Perioperative Risk Factors for Postoperative Delirium in Patients Undergoing Esophagectomy

Background Postoperative delirium affects up to 50% of patients undergoing esophagectomy and is associated with negative outcomes. The perioperative risk factors for delirium in this population are not well understood. We conducted this study to assess perioperative risk factors for postoperative delirium among esophagectomy patients. Methods We performed a secondary data analysis of patients enrolled in a randomized controlled trial evaluating the efficacy of haloperidol prophylaxis postoperatively in reducing delirium among esophagectomy patients. Postoperative delirium was assessed twice daily using the Confusion Assessment Method for the ICU. Univariate and logistic regression analyses were performed to examine the association between perioperative variables and development of postoperative delirium. Results Of 84 consecutive esophagectomy patients, 27 (32%) developed postoperative delirium. Patients who developed postoperative delirium had higher APACHE II scores [22.1 (6.5) versus 17.4 (6.8); p=0.003], longer mechanical ventilation days [1.7 (1.4) versus 1.0 (1.1); p=0.001], and longer ICU days [5.1 (2.6) versus 2.6 (1.6); p<0.001]. In a logistic regression model, only ICU length of stay was found to have significant association with postoperative delirium [OR 1.65; 95% CI 1.21-2.25]. Conclusions ICU length of stay was significantly associated with postoperative delirium. Other perioperative factors including duration of surgery, blood loss, and hemoglobin levels were not significantly associated with postoperative delirium

Far-Term Exploration of Advanced Single-Aisle Subsonic Transport Aircraft Concepts

Far-term single-aisle class aircraft concepts for potential entry-into-service of 2045 were investigated using an Interactive Reconfigurable Matrix of Alternatives (IRMA) approach. The configurations identified through this design space exploration were then distilled into three advanced aircraft concepts best characterizing the prominent features identified through the IRMA exploration. These three aircraft concepts were then configured and sized for a 150-passenger capacity and a 3,500 nautical mile design mission. Mission block fuel burn was estimated and compared to a far-term conventional configuration baseline concept and a 2005 l. These comparisons suggest considerable potential improvements in fuel efficiency from the investigated advanced concepts

A dual role for A-type lamins in DNA double-strand break repair

A-type lamins are emerging as regulators of nuclear organization and function. Changes in their expression are associated with cancer and mutations are linked to degenerative diseases—laminopathies. Although a correlation exists between alterations in lamins and genomic instability, the molecular mechanisms remain largely unknown. We previously found that loss of A-type lamins leads to degradation of 53BP1 protein and defective long-range non-homologous end-joining (NHEJ) of dysfunctional telomeres. Here, we determined how loss of A-type lamins affects the repair of short-range DNA double-strand breaks (DSBs) induced by ionizing radiation (IR). We find that lamins deficiency allows activation of the DNA damage response, but compromises the accumulation of 53BP1 at IR-induced foci (IRIF), hindering the fast phase of repair corresponding to classical-NHEJ. Importantly, reconstitution of 53BP1 is sufficient to rescue long-range and short-range NHEJ. Moreover, we demonstrate an unprecedented role for A-type lamins in the maintenance of homologous recombination (HR). Depletion of lamins compromises HR by a mechanism involving transcriptional downregulation of BRCA1 and RAD51 by the repressor complex formed by the Rb family member p130 and E2F4. In line with the DNA repair defects, lamins-deficient cells exhibit increased radiosensitivity. This study demonstrates that A-type lamins promote genomic stability by maintaining the levels of proteins with key roles in DNA DSBs repair by NHEJ and HR. Our results suggest that silencing of A-type lamins by DNA methylation in some cancers could contribute to the genomic instability that drives malignancy. In addition, lamins-deficient tumor cells could represent a good target for radiation therapy

Plasma-derived proteomic biomarkers in human leukocyte antigen-haploidentical or human leukocyte antigen-matched bone marrow transplantation using post-transplantation cyclophosphamide

Recent studies have suggested that plasma-derived proteins may be potential biomarkers relevant for graft-versus-host disease and/or non-relapse mortality occurring after allogeneic blood or marrow transplantation. However, none of these putative biomarkers have been assessed in patients treated either with human leukocyte antigen-haploidentical blood or marrow transplantation or with post-transplantation cyclophosphamide, which has been repeatedly associated with low rates of severe acute graft-versus-host disease, chronic graft-versus-host disease, and non-relapse mortality. We explored whether seven of these plasma-derived proteins, as measured by enzyme-linked immunosorbent assays, were predictive of clinical outcomes in post-transplantation cyclophosphamide-treated patients using plasma samples collected at serial predetermined timepoints from patients treated on prospective clinical studies of human leukocyte antigen-haploidentical (n=58; clinicaltrials.gov Identifier: 00796562) or human leukocyte antigen-matched-related or -unrelated (n=100; clinicaltrials.gov Identifiers: 00134017 and 00809276) T-cell-replete bone marrow transplantation. Day 30 levels of interleukin-2 receptor α, tumor necrosis factor receptor 1, serum STimulation-2 (IL1RL1 gene product), and regenerating islet-derived 3-α all had high areas under the curve of 0.74–0.97 for predicting non-relapse mortality occurrence by 3 months post-transplant in both the human leukocyte antigen-matched and human leukocyte antigen-haploidentical cohorts. In both cohorts, all four of these proteins were also predictive of subsequent non-relapse mortality occurring by 6, 9, or 12 months post-transplant and were significantly associated with non-relapse mortality in univariable analyses. Furthermore, day 30 elevations of interleukin-2 receptor α were associated with grade II–IV and III–IV acute graft-versus-host disease occurring after day 30 in both cohorts. These data confirm that plasma-derived proteins previously assessed in other transplantation platforms appear to retain prognostic and predictive utility in patients treated with post-transplantation cyclophosphamide

Why do women not use antenatal services in low and middle income countries? A metasynthesis of qualitative studies

Background: Almost 50% of women in low & middle income countries (LMIC’s) don’t receive adequate antenatal care. Women’s views can offer important insights into this problem. Qualitative studies exploring inadequate use of antenatal services have been undertaken in a range of countries, but the findings are not easily transferable. We aimed to inform the development of future antenatal care programmes through a synthesis of findings in all relevant qualitative studies. Methods and Findings: Using a pre-determined search strategy, we identified robust qualitative studies reporting on the views and experiences of women in LMIC’s who received inadequate antenatal care. We used meta-ethnographic techniques to generate themes and a line of argument synthesis. We derived policy relevant hypotheses from the findings. We included 21 papers representing the views of more than 1230 women from 15 countries. Three key themes were identified: ‘Pregnancy as socially risky and physiologically healthy’; ‘Resource use and survival in conditions of extreme poverty’and ‘Not getting it right first time’. The line of argument synthesis describes a dissonance between programme design and cultural contexts that may restrict access and discourage return visits. We hypothesize that centralized, risk-focused antenatal care programmes may be at odds with the resources, beliefs and experiences of pregnant women who underuse antenatal services. Conclusions: Our findings suggest that there may be a mis-alignment between current antenatal provision and the social and cultural context of some women in LMIC’s. Antenatal care provision that is theoretically and contextually at odds with local contextual beliefs and experiences are likely to be underused, especially when attendance generates increased personal risks of lost family resource or physical danger during travel; when the promised care is not delivered due to resource constraints; and when women experience covert or overt abuse in care settings

Re-thinking Secularism in Post-Independence Tunisia

The victory of a Tunisian Islamist party in the elections of October 2011 seems a paradox for a country long considered the most secular in the Arab world and raises questions about the nature and limited reach of secularist policies imposed by the state since independence. Drawing on a definition of secularism as a process of defining, managing, and intervening in religious life by the state, this paper identifies how under Habib Bourguiba and Zine al-Abidine Ben Ali the state sought to subordinate religion and to claim the sole right to interpret Islam for the public in an effort to win the monopoly over religious symbolism and, with it, political control. Both Bourguiba and Ben Ali relied on Islamic references for legitimacy, though this recourse to religion evolved to face changing contexts, and both sought to define Islam on their own terms. Bourguiba sought to place himself personally at the summit of power, while under Ben Ali the regime forged an authoritarian consensus of security, unity, and ‘tolerance’. In both cases the state politicised Islam but failed to maintain a monopoly over religious symbolism, facing repeated religious challenges to its political authority

Genome-level analysis of genetic regulation of liver gene expression networks

Liver is the primary site for metabolism of nutrients, drugs and chemical agents. While metabolic pathways are complex and tightly regulated, genetic variation among individuals, reflected in variation in gene expression levels, introduces complexity into research on liver disease. This study aimed to dissect genetic networks that control liver gene expression by combining large-scale quantitative mRNA expression analysis with genetic mapping in a reference population of BXD recombinant inbred mouse strains for which extensive SNP, haplotype and phenotypic data is publicly available. We profiled gene expression in livers of naive mice of both sexes from C57BL/6J, DBA/2J, B6D2F1, and 37 BXD strains using Agilent oligonucleotide microarrays. This data was used to map quantitative trait loci (QTLs) responsible for variation in expression of about 19,000 transcripts. We identified polymorphic cis- and trans-acting loci, including several loci that control expression of large numbers of genes in liver, by comparing the physical transcript position with the location of the controlling QTL. The data is available through a public web-based resource (www.genenetwork.org) that allows custom data mining, identification of co-regulated transcripts and correlated phenotypes, cross-tissue and –species comparisons, as well as testing of a broad array of hypotheses

Short-term tissue decomposition alters stable isotope values and C:N ratio, but does not change relationships between lipid content, C:N ratio, and Δδ13C in marine animals

Measures (e.g. δ15N, δ13C, %C, %N and C:N) derived from animal tissues are commonlyused to estimate diets and trophic interactions. Since tissue samples are often exposed toair or kept chilled in ice over a short-term during sample preparation, they may degrade.Herein, we hypothesize that tissue decomposition will cause changes in these measures. Inthis study, we kept marine fish, crustacean and mollusc tissues in air or ice over 120 h (5days). We found that tissue decomposition in air enriched δ15N (range 0.6½ to 1.3½) andδ13C (0.2½ to 0.4½), decreased %N (0.47 to 3.43 percentage points from staring values of~13%) and %C (4.53 to 8.29 percentage points from starting values of ~43%), and subsequentlyincreased C:N ratio (0.14 to 0.75). In air, while such changes to δ13C were relativelyminor and therefore likely tolerable, changes in δ15N, %N, %C and C:N ratio should be interpretedwith caution. Ice effectively reduced the extent to which decomposition enrichedδ15N ( 0.4½) and δ13C ( 0.2½), and eliminated decomposition in C:N ratio, %N and %C.In our second experiment, for fish tissues in either air or ice over 120 h, we observed noeffects of decomposition on relationships between lipid content, C:N ratio, and Δδ13C(change in δ13C after lipid removal), which are employed to correct δ13C for samples containinglipid. We also confirmed that lipid in tissues caused large errors when estimatingδ13C (mean ± standard error = -1.8½ ± 0.1½, range -0.6½ to -3.8½), and showed both lipidextraction and mathematical correction performed equally well to correct for lipids when estimatingδ13C. We, therefore, recommend that specimens of marine animals should be keptin ice during sample preparation for a short-term, as it is an effective means for minimizingchanges of the stable isotope measures in their tissue