Abstract
The Drosophila tko25t point mutation in the gene encoding mitoribosomal protein S12 produces a complex phenotype of multiple respiratory chain deficiency, developmental delay, ...bang-sensitivity, impaired hearing, sugar and antibiotic sensitivity, and impaired male courtship. Its phenotypic severity was previously shown to be alleviated by inbreeding and to vary with mitochondrial genetic background. Here, we show similarly profound effects conferred by nuclear genetic background. We backcrossed tko25t into each of 2 standard nuclear backgrounds, Oregon R and w1118, the latter used as recipient line in many transgenic applications requiring selection for the white minigene marker. In the w1118 background, tko25t flies showed a moderate developmental delay and modest bang-sensitivity. In the Oregon R background, males showed longer developmental delay and more severe bang-sensitivity, and we were initially unable to produce homozygous tko25t females in sufficient numbers to conduct a meaningful analysis. When maintained as a balanced stock over 2 years, tko25t flies in the Oregon R background showed clear phenotypic improvement though were still more severely affected than in the w1118 background. Phenotypic severity did not correlate with the expression level of the tko gene. Analysis of tko25t hybrids between the 2 backgrounds indicated that phenotypic severity was conferred by autosomal, X-chromosomal, and parent-of-origin-dependent determinants. Although some of these effects may be tko25t specific, we recommend that, in order to minimize genetic drift and confounding background effects, the genetic background of nonlethal mutants should be controlled by regular backcrossing, even if stocks are usually maintained over a balancer chromosome.
Jacobs, Tuomela, and Lillsunde backcross tko25t, a mutation in Drosophila affecting mitochondria, into two commonly used wild-type nuclear backgrounds. Despite the presence of balancer chromosomes—and without deliberate selection—the backcrosses gave systematically different phenotypes that evolved over two years in the laboratory. Their results underscore the potential effects genetic background and drift can have on mutant phenotypes, especially when studying the genetics of multicomponent structures, and they recommend regular backcrossing to control for confounding background effects.
As aircraft have become more reliable, humans have played a progressively more important causal role in aviation accidents. Consequently, a growing number of aviation organizations are tasking their ...safety personnel with developing accident investigation and other safety programs to address the highly complex and often nebulous issue of human error. Yet, many safety professionals are illequipped to perform these new duties.
The purpose of the present book is to remedy this situation by presenting a comprehensive, userfriendly framework to assist practitioners in effectively investigating and analyzing human error in aviation. Coined the Human Factors Analysis and Classification System (HFACS), its framework is based on James Reason's (1990) well-known "Swiss cheese" model of accident causation. In essence, HFACS bridges the gap between theory and practice in a way that helps improve both the quantity and quality of information gathered in aviation accidents and incidents.
The HFACS framework was originally developed for, and subsequently adopted by, the U.S. Navy/Marine Corps as an accident investigation and data analysis tool. The U.S. Army, Air Force, and Coast Guard, as well as other military and civilian aviation organizations around the world are also currently using HFACS to supplement their preexisting accident investigation systems. In addition, HFACS has been taught to literally thousands of students and safety professionals through workshops and courses offered at professional meetings and universities. Indeed, HFACS is now relatively well known within many sectors of aviation and an increasing number of organizations worldwide are interested in exploring its usage. Consequently, the authors currently receive numerous requests for more information about the system on what often seems to be a daily basis.
The loyalty investigations triggered by the Red Scare of the 1940s and 1950s marginalized many talented women and men who had entered government service during the Great Depression seeking to promote ...social democracy as a means to economic reform. Their influence over New Deal policymaking and their alliances with progressive labor and consumer movements elicited a powerful reaction from conservatives, who accused them of being subversives. Landon Storrs draws on newly declassified records of the federal employee loyalty program--created in response to fears that Communists were infiltrating the U.S. government--to reveal how disloyalty charges were used to silence these New Dealers and discredit their policies.
Because loyalty investigators rarely distinguished between Communists and other leftists, many noncommunist leftists were forced to leave government or deny their political views. Storrs finds that loyalty defendants were more numerous at higher ranks of the civil service than previously thought, and that many were women, or men with accomplished leftist wives. Uncovering a forceful left-feminist presence in the New Deal, she shows how opponents on the Right exploited popular hostility to powerful women and their "effeminate" spouses. The loyalty program not only destroyed many promising careers, it prohibited discussion of social democratic policy ideas in government circles, narrowing the scope of political discourse to this day.
Through a gripping narrative based on remarkable new sources, Storrs demonstrates how the Second Red Scare undermined the reform potential of the New Deal and crippled the American welfare state.
Brachytherapy for gynecological cancer is reported to cause pain, anxiety, and distress with no clear guidance for optimizing patient experiences. The aim of this study was to explore patient ...experiences of brachytherapy and views on improvement.
Semistructured interviews were undertaken with patients who had received brachytherapy for locally advanced cervical cancer. Two cohorts were recruited: cohort 1 had recently had brachytherapy, and cohort 2 was a year post brachytherapy. Four recruitment sites were selected, where brachytherapy is given in different ways, some with short day case procedures and others having 1 or 2 overnight stays with applicators in place. Consecutive patients were invited to interview. Participants were asked to retell their brachytherapy story, with views on their care and ideas for improvement. Interviews were audio recorded, transcribed, and data analyzed following Braun and Clarke's method for reflexive thematic analysis.
Thirty-five interviews were conducted (20 in cohort 1 and 15 in cohort 2). Participant's ages ranged from 28 to 87 years. The interview duration ranged from 22 to 78 minutes. Difficult and traumatic experiences were reported, including periods of severe pain and perceptions of poor care. However, some participants described positive experiences and what went well.
Three themes were developed: (1) how the patient got through it, (2) unpleasantness, discomfort, and the aftermath, and (3) emotional consequences and trauma. Some aspects of medium and long duration brachytherapy were found to be more problematic compared with short duration brachytherapy. Exploring experiences at 1-year post brachytherapy has provided insights into the long-lasting impact of brachytherapy experiences.
Hearing the patient voice has demonstrated that further work is needed to improve patient care in modern brachytherapy techniques using different regimens and durations, to minimize difficult and traumatic patient experiences. Study insights will inform future work to develop clinical care recommendations.
Condensed abstract:
We randomized 3398 patients hospitalized with COVID-19 not yet requiring intensive care unit (ICU) management to prophylactic-dose enoxaparin, therapeutic-dose enoxaparin or ...therapeutic-dose apixaban at 76 centers in 10 countries. The 30-day primary composite outcome of all-cause mortality, requirement for ICU level-of-care, systemic thromboembolism, or ischemic stroke was not significantly reduced in the combined therapeutic-dose anticoagulation groups compared with prophylactic-dose anticoagulation. However, fewer patients who were treated with therapeutic-dose anticoagulation required intubation or died. The benefits of therapeutic-dose anticoagulation were most strongly evident in higher-risk patients.
