Parallel Search with no Coordination

We consider a parallel version of a classical Bayesian search problem. $k$ agents are looking for a treasure that is placed in one of the boxes indexed by $\mathbb{N}^+$ according to a known distribution $p$. The aim is to minimize the expected time until the first agent finds it. Searchers run in parallel where at each time step each searcher can "peek" into a box. A basic family of algorithms which are inherently robust is \emph{non-coordinating} algorithms. Such algorithms act independently at each searcher, differing only by their probabilistic choices. We are interested in the price incurred by employing such algorithms when compared with the case of full coordination. We first show that there exists a non-coordination algorithm, that knowing only the relative likelihood of boxes according to $p$, has expected running time of at most $10+4(1+\frac{1}{k})^2 T$, where $T$ is the expected running time of the best fully coordinated algorithm. This result is obtained by applying a refined version of the main algorithm suggested by Fraigniaud, Korman and Rodeh in STOC'16, which was designed for the context of linear parallel search.We then describe an optimal non-coordinating algorithm for the case where the distribution $p$ is known. The running time of this algorithm is difficult to analyse in general, but we calculate it for several examples. In the case where $p$ is uniform over a finite set of boxes, then the algorithm just checks boxes uniformly at random among all non-checked boxes and is essentially $2$ times worse than the coordinating algorithm.We also show simple algorithms for Pareto distributions over $M$ boxes. That is, in the case where $p(x) \sim 1/x^b$ for $0< b < 1$, we suggest the following algorithm: at step $t$ choose uniformly from the boxes unchecked in ${1, . . . ,min(M, \lfloor t/\sigma\rfloor)}$, where $\sigma = b/(b + k - 1)$. It turns out this algorithm is asymptotically optimal, and runs about $2+b$ times worse than the case of full coordination

The Circumnuclear Star Formation Environment of NGC 6946: Br γ and H_2 Results from Keck Integral Field Spectroscopy

We present a 3-dimensional data cube of the K band continuum and the Brγ, H_2 S(0) and S(1)lines within the central 18.”5 x 13.”8 (520 pc x 390 pc) region of NGC6946. Data were obtained using OSIRIS, a near-infrared Integral Field Unit at Keck Observatory, with Laser Guide Star Adaptive Optics. The 0."3 resolution allows us to investigate the stellar bulge and the forming star clusters in the nuclear region on 10 pc scales. We detect giant H II regions associated with massive young star clusters in the nuclear spiral/ring (R~30 pc) and in the principal shocks along the nuclear bar. Comparisons of the Br γ fluxes with Pa α line emission and radio continuum indicate A_K ~ 3, A_V ~ 25 for the nuclear star forming regions. The most luminous H II regions are restricted to within 70 pc of the center, despite the presence of high gas columns at larger radii (R~200 pc). H_2 emission is restricted to clouds within R~60 pc of the center, and in this sense resembles the distribution of the HCN line emission. We propose that gas-assisted migration of the young star clusters is contributing to the buildup of the nuclear bar and nuclear star cluster (R<30 pc) in this galaxy

Discovery of molecular subtypes in leiomyosarcoma through integrative molecular profiling.

Leiomyosarcoma (LMS) is a soft tissue tumor with a significant degree of morphologic and molecular heterogeneity. We used integrative molecular profiling to discover and characterize molecular subtypes of LMS. Gene expression profiling was performed on 51 LMS samples. Unsupervised clustering showed three reproducible LMS clusters. Array comparative genomic hybridization (aCGH) was performed on 20 LMS samples and showed that the molecular subtypes defined by gene expression showed distinct genomic changes. Tumors from the muscle-enriched cluster showed significantly increased copy number changes (P=0.04). A majority of the muscle-enriched cases showed loss at 16q24, which contains Fanconi anemia, complementation group A, known to have an important role in DNA repair, and loss at 1p36, which contains PRDM16, of which loss promotes muscle differentiation. Immunohistochemistry (IHC) was performed on LMS tissue microarrays (n=377) for five markers with high levels of messenger RNA in the muscle-enriched cluster (ACTG2, CASQ2, SLMAP, CFL2 and MYLK) and showed significantly correlated expression of the five proteins (all pairwise P&lt;0.005). Expression of the five markers was associated with improved disease-specific survival in a multivariate Cox regression analysis (P&lt;0.04). In this analysis that combined gene expression profiling, aCGH and IHC, we characterized distinct molecular LMS subtypes, provided insight into their pathogenesis, and identified prognostic biomarkers

Accuracy of identification of tissue types in endoscopic esophageal mucosal biopsies used for molecular biology studies

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Laboratory Focus on Improving the Culture of Biosafety: Statewide Risk Assessment of Clinical Laboratories That Process Specimens for Microbiologic Analysis

The Wisconsin State Laboratory of Hygiene challenged Wisconsin laboratories to examine their biosafety practices and improve their culture of biosafety. One hundred three clinical and public health laboratories completed a questionnaire-based, microbiology-focused biosafety risk assessment. Greater than 96% of the respondents performed activities related to specimen processing, direct microscopic examination, and rapid nonmolecular testing, while approximately 60% performed culture interpretation. Although they are important to the assessment of risk, data specific to patient occupation, symptoms, and travel history were often unavailable to the laboratory and, therefore, less contributory to a microbiology-focused biosafety risk assessment than information on the specimen source and test requisition. Over 88% of the respondents complied with more than three-quarters of the mitigation control measures listed in the survey. Facility assessment revealed that subsets of laboratories that claim biosafety level 1, 2, or 3 status did not possess all of the biosafety elements considered minimally standard for their respective classifications. Many laboratories reported being able to quickly correct the minor deficiencies identified. Task assessment identified deficiencies that trended higher within the general (not microbiology-specific) laboratory for core activities, such as packaging and shipping, direct microscopic examination, and culture modalities solely involving screens for organism growth. For traditional microbiology departments, opportunities for improvement in the cultivation and management of highly infectious agents, such as acid-fast bacilli and systemic fungi, were revealed. These results derived from a survey of a large cohort of small- and large-scale laboratories suggest the necessity for continued microbiology-based understanding of biosafety practices, vigilance toward biosafety, and enforcement of biosafety practices throughout the laboratory setting

Results From the Periodontitis and Vascular Events (PAVE) Study: A Pilot Multicentered, Randomized, Controlled Trial to Study Effects of Periodontal Therapy in a Secondary Prevention Model of Cardiovascular Disease

Background- In the Periodontitis and Vascular Events (PAVE) pilot study, periodontal therapy was provided as an intervention in a secondary cardiac event prevention model through five coordinated cardiac-dental centers. Methods- Subjects were randomized to either community care or protocol provided scaling and root planing to evaluate effects on periodontal status and systemic levels of high-sensitivity Creactive protein (hs-CRP). Results- After 6 months, there was a significant reduction in mean probing depth and extent of 4- or 5-mm pockets. However, there were no significant differences in attachment levels, bleeding upon probing, or extent of subgingival calculus comparing subjects assigned to protocol therapy (n = 151) to those assigned to community care (n = 152). Using intent-to-treat analyses, there was no significant effect on serum hs-CRP levels at 6 months. However, 48% of the subjects randomized to community care received preventive or periodontal treatments. Secondary analyses demonstrated that consideration of any preventive or periodontal care (i.e., any treatment) compared to no treatment showed a significant reduction in the percentage of people with elevated hs-CRP (values >3 mg/l)at 6 months. However, obesity nullified the periodontal treatment effects on hs-CRP reduction. The adjusted odds ratio for hs-CRP levels >3 mg/l at 6 months for any treatment versus no treatment among non-obese individuals was 0.26 (95%confidence interval: 0.09 to 0.72), adjusting for smoking, marital status, and gender. Conclusion- This pilot study demonstrated the critical role of considering obesity as well as rigorous preventive and periodontal care in trials designed to reduce cardiovascular risk. Originally published Journal of Periodontology, Vol. 80, No. 2, Feb 200

Study protocol: a randomised controlled trial investigating the effect of exercise training on peripheral blood gene expression in patients with stable angina

Background: Exercise training has been shown to reduce angina and promote collateral vessel development in patients with coronary artery disease. However, the mechanism whereby exercise exerts these beneficial effects is unclear. There has been increasing interest in the use of whole genome peripheral blood gene expression in a wide range of conditions to attempt to identify both novel mechanisms of disease and transcriptional biomarkers. This protocol describes a study in which we will assess the effect of a structured exercise programme on peripheral blood gene expression in patients with stable angina, and correlate this with changes in angina level, anxiety, depression, and exercise capacity. Methods/Design: Sixty patients with stable angina will be recruited and randomised 1: 1 to exercise training or conventional care. Patients randomised to exercise training will attend an exercise physiology laboratory up to three times weekly for supervised aerobic interval training sessions of one hour in total duration. Patients will undergo assessments of angina, anxiety, depression, and peripheral blood gene expression at baseline, after six and twelve weeks of training, and twelve weeks after formal exercise training ceases. Discussion: This study will provide comprehensive data on the effect of exercise training on peripheral blood gene expression in patients with angina. By correlating this with improvement in angina status we will identify candidate peripheral blood transcriptional markers predictive of improvements in angina level in response to exercise training

Impact of Th1 CD4 Follicular Helper T Cell Skewing on Antibody Responses to an HIV-1 Vaccine in Rhesus Macaques.

Generating durable humoral immunity through vaccination depends upon effective interactions of follicular helper T (Tfh) cells with germinal center (GC) B cells. Th1 polarization of Tfh cells is an important process shaping the success of Tfh-GC B cell interactions by influencing costimulatory and cytokine-dependent Tfh help to B cells. However, the question remains as to whether adjuvant-dependent modulation of Tfh cells enhances HIV-1 vaccine-induced antienvelope (anti-Env) antibody responses. We investigated whether an HIV-1 vaccine platform designed to increase the number of Th1-polarized Tfh cells enhances the magnitude and quality of anti-Env antibodies. Utilizing a novel interferon-induced protein 10 (IP-10)-adjuvanted HIV-1 DNA prime followed by a monophosphoryl lipid A and QS-21 (MPLA+QS-21)-adjuvanted Env protein boost (DIP-10 PALFQ) in macaques, we observed higher anti-Env serum IgG titers with greater cross-clade reactivity, specificity for V1V2, and effector functions than in macaques primed with DNA lacking IP-10 and boosted with MPLA-plus-alum-adjuvanted Env protein (DPALFA) The DIP-10 PALFQ vaccine regimen elicited higher anti-Env IgG1 and lower IgG4 antibody levels in serum, showing for the first time that adjuvants can dramatically impact the IgG subclass profile in macaques. The DIP-10 PALFQ regimen also increased vaginal and rectal IgA antibodies to a greater extent. Within lymph nodes, we observed augmented GC B cell responses and the promotion of Th1 gene expression profiles in GC Tfh cells. The frequency of GC Tfh cells correlated with both the magnitude and avidity of anti-Env serum IgG. Together, these data suggest that adjuvant-induced stimulation of Th1-Tfh cells is an effective strategy for enhancing the magnitude and quality of anti-Env antibody responses.IMPORTANCE The results of the RV144 trial demonstrated that vaccination could prevent HIV transmission in humans and that longevity of anti-Env antibodies may be key to this protection. Efforts to improve upon the prime-boost vaccine regimen used in RV144 have indicated that booster immunizations can increase serum anti-Env antibody titers but only transiently. Poor antibody durability hampers efforts to develop an effective HIV-1 vaccine. This study was designed to identify the specific elements involved in the immunological mechanism necessary to produce robust HIV-1-specific antibodies in rhesus macaques. By clearly defining immune-mediated pathways that improve the magnitude and functionality of the anti-HIV-1 antibody response, we will have the foundation necessary for the rational development of an HIV-1 vaccine