Tempering the Adversary: An Exploration into the Applications of Game Theoretic Feature Selection and Regression

Most modern machine learning algorithms tend to focus on an average-case approach, where every data point contributes the same amount of influence towards calculating the fit of a model. This per-data point error (or loss) is averaged together into an overall loss and typically minimized with an objective function. However, this can be insensitive to valuable outliers. Inspired by game theory, the goal of this work is to explore the utility of incorporating an optimally-playing adversary into feature selection and regression frameworks. The adversary assigns weights to the data elements so as to degrade the modeler\u27s performance in an optimal manner, thereby forcing the modeler to construct a more robust solution. A tuning parameter enables tempering of the power wielded by the adversary, allowing us to explore the spectrum between average case and worst case. By formulating our method as a linear program, it can be solved efficiently, and can accommodate sub-population constraints, a feature that other related methods cannot easily implement. We feel that the need to generate models while understanding the influence of sub-population constraints should be particularly prominent in biomedical literature, and though our method was developed in response to the ubiquity of sub-population data and outliers that exist in this realm, our method is generic and can be applied to data sets that are not exclusively biomedical in nature. We additionally explore the implementation of our method as an adversarial regression problem. Here, instead of providing the user with a fitting of parameters for the model, we provide the user with an ensemble of parameters which can be tuned based on sensitivity to outliers and various sub-population constraints. Finally, to help foster a better understanding of various data sets, we will discuss potential automated applications of our method which will enable data scientists to explore underlying relationships and sensitivities that may be a consequence of sub-populations and meaningful outliers

Observations Suggesting a Possible Link Between Gammacarboxyglutamic Acid and Porcine Bioprosthetic Valve Calcification

Observations that link gammacarboxyglutamic acid (Gla) peptides with ectopic calcification are accumulating in the literature and may be summarized as follows: 1) Gla peptides selectively bind calcium and hydroxyapatite. 2) The presence of detectable levels of Gla in calcified tissue is concurrent with the onset of mineralization. 3) In an animal model, osteocalcin (a Gla-containing protein) accounts for more than 90% of all the Gla found in the resulting subcutaneously implanted calcified leaflet. 4) Vitamin D stimulates osteocalcin synthesis in cultures of osteosarcoma cells, and in vitamin D deficient rats subcutaneously implanted valve leaflets are not calcified. 5) Gla content and the degree of calcification in degenerated porcine bioprosthetic valves removed from humans are positively correlated. 6) Porcine bioprosthetic valves implanted in children are calcified more rapidly than those of adults, and the normal GIa levels in the urine of children are more than twice those of normal adults

Technological memory aid use by people with acquired brain injury

Evans, Wilson, Needham, and Brentnall (2003) investigated memory aid use by people with acquired brain injury (ABI) and found little use of technological memory aids. The present study aims to investigate use of technological and other memory aids and strategies 10 years on, and investigate what predicts use. People with ABI and self-reported memory impairments (n = 81) completed a survey containing a memory aid checklist, demographic questions and memory questionnaires. Chi-square analysis showed that 10 of 18 memory aids and strategies were used by significantly more people in the current sample than in Evans et al. (2003). The most commonly used strategies were leaving things in noticeable places (86%) and mental retracing of steps (77%). The most commonly used memory aids were asking someone to remind you (78%), diaries (77%), lists (78%), and calendars (79%) and the most common technologies used were mobile phone reminders (38%) and alarms/timers (38%). Younger people who used more technology prior to their injury and who use more non-technological memory aids currently were more likely to use technology. Younger people who used more memory aids and strategies prior to their injury and who rated their memory as poorer were more likely to use all types of memory aids and strategies

Probiotics for people with hepatic encephalopathy

Background Hepatic encephalopathy is a disorder of brain function as a result of liver failure or portosystemic shunt or both. Both hepatic encephalopathy (clinically overt) and minimal hepatic encephalopathy (not clinically overt) significantly impair patient’s quality of life and daily functioning, and represent a significant burden on healthcare resources. Probiotics are live micro‐organisms, which when administered in adequate amounts, may confer a health benefit on the host. Objectives To determine the beneficial and harmful effects of probiotics in any dosage, compared with placebo or no intervention, or with any other treatment for people with any grade of acute or chronic hepatic encephalopathy. This review did not consider the primary prophylaxis of hepatic encephalopathy. Search methods We searched The Cochrane Hepato‐Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, conference proceedings, reference lists of included trials, and the World Health Organization International Clinical Trials Registry Platform until June 2016. Selection criteria We included randomised clinical trials that compared probiotics in any dosage with placebo or no intervention, or with any other treatment in people with hepatic encephalopathy. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. We conducted random‐effects model meta‐analysis due to obvious heterogeneity of participants and interventions. We defined a P value of 0.05 or less as significant. We expressed dichotomous outcomes as risk ratio (RR) and continuous outcomes as mean difference (MD) with 95% confidence intervals (CI). Main results We included 21 trials with 1420 participants, of these, 14 were new trials. Fourteen trials compared a probiotic with placebo or no treatment, and seven trials compared a probiotic with lactulose. The trials used a variety of probiotics; the most commonly used group of probiotic was VSL#3, a proprietary name for a group of eight probiotics. Duration of administration ranged from 10 days to 180 days. Eight trials declared their funding source, of which six were independently funded and two were industry funded. The remaining 13 trials did not disclose their funding source. We classified 19 of the 21 trials at high risk of bias. We found no effect on all‐cause mortality when probiotics were compared with placebo or no treatment (7 trials; 404 participants; RR 0.58, 95% CI 0.23 to 1.44; low‐quality evidence). No‐recovery (as measured by incomplete resolution of symptoms) was lower for participants treated with probiotic (10 trials; 574 participants; RR 0.67, 95% CI 0.56 to 0.79; moderate‐quality evidence). Adverse events were lower for participants treated with probiotic than with no intervention when considering the development of overt hepatic encephalopathy (10 trials; 585 participants; RR 0.29, 95% CI 0.16 to 0.51; low‐quality evidence), but effects on hospitalisation and change of/or withdrawal from treatment were uncertain (hospitalisation: 3 trials, 163 participants; RR 0.67, 95% CI 0.11 to 4.00; very low‐quality evidence; change of/or withdrawal from treatment: 9 trials, 551 participants; RR 0.70, 95% CI 0.46 to 1.07; very low‐quality evidence). Probiotics may slightly improve quality of life compared with no intervention (3 trials; 115 participants; results not meta‐analysed; low‐quality evidence). Plasma ammonia concentration was lower for participants treated with probiotic (10 trials; 705 participants; MD ‐8.29 μmol/L, 95% CI ‐13.17 to ‐3.41; low‐quality evidence). There were no reports of septicaemia attributable to probiotic in any trial. When probiotics were compared with lactulose, the effects on all‐cause mortality were uncertain (2 trials; 200 participants; RR 5.00, 95% CI 0.25 to 102.00; very low‐quality evidence); lack of recovery (7 trials; 430 participants; RR 1.01, 95% CI 0.85 to 1.21; very low‐quality evidence); adverse events considering the development of overt hepatic encephalopathy (6 trials; 420 participants; RR 1.17, 95% CI 0.63 to 2.17; very low‐quality evidence); hospitalisation (1 trial; 80 participants; RR 0.33, 95% CI 0.04 to 3.07; very low‐quality evidence); intolerance leading to discontinuation (3 trials; 220 participants; RR 0.35, 95% CI 0.08 to 1.43; very low‐quality evidence); change of/or withdrawal from treatment (7 trials; 490 participants; RR 1.27, 95% CI 0.88 to 1.82; very low‐quality evidence); quality of life (results not meta‐analysed; 1 trial; 69 participants); and plasma ammonia concentration overall (6 trials; 325 participants; MD ‐2.93 μmol/L, 95% CI ‐9.36 to 3.50; very low‐quality evidence). There were no reports of septicaemia attributable to probiotic in any trial. Authors' conclusions The majority of included trials suffered from a high risk of systematic error (‘bias’) and a high risk of random error (‘play of chance’). Accordingly, we consider the evidence to be of low quality. Compared with placebo or no intervention, probiotics probably improve recovery and may lead to improvements in the development of overt hepatic encephalopathy, quality of life, and plasma ammonia concentrations, but probiotics may lead to little or no difference in mortality. Whether probiotics are better than lactulose for hepatic encephalopathy is uncertain because the quality of the available evidence is very low. High‐quality randomised clinical trials with standardised outcome collection and data reporting are needed to further clarify the true efficacy of probiotics

The contribution of δ subunit-containing GABAA receptors to phasic and tonic conductance changes in cerebellum, thalamus and neocortex

We have made use of the delta subunit-selective allosteric modulator DS2 (4-chloro-N-[2-(2-thienyl)imidazo[1,2-a]pyridine-3-yl benzamide) to assay the contribution of delta-GABAARs to tonic and phasic conductance changes in the cerebellum, thalamus and neocortex. In cerebellar granule cells, an enhancement of the tonic conductance was observed for DS2 and the orthosteric agonist THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol). As expected, DS2 did not alter the properties of GABAA receptor-mediated inhibitory postsynaptic synaptic currents (IPSCs) supporting a purely extrasynaptic role for delta-GABAARs in cerebellar granule cells. DS2 also enhanced the tonic conductance recorded from thalamic relay neurons of the visual thalamus with no alteration in IPSC properties. However, in addition to enhancing the tonic conductance DS2 also slowed the decay of IPSCs recorded from layer II/III neocortical neurons. A slowing of the IPSC decay also occurred in the presence of the voltage-gated sodium channel blocker TTX. Moreover, under conditions of reduced GABA release the ability of DS2 to enhance the tonic conductance was attenuated. These results indicate that delta-GABAARs can be activated following vesicular GABA release onto neocortical neurons and that the actions of DS2 on the tonic conductance may be influenced by the ambient GABA levels present in particular brain regions

TB195: Element Concentrations in Maine Forest Vegetation and Soils

Bioaccumulation of trace metals in plant tissues can present a health risk to wildlife, and potentially to humans. The Passamaquoddy Tribe in Maine was concerned about health risks of cadmium (Cd) because of a health advisory for moose liver and kidney consumption due to high Cd levels. In addition to Cd, this study evaluated concentrations of aluminum (Al), calcium (Ca), copper (Cu), iron (Fe), potassium (K), magnesium (Mg), manganese (Mn), nickel (Ni), phosphorus (P), lead (Pb), and zinc (Zn) in four common terrestrial moose-browse species, associated forest soils, and two species of aquatic vegetation on Passamaquoddy tribal land in eastern Maine. Elements were organized into three groups (A, B, and C) based on the patterns of concentration differences in vegetation among ecosystem types. Elements in group A included the nutrients Ca, K, Mg, and P and showed a pattern of significantly higher concentrations in hardwood and aquatic vegetation compared to softwoods. Group B elements included the four metals, Cd, Cu, Mn, and Zn, and exhibited a pattern of higher concentrations in hardwoods compared to softwoods and aquatic vegetation. Group C elements did not fit the patterns of group A or group B and included the remaining four elements Al, Fe, Ni, and Pb. Total O horizon soil concentration means for all elements, except Ni and Pb, were significantly higher in hardwood compared to softwood forest types. This study provides uncommon and important baseline vegetation and soil trace metal concentrations from a remote region in Maine of interest to environmental professionals.https://digitalcommons.library.umaine.edu/aes_techbulletin/1013/thumbnail.jp

Probiotics for patients with hepatic encephalopathy

Background Hepatic encephalopathy is a disorder of brain function as a result of liver failure and/or portosystemic shunt. Both hepatic encephalopathy (clinically overt) and minimal hepatic encephalopathy (not clinically overt) significantly impair patient’s quality of life and daily functioning and represent a significant burden on health care resources. Probiotics are live microorganisms, which when administered in adequate amounts may confer a health benefit on the host. Objectives To quantify the beneficial and harmful effects of any probiotic in any dosage, compared with placebo or no intervention, or with any other treatment for patients with any grade of acute or chronic hepatic encephalopathy as assessed from randomised trials. Search methods We searched the The Cochrane Hepato‐Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, conference proceedings, reference lists of included trials and the WHO international clinical trials registry until April 2011 registry platform to identify new and ongoing trials. Selection criteria We included randomised trials that compared probiotics in any dosage with placebo or no intervention, or with any other treatment in patients with hepatic encephalopathy. Data collection and analysis Three authors independently assessed the risk of bias of the included trials and extracted data on relevant outcomes, with differences resolved by consensus. We conducted random‐effects model meta‐analysis due to obvious heterogeneity of patients and interventions. A P value of 0.05 or less was defined as significant. Dichotomous outcomes are expressed as risk ratio (RR) and continuous outcomes as mean difference (MD) with 95% confidence intervals (CI). Main results We included seven trials of which 550 participants were randomised. Four of the seven trials compared a probiotic with placebo or no treatment in 245 participants, another trial compared a probiotic with lactulose in 40 participants , and the remaining two trials compared a probiotic with both placebo and lactulose in 265 participants. Each trial used different types of probiotics. Duration of administration of the experimental intervention varied from 10 days to 180 days. Two trials were industry funded, and five were unclear about origin of funding. All trials had high risk of bias. When probiotics were compared with no treatment, there was no significant difference in all‐cause mortality (2 trials, 105 participants; 1/57 (2%) versus 1/48 (2%): RR 0.72; 95% CI 0.08 to 6.60), lack of recovery (4 trials, 206 participants; 54/107 (50%) versus 68/99 (69%): RR 0.72; 95% CI 0.49 to 1.05), adverse events (3 trials, 145 participants; 2/77 (3%) versus 6/68 (9%): RR 0.34; 95% CI 0.08 to 1.42), quality of life (1 trial, 20 participants contributed to the physical quality of life measurement, 20 participants contributed to the mental quality of life: MD Physical 0.00; 95% CI ‐5.47 to 5.47; MD Mental 4.00; 95% CI ‐1.82 to 9.82), or change of/or withdrawal from treatment (3 trials, 175 participants; 11/92 (12%) versus 7/83 (8%): RR 1.28; 95% CI 0.52 to 3.19). No trial reported sepsis or duration of hospital stay as an outcome. Plasma ammonia concentration was significantly lower for participants treated with probiotic at one month (3 trials, 226 participants: MD ‐2.99 μmol/L; 95% CI ‐5.70 to ‐0.29) but not at two months (3 trials, 181 participants: MD ‐1.82 μmol/L; 95% CI ‐14.04 to 10.41). Plasma ammonia decreased the most in the participants treated with probiotic at three months (1 trial, 73 participants: MD ‐6.79 μmol/L; 95% CI ‐10.39 to ‐3.19). When probiotics were compared with lactulose no trial reported all‐cause mortality, quality of life, duration of hospital stay, or septicaemia. There were no significant differences in lack of recovery (3 trials, 173 participants; 47/87 (54%) versus 44/86 (51%): RR 1.05; 95% CI 0.75 to 1.47), adverse events (2 trials, 111 participants; 3/56 (5%) versus 6/55 (11%): RR 0.57; 95% CI 0.06 to 5.74), change of/or withdrawal from treatment at one month (3 trials, 190 participants; 8/95 (8%) versus 7/95 (7%): RR 1.10; 95% CI 0.40 to 3.03), plasma ammonia concentration (2 trials, 93 participants: MD ‐6.61 μmol/L; 95% CI ‐30.05 to 16.84), or change in plasma ammonia concentration (1 trial, 77 participants: MD 1.16 μmol/L; 95% CI ‐1.96 to 4.28). Authors' conclusions The trials we located suffered from a high risk of systematic errors ('bias') and high risk of random errors ('play of chance'). While probiotics appear to reduce plasma ammonia concentration when compared with placebo or no intervention, we are unable to conclude that probiotics are efficacious in altering clinically relevant outcomes. Demonstration of unequivocal efficacy is needed before probiotics can be endorsed as effective therapy for hepatic encephalopathy. Further randomised clinical trials are needed

Phospholipase D promotes Arcanobacterium haemolyticum adhesion via lipid raft remodeling and host cell death following bacterial invasion

<p>Abstract</p> <p>Background</p> <p><it>Arcanobacterium haemolyticum </it>is an emerging bacterial pathogen, causing pharyngitis and more invasive infections. This organism expresses an unusual phospholipase D (PLD), which we propose promotes bacterial pathogenesis through its action on host cell membranes. The <it>pld </it>gene is found on a genomic region of reduced %G + C, suggesting recent horizontal acquisition.</p> <p>Results</p> <p>Recombinant PLD rearranged HeLa cell lipid rafts in a dose-dependent manner and this was inhibited by cholesterol sequestration. PLD also promoted host cell adhesion, as a <it>pld </it>mutant had a 60.3% reduction in its ability to adhere to HeLa cells as compared to the wild type. Conversely, the <it>pld </it>mutant appeared to invade HeLa cells approximately two-fold more efficiently as the wild type. This finding was attributable to a significant loss of host cell viability following secretion of PLD from intracellular bacteria. As determined by viability assay, only 15.6% and 82.3% of HeLa cells remained viable following invasion by the wild type or <it>pld </it>mutant, respectively, as compared to untreated HeLa cells. Transmission electron microscopy of HeLa cells inoculated with <it>A. haemolyticum </it>strains revealed that the <it>pld </it>mutant was contained within intracellular vacuoles, as compared to the wild type, which escaped the vacuole. Wild type-infected HeLa cells also displayed the hallmarks of necrosis. Similarly inoculated HeLa cells displayed no signs of apoptosis, as measured by induction of caspase 3/7, 8 or 9 activities.</p> <p>Conclusions</p> <p>These data indicate that PLD enhances bacterial adhesion and promotes host cell necrosis following invasion, and therefore, may be important in the disease pathogenesis of <it>A. haemolyticum </it>infections.</p