Conducting A/B Experiments with a Scalable Architecture

A/B experiments are commonly used in research to compare the effects of changing one or more variables in two different experimental groups - a control group and a treatment group. While the benefits of using A/B experiments are widely known and accepted, there is less agreement on a principled approach to creating software infrastructure systems to assist in rapidly conducting such experiments. We propose a four-principle approach for developing a software architecture to support A/B experiments that is domain agnostic and can help alleviate some of the resource constraints currently needed to successfully implement these experiments: the software architecture (i) must retain the typical properties of A/B experiments, (ii) capture problem solving activities and outcomes, (iii) allow researchers to understand the behavior and outcomes of participants in the experiment, and (iv) must enable automated analysis. We successfully developed a software system to encapsulate these principles and implement it in a real-world A/B experiment

Synovial cell metabolism and chronic inflammation in rheumatoid arthritis

Metabolomic studies of body fluids show that immune-mediated inflammatory diseases such as rheumatoid arthritis (RA) are associated with metabolic disruption. This is likely to reflect the increased bioenergetic and biosynthetic demands of sustained inflammation and changes to nutrient and oxygen availability in damaged tissue. The synovial membrane lining layer is the principle site of inflammation in RA. Here the resident cells are the fibroblast-like synoviocytes (FLS) and the synovial tissue macrophages (STM), which are transformed toward overproduction of enzymes which degrade cartilage and bone, and cytokines which promote immune cell infiltration. Recent studies have shown metabolic changes in both FLS and macrophages from RA patients and these may be therapeutically targetable. However, as the origins and subset specific functions of synoviocytes are poorly understood and the signaling modules which control metabolic deviation in RA synovial cells are yet to be explored, significant additional research is needed to translate these findings toward clinical application. Furthermore, in many inflamed tissues, different cell types can forge metabolic collaborations through solute carriers (SLC) in their membranes, to meet a high demand for energy or biomolecules. Such relationships are likely to exist in the synovium and are yet to be explored. Finally, it is not yet known whether metabolic change is a consequence of disease or if primary changes to cellular metabolism might underlie or contribute to early stage disease pathogenesis. This article collates what is known about metabolism in synovial tissue cells and highlights future research directions in this area

The Drinfel'd twisted XYZ model

We construct a factorizing Drinfel'd twist for a face type model equivalent to the XYZ model. Completely symmetric expressions for the operators of the monodromy matrix are obtained.Comment: 15 pages, 4 figures, second preprint no. added, reference [14] added, typos correcte

The Maximal U(1)LU(1)_L Inverse Seesaw from d=5d=5 Operator and Oscillating Asymmetric Sneutrino Dark Matter

The maximal $U(1)_L$ supersymmetric inverse seesaw mechanism (M$L$SIS) provides a natural way to relate asymmetric dark matter (ADM) with neutrino physics. In this paper we point out that, M$L$SIS is a natural outcome if one dynamically realizes the inverse seesaw mechanism in the next-to minimal supersymmetric standard model (NMSSM) via the dimension-five operator $(N)^2S^2/M_*$, with $S$ the NMSSM singlet developing TeV scale VEV; it slightly violates lepton number due to the suppression by the fundamental scale $M_*$, thus preserving $U(1)_L$ maximally. The resulting sneutrino is a distinguishable ADM candidate, oscillating and favored to have weak scale mass. A fairly large annihilating cross section of such a heavy ADM is available due to the presence of singlet.Comment: journal versio

Increased Variability of Thailand\u27s Chao Phraya River Peak Season Flow and Its Association With ENSO Variability: Evidence From Tree Ring δ\u3csup\u3e18\u3c/sup\u3eO

We present a statistically robust reconstruction of Thailand\u27s Chao Phraya River peak season streamflow (CPRPF) that spans the 202 years from 1804 to 2005 CE. Our reconstruction is based on tree ring δ18O series derived from three Pinus merkusii sites from Laos and Thailand. The regional δ18O index accounts for 57% of the observed variance of CPRPF. Spatial correlation and 21‐year running correlation analyses reveal that CPRPF is greatly influenced by regional precipitation variations associated with the El Niño–Southern Oscillation (ENSO). Periods of enhanced and reduced ENSO activity are associated with strong and weak ENSO‐streamflow correlation, respectively. At the longer timescale, the Pacific Decadal Oscillation (PDO) appears to modulate the ENSO‐streamflow correlations, with the most extreme flood events along the Chao Phraya River occurring during periods of increased frequency of La Niña events that coincide with extended cold phases of the PDO. The CPRPF reconstruction could aid management planning for Thailand\u27s water resources

Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin

Pathological processes involved in the initiation of rheumatoid synovitis remain unclear. We undertook the present study to identify immune and stromal processes that are present soon after the clinical onset of rheumatoid arthritis ( RA) by assessing a panel of T cell, macrophage, and stromal cell related cytokines and chemokines in the synovial fluid of patients with early synovitis. Synovial fluid was aspirated from inflamed joints of patients with inflammatory arthritis of duration 3 months or less, whose outcomes were subsequently determined by follow up. For comparison, synovial fluid was aspirated from patients with acute crystal arthritis, established RA and osteoarthritis. Rheumatoid factor activity was blocked in the synovial fluid samples, and a panel of 23 cytokines and chemokines measured using a multiplex based system. Patients with early inflammatory arthritis who subsequently developed RA had a distinct but transient synovial fluid cytokine profile. The levels of a range of T cell, macrophage and stromal cell related cytokines ( e. g. IL-2, IL-4, IL-13, IL-17, IL-15, basic fibroblast growth factor and epidermal growth factor) were significantly elevated in these patients within 3 months after symptom onset, as compared with early arthritis patients who did not develop RA. In addition, this profile was no longer present in established RA. In contrast, patients with non-rheumatoid persistent synovitis exhibited elevated levels of interferon-gamma at initiation. Early synovitis destined to develop into RA is thus characterized by a distinct and transient synovial fluid cytokine profile. The cytokines present in the early rheumatoid lesion suggest that this response is likely to influence the microenvironment required for persistent RA

A cost effectiveness analysis of the preferred antidotes for acute paracetamol poisoning patients in Sri Lanka

Background: Acute paracetamol poisoning is a rapidly increasing problem in Sri Lanka. The antidotes are expensive and yet no health economic evaluation has been done on the therapy for acute paracetamol poisoning in the developing world. The aim of this study is to determine the cost effectiveness of using N-acetylcysteine over methionine in the management of acute paracetamol poisoning in Sri Lanka. Methods:Economic analysis was applied using public healthcare system payer perspective. Costs were obtained from a series of patients admitted to the National Hospital of Sri Lanka with a history of acute paracetamol overdose. Evidence on effectiveness was obtained from a systematic review of the literature. Death due to hepatotoxicity was used as the primary outcome of interest. Analysis and development of decision tree models was done using Tree Age Pro 2008. Results: An affordable treatment threshold of Sri Lankan rupees 1,537,120/death prevented was set from the expected years of productive life gained and the average contribution to GDP. A cost-minimisation analysis was appropriate for patients presenting within 10 hours and methionine was the least costly antidote. For patients presenting 10-24 hours after poisoning, n-acetylcysteine was more effective and the incremental cost effectiveness ratio of Sri Lankan rupees 316,182/life saved was well under the threshold. One-way and multi-way sensitivity analysis also supported methionine for patients treated within 10 hours and n-acetylcysteine for patients treated within 10-24 hours as preferred antidotes.Conclusions: Post ingestion time is an important determinant of preferred antidotal therapy for acute paracetamol poisoning patients in Sri Lanka. Using n-acetylcysteine in all patients is not cost effective. On economic grounds, methionine should become the preferred antidote for Sri Lankan patients treated within 10 hours of the acute ingestion and n-acetylcysteine should continue to be given to patients treated within 10-24 hours

Asymmetric Inelastic Inert Doublet Dark Matter from Triplet Scalar Leptogenesis

The nature of dark matter (DM) particles and the mechanism that provides their measured relic abundance are currently unknown. In this paper we investigate inert scalar and vector like fermion doublet DM candidates with a charge asymmetry in the dark sector, which is generated by the same mechanism that provides the baryon asymmetry, namely baryogenesis-via-leptogenesis induced by decays of scalar triplets. At the same time the model gives rise to neutrino masses in the ballpark of oscillation experiments via type II seesaw. We discuss possible sources of depletion of asymmetry in the DM and visible sectors and solve the relevant Boltzmann equations for quasi-equilibrium decay of triplet scalars. A Monte-Carlo-Markov-Chain analysis is performed for the whole parameter space. The survival of the asymmetry in the dark sector leads to inelastic scattering off nuclei. We then apply bayesian statistic to infer the model parameters favoured by the current experimental data, in particular the DAMA annual modulation and Xenon100 exclusion limit. The latter strongly disfavours asymmetric scalar doublet DM of mass \mathcal{O}(\TeV) as required by DM-$\bar{\rm DM}$ oscillations, while an asymmetric vector like fermion doublet DM with mass around 100 GeV is a good candidate for DAMA annual modulation yet satisfying the constraints from Xenon100 data.Comment: 35 pages and 15 figures, references adde

Asymmetric WIMP dark matter

In existing dark matter models with global symmetries the relic abundance of dark matter is either equal to that of anti-dark matter (thermal WIMP), or vastly larger, with essentially no remaining anti-dark matter (asymmetric dark matter). By exploring the consequences of a primordial asymmetry on the coupled dark matter and anti-dark matter Boltzmann equations we find large regions of parameter space that interpolate between these two extremes. Interestingly, this new asymmetric WIMP framework can accommodate a wide range of dark matter masses and annihilation cross sections. The present-day dark matter population is typically asymmetric, but only weakly so, such that indirect signals of dark matter annihilation are not completely suppressed. We apply our results to existing models, noting that upcoming direct detection experiments will constrain a large region of the relevant parameter space.Comment: 32 pages, 6 figures, updated references, updated XENON100 bounds, typo in figure caption correcte