Generalized Query-Based Active Learning to Identify Differentially Methylated Regions in DNA

Active learning is a supervised learning technique that reduces the number of examples required for building a successful classifier, because it can choose the data it learns from. This technique holds promise for many biological domains in which classified examples are expensive and time-consuming to obtain. Most traditional active learning methods ask very specific queries to the Oracle (e.g., a human expert) to label an unlabeled example. The example may consist of numerous features, many of which are irrelevant. Removing such features will create a shorter query with only relevant features, and it will be easier for the Oracle to answer. We propose a generalized query-based active learning (GQAL) approach that constructs generalized queries based on multiple instances. By constructing appropriately generalized queries, we can achieve higher accuracy compared to traditional active learning methods. We apply our active learning method to find differentially DNA methylated regions (DMRs). DMRs are DNA locations in the genome that are known to be involved in tissue differentiation, epigenetic regulation, and disease. We also apply our method on 13 other data sets and show that our method is better than another popular active learning technique

Submission of Written Evidence to the All Party Parliamentary Group Inquiry into the Use of Armed Drones: Drone Strikes, Legal Reasoning and the Need for Transparency

As researchers involved in studying the specific ways in which drone strikes are conducted in real-time, in this submission we suggest there are two areas where the APPG might conclude much greater information is needed on the use of armed drones. First, more information is needed on the role that legal considerations actually play in decisions around targeting in the context of drone strikes. Legal frameworks do not interpret themselves and it is important, therefore, to investigate how they are being interpreted as part of the work of conducting drone operations. Second, in order to properly understand how legal frameworks are being interpreted during missions, much more information is needed on the operational context than is currently publicly available. In the case of the UK’s drone operations, there is a great deal that simply is not known. Greater disclosure in both of the above areas – i.e., in relation to interpretations of legality in combat situations and the wider operational context such interpretations are undertaken within – would enhance accountability and transparency around those operations and begin to address concerns around the secrecy and erosion of democratic oversight that have been raised with respect to them. At a minimum, this would require the release of all data relating to at least a sample of successful and unsuccessful strikes including audio, video, imagery, digital communications and available intelligence alongside much more extensive information about the operational infrastructures including legal governance arrangements that those drone strikes were enabled by. If the UK’s drone programme is to become more publicly accountable, we believe these are areas the Inquiry should treat as priorities

How Low Can We Go?: Comparing Long-term Oncologic Outcomes for APR and LAR in Very Low Rectal Cancer

Management of very low rectal cancer is one of the most challenging issues faced by colorectal surgeons. For tumors in the mid and upper rectum, procedures can be done to resect the cancer while maintaining continence, a major determinant of post-operative quality of life. In the low rectum, however, to optimize oncologic outcomes, many surgeons feel compelled to pursue abdominoperineal (APR) over low anterior resection (LAR), a sphincter-preserving procedure. It was hypothesized that after robust adjustment, procedure choice will not be associated with a difference in disease-free survival in the resection of tumors in the low rectum. To analyze this, the US Rectal Cancer Collaborative Database, a comprehensive, multi-center dataset obtained from six institutions between 2010 and 2016, was queried. Patients undergoing TME resection for Stage I-III very low rectal cancers (involvement) were selected for this study. Patients were categorized by procedure- LAR vs APR. Primary outcome was five-year disease-free survival. Secondary outcomes included overall survival, recurrence, length of stay, and complications. An adjusted analysis was performed to account for all known potential confounders. 431 patients with very low rectal cancer treated by either APR or LAR were identified. 154 (35.7%) underwent APR. The overall recurrence rate was 19.6%. Median follow-up time was 42.5 months. An analysis adjusted for age, gender, BMI, ASA class, and pathologic stage observed no difference in disease free survival between operative types (HR=0.90, 95% CI [0.53-1.52], p=0.70). Similarly, secondary outcomes demonstrated no significant difference between operation types, including length of stay (Beta: 0.04, Std. error = 0.25, p = 0.54), overall survival (HR=1.29, 95% CI [0.71-2.32], p=0.39), or complications (OR = 1.53, 95% CI [0.94 - 2.50], p=0.09). In this analysis, no significant difference in disease-free survival or overall survival was observed between patients undergoing APR or LAR for very low rectal cancer. This comprehensive study supports the treatment of very low rectal cancer, less than 5cm from the anorectal ring with no sphincter involvement, by either abdominal perineal or low anterior resection. Further studies may focus on patient-reported and quality of life outcomes which may influence decision-making

FEL research and development at STFC Daresbury laboratory

In this paper we present an overview of current and proposed FEL developments at STFC Daresbury Laboratory in the UK. We discuss progress on the ALICE IR-FEL since first lasing in October 2010, covering the optimisation of the FEL performance, progress on the demonstration of a single shot cross correlation experiment and the results obtained so far with a Scanning Near-Field Optical Microscopy beamline. We discuss a proposal for a 250 MeV single pass FEL test facility named CLARA to be built at Daresbury and dedicated to research for future light source applications. Finally we present a brief overview of other recent research highlights

Screening for Alcoholism Among Medical Inpatients: How Important Is Corroboration of Patient Self-Report?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65580/1/j.1530-0277.1998.tb03925.x.pd

Highly phosphorescent perfect green emitting iridium(III) complex for application in OLEDs

A novel iridium complex, [bis-(2-phenylpyridine)(2-carboxy-4-dimethylaminopyridine)iridium(III)] (N984), was synthesized and characterized using spectroscopic and electrochemical methods; a solution processable OLED device incorporating the N984 complex displays electroluminescence spectra with a narrow bandwidth of 70 nm at half of its intensity, with colour coordinates of x = 0.322; y = 0.529 that are very close to those suggested by the PAL standard for a green emitter.Bolink, Henk, [email protected] ; Coronado Miralles, Eugenio, [email protected] ; Garcia Santamaria, Sonsoles Amor, [email protected]

Prevalence, characteristics, and impacts of work-related musculoskeletal disorders: a survey among physical therapists in the State of Kuwait

<p>Abstract</p> <p>Background</p> <p>Physical therapists working in the State of Kuwait are at risk of work-related musculoskeletal disorders (WMSDs). However, prevalence rates and risk factors are not well documented. The objective of this study was to determine the prevalence, characteristics, and impacts of WMSDs among physical therapists in the State of Kuwait.</p> <p>Methods</p> <p>A self-administered questionnaire was distributed to 350 physical therapists. The questionnaire gathered demographic data as well as information on occurrence of musculoskeletal complaints in the previous 12 months. Descriptive statistics, frequency, and Chi-square analyses were used.</p> <p>Results</p> <p>The response rate to the questionnaire was 63% (222/350). Of the 212 responders included in the study, the one-year prevalence of WMSDs was 47.6%, with lower back complaints as the most common (32%). This was followed by neck (21%), upper back (19%), shoulder (13%), hand/wrist (11%), knee (11%), ankle/foot (6%), elbow (4%), and hip/thigh (3%) complaints. The frequency of WMSDs was not gender related (except lower back, neck, and shoulder complaints) nor was it related to age (except lower back complaints), working venues (except hand/wrist), working hours, area of specialty, or exercise. WMSDs' impact on work was minor.</p> <p>Conclusions</p> <p>WMSDs among physical therapists in Kuwait were common, with lower back and neck affected most. Lower back and neck WMSDs were related to the participant's demographics. Hand/wrist WMSDs were related to work settings. Further research is needed to investigate the effect of risk factors as physical load, psychosocial load, and general health status on prevalence musculoskeletal disorders.</p

Formation of the Food Vacuole in Plasmodium falciparum: A Potential Role for the 19 kDa Fragment of Merozoite Surface Protein 1 (MSP119)

Plasmodium falciparum Merozoite Surface Protein 1 (MSP1) is synthesized during schizogony as a 195-kDa precursor that is processed into four fragments on the parasite surface. Following a second proteolytic cleavage during merozoite invasion of the red blood cell, most of the protein is shed from the surface except for the C-terminal 19-kDa fragment (MSP119), which is still attached to the merozoite via its GPI-anchor. We have examined the fate of MSP119 during the parasite's subsequent intracellular development using immunochemical analysis of metabolically labeled MSP119, fluorescence imaging, and immuno-electronmicroscopy. Our data show that MSP119 remains intact and persists to the end of the intracellular cycle. This protein is the first marker for the biogenesis of the food vacuole; it is rapidly endocytosed into small vacuoles in the ring stage, which coalesce to form the single food vacuole containing hemozoin, and persists into the discarded residual body. The food vacuole is marked by the presence of both MSP119 and the chloroquine resistance transporter (CRT) as components of the vacuolar membrane. Newly synthesized MSP1 is excluded from the vacuole. This behavior indicates that MSP119 does not simply follow a classical lysosome-like clearance pathway, instead, it may play a significant role in the biogenesis and function of the food vacuole throughout the intra-erythrocytic phase

Body Size Evolution in Extant Oryzomyini Rodents: Cope's Rule or Miniaturization?

At the macroevolutionary level, one of the first and most important hypotheses that proposes an evolutionary tendency in the evolution of body sizes is “Cope's rule". This rule has considerable empirical support in the fossil record and predicts that the size of species within a lineage increases over evolutionary time. Nevertheless, there is also a large amount of evidence indicating the opposite pattern of miniaturization over evolutionary time. A recent analysis using a single phylogenetic tree approach and a Bayesian based model of evolution found no evidence for Cope's rule in extant mammal species. Here we utilize a likelihood-based phylogenetic method, to test the evolutionary trend in body size, which considers phylogenetic uncertainty, to discern between Cope's rule and miniaturization, using extant Oryzomyini rodents as a study model. We evaluated body size trends using two principal predictions: (a) phylogenetically related species are more similar in their body size, than expected by chance; (b) body size increased (Cope's rule)/decreased (miniaturization) over time. Consequently the distribution of forces and/or constraints that affect the tendency are homogenous and generate this directional process from a small/large sized ancestor. Results showed that body size in the Oryzomyini tribe evolved according to phylogenetic relationships, with a positive trend, from a small sized ancestor. Our results support that the high diversity and specialization currently observed in the Oryzomyini tribe is a consequence of the evolutionary trend of increased body size, following and supporting Cope's rule