Potential innovation in Plant research through the use of gene-edited and genetically modified plants iscurrently being hindered by inefficient and costly plant transformation. We show that naturally occurring carbon dots (quasi-spherical, <10nm nanoparticles) can act as a fast vehicle for carrying plasmids into mature plant cells, resulting in transient plant transformation in a number of important crop species with no negative impacts on photosynthesis or growth. We further show that GFP, Cas9, and gRNA introduced into wheat via foliar application (spraying on) of plasmid coated carbon dots are expressed and, in the case of Cas9, make genome edits in SPO11 genes. Therefore, we present a protocol for spray-on gene editing that is simple, inexpensive, fast, transforms in planta, and is applicable to multiple crop species. We believe this technique creates many opportunities for the future of plant transformation in research and shows great promise for plant protein production systems.Recent advances in plant biotech, particularly manipulation of photosynthesis, have shown the ability to obtain huge increases in plant efficiency and yield. For example, the RIPE project 1 obtained up to a 15% increase in biomass 2 and a ∼40% increase in productivity 3 by reducing photoprotection latency times and by avoiding photorespiration. These examples show the true power of GM -not only could these changes increase global food security (a growing issue with our population still increasing 4,5 , and climate change conferring multiple environmental stresses 6-8 ), but since these advances also increase the amount of carbon being fixed, it could have potential for also mitigating climate change 9,10 . This is important because, as noted, the effects of climate change exacerbate food insecurity further.Plant biotechnology can also enhance food security and biomass production by improving crop resistance to herbivores, pests, and environmental stresses. Additionally, GM techniques can enhance the nutritional value of the food produced, as seen with purple tomatoes 11,12 , enhancing the lipid content of oil crops to provide an alternative to dwindling fish oil stocks 13,14 and improving the quality of staple crops such as wheat 15,16 .However, the scope extends beyond edible compounds, as plant biotech is allowing the production of biofuels 17 , and has shown success producing pharmaceuticals 18 , including the efficient and speedy production of vaccines 19 . These advancements have been aided by new fields such as Synthetic biology, and gene editing tools becoming more versatile and useable.However, there is currently a significant bottleneck 20 limiting the potential application of these ideas and advances, and that is the cost, both in time and resources, of current plant transformation methods. All plant transformation must currently utilise either Agrobacterium tumefaciens 21 , biolistics 22 , or regeneration from PEG transformed protoplasts 23 , as a vehicle to introduce DNA, regardless of whether the changes are transient (n...
Iridescence is a taxonomically widespread and striking form of animal coloration, yet despite advances in understanding its mechanism, its function and adaptive value are poorly understood. We test a counterintuitive hypothesis about the function of iridescence: that it can act as camouflage through interference with object recognition. Using an established insect visual model (Bombus terrestris), we demonstrate that both diffraction grating and multilayer iridescence impair shape recognition (although not the more subtle form of diffraction grating seen in some flowers), supporting the idea that both strategies can be effective means of camouflage. We conclude that iridescence produces visual signals that can confuse potential predators, and this might explain the high frequency of iridescence in many animal taxa.
Introduction: The national Venous Thromboembolism (VTE) Prevention Programme in England was launched in 2010 and incorporates standardised guidance on risk assessment (RA) and thromboprophylaxis (TP) with a requirement for root cause analysis of all episodes of hospital associated thrombosis (HAT), defined as any VTE occurring whilst an inpatient or within 90 days of discharge. We previously reported findings of root cause analysis for HAT over 2010 - 2012, demonstrating that achieving a 90% risk assessment rate resulted in a significant reduction in the incidence of HAT. We update our findings on the impact of implementation of the national programme on the incidence of HAT, proportion of potentially preventable HAT episodes, and mortality from hospital-associated pulmonary embolism (PE). As appropriate TP only reduces the risk of VTE by two-thirds, we also looked at risk factors for TP failure. Methods: We examined HAT data collected from the root cause analysis programme at King's College Hospital from April 2011 to March 2015. Further data were gathered through retrospective review of patient notes. VTE risk factors for HAT attributed to TP failure were compared to a "non-HAT" group, (patients who received appropriate TP and did not develop HAT) drawn from VTE prevention audit data from 2013-2014. Episodes of HAT that developed following inadequate prescription or administration of either anticoagulant or mechanical TP were deemed as "potentially preventable" episodes. Results: Across the four-year study period there were 725 episodes of HAT, giving an incidence of 3.28 episodes per 1000 hospital admissions. There was no significant change in incidence from 2011-2015. The median age of the cohort was 64 years (IQR = 27 years). 56.7% (n = 411) of the HAT episodes were deep vein thromboses, of which 54.7% (n = 225) involved the proximal vasculature. PE accounted for 41.7% (n = 302) episodes, of which 10.9% (n = 33) were fatal events. HAT developed following medical, surgical or obstetric admission in 43.3% (n = 314), 54.6% (n = 396) and 2.1% (n = 15) respectively. VTE risk factors were present in 97.9% (n = 710) of patients with HAT with concomitant bleeding risk factors in 37.1% (n = 269). Consistently, the most common outcome of root cause analysis was TP failure (47.6% overall, n = 345) with no significant trend across the study period; 19.7% (n = 143) of episodes were attributed to inadequate anticoagulant TP, 26.1% (n = 189) to contraindication to anticoagulant TP, 4.4% (n = 32) to contraindication to all forms of TP, and 2.2% (n = 16) episodes were unexpected (HAT occurring in a patient without identifiable VTE risk factors). There has been a significant reduction in the proportion of potentially preventable HAT episodes from 38.2% (n = 66) in 2011-2012 to 20.3% (n = 39) in 2014-2015 (p < 0.001). Furthermore, the proportion of fatal PE reduced over the study period from 16.0% (n = 12) of HAT in 2011-2012 to 6.3% (n = 5) of HAT in 2014-2015 (p = 0.049). The audit of VTE prevention practice over 2013/14 included 515 patients, of which 423 (82.1%) received appropriate TP and did not develop HAT. Compared to this group, patients with HAT attributed to TP failure had more risk factors (3.1 vs. 2.7, p < 0.002), were more likely to be over 60 years of age (59.4% vs. 42.3%, p = 0.01), or to have had orthopaedic surgery(6.7% vs. 1.8%, p = 0.001). Discussion: Implementation of a comprehensive VTE prevention programme incorporating root cause analysis of HAT has led to a significant fall in the proportion of HAT that were potentially preventable with a corresponding reduction in mortality attributed to PE. However, there has been no change in the overall incidence of HAT with a rise in cases associated with TP failure. Further research is required to optimise TP in high VTE risk groups. Disclosures Arya: Bayer plc: Research Funding.
There are clearly demonstrated links between unprovoked venous thromboembolism (VTE) and underlying malignancy. Previous studies have shown an incidence between 3 and 13% of subsequent cancer diagnoses in patients with unprovoked VTE. National guidance issued in the United Kingdom, 2012 recommend that all patients with a first unprovoked VTE are investigated for occult malignancy with a thorough history and examination, full blood count, liver function tests, calcium, chest X-ray and urinalysis with directed investigation of any positive findings. Additionally, abdomino-pelvic CT scans (and mammography in women) should be considered for all patients over 40 years with first unprovoked VTE without positive findings on basic investigations. We retrospectively reviewed all patients diagnosed with unprovoked VTE at King's College Hospital between April 2014 and March 2015, and results were followed up to July 2015. We excluded as provoked VTEs all cases associated with trauma, known malignancy, recent surgery or hospitalisation, prolonged immobilisation, long-haul travel, hormonal therapy, intravenous drug use, pregnancy or the puerperium. We examined extent of investigations performed and reviewed the incidence of occult malignancy in those with a first unprovoked VTE. Over the period of study, 544 patients were objectively diagnosed with pulmonary embolism (PE) or deep vein thrombosis (DVT). Of these, 140 cases were unprovoked in nature. 75/140 (53.6%) were male, with a median age of 56 years (range 22-97). All 140 patients had initial clinical assessment and bloods tests. 113 (80.7%) patients also had chest X-ray screening performed. Of the remaining 27 patients, 4 were not followed up in our centre. 75 (53.6%) patients had tumour markers taken, 74 (52.9%) patients had abdominal imaging (of which 61, 82.4% had CT abdomen and pelvis, remainder ultrasound) and 3 women had mammography. Tumour markers were abnormal in 26/75 (34.7%). Abdominal imaging was abnormal in 33/66 (50.0%) patients without a subsequent diagnosis of malignancy, with 18/66 (27.3%) requiring additional investigation to definitively exclude malignancy. 8/136 (5.9%) cases of occult malignancy were identified (see Table for characteristics). The majority of patients found to have occult malignancy were diagnosed at an advanced stage, with high subsequent mortality rates and minimal opportunity for intervention. Our findings compare favourably with the findings of the SOME trial with a low incidence of occult malignancy and questionable value of routine abdomino-pelvic imaging for otherwise asymptomatic patients with first unprovoked VTE. Such screening is likely to incur anxiety for patients, incidental findings and higher costs without demonstrable patient benefit. Abnormal tumour markers were common and non-specific and should not be performed routinely following unprovoked VTE. Targeted investigation for individuals with suggestive clinical features or abnormalities on baseline bloods, chest X-ray or urinalysis should be considered. Table 1. Characteristics of patients identified with occult malignancy, time to cancer diagnosis, staging of cancer, treatment received, and mortality Cancer Age/Gender VTE Abnormal basic screen# Tumour markers Time to cancer diagnosis (days) Stage/treatment Time to death* (days) Endometrial 52F Distal DVT No Not done 131 T1aM0N0 ¨C surgery (TAH + BSO) N/A Endometrial 57F Distal DVT Yes CA125 3383 0 No formal staging, metastatic disease, no treatment 45 Pancreatic 52M Proximal DVT Yes CA125 2832 17 No formal staging, metastatic disease, no treatment 19 Pancreatic 57M PE Yes CA125 583, CEA 96 20 No formal staging, metastatic disease, no treatment 65 Lung 85F PE Yes Not done 85 T3N1M1a ¨C chemotherapy N/A Lung 81M PE Yes Not done 0 T4N3M1b ¨C for palliation only 49 Ovarian 69F PE Yes CA125 1224, CEA 6 0 No formal staging, metastatic disease, no treatment 16 Unknown primary 97F Proximal DVT Yes AFP 29, CEA 626, CA125 316 1 No formal staging, metastatic disease, for palliation 6 #basic screen includes clinical assessment, renal/liver function, calcium, chest X-ray and urinalysis; *from time of VTE diagnosis Disclosures Arya: Bayer plc: Research Funding.
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