The Roles of Laparoscopic Liver Resection and Hypoxia Inducible Factor in the Pathophysiology of Liver cancer

In the last 20 years laparoscopic liver resection has been increasingly practised. However its role in the treatment of liver cancer remains under scrutiny. I performed a pilot study at a specialist HPB unit assessing the results of the laparoscopic resections of one surgeon and comparing them to the results of matched cases on whom he had performed open resection. The resection technique was radiofrequency assisted resection pioneered in this unit. I also analysed the resected tissue to investigate any differential effect on cell characteristics of the 2 operative techniques. Operative time was significantly longer in laparoscopic cases and time to recurrence of R0 resections significantly shorter. Resected tissue demonstrated significantly higher levels of the hypoxia inducible factor-2 and CD10, a recognised poor prognostic marker in primary colorectal tumours. I hypothesised that livers resected laparoscopically are under a relative hypoxia because of the increased intraabdominal pressure associated with the pneumoperitoneum and tumours cells therefore have a positive selection advantage. In the setting of longer resection times this may compromise the oncological result of the surgery causing earlier recurrence. Using a established model of HIF activation, I showed that poor prognostic marker CD10 may be a function of hypoxia inducible regulation. Certainly I was able to replicate data from cervical squamous epithelia demonstrating that both in benign, dysplastic and malignant tissue, HIF expression corresponded to a reduced cell E-cadherin expression that may allow a more malignant potential. I also analysed the effect of RF ablation on circulating tumour cells in palliative irresectable cancers and in the context of both open and laparoscopic liver resection. This showed only a transient rise in both resectional techniques, (open and lap) that would unlikely count for the differential oncological outcome previously demonstrated in the pilot study. In keeping with current international opinion, further work is required to verify the role of laparoscopic liver resection in liver cancer

Learning Enhancement for Active Student Community Engagement (LEAPSE).

This project explored the potential of public-student engagement to enhance the student experience through active community and public engagement activities. The project evaluates existing models of public engagement activities to build capacity in both the University and communities to gain greater benefit from the potential such co-generative relationships can provide. This project focused on one university with the intention of complementing this primary activity with collecting case study material from a range of contexts. The context for graduate employment is rapidly changing and there is evidence that students derive benefits when their programmes include opportunities for authentic engagement with real-world problems. There is evidence to suggest that communities can benefit from genuine engagement with universities and their staff and students. Over a two-year period at the University of Gloucestershire, the project team worked with academics, students and community groups with the aim that universities and communities can make the most of the relationships and in particular to enhance the students’ experience. This exciting and innovative project worked closely with the National Coordination Centre for Public Engagement to ensure transferability of the project outcomes and to promote outputs from the project. It finds that an estimated 63% students at the University of Gloucestershire are engaged in voluntary work of some kind (63% nationally), of whom, 22% have arranged this through the University or the Student Union (SU) (38 % nationally). Work carried out as part of a project to log voluntary and community engagement across the university involving staff and students has found that approximately 10,000 hours of voluntary work has been carried out in the 2012/13 academic year. The range of work makes understanding and planning this kind of engagement complex. This comprises • Individual self-organised voluntary work, such as brownie or cub scout leadership. • Individual volunteering through a university programme, such as a sports programme working with local teams, or a school mentoring programme (though some of these are paid and therefore not included here). • Individual or team volunteering through Student Union brokerage, such as the SU-run VolunteerShop, campus-based community gardens and an annual tea dance for elderly residents living near the university. • Individual voluntary work within the context of an internship or placement, which may or may not include work for academic credit, such as for a local community project or voluntary organisation, such as the for sports clubs. However, this does not include undergraduate community based research as part of a module that can also account for a considerable contribution of time, effort and expertise

An Intraocular Pressure Polygenic Risk Score Stratifies Multiple Primary Open-Angle Glaucoma Parameters Including Treatment Intensity

Purpose: To examine the combined effects of common genetic variants associated with intraocular pressure (IOP) on primary open-angle glaucoma (POAG) phenotype using a polygenic risk score (PRS) stratification. Design: Cross-sectional study. Participants: For the primary analysis, we examined the glaucoma phenotype of 2154 POAG patients enrolled in the Australian and New Zealand Registry of Advanced Glaucoma, including patients recruited from the United Kingdom. For replication, we examined an independent cohort of 624 early POAG patients. Methods Using IOP genome-wide association study summary statistics, we developed a PRS derived solely from IOP-associated variants and stratified POAG patients into 3 risk tiers. The lowest and highest quintiles of the score were set as the low- and high-risk groups, respectively, and the other quintiles were set as the intermediate risk group. Main Outcome Measures: Clinical glaucoma phenotype including maximum recorded IOP, age at diagnosis, number of family members affected by glaucoma, cup-to-disc ratio, visual field mean deviation, and treatment intensity. Results: A dose–response relationship was found between the IOP PRS and the maximum recorded IOP, with the high genetic risk group having a higher maximum IOP by 1.7 mmHg (standard deviation [SD], 0.62 mmHg) than the low genetic risk group (P = 0.006). Compared with the low genetic risk group, the high genetic risk group had a younger age of diagnosis by 3.7 years (SD, 1.0 years; P < 0.001), more family members affected by 0.46 members (SD, 0.11 members; P < 0.001), and higher rates of incisional surgery (odds ratio, 1.5; 95% confidence interval, 1.1–2.0; P = 0.007). No statistically significant difference was found in mean deviation. We further replicated the maximum IOP, number of family members affected by glaucoma, and treatment intensity (number of medications) results in the early POAG cohort (P ≤ 0.01). Conclusions: The IOP PRS was correlated positively with maximum IOP, disease severity, need for surgery, and number of affected family members. Genes acting via IOP-mediated pathways, when considered in aggregate, have clinically important and reproducible implications for glaucoma patients and their close family members

The recent intellectual structure of geography

An active learning project in an introductory graduate course used multidimensional scaling of the name index in Geography in America at the Dawn of the 21st Century, by Gary Gaile and Cort Willmott, to reveal some features of the discipline\u27s recent intellectual structure relevant to the relationship between human and physical geography. Previous analyses, dating to the 1980s, used citation indices or Association of American Geographers spe- cialty-group rosters to conclude that either the regional or the methods and environmental subdisciplines bridge human and physical geography. The name index has advantages over those databases, and its analysis reveals that the minimal connectivity that occurs between human and physical geography has recently operated more through environmental than through either methods or regional subdisciplines

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Peer reviewedPublisher PD

The Allen Telescope Array Pi GHz Sky Survey I. Survey Description and Static Catalog Results for the Bootes Field

The Pi GHz Sky Survey (PiGSS) is a key project of the Allen Telescope Array. PiGSS is a 3.1 GHz survey of radio continuum emission in the extragalactic sky with an emphasis on synoptic observations that measure the static and time-variable properties of the sky. During the 2.5-year campaign, PiGSS will twice observe ~250,000 radio sources in the 10,000 deg^2 region of the sky with b > 30 deg to an rms sensitivity of ~1 mJy. Additionally, sub-regions of the sky will be observed multiple times to characterize variability on time scales of days to years. We present here observations of a 10 deg^2 region in the Bootes constellation overlapping the NOAO Deep Wide Field Survey field. The PiGSS image was constructed from 75 daily observations distributed over a 4-month period and has an rms flux density between 200 and 250 microJy. This represents a deeper image by a factor of 4 to 8 than we will achieve over the entire 10,000 deg^2. We provide flux densities, source sizes, and spectral indices for the 425 sources detected in the image. We identify ~100$ new flat spectrum radio sources; we project that when completed PiGSS will identify 10^4 flat spectrum sources. We identify one source that is a possible transient radio source. This survey provides new limits on faint radio transients and variables with characteristic durations of months.Comment: Accepted for publication in ApJ; revision submitted with extraneous figure remove

Characterizing the Optical Variability of Bright Blazars: Variability-based Selection of Fermi Active Galactic Nuclei

We investigate the use of optical photometric variability to select and identify blazars in large-scale time-domain surveys, in part to aid in the identification of blazar counterparts to the ∼30% of γ -ray sources in the Fermi 2FGL catalog still lacking reliable associations. Using data from the optical LINEAR asteroid survey, we characterize the optical variability of blazars by fitting a damped random walk model to individual light curves with two main model parameters, the characteristic timescales of variability τ , and driving amplitudes on short timescales σ . Imposing cuts on minimum τ and σ allows for blazar selection with high efficiency E and completeness C. To test the efficacy of this approach, we apply this method to optically variable LINEAR objects that fall within the several arcminute error ellipses of γ -ray sources in the Fermi 2FGL catalog. Despite the extreme stellar contamination at the shallow depth of the LINEAR survey, we are able to recover previously associated optical counterparts to Fermi active galactic nuclei with E ≥ 88% and C = 88% in Fermi 95% confidence error ellipses having semimajor axis r < 8'. We find that the suggested radio counterpart to Fermi source 2FGL J1649.6+5238 has optical variability consistent with other γ -ray blazars and is likely to be the γ -ray source. Our results suggest that the variability of the non-thermal jet emission in blazars is stochastic in nature, with unique variability properties due to the effects of relativistic beaming. After correcting for beaming, we estimate that the characteristic timescale of blazar variability is ∼3 years in the rest frame of the jet, in contrast with the ∼320 day disk flux timescale observed in quasars. The variability-based selection method presented will be useful for blazar identification in time-domain optical surveys and is also a probe of jet physics

The Baryon Oscillation Spectroscopic Survey of SDSS-III

The Baryon Oscillation Spectroscopic Survey (BOSS) is designed to measure the scale of baryon acoustic oscillations (BAO) in the clustering of matter over a larger volume than the combined efforts of all previous spectroscopic surveys of large scale structure. BOSS uses 1.5 million luminous galaxies as faint as i=19.9 over 10,000 square degrees to measure BAO to redshifts z<0.7. Observations of neutral hydrogen in the Lyman alpha forest in more than 150,000 quasar spectra (g<22) will constrain BAO over the redshift range 2.15<z<3.5. Early results from BOSS include the first detection of the large-scale three-dimensional clustering of the Lyman alpha forest and a strong detection from the Data Release 9 data set of the BAO in the clustering of massive galaxies at an effective redshift z = 0.57. We project that BOSS will yield measurements of the angular diameter distance D_A to an accuracy of 1.0% at redshifts z=0.3 and z=0.57 and measurements of H(z) to 1.8% and 1.7% at the same redshifts. Forecasts for Lyman alpha forest constraints predict a measurement of an overall dilation factor that scales the highly degenerate D_A(z) and H^{-1}(z) parameters to an accuracy of 1.9% at z~2.5 when the survey is complete. Here, we provide an overview of the selection of spectroscopic targets, planning of observations, and analysis of data and data quality of BOSS.Comment: 49 pages, 16 figures, accepted by A

Does childhood trauma predict poorer metacognitive abilities in people with first-episode psychosis?

Research suggests that people with first-episode psychosis (FEP) report more childhood traumas and have lower metacognitive abilities than non-clinical controls. Childhood trauma negatively affects metacognitive development in population studies, while the association remains largely unexplored in FEP populations. Metacognition refers to the identification of thoughts and feelings and the formation of complex ideas about oneself and others. This study hypothesized that childhood trauma would be associated with lower metacognitive abilities in people with FEP. In a representative sample of 92 persons with non-affective FEP, we assessed childhood trauma, metacognitive abilities and symptoms of psychosis. We used the Childhood Trauma Questionnaire (CTQ) and the Metacognitive Assessment Scale––Abbreviated which includes Self-reflectivity, Awareness of the Mind of the Other, Decentration and Mastery. Hierarchical regression analyses were performed with metacognitive domains as outcome variables and childhood traumas as independent variables, while controlling for age, gender, first-degree psychiatric illness and negative symptoms. We found few significant associations between the different types of childhood trauma and metacognitive domains, and they suggested childhood trauma are associated with better metacognitive abilities. Study limitations included the cross-sectional design and use of self-report measures. Future studies could preferably be prospective and include different measures of psychopathology and neuropsychology

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management