Inert coupling of IRDye800CW to monoclonal antibodies for clinical optical imaging of tumor targets

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Genomic Signature-Based Identification of Influenza A Viruses Using RT-PCR/Electro-Spray Ionization Mass Spectrometry (ESI-MS) Technology

BACKGROUND: The emergence and rapid spread of the 2009 H1N1 pandemic influenza A virus (H1N1pdm) in humans highlights the importance of enhancing the capability of existing influenza surveillance systems with tools for rapid identification of emerging and re-emerging viruses. One of the new approaches is the RT-PCR electrospray ionization mass spectrometry (RT-PCR/ESI-MS) technology, which is based on analysis of base composition (BC) of RT-PCR amplicons from influenza "core" genes. Combination of the BC signatures represents a "genomic print" of an influenza A virus. METHODOLOGY/PRINCIPAL FINDINGS: Here, 757 samples collected between 2006 and 2009 were tested, including 302 seasonal H1N1, 171 H3N2, 7 swine triple reassortants, and 277 H1N1pdm viruses. Of the 277 H1N1pdm samples, 209 were clinical specimens (throat, nasal and nasopharyngeal swabs, nasal washes, blood and sputum). BC signatures for the clinical specimen from one of the first cases of the 2009 pandemic, A/California/04/2009, confirmed it as an unusual, previously unrecognized influenza A virus, with "core" genes related to viruses of avian, human and swine origins. Subsequent analysis of additional 276 H1N1pdm samples revealed that they shared the genomic print of A/California/04/2009, which differed from those of North American swine triple reassortant viruses, seasonal H1N1 and H3N2 and other viruses tested. Moreover, this assay allowed distinction between "core" genes of co-circulating groups of seasonal H1N1, such as clades 2B, 2C, and their reassortants with dual antiviral resistance to adamantanes and oseltamivir. CONCLUSIONS/SIGNIFICANCE: The RT-PCR/ESI-MS assay is a broad range influenza identification tool that can be used directly on clinical specimens for rapid and accurate detection of influenza virus genes. The assay differentiates the H1N1pdm from seasonal and other nonhuman hosts viruses. Although not a diagnostic tool, this assay demonstrates its usefulness and robustness in influenza virus surveillance and detection of novel and unusual viruses with previously unseen genomic prints

Multi-objective optimization for optimum tolerance synthesis with process and machine selection using a genetic algorithm

This paper presents a new approach to the tolerance synthesis of the component parts of assemblies by simultaneously optimizing three manufacturing parameters: manufacturing cost, including tolerance cost and quality loss cost; machining time; and machine overhead/idle time cost. A methodology has been developed using the Genetic Algorithm (GA) technique to solve this multi-objective optimization problem. The effectiveness of the proposed methodology has been demonstrated by solving a wheel mounting assembly problem consisting of five components, two subassemblies, two critical dimensions, two functional tolerances, and eight operations. Significant cost saving can be achieved by employing this methodology

Selective targeting of microglia by quantum dots

<p>Abstract</p> <p>Background</p> <p>Microglia, the resident immune cells of the brain, have been implicated in brain injury and various neurological disorders. However, their precise roles in different pathophysiological situations remain enigmatic and may range from detrimental to protective. Targeting the delivery of biologically active compounds to microglia could help elucidate these roles and facilitate the therapeutic modulation of microglial functions in neurological diseases.</p> <p>Methods</p> <p>Here we employ primary cell cultures and stereotaxic injections into mouse brain to investigate the cell type specific localization of semiconductor quantum dots (QDs) in vitro and in vivo. Two potential receptors for QDs are identified using pharmacological inhibitors and neutralizing antibodies.</p> <p>Results</p> <p>In mixed primary cortical cultures, QDs were selectively taken up by microglia; this uptake was decreased by inhibitors of clathrin-dependent endocytosis, implicating the endosomal pathway as the major route of entry for QDs into microglia. Furthermore, inhibiting mannose receptors and macrophage scavenger receptors blocked the uptake of QDs by microglia, indicating that QD uptake occurs through microglia-specific receptor endocytosis. When injected into the brain, QDs were taken up primarily by microglia and with high efficiency. In primary cortical cultures, QDs conjugated to the toxin saporin depleted microglia in mixed primary cortical cultures, protecting neurons in these cultures against amyloid beta-induced neurotoxicity.</p> <p>Conclusions</p> <p>These findings demonstrate that QDs can be used to specifically label and modulate microglia in primary cortical cultures and in brain and may allow for the selective delivery of therapeutic agents to these cells.</p

The dominant Anopheles vectors of human malaria in the Asia-Pacific region: occurrence data, distribution maps and bionomic précis

<p>Abstract</p> <p>Background</p> <p>The final article in a series of three publications examining the global distribution of 41 dominant vector species (DVS) of malaria is presented here. The first publication examined the DVS from the Americas, with the second covering those species present in Africa, Europe and the Middle East. Here we discuss the 19 DVS of the Asian-Pacific region. This region experiences a high diversity of vector species, many occurring sympatrically, which, combined with the occurrence of a high number of species complexes and suspected species complexes, and behavioural plasticity of many of these major vectors, adds a level of entomological complexity not comparable elsewhere globally. To try and untangle the intricacy of the vectors of this region and to increase the effectiveness of vector control interventions, an understanding of the contemporary distribution of each species, combined with a synthesis of the current knowledge of their behaviour and ecology is needed.</p> <p>Results</p> <p>Expert opinion (EO) range maps, created with the most up-to-date expert knowledge of each DVS distribution, were combined with a contemporary database of occurrence data and a suite of open access, environmental and climatic variables. Using the Boosted Regression Tree (BRT) modelling method, distribution maps of each DVS were produced. The occurrence data were abstracted from the formal, published literature, plus other relevant sources, resulting in the collation of DVS occurrence at 10116 locations across 31 countries, of which 8853 were successfully geo-referenced and 7430 were resolved to spatial areas that could be included in the BRT model. A detailed summary of the information on the bionomics of each species and species complex is also presented.</p> <p>Conclusions</p> <p>This article concludes a project aimed to establish the contemporary global distribution of the DVS of malaria. The three articles produced are intended as a detailed reference for scientists continuing research into the aspects of taxonomy, biology and ecology relevant to species-specific vector control. This research is particularly relevant to help unravel the complicated taxonomic status, ecology and epidemiology of the vectors of the Asia-Pacific region. All the occurrence data, predictive maps and EO-shape files generated during the production of these publications will be made available in the public domain. We hope that this will encourage data sharing to improve future iterations of the distribution maps.</p

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Prevention of acute kidney injury and protection of renal function in the intensive care unit

Acute renal failure on the intensive care unit is associated with significant mortality and morbidity. To determine recommendations for the prevention of acute kidney injury (AKI), focusing on the role of potential preventative maneuvers including volume expansion, diuretics, use of inotropes, vasopressors/vasodilators, hormonal interventions, nutrition, and extracorporeal techniques. A systematic search of the literature was performed for studies using these potential protective agents in adult patients at risk for acute renal failure/kidney injury between 1966 and 2009. The following clinical conditions were considered: major surgery, critical illness, sepsis, shock, and use of potentially nephrotoxic drugs and radiocontrast media. Where possible the following endpoints were extracted: creatinine clearance, glomerular filtration rate, increase in serum creatinine, urine output, and markers of tubular injury. Clinical endpoints included the need for renal replacement therapy, length of stay, and mortality. Studies are graded according to the international Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) group system Several measures are recommended, though none carries grade 1A. We recommend prompt resuscitation of the circulation with special attention to providing adequate hydration whilst avoiding high-molecular-weight hydroxy-ethyl starch (HES) preparations, maintaining adequate blood pressure using vasopressors in vasodilatory shock. We suggest using vasopressors in vasodilatory hypotension, specific vasodilators under strict hemodynamic control, sodium bicarbonate for emergency procedures administering contrast media, and periprocedural hemofiltration in severe chronic renal insufficiency undergoing coronary intervention

Appendicitis and appendectomy: a retrospective survey in South Indian population.

Appendectomy is the surgical procedure of removal of appendix. The inflamed or diseased condition of appendix also known as appendicitis is a common occurrence and is a surgical emergency. It commonly occurs due to obstruction of its lumen. The comprehensive information about the trends in the clinical profile of the appendicitis and appendectomy and pattern of its variation with respect to age and gender may help in clinical updates. Hence, this study included a review of case records of all appendectomy patients in a South Indian hospital since the last five years. The data was collected and analysed statistically. A total of 2402 appendectomy operations were found since the last five years (2006-2010). Among them, 1114 cases were males (46%) and 1288 were females (54%).Total number of 1961 (81.6%) cases of appendectomies were performed for the removal of an inflamed appendix and in remaining 441 (18.4%) cases, appendectomy was done along with the other procedures such as hysterectomy, and colectomy. The incidence of appendicitis and appendectomy were higher in females. The survey revealed, higher incidence rate among 16-30 year age group followed by 31-45 and 1-15 years

Not Available

Not AvailableIn vitro rumen methane output (IRMO) of over 200 feed/feed mix samples representing approximately 74 feed types was investigated in a series of completely randomized experiments. The samples comprised dry fodder, grass, tree leaves, cultivated grasses, cereal by-products, cereal grains, oilseed/meals, compound feeds and total mixed rations (TMRs) from the tropical regions. These samples were subjected to three in vitro gas production tests at 39 °C in 100 ml Heberle syringes. The first incubation was conducted with 200 mg dry matter (DM) substrate for 96 h to determine half-time gas production (t 1/2, h) value of each sample. The second and third incubations were carried out simultaneously. The second incubation was done with 200 mg DM substrate until t 1/2 time to determine IRMO and third with 500 mg DM to estimate in vitro dry matter digestibility (IVDMD) of each samples, respectively. The IRMO was expressed as ml/100 mg digestible substrate. Crude protein content (g/kg DM) was lowest in dry fodder samples and highest in oilseed meals, whereas it was similar in local grass and tree leaves. The IVDMD values ranged from 0·48 to 0·87; the lowest digestibility was recorded in tree leaves. The potential gas production (PGP, ml/200 mg DM) ranged from 9·76 to 61·3. The PGP from grasses and compound feeds was similar, whereas it was lowest in tree leaves. The rate constant (mg/h) was maximum in compound feed followed by oilseed meal. The rate constant was similar among other group of feedstuffs. The t 1/2 time ranged from 9·8 to 19·4 h. The highest t 1/2 time was recorded in local grass samples followed by dry fodder and cultivated grasses. However, they were similar among tree leaves, cereal grains, by-products and compound feeds. The methane % in the total gas varied from 9·79 (tree leaves) to 20·2 (local grasses). Among straw, IRMO varied from 3·88 (Zea mays fodder) to 12·0 (Sorghum vulgare) and it was lower in fruit tree leaves than cultivated grasses. Among protein and energy sources, IRMO was higher in cereal by-products as compared with cereal grains, oil meals and compound feed. The IRMO was similar among TMR, irrespective of the composition of the concentrate mixture. Nevertheless, it varied with the amount of concentrate in the TMR. This is the first exhaustive data on IRMO from the tropical region. Because of the substantial amount of dietary gross energy lost in methane, knowledge of the methane output from these feed ingredients will help in formulating low methane emitting diets for ruminants. Incorporation of tropical tree leaves in the diets and feeding TMR are potential strategies to reduce enteric methane emission in ruminants.ICA