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Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.
To assess the safety of, and subsequent allergy documentation associated with, an antimicrobial stewardship intervention consisting of test-dose challenge procedures prompted by an electronic guideline for hospitalized patients with reported β-lactam allergies.
Retrospective cohort study.
Large healthcare system consisting of 2 academic and 3 community acute-care hospitals between April 2016 and December 2017.
We evaluated β-lactam antibiotic test-dose outcomes, including adverse drug reactions (ADRs), hypersensitivity reactions (HSRs), and electronic health record (EHR) allergy record updates. HSR predictors were examined using a multivariable logistic regression model. Modification of the EHR allergy record after test doses considered relevant allergy entries added, deleted, and/or specified.
We identified 1,046 test-doses: 809 (77%) to cephalosporins, 148 (14%) to penicillins, and 89 (9%) to carbapenems. Overall, 78 patients (7.5%; 95% confidence interval [CI], 5.9%–9.2%) had signs or symptoms of an ADR, and 40 (3.8%; 95% CI, 2.8%–5.2%) had confirmed HSRs. Most HSRs occurred at the second (ie, full-dose) step (68%) and required no treatment beyond drug discontinuation (58%); 3 HSR patients were treated with intramuscular epinephrine. Reported cephalosporin allergy history was associated with an increased odds of HSR (odds ratio [OR], 2.96; 95% CI, 1.34–6.58). Allergies were updated for 474 patients (45%), with records specified (82%), deleted (16%), and added (8%).
This antimicrobial stewardship intervention using β-lactam test-dose procedures was safe. Overall, 3.8% of patients with β-lactam allergy histories had an HSR; cephalosporin allergy histories conferred a 3-fold increased risk. Encouraging EHR documentation might improve this safe, effective, and practical acute-care antibiotic stewardship tool.
Embracing disciplinary approaches ranging from the archaeological to the historical, the sociological to the literary, this collection offers new insights into key texts and interpretive problems in the history of England and the continent between the eighth and thirteenth centuries. Topics range from Bede's use and revision of the anonymous Life of St Cuthbert and the redeployment of patristic texts in later continental and Anglo-Saxon ascetic and hagiographical texts, to Robert Curthose's interaction with the Norman episcopate and the revival of Roman legal studies, to the dynamics of aristocratic friendship in the Anglo-Norman realm, and much more. The volume also includes two methodologically rich studies of vital aspects of the historical landscape of medieval England: rivers and forests.
William North teaches in the Department of History, Carleton College.
Contributors: Richard Allen, Uta-Renate Blumenthal, Ruth Harwood Cline, Thomas Cramer, Mark Gardiner, C. Stephen Jaeger, David A.E. Pelteret, Sally Shockro, Rebecca Slitt, Timothy Smit
Information technology is considered a potentially transformative element in the field of health care by payers, providers, vendors, and consumers alike. Because of this transformative potential, health information technology (HIT) adoption is viewed by many as a key component of health system reform. HIT is in its earliest stages, with diffusion of the technology still relatively limited; at the same time, there is growing awareness of its potential to affect the operation of the entire health care system as a result of the vast amount of information that will become available to both health professionals and patients.
We stand on the edge of change. The Republican coalition is frayed, and its trusty issues — slash taxes, cut programs, deregulate industry, preach morals — have worn thin. Will the Democrats seize the opportunity and capture the political system? Or will Republicans refresh themselves and win a new lease on power? The contest will center on clashing visions and competing programs; since national health insurance is perhaps the Democrats’ signature program, health reform will be, once again, at the eye of the political storm.
The decade of the 1990s was unprecedented in the history of the modern academic health centers (AHCs) in the United States, as it was for health care institutions generally. The nation's 125 AHCs had for the previous 40 years grown steadily larger, more powerful, and more lustrous. They had built or acquired hospitals, outpatient buildings, and research facilities. Their faculties had captured an enviable share of Nobel prizes in their fields and pioneered life-saving treatments for cardiovascular disease, cancer, and other illnesses. Despite occasional storms associated with the introduction of new Medicare payment policies (i.e., diagnosis-related groups or DRGs and the resource-based relative value system or RBRVS), AHCs' clinical facilities had mostly sailed to higher volumes of patient care, higher clinical income, and increasing fiscal reserves. If few administrators or board members from parent universities understood the intricacies of these complex medical institutions – their peculiar organizational structures, accounting practices, promotion rituals, and cultures – well, there were other parts of the university that were both more comprehensible and more problematic. Academic health centers did not appear broken, or to need fixing.
All that changed dramatically for many AHCs and their parent universities in the middle and late 1990s. Out of a seemingly clear horizon, a tidal wave of red ink crashed across the balance sheets of some of the nation's most eminent and heretofore invulnerable AHCs.
It is difficult to quantify the mechanism(s) responsible for competition-induced yield loss using traditional experimental techniques. A technique using yield and 13C discrimination (Δ) for wheat, a C3 plant, has been developed to separate total yield loss (TYL) into yield loss due to N (YLNS) and water (YLWS) stresses. The objective of this research was to determine whether the Δ approach could be used in corn, a C4 plant, to separate TYL into YLNS and yield loss due to a combination of water and light stresses (YLWLS). The field study had a factorial design using five corn densities and five N rates and was conducted in western Nebraska in 1999 and 2000. Relationships for YLNS and YLWLS with TYL were derived from only a portion of the yield and Δ data collected in 1999 and validated based on the remaining data collected in 1999 and 2000. In 1999, 20 to 40% of TYL was due to YLWLS, whereas in 2000, a dry year, YLWLS accounted for 60 to 80% of the TYL. Results from using the Δ-based approach were consistent with analysis of variance results. For example, calculated YLWLS values were related to measured YLWLS by the equation: calculated YLWLS = 19 + 0.91 (measured YLWLS) (r2 = 0.95; P < 0.01). The Δ approach, based on a plant's physiological response to the environment, can be used to separate and quantify competition-induced YLNS and YLWLS in corn.
Endometriosis originates in the uterine lining and affects ~20% of reproductive-age women. The disease often causes chronic pelvic pain, affects ovulatory function and influences fertility. Although laparoscopic diagnosis of uterine endometriosis is quite specific, direct visualisation can be difficult or inaccurate in some circumstances, and it is not useful for diagnosing extra-abdominal disease. Laparoscopy is an invasive procedure, has significant morbidity and cannot be carried out frequently to monitor efficacy of therapy and the possibility of recurrence. Thus, a specific, non-invasive diagnostic test is required. One intriguing area of research uses the technology of radioimmunotargeting, which has previously been used for cancer detection. This technique could have potential for the specific detection and eventual treatment of endometriosis. A marker, eosinophil peroxidase (EPO), has been identified that is expressed in ~90% of endometriosis specimens, and is not expressed or only weakly expressed in normal endometrium. The US Food and Drug Administration has approved a monoclonal antibody to EPO for investigation as an immunoimaging agent in cancers that exhibit eosinophilia. EPO targeting using this antibody could be useful for detecting and/or treating endometriosis.
Single wafer amorphous silicon deposition was characterized through process modeling and film characterization for application in semiconductor production. DOE methodology was used to determine the main deposition parameters, and the responses were limited to device production requirement properties of surface roughness, deposition rate and degree of crystallinity of the as-deposited film. The data trends and models show that deposition temperature and silane flow are the main factors. Increasing either or both factor increases the deposition rate and the surface roughness. The surface morphology, evaluated by AFM, SEM and TEM, was found to be rougher at extreme growth conditions than the poly crystalline film formed after anneal. The as-deposited surface morphology was not a result of pre-anneal crystal formations as determined by TEM cross sections of samples before and after anneal. Lack of crystalinity is important for impurity diffusion considerations. Device application of the single wafer a-Si process will be a compromise between growth rate (and associated throughput) and surface roughness that can be tolerated.
Twelve per cent of a series of 284 patients with vestibular schwannoma presented with sudden deafness. If sudden sensorineural hearing loss is present then it is very likely to be the main presenting symptom. The mean length of patients' history is eight months shorter in this group than in the non-sudden deafness group. Sixteen per cent of vestibular schwannoma patients without sudden deafness present with a 'dead' ear whereas 29.5 per cent of those presenting with sudden deafness have total hearing loss. There was no significant difference between the sudden deafness group and the 'all others' group with regard to tumour size, udiogram shape, caloric test, imbalance, and facial numbness. Although the numbers of patients with sudden deafness in this series were too small to reach significance, on the basis of the clinical correlation of vestibular schwannoma morphology it is possible to postulate that compression of the vasculature within the bony internal auditory canal by a laterally arising tumour may be the aetiological factor and may be more likely to occur than in more medially arising tumours.
A strong correlation has been established between TiN substrate anneal ambient and electromigration performance of Al-based alloys. Excellent electromigration lifetimes were measured for AlSiCu (and AlCu) films on sputtered TiN substrates annealed in N2 and slowly cooled down in furnace. The films annealed in N2-O2 and N2-H2 showed poorer electromigration performance, in that order. Stronger Al (111) texture, larger median grain size and uniform grain size distribution have been responsible for the improved electromigration performance of the N2-annealed (furnace-cooled) films. On the contrary, Al alloy films on TiN substrates annealed in N2 (but air-cooled), N2-O2, or N2-H2 ambient showed weaker Al (111) textures and smaller median grain sizes.
Genetic diagnostic techniques increasingly permit the detection of predisposition to illness long before the onset of the disease process itself. Medicine is on the verge of becoming a predictive science as well as a diagnostic and therapeutic one. Genetic diagnosis could have profound effects on many aspects of our health care system, including the prestige and effectiveness of preventive medicine, the competitive behavior of health care organizations and insurance companies, access to private health insurance, the ability of primary care physicians to serve as gatekeepers, and other matters. This article examines the range of potential effects of the new genetic diagnostics on the organization and financing of health care. For purposes of illustration the authors examine in detail the possible consequences of genetic tests for predisposition to two diseases: Reye's Syndrome and lung cancer in smokers.
For some observers, the artificial heart represents the latest, and perhaps the most flagrant example of the health system's tendency to favor the rapid introduction of expensive but ineffective technologies over efforts to prevent disease and to improve access to care (5;6;19;44;45). Even if it can be perfected, they argue, its opportunity cost in terms of other foregone health benefits would be exorbitant. The ultimate failing of the health care system, it would seem, is its failure to establish mechanisms to select among alternative uses of resources. If such mechanisms had existed, some critics believe that the quest for an artificial heart never would have begun and certainly its premature clinical uses could have been prevented (6;45).