Keratinocyte carcinoma in organ transplant recipients Menzies, S.; O'Leary, E.; Callaghan, G. ...
British journal of dermatology (1951),
November 2019, 2019-11-00, 20191101, Letnik:
181, Številka:
5
Journal Article
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Summary
Skin cancer commonly affects people who have received a solid organ transplant (heart, lung, liver and kidney). Transplant patients can get multiple skin cancers, some of which can grow very ...quickly. The commonest types of skin cancer are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Immunosuppressant medication is used to prevent rejection of the transplanted organ. This alters the body's immune system, which in turn means that transplant patients are more prone to skin cancers that can grow rapidly. Over the last 20 years, newer immunosuppressants have been introduced which are thought to lessen the risk of skin cancer. Previous studies have shown a lower risk of SCC with the newer medication, but no study to date has looked at BCC rates. This study, from Ireland, aimed to find out if the rate of skin cancer in transplant patients has reduced over the last 20 years, spanning the introduction of newer immunosuppressive medications. The National Cancer Registry of Ireland registers all skin cancers for the Republic of Ireland. The authors looked at the rate of skin cancer in people who received a solid organ transplant and compared this to the rate of skin cancer in the general population. They found that the rate of SCC and BCC in patients who received an organ transplant has significantly reduced over the last two decades. This change in risk of skin cancer coincided with changes in immunosuppressant medication, along with focused education and regular skin cancer screening for transplant recipients.
Linked Article: Menzies et al. Br J Dermatol 2019; 181:983–991
Summary Background The nuclear transcription factor c-Jun is preferentially expressed in basal-cell carcinoma. Dz13 is a deoxyribozyme that targets JUN messenger RNA and has inhibited the growth of a ...range of tumours in mice. We did a phase 1 study to assess safety and tolerability in human beings. Methods Adults with nodular basal-cell carcinoma were recruited from Royal Prince Alfred Hospital, Sydney, Australia, between September, 2010, and October, 2011. Patients were assigned to receive one intratumoral injected dose of 10, 30, or 100 μg Dz13, in a 50 μL volume of lipid carrier, and were assessed for adverse effects in the first 24 h then at 7, 14, and 28 days after injection. Treated tumours were surgically excised 14 days after injection and compared with the baseline biopsy samples for expression of c-Jun and tumorigenesis markers. Findings Nine patients were recruited, of whom three received each dose of Dz13. All patients completed the study with no drug-related serious adverse events. No systemic Dz13 exposure was detected. c-Jun expression was reduced in the excised tumours of all nine (100%) patients, compared with baseline, and histological tumour depth had decreased in five (56%) of nine. Proportions of cells positive for caspases 3, 8, and 9 and P53 were increased, but those of cells positive for Bcl-2 and MMP-9 were decreased. Infiltration by inflammatory and immune cells was stimulated. Interpretation Dz13 was safe and well tolerated after single intratumoral injections at all doses. Funding Cancer Institute NSW, Cancer Council Australia, and National Health and Medical Research Council.
The effects of three preslaughter diets on heifer beef quality were investigated. Heifers (n = 45) were divided into three groups and fed for ad libitum consumption either maize silage, grass silage, ...or a 50:50 mixture of maize silage and grass silage. Meat quality was determined by measuring color, lipid oxidation, alpha-tocopherol levels, and fatty acid composition. Beef from the maize silage group had poorest color stability (P < 0.05), whereas beef from the grass silage diet had best (P < 0.05) color stability. The visual panel least preferred the maize silage group after 2 or more days of display, and lipid oxidation was significantly (P < 0.001) higher in this group compared to the 50:50 maize:grass silage and grass silage groups. There was a significant (P < 0.001) difference in the alpha-tocopherol levels detected in the meat from the three dietary groups. Alpha-tocopherol levels increased in the order: maize silage < 50:50 maize:grass silage < grass silage, at levels of 2.08, 2.95, and 3.84 microg/g meat, respectively. Fatty acid analysis indicated 18:3 was significantly (P < 0.001) lower in the maize silage-fed group than in the maize:grass silage and grass silage groups. However, 18:3 was significantly (P < 0.001) higher in the grass silage group than in the other two groups. There were no significant differences in all other fatty acids among the three dietary groups. It was concluded that beef from grass silage-fed animals had better overall quality in terms of color, lipid oxidation, and alpha-tocopherol levels than beef from maize silage fed animals.
We describe the design and x-ray emission properties (temporal, spatial, and spectral) of Dry Pinch I, a portable X-pinch driver developed at Imperial College London. Dry Pinch I is a direct ...capacitor discharge device, 300 × 300 × 700 mm3 in size and ∼50 kg in mass, that can be used as an external driver for x-ray diagnostics in high-energy-density physics experiments. Among key findings, the device is shown to reliably produce 1.1 ± 0.3 ns long x-ray bursts that couple ∼50 mJ of energy into photon energies from 1 to 10 keV. The average shot-to-shot jitter of these bursts is found to be 10 ± 4.6 ns using a combination of x-ray and current diagnostics. The spatial extent of the x-ray hot spot from which the radiation emanates agrees with previously published results for X-pinches—suggesting a spot size of 10 ± 6 µm in the soft energy region (1–10 keV) and 190 ± 100 µm in the hard energy region (>10 keV). These characteristics mean that Dry Pinch I is ideally suited for use as a probe in experiments driven in the laboratory or at external facilities when more conventional sources of probing radiation are not available. At the same time, this is also the first detailed investigation of an X-pinch operating reliably at current rise rates of less than 1 kA/ns.
The differences in phenotypic plasticity between invasive (North American) and native (German) provenances of the invasive plant Lythrum salicaria (purple loosestrife) were examined using a ...multivariate reaction norm approach testing two important attributes of reaction norms described by multivariate vectors of phenotypic change: the magnitude and direction of mean triat differences between environments. Data were collected for six life history traits from native and invasive plants using a split-plot design with experimentally manipulated water and nutrient levels. We found significant differences between native and invasive plants in multivariate phenotypic plasticity for comparisons between low and high water treatments within low nutrient levels, between low and high nutrient levels within high water treatments, and for comparisons that included both a water and nutrient level change. The significant genotype × environment (G × E) effects support the argument that invasiveness of purple loosestrife is closely associated with the interaction of high levels of soil nutrient and flooding water regime. Our results indicate that native and invasive plants take different strategies for growth and reproduction; native plants flowered earlier and allocated more to flower production, while invasive plants exhibited an extended period of vegetative growth before flowering to increase height and allocation to clonal reproduction, which may contribute to increased fitness and invasiveness in subsequent years.
Notch signaling is a component of a wide variety of developmental processes in many organisms. Notch activity can be modulated by O-fucosylation (mediated by protein O-fucosyltransferase-1) and ...Fringe, a β1,3-N-acetylglucosaminyltransferase that modifies O-fucose in the context of epidermal growth factor-like (EGF) repeats. Fringe was initially described in Drosophila, and three mammalian homologues have been identified, Manic fringe, Lunatic fringe, and Radical fringe. Here for the first time we have demonstrated that, similar to Manic and Lunatic, Radical fringe is also a fucose-specific β1,3-N-acetylglucosaminyltransferase. The fact that three Fringe homologues exist in mammals raises the question of whether and how these enzymes differ. Although Notch contains numerous EGF repeats that are predicted to be modified by O-fucose, previous studies in our laboratory have demonstrated that not all O-fucosylated EGF repeats of Notch are further modified by Fringe, suggesting that the Fringe enzymes can differentiate between them. In this work, we have sought to identify specificity determinants for the recognition of an individual O-fucosylated EGF repeat by the Fringe enzymes. We have also sought to determine differences in the biochemical behavior of the Fringes with regard to their in vitro enzymatic activities. Using both in vivo and in vitro experiments, we have found two amino acids that appear to be important for the recognition of an O-fucosylated EGF repeat by all three mammalian Fringes. These amino acids provide an initial step toward defining sequences that will allow us to predict which O-fucosylated EGF repeats are modified by the Fringes.
Diagnosis of skin cancer requires medical expertise, which is scarce. Mobile phone-powered artificial intelligence (AI) could aid diagnosis, but it is unclear how this technology performs in a ...clinical scenario. Our primary aim was to test in the clinic whether there was equivalence between AI algorithms and clinicians for the diagnosis and management of pigmented skin lesions.
In this multicentre, prospective, diagnostic, clinical trial, we included specialist and novice clinicians and patients from two tertiary referral centres in Australia and Austria. Specialists had a specialist medical qualification related to diagnosing and managing pigmented skin lesions, whereas novices were dermatology junior doctors or registrars in trainee positions who had experience in examining and managing these lesions. Eligible patients were aged 18–99 years and had a modified Fitzpatrick I–III skin type; those in the diagnostic trial were undergoing routine excision or biopsy of one or more suspicious pigmented skin lesions bigger than 3 mm in the longest diameter, and those in the management trial had baseline total-body photographs taken within 1–4 years. We used two mobile phone-powered AI instruments incorporating a simple optical attachment: a new 7-class AI algorithm and the International Skin Imaging Collaboration (ISIC) AI algorithm, which was previously tested in a large online reader study. The reference standard for excised lesions in the diagnostic trial was histopathological examination; in the management trial, the reference standard was a descending hierarchy based on histopathological examination, comparison of baseline total-body photographs, digital monitoring, and telediagnosis. The main outcome of this study was to compare the accuracy of expert and novice diagnostic and management decisions with the two AI instruments. Possible decisions in the management trial were dismissal, biopsy, or 3-month monitoring. Decisions to monitor were considered equivalent to dismissal (scenario A) or biopsy of malignant lesions (scenario B). The trial was registered at the Australian New Zealand Clinical Trials Registry ACTRN12620000695909 (Universal trial number U1111–1251–8995).
The diagnostic study included 172 suspicious pigmented lesions (84 malignant) from 124 patients and the management study included 5696 pigmented lesions (18 malignant) from the whole body of 66 high-risk patients. The diagnoses of the 7-class AI algorithm were equivalent to the specialists’ diagnoses (absolute accuracy difference 1·2% 95% CI –6·9 to 9·2) and significantly superior to the novices’ ones (21·5% 13·1 to 30·0). The diagnoses of the ISIC AI algorithm were significantly inferior to the specialists’ diagnoses (–11·6% –20·3 to –3·0) but significantly superior to the novices’ ones (8·7% –0·5 to 18·0). The best 7-class management AI was significantly inferior to specialists’ management (absolute accuracy difference in correct management decision –0·5% 95% CI –0·7 to –0·2 in scenario A and –0·4% –0·8 to –0·05 in scenario B). Compared with the novices’ management, the 7-class management AI was significantly inferior (–0·4% –0·6 to –0·2) in scenario A but significantly superior (0·4% 0·0 to 0·9) in scenario B.
The mobile phone-powered AI technology is simple, practical, and accurate for the diagnosis of suspicious pigmented skin cancer in patients presenting to a specialist setting, although its usage for management decisions requires more careful execution. An AI algorithm that was superior in experimental studies was significantly inferior to specialists in a real-world scenario, suggesting that caution is needed when extrapolating results of experimental studies to clinical practice.
MetaOptima Technology.
Attempts were made to determine which specific aspects of inpatient care are most important to patients and to document patients' perceptions of those aspects of care in hospitals nationwide. Another ...goal was to assess the extent to which variations in reported quality of care might be related to characteristics of patients. Of particular interest was whether patients with fewer resources, older patients, or patients in poorer health were more likely to report problems with their care. Interviews focused on events that indicate the quality of care in several clinically important areas of which patients are the best judges, namely: 1. patient education and communication with providers, 2. respect for patients' needs and preferences, 3. the provision of emotional and physical comfort, 4. family involvement, and 5. discharge preparation. Studies that elicit reports from patients increasingly are viewed as an important method of assessing hospital care.
Differential cross sections for π−p and π+p elastic scattering were measured at five energies between 19.9 and 43.3 MeV. The use of the CHAOS magnetic spectrometer at TRIUMF, supplemented by a range ...telescope for muon background suppression, provided simultaneous coverage of a large part of the full angular range, thus allowing very precise relative cross section measurements. The absolute normalisation was determined with a typical accuracy of 5%. This was verified in a simultaneous measurement of muon proton elastic scattering. The measured cross sections show some deviations from phase shift analysis predictions, in particular at large angles and low energies. From the new data we determine the real part of the isospin forward scattering amplitude.
The aim of this investigation was to quantify the scale of variation in the eating quality of two commercial beef muscles,
M. longissimus dorsi (LD) and
M. semimembranosus (Sm). Both the LD and Sm ...were excised from steers (
n=81) and heifers (
n=81) (classification grade O4H, O4L, R4H, R4L) within 48 h postmortem, vacuum packaged and stored at 4 °C until tested for eating quality at 14 days postmortem. Quality measurements analysed were: pH, Warner Bratzler shear force, sensory attributes, sarcomere length, Hunter
L a b muscle and subcutaneous fat colour and chemical composition. Extent of variation in many eating quality measurements, with the exception of most sensory attributes and subcutaneous fat colour, depended on gender, classification grade or a combination of both. The LD was more variable than the Sm for most quality attributes and heifers were more variable than steers. No one carcass grade was more variable over all attributes analysed; with different grades causing higher or lower variances within certain attributes. Knowledge of the current scale of variation in the eating quality of beef is required by the meat industry, and is one that requires further research.
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