Factors affecting the establishment of Leptospermum scoparium J.R. et G. Forst. (manuka) : a thesis presented in partial fulfillment of the requirements for the degree of Master of Agricultural Science at Massey University

L. scoparium is one of New Zealand's most important weeds of unploughable infertile hill country. The plant is an indigenous shrub, characteristic of the early stages of succession to forest in a wide range of habitats (Cockayne, 1928). In the eight years prior to 1959/60 nearly 40,000 acres of unimproved grassland reverted to scrub, fern and second growth each year. L. scoparium is one of the most important components of the scrub, fern and second growth category. By 1959/60 the total area of reverted land in New Zealand was 5.7 million acres of which 3.65 million were in the North Island. (Rigg, 1962). Control of L. scoparium on unploughable hill country has been limited to pulling, cutting, or cutting and burning, depending on stage of growth. Chemical methods and standing burns have generally proved unsuccessful. Most methods are expensive. Levy (1932, 1940, 1946) postulated that establishment of L. scoparium in pasture could be prevented by good farming techniques. Today there is a growing body of practical evidence to support this hypothesis (Suckling, 1959; New Zealand Farmer 83 (42, 43, 45)). This study was carried out to determine what intrinsic factors favour the establishment of L. scoparium, and the quantitative effect of farm management techniques on this process

A model for incorporating a clinically-feasible exercise test in paraplegic annual reviews : a tool for stratified cardiopulmonary stress performance classification and monitoring

To identify and characterize an exercise test for use in routine spinal cord injury clinical review, and (ii) to describe levels of, and factors affecting, cardiopulmonary stress performance during exercise in the chronic paraplegic population in Scotland, UK. Cross-sectional study Queen Elizabeth National Spinal Injuries Unit (Glasgow, Scotland) 48 subjects with chronic paraplegia resulting from spinal cord injury at neurological levels T2-L2 Peak oxygen uptake, peak power output, gas exchange threshold and peak heart rate were determined from an incremental arm-cranking exercise test. Using a general linear model, the effects of gender, high (injury level above T6) versus low paraplegia, time since injury, body mass and age on peak oxygen uptake and peak power output were investigated. All 48 subjects completed the arm-cranking exercise test, which was shown to be practical for fitness screening in paraplegia. Men (n=38) had a peak oxygen uptake of 1.302 +/- 0.326 l.min-1 (mean +/- s.d.) and peak power output of 81.6 +/- 23.2W, which was significantly higher than for women (n=10), at 0.832 +/- 0.277 l.min-1 and 50.1 +/- 27.8 W, respectively. There was large intersubject variability in cardiopulmonary performance during arm-cranking exercise testing, but the overall mean for the Scottish population was lower than reference values from other countries. Arm-cranking exercise tests are feasible in the clinical environment. The motivation for their implementation is threefold: (i) to determine cardiopulmonary stress performance of individual paraplegic patients, (ii) to stratify patients into cardiovascular risk categories, and (iii) to monitor the effects of targeted exercise prescription

Combination immunotherapy induces distinct T-cell repertoire responses when administered to patients with different malignancies.

BackgroundCTLA-4 blockade with ipilimumab is Food and Drug Administration-approved for melanoma as a monotherapy and has been shown to modulate the circulating T-cell repertoire. We have previously reported clinical trials combining CTLA-4 blockade with granulocyte-macrophage colony-stimulating factor (GM-CSF) in metastatic melanoma patients and in metastatic castration resistant prostate cancer (mCRPC) patients. Here, we investigate the effect that cancer type has on circulating T cells in metastatic melanoma and mCRPC patients, treated with ipilimumab and GM-CSF.MethodsWe used next-generation sequencing of T-cell receptors (TCR) to compare the circulating T cells of melanoma and mCRPC patients receiving the same treatment with ipilimumab and GM-CSF by Wilcoxon rank sum test. Flow cytometry was utilized to investigate specific T-cell populations. TCR sequencing results were correlated with each T-cell subpopulation by Spearman's rank correlation coefficient. Of note, 14 metastatic melanoma patients had samples available for TCR sequencing and 21 had samples available for flow cytometry analysis; 37 mCRPC patients had samples available for sequencing of whom 22 have TCR data available at both timepoints; 20 of these patients had samples available for flow cytometry analysis and 16 had data available at both timepoints.ResultsWhile melanoma and mCRPC patients had similar pretreatment circulating T-cell counts, treatment induces greater expansion of circulating T cells in melanoma patients. Metastatic melanoma patients have a higher proportion of clones that increased more than fourfold after the treatment compared with mCRPC patients (18.9% vs 11.0%, p=0.017). Additionally, melanoma patients compared with mCRPC patients had a higher ratio of convergent frequency (1.22 vs 0.60, p=0.012). Decreases in clonality induced by treatment are associated with baseline CD8+ T-cell counts in both patient groups, but are more pronounced in the melanoma patients (r=-0.81, p<0.001 vs r=-0.59, p=0.02).Trial registration numbersNCT00064129; NCT01363206

Network planning case study utilising real-time thermal ratings and computational fluid dynamics

Real-Time Thermal Ratings (RTTR) has a natural synergy with wind generation, since during periods of high local wind speed increased wind farm output coincides with uplifted line ratings. This paper describes a network planning study on a real section of UK distribution network. The study considers a branch of 132kV network connecting several wind farms to the grid. By assessing the local wind conditions in the area surrounding the wind farm and proposed overhead line, the study predicts the increase in energy throughput, and hence accommodated generation, for different routes considered for the overhead line. The locations of thermal bottlenecks in the proposed routes are identified. The study shows that a wind farm of 140MW can be connected to a conductor which could only support 90MW based on its static rating, and if the route is chosen correctly only 1% of the energy yield will be constrained

Risk score predicts high-grade prostate cancer in DNA-methylation positive, histopathologically negative biopsies.

BACKGROUND: Prostate cancer (PCa) diagnosis is challenging because efforts for effective, timely treatment of men with significant cancer typically result in over-diagnosis and repeat biopsies. The presence or absence of epigenetic aberrations, more specifically DNA-methylation of GSTP1, RASSF1, and APC in histopathologically negative prostate core biopsies has resulted in an increased negative predictive value (NPV) of ∼90% and thus could lead to a reduction of unnecessary repeat biopsies. Here, it is investigated whether, in methylation-positive men, DNA-methylation intensities could help to identify those men harboring high-grade (Gleason score ≥7) PCa, resulting in an improved positive predictive value. METHODS: Two cohorts, consisting of men with histopathologically negative index biopsies, followed by a positive or negative repeat biopsy, were combined. EpiScore, a methylation intensity algorithm was developed in methylation-positive men, using area under the curve of the receiver operating characteristic as metric for performance. Next, a risk score was developed combining EpiScore with traditional clinical risk factors to further improve the identification of high-grade (Gleason Score ≥7) cancer. RESULTS: Compared to other risk factors, detection of DNA-methylation in histopathologically negative biopsies was the most significant and important predictor of high-grade cancer, resulting in a NPV of 96%. In methylation-positive men, EpiScore was significantly higher for those with high-grade cancer detected upon repeat biopsy, compared to those with either no or low-grade cancer. The risk score resulted in further improvement of patient risk stratification and was a significantly better predictor compared to currently used metrics as PSA and the prostate cancer prevention trial (PCPT) risk calculator (RC). A decision curve analysis indicated strong clinical utility for the risk score as decision-making tool for repeat biopsy. CONCLUSIONS: Low DNA-methylation levels in PCa-negative biopsies led to a NPV of 96% for high-grade cancer. The risk score, comprising DNA-methylation intensity and traditional clinical risk factors, improved the identification of men with high-grade cancer, with a maximum avoidance of unnecessary repeat biopsies. This risk score resulted in better patient risk stratification and significantly outperformed current risk prediction models such as PCPTRC and PSA. The risk score could help to identify patients with histopathologically negative biopsies harboring high-grade PCa. Prostate 76:1078-1087, 2016. © 2016 The Authors. The Prostate Published by Wiley Periodicals, Inc.MDxHealthThis is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Wiley

A core outcome set for localised prostate cancer effectiveness trials

Objective: To develop a core outcome set (COS) applicable for effectiveness trials of all interventions for localised prostate cancer. Background: Many treatments exist for localised prostate cancer, although it is unclear which offers the optimal therapeutic ratio. This is confounded by inconsistencies in the selection, definition, measurement and reporting of outcomes in clinical trials. Subjects and methods: A list of 79 outcomes was derived from a systematic review of published localised prostate cancer effectiveness studies and semi-structured interviews with 15 prostate cancer patients. A two-stage consensus process involving 118 patients and 56 international healthcare professionals (HCPs) (cancer specialist nurses, urological surgeons and oncologists) was undertaken, consisting of a three-round Delphi survey followed by a face-to-face consensus panel meeting of 13 HCPs and 8 patients. Results: The final COS included 19 outcomes. Twelve apply to all interventions: death from prostate cancer, death from any cause, local disease recurrence, distant disease recurrence/metastases, disease progression, need for salvage therapy, overall quality of life, stress urinary incontinence, urinary function, bowel function, faecal incontinence, sexual function. Seven were intervention-specific: perioperative deaths (surgery), positive surgical margin (surgery), thromboembolic disease (surgery), bothersome or symptomatic urethral or anastomotic stricture (surgery), need for curative treatment (active surveillance), treatment failure (ablative therapy), and side effects of hormonal therapy (hormone therapy). The UK-centric participants may limit the generalisability to other countries, but trialists should reason why the COS would not be applicable. The default position should not be that a COS developed in one country will automatically not be applicable elsewhere. Conclusion: We have established a COS for trials of effectiveness in localised prostate cancer, applicable across all interventions which should be measured in all localised prostate cancer effectiveness trials

Disease and Healing in Ancient Societies: Dental Calculus Residues and Skeletal Pathology Data Indicate Age and Sex-Biased Medicinal Practices among Native Californians

The health of humans is intricately linked to the substances - both food and non-dietary items -we ingest. Adverse health outcomes related to smoking of products like tobacco and other psychoactive substances are clearly established in modern populations but are less well understood for ancient communities. Grasping these dynamics is further complicated by the curative, religious, and medicinal context of many of these substances, which have often been commodified, refined, and altered in recent history. As part of a larger collaboration with the Muwekma Ohlone Tribe dedicated to understanding medicinal plant use among native Californians, we present a summary of new metabolomic data from three Middle and Late-period ancestral heritage Ohlone sites: Thámien Rúmmeytak (CA-SCL-128), ’Ayttakiš ’Éete Hiramwiš Trépam-tak (CA-ALA-677/H/H), and Sii Tuupentak (CA-ALA-565/H/H). Using a UPLC-MS platform, we analyze chemical residues from 95 human dental calculus samples from 50 burials. Employing multivariate statistics, we co-analyzed demographic and skeletal pathology data with chemical residue profiles. We considered skeletal markers for a series of oral and postcranial health conditions. Results indicate sex and age biases in consumption patterns. Periodontitis stands out as the most significant local factor for changes in the oral metabolome. However, while chemical markers of oral diseases may be related to pathogen activity, associations between residues and postcranial conditions such as osteoarthritis suggest traditional curative practices and the ingestion of medicinal substances. Hence, our study yields new insights into the broader context of illness and healing in the past

Anomalous Purcell decay of strongly driven inhomogeneous emitters coupled to a cavity

We perform resonant fluorescence lifetime measurements on a nanocavity-coupled erbium ensemble as a function of cavity-laser detuning and pump power. Our measurements reveal an anomalous suppression of the ensemble decay lifetime at zero cavity detuning and high pump fluence. We capture qualitative aspects of this decay rate suppression using a Tavis-Cummings model of non-interacting spins coupled to a common cavity.Comment: 4 figure

Metaphor in organizational research: Context, modalities and implications for research introduction

We provide a general overview of previous work which has explored the use of metaphors in organizational research. Differences in focus and form of research on metaphors are noted. Work in organization theory (OT) and organizational communication (OC) generally features prescriptive metaphors that aid the practice of theorizing and research; research in organizational development (OD) tends to use metaphors for intervention in individual and group decision-making; while studies of organizational behaviour (OB) emphasize the metaphors-in-use within individuals' sensemaking accounts of critical events within their organization. Alongside these differences in focus, the form of metaphor analysis also differs across these contexts, ranging from text- and discourse-based analysis to the analysis of non-linguistic modalities such as pictorial signs, gestures and artefacts. Based on our overview of previous work, we call for greater attention to methodological issues around metaphor identification and analysis and outline a number of directions for further research