An effective non-parametric method for globally clustering genes from expression profiles

Clustering is widely used in bioinformatics to find gene correlation patterns. Although many algorithms have been proposed, these are usually confronted with difficulties in meeting the requirements of both automation and high quality. In this paper, we propose a novel algorithm for clustering genes from their expression profiles. The unique features of the proposed algorithm are twofold: it takes into consideration global, rather than local, gene correlation information in clustering processes; and it incorporates clustering quality measurement into the clustering processes to implement non-parametric, automatic and global optimal gene clustering. The evaluation on simulated and real gene data sets demonstrates the effectiveness of the algorithm. <br /

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Emerging issues and current trends in assistive technology use 2007-1010: practising, assisting and enabling learning for all

Following an earlier review in 2007, a further review of the academic literature relating to the uses of assistive technology (AT) by children and young people was completed, covering the period 2007-2011. As in the earlier review, a tripartite taxonomy: technology uses to train or practise, technology uses to assist learning and technology uses to enable learning, was used in order to structure the findings. The key markers for research in this field and during these three years were user involvement, AT on mobile mainstream devices, the visibility of AT, technology for interaction and collaboration, new and developing interfaces and inclusive design principles. The paper concludes by locating these developments within the broader framework of the Digital Divide

Control of Visceral Leishmaniasis in Latin America—A Systematic Review

Visceral leishmaniasis is a vector-borne disease characterized by fever, spleen and liver enlargement, and low blood cell counts. In the Americas VL is zoonotic, with domestic dogs as main animal reservoirs, and is caused by the intracellular parasite Leishmania infantum (syn. Leishmania chagasi). Humans acquire the infection through the bite of an infected sand fly. The disease is potentially lethal if untreated. VL is reported from Mexico to Argentina, with recent trends showing a rapid spread in Brazil. Control measures directed against the canine reservoir and insect vectors have been unsuccessful, and early detection and treatment of human cases remains as the most important strategy to reduce case fatality. Well-designed studies evaluating diagnosis, treatment, and prevention/control interventions are scarce. The available scientific evidence reasonably supports the use of rapid diagnostic tests for the diagnosis of human disease. Properly designed randomized controlled trials following good clinical practices are needed to inform drug policy. Routine control strategies against the canine reservoirs and insect vectors are based on weak and conflicting evidence, and vector control strategies and vaccine development should constitute research priorities

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

ICAR: endoscopic skull‐base surgery

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Nitrous oxide emissions from in situ deposition of ¹⁵N-labeled ryegrass litter in a pasture soil

During pasture grazing, freshly harvested herbage (litterfall) is dropped onto soils from the mouths of dairy cattle, potentially inducing nitrous oxide (N₂O) emissions. Although the Intergovernmental Panel on Climate Change (IPCC) recommends accounting for N₂O emissions from arable crop residues in national inventories, emissions from the litterfall of grazed pasture systems are not recognized. The objective of this study was to investigate the potential of litterfall to contribute to N₂O emissions in a field study located on a pasture site in Canterbury, New Zealand (43°38.50' S, 172°27.17' E). We applied ¹⁵N-labeled perennial ryegrass (Lolium perenne L.) to the surface of a pastoral soil (Temuka clay loam) and, for up to 139 d thereafter, quantified the contribution of herbage decomposition to N₂O production and soil N dynamics. Litterfall contributed to the ¹⁵N enrichment of soil NO₃-N and N₂O-N pools. After 49 d, ¹⁵N recovery as N₂O equated to 0.93% of the surface-applied litter ¹⁵N, with 38 to 75% of the cumulative N₂O flux occurring within 4 to 10 d of treatment application. Emissions of N₂O likely resulted from ammonification followed by a coupling of nitrification and denitrification during litter decomposition on the soil surface. The emission factor of the litter deposited in situ was 1.2 ± 0.2%, which is not substantially greater than the IPCC default emission factor value of 1% for crop residues. Further in situ studies using different pasture species and litterfall rates are required to understand the microbial processes responsible for litter-induced N₂O emissions

Effect of soil moisture and bovine urine on microbial stress

While many studies have examined the cycling of urinary nutrients, few have focused on the effects ruminant urine might have on the soil microbial community. Urine application can cause microbial communities to become stressed, potentially changing community composition and microbial function with subsequent effects on nutrient dynamics. Identification of the factors that stress microbes may assist in explaining ruminant urine effects on nutrient cycling. In this laboratory study bovine urine, with either a high (15.0 g K⁺ l⁻1) or low (10.4 g K⁺ l⁻1) salt concentration, was added to repacked soil cores maintained at high or low soil moisture contents (70 or 35% water-filled pore space, respectively). Control cores did not receive urine. Microbial stress was measured using phospholipid fatty acid (PLFA) biomarker ratios. Urine addition increased stress as indicated by a decrease in the iso15:0/anteiso15:0 PLFA ratio from >1.35 to <0.95 in both wet and dry soils and by an increase in the 18:1ω9trans/18:1ω9cis PLFA ratio from 1.4 to 1.9 from day 8 onwards in wet soils. Higher stress was indicated by a lower Gram-positive/Gram-negative PLFA ratio in the urine treatments than in the control treatments on day 29 and this may have been a response to the reduction in substrate availability as the experiment progressed. The PLFA biomarkers showed that the salt treatments did not induce stress. Stress induced by urine addition and wet soil treatments was also indicated by principal component analyses and the metabolic quotient for CO₂, respectively. Thus microbial stress was induced by both urine addition and high soil moisture content, but not specifically by increasing the urinary salt concentration