Privacy Impact Assessments for Digital Repositories

Trustworthy data repositories ensure the security of their collections. We argue they should also ensure the security of researcher and human subject data. Here we demonstrate the use of a privacy impact assessment (PIA) to evaluate potential privacy risks to researchers using the ICPSR’s Open Badges Research Credential System as a case study. We present our workflow and discuss potential privacy risks and mitigations for those risks. [This paper is a conference pre-print presented at IDCC 2020 after lightweight peer review.]&nbsp

Diet as prophylaxis and treatment for venous thromboembolism?

<p>Abstract</p> <p>Background</p> <p>Both prophylaxis and treatment of venous thromboembolism (VTE: deep venous thrombosis (DVT) and pulmonary emboli (PE)) with anticoagulants are associated with significant risks of major and fatal hemorrhage. Anticoagulation treatment of VTE has been the standard of care in the USA since before 1962 when the U.S. Food and Drug Administration began requiring randomized controlled clinical trials (RCTs) showing efficacy, so efficacy trials were never required for FDA approval. In clinical trials of 'high VTE risk' surgical patients before the 1980s, anticoagulant prophylaxis was clearly beneficial (fatal pulmonary emboli (FPE) without anticoagulants = 0.99%, FPE with anticoagulants = 0.31%). However, observational studies and RCTs of 'high VTE risk' surgical patients from the 1980s until 2010 show that FPE deaths without anticoagulants are about one-fourth the rate that occurs during prophylaxis with anticoagulants (FPE without anticoagulants = 0.023%, FPE while receiving anticoagulant prophylaxis = 0.10%). Additionally, an FPE rate of about 0.012% (35/28,400) in patients receiving prophylactic anticoagulants can be attributed to 'rebound hypercoagulation' in the two months after stopping anticoagulants. Alternatives to anticoagulant prophylaxis should be explored.</p> <p>Methods and Findings</p> <p>The literature concerning dietary influences on VTE incidence was reviewed. Hypotheses concerning the etiology of VTE were critiqued in relationship to the rationale for dietary versus anticoagulant approaches to prophylaxis and treatment.</p> <p>Epidemiological evidence suggests that a diet with ample fruits and vegetables and little meat may substantially reduce the risk of VTE; vegetarian, vegan, or Mediterranean diets favorably affect serum markers of hemostasis and inflammation. The valve cusp hypoxia hypothesis of DVT/VTE etiology is consistent with the development of VTE being affected directly or indirectly by diet. However, it is less consistent with the rationale of using anticoagulants as VTE prophylaxis. For both prophylaxis and treatment of VTE, we propose RCTs comparing standard anticoagulation with low VTE risk diets, and we discuss the statistical considerations for an example of such a trial.</p> <p>Conclusions</p> <p>Because of (a) the risks of biochemical anticoagulation as anti-VTE prophylaxis or treatment, (b) the lack of placebo-controlled efficacy data supporting anticoagulant treatment of VTE, (c) dramatically reduced hospital-acquired FPE incidence in surgical patients without anticoagulant prophylaxis from 1980 - 2010 relative to the 1960s and 1970s, and (d) evidence that VTE incidence and outcomes may be influenced by diet, randomized controlled non-inferiority clinical trials are proposed to compare standard anticoagulant treatment with potentially low VTE risk diets. We call upon the U. S. National Institutes of Health and the U.K. National Institute for Health and Clinical Excellence to design and fund those trials.</p

The eukaryotic initiation factor 2 kinase GCN2 protects against hepatotoxicity during asparaginase treatment

Asparaginase is an important drug in the treatment regimen for acute lymphoblastic leukemia. Asparaginase depletes circulating asparagine and glutamine, activating an amino acid stress response (AAR) involving phosphorylation of eukaryotic initiation factor 2 (eIF2) by general control nonderepressible kinase 2 (GCN2). We hypothesized that GCN2 functions to mitigate hepatic stress during asparaginase therapy by activating the AAR. To test this idea, C57BL/6J wild-type mice (Gcn2(+/+)) and those deleted for Gcn2 (Gcn2(-/-)) were injected with asparaginase or saline excipient one time daily for 1 or 6 days. In liver, increased phosphorylation of eIF2 and mRNA expression of AAR target genes activating transcription factor 4, asparagine synthetase, eIF4E-binding protein 1, and CAAT enhancer-binding protein homologous protein were significantly blunted or blocked in the liver of Gcn2(-/-) mice. Loss of AAR during asparaginase coincided with increases in mammalian target of rapamycin signaling, hepatic triglyceride accumulation, and DNA damage in association with genetic markers of oxidative stress (glutathione peroxidase) and inflammation (tumor necrosis factor alpha-α). Although asparaginase depleted circulating asparagine in both Gcn2(+/+) and Gcn2(-/-) mice, all other amino acids, including plasma glutamine, were elevated in the plasma of Gcn2(-/-) mice. This study shows that loss of GCN2 promotes oxidative stress and inflammatory-mediated DNA damage during asparaginase therapy, suggesting that patients with reduced or dysfunctional AAR may be at risk of developing hepatic complications during asparaginase treatment

Estimates of parameters between direct and maternal genetic effects for weaning weight and direct genetic effects for carcass traits in crossbred cattle

Estimates of heritabilities and genetic correlations were obtained for weaning weight records of 23,681 crossbred steers and heifers and carcass records from 4,094 crossbred steers using animal models. Carcass traits included hot carcass weight; retail product percentage; fat percentage; bone percentage; ribeye area; adjusted fat thickness; marbling score, Warner- Bratzler shear force and kidney, pelvic and heart fat percentage. Weaning weight was modeled with fixed effects of age of dam, sex, breed combination, and birth year, with calendar birth day as a covariate and random direct and maternal genetic and maternal permanent environmental effects. The models for carcass traits included fixed effects of age of dam, line, and birth year, with covariates for weaning and slaughter ages and random direct and maternal effects. Direct and maternal heritabilities for weaning weight were 0.4 ± 0.02 and 0.19 ± 0.02, respectively. The estimate of direct-maternal genetic correlation for weaning weight was negative (−0.18 ± 0.08). Heritabilities for carcass traits of steers were moderate to high (0.34 to 0.60). Estimates of genetic correlations between direct genetic effects for weaning weight and carcass traits were small except with hot carcass weight (0.70), ribeye area (0.29), and adjusted fat thickness (0.26). The largest estimates of genetic correlations between maternal genetic effects for weaning weight and direct genetic effects for carcass traits were found for hot carcass weight (0.61), retail product percentage (−0.33), fat percentage (0.33), ribeye area (0.29), marbling score (0.28) and adjusted fat thickness (0.25), indicating that maternal effects for weaning weight may be correlated with genotype for propensity to fatten in steers