PURPOSE OF REVIEWGermline pathogenic TP53 mutation may predispose to multiple cancers but penetrance and cancer patterns remain incompletely documented. We have analyzed international agency for ...research on cancer TP53 database to reevaluate age and variant-dependent tumor patterns.
RECENT FINDINGSGenome-wide studies suggest that germline variants are more frequent than estimated prevalence of Li–Fraumeni syndrome (LFS), suggesting that many carriers of potentially pathogenic mutations may not develop the syndrome. Carriers of a germline TP53 mutation who are detected in a clinical context have a penetrance of 80% at age 70. Penetrance varies according to age, sex and mutation type. Temporal tumor patterns show distinct phases, with childhood phase (0–15 years, 22% of all cancers) characterized by adrenal cortical carcinoma, choroid plexus carcinoma, rhabdomyosarcoma and medulloblastoma; early adulthood phase (16–50 years, 51%) including breast cancer, osteosarcoma, soft tissue sarcomas, leukemia, astrocytoma and glioblastoma, colorectal and lung cancer; late adulthood phase (51–80 years, 27%) including pancreatic and prostate cancer.
SUMMARYGermline pathogenic variants in TP53 gene have different consequences according to cell, tissue, context and age. The occurrence of frequent variants in patients with no criteria suggestive of LFS calls for attention in predicting individual risk and highlights the need of additional predictors for assigning carriers to appropriate surveillance programs.
•The J-value now validated against pan-national data from 180 nations.•A validated, objective safety assessment method now available.•The J-value has explained the Preston and Bristol curves.•The ...life expectancy ratio measures national development.•The life expectancy ratio falls from ⅔ to ½ as a country gets richer.•1st objective measurement of the pure time discount rate.
The J-value is an objective method for determining when life extending measures are sensible, applicable to both manufacturing and service industries, including public health and healthcare. A model of human decision making based on the J-value is able to explain the shape of the Preston curve that relates life expectancy at birth and gross domestic product (GDP) per head for all the nations in the world. Making a number of reasonable assumptions, a J-value model produces a population-average life expectancy, which may be translated easily into a corresponding life expectancy at birth when life expectancy is not modified by discounting (net discount rate equals zero). The resultant values may be tested against pan-national data, showing a very good match. Thus the shape of the Preston curve has been explained and, at the same time, validation has been provided for the J-value model. A perturbation analysis shows that the J-value explanation for the Preston curve starts to break down as the net discount rate is increased above zero. Thus the Preston curve may be seen to validate the J-value model at a net discount rate of zero, but not at higher net discount rates. The result allows a closed-form expression to be derived for the first time for the pure time discount rate, namely the product of the rate of economic growth and the complement of risk-aversion. A further conclusion from the work is that no discernable limit is apparent before the age of 100 to the process by which people live longer as they get richer; such an intrinsic limit might be overcome by future improved medical technology.
•J-value has assessed population relocations after Chernobyl and Fukushima Daiichi.•Relocation was unjustified for 75% of the 335,000 people relocated after Chernobyl.•Relocation was unjustified for ...the 160,000 people relocated after Fukushima.•Loss of life expectancy is a simple but accurate way of conveying radiation risk.•The J-value builds on loss of life expectancy to provide objective guidance.
The policies of population relocation put in train following the severe nuclear reactor accidents at Chernobyl in 1986 and Fukushima Daiichi in 2011 are examined using the Judgement- or J-value. Here relocation is taken to mean a movement of people that is long-term or permanent. A review is made of a 1992 IAEA/CEC study of the Chernobyl countermeasures, which includes data from which the effectiveness of the 1986 and post-1990 relocations may be judged using the J-value. The present analysis provides endorsement of that study’s conclusion that the post-1990 relocation of 220,000 members of the public could not be justified on the grounds of radiological health benefit. Moreover, application of the J-value suggests that the first Chernobyl relocation is economically defensible for between 26% and 62% of the roughly 115,000 people actually moved in 1986. Thus only between 9% and 22% of the 335,000 people finally relocated after Chernobyl were justifiable, based on the J-value and the data available. Nor does the J-value support the relocation of the 160,000 people moved out on a long-term basis after the Fukushima Daiichi nuclear accident. The J-value results for these very severe nuclear accidents should inform the decisions of those deciding how best to respond to a big nuclear accident in the future. The overall conclusion is that relocation should be used sparingly if at all after any major nuclear accident. It is recognised that medical professionals are seeking a good way to communicate radiation risks in response to frequent requests from the general public for information and explanation in a post-accident situation. Radiation-induced loss of life expectancy, which lies at the heart of the application of the J-value to nuclear accidents, is proposed as an information-rich yet easy to understand statistic that the medical profession and others may find helpful in this regard.
Ecosystem engineers are species that have a role in creating and maintaining certain habitat traits that are important for other species. Burrowing species do this by creating subterranean refugia ...from predation and thermal extremes, but also providing foraging opportunities through soil movement and by increasing local landscape heterogeneity. In this study, we used camera traps to monitor the burrows of greater bilbies (Macrotis lagotis), a vulnerable Australian marsupial, in an area subject to frequent disturbance by fire. We tested the hypothesis that bilby burrows provide refuge for other species and therefore their presence increases biodiversity. In total, 45 taxa – 22 bird, 16 reptile and 7 mammal taxa – were recorded interacting with 127 burrows across 7 sites. Species richness was greater at burrows compared with vegetation away from burrows, while abundance was no different. There was no difference in species assemblage for bilby burrows that were actively maintained by bilbies compared with abandoned burrows, although there was more activity at bilby maintained burrows. A wildfire allowed us to test the ad hoc hypothesis that the use of bilby burrows was greater when vegetation cover was removed by fire. We recorded significant differences in species assemblage interacting with burrows after fire, although overall species richness and abundance did not change. The response of individual species was variable; for example, burrows provide a refuge for smaller species (such as mice and small reptiles), and may therefore protect them from the effects of fire. Where they persist, bilbies provide an important ecosystem engineering service, as their burrows support a broad range of species. Further reduction in the distribution of the bilby is therefore likely to have a flow‐on effect on biodiversity, impacting species that use their burrows for refuge.
Ecosystem engineers are species that have a role in creating and maintaining certain habitat traits that are important for other species. Bilby burrows provide important refuge for environmental extremes in the Australian arid zone, and in this study a wide variety of mammals, birds and reptiles were recorded at the entrance to burrows using camera traps. Where they persist, bilbies provide an important ecosystem engineering service, as their burrows support a broad range of species. Further reduction in the distribution of the bilby is therefore likely to have a flow‐on effect on biodiversity, impacting species that use their burrows for refuge.
Critical thinking (CT) is purposeful, self-regulatory judgment that results in interpretation, analysis, evaluation, and inference, as well as explanations of the considerations on which that ...judgment is based. This article summarizes the available empirical evidence on the impact of instruction on the development and enhancement of critical thinking skills and dispositions and student achievement. The review includes 341 effects sizes drawn from quasi- or true-experimental studies that used standardized measures of CT as outcome variables. The weighted random effects mean effect size (g+) was 0.30 (p < .001). The collection was heterogeneous (p < 001). Results demonstrate that there are effective strategies for teaching CT skills, both generic and content specific, and CT dispositions, at all educational levels and across all disciplinary areas. Notably, the opportunity for dialogue, the exposure of students to authentic or situated problems and examples, and mentoring had positive effects on CT skills.
•J-value shows remedial measures after Chernobyl and Fukushima Daiichi to be worthwhile.•Remediation proportionate to the risk should be instituted.•Remediation rather than relocation should be ...highest on the agenda of decision makers responding to a big nuclear accident.•The results will be of strong interest and value to public, politicians and regulators alike.•The results promote the optimal application of resources to protect the real interests of the people living nearby.
Actions set in train shortly after the accidents at Chernobyl (1986), and Fukushima Daiichi (2011) had the aim of reducing the more immediate health effects on people living near the plants, with population relocation being especially prominent. The important topic of relocation is the subject of a companion paper, and this article will concentrate on other measures, such as soil treatment and urban decontamination, that have been put in place to reduce the radiation risks in the medium and long term to people living and farming in areas subject to some degree of radioactive contamination. The J-value method of risk assessment has been used to judge the cost-effectiveness of a range of agricultural and urban remediation actions. Many remedial measures instituted after the Chernobyl and Fukushima Daiichi accidents have been found to be highly cost-effective.
Teaching methods that individualize and adapt instructional conditions to K-12 learners' needs, abilities, and interests help improve learning achievement. The most important variables are the ...teacher's role in the classroom as a guide and mentor and the adaptability of learning activities and materials. This Campbell systematic review assesses the overall impact on student achievement of processes and methods that are more student-centered versus less student-centered. It also considers the strength of student-centered practices in four teaching domains: (1) Flexibility: Degree to which students can contribute to course design, selecting study materials, and stating learning objectives; (2) Pacing of instruction: Students can decide how fast to progress through course content and whether this progression is linear or iterative; (3) Teacher's role: Ranging from authority figure and sole source of information, to teacher as equal partner in the learning process; and (4) Adaptability: Degrees of manipulating learning environments, materials, and activities to make them more student-centered. This review presents evidence from 299 studies (covering 43,175 students in a formal school setting) yielding 365 estimates of the impact of teaching practices. The studies spanned the period 2000-2017 and were mostly carried out in the United States, Europe, and Australia. This review confirms previous research on the effectiveness of student-centered and active learning. It goes further in suggesting the teacher's role promotes effective student-centered learning, and excessive student control over pacing appears to inhibit it.
•An extra year of sheep restrictions would extend the life of the average UK consumer by 8 seconds.•Gains of seconds are below the de minimis quantum of life expectancy and trivial.•An extreme ...consumer eating exclusively the most contaminated sheep meat would lose only 2½ hours’ life expectancy.•Only 360 extreme consumers are possible, and the J-value for stopping their consumption is way too high.•Sheep meat restrictions should have been lifted earlier.
Following the accident at the Chernobyl Nuclear Power Plant in 1986, the United Kingdom Government imposed restrictions on the consumption of sheep meat that became contaminated by nuclear fallout to ensure it was extremely unlikely that any consumers would receive an unacceptable dose. The international context for the restrictions is summarized and a brief review of the strategies employed by the UK is presented. An analysis using the J-value framework, including the de minimis quantum of life expectancy, is made of the cost effectiveness of the sheep meat restrictions in force until 2012, in terms of 4 categories of consumer ranging from the average to the extreme. The paper shows that the risk to the general population was very low indeed at the time the restrictions were removed in 2012. Retaining the restrictions for an extra year, would have averted the dose to the average consumer by a fraction of a microSievert, corresponding to a gain in life expectancy of 8s. Meanwhile for the ICRP Representative Person, the gain in life expectancy from retaining the restrictions for an extra year ranged between 17 and 25s. These gains are nugatory, as they are a factor of between 8 and 23 below the de minimis quantum of life expectancy. This new measure provides a meaningful quantitative criterion for judging when the radiation exposure of a large population is trivial in the sense used by the ICRP. The gains in life expectancy for the Field Representative Person and the Extreme Consumer were above the trivial level, but the associated J-values were 10 and 40, an order of magnitude or more above the value of unity where a case could be made for retaining the restrictions for another year. The high J-values and/or de minimis life expectancy ratios suggest that the food restrictions could almost certainly have been ended earlier. Also discussed are: the choice of the Representative Person, the role of intervention levels, the extent to which conservatisms in analysis are warranted and how socio-political factors in decision making can be taken into account in a transparent way.
We present measurements of the spatial clustering of galaxies with stellar masses >10 super(11) M sub(z), infrared luminosities >10 super(12) L sub(z)(-), and star formation rates >200 M sub(z) yr ...super(-1) in two redshift intervals: 1.5 < z < 2.0 and 2 < z < 3. Both samples cluster moderately strongly, with spatial correlation lengths of r sub(0) = 6.14 c 0.84 h super(-1) Mpc for the 2 < z < 3 sample and r sub(0) = 5.36 c 1.28 h super(-1) Mpc for the 1.5 < z < 2.0 sample. These clustering amplitudes are consistent with both populations residing in dark matter halos with masses of 67 x 10 super(12) M sub(z), which is comparable to that seen for optical QSOs at the same epochs. We infer that a minimum dark matter halo mass is an important factor for all forms of luminous, obscured activity in galaxies at z > 1, both starbursts and active galactic nuclei. Adopting plausible models for the growth of dark matter halos with redshift, the halos hosting the 2 < z < 3 sample will likely host poor to rich clusters of galaxies at z = 0, whereas the halos hosting the 1.5 < z < 2.0 sample will likely host >L super(*) elliptical galaxies or poor clusters at z = 0. We conclude that ultraluminous infrared galaxies (ULIRGs) at z 6 2.5 likely signpost stellar buildup in galaxies that will reside in clusters at z = 0 and that ULIRGs at z 6 1.7 signpost stellar buildup in sources that will either become >L super(*) elliptical galaxies or reside in poor clusters at z = 0.