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In recent decades, anthropogenic greenhouse gas emissions have led to heatwaves becoming significantly more intense, many of which resulting in substantial impacts on human health. In 2009, the state of Victoria, Australia, experienced several days of maximum temperatures soaring 12-15°C above the climatological mean and a considerable rise in excess heat-related human mortality. We attempt to directly quantify the heat-related human fatalities of the 2009 heatwave attributable to anthropogenic climate change.For our analysis, we focus on changes in return values of the heat-related death toll. Furthermore, we use a combination of two types of modeling tools. The first is a collection of large initial-condition ensembles of atmosphere-only model simulations from the weather@home/ANZ and C20C+ D&A projects as well as large initial-condition ensembles of simulations from models taking part in the Coupled Model Intercomparison Project Phase 6. For the attribution assessment we compare factual model outcomes from year-2009 era periods from historical simulations to counterfactual outcomes. The second modeling tool is an empirical function linking heat-related human deaths to exceedance of temperature percentile thresholds. This function categorizes heatwave days based on three consecutive percentile windows starting at the 95th, 97.5th, and the 99th percentile, respectively.The climate-mortality model combinations show considerable agreement with most models attributing approximately one third of excess heat-related deaths during conditions comparable to the 2009 Victoria heatwave to anthropogenic climate change. Our analysis indicates that without substantial climate change mitigation and adaptation efforts, to reduce exposure and vulnerability, further increases in heat-related mortality risk are to be expected., The 28th IUGG General Assembly (IUGG2023) (Berlin 2023)

Primary and other natural forest loss and degradation continue to increase, especially in the tropics,1–3 despite increasing recognition of the importance and significant value of the carbon and multiple other benefits provided by forests, and especially primary forests.4,5 Effective protection and management of forests at a landscape level are key activities within global efforts to address the climate emergency and the biodiversity crisis.

It has regularly been stated that consumer demand for CSR is larger than ever, but do consumers really want to be informed about the ethical behaviour of brands? Does digital media have an impact on meaningful CSR communication? A research analysing consumer reaction to social media posts about CSR is limited. Using mixed method, this study examined the UK consumer attitudes towards CSR and its communication in digital media plus its consequent effect on purchasing intentions. Results indicate that consumers are more likely to evaluate a brand higher if made aware of CSR activity, which in turn affects purchase intention. Consumers have fairly positive attitudes about CSR communicated on digital media, but may react negatively if the message contradicts prior behaviour of the brand. Overall, the study show support for the communication of digital media but brands looking to enhance a damaged reputation must take great consideration over the message at hand.

To demonstrate that the use of 3D/4D HDLive increases the image quality in the diagnosis of benign cystic ovarian teratomas.3D/HDLive ultrasound (US) was used in 31 cases of suspected ovarian cystic teratoma using vaginal 2D US. The following pathognomonic images of mature cystic teratomas were considered for diagnosis: 1) a cystic, unilocular lesion with a densely echogenic tubercle (Rokitansky nodule); 2) a diffuse or partially echogenic mass usually demonstrating sound attenuation; 3) fluid-fluid/fat-fluid levels; 4) dermoid mesh with hyperechogenic calcifications indicating the presence of bone, teeth, or other ectodermally-derived structure; 5) multiple mobile spherical structures (fat globules).Dermoids present a wide spectrum of images depending on the predominant tissue type. In the vast majority of cases there are dense echogenic structures that correspond to complex masses of fatty tissue, sebum, hair, epithelial remnants, along with cartilage or bone. If we catalogue all the images together, the pathognomonic of dermoid are: 1) cystic or solid cystic lesions with a Rokitansky nodule, with bone, teeth or cartilage (six cases, 22.2%); 2) a solid mass with or without attenuation that corresponds with pure sebum (five cases, 18.5%); 3) a diffuse mass with fine bands that correspond with hair inside sebum (four cases, 12.9%) and that may form meshes or plugs corresponding with a mixture of fat, sebum, and hair (three cases, 11.5%).HDLive U.S. provides some images of exceptional quality that enhance the definition of the structures of these tumors (fat, hair, cartilage, bone, etc.) compared to 2D/3D/4D.

Aim To describe the clinical and radiological features of four new families with a childhood presentation of COL4A1 mutation. Method We retrospectively reviewed the clinical presentation. Investigations included radiological findings and COL4A1 mutation analysis of the four cases. Affected family members were identified. COL4A1 mutation analysis was performed in all index cases and, where possible, in affected family members. Results The three male and one female index cases presented with recurrent childhood-onset stroke, infantile hemiplegia/spastic quadriplegia, and infantile spasms. Additional features such as congenital cataracts and anterior segment dysgenesis were present. Microcephaly and developmental delay/learning difficulties were present in three cases. Three cases had one or more family member affected in multiple generations, with a total of 11 such individuals identified. The clinical features showed a wide intrafamilial variation. Magnetic resonance imaging (MRI) showed bilateral white matter change in all cases, except in one mutation-positive family member. Unilateral or bilateral porencephaly was present in cases with infantile hemiplegia, and a diagnosis of clinical stroke was supported by the presence of intracerebral haemorrhage. The age at diagnosis was between 1year and 6years for the children with presentation in infancy and 12months after stroke in a 14-year-old male. Three new pathogenic mutations were identified in the COL4A1 gene. Interpretation COL4A1 mutations can present in children with infantile hemiplegia/quadriplegia, stroke or epilepsy, and a motor disorder. The presence of eye features and white matter change on MRI in childhood can help point towards the diagnosis. Once the diagnosis is made, a careful search can identify affected family members. © The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.

Transvaginal three-dimensional (3-D) and color Doppler ultrasound were used to establish a first-trimester definitive diagnosis and classification of thoracoomphalopagus conjoined twins following two-dimensional (2-D) transabdominal and transvaginal scans that indicated twin gestation of uncertain classification. Color Doppler in combination with 3-D ultrasound can be a useful complement to 2-D ultrasound to confirm early diagnosis and determine the extent of organ sharing and definitive classification of conjoined twins.

Subchorionic placental cysts are ominous findings. When attached near the umbilical cord insertion, the risk of umbilical cord constriction is increased. This may cause fetal growth retardation and intrauterine asphyxia. This article reports a case of subchorionic placental cyst diagnosed in the first trimester by transvaginal ultrasound. Color Doppler ultrasound demonstrated a reduction of the umbilical cord bloodstream as the cyst increased in size. Fetal growth retardation was evident in the third trimester.

Color Doppler sonography offers the opportunity to evaluate the umbilical cord and to study blood velocity wave forms within the cord. Funic (cord) presentation can be diagnosed unequivocally with color Doppler sonography. Because funic presentation is likely to be the harbinger of cord prolapse, the morbidity and mortality associated with cord prolapse can be prevented if funic presentation is diagnosed before membrane rupture. This article describes the first case in the obstetric literature of funic presentation diagnosed with color Doppler sonography. The potential complications associated with cord prolapse were avoided with a cesarean section.

Pregnant patients with symptomatic and asymptomatic urinary tract infections were treated with a long and a short antibiotic regimen. Two hundred two patients were randomized prospectively to a single oral dose of 3.5 g ampicillin plus 1 g probenecid (98 patients) versus 500 mg ampicillin orally four times a day for 10 days (104 patients). The multiple-dose cure rate was statistically significantly better than that of the single-dose regimen (67.3% versus 57.1%, respectively). Interestingly, for resistant organisms, the cure rate for the long and short regimens was similar (48% versus 43%, respectively). In vitro susceptibility testing does not appear to be a good predictor of cure, at least for the single-dose group. Single-dose therapy with ampicillin and probenecid does not provide an optimal cure rate or prevent reinfection during pregnancy. Possible reasons for these findings are discussed.

Paracetamol disposition following a single oral 1 g dose of the drug was compared in groups (n = 12) of healthy young adult male Caucasians and Chinese. There was no difference between the groups in terms of paracetamol oral clearance, elimination half-life, or partial metabolic (glucuronidation, sulphation, oxidation) and renal clearances. The results demonstrate that drug glucuronidation is not universally impaired in Chinese and, together with previously published data, that paracetamol glucuronidation is minimally affected by race.

Tactile acuity, body schema and motor control and clinical outcome measures – A comparison study of adults with chronic low back pain and matched controls Chronic low back pain (CLBP) is common, often lacks discernible aetiology and contributes to morbidity and low quality of life. Treatments often focus on pain relief and improving motor function but outcomes remain moderate and many experience ongoing pain. In Complex Regional Pain Syndrome and Phantom Limb Pain, the cortical neurophysiology and specific sensory outputs are altered. Interventions to reverse these impairments coincide with a reduction in pain intensity. Sharing similar neurophysiological characteristics, it’s plausible that similar approaches may improve CLBP outcomes so identification of similar features in this group is needed. We conducted a systematic review regarding the questions: Are two-point discrimination threshold (TPDT) and body schema (BS) altered in adults with CLBP and do they relate to impaired lumbopelvic motor control (LMC)? This review initiated stage two; data collection to investigate TPDT, BS, LMC, back-perception, disability, kinesiophobia and clinical outcome measures in adults with CLBP and matched controls. Following a systematic review to guide our study, we aimed to identify differences in tactile acuity, body schema, lumbopelvic motor function and association with clinical outcome measures when measured in adults with chronic low back pain and matched controls. Using a systematic search strategy, a literature search of 12 bibliographic databases, grey literature, Google Scholar and the reference lists of included articles was undertaken over 5 months to Feb 2016. Studies involving adults aged 18 or older with CLBP longer than 3 months duration were included. Pregnancy, 6 months post-partum, central neurological conditions and nerve root pathologies were exclusion criteria. Two independent reviewers’ assessed for quality using an adapted Downs and Black Quality Index Score. Studies of high (≥70%) or medium (60-69%) quality involving adults with CLBP ≥3 month’s duration were included. Varied research designs led to a narrative data synthesis. In stage two, data collection was undertaken in two matched groups (CLBP and control) using established measures of TPDT and tactile threshold on the low back and finger-tip of dominant hand, low back laterality discrimination, lumbopelvic motor control and outcome measures such as disability, kinesiophobia, back-perception and pain. The review identified 335 studies. Following inclusion and exclusion screening, nine met the selection criteria and were included in the data extraction process. Assessment revealed similar quality strengths with eight of high and one of medium quality. Only one reported power. Sample sizes ranged from six to 51 with a total of 398 participants. All included male and female participants with a mean age of 44.2 years. The studies utilised different techniques and populations to explore tactile discrimination, body schema and motor function but critically; none explored all three. Stage two data collection has been completed in 62 adults (31 per group) and data analysis is underway. Preliminary results reveal significant between group differences for TPDT, disability, kinesiophobia, back-perception and motor-function. Lateral discrimination and associations have yet to be analysed and results will be presented in the final poster as; a) differences between groups and b) relationships to outcome measures. Our systematic review revealed TPDT to be altered in those with CLBP and is related to altered LMC. Body schema tasks may also be altered but the evidence is limited. The relationship between BS and LMC remains unknown and the relationships to other clinical measures are unclear. Data analysis is underway and some of our results correspond with the systematic review (TPDT, LMC) but others do not (BS). Association analysis continue and further results and conclusions will be presented on the poster once complete.

In Europe and the UK, grass pollen is the single most important outdoor aeroallergen; 27% of the population are sensitised to grass pollen. Grass pollen allergy has been linked to increased risk of allergic asthma exacerbations, which can lead to hospitalisation and fatalities. Sensitivity towards grass pollen varies between species, of which there are over 150 in the UK. However, due to few unique morphological features, grass pollen from different species cannot be discriminated using traditional observational methods. Currently, there is no way of detecting, modelling or forecasting the aerial-dispersion of pollen from the biodiversity of UK grasses. Consequently, grasses are coalesced into a single group in the UK forecast. PollerGEN is an interdisciplinary NERC project with the aim of revolutionising the way that pollen dispersion is measured and forecast, with concomitant synergies for understanding the ecology of aerial dispersed pollen. In collaboration with the UK Met Office, a key goal is to build a more accurate forecast of individual grass pollen species. Using environmental genomics, we will identify which species of grass pollen are present during the summer months across 16 specific collection sites in the UK, and measure the abundance of the different allergenic species of grass. The information will be used to model the spatial and temporal deposition of different species of grass pollen and identify linkages to human health. The project therefore aims to provide a paradigm shift in our understanding of the ecology of windborne pollen in time and space and inform the public about the timing and environmental factors that put them at risk of exposure to pollen they are allergic to; a key strategy in the prevention of allergy and asthma attacks.

A recent analysis of blindness and vision impairment trends over the past 30 years by the Vision Loss Expert Group for the Global Burden of Disease Study revealed that glaucoma remains the leading cause of irreversible blindness worldwide in an ageing population. The mechanisms underlying retinal ganglion cell degeneration in glaucoma are not fully understood. This thesis examines two key features of glaucomatous neurodegeneration, namely impairment of optic nerve axonal transport and dysregulation of aqueous outflow. First we demonstrate the continued need to develop new diagnostic and therapeutic approaches for glaucoma by assessing rates of glaucoma progression in the local Cambridge population. We show there is still a clear rate of progression despite tertiary level access to the best treatments currently available. We describe a new non-invasive tool to assess and quantify the dysregulation of aqueous outflow. Despite being a key therapeutic target in current clinical practice, our understanding of this system is derived largely from post-mortem studies, indirect estimates or, more recently, invasive techniques that alter the physiology of aqueous outflow and are limited in the information they provide. There are currently no non-invasive techniques available that directly visualise detailed aqueous outflow in vivo. We use a non-invasive imaging modality developed to image the anterior microcirculation of the human eye – haemoglobin video imaging – to examine aqueous outflow into the episcleral venous circulation in detail, and to observe and quantify alterations in aqueous outflow following treatments that aim to selectively target this pathway. We then evaluate a combined receptor-ligand gene therapy onstruct which overexpresses brain derived neurotrophic factor and its receptor tropomyosin kinase B on optic nerve axonal transport and retinal ganglion cell function. We use a rat glaucoma model and a humanised tauopathy model of reduced axonal transport and showed combined overexpression is more effective in stimulating axonal transport than either receptor administration or ligand administration alone. We also demonstrate functional recovery in the glaucoma model. Furthermore, we offer promising evidence there may be an improvement in short term memory loss in the tauopathy model, suggesting that this strategy to target intrinsic mechanisms to improve neuronal function and facilitate repair may be relevant to multiple neurodegenerative diseases. We then assess whether manipulating the degenerative process could also be associated with optic nerve regeneration in experimental glaucoma. We demonstrate for the first time the glaucomatous optic nerve also has the potential to regenerate using strategies previously only used after traumatic injury.

Ganglion cell death in glaucoma is caused by a variety of insults that include ischemia, insufficient neurotrophic support and oxidative stress. Experimental studies were therefore conducted on cell cultures to determine how serum deprivation (to mimic insufficient neurotrophic support) or oxidative glutamate toxicity (GB), cause oxidative stress and induce retinal cell death. Moreover, studies were carried out to deduce whether selected sulphur containing compounds can blunt any negative influences to cells in culture and/or a defined ischaemic insult to the rat retina in situ, as this might suggest their use for the treatment of glaucoma. Serum deprivation and GB caused generation of reactive oxygen species (ROS) and apoptosis-like death to transformed retinal ganglion cells (RGC-5 cells). RGC-5 cells were more susceptible to the detrimental effects of GB than serum deprivation. RGC-5 cells subjected to serum deprivation appear to die by mechanisms that resemble classical apoptosis more closely than that caused by GB and the phase between the maximal generation of ROS and cell death were different. Cell death caused by serum deprivation was caspase-dependent but this was not the case for GB. Moreover, of the two sulphur compounds sulbutiamine and N-acetyl cysteine (NAC), sulbutiamine blunts the effect of serum deprivation more effectively. In addition, the pan caspase inhibitor z-VAD-fmk attenuated the negative effect of serum deprivation to RGC-5 cells while the necroptosis inhibitor (necrostsatin-1) counteracted solely the insult of GB. The sulphur containing compounds, ACS1 and ACS 67 which release hydrogen sulphide (H2S) slowly and NAC (a pro-cysteine GSH precursor) attenuated GB-induced cell death of RGC-5 cells. In contrast, sulbutiamine (a lipophilic thiolic thiamine derivative) was particularly effective in protecting RGC-5 cells from an insult of serum deprivation. Moreover, all of the sulphur compounds directly sequestered different types of ROS but with varying efficiency. Common features by which all tested sulphur containing agents seem to elicit a mode of action include the stimulation of GSH and the antioxidant enzyme glutathione-S-transferase (GST) as well as to scavenge excess free radicals. Moreover, the slow release of H2S from the ACS compounds appears to protect cells from oxidative stress through increasing the level of GSH, modulation of the cystine uptake transporter xCT, stimulation of the oxidative stress related transcription factor Nrf2 and the stimulation of pro-survival signalling pathways. The slow releasing H2S sulphur compound ACS67 also counteracts a number of detrimental influences to the rat retina in situ because of ischemia/reperfusion that includes damage to their ganglion cells. This suggests that such sulphur compounds might find a use in the treatment of glaucoma where ischemia probably plays a part in the disease process.

The general aim of the thesis was to deduce whether selected naturally occurring flavonoids (genistein, epicatechin gallate (EC), epigallocatechin gallate (EGCG), baicalin) attenuate various secondary insults that may cause death of ganglion cells in primary open angle glaucoma (POAG). An ischemic insult to the rat retina significantly causes the inner retina to degenerate indexed by changes of various antigens, proteins and mRNAs located to amacrine and ganglion cells. These changes are blunted in animals treated with genistein as has been shown for ECGC. Studies conducted on cells (RGC-5 cells) in culture showed that hydrogen peroxide, L-buthionine sulfoximine (BSO)/glutamate and serum deprivation (mimicking oxidative stress), rotenone, sodium azide (affecting mitochondria function in specific ways) and light (where the mitochondria are generally affected) all generated reactive oxygen species and caused death of RGC-5 cells. EGCG was able to attenuate cell death caused by hydrogen peroxide, sodium azide and rotenone. Only EC was able to attenuate BSO/glutamate-induced cell death, in addition to cell death caused by hydrogen peroxide and rotenone. Genistein had no positive effect on cell death in experiments carried out on RGC-5 cells. Exposure of RGC-5 cells to flavonoids showed that EC and EGCG increased the mRNA expression of endogenous antioxidants such as HO-1 (heme oxygenase 1) and Nrf-2 (nuclear erythroid factor-2-related factor 2). Light insult, rotenone and sodium azide activate the p38 (protein kinase 38) pathway, while only light and rotenone activate the JNK (c-Jun amino-terminal kinase) pathway. Serum deprivation affects mitochondrial apoptotic proteins causing an increase in the ratio of Bax/Bcl2 (Bax: Bcl-2-associated X protein; Bcl-2: B-cell lymphoma 2). An insult of light to RGC-5 cells, unlike that induced by sodium azide, is inhibited by necrostatin-1 and causes an activation of AIF (apoptosis-inducing factor) with alpha-fodrin being unaffected. These studies suggest that ganglion cell death caused by insults as may occur in POAG involves various cellular signaling pathways. The selected flavonoids have diverse actions in increasing cellular defense mechanisms, and in negating the effects of ischemia and specific types of oxidative stress. The results argue for the possible use of flavonoids in the treatment of POAG to slow down ganglion cell death.

Leber Hereditary Optic Neuropathy (LHON) is a maternally inherited form of visual loss, due to selective degeneration of retinal ganglion cells. Despite the established aetiological association between LHON and mitochondrial DNA mutations affecting complex I of the electron transport chain, the pathophysiology of this disorder remains obscure. Primary rat retinal cultures were exposed to increasing concentrations of rotenone to titrate complex I inhibition. Neural cells were more sensitive than Mfiller glial cells to rotenone toxicity. Rotenone induced an increase in mitochondrial-derived free radicals and lipid peroxidation. Sodium -dependent glutamate uptake, which is mostly mediated by the glutamate transporter GLAST expressed by Mfiller glial cells, was reduced dose-dependently by rotenone with no changes in GLAST expression. Our findings suggest that complex 1-derived free radicals and disruption of glutamate transport might represent key elements for explaining the selective retinal ganglion cell death in LHON. (c) 2006 Elsevier Inc. All rights reserved.