Proteomic profiling of urinary proteins in renal cancer by surface enhanced laser desorption ionisation (SELDI) and neural-network analysis: Identification of key issues affecting potential clinical utility.

Recent advances in proteomic profiling technologies, such as surface enhanced laser desorption ionization mass spectrometry, have allowed preliminary profiling and identification of tumor markers in biological fluids in several cancer types and establishment of clinically useful diagnostic computational models. There are currently no routinely used circulating tumor markers for renal cancer, which is often detected incidentally and is frequently advanced at the time of presentation with over half of patients having local or distant tumor spread. We have investigated the clinical utility of surface enhanced laser desorption ionization profiling of urine samples in conjunction with neural-network analysis to either detect renal cancer or to identify proteins of potential use as markers, using samples from a total of 218 individuals, and examined critical technical factors affecting the potential utility of this approach. Samples from patients before undergoing nephrectomy for clear cell renal cell carcinoma (RCC; n 48), normal volunteers (n 38), and outpatients attending with benign diseases of the urogenital tract (n 20) were used to successfully train neural-network models based on either presence/absence of peaks or peak intensity values, resulting in sensitivity and specificity values of 98.3–100%. Using an initial “blind” group of samples from 12 patients with RCC, 11 healthy controls, and 9 patients with benign diseases to test the models, sensitivities and specificities of 81.8–83.3% were achieved. The robustness of the approach was subsequently evaluated with a group of 80 samples analyzed “blind” 10 months later, (36 patients with RCC, 31 healthy volunteers, and 13 patients with benign urological conditions). However, sensitivities and specificities declined markedly, ranging from 41.0% to 76.6%. Possible contributing factors including sample stability, changing laser performance, and chip variability were examined, which may be important for the long-term robustness of such approaches, and this study highlights the need for rigorous evaluation of such factors in future studies

Early Results from the Lunar Atmosphere and Dust Environment Explorer (LADEE)

On 6 September, 2013, a near-perfect launch of the first Minotaur V rocket successfully carried NASA's Lunar Atmosphere and Dust Environment Explorer (LADEE) into a high-eccentricity geocentric orbit. After 30 days of phasing, LADEE arrived at the Moon on 6 October, 2013. LADEE's science objectives are twofold: (1) Determine the composition of the lunar atmosphere, investigate processes controlling its distribution and variability, including sources, sinks, and surface interactions; (2) Characterize the lunar exospheric dust environment, measure its spatial and temporal variability, and effects on the lunar atmosphere, if any. After a successful commissioning phase, the three science instruments have made systematic observations of the lunar dust and exospheric environment. These include initial observations of argon, neon and helium exospheres, and their diurnal variations; the lunar micrometeoroid impact ejecta cloud and its variations; spatial and temporal variations of the sodium exosphere; and the search for sunlight extinction caused by dust. LADEE also made observations of the effects of the Chang'e 3 landing on 14 December 2013

Effect of local anaesthetic infiltration on chronic postsurgical pain after total hip and knee replacement:The APEX randomised controlled trials

Total hip replacement (THR) and total knee replacement (TKR) are usually effective at relieving pain; however, 7% to 23% of patients experience chronic postsurgical pain. These trials aimed to investigate the effect of local anaesthetic wound infiltration on pain severity at 12 months after primary THR or TKR for osteoarthritis. Between November 2009 and February 2012, 322 patients listed for THR and 316 listed for TKR were recruited into a single-centre double-blind randomised controlled trial. Participants were randomly assigned (1:1) to receive local anaesthetic infiltration and standard care or standard care alone. Participants and outcomes assessors were masked to group allocation. The primary outcome was pain severity on the WOMAC Pain Scale at 12 months after surgery. Analyses were conducted using intention-to-treat and per-protocol approaches. In the hip trial, patients in the intervention group had significantly less pain at 12 months postoperative than patients in the standard care group (differences in means: 4.74; 95% confidence interval [CI]: 0.95-8.54; P = 0.015), although the difference was not clinically significant. Post hoc analysis found that patients in the intervention group were more likely to have none to moderate pain than severe pain at 12 months than those in the standard care group (odds ratio: 10.19; 95% CI: 2.10-49.55; P = 0.004). In the knee trial, there was no strong evidence that the intervention influenced pain severity at 12 months postoperative (difference in means: 3.83; 95% CI: −0.83 to 8.49; P = 0.107). In conclusion, routine use of infiltration could be beneficial in improving long-term pain relief for some patients after THR

Optical variability properties of high luminosity AGN classes

We present the results of a comparative study of the intra-night optical variability (INOV) characteristics of radio-loud and radio-quiet quasars, which involves a systematic intra-night optical monitoring of seven sets of high luminosity AGNs covering the redshift range {\it z} $\simeq 0.2$ to {\it z} $\simeq 2.2$. The sample, matched in the optical luminosity -- redshift (M$_B$ -- z) plane, consists of seven radio-quiet quasars (RQQs), eight radio lobe-dominated quasars (LDQs), six radio core-dominated quasars (CDQs) and five BL Lac objects (BLs). Systematic CCD observations, aided by a careful data analysis procedure, have allowed us to detect INOV with amplitudes as low as 1%. Present observations cover a total of 113 nights (720 hours) with only a single quasar monitored as continuously as possible on a night. Considering cases of only unambiguous detections of INOV we have estimated duty cycles (DCs) of 17%, 12%, 20% and 72% respectively for RQQs, LDQs, CDQs, and BLs. The low amplitude and low DC of INOV shown by RQQs compared to BLs can be understood in terms of their having optical synchrotron jets which are modestly misdirected from us. From our fairly extensive dataset, no unambiguous general trend of a correlation between the INOV amplitude and the apparent optical brightness of the quasar is noticed.Comment: 36 pages, 14 Figures, due to large size Fig. 5,6,11 and 12 are not included. Intersted people contact to [email protected]. Submitted to Journal of Astrophysics and Astronom

‘It Takes Two Hands to Clap’: How Gaddi Shepherds in the Indian Himalayas Negotiate Access to Grazing

This article examines the effects of state intervention on the workings of informal institutions that coordinate the communal use and management of natural resources. Specifically it focuses on the case of the nomadic Gaddi shepherds and official attempts to regulate their access to grazing pastures in the Indian Himalayas. It is often predicted that the increased presence of the modern state critically undermines locally appropriate and community-based resource management arrangements. Drawing on the work of Pauline Peters and Francis Cleaver, I identify key instances of socially embedded ‘common’ management institutions and explain the evolution of these arrangements through dynamic interactions between individuals, communities and the agents of the state. Through describing the ‘living space’ of Gaddi shepherds across the annual cycle of nomadic migration with their flocks I explore the ways in which they have been able to creatively reinterpret external interventions, and suggest how contemporary arrangements for accessing pasture at different moments of the annual cycle involve complex combinations of the formal and the informal, the ‘traditional’ and the ‘modern’

Human umbilical cord perivascular cells improve human pancreatic islet transplant function by increasing vascularization

Islet transplantation is an efficacious therapy for type 1 diabetes; however, islets from multiple donor pancreata are required, and a gradual attrition in transplant function is seen. Here, we manufactured human umbilical cord perivascular mesenchymal stromal cells (HUCPVCs) to Good Manufacturing Practice (GMP) standards. HUCPVCs showed a stable phenotype while undergoing rapid ex vivo expansion at passage 2 (p2) to passage 4 (p4) and produced proregenerative factors, strongly suppressing T cell responses in the resting state and in response to inflammation. Transplanting an islet equivalent (IEQ):HUCPVC ratio of 1:30 under the kidney capsule in diabetic NSG mice demonstrated the fastest return to normoglycemia by 3 days after transplant: Superior glycemic control was seen at both early (2.7 weeks) and later stages (7, 12, and 16 weeks) versus ratios of 1:0, 1:10, and 1:50, respectively. Syngeneic islet transplantation in immunocompetent mice using the clinically relevant hepatic portal route with a marginal islet mass showed that mice transplanted with an IEQ:HUCPVC ratio of 1:150 had superior glycemic control versus ratios of 1:0, 1:90, and 1:210 up to 6 weeks after transplant. Immunodeficient mice transplanted with human islets (IEQ:HUCPVC ratio of 1:150) exhibited better glycemic control for 7 weeks after transplant versus islet transplant alone, and islets transplanted via the hepatic portal vein in an allogeneic mouse model using a curative islet mass demonstrated delayed rejection of islets when cotransplanted with HUCPVCs (IEQ:HUCPVC ratio of 1:150). The immunosuppressive and proregenerative properties of HUCPVCs demonstrated long-term positive effects on graft function in vivo, indicating that they may improve long-term human islet allotransplantation outcomes

Low-Multiplicity Burst Search At The Sudbury Neutrino Observatory

Results are reported from a search for low-multiplicity neutrino bursts in the Sudbury Neutrino Observatory. Such bursts could indicate the detection of a nearby core-collapse supernova explosion. The data were taken from Phase I (1999 November-2001 May), when the detector was filled with heavy water, and Phase II (2001 July-2003 August), when NaCl was added to the target. The search was a blind analysis in which the potential backgrounds were estimated and analysis cuts were developed to eliminate such backgrounds with 90% confidence before the data were examined. The search maintained a greater than 50% detection probability for standard supernovae occurring at a distance of up to 60 kpc for Phase I and up to 70 kpc for Phase II. No low-multiplicity bursts were observed during the data-taking period.Natural Sciences and Engineering Research Council, CanadaIndustry Canada, CanadaNational Research Council, CanadaNorthern Ontario Heritage Fund, CanadaAtomic Energy of Canada, Ltd., CanadaOntario Power Generation, CanadaHigh Performance Computing Virtual Laboratory, CanadaCanada Foundation for Innovation, CanadaCanada Research Chairs, CanadaDepartment of Energy, USNational Energy Research Scientific Computing Center, USAlfred P. Sloan Foundation, USScience and Technology Facilities Council, UKFundacao para a Ciencia e a Technologia, PortugalAstronom

Type 2 alveolar cells are stem cells in adult lung

Gas exchange in the lung occurs within alveoli, air-filled sacs composed of type 2 and type 1 epithelial cells (AEC2s and AEC1s), capillaries, and various resident mesenchymal cells. Here, we use a combination of in vivo clonal lineage analysis, different injury/repair systems, and in vitro culture of purified cell populations to obtain new information about the contribution of AEC2s to alveolar maintenance and repair. Genetic lineage-tracing experiments showed that surfactant protein C–positive (SFTPC-positive) AEC2s self renew and differentiate over about a year, consistent with the population containing long-term alveolar stem cells. Moreover, if many AEC2s were specifically ablated, high-resolution imaging of intact lungs showed that individual survivors undergo rapid clonal expansion and daughter cell dispersal. Individual lineage-labeled AEC2s placed into 3D culture gave rise to self-renewing “alveolospheres,” which contained both AEC2s and cells expressing multiple AEC1 markers, including HOPX, a new marker for AEC1s. Growth and differentiation of the alveolospheres occurred most readily when cocultured with primary PDGFRα+ lung stromal cells. This population included lipofibroblasts that normally reside close to AEC2s and may therefore contribute to a stem cell niche in the murine lung. Results suggest that a similar dynamic exists between AEC2s and mesenchymal cells in the human lung