Self-degradation of heat shock proteins

The 70-kDa heat shock protein of Drosophila decays in vivo at a much faster rate than other abundantly labeled proteins. Degradation also occurs in vitro, even during electrophoresis. It appears that this degradation is not mediated by a general protease and that the 70-kDa heat shock protein has a slow proteolytic action upon itself. Heat-induced proteins in CHO cells and a mouse cell line also degrade spontaneously in vitro, as do certain non-heat shock proteins from Drosophila tissues as well as the cell lines

50 Years of Test (Un)fairness: Lessons for Machine Learning

Quantitative definitions of what is unfair and what is fair have been introduced in multiple disciplines for well over 50 years, including in education, hiring, and machine learning. We trace how the notion of fairness has been defined within the testing communities of education and hiring over the past half century, exploring the cultural and social context in which different fairness definitions have emerged. In some cases, earlier definitions of fairness are similar or identical to definitions of fairness in current machine learning research, and foreshadow current formal work. In other cases, insights into what fairness means and how to measure it have largely gone overlooked. We compare past and current notions of fairness along several dimensions, including the fairness criteria, the focus of the criteria (e.g., a test, a model, or its use), the relationship of fairness to individuals, groups, and subgroups, and the mathematical method for measuring fairness (e.g., classification, regression). This work points the way towards future research and measurement of (un)fairness that builds from our modern understanding of fairness while incorporating insights from the past.Comment: FAT* '19: Conference on Fairness, Accountability, and Transparency (FAT* '19), January 29--31, 2019, Atlanta, GA, US

Dynamic Career Models and Inequality Research: A Reexamination of the Sørensen Model

This article presents a reexamination of the Sørensen model. This model derives the pattern of individual careers from structural considerations. If longitudinal data on individual careers are available, Sørensen's model provides two methods to infer the underlying structural parameter. This structural parameter gives a useful measure for unequal career chances. An implementation of these methods, using firm data, shows, however, that they lead to contradictory conclusions; this is shown to be the result of some unrealistic assumptions Sørensen uses in his derivation. Some more realistic assumptions are suggested that produce reasonable results. Finally, it is shown that despite these modifications, the main conclusions of the Sørensen model are preserved. This seems to be promising for future work with this model

A hospital-site controlled intervention using audit and feedback to implement guidelines concerning inappropriate treatment of catheter-associated asymptomatic bacteriuria

<p>Abstract</p> <p>Background</p> <p>Catheter-associated urinary tract infection (CAUTI) is one of the most common hospital-acquired infections. However, many cases treated as hospital-acquired CAUTI are actually asymptomatic bacteriuria (ABU). Evidence-based guidelines recommend that providers neither screen for nor treat ABU in most catheterized patients, but there is a significant gap between these guidelines and clinical practice. Our objectives are (1) to evaluate the effectiveness of an audit and feedback intervention for increasing guideline-concordant care concerning catheter-associated ABU and (2) to measure improvements in healthcare providers' knowledge of and attitudes toward the practice guidelines associated with the intervention.</p> <p>Methods/Design</p> <p>The study uses a controlled pre/post design to test an intervention using audit and feedback of healthcare providers to improve their compliance with ABU guidelines. The intervention and the control sites are two VA hospitals. For objective 1 we will review medical records to measure the clinical outcomes of inappropriate screening for and treatment of catheter-associated ABU. For objective 2 we will survey providers' knowledge and attitudes. Three phases of our protocol are proposed: the first 12-month phase will involve observation of the baseline incidence of inappropriate screening for and treatment of ABU at both sites. This surveillance for clinical outcomes will continue at both sites throughout the study. Phase 2 consists of 12 months of individualized audit and feedback at the intervention site and guidelines distribution at both sites. The third phase, also over 12 months, will provide unit-level feedback at the intervention site to assess sustainability. Healthcare providers at the intervention site during phase 2 and at both sites during phase 3 will complete pre/post surveys of awareness and familiarity (knowledge), as well as of acceptance and outcome expectancy (attitudes) regarding the relevant practice guidelines.</p> <p>Discussion</p> <p>Our proposal to bring clinical practice in line with published guidelines has significant potential to decrease overdiagnosis of CAUTI and associated inappropriate antibiotic use. Our study will also provide information about how to maximize effectiveness of audit and feedback to achieve guideline adherence in the inpatient setting.</p> <p>Trial Registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01052545">NCT01052545</a></p

An Ethnohistorical Perspective on Cheyenne Demography

Administrative censuses of the Southern Cheyenne Indians from 1880,1891, and 1900 permit family reconstitution, identification of residence groups, and comparisons of fertility between monogamous and polygynous women, when the records are approached by ethnohistori cal methods. This approach includes an awareness of the aboriginal adoption practices, kinship system, and naming practices. It is argued that the biases and distortions of administrative records can be effectively corrected to add to our store of information on band and tribal societies.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

The association between clinical integration of care and transfer of veterans with acute coronary syndromes from primary care VHA hospitals

BACKGROUND: Few studies report on the effect of organizational factors facilitating transfer between primary and tertiary care hospitals either within an integrated health care system or outside it. In this paper, we report on the relationship between degree of clinical integration of cardiology services and transfer rates of acute coronary syndrome (ACS) patients from primary to tertiary hospitals within and outside the Veterans Health Administration (VHA) system. METHODS: Prospective cohort study. Transfer rates were obtained for all patients with ACS diagnoses admitted to 12 primary VHA hospitals between 1998 and 1999. Binary variables measuring clinical integration were constructed for each primary VHA hospital reflecting: presence of on-site VHA cardiologist; referral coordinator at the associated tertiary VHA hospital; and/or referral coordinator at the primary VHA hospital. We assessed the association between the integration variables and overall transfer from primary to tertiary hospitals, using random effects logistic regression, controlling for clustering at two levels and adjusting for patient characteristics. RESULTS: Three of twelve hospitals had a VHA cardiologist on site, six had a referral coordinator at the tertiary VHA hospital, and four had a referral coordinator at the primary hospital. Presence of a VHA staff cardiologist on site and a referral coordinator at the tertiary VHA hospital decreased the likelihood of any transfer (OR 0.45, 95% CI 0.27–0.77, and 0.46, p = 0.002, CI 0.27–0.78). Conversely, having a referral coordinator at the primary VHA hospital increased the likelihood of transfer (OR 6.28, CI 2.92–13.48). CONCLUSIONS: Elements of clinical integration are associated with transfer, an important process in the care of ACS patients. In promoting optimal patient care, clinical integration factors should be considered in addition to patient characteristics

Genetic and Epigenetic Factors at COL2A1 and ABCA4 Influence Clinical Outcome in Congenital Toxoplasmosis

Background: Primary Toxoplasma gondii infection during pregnancy can be transmitted to the fetus. At birth, infected infants may have intracranial calcification, hydrocephalus, and retinochoroiditis, and new ocular lesions can occur at any age after birth. Not all children who acquire infection in utero develop these clinical signs of disease. Whilst severity of disease is influenced by trimester in which infection is acquired by the mother, other factors including genetic predisposition may contribute.Methods and Findings: In 457 mother-child pairs from Europe, and 149 child/parent trios from North America, we show that ocular and brain disease in congenital toxoplasmosis associate with polymorphisms in ABCA4 encoding ATP-binding cassette transporter, subfamily A, member 4. Polymorphisms at COL2A1 encoding type II collagen associate only with ocular disease. Both loci showed unusual inheritance patterns for the disease allele when comparing outcomes in heterozygous affected children with outcomes in affected children of heterozygous mothers. Modeling suggested either an effect of mother's genotype, or parent-of-origin effects. Experimental studies showed that both ABCA4 and COL2A1 show isoform-specific epigenetic modifications consistent with imprinting.Conclusions: These associations between clinical outcomes of congenital toxoplasmosis and polymorphisms at ABCA4 and COL2A1 provide novel insight into the molecular pathways that can be affected by congenital infection with this parasite

Use of outpatient care in VA and Medicare among disability-eligible and age-eligible veteran patients

<p>Abstract</p> <p>Background</p> <p>More than half of veterans who use Veterans Health Administration (VA) care are also eligible for Medicare via disability or age, but no prior studies have examined variation in use of outpatient services by Medicare-eligible veterans across health system, type of care or time.</p> <p>Objectives</p> <p>To examine differences in use of VA and Medicare outpatient services by disability-eligible or age-eligible veterans among veterans who used VA primary care services and were also eligible for Medicare.</p> <p>Methods</p> <p>A retrospective cohort study of 4,704 disability- and 10,816 age-eligible veterans who used VA primary care services in fiscal year (FY) 2000. We tracked their outpatient utilization from FY2001 to FY2004 using VA administrative and Medicare claims data. We examined utilization differences for primary care, specialty care, and mental health outpatient visits using generalized estimating equations.</p> <p>Results</p> <p>Among Medicare-eligible veterans who used VA primary care, disability-eligible veterans had more VA primary care visits (<it>p </it>< 0.001) and more VA specialty care visits (<it>p </it>< 0.001) than age-eligible veterans. They were more likely to have mental health visits in VA (<it>p </it>< 0.01) and Medicare-reimbursed visits (<it>p </it>< 0.01). Disability-eligible veterans also had more total (VA+Medicare) visits for primary care (<it>p </it>< 0.01) and specialty care (<it>p </it>< 0.01), controlling for patient characteristics.</p> <p>Conclusions</p> <p>Greater use of primary care and specialty care visits by disability-eligible veterans is most likely related to greater health needs not captured by the patient characteristics we employed and eligibility for VA care at no cost. Outpatient care patterns of disability-eligible veterans may foreshadow care patterns of veterans returning from Afghanistan and Iraq wars, who are entering the system in growing numbers. This study provides an important baseline for future research assessing utilizations among returning veterans who use both VA and Medicare systems. Establishing effective care coordination protocols between VA and Medicare providers can help ensure efficient use of taxpayer resources and high quality care for disabled veterans.</p

Attenuation of the Sensing Capabilities of PhoQ in Transition to Obligate Insect–Bacterial Association

Sodalis glossinidius, a maternally inherited endosymbiont of the tsetse fly, maintains genes encoding homologues of the PhoP-PhoQ two-component regulatory system. This two-component system has been extensively studied in facultative bacterial pathogens and is known to serve as an environmental magnesium sensor and a regulator of key virulence determinants. In the current study, we show that the inactivation of the response regulator, phoP, renders S. glossinidius sensitive to insect derived cationic antimicrobial peptides (AMPs). The resulting mutant strain displays reduced expression of genes involved in the structural modification of lipid A that facilitates resistance to AMPs. In addition, the inactivation of phoP alters the expression of type-III secretion system (TTSS) genes encoded within three distinct chromosomal regions, indicating that PhoP-PhoQ also serves as a master regulator of TTSS gene expression. In the absence of phoP, S. glossinidius is unable to superinfect either its natural tsetse fly host or a closely related hippoboscid louse fly. Furthermore, we show that the S. glossinidius PhoQ sensor kinase has undergone functional adaptations that result in a substantially diminished ability to sense ancestral signals. The loss of PhoQ's sensory capability is predicted to represent a novel adaptation to the static symbiotic lifestyle, allowing S. glossinidius to constitutively express genes that facilitate resistance to host derived AMPs