogenous metal-binding protein concentrations during lactation have been reported. Using Cd/hemoglobin radioassay, this study detected significant increases in metallothionein (MT) concentrations in liver (4-fold), kidneys (2-fold), and duodenum (2-fold), but not jejunum, of mouse dams on days 13 and 20 of lactation. These increases occurred in the absence of cadmium exposure and were specific to the lactation period; dams 5 days after weaning showed MT levels that were similar to those of nonpregnant (NP) mice. Similarly, Northern blot analyses of livers from lactating mice demonstrated that MT mRNA concentrations in maternal liver during mid-lactation were 6-fold higher than those observed 5 days after pups were weaned. Gel filtration of final supernatants from the Cd/hemoglobin assay confirmed that the Cd-binding molecule induced during lactation was indeed metallothionein. In addition, chromatographic analyses of cytosols from tissues taken from dams administered small amounts of Cd (66 ng/mouse) showed that the trace amounts of Cd absorbed through the maternal gastrointestinal tract during mid-lactation were also bound to the MT. These results indicate MT induction in mouse dams occurs as a physiological consequence of lactation, requiring no external stimulus. This induced MT participates in binding low levels of dietary cadmium consumed by the dam. During lactation, elevated maternal MT may affect pathways for essential trace metals as well as sequester toxic metals harmful to the neonate. Multiparous humans may have increased risk of accumulating environmental Cd.
Animals↗
Bacterial arthritis.
The septic arthritis literature of 2000 revisited several topics previously examined in some detail. These include septic arthritis in rheumatoid arthritis, rheumatic manifestations of bacterial endocarditis, and infectious complications of prosthetic joints. The trend in antibiotic prophylaxis to prevent late infections in total joint replacement is to narrow the targeted hosts to those most at risk, to define the procedures associated with the greatest risk of bacteremia, and to simplify the antibiotic regimen. The diagnoses of septic arthritis of the lumbar facet joint and septic arthritis caused by direct inoculation of bacteria by a foreign object penetrating the joint are facilitated by noninvasive imaging technologies. Septic arthritis caused by uncommon microorganisms and septic arthritis in immunocompromised hosts are other noteworthy topics in this year's literature.
Arthritis, Infectious↗
Computer-assisted transurethral laser resection of the prostate (CALRP): theoretical and experimental motion plan.
Computer-Assisted transurethral laser resection of the prostate (CALRP) is a treatment modality that was designed and developed based on an integrated system of computer, robotics and laser technology in association with a minimally invasive surgery known as laser transurethral resection of the prostate (LRP). CALRP possesses complementary capabilities that could remedy many of the problems faced by surgeons in conventional LRP by delivering a treatment with repeatability and reliability. The work deals primarily in determining the feasibility study of the computer-assisted lasing motion plan (planned motion sequence controlled by a program) for LRP. A theoretical motion plan that analyzes numerically the lasing motion of the fiber was designed by calculating the profile removal rate and in vitro experiments conducted on human cadaveric prostate to verify and validate the designed motion plan. The novel motion plan, which was executed experimentally using the LaserTrode lightguide, accomplished the objective of resecting the enlarged prostate with the aid of computer and robotics technology.
Cadaver↗
Experimental study of transurethral robotic laser resection of the prostate using the LaserTrode lightguide.
A longer operating time and steeper learning curve in mastering the techniques for transurethral laser resection of the prostate are the main problems faced by surgeons in addition to the existing ones in standard transurethral resection of the prostate (TURP). However, these disadvantages can be alleviated with the introduction of a treatment procedure designed and developed based on an integrated system of computer, robotics and laser technology. In vitro experiments were carried out to determine variables affecting the vaporization and coagulation lesions, in order to study the effectiveness and feasibility of robotics for this procedure. Human cadaveric prostates and fresh tauted chicken breast tissues were irradiated with different parameters using the LaserTrode lightguide in contact with the tissue. The effects of irrigant flow rate, fiber/tissue angle of inclination, number of passes, direction, speed and power of lase on the volume of tissue vaporized and coagulated, were assessed. The final phase of the experiments includes executing the robotic motion plan for the laser resection procedure on the human cadaveric prostate tissue embedded in an anatomically alike prostate phantom. It was concluded from our study that power and speed of lase are the most significant parameters influencing the volume of the vaporized and coagulated lesion. Comparison of removal rate using the new treatment procedure of robotic laser resection of the prostate with TURP and HoLRP evinced equivalent results.
Animals↗
SCH-202676: An allosteric modulator of both agonist and antagonist binding to G protein-coupled receptors.
A novel thiadiazole compound, SCH-202676 (N-(2,3-diphenyl-1,2, 4-thiadiazol-5-(2H)-ylidene)methanamine), has been identified as an inhibitor of both agonist and antagonist binding to G protein-coupled receptors (GPCRs). SCH-202676 inhibited radioligand binding to a number of structurally distinct, heterologously expressed GPCRs, including the human mu-, delta-, and kappa-opioid, alpha- and beta-adrenergic, muscarinic M1 and M2, and dopaminergic D1 and D2 receptors, but not to the tyrosine kinase epidermal growth factor receptor. SCH-202676 had no direct effect on G protein activity as assessed by [35S]guanosine-5'-O-(gamma-thio)triphosphate binding to purified recombinant G(oalpha)- or G(betagamma)-stimulated ADP-ribosylation of G(oalpha) by pertussis toxin. In addition, SCH-202676 inhibited antagonist binding to the beta2-adrenergic receptor expressed in Escherichia coli, a system devoid of classical heterotrimeric G proteins. SCH-202676 inhibited radiolabeled agonist and antagonist binding to the alpha2a-adrenergic receptor with an IC50 value of 0.5 microM, decreased the Bmax value of the binding sites with a slight increase in the KD value, and inhibited agonist-induced activation of the receptor. The effects of SCH-202676 were reversible. Incubation of plasma membranes with 10 microM SCH-202676 did not alter subsequent radioligand binding to the alpha2a-adrenergic receptor and the dopaminergic D1 receptor. Taken together, our data suggest that SCH-202676 has the unique ability to allosterically regulate agonist and antagonist binding to GPCRs in a manner that is both selective and reversible. The scope of the data presented suggests this occurs by direct interaction with a structural motif common to a large number of GPCRs or by activation/inhibition of an unidentified accessory protein that regulates GPCR function.
Adrenergic Agents↗
Visual search for traffic signs: the effects of clutter, luminance, and aging.
Latency and eye movement measures were used to examine the effects of aging, clutter, and luminance on visual search for traffic signs embedded in digitized images of driving scenes. Initially 14 older and 14 younger observers classified daytime and nighttime traffic scenes as containing low or high amounts of clutter. Next, an independent sample of 14 younger and 14 older participants searched for traffic signs contained within these scenes. Errors were more common among the elderly. Search efficiency declined with increased clutter and with aging. However, relative to the young, older adults did not suffer disproportionately as a result of increased clutter. The methods developed might be profitably employed to assess sign conspicuity and sign acquisition during driving.
Accidents, Traffic↗
Evapotranspiration for domestic wastewater reuse in remote indigenous communities of Australia.
In the past sewage ponding in indigenous settlements was commonplace as a result of overcrowding combined with inappropriate septic tank and leach drain design, installation and operation. The response over the past 10 years has been to develop reticulated sewerage systems to lagoons when the funds become available. These are often successful in terms of operation, improved public health and low maintenance but are expensive and wasteful of limited water supplies. Evapotranspiration (ET) is an effective method for on-site domestic effluent disposal in areas of Western Australia with soils of low permeability. Evapotranspiration systems have been established in a number of communities both for research/demonstration and as specified by architects. The systems usually follow two septic tanks for the disposal of all domestic effluent. A case study will be presented for a remote indigenous community where the ET systems installed for greywater only have been monitored over the last two years since installation. The use of evapotranspiration has enabled reuse of effluent for successful examples of revegetation and food production and points to the need for a holistic approach to design and service delivery in these communities that includes a total environmental management plan.
Conservation of Natural Resources↗