An investigation into aortic calcification and its relevance to short- and long-term outcome following colorectal cancer resection

Cardiovascular disease and colorectal cancer are major causes of death worldwide. The interaction between host and tumour in patients with operable colorectal cancer may be influenced by the presence of cardiovascular disease. Recently, the burden of abdominal aortic calcification has been identified as a potential driver of inferior outcome following abdominal surgery. The present thesis systematically examines the relationship between the degree of aortic calcification and outcome following elective colorectal cancer resection with particular focus on: • Derivation and validation of an objective score reflecting the burden of calcification • The relationship between the degree of aortic calcification, postoperative complications and survival • Response to radiotherapy and tolerance and completion of adjuvant chemotherapy • The degree of tumour hypoxia evident on immunohistochemical staining • Potential mediating factors including the presence of systemic inflammation and comorbidity • The correlation between aortic calcification and dynamic measures of cardiorespiratory fitness • The use of a novel imaging technique for preoperative assessment of mesenteric flow

Vascular calcification and response to neoadjuvant therapy in locally advanced rectal cancer: an exploratory study

Purpose: Patients with locally advanced rectal cancer (LARC) may experience a clinical complete response (cCR) to neoadjuvant chemoradiotherapy (NACRT) and opt for non-operative management. Pathological factors that relate to NACRT response have been well described. Host factors associated with response, however, are poorly defined. Calcification of the aortoiliac (AC) vessels supplying the rectum may influence treatment response. Methods: Patients with LARC having NACRT prior to curative surgery at Glasgow Royal Infirmary (GRI) and St Mark’s hospital (SMH) between 2008 and 2016 were identified. AC was scored on pre-treatment CT imaging. NACRT response was assessed using pathologic complete response (pCR) rates, tumour regression grades (TRGs), the NeoAdjuvant Rectal score and T-/N-downstaging. Associations were assessed using Chi-squared, Mantel–Haenszel and Fisher’s exact tests. Results: Of 231 patients from GRI, 79 (34%) underwent NACRT for LARC. Most were male (58%), aged over 65 (51%) with mid- to upper rectal tumours (56%) and clinical T3/4 (95%), node-positive (77%) disease. pCR occurred in 10 patients (13%). Trends were noted between higher clinical T stage and poor response by Royal College of Pathologist’s TRG (p = 0.021) and tumour height > 5 cm and poor response by Mandard TRG (0.068). In the SMH cohort, 49 of 333 (15%) patients underwent NACRT; 8 (16%) developed a pCR. AC was not associated with NACRT response in either cohort. Conclusions: AC was not associated with NACRT response in this cohort. Larger contemporary cohorts are required to better assess host determinants of NACRT response and develop predictive models to improve patient selection

Deletion at ITPR1 Underlies Ataxia in Mice and Spinocerebellar Ataxia 15 in Humans

We observed a severe autosomal recessive movement disorder in mice used within our laboratory. We pursued a series of experiments to define the genetic lesion underlying this disorder and to identify a cognate disease in humans with mutation at the same locus. Through linkage and sequence analysis we show here that this disorder is caused by a homozygous in-frame 18-bp deletion in Itpr1 (Itpr1Δ18/Δ18), encoding inositol 1,4,5-triphosphate receptor 1. A previously reported spontaneous Itpr1 mutation in mice causes a phenotype identical to that observed here. In both models in-frame deletion within Itpr1 leads to a decrease in the normally high level of Itpr1 expression in cerebellar Purkinje cells. Spinocerebellar ataxia 15 (SCA15), a human autosomal dominant disorder, maps to the genomic region containing ITPR1; however, to date no causal mutations had been identified. Because ataxia is a prominent feature in Itpr1 mutant mice, we performed a series of experiments to test the hypothesis that mutation at ITPR1 may be the cause of SCA15. We show here that heterozygous deletion of the 5′ part of the ITPR1 gene, encompassing exons 1–10, 1–40, and 1–44 in three studied families, underlies SCA15 in humans

Enhanced psychological care in cardiac rehabilitation services for patients with new-onset depression:the CADENCE feasibility study and pilot RCT

BACKGROUND: Around 19% of people screened by UK cardiac rehabilitation programmes report having moderate or severe symptoms of depression. These individuals are at an increased risk of cardiac mortality and morbidity, reduced quality of life and increased use of health resources compared with their non-depressed counterparts. Maximising psychological health is a goal of cardiac rehabilitation, but psychological care is patchy.OBJECTIVE(S): To examine the feasibility and acceptability of embedding enhanced psychological care (EPC) within cardiac rehabilitation, we tested the feasibility of developing/implementing EPC and documented the key uncertainties associated with undertaking a definitive evaluation.DESIGN: A two-stage multimethods study; a feasibility study and a qualitative evaluation, followed by an external pilot cluster randomised controlled trial (RCT) with a nested qualitative study.SETTING: UK comprehensive cardiac rehabilitation teams.PARTICIPANTS: Adults eligible for cardiac rehabilitation following an acute coronary syndrome with new-onset depressive symptoms on initial nurse assessment. Patients who had received treatment for depression in the preceding 6 months were excluded.INTERVENTIONS: The EPC intervention comprised nurse-led mental health-care co-ordination and behavioural activation within cardiac rehabilitation. The comparator was usual cardiac rehabilitation care.MAIN OUTCOME MEASURES: Measures at baseline, and at the 5- (feasibility and pilot) and 8-month follow-ups (pilot only). Process measures related to cardiac team and patient recruitment, and participant retention. Outcomes included depressive symptoms, cardiac mortality and morbidity, anxiety, health-related quality of life and service resource use. Interviews explored participant and nurses' views and experiences.RESULTS: Between September 2014 and May 2015, five nurses from four teams recruited participants into the feasibility study. Of the 203 patients screened, 30 were eligible and nine took part (the target was 20 participants). At interview, participants and nurses gave valuable insights into the EPC intervention design and delivery. Although acceptable, the EPC delivery was challenging for nurses (e.g. the ability to allocate sufficient time within existing workloads) and the intervention was modified accordingly. Between December 2014 and February 2015, 8 out of 20 teams approached agreed to participate in the pilot RCT [five were randomised to the EPC arm and three were randomised to the usual-care (UC) arm]. Of the 614 patients screened, 55 were eligible and 29 took part (the target was 43 participants). At baseline, the trial arms were well matched for sex and ethnicity, although the EPC arm participants were younger, from more deprived areas and had higher depression scores than the UC participants. A total of 27 out of 29 participants were followed up at 5 months. Interviews with 18 participants (12 in the EPC arm and six in the UC arm) and seven nurses who delivered EPC identified that both groups acknowledged the importance of receiving psychological support embedded within routine cardiac rehabilitation. For those experiencing/delivering EPC, the intervention was broadly acceptable, albeit challenging to deliver within existing care.LIMITATIONS: Both the feasibility and the pilot studies encountered significant challenges in recruiting patients, which limited the power of the pilot study analyses.CONCLUSIONS: Cardiac rehabilitation nurses can be trained to deliver EPC. Although valued by both patients and nurses, organisational and workload constraints were significant barriers to implementation in participating teams, suggesting that future research may require a modified approach to intervention delivery within current service arrangements. We obtained important data informing definitive research regarding participant recruitment and retention, and optimal methods of data collection.FUTURE RESEARCH: Consideration should be given to the delivery of EPC by dedicated mental health practitioners, working closely with cardiac rehabilitation services.TRIAL REGISTRATION: Current Controlled Trials ISRCTN34701576.FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 30. See the NIHR Journals Library website for further project information.</p

Crop Updates 2009 - Genetically Modified Crops, Nutrition, Soils, & Others

This session covers fifteen papers from different authors: 1. Performance of Canola Breeders Roundup Ready® canola hybrid CHYB-166 in 2008, Wallace Cowling, Canola Breeders Western Australia Pty Ltd 2. The implications of GM glyphosate resistant lupin, Art Diggle, Caroline Peek, Frank D’Emden, Fiona Evans, Bob French, Rob Grima, Sam Harburg, Abul Hashem,, John Holmes, Jeremy Lemon, Peter Newman, Janet Paterson, Steve Penny,Department of Agriculture and Food, Peter Portmann, Agriconnect 3. Nufarm Roundup Ready® Canola Systems Trials— 2008 Mark Slatter, Research and Development Officer, Victoria, Nufarm (0438 064 845) Angus MacLennan, Business Development Manager, New South Wales, Nufarm (0408 358 024) Cooperators: Monsanto, Nuseed, Pacific Seeds, Pioneer Seeds 4. Roundup Ready® canola—2008 Limited Commercial Release. Getting the system right, Andrew Wells and Mark Slatter, Nufarm Australia Limited (Reprint from 2008 GRDC Cropping Updates with Introductory note) NUTRITION 5. Fertilising in a changing price environment, Bill Bowden1, Wayne Pluske2 and Jeremy Lemon1, 1Department of Agriculture and Food, 2Back Paddock Company 6. Making better fertiliser for Western Australian cropping systems, Wen Chen1 2, Geoff Anderson1, Ross Brennan1and Richard Bell2 1Department of Agriculture and Food, 2School of Environmental Science, Murdoch University 7. The nitrogen fertiliser replacement value of biosolids from wastewater treatment, Hannah Rigby1, Deborah Pritchard1, David Collins1, Katrina Walton2, David Allen2 and Nancy Penney31School of Agriculture and Environment,Curtin University of Technology, Muresk Campus, 2Chemistry Centre of Western Australia 3Water Corporation of Western Australia 8. Fertilising to soil type (usually) pays, Michael Robertson, Bill Bowden and Roger Lawes, CSIRO, Floreat and Department of Agriculture and Food SOILS 9. Management of subsoil acidity and compaction using a combination of lime, deep ripping and controlled traffic, Stephen Davies, Chris Gazey, Breanne Best and David Gartner, Department of Agriculture and Food 10. Optimising gypsum applications through remote sensing and Variable Rate Technology, Frank D’Emden, Department of Agriculture and Food and Quenten Knight,Precision Agronomics Australia 11. Case study of a 17 year agricultural lime trial, Chris Gazey1, Joel Andrew2and Ryan Pearce3 1Department of Agriculture and Food; 2Precision SoilTech; 3ConsultAg 12. Soil organic carbon in WA agricultural soils, FC Hoyle and A Bennett, Department of Agriculture and Food OTHER 13. Is the no-till revolution complete in WA? Frank D’Emden1, Rick Llewellyn2 and Ken Flower3 1Department of Agriculture and Food, 2CSIRO Sustainable Ecosystems, 3University of Western Australia 14. Progression Planning (The Concept), Julian Krieg and Owen Catto, Wheatbelt Men’s Health 15. Is the Department of Agriculture and Food still a primary source of cropping information? Cindy Parsons, Department of Agriculture and Foo

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Post-Operative Functional Outcomes in Early Age Onset Rectal Cancer

Background: Impairment of bowel, urogenital and fertility-related function in patients treated for rectal cancer is common. While the rate of rectal cancer in the young (&lt;50 years) is rising, there is little data on functional outcomes in this group. Methods: The REACCT international collaborative database was reviewed and data on eligible patients analysed. Inclusion criteria comprised patients with a histologically confirmed rectal cancer, &lt;50 years of age at time of diagnosis and with documented follow-up including functional outcomes. Results: A total of 1428 (n=1428) patients met the eligibility criteria and were included in the final analysis. Metastatic disease was present at diagnosis in 13%. Of these, 40% received neoadjuvant therapy and 50% adjuvant chemotherapy. The incidence of post-operative major morbidity was 10%. A defunctioning stoma was placed for 621 patients (43%); 534 of these proceeded to elective restoration of bowel continuity. The median follow-up time was 42 months. Of this cohort, a total of 415 (29%) reported persistent impairment of functional outcomes, the most frequent of which was bowel dysfunction (16%), followed by bladder dysfunction (7%), sexual dysfunction (4.5%) and infertility (1%). Conclusion: A substantial proportion of patients with early-onset rectal cancer who undergo surgery report persistent impairment of functional status. Patients should be involved in the discussion regarding their treatment options and potential impact on quality of life. Functional outcomes should be routinely recorded as part of follow up alongside oncological parameters

Early Diagnosis of HIV Infection in Infants - One Caribbean and Six Sub-Saharan African Countries, 2011-2015.

Pediatric human immunodeficiency virus (HIV) infection remains an important public health issue in resource-limited settings. In 2015, 1.4 million children aged 50% decline. The most common challenges for access to testing for early infant diagnosis included difficulties in specimen transport, long turnaround time between specimen collection and receipt of results, and limitations in supply chain management. Further reductions in HIV mortality in children can be achieved through continued expansion and improvement of services for early infant diagnosis in PEPFAR-supported countries, including initiatives targeted to reach HIV-exposed infants, ensure access to programs for early infant diagnosis of HIV, and facilitate prompt linkage to treatment for children diagnosed with HIV infection

Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking

The potential of the diverse chemistries present in natural products (NP) for biotechnology and medicine remains untapped because NP databases are not searchable with raw data and the NP community has no way to share data other than in published papers. Although mass spectrometry techniques are well-suited to high-throughput characterization of natural products, there is a pressing need for an infrastructure to enable sharing and curation of data. We present Global Natural Products Social molecular networking (GNPS, http://gnps.ucsd.edu), an open-access knowledge base for community wide organization and sharing of raw, processed or identified tandem mass (MS/MS) spectrometry data. In GNPS crowdsourced curation of freely available community-wide reference MS libraries will underpin improved annotations. Data-driven social-networking should facilitate identification of spectra and foster collaborations. We also introduce the concept of ‘living data’ through continuous reanalysis of deposited data