Active transforming growth factor-β is associated with phenotypic changes in granulomas after drug treatment in pulmonary tuberculosis

Background: Tuberculosis (TB) chemotherapy clears bacterial burden in the lungs of patients and allows the tuberculous lesions to heal through a fibrotic process. The healing process leaves pulmonary scar tissue that can impair lung function. The goal of this study was to identify fibrotic mediators as a stepping-stone to begin exploring mechanisms of tissue repair in TB. Methods: Hematoxylin and eosin staining and Masson's trichrome stain were utilized to determine levels of collagenization in tuberculous granulomas from non-human primates. Immunohistochemistry was then employed to further interrogate these granulomas for markers associated with fibrogenesis, including transforming growth factor-β (TGFβ), α-smooth muscle actin (αSMA), phosphorylated SMAD-2/3, and CD163. These markers were compared across states of drug treatment using one-way ANOVA, and Pearson's test was used to determine the association of these markers with one another. Results: TGFβ and αSMA were present in granulomas from primates with active TB disease. These molecules were reduced in abundance after TB chemotherapy. Phosphorylated SMAD-2/3, a signaling intermediate of TGFβ, was observed in greater amounts after 1 month of drug treatment than in active disease, suggesting that this particular pathway is blocked in active disease. Collagen production during tissue repair is strongly associated with TGFβ in this model, but not with CD163+ macrophages. Conclusions: Tissue repair and fibrosis in TB that occurs during drug treatment is associated with active TGFβ that is produced during active disease. Further work will identify mechanisms of fibrosis and work towards mitigating lung impairment with treatments that target those mechanisms

Randomised trial of once-daily vilanterol in children with asthma on inhaled corticosteroid therapy

GSK (ClinicalTrials.gov identifier NCT01573767

Smoothed Analysis of the Minimum-Mean Cycle Canceling Algorithm and the Network Simplex Algorithm

The minimum-cost flow (MCF) problem is a fundamental optimization problem with many applications and seems to be well understood. Over the last half century many algorithms have been developed to solve the MCF problem and these algorithms have varying worst-case bounds on their running time. However, these worst-case bounds are not always a good indication of the algorithms' performance in practice. The Network Simplex (NS) algorithm needs an exponential number of iterations for some instances, but it is considered the best algorithm in practice and performs best in experimental studies. On the other hand, the Minimum-Mean Cycle Canceling (MMCC) algorithm is strongly polynomial, but performs badly in experimental studies. To explain these differences in performance in practice we apply the framework of smoothed analysis. We show an upper bound of $O(mn^2\log(n)\log(\phi))$ for the number of iterations of the MMCC algorithm. Here $n$ is the number of nodes, $m$ is the number of edges, and $\phi$ is a parameter limiting the degree to which the edge costs are perturbed. We also show a lower bound of $\Omega(m\log(\phi))$ for the number of iterations of the MMCC algorithm, which can be strengthened to $\Omega(mn)$ when $\phi=\Theta(n^2)$. For the number of iterations of the NS algorithm we show a smoothed lower bound of $\Omega(m \cdot \min \{ n, \phi \} \cdot \phi)$.Comment: Extended abstract to appear in the proceedings of COCOON 201

Two Cheers For Diversity: An Experimental Study Of Micro-level Heterogeneity In Problemistic Search

In this paper, we argue for an expanded view of problemistic search. Recent behavioral theory research suggests that individual search preferences influence problemistic search. We draw on this to challenge the view of problemistic search as a centrally directed organizational process that proceeds sequentially from local to distant search. We argue that search activities in organizations are heterogeneous – some individuals will first engage in local search while others may move directly to distant search. We propose that problemistic search at the macroorganizational level is therefore the result of a mix of local and distant search activities at the micro-level that shifts towards distant search in response to negative performance evaluation. We test this idea in a laboratory experiment using a repetitive task and performance feedback

Spatially valid proprioceptive cues improve the detection of a visual stimulus

Vision and proprioception are the main sensory modalities that convey hand location and direction of movement. Fusion of these sensory signals into a single robust percept is now well documented. However, it is not known whether these modalities also interact in the spatial allocation of attention, which has been demonstrated for other modality pairings. The aim of this study was to test whether proprioceptive signals can spatially cue a visual target to improve its detection. Participants were instructed to use a planar manipulandum in a forward reaching action and determine during this movement whether a near-threshold visual target appeared at either of two lateral positions. The target presentation was followed by a masking stimulus, which made its possible location unambiguous, but not its presence. Proprioceptive cues were given by applying a brief lateral force to the participant’s arm, either in the same direction (validly cued) or in the opposite direction (invalidly cued) to the on-screen location of the mask. The d′ detection rate of the target increased when the direction of proprioceptive stimulus was compatible with the location of the visual target compared to when it was incompatible. These results suggest that proprioception influences the allocation of attention in visual spac

Travelling on Graphs with Small Highway Dimension

We study the Travelling Salesperson (TSP) and the Steiner Tree problem (STP) in graphs of low highway dimension. This graph parameter was introduced by Abraham et al. [SODA 2010] as a model for transportation networks, on which TSP and STP naturally occur for various applications in logistics. It was previously shown [Feldmann et al. ICALP 2015] that these problems admit a quasi-polynomial time approximation scheme (QPTAS) on graphs of constant highway dimension. We demonstrate that a significant improvement is possible in the special case when the highway dimension is 1, for which we present a fully-polynomial time approximation scheme (FPTAS). We also prove that STP is weakly NP-hard for these restricted graphs. For TSP we show NP-hardness for graphs of highway dimension 6, which answers an open problem posed in [Feldmann et al. ICALP 2015]

Altered serological and cellular reactivity to H-2 antigens after target cell infection with vaccinia virus

MICE generate cytotoxic T lymphocytes (CTL) which are able to lyse virus infected target cells in vitro after infection with lymphocytic choriomeningitis virus (LCMV) and pox-viruses1−3. CTL kill syngeneic and semiallogenic infected cells but not allogenic infected targets. Target cell lysis in these systems seems to be restricted by H-2 antigens, especially by the K or D end of the major histocompatibility complex (MHC). In experiments where virus specific sensitised lymphocytes kill virus infected allogenic target cells4 the effector lymphocytes have not been characterised exactly. Recent investigations suggest that the active cell in this assay, at least in the measles infection, is a non-thymus derived cell (H. Kreth, personal communication). An H-2 restriction of cell mediated cytolysis (CMC) to trinitrophenol (TNP)-modified lymphocytes has also been described5. Zinkernagel and Doherty6 postulated that the CTL is directed against syngeneic H-2 antigens and viral antigens and they suggested an alteration of H-2 induced by the LCMV infection. Earlier7 we found a close topological relationship between H-2 antigens and the target antigen(s) responsible for CMC in the vaccinia system. Here we report experiments which were carried out to prove alteration of H-2 after infection of L-929 fibroblasts with vaccinia virus

Honeybee Colony Vibrational Measurements to Highlight the Brood Cycle

Insect pollination is of great importance to crop production worldwide and honey bees are amongst its chief facilitators. Because of the decline of managed colonies, the use of sensor technology is growing in popularity and it is of interest to develop new methods which can more accurately and less invasively assess honey bee colony status. Our approach is to use accelerometers to measure vibrations in order to provide information on colony activity and development. The accelerometers provide amplitude and frequency information which is recorded every three minutes and analysed for night time only. Vibrational data were validated by comparison to visual inspection data, particularly the brood development. We show a strong correlation between vibrational amplitude data and the brood cycle in the vicinity of the sensor. We have further explored the minimum data that is required, when frequency information is also included, to accurately predict the current point in the brood cycle. Such a technique should enable beekeepers to reduce the frequency with which visual inspections are required, reducing the stress this places on the colony and saving the beekeeper time

Self-Affirmation Improves Problem-Solving under Stress

High levels of acute and chronic stress are known to impair problem-solving and creativity on a broad range of tasks. Despite this evidence, we know little about protective factors for mitigating the deleterious effects of stress on problem-solving. Building on previous research showing that self-affirmation can buffer stress, we tested whether an experimental manipulation of self-affirmation improves problem-solving performance in chronically stressed participants. Eighty undergraduates indicated their perceived chronic stress over the previous month and were randomly assigned to either a self-affirmation or control condition. They then completed 30 difficult remote associate problem-solving items under time pressure in front of an evaluator. Results showed that self-affirmation improved problem-solving performance in underperforming chronically stressed individuals. This research suggests a novel means for boosting problem-solving under stress and may have important implications for understanding how self-affirmation boosts academic achievement in school settings. © 2013 Creswell et al

Effect of maternal panic disorder on mother-child interaction and relation to child anxiety and child self-efficacy

To determine whether mothers with panic disorder with or without agoraphobia interacted differently with their children than normal control mothers, 86 mothers and their adolescents (aged between 13 and 23 years) were observed during a structured play situation. Maternal as well as adolescent anxiety status was assessed according to a structured diagnostic interview. Results showed that mothers with panic disorder/agoraphobia showed more verbal control, were more criticizing and less sensitive during mother-child interaction than mothers without current mental disorders. Moreover, more conflicts were observed between mother and child dyadic interactions when the mother suffered from panic disorder. The comparison of parenting behaviors among anxious and non-anxious children did not reveal any significant differences. These findings support an association between parental over-control and rejection and maternal but not child anxiety and suggest that particularly mother anxiety status is an important determinant of parenting behavior. Finally, an association was found between children’s perceived self-efficacy, parental control and child anxiety symptoms