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Optical palpation is an emerging elastography technique that generates two-dimensional images of mechanical stress at the tissue surface, with clinical applications such as intraoperative cancer detection and scar assessment. It has been implemented using various imaging systems, however, an analysis of how deformation of the sample and layer influences image formation has not been performed. Here, an analysis framework is presented, which assesses performance independently of the imaging system used. Optical palpation of varying samples and layers is simulated using finite element analysis and validated with experiments on silicone phantoms, providing a characterization of detectability, feature resolution, and contrast ratio. Using our framework, we demonstrate that computational optical palpation, which incorporates realistic assumptions of layer deformation, improves the feature resolution up to a factor of four. This framework can guide the development of optical palpation and aid in the selection of appropriate imaging system and layer properties for a given application.
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Healthy Longevity Medicine aims to optimize health by targeting aging processes across the lifespan. Addressing accelerated aging involves adaptation of lifestyle and the use of geroprotective drugs and supplements, including nutritional supplements and bioactive compounds. The Food and Drug Administration, under the Dietary Supplement Health and Education Act, categorizes bioactive compounds and medicinal products as dietary supplements. While numerous companies sell ingredients that can be deemed geroprotectors, there's limited oversight in their quality control. Governmental safety authorities only verify the presence of prohibited compounds, not the accuracy of ingredients listed on labels.Here, Nicotinamide mononucleotide and Urolithin A supplements, easily accessible online or in pharmacies, were tested for their active ingredient content. Results showed a significant deviation from the labeled amounts, ranging from + 28.6% to -100%. This indicates a considerable disparity in the quality of geroprotective supplements.To address this variability, collaboration between and within societies representing healthcare professionals, industry and regulatory bodies is imperative to ensure the quality of geroprotective supplements.
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Spirometry and peak cough flow testing (PCF) are commonly used in the respiratory assessment of children with a neuromuscular disorder (NMD). Testing uses two different machines, increases laboratory time, costs and resource utilisation. No studies have assessed the correlation between peak expiratory flow (PEF) obtained from spirometry and PCF in children with NMD using one device. An audit of children with a NMD managed at the Children's Hospital at Westmead in 2022-2024 aged < 20 years who performed spirometry and PCF testing on the same device (Vyaire Body BoxTM, Ultrasonic flow meter-based, or Vyaire PneumotachographTM, Pneumotach flow meter-based; Germany) was conducted to assess the correlation between PCF and PEF. Fifty-one sets of testing were identified, and 40 subjects (9F) had reproducible testing and were included. Median (range) age was 14.95 (7.20-19.00) years. Median PEF (L/min) was 4.05 (1.22-10.26) and median PCF (L/min) was 4.29 (1.69-10.82). PEF and PCF had a strong Pearson's correlation coefficient, (R = 0.97, p = 0.03). The coefficient of determination was 0.93. If laboratory resources permit, spirometry should be the test of choice for children with NMD. On average, spirometry required multiple practices to achieve reproducibility to meet ATS/ERS standards. PCF testing can be utilised for children where performing technically acceptable spirometry is not possible.
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AIM: To explore the relationship between postural changes in lung function and polysomnography (PSG) in children with Duchenne muscular dystrophy (DMD). METHODS: In this prospective cross-sectional study, children with DMD performed spirometry in sitting and supine positions. A control group of age and gender matched healthy children also underwent postural lung function testing. PSG was performed within six months of spirometry. RESULTS: Seventeen children with DMD, aged 12.3 ± 3 years performed sitting spirometry. 14 (84%) performed acceptable spirometry in the supine position. Mean FEV1sit and FVCsit were 77% (SD ± 22) and 74% (SD ± 20.4) respectively, with mean% ΔFVC(sit-sup) 9% (SD ± 11) (range 2% to 20%), and was significantly greater than healthy controls 4% (n = 30, SD ± 3, P < 0.001). PSG data on the 14 DMD children with acceptable supine spirometry showed total AHI 6.9 ± 5.9/hour (0.3 to 29), obstructive AHI 5.2 ± 4.0/hour (0.2 to 10), and REM AHI 14.1 ± -5.3/hour (0.1 to 34.7). ΔFVC(sit-sup) had poor correlation with hypoventilation on polysomnography. CONCLUSION: Children with DMD and mild restrictive lung disease showed greater postural changes in spirometry than healthy controls but lower supine spirometry was not predictive of sleep hypoventilation.
Subject(s)
Muscular Dystrophy, Duchenne , Child , Humans , Muscular Dystrophy, Duchenne/complications , Hypoventilation , Cross-Sectional Studies , Prospective Studies , Spirometry , SleepABSTRACT
Background: Many deaths globally are attributable to non-communicable disease, and four-fifths of these deaths are in low- and middle-income countries. Globally, COPD is currently the third leading cause of mortality. Research Question: 1) To determine the prevalence and burden of symptoms and concerns, and 2) determine predicting factors of symptom burden among patients with COPD. Methods: A cross-sectional survey was conducted at eight primary care sites in Western Cape. We collected socio-demographic data (age, gender, smoking status, number of missed doses of prescribed medication in the last seven days) and clinical data (PEF and KPS). The Memorial Symptom Assessment Scale (MSAS), the Medical Outcomes Study, Social Support Survey (MOS-SSS), the London Chest Activity of Daily Living Scale (LCADLS) and the COPD Assessment Test (CAT) (impairment on person's life) were administered to patients. We conducted ordered logistic regression analysis to assess factors associated with the burden of symptoms. MSAS subscales: 1) Global symptom distress index, 2) physical symptom distress and 3) psychological symptom distress were dependent outcomes. We constructed three ordinal logistic regression models for each of the three subscales. Covariates were MOS-SSS, LCADLS, CAT, demographic and clinical variables. Results: We recruited n=387 patients, mean age 59.5 years, 53.0% female. In multivariate analysis, each of the three models (ie, global, psychological and physical symptom distress) was positively associated with impairment on person's life p<0.001, difficulty to perform activities of daily living p<0.001, and low social support p<0.001. Old age was associated with lower global symptom distress (p=0.004), psychological and (0.014) physical distress (0.005). Missing 1 or more doses of medication was associated with higher levels of global (0.004) and physical (0.005) symptom distress. Interpretation: The high prevalence and burden of physical and psychological symptoms provides strong evidence of the need for integrating person-centred assessment and management of symptoms in primary care settings.
Subject(s)
Asthma , Pulmonary Disease, Chronic Obstructive , Humans , Female , Male , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/epidemiology , Activities of Daily Living , Prevalence , Cross-Sectional Studies , South Africa/epidemiology , Primary Health CareABSTRACT
INTRODUCTION: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children and causes short- and long-term disability. Optimal management requires pharmacologic and non-pharmacologic interventions. Few studies have explored the youth and family experience of the management of JIA. This study's objective was to explore the management experience of youth with JIA and their parents. METHODS: This qualitative study used semi-structured interviews with youth 12-18 years of age with JIA receiving biological medication and parents of children with JIA on biological medication. Participants were recruited in clinics using convenience sampling. A thematic analysis approach was employed for data analysis. RESULTS: Nine youth and 14 parents participated. Four themes were identified that encompassed an overarching theme of participants managing JIA within the context of their life: aspects of life affected by JIA and its management, lived experience with JIA management, medication decision-making, and involvement in decision-making. Juvenile idiopathic arthritis management is situated within the context of their life but is normally (outside acute events) not central. CONCLUSION: Two dimensions were added to those in the literature: parents' overall approaches to health and the sense of urgency surrounding decision-making. Our findings reinforce the importance of person- and family-centred care in paediatric rheumatology. That is, identifying what matters most to youth and their parents given their current life circumstances to provide a foundation for discussions of how they want to manage their JIA.
Subject(s)
Arthritis, Juvenile , Rheumatic Diseases , Child , Humans , Adolescent , Arthritis, Juvenile/therapy , Qualitative Research , Research Design , Parents , Quality of LifeABSTRACT
Camel trypanosomiasis (Surra) is endemic in the Horn of Africa. Understanding the spatiotemporal variations in Surra prevalence, vector dynamics, and host-related risk factors is important in developing effective control strategies. A repeated cross-sectional study was conducted to determine the Surra parasitological prevalence, livestock reservoirs, vector density/diversity, and host-related risk factors in Kenya. Random samples of 847, 1079, and 824 camels were screened at the start of the dry season, peak dry season, and during the rainy season, respectively. Blood samples were examined using the dark ground/phase contrast buffy-coat technique, and Trypanosoma species were identified based on their movement and morphology in wet and stained thin smears. Reservoir status for Trypanosoma evansi was assessed in 406 cattle and 372 goats. A rainy and dry seasons entomological surveys were conducted to determine the Surra vector abundance/diversity and spatiotemporal density changes. Surra prevalence was 7.1%, 3.4%, and 4.1% at the start of the dry season, peak dry season, and rainy season, respectively. Camel co-infections by Trypanozoon (T. evansi or Trypanosoma brucei brucei) and Trypanosoma vivax were recorded. Spatial variations in Surra prevalence were recorded at the beginning of dry (X (7, N = 846) 2 = 110.9, p ≤ 0.001), peak dry (X (7, N = 1079) 2 = 42.2, p ≤ 0.001), and rainy (X (7, N = 824) 2 = 29.1, p ≤ 0.001) seasons. The screened cattle and goats tested negative for Trypanozoon (T. evansi or T. b. brucei), while two cattle tested positive for Trypanosoma congolense. Biting fly catches were composed of a single species from Tabanus, Atylotus, Philoliche, Chrysops, and Stomoxys genera. The total catches for Philoliche, Chrysops, and Stomoxys were higher in the rainy than dry season consistent with the prevalence results. Surra remains an important camel disease in the region with its prevalence varying in space and time. Camel co-infections by Trypanozoon (T. evansi or T. b. brucei) and T. vivax necessitate proper diagnosis of suspected cases and targeted therapy.
ABSTRACT
Trypanocidal resistance is a major cause of treatment failure. This study evaluated the sensitivity of Trypanosoma evansi field isolates collected from Marsabit and Isiolo counties, Kenya. A total of 2,750 camels were screened using parasitological tests for trypanosomes. Of the screened camels, 113 tested positive from which 40 T. evansi isolates were tested using the single dose mice sensitivity test. Five treatment groups each comprising of 6 mice were inoculated intraperitoneally with 1x105 trypanosomes of each isolate and treated 24 hours later with isometamidium chloride at 1 mg/kg, homidium chloride at 1mg/kg, diminazene aceturate at 20 mg/kg and quinapyramine sulphate & chloride at 1 mg/kg. The fifth group was left untreated (positive control). The mice were monitored daily for 60 days. A survey on camel owners' practices that influence development of resistance to trypanocidal drugs was then conducted. Results indicated presence of drug resistance in all the 7 study sites that had infected camels. Seven of the isolates tested were resistant to diminazene aceturate whereas, 28, 33 and 34 were resistant to isometamidium chloride, quinapyramine sulphate & chloride and homidium chloride, respectively. Seven (17.5%) isolates of the 40 tested were sensitive to all 4 drugs, whereas, 7.5%, 10%,55% and 10% were resistant to 1,2,3 and 4 drugs, respectively. The prevalence of multiple drug resistance was 75%. Survey data indicated that camel management practices influenced the prevalence and degree of drug resistance. In conclusion, the multiple drug resistance observed in the two counties may not be an indication of total trypanocidal drug failure. Judicious treatment of confirmed trypanosomiasis cases with correct dosage would still be effective in controlling the disease since the observed resistance was at the population and not clonal level. However, integrated control of the disease and the vectors using available alternative methods is recommended to reduce drug use.
Subject(s)
Trypanocidal Agents , Trypanosoma , Trypanosomiasis, African , Mice , Animals , Trypanocidal Agents/pharmacology , Trypanocidal Agents/therapeutic use , Camelus , Trypanosomiasis, African/drug therapy , Trypanosomiasis, African/veterinary , Kenya , Chlorides/pharmacology , Phenanthridines/pharmacology , Phenanthridines/therapeutic use , Diminazene/pharmacology , Diminazene/therapeutic use , Drug ResistanceABSTRACT
In humans and non-human primates (NHPs), motion and stereopsis are processed within fine-scale cortical sites, including V2 thick stripes and their extensions into areas V3 and V3A that are believed to be under the influence of magnocellular stream. However, in both species, the relative functional organization (overlapping vs. none overlapping) of these sites remains unclear. Using high-resolution functional MRI (fMRI), we found evidence for two minimally-overlapping channels within human extrastriate areas that contribute to processing motion and stereopsis. Across multiple experiments that included different stimuli (random dots, gratings, and natural scenes), the functional selectivity of these channels for motion vs. stereopsis remained consistent. Furthermore, an analysis of resting-state functional connectivity revealed stronger functional connectivity within the two channels rather than between them. This finding provides a new perspective toward the mesoscale organization of the magnocellular stream within the human extrastriate visual cortex, beyond our previous understanding based on animal models.
Subject(s)
Rivers , Visual Cortex , Animals , Humans , Visual Pathways , Depth Perception , Visual Cortex/diagnostic imaging , Magnetic Resonance Imaging , Brain MappingABSTRACT
OBJECTIVE: Automated dispensing cabinets, or ADCs, are often used at health care facilities to aid in the medication-use process. Although ADCs minimize certain medication errors, they introduce a new type of error involving overrides. Although helpful when used appropriately in emergencies, overrides bypass pharmacist verification and increase potential for patient harm through drug-drug interactions, medication allergies, inappropriate dosing, and more. The purpose of this study was to evaluate automated dispensing cabinets override pulls in a pediatric hospital's emergency department. The authors sought to discover whether overridden medications were being administered before verification (indicating it was needed emergently, thus justifying override) or after verification (indicating the override did not result in quicker administration and/or the medication was not emergent). METHODS: This was a retrospective, observational study. Data were collected from electronic health record reports from a 343-bed pediatric hospital's emergency department from October 13, 2019, to December 22, 2019. RESULTS: A total of 445 override pulls were identified during this time, and after data analysis, 99 override pulls remained in the data set. Overall, time from input of prescription into the electronic medical record to medication override was approximately 4 minutes. Pharmacist verification also took a median of four minutes after prescription input. However, administration took twice as long, at 8 minutes. On average, pharmacist verification occurred 4 minutes before medication administration. CONCLUSION: This research from a pediatric emergency department suggests that most situations did not require an immediate administration, and perhaps an override was unnecessary and could have been avoided.
Subject(s)
Medication Errors , Medication Systems, Hospital , Child , Emergency Service, Hospital , Humans , Medication Errors/prevention & control , Pharmaceutical Preparations , Pharmacists , Retrospective StudiesABSTRACT
INTRODUCTION: Health and social care services worldwide need to support ageing populations to live well with advanced progressive conditions while adapting to functional decline and finitude. We aimed to identify and map common elements of effective geriatric and palliative care services and consider their scalability and generalisability to high, middle and low-income countries. METHODS: Tertiary systematic review (Cochrane Database of Systematic Reviews, CINAHL, Embase, January 2000-October 2019) of studies in geriatric or palliative care that demonstrated improved quality of life and/or health service use outcomes among older people with advanced progressive conditions. Using frameworks for health system analysis, service elements were identified. We used a staged, iterative process to develop a 'common components' logic model and consulted experts in geriatric or palliative care from high, middle and low-income countries on its scalability. RESULTS: 78 studies (59 geriatric and 19 palliative) spanning all WHO regions were included. Data were available from 17 739 participants. Nearly half the studies recruited patients with heart failure (n=36) and one-third recruited patients with mixed diagnoses (n=26). Common service elements (≥80% of studies) included collaborative working, ongoing assessment, active patient participation, patient/family education and patient self-management. Effective services incorporated patient engagement, patient goal-driven care and the centrality of patient needs. Stakeholders (n=20) emphasised that wider implementation of such services would require access to skilled, multidisciplinary teams with sufficient resource to meet patients' needs. Identified barriers to scalability included the political and societal will to invest in and prioritise palliative and geriatric care for older people, alongside geographical and socioeconomic factors. CONCLUSION: Our logic model combines elements of effective services to achieve optimal quality of life and health service use among older people with advanced progressive conditions. The model transcends current best practice in geriatric and palliative care and applies across the care continuum, from prevention of functional decline to end-of-life care. PROSPERO REGISTRATION NUMBER: CRD42020150252.
Subject(s)
Quality of Life , Terminal Care , Aged , Humans , Palliative Care , Patient Acceptance of Health CareABSTRACT
Irradiation of tumor cell lines is a useful way to investigate the effects of ionizing radiation on biological molecules. We designed an easy and reproducible approach for in vitro experimental high dose rate brachytherapy, which was simulated by a Monte Carlo code and dosimetrically characterized by experimental methods to evaluate the correspondence between planned doses and doses absorbed by the cells. This approach is an acrylic platform containing T25 tissue culture flasks and multiwell tissue culture plates. It allows nine parallel needles carrying an 192Ir source to irradiate the adherent cells. The whole system composed of the acrylic platform, tissue culture flasks and 192Ir source tracking was simulated by the Monte Carlo N-Particle transport code (MCNPX). Dosimetric measurements were taken by well ionization chamber and radiochromic films. There was a slight difference, averaging from 2% to 7%, between the MCNPX results and film dosimetry results regarding uniform radiation created by the source arrangement. The results showed different values for planned and measured doses in each cell culture plate, which was attributed to the non-equivalent water material used and to the lack of full scattering coming from the top of the platform. This last contribution was different for each tissue culture plate and an individual dose correction factor was calculated. The dose correction factor must be applied to match the planned dose and the actual doses absorbed by the cells. The designed approach is an efficient tool for in vitro brachytherapy experiments for most commercial cell culture plates.
Subject(s)
Brachytherapy/methods , Radiotherapy Dosage , Humans , In Vitro Techniques , Monte Carlo MethodABSTRACT
The gravity field of a small body provides insight into its internal mass distribution. We used two approaches to measure the gravity field of the rubble-pile asteroid (101955) Bennu: (i) tracking and modeling the spacecraft in orbit about the asteroid and (ii) tracking and modeling pebble-sized particles naturally ejected from Bennu's surface into sustained orbits. These approaches yield statistically consistent results up to degree and order 3, with the particle-based field being statistically significant up to degree and order 9. Comparisons with a constant-density shape model show that Bennu has a heterogeneous mass distribution. These deviations can be modeled with lower densities at Bennu's equatorial bulge and center. The lower-density equator is consistent with recent migration and redistribution of material. The lower-density center is consistent with a past period of rapid rotation, either from a previous Yarkovsky-O'Keefe-Radzievskii-Paddack cycle or arising during Bennu's accretion following the disruption of its parent body.
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AIM: To investigate the dissemination of Salmonella spp. within four levels of government hospitals in KwaZulu-Natal, South Africa. METHODS: The identification of Salmonella spp. was performed by amplification of the invA gene. Isolates were subjected to antimicrobial susceptibility testing and molecular characterization of eight resistance genes (qnrA, qnrB, qnrS, tetA, tetB, tetC, tetG, ermB) and three virulence genes (sitC, spvA, spv). Genetic relatedness between isolates was determined using enterobacterial repetitive intergenic consensus (ERIC) polymerase chain reaction. FINDINGS: Ninety-four isolates were obtained. The largest source of isolates was the regional hospital. Paediatric wards had the highest prevalence of isolates. Nurses' tables contained the most isolates out of all sites sampled. Twenty-two clusters indicating diverse isolates were obtained via molecular typing. Four main ERIC types were identified, each unique to a specific hospital. A possibility of dissemination across the wards was noted as highly related isolates were present at various sites within the wards. Many of these sites were highly trafficked areas by healthcare staff. Ten multi-drug-resistant isolates were found. CONCLUSIONS: This study suggests that infection prevention and control strategies that involve environmental cleaning and decontamination may not be enough, or adhered to sufficiently, to prevent the dissemination of Salmonella spp.
Subject(s)
Hospitals, Public/statistics & numerical data , Salmonella Infections/microbiology , Salmonella/genetics , Anti-Bacterial Agents/pharmacology , Drug Resistance, Multiple, Bacterial , Genes, Bacterial , Humans , Infection Control/methods , Microbial Sensitivity Tests , Polymerase Chain Reaction , Public Health , Salmonella/classification , Salmonella/drug effects , Salmonella Infections/epidemiology , South Africa , VirulenceABSTRACT
Epidermolysis Bullosa (EB) is a group of rare genetic disorders resulting in skin fragility and other symptoms. Commissioned by DEBRA International and funded by DEBRA Norway, this evidence-bases guideline provides recommendations to optimise psychosocial wellbeing in EB.An international multidisciplinary panel of social and health care professionals (HCP) and people living with EB was formed. A systematic international literature review was conducted by the panel following the Scottish Intercollegiate Guidelines Network (SIGN) methodology. The resulting papers underwent systematic selection and critique processes. Included papers were allocated to 6 different outcome groups to allow data synthesis and exploration: quality of life, coping, family, wellbeing, access to HCP and pain. Based on the evidence in those papers, recommendations were made for individuals living with EB, family and caregivers and HCP working in the field.Few studies have investigated interventions and which factors lead to better outcomes, but general recommendations can be made. EB is a complex disease impacting enormously on every aspect of psychosocial life. People and families living with EB need access to multidisciplinary support, including psychological guidance, in order to improve quality of life and psychosocial wellbeing. Interventions should stimulate social participation to prevent isolation. People with EB and their families should be able to access a supportive network. HCP should be well supported and educated about the complexity of EB. They should work collaboratively with those around the individual with EB (e.g. schools, employers etc.) to provide psychosocial opportunity and care.Attention should be paid to the psychosocial impact of EB as well as physical needs. Directions for research are indicated.
Subject(s)
Epidermolysis Bullosa/psychology , Adaptation, Psychological/physiology , Epidermolysis Bullosa/physiopathology , Humans , Quality of LifeABSTRACT
Thanks to advances in modern medicine over the past century, the world's population has experienced a marked increase in longevity. However, disparities exist that lead to groups with both shorter lifespan and significantly diminished health, especially in the aged. Unequal access to proper nutrition, healthcare services, and information to make informed health and nutrition decisions all contribute to these concerns. This in turn has hastened the ageing process in some and adversely affected others' ability to age healthfully. Many in developing as well as developed societies are plagued with the dichotomy of simultaneous calorie excess and nutrient inadequacy. This has resulted in mental and physical deterioration, increased non-communicable disease rates, lost productivity and quality of life, and increased medical costs. While adequate nutrition is fundamental to good health, it remains unclear what impact various dietary interventions may have on improving healthspan and quality of life with age. With a rapidly ageing global population, there is an urgent need for innovative approaches to health promotion as individual's age. Successful research, education, and interventions should include the development of both qualitative and quantitative biomarkers and other tools which can measure improvements in physiological integrity throughout life. Data-driven health policy shifts should be aimed at reducing the socio-economic inequalities that lead to premature ageing. A framework for progress has been proposed and published by the World Health Organization in its Global Strategy and Action Plan on Ageing and Health. This symposium focused on the impact of nutrition on this framework, stressing the need to better understand an individual's balance of intrinsic capacity and functional abilities at various life stages, and the impact this balance has on their mental and physical health in the environments they inhabit.
Subject(s)
Healthy Aging/physiology , Longevity/physiology , Nutrition Therapy , Aged , Aged, 80 and over , Aging/physiology , Animals , Biomarkers , Energy Intake , Female , Frailty , Health Education , Health Promotion , Humans , Male , Mice , Middle Aged , Nutritional Physiological Phenomena , Nutritional Status , Quality of Life , Socioeconomic Factors , World Health OrganizationABSTRACT
The Mara River basin is a trans-boundary basin of international importance. It forms the headwaters of the Nile River and serves as the primary dry season water source for an estimated 1.1 million rural people and the largest remaining overland migration of 1.4 million wildebeest in the Serengeti-Mara Ecosystem. Changes throughout the basin are impacting the quantity and quality of the Mara River, yet the historical context of environmental conditions in the basin is not well known. We collected sediment cores throughout the wetland at the mouth of the Mara River, and we used isotopic dating methods and a suite of analyses to examine historical patterns of sediment quantity and source, mercury contamination, and carbon and nutrient loading. Our results show that ecological conditions in the Mara River basin were fairly stable over paleoecological time scales (2000-1000â¯years before present), but there has been a period of rapid change in the basin over the last 250â¯years, particularly since the 1960s. A shift in the source and quantity of sediments in the river began in the late 1700s and became much more pronounced in the 1950s and 1960s, coincident with increasing mercury concentrations. The quantity of sediment from the Upper Mara increased, particularly since 1960, but the proportion of total sediment from this region decreased as the Talek and Middle Mara portions of the basin began producing more sediment. The decadal oscillation in sediment accumulation was congruent with known periods of extreme precipitation events. Carbon and nitrogen loading also increased since the 1960s, and the shift in the isotopic ratio of nitrogen provides evidence for increased anthropogenic loading. Altogether, these data likely reflect patterns of change also experienced in other basins throughout East Africa.
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Uveal melanoma is a rare, but deadly, form of eye cancer that arises from melanocytes within the uveal tract. Although advances have emerged in treatment of the primary tumour, patients are still faced with vision loss, eye enucleation and lethal metastatic spread of the disease. Approximately 50% of uveal melanoma patients develop metastases, which occur most frequently in the liver. Metastatic patients encounter an extremely poor prognosis; as few as 8% survive beyond 2 years. Understanding of the genetic underpinnings of this fatal disease evolved in recent years with the identification of new oncogenic mutations that drive uveal melanoma pathogenesis. Despite this progress, the lack of successful therapies or a proven standard-of-care for uveal melanoma highlights the need for new targeted therapies. This review focuses on the recently identified CYSLTR2 oncogenic mutation in uveal melanoma. Here, we evaluate the current status of uveal melanoma and investigate how to better understand the role of this CYSLTR2 mutation in the disease and implications for patients harbouring this mutation.
Subject(s)
Melanoma/etiology , Melanoma/metabolism , Oncogene Proteins/genetics , Oncogene Proteins/metabolism , Receptors, Leukotriene/genetics , Receptors, Leukotriene/metabolism , Uveal Neoplasms/etiology , Uveal Neoplasms/metabolism , Animals , Biomarkers, Tumor , Carcinogenesis , Disease Models, Animal , Genetic Predisposition to Disease , Genetic Variation , Heterografts , Humans , Melanoma/drug therapy , Melanoma/epidemiology , Molecular Targeted Therapy , Prognosis , Signal Transduction , Uveal Neoplasms/drug therapy , Uveal Neoplasms/epidemiologyABSTRACT
We utilized femtosecond time-resolved resonant inelastic X-ray scattering and ab initio theory to study the transient electronic structure and the photoinduced molecular dynamics of a model metal carbonyl photocatalyst Fe(CO)5 in ethanol solution. We propose mechanistic explanation for the parallel ultrafast intra-molecular spin crossover and ligation of the Fe(CO)4 which are observed following a charge transfer photoexcitation of Fe(CO)5 as reported in our previous study [Wernet et al., Nature 520, 78 (2015)]. We find that branching of the reaction pathway likely happens in the (1)A1 state of Fe(CO)4. A sub-picosecond time constant of the spin crossover from (1)B2 to (3)B2 is rationalized by the proposed (1)B2 â (1)A1 â (3)B2 mechanism. Ultrafast ligation of the (1)B2 Fe(CO)4 state is significantly faster than the spin-forbidden and diffusion limited ligation process occurring from the (3)B2 Fe(CO)4 ground state that has been observed in the previous studies. We propose that the ultrafast ligation occurs via (1)B2 â (1)A1 â (1)A' Fe(CO)4EtOH pathway and the time scale of the (1)A1 Fe(CO)4 state ligation is governed by the solute-solvent collision frequency. Our study emphasizes the importance of understanding the interaction of molecular excited states with the surrounding environment to explain the relaxation pathways of photoexcited metal carbonyls in solution.
ABSTRACT
Nb K-edge x-ray absorption spectroscopy is utilized to investigate the changes in the local structure of the A-site deficient double perovskite La1/3NbO3 which undergoes a pressure induced irreversible amorphization. EXAFS results show that with increasing pressure up to 7.5 GPa, the average Nb-O bond distance decreases in agreement with the expected compression and tilting of the NbO6 octahedra. On the contrary, above 7.5 GPa, the average Nb-O bond distance show a tendency to increase. Significant changes in the Nb K-edge XANES spectrum with evident low energy shift of the pre-peak and the absorption edge is found to happen in La1/3NbO3 above 6.3 GPa. These changes evidence a gradual reduction of the Nb cations from Nb(5+) towards Nb(4+) above 6.3 GPa. Such a valence change accompanied by the elongation of the average Nb-O bond distances in the octahedra, introduces repulsion forces between non-bonding adjacent oxygen anions in the unoccupied A-sites. Above a critical pressure, the Nb reduction mechanism can no longer be sustained by the changing local structure and amorphization occurs, apparently due to the build-up of local strain. EXAFS and XANES results indicate two distinct pressure regimes having different local and electronic response in the La1/3NbO3 system before the occurence of the pressure induced amorphization at â¼14.5 GPa.