Total Number of Alterations in Liquid Biopsies Is an Independent Predictor of Survival in Patients With Advanced Cancers.

PurposeStudies have demonstrated an association between quantity of circulating tumor DNA (ctDNA) and poorer survival. We investigated the relationship between percent ctDNA (%ctDNA), total number of ctDNA alterations, and overall survival (OS) in liquid biopsies.Materials and methodsOverall, 418 patients with blood-based next-generation sequencing (54 to 73 genes) were analyzed. Eligible patients included those who had advanced/metastatic solid tumor malignancies and never received immunotherapy treatment, which may alter the survival curve in patients with high mutational burden.ResultsPatients with a high (≥ 5%) %ctDNA had significantly shorter OS versus those with intermediate (≥ 0.4% to < 5%) or low (< 0.4%) values (median OS, 7.0 v 14.1 v not reached [NR] months, respectively; P < .0001). Patients with a high (≥ 5) total number of alterations had significantly shorter OS versus those with intermediate (≥ 1.46 to < 5), low (< 1.46), or no alterations (median OS, 4.6 v 11.7 v 21.3 v NR months, respectively; P < .0001). The total number of alterations correlated with %ctDNA (r = 0.85; 95% CI, 0.81 to 0.87; P < .0001). However, only an intermediate to high total number of alterations (≥ 1.46) was an independent predictor of worse OS (hazard ratio, 1.96; 95% CI, 1.30 to 2.96; P = .0014; multivariate analysis).ConclusionWe demonstrate that the total number of alterations and %ctDNA have prognostic value and correlate with one another, but only the total number of alterations was independently associated with survival outcomes. Our findings suggest that the total number of alterations in plasma may be an indicator of more aggressive tumor biology and therefore poorer survival

Changes in Intergenerational Mobility in Britain

This paper compares and contrasts estimates of the extent of intergenerational income mobility over time in Britain. Estimates based on two British birth cohorts show that mobility appears to have fallen in a cross-cohort comparison of people who grew up in the 1960s and 1970s (the 1958 birth cohort) as compared to a cohort who grew up in the 1970s and 1980s (the 1970 birth cohort). The sensitivity of labour market earnings to parental income rises, thereby showing less intergenerational mobility for the more recent cohort. This supports theoretical notions that the widening wage and income distribution that occurred from the late 1970s onwards slowed down the extent of mobility up or down the distribution across generations.Intergenerational Mobility, Earnings, Family Income, Education.

Changes in Intergenerational Mobility in Britain

This paper compares and contrasts estimates of the extent of intergenerational income mobility over time in Britain. Estimates based on two British birth cohorts show that mobility appears to have fallen in a cross-cohort comparison of people who grew up in the 1960s and 1970s (the 1958 birth cohort) as compared to a cohort who grew up in the 1970s and 1980s (the 1970 birth cohort). The sensitivity of labour market earnings to parental income rises, thereby showing less intergenerational mobility for the more recent cohort. This supports theoretical notions that the widening wage and income distribution that occurred from the late 1970s onwards slowed down the extent of mobility up or down the distribution across generations.

Changes in Intergenerational Mobility in Britain

This paper flatly contradicts the common view that anyone can make it in modern Britain. Indeed, rather then weakening, the link between an individual's earnings and those of his or her parents has strengthened. An important part of the explanation is that the expansion of higher education has benefited people from rich families much more than those from poor families. The extent of intergenerational mobility is frequently seen as a measure of the degree of equality of opportunity in society and considerable research has been devoted to obtaining an accurate estimate of it for a number of countries. However little is known about how these connections have altered through time. Sharp increases in educational attainment and rises in earnings (and living standards in general) in more recent generations mean that many observers seem to think that we now live in a more mobile, meritocratic society than in the past. Contrary to this, this research seems to show that where you come from matters more now than in the past. It appears that the extent of intergenerational mobility has actually fallen. The research uses unique data that follow two cohorts of children (one born in 1958, one born in 1970) through childhood and into adulthood. The latest data, collected in 2000, make it possible, for the first time, for researchers to get a good measure of the adult earnings of the second cohort. The key findings are: [1]The connection between earnings and parental income has strengthened for the more recent cohort. Estimates of the relationship between childhood family income and son's adult earnings show that for the 1958 cohort, a son from a family with twice as much income as a second family will earn about 12 percent more in his early thirties than a son from the second family. In the 1970 cohort, the same figure is 25 percent. Therefore, the degree of intergenerational transmission has risen by 13 percentage points. Results for daughters are very similar; [2] Part of the fall in mobility across generations is due to the fact that the expansion of the higher education system has benefited people from rich fa milies much more than those from poor families. This is particularly the case for daughters. The results show that differences in educational attainment across family background have led to a decline in equality of opportunity. This is despite the large expansion in postcompulsory schooling that occurred between the two cohorts. This may be unexpected to some observers, who see great gains in education and earnings from one generation to another and leave the story there. - But these gains have been unequally distributed across society. The majority of beneficiaries have been children from families who were already doing well. If, as seems to have happened, able children from lower income families are excluded from the expansion of education, this will lower national productivity and income in the long run. The implication for government policy is clear. If equality of opportunity is a serious goal of government, it can be facilitated in a way that can enhance economic welfare via policies directed at high ability children whose parents are doing less well.

Ignite: October 1968

This alternative newspaper was published at the University of North Dakota in October 1968 and feature articles written at University, as well as re-prints from national publications. This issue features the following articles: Huey Newton Convicted by Racist Jury by Bill Freeland; Organized Crime on Campus by Janelle Hongess (the editor of Ignite); Columbia by Paul Goodman; and Quotations from Chairman Lew.https://commons.und.edu/und-books/1068/thumbnail.jp

The evolution of barriers to exploitation: Sometimes the Red Queen can take a break.

We propose a general barrier theory as an evolutionary framework for understanding coevolutionary effects of conflicts of interest in natural and human systems. It is generalized from the barrier theory of cancer, which describes how cancer develops through the evasion of mechanisms, that block unregulated cellular reproduction and survival. Barriers are naturally evolved or artificially implemented mechanisms for blocking exploitation; restraints are mechanisms that impede but do not block exploitation. When conflicts of interest arise, selection will favor exploiters that are capable of overcoming barriers and restraints. When barriers are in place, they halt, at least temporarily, coevolutionary arms races (the Red Queen can stop running). Barriers occur in a broad spectrum of interactions characterized by conflicts of interest: barriers to cellular survival (apoptosis) and reproduction (cell cycle arrest) may block a virus from replicating its genome through reproduction of its host cell. Vaccines may completely protect against targeted pathogens. A plant may escape herbivory by evolving defensive chemicals that block herbivory. Obligate mutualisms may evolve when barriers to horizontal transmission favor symbionts that increasingly lose mechanisms that contribute to horizontal transmission. Here, we show how the barrier theory applies across a spectrum of natural and social systems

Fifty Years of Organizational Behavior from Multiple Perspectives

Many of the underlying themes in the field of organizational behavior reveal the strains between basic and applied research, qualitative and quantitative preferences, gradations of analysis, and the relative importance of research and practice

Can evidence-based medicine and clinical quality improvement learn from each other?

The considerable gap between what we know from research and what is done in clinical practice is well known. Proposed responses include the Evidence-Based Medicine (EBM) and Clinical Quality Improvement. EBM has focused more on ‘doing the right things’—based on external research evidence—whereas Quality Improvement (QI) has focused more on ‘doing things right’—based on local processes. However, these are complementary and in combination direct us how to ‘do the right things right’. This article examines the differences and similarities in the two approaches and proposes that by integrating the bedside application, the methodological development and the training of these complementary disciplines both would gain