Even-longer-term stability of spontaneous otoacoustic emissions.

This report is an addendum to a previous report by Burns [(2009). J. Acoust. Soc. Am. 125, 3166-3176] that measured spontaneous otoacoustic emissions (SOAEs) in 18 subjects, whose ages at the time of initial measurement ranged from 6 to 42 yr, for follow-up periods of up to 19.5 yr. The major finding of that report was that the frequencies of all SOAEs, in all subjects, declined over time, with an average decline of 0.25% per year. In this report seven SOAEs in the oldest subject were measured for an additional 13.7 yr, for a total follow-up of 33 yr, to age 75.

Genome-wide mapping of IBD segments in an Ashkenazi PD cohort identifies associated haplotypes.

The recent series of large genome-wide association studies in European and Japanese cohorts established that Parkinson disease (PD) has a substantial genetic component. To further investigate the genetic landscape of PD, we performed a genome-wide scan in the largest to date Ashkenazi Jewish cohort of 1130 Parkinson patients and 2611 pooled controls. Motivated by the reduced disease allele heterogeneity and a high degree of identical-by-descent (IBD) haplotype sharing in this founder population, we conducted a haplotype association study based on mapping of shared IBD segments. We observed significant haplotype association signals at three previously implicated Parkinson loci: LRRK2 (OR = 12.05, P = 1.23 × 10(-56)), MAPT (OR = 0.62, P = 1.78 × 10(-11)) and GBA (multiple distinct haplotypes, OR > 8.28, P = 1.13 × 10(-11) and OR = 2.50, P = 1.22 × 10(-9)). In addition, we identified a novel association signal on chr2q14.3 coming from a rare haplotype (OR = 22.58, P = 1.21 × 10(-10)) and replicated it in a secondary cohort of 306 Ashkenazi PD cases and 2583 controls. Our results highlight the power of our haplotype association method, particularly useful in studies of founder populations, and reaffirm the benefits of studying complex diseases in Ashkenazi Jewish cohorts.

Gene flow from North Africa contributes to differential human genetic diversity in southern Europe.

Human genetic diversity in southern Europe is higher than in other regions of the continent. This difference has been attributed to postglacial expansions, the demic diffusion of agriculture from the Near East, and gene flow from Africa. Using SNP data from 2,099 individuals in 43 populations, we show that estimates of recent shared ancestry between Europe and Africa are substantially increased when gene flow from North Africans, rather than Sub-Saharan Africans, is considered. The gradient of North African ancestry accounts for previous observations of low levels of sharing with Sub-Saharan Africa and is independent of recent gene flow from the Near East. The source of genetic diversity in southern Europe has important biomedical implications; we find that most disease risk alleles from genome-wide association studies follow expected patterns of divergence between Europe and North Africa, with the principal exception of multiple sclerosis.

North African Jewish and non-Jewish populations form distinctive, orthogonal clusters.

North African Jews constitute the second largest Jewish Diaspora group. However, their relatedness to each other; to European, Middle Eastern, and other Jewish Diaspora groups; and to their former North African non-Jewish neighbors has not been well defined. Here, genome-wide analysis of five North African Jewish groups (Moroccan, Algerian, Tunisian, Djerban, and Libyan) and comparison with other Jewish and non-Jewish groups demonstrated distinctive North African Jewish population clusters with proximity to other Jewish populations and variable degrees of Middle Eastern, European, and North African admixture. Two major subgroups were identified by principal component, neighbor joining tree, and identity-by-descent analysis-Moroccan/Algerian and Djerban/Libyan-that varied in their degree of European admixture. These populations showed a high degree of endogamy and were part of a larger Ashkenazi and Sephardic Jewish group. By principal component analysis, these North African groups were orthogonal to contemporary populations from North and South Morocco, Western Sahara, Tunisia, Libya, and Egypt. Thus, this study is compatible with the history of North African Jews-founding during Classical Antiquity with proselytism of local populations, followed by genetic isolation with the rise of Christianity and then Islam, and admixture following the emigration of Sephardic Jews during the Inquisition.

A genome-wide scan of Ashkenazi Jewish Crohn's disease suggests novel susceptibility loci.

Crohn's disease (CD) is a complex disorder resulting from the interaction of intestinal microbiota with the host immune system in genetically susceptible individuals. The largest meta-analysis of genome-wide association to date identified 71 CD-susceptibility loci in individuals of European ancestry. An important epidemiological feature of CD is that it is 2-4 times more prevalent among individuals of Ashkenazi Jewish (AJ) descent compared to non-Jewish Europeans (NJ). To explore genetic variation associated with CD in AJs, we conducted a genome-wide association study (GWAS) by combining raw genotype data across 10 AJ cohorts consisting of 907 cases and 2,345 controls in the discovery stage, followed up by a replication study in 971 cases and 2,124 controls. We confirmed genome-wide significant associations of 9 known CD loci in AJs and replicated 3 additional loci with strong signal (p<5×10⁻6). Novel signals detected among AJs were mapped to chromosomes 5q21.1 (rs7705924, combined p = 2×10⁻8; combined odds ratio OR = 1.48), 2p15 (rs6545946, p = 7×10⁻9; OR = 1.16), 8q21.11 (rs12677663, p = 2×10⁻8; OR = 1.15), 10q26.3 (rs10734105, p = 3×10⁻8; OR = 1.27), and 11q12.1 (rs11229030, p = 8×10⁻9; OR = 1.15), implicating biologically plausible candidate genes, including RPL7, CPAMD8, PRG2, and PRG3. In all, the 16 replicated and newly discovered loci, in addition to the three coding NOD2 variants, accounted for 11.2% of the total genetic variance for CD risk in the AJ population. This study demonstrates the complementary value of genetic studies in the Ashkenazim.

The history of African gene flow into Southern Europeans, Levantines, and Jews.

Previous genetic studies have suggested a history of sub-Saharan African gene flow into some West Eurasian populations after the initial dispersal out of Africa that occurred at least 45,000 years ago. However, there has been no accurate characterization of the proportion of mixture, or of its date. We analyze genome-wide polymorphism data from about 40 West Eurasian groups to show that almost all Southern Europeans have inherited 1%-3% African ancestry with an average mixture date of around 55 generations ago, consistent with North African gene flow at the end of the Roman Empire and subsequent Arab migrations. Levantine groups harbor 4%-15% African ancestry with an average mixture date of about 32 generations ago, consistent with close political, economic, and cultural links with Egypt in the late middle ages. We also detect 3%-5% sub-Saharan African ancestry in all eight of the diverse Jewish populations that we analyzed. For the Jewish admixture, we obtain an average estimated date of about 72 generations. This may reflect descent of these groups from a common ancestral population that already had some African ancestry prior to the Jewish Diasporas.

Abraham's children in the genome era: major Jewish diaspora populations comprise distinct genetic clusters with shared Middle Eastern Ancestry.

For more than a century, Jews and non-Jews alike have tried to define the relatedness of contemporary Jewish people. Previous genetic studies of blood group and serum markers suggested that Jewish groups had Middle Eastern origin with greater genetic similarity between paired Jewish populations. However, these and successor studies of monoallelic Y chromosomal and mitochondrial genetic markers did not resolve the issues of within and between-group Jewish genetic identity. Here, genome-wide analysis of seven Jewish groups (Iranian, Iraqi, Syrian, Italian, Turkish, Greek, and Ashkenazi) and comparison with non-Jewish groups demonstrated distinctive Jewish population clusters, each with shared Middle Eastern ancestry, proximity to contemporary Middle Eastern populations, and variable degrees of European and North African admixture. Two major groups were identified by principal component, phylogenetic, and identity by descent (IBD) analysis: Middle Eastern Jews and European/Syrian Jews. The IBD segment sharing and the proximity of European Jews to each other and to southern European populations suggested similar origins for European Jewry and refuted large-scale genetic contributions of Central and Eastern European and Slavic populations to the formation of Ashkenazi Jewry. Rapid decay of IBD in Ashkenazi Jewish genomes was consistent with a severe bottleneck followed by large expansion, such as occurred with the so-called demographic miracle of population expansion from 50,000 people at the beginning of the 15th century to 5,000,000 people at the beginning of the 19th century. Thus, this study demonstrates that European/Syrian and Middle Eastern Jews represent a series of geographical isolates or clusters woven together by shared IBD genetic threads.

Quantifying and Remediating the New Graduate Nurse Resident Academic-Practice Gap Using Online Patient Simulation.

BACKGROUND: There is an ever-widening academic-practice gap. Less than one third of new graduates demonstrate entry-level competencies required for practice. Hospitals expend many resources to create nurse residency programs to remediate this gap. Online interactive case simulation is effective to increase competencies and decrease the length of orientation and rate of turnover. The aims of this pilot research study were to quantify the academic-practice gap and to strengthen areas of development for competent and safe clinical practice through use of an online patient simulation program. METHOD: A pretest-posttest quasi-experimental study using an online patient simulation program was implemented in a convenience sample of nurse residents over 16 months. RESULTS: Twenty-nine residents completed more than 3,400 patient simulations. Improvement in pretest and posttest metrics included 100% of nurse residents committing a sentinel error event decreased to 20.7%, 766 medication errors decreased to 160, and failed-to-rescue an average of 81% of the time decreased to 23%. CONCLUSION: Interactive online patient simulation programs provide a powerful learning methodology in which learners improve patient safety and reduce failures to rescue. [J Contin Educ Nurs. 2021;52(5):240-247.].

Long-term stability of spontaneous otoacoustic emissions.

Spontaneous otoacoustic emissions (SOAEs) were measured longitudinally for durations up to 19.5 years. Initial ages of the subjects ranged from 6 to 41 years. The most compelling finding was a decrease in frequency of all emissions in all subjects, which was approximately linear in %/year and averaged 0.25%/year. SOAE levels also tended to decrease with age, a trend that was significant, but not consistent across emissions, either within or across subjects. Levels of individual SOAEs might decrease, increase, or remain relatively constant with age. Several types of frequency/level instabilities were noted in which some SOAEs within an ear interacted such that their levels were negatively correlated. These instabilities often persisted for many years. SOAEs were also measured in two females over the course of their pregnancies. No changes in SOAE levels or frequencies were seen, that were larger than have been reported in females over a menstrual cycle, suggesting that levels of female gonadal hormones do not have a significant direct effect on SOAE frequencies or levels.

A 5-year observational study of lung-protective ventilation in the operating room: a single-center experience.

PURPOSE: We assessed the evolution of lung-protective ventilation strategies during anesthesia and identified factors associated with the selection of a nonprotective ventilation strategy. METHODS: This retrospective observational study covered a 5-year period from March 2006 to March 2011. It included 45575 adult patients who underwent intubation de novo in the operating room. We considered a tidal volume (VT) greater than 10 mL/kg of ideal body weight (IBW) and/or positive end-expiratory pressure (PEEP) less than 5 cm H2O as not lung protective. We evaluated the use of nonprotective ventilation strategies over time in men and women, by American Society of Anesthesiologists classification, and for elective vs emergent surgery. RESULTS: Over the duration of the study, there was a significant reduction in the percentage of patients receiving a VT greater than 10 mL/kg IBW (28.5%-16.3%, P < .001), zero PEEP (27.5%-18.2%, P < .001), and VT greater than 10 mL/kg IBW with PEEP less than 5 cm H2O (13.4%-8.0%, P < .001). The odds of receiving nonprotective ventilation were greater for women than for men, in the first year compared with the last year, and for elective compared with emergent surgery. CONCLUSION: Although use of nonprotective ventilation decreased over time, an important percentage of patients continue to receive nonprotective ventilation.

Think they're drunk? Alcohol servers and the identification of intoxication.

Despite alcohol server training programs and legal liability aimed at controlling intoxication, server intervention appears to be rare. Given the difficulty in assessing intoxication, it can be assumed that improvement in assessment skills would increase the likelihood of intervention. Unfortunately, little is known regarding practices servers use to identify intoxication. In order to build a more informed base for policy formation and server training, the focus of this inquiry was to examine practices used by servers to assess intoxication. The analysis was based upon questionnaires mailed to a random probability sample of licensed servers from one state (N = 822). Indicators found to be most important were examined in relation to a variety of occupational characteristics. Implications for training curricula, policy formation, and future research are discussed.

Morphologic diagnosis of thrombotic thrombocytopenic purpura.

The diagnosis of thrombotic thrombocytopenic purpura (TTP) rests on evidence of microangiopathic hemolytic anemia and thrombocytopenia in the absence of disseminated intravascular coagulation and other known causes of thrombotic microangiopathy. Highly specific diagnostic tools such as serum levels of ADAMTS13 are not routinely available for immediate clinical diagnosis. The presence of schistocytes on a blood smear is the morphologic hallmark of the disease, but no guidelines exist as to the number of schistocytes required to differentiate TTP from other thrombotic microangiopathies. We studied 6 patients with TTP and compared their schistocyte counts with those of 40 normal subjects, 28 patients with chronic renal disease, 5 with preeclampsia, and 5 with normal functioning mechanical heart valves. The mean schistocyte count for the TTP patients was 8.35% versus 0.05% for normal subjects, 0.2% for renal patients, 0.25% for preeclamptic patients, and 0.18% for patients with mechanical valves (P < 0.001). Schistocytes were found on 100% of blood films of TTP patients and ranged from 1.0% to 18.4% of red cells. Schistocytes are found on the smears of 58% of normal individuals and on 80-100% of the other patient groups studied, but always comprise less than 0.5% of the red cell population. An initial schistocyte count of greater than 1% strongly suggests a diagnosis of TTP in the absence of other known causes of thrombotic microangiopathy.