Altered distribution of mucosal NK cells during HIV infection.

The human gut mucosa is a major site of human immunodeficiency virus (HIV) infection and infection-associated pathogenesis. Increasing evidence shows that natural killer (NK) cells have an important role in control of HIV infection, but the mechanism(s) by which they mediate antiviral activity in the gut is unclear. Here, we show that two distinct subsets of NK cells exist in the gut, one localized to intraepithelial spaces (intraepithelial lymphocytes, IELs) and the other to the lamina propria (LP). The frequency of both subsets of NK cells was reduced in chronic infection, whereas IEL NK cells remained stable in spontaneous controllers with protective killer immunoglobulin-like receptor/human leukocyte antigen genotypes. Both IEL and LP NK cells were significantly expanded in immunological non-responsive patients, who incompletely recovered CD4+ T cells on highly active antiretroviral therapy (HAART). These data suggest that both IEL and LP NK cells may expand in the gut in an effort to compensate for compromised CD4+ T-cell recovery, but that only IEL NK cells may be involved in providing durable control of HIV in the gut

Comparison of Self-Reported Alcohol Consumption to Phosphatidylethanol Measurement among HIV-Infected Patients Initiating Antiretroviral Treatment in Southwestern Uganda

Background: Alcohol consumption among HIV-infected patients may accelerate HIV disease progression or reduce antiretroviral therapy adherence. Self-reported alcohol use is frequently under-reported due to social desirability and recall bias. The aim of this study was to compare self-reported alcohol consumption to phosphatidylethanol (PEth), a biomarker of alcohol consumption, and to estimate the correlation between multiple measures of self-reported alcohol consumption with PEth. Methods: The Uganda AIDS Rural Treatment Outcomes (UARTO) cohort is located in southwestern Uganda and follows patients on ART to measure treatment outcomes. Patients complete standardized questionnaires quarterly including questions on demographics, health status and alcohol consumption. Baseline dried blood spots (DBS) were collected and retrieved to measure PEth. Results: One hundred fifty samples were tested, and 56 (37.3%) were PEth positive (≥8 ng/mL). Of those, 51.7% did not report alcohol use in the past month. Men were more likely to under-report compared to women, OR 2.9, 95% CI = 1.26, 6.65) and those in the higher economic asset categories were less likely to under-report compared to those in the lowest category (OR = 0.41 95% CI: 0.17, 0.94). Among self-reported drinkers (n = 31), PEth was highly correlated with the total number of drinking days in the last 30 (Spearman R = 0.73, p<0.001). Conclusions: Approximately half of HIV infected patients initiating ART and consuming alcohol under-report their use of alcohol. Given the high prevalence, clinicians should assess all patients for alcohol use with more attention to males and those in lower economic asset categories who deny alcohol use. Among those reporting current drinking, self-reported drinking days is a useful quantitative measure

How do validated measures of functional outcome compare with commonly used outcomes in administrative database research for lumbar spinal surgery?

Clinical interpretation of health services research based on administrative databases is limited by the lack of patient-reported functional outcome measures. Reoperation, as a surrogate measure for poor outcome, may be biased by preferences of patients and surgeons and may even be planned a priori. Other available administrative data outcomes, such as postoperative cross sectional imaging (PCSI), may better reflect changes in functional outcome. The purpose was to determine if postoperative events captured from administrative databases, namely reoperation and PCSI, reflect outcomes as derived by validated functional outcome measures (short form 36 scores, Oswestry disability index) for patients who underwent discretionary surgery for specific degenerative conditions of the lumbar spine such as disc herniation, spinal stenosis, degenerative spondylolisthesis, and isthmic spondylolisthesis. After reviewing the records of all patients surgically treated for disc herniation, spinal stenosis, degenerative spondylolisthesis, and isthmic spondylolisthesis at our institution, we recorded the occurrence of PCSI (MRI or CT-myelograms) and reoperations, as well as demographic, surgical, and functional outcome data. We determined how early (within 6 months) and intermediate (within 18 months) term events (PCSI and reoperations) were associated with changes in intermediate (minimum 1 year) and late (minimum 2 years) term functional outcome, respectively. We further evaluated how early (6–12 months) and intermediate (12–24 months) term changes in functional outcome were associated with the subsequent occurrence of intermediate (12–24 months) and late (beyond 24 months) term adverse events, respectively. From 148 surgically treated patients, we found no significant relationship between the occurrence of PCSI or reoperation and subsequent changes in functional outcome at intermediate or late term. Similarly, earlier changes in functional outcome did not have any significant relationship with subsequent occurrences of adverse events at intermediate or late term. Although it may be tempting to consider administrative database outcome measures as proxies for poor functional outcome, we cannot conclude that a significant relationship exists between the occurrence of PCSI or reoperation and changes in functional outcome

Incremental bounded model checking for embedded software

Program analysis is on the brink of mainstream usage in embedded systems development. Formal verification of behavioural requirements, finding runtime errors and test case generation are some of the most common applications of automated verification tools based on bounded model checking (BMC). Existing industrial tools for embedded software use an off-the-shelf bounded model checker and apply it iteratively to verify the program with an increasing number of unwindings. This approach unnecessarily wastes time repeating work that has already been done and fails to exploit the power of incremental SAT solving. This article reports on the extension of the software model checker CBMC to support incremental BMC and its successful integration with the industrial embedded software verification tool BTC EMBEDDED TESTER. We present an extensive evaluation over large industrial embedded programs, mainly from the automotive industry. We show that incremental BMC cuts runtimes by one order of magnitude in comparison to the standard non-incremental approach, enabling the application of formal verification to large and complex embedded software. We furthermore report promising results on analysing programs with arbitrary loop structure using incremental BMC, demonstrating its applicability and potential to verify general software beyond the embedded domain

Vision and Foraging in Cormorants: More like Herons than Hawks?

Background Great cormorants (Phalacrocorax carbo L.) show the highest known foraging yield for a marine predator and they are often perceived to be in conflict with human economic interests. They are generally regarded as visually-guided, pursuit-dive foragers, so it would be expected that cormorants have excellent vision much like aerial predators, such as hawks which detect and pursue prey from a distance. Indeed cormorant eyes appear to show some specific adaptations to the amphibious life style. They are reported to have a highly pliable lens and powerful intraocular muscles which are thought to accommodate for the loss of corneal refractive power that accompanies immersion and ensures a well focussed image on the retina. However, nothing is known of the visual performance of these birds and how this might influence their prey capture technique. Methodology/Principal Findings We measured the aquatic visual acuity of great cormorants under a range of viewing conditions (illuminance, target contrast, viewing distance) and found it to be unexpectedly poor. Cormorant visual acuity under a range of viewing conditions is in fact comparable to unaided humans under water, and very inferior to that of aerial predators. We present a prey detectability model based upon the known acuity of cormorants at different illuminances, target contrasts and viewing distances. This shows that cormorants are able to detect individual prey only at close range (less than 1 m). Conclusions/Significance We conclude that cormorants are not the aquatic equivalent of hawks. Their efficient hunting involves the use of specialised foraging techniques which employ brief short-distance pursuit and/or rapid neck extension to capture prey that is visually detected or flushed only at short range. This technique appears to be driven proximately by the cormorant's limited visual capacities, and is analogous to the foraging techniques employed by herons

Combinatorial RNA Design: Designability and Structure-Approximating Algorithm

In this work, we consider the Combinatorial RNA Design problem, a minimal instance of the RNA design problem which aims at finding a sequence that admits a given target as its unique base pair maximizing structure. We provide complete characterizations for the structures that can be designed using restricted alphabets. Under a classic four-letter alphabet, we provide a complete characterization of designable structures without unpaired bases. When unpaired bases are allowed, we provide partial characterizations for classes of designable/undesignable structures, and show that the class of designable structures is closed under the stutter operation. Membership of a given structure to any of the classes can be tested in linear time and, for positive instances, a solution can be found in linear time. Finally, we consider a structure-approximating version of the problem that allows to extend bands (helices) and, assuming that the input structure avoids two motifs, we provide a linear-time algorithm that produces a designable structure with at most twice more base pairs than the input structure.Comment: CPM - 26th Annual Symposium on Combinatorial Pattern Matching, Jun 2015, Ischia Island, Italy. LNCS, 201

Comparison of Genome-Wide Association Scans for Quantitative and Observational Measures of Human Hair Curvature.

Previous genetic studies on hair morphology focused on the overall morphology of the hair using data collected by self-report or researcher observation. Here, we present the first genome-wide association study (GWAS) of a micro-level quantitative measure of hair curvature. We compare these results to GWAS results obtained using a macro-level classification of observable hair curvature performed in the same sample of twins and siblings of European descent. Observational data were collected by trained observers, while quantitative data were acquired using an Optical Fibre Diameter Analyser (OFDA). The GWAS for both the observational and quantitative measures of hair curvature resulted in genome-wide significant signals at chromosome 1q21.3 close to the trichohyalin (TCHH) gene, previously shown to harbor variants associated with straight hair morphology in Europeans. All genetic variants reaching genome-wide significance for both GWAS (quantitative measure lead single-nucleotide polymorphism [SNP] rs12130862, p = 9.5 × 10-09; observational measure lead SNP rs11803731, p = 2.1 × 10-17) were in moderate to very high linkage disequilibrium (LD) with each other (minimum r2 = .45), indicating they represent the same genetic locus. Conditional analyses confirmed the presence of only one signal associated with each measure at this locus. Results from the quantitative measures reconfirmed the accuracy of observational measures

Reliability of the interRAI suite of assessment instruments: a 12-country study of an integrated health information system

<p>Abstract</p> <p>Background</p> <p>A multi-domain suite of instruments has been developed by the interRAI research collaborative to support assessment and care planning in mental health, aged care and disability services. Each assessment instrument comprises items common to other instruments and specialized items exclusive to that instrument. This study examined the reliability of the items from five instruments supporting home care, long term care, mental health, palliative care and post-acute care.</p> <p>Methods</p> <p>Paired assessments on 783 individuals across 12 nations were completed within 72 hours of each other by trained assessors who were blinded to the others' assessment. Reliability was tested using weighted kappa coefficients.</p> <p>Results</p> <p>The overall kappa mean value for 161 items which are common to 2 or more instruments was 0.75. The kappa mean value for specialized items varied among instruments from 0.63 to 0.73. Over 60% of items scored greater than 0.70.</p> <p>Conclusion</p> <p>The vast majority of items exceeded standard cut-offs for acceptable reliability, with only modest variation among instruments. The overall performance of these instruments showed that the interRAI suite has substantial reliability according to conventional cut-offs for interpreting the kappa statistic. The results indicate that interRAI items retain reliability when used across care settings, paving the way for cross domain application of the instruments as part of an integrated health information system.</p