To generate a nomogram to predict parotid gland (PG) overdose and to quantify the dosimetric benefit of weekly replanning based on its findings, in the context of intensity-modulated radiotherapy ...(IMRT) for locally-advanced head and neck carcinoma (LAHNC).
Twenty LAHNC patients treated with radical IMRT underwent weekly computed tomography (CT) scans during IMRT. The cumulated PG dose was estimated by elastic registration. Early predictors of PG overdose (cumulated minus planned doses) were identified, enabling a nomogram to be generated from a linear regression model. Its performance was evaluated using a leave-one-out method. The benefit of weekly replanning was then estimated for the nomogram-identified PG overdose patients.
Clinical target volume 70 (CTV70) and the mean PG dose calculated from the planning and first weekly CTs were early predictors of PG overdose, enabling a nomogram to be generated. A mean PG overdose of 2.5Gy was calculated for 16 patients, 14 identified by the nomogram. All patients with PG overdoses >1.5Gy were identified. Compared to the cumulated delivered dose, weekly replanning of these 14 targeted patients enabled a 3.3Gy decrease in the mean PG dose.
Based on the planning and first week CTs, our nomogram allowed the identification of all patients with PG overdoses >2.5Gy to be identified, who then benefitted from a final 4Gy decrease in mean PG overdose by means of weekly replanning.
To evaluate noninvasive and clinically translatable magnetic resonance (MR) imaging biomarkers of therapeutic response in the TH-MYCN transgenic mouse model of aggressive, MYCN-amplified ...neuroblastoma.
All experiments were performed in accordance with the local ethical review panel and the UK Home Office Animals Scientific Procedures Act 1986 and with the UK National Cancer Research Institute guidelines for the welfare of animals in cancer research. Multiparametric MR imaging was performed of abdominal tumors found in the TH-MYCN model. T2-weighted MR imaging, quantitation of native relaxation times T1 and T2, the relaxation rate R2*, and dynamic contrast-enhanced MR imaging were used to monitor tumor response to cyclophosphamide (25 mg/kg), the vascular disrupting agent ZD6126 (200 mg/kg), or the antiangiogenic agent cediranib (6 mg/kg, daily). Any significant changes in the measured parameters, and in the magnitude of the changes after treatment between treated and control cohorts, were identified by using Student two-tailed paired and unpaired t test, respectively, with a 5% level of significance.
Treatment with cyclophosphamide or cediranib induced a 54% or 20% reduction in tumor volume at 48 hours, respectively (P < .005 and P < .005, respectively; P < .005 and P < .005 versus control, respectively). Treatment with ZD6126 induced a 45% reduction in mean tumor volume 24 hours after treatment (P < .005; P < .005 versus control). The antitumor activity of cyclophosphamide, cediranib, and ZD6126 was consistently associated with a decrease in tumor T1 (P < .005, P < .005, and P < .005, respectively; P < .005, P < .005, and P < .005 versus control, respectively) and with a correlation between therapy-induced changes in native T1 and changes in tumor volume (r = 0.56; P < .005). Tumor response to cediranib was also associated with a decrease in the dynamic contrast-enhanced MR imaging-derived volume transfer constant (P = .07; P < .05 versus control) and enhancing fraction (P < .05; P < .01 versus control), and an increase in R2* (P < .005; P < .05 versus control).
The T1 relaxation time is a robust noninvasive imaging biomarker of response to therapy in tumors in TH-MYCN mice, which emulate high-risk neuroblastoma in children. T1 measurements can be readily implemented on clinical MR systems and should be investigated in translational clinical trials of new targeted therapies for pediatric neuroblastoma.
http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120128/-/DC1.
An increasing number of older people are living with chronic kidney disease (CKD). Many have complex healthcare needs and are at risk of deteriorating health and functional status, which can ...adversely affect their quality of life. Comprehensive geriatric assessment (CGA) is an effective intervention to improve survival and independence of older people, but its clinical utility and cost-effectiveness in frail older people living with CKD is unknown.
The GOAL Trial is a pragmatic, multi-centre, open-label, superiority, cluster randomised controlled trial developed by consumers, clinicians, and researchers. It has a two-arm design, CGA compared with standard care, with 1:1 allocation of a total of 16 clusters. Within each cluster, study participants ≥ 65 years of age (or ≥ 55 years if Aboriginal or Torres Strait Islander (First Nations Australians)) with CKD stage 3-5/5D who are frail, measured by a Frailty Index (FI) of > 0.25, are recruited. Participants in intervention clusters receive a CGA by a geriatrician to identify medical, social, and functional needs, optimise medication prescribing, and arrange multidisciplinary referral if required. Those in standard care clusters receive usual care. The primary outcome is attainment of self-identified goals assessed by standardised Goal Attainment Scaling (GAS) at 3 months. Secondary outcomes include GAS at 6 and 12 months, quality of life (EQ-5D-5L), frailty (Frailty Index - Short Form), transfer to residential aged care facilities, cost-effectiveness, and safety (cause-specific hospitalisations, mortality). A process evaluation will be conducted in parallel with the trial including whether the intervention was delivered as intended, any issue or local barriers to intervention delivery, and perceptions of the intervention by participants. The trial has 90% power to detect a clinically meaningful mean difference in GAS of 10 units.
This trial addresses patient-prioritised outcomes. It will be conducted, disseminated and implemented by clinicians and researchers in partnership with consumers. If CGA is found to have clinical and cost-effectiveness for frail older people with CKD, the intervention framework could be embedded into routine clinical practice. The implementation of the trial's findings will be supported by presentations at conferences and forums with clinicians and consumers at specifically convened workshops, to enable rapid adoption into practice and policy for both nephrology and geriatric disciplines. It has potential to materially advance patient-centred care and improve clinical and patient-reported outcomes (including quality of life) for frail older people living with CKD.
ClinicalTrials.gov NCT04538157. Registered on 3 September 2020.
BackgroundVentilator-associated pneumonia (VAP) is the most commonly fatal nosocomial infection. Clinical diagnosis of VAP remains notoriously inaccurate. The hypothesis was tested that significantly ...augmented inflammatory markers distinguish VAP from conditions closely mimicking VAP.MethodsA prospective, observational cohort study was carried out in two university hospital intensive care units recruiting 73 patients with clinically suspected VAP, and a semi-urban primary care practice recruiting a reference group of 21 age- and sex-matched volunteers.Growth of pathogens at >104 colony-forming units (cfu)/ml of bronchoalveolar lavage fluid (BALF) distinguished VAP from “non-VAP”. Inflammatory mediators were quantified in BALF and serum. Mediators showing significant differences between patients with and without VAP were analysed for diagnostic utility by receiver operator characteristic (ROC) curves.ResultsSeventy-two patients had recoverable lavage—24% had VAP. BALF interleukin-1β (IL-1β), IL-8, granulocyte colony-stimulating factor and macrophage inflammatory protein-1α were significantly higher in the VAP group (all p<0.005). Using a cut-off of 10 pg/ml, BALF IL-1β generated negative likelihood ratios for VAP of 0.09. In patients with BALF IL-1β <10 pg/ml the post-test probability of VAP was 2.8%. Using a cut-off value for IL-8 of 2 ng/ml, the positive likelihood ratio was 5.03. There was no difference in cytokine levels between patients with sterile BALF and those with growth of <104 cfu/ml.ConclusionsBALF IL-1β and IL-8 are amongst the strongest markers yet identified for accurately demarcating VAP within the larger population of patients with suspected VAP. These findings have potential implications for reduction in unnecessary antibiotic use but require further validation in larger populations.
Background. The purpose of this study was to describe the prevalence and extent of coronary artery calcification (CAC) in subjects with chronic kidney disease (CKD) stages 3 and 4 comparing those ...with and without diabetes. We also wished to determine if the presence of peripheral artery calcification (PAC) would assist in identifying patients positive for CAC. Methods. CAC was detected by multi-slice computed tomography and PAC was detected by plain foot radiography. Study population was 112 patients, 54 with diabetes and 58 without, all asymptomatic for heart disease. Demographic and laboratory data were collected and analysed. Results. The prevalence of CAC in CKD patients was 76 and 46.5% with and without diabetes, respectively. Patients with diabetes had higher CAC scores with more vessels affected, and in the presence of diabetes men and women had the same risk for CAC. In patients with diabetes, age was the unique explanatory variable for detecting the presence of CAC, while age and smoking history predicted severity. In patients without diabetes, age, male gender, body mass index, estimated glomerular filtration rate and serum phosphate levels predicted the presence of CAC, while parathyroid hormone predicted severity. Prevalence of PAC was 63 and 12% in subjects with and without diabetes. PAC detected by foot radiography was not an adequate alternative-screening marker for identifying patients with CAC. Conclusions. CAC is common in CKD stages 3 and 4 patients, especially in men and women with diabetes.
Ages at menarche and first birth are established risk factors for breast cancer. The interval between these ages may also affect risk, since the breast is more susceptible to carcinogenic insults ...during this period than during the parous period. However, few investigators have studied this relation. Using logistic regression, the authors evaluated associations between the timing of reproductive events and breast cancer risk among 4,013 cases and 4,069 controls enrolled in a multicenter, population-based US case-control study of White and African-American women (1994–1998). For White, parous premenopausal and postmenopausal women, those who had an interval of ≥16 years between the ages of menarche and first birth had 1.5-fold (95% confidence interval (CI): 1.0, 2.2) and 1.4-fold (95% CI: 1.1, 1.8) increased risks of breast cancer, respectively, in comparison with those who had ≤5 years between these ages. Adjusting for age at first birth altered these risk estimates somewhat, to odds ratios of 1.5 (95% CI: 0.8, 2.9) and 1.0 (95% CI: 0.6, 1.5), respectively. These associations were stronger for lobular and hormone-receptor-positive tumors but were absent among premenopausal African-American women. The authors conclude that the interval between age at menarche and age at first birth is associated with the risk of hormonally sensitive types of breast cancer, particularly among White women.
BackgroundIn the chronic stage of stroke, previous work has shown that the worse the hand motor deficit, the greater the shift of primary motor cortex (M1) activation towards the contralesional ...hemisphere (ie, unphysiological) balance. Whether the same relationship applies at earlier stages of recovery in serially studied patients is not known.MethodsfMRI of fixed-rate auditory-cued affected index-thumb tapping was obtained at two time points (mean 36 and 147 days poststroke) in a cohort of nine patients with ischaemic stroke (age: 56±9 years; three women/six men; seven subcortical, one medullary and one cortical). On each fMRI day, the unaffected/affected ratio of maximal index tapping rate (IT-R) was obtained. To assess the M1 hemispheric activation balance, the authors computed the classic Laterality Index (LI). The correlation between LI and IT-R was computed for each time point separately.ResultsThe expected correlation between LI-M1 and IT-R, that is, motor performance worse with more unphysiological LI, prevailed at both time points (Kendall p=0.008 and 0.058, respectively), with no statistically significant difference between the two regressions. The same analysis for the dorsal premotor cortex and the supplementary motor area showed no significant correlation at either time-point.ConclusionThese results from a small cohort of longitudinally assessed patients suggest that the relationship between M1 laterality index and hand motor performance appears independent of time since onset of stroke. This in turn may suggest that attempting to restore the hemispheric balance by enhancing ipsilesional M1 and/or constraining contralesional M1 activity may have consistent efficacy throughout recovery.
The causes of decadal variations in global warming are poorly understood, however it is widely understood that variations in ocean heat content (OHC) are linked with variations in surface warming. To ...investigate the forced response of OHC to anthropogenic aerosols (AA), we use an ensemble of historical simulations, which were carried out using a range of anthropogenic aerosol forcing magnitudes in a CMIP6‐era global circulation model. We find that the centennial scale linear trends in historical OHC are significantly sensitive to AA forcing magnitude (−3.0 ± 0.1 × 105 (J m−3 century−1)/(W m−2), R2 = 0.99), but interannual to multi‐decadal variability in global OHC appear largely independent of AA forcing magnitude. Comparison with observations find consistencies in different depth ranges and at different time scales with all but the strongest aerosol forcing magnitude, at least partly due to limited observational accuracy. We find that OHC is sensitive to aerosol forcing magnitude across much of the tropics and sub‐tropics, and stronger negative forcing induces more ocean cooling. The polar regions and North Atlantic show the strongest heat content trends, and also show the strongest dependence on aerosol forcing magnitude. However, the OHC response to increasing aerosol forcing magnitude in the North Atlantic and Southern Ocean is either dominated by internal variability, or strongly state dependent, showing different behavior in different time periods. Our results suggest the response to aerosols in these regions is a complex combination of influences from ocean transport, atmospheric forcings, and sea ice.
Plain Language Summary
As well as emitting greenhouse gases that warm the planet, throughout the industrial era humans have also released substances known as aerosols into the atmosphere. In general, these aerosols reflect heat arriving at the surface of the planet and cause cooling, however we don't have a good idea how changes in the amounts of these aerosols changes ocean warming. Most of the heat that has built up in the climate system has gone into the ocean, so this is important to understand. We use a large computer model to look at how the ocean would have warmed with different levels of aerosols from humans in atmosphere, keeping other things like greenhouse gases the same. We find that the amount of aerosols in the atmosphere strongly affects the warming of the global ocean on timescales of many decades to hundreds of years. Whilst most of the ocean cools when more aerosols are added, parts of the Southern and North Atlantic oceans show different behavior. What is going on in these regions is probably the result of many things, such as changes in ocean currents, in sea ice, as well as in the amount of aerosols and where they are being emitted.
Key Points
Climate model analysis shows centennial trends of historical global ocean heat content (OHC) depend on anthropogenic aerosol forcing strength
Increased aerosol forcing leads to general cooling of the global ocean, but with significant regional and decadal variations
The strongest responses to aerosol forcing coincide with the strongest OHC trends, in the Southern and North Atlantic oceans
Review of Particle Physics Workman, R L; Klempt, E; Agashe, K ...
Progress of theoretical and experimental physics,
08/2022, Letnik:
2022, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Abstract
The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 2,143 new measurements from 709 papers, we list, evaluate, and average measured ...properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as supersymmetric particles, heavy bosons, axions, dark photons, etc. Particle properties and search limits are listed in Summary Tables. We give numerous tables, figures, formulae, and reviews of topics such as Higgs Boson Physics, Supersymmetry, Grand Unified Theories, Neutrino Mixing, Dark Energy, Dark Matter, Cosmology, Particle Detectors, Colliders, Probability and Statistics. Among the 120 reviews are many that are new or heavily revised, including a new review on Machine Learning, and one on Spectroscopy of Light Meson Resonances.
The Review is divided into two volumes. Volume 1 includes the Summary Tables and 97 review articles. Volume 2 consists of the Particle Listings and contains also 23 reviews that address specific aspects of the data presented in the Listings.
The complete Review (both volumes) is published online on the website of the Particle Data Group (pdg.lbl.gov) and in a journal. Volume 1 is available in print as the PDG Book. A Particle Physics Booklet with the Summary Tables and essential tables, figures, and equations from selected review articles is available in print, as a web version optimized for use on phones, and as an Android app.
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