Freedom of Information Act and Libraries

The Freedom of Information Act (FOIA) makes government information accessible to everyone, including libraries and library patrons. The Patriot Act has undermined the FOIA and put the freedom to read at risk

A Subset of Latency-Reversing Agents Expose HIV-Infected Resting CD4⁺ T-Cells to Recognition by Cytotoxic T-Lymphocytes

Resting CD4⁺ T-cells harboring inducible HIV proviruses are a critical reservoir in antiretroviral therapy (ART)-treated subjects. These cells express little to no viral protein, and thus neither die by viral cytopathic effects, nor are efficiently cleared by immune effectors. Elimination of this reservoir is theoretically possible by combining latency-reversing agents (LRAs) with immune effectors, such as CD8⁺ T-cells. However, the relative efficacy of different LRAs in sensitizing latently-infected cells for recognition by HIV-specific CD8⁺ T-cells has not been determined. To address this, we developed an assay that utilizes HIV-specific CD8⁺ T-cell clones as biosensors for HIV antigen expression. By testing multiple CD8⁺ T-cell clones against a primary cell model of HIV latency, we identified several single agents that primed latently-infected cells for CD8⁺ T-cell recognition, including IL-2, IL-15, two IL-15 superagonists (IL-15SA and ALT-803), prostratin, and the TLR-2 ligand Pam₃CSK₄. In contrast, we did not observe CD8⁺ T-cell recognition of target cells following treatment with histone deacetylase inhibitors or with hexamethylene bisacetamide (HMBA). In further experiments we demonstrate that a clinically achievable concentration of the IL-15 superagonist ‘ALT-803’, an agent presently in clinical trials for solid and hematological tumors, primes the natural ex vivo reservoir for CD8⁺ T-cell recognition. Thus, our results establish a novel experimental approach for comparative evaluation of LRAs, and highlight ALT-803 as an LRA with the potential to synergize with CD8⁺ T-cells in HIV eradication strategies.United States. National Institutes of Health (AI111860

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

“Nanosized Voltmeter” Enables Cellular-Wide Electric Field Mapping

Previously, all biological measurements of intracellular electric fields (E fields), using voltage dyes or patch/voltage clamps, were confined to cellular membranes, which account for <0.1% of the total cellular volume. These membrane-dependent techniques also frequently require lengthy calibration steps for each cell or cell type measured. A new 30-nm “photonic voltmeter”, 1000-fold smaller than existing voltmeters, enables, to our knowledge, the first complete three-dimensional E field profiling throughout the entire volume of living cells. These nanodevices are calibrated externally and then applied for E field determinations inside any live cell or cellular compartment, with no further calibration steps. The results indicate that the E fields from the mitochondrial membranes penetrate much deeper into the cytosol than previously estimated, indicating that, electrically, the cytoplasm cannot be described as a simple homogeneous solution, as often approximated, but should rather be thought of as a complex, heterogeneous hydrogel, with distinct microdomains

Investigation of body image as a mediator of the effects of bowel and GI symptoms on psychological distress in female survivors of rectal and anal cancer

PURPOSE: Treatment for rectal and anal cancer (RACa) can result in persistent bowel and gastrointestinal (GI) dysfunction. Body image problems may develop over time and exacerbate symptom-related distress. RACa survivors are an understudied group, however, and factors contributing to post-treatment well-being are not well understood. This study examined whether poorer body image explained the relation between symptom severity and psychological distress. METHODS: Participants (N=70) completed the baseline assessment of a sexual health intervention study. Bootstrap methods tested body image as a mediator between bowel and GI symptom severity and two indicators of psychological distress (depressive and anxiety symptoms), controlling for relevant covariates. Measures included the EORTC-QLQ-CR38 Diarrhea, GI Symptoms, and Body Image subscales and Brief Symptom Index Depression and Anxiety subscales. RESULTS: Women averaged 55 years old (SD=11.6), White (79%), and 4-years post-treatment. Greater Depression related to poorer body image (r=−.61) and worse diarrhea (r=.35) and GI symptoms (r=.48). Greater Anxiety related to poorer body image (r=−.42) and worse GI symptoms (r=.45), but not diarrhea (r=.20). Body image mediated the effects of bowel and GI symptoms on Depression, but not on Anxiety. CONCLUSIONS: Long-term bowel and GI dysfunction are distressing and affect how women perceive and relate to their bodies, exacerbating survivorship difficulties. Interventions to improve adjustment post-treatment should address treatment side effects, but also target body image problems to alleviate depressive symptoms. Reducing anxiety may require other strategies. Body image may be a key modifiable factor to improve well-being in this understudied population. Longitudinal research is needed to confirm findings