Perfect State Transfer in Laplacian Quantum Walk

For a graph $G$ and a related symmetric matrix $M$, the continuous-time quantum walk on $G$ relative to $M$ is defined as the unitary matrix $U(t) = \exp(-itM)$, where $t$ varies over the reals. Perfect state transfer occurs between vertices $u$ and $v$ at time $\tau$ if the $(u,v)$-entry of $U(\tau)$ has unit magnitude. This paper studies quantum walks relative to graph Laplacians. Some main observations include the following closure properties for perfect state transfer: (1) If a $n$-vertex graph has perfect state transfer at time $\tau$ relative to the Laplacian, then so does its complement if $n\tau$ is an integer multiple of $2\pi$. As a corollary, the double cone over any $m$-vertex graph has perfect state transfer relative to the Laplacian if and only if $m \equiv 2 \pmod{4}$. This was previously known for a double cone over a clique (S. Bose, A. Casaccino, S. Mancini, S. Severini, Int. J. Quant. Inf., 7:11, 2009). (2) If a graph $G$ has perfect state transfer at time $\tau$ relative to the normalized Laplacian, then so does the weak product $G \times H$ if for any normalized Laplacian eigenvalues $\lambda$ of $G$ and $\mu$ of $H$, we have $\mu(\lambda-1)\tau$ is an integer multiple of $2\pi$. As a corollary, a weak product of $P_{3}$ with an even clique or an odd cube has perfect state transfer relative to the normalized Laplacian. It was known earlier that a weak product of a circulant with odd integer eigenvalues and an even cube or a Cartesian power of $P_{3}$ has perfect state transfer relative to the adjacency matrix. As for negative results, no path with four vertices or more has antipodal perfect state transfer relative to the normalized Laplacian. This almost matches the state of affairs under the adjacency matrix (C. Godsil, Discrete Math., 312:1, 2011).Comment: 26 pages, 5 figures, 1 tabl

Clinical characteristics and patient-reported outcomes in patients with inadequately controlled rheumatoid arthritis despite ongoing treatment

Background Despite the wide array of treatments available for rheumatoid arthritis (RA), some patients continue to report unmet clinical needs. We investigated the extent of inadequate disease control in patients with RA. Methods Data were drawn from the Adelphi 2014 RA Disease-Specific Program in France, Germany, Italy, Spain and the UK. Rheumatologists provided patient demographics, comorbidities, satisfaction with RA control and other clinical details. Patients reported their level of satisfaction and completed the EuroQoL 5-Dimensions Health Questionnaire and Work Productivity and Activity Impairment Questionnaire. Patients had been on their current therapy 653 months and had 28-joint disease activity scores (DAS28) reported. Adequately controlled (DAS28 643.2) and inadequately controlled (DAS28 >3.2) patient cohorts were compared using univariate tests. Results Of 1147 patients, 74% were women, the mean age was 52 years and the mean time since RA diagnosis was 7 years. Twenty-seven percent of patients had inadequately controlled RA, whereas 73% had adequately controlled RA. Inadequately controlled patients were more affected clinically versus adequately controlled patients; 69% vs 13% had moderate/severe RA, the current level of pain was 4.6 vs 2.3, and 67% vs 41% experienced flares, respectively (all p<0.0001). Inadequately controlled patients had higher rates of depression (16% vs 5%; p<0.0001), worse health state, greater work and activity impairment, and lower satisfaction rates among the patients and their physicians than the adequately controlled cohort. Conclusion RA was insufficiently controlled in over a quarter of patients despite their current therapy and this had a negative impact on the patients

Composition of free and adherent ruminal bacteria: inaccuracyof the microbial nutrient supply estimates obtained using freebacteria as reference samples and 15N as the marker

Previous studies have indicated that 15N enrichment of solid-associated bacteria (SAB) may be predicted from the same value in liquid-associated bacteria (LAB). The aims of this study were to confirm this and to measure the error in the nutrient supply from SAB, when LAB are used as the reference sample. For this purpose, the chemical and amino acid (AA) compositions of both the bacterial populations were studied in four experiments carried out on different groups of three rumen cannulated wethers. Diets (one in Experiments 1 and 4 and three in Experiments 2 and 3) had forage-to-concentrate ratios (dry matter (DM) basis) between 2 : 1 and 40 : 60, and were consumed at intake levels between 40 and 75 g DM/kg (BW) 0.75. The bacteria samples were isolated after continuous infusion of ( 15NH 4) 2SO 4 (40, 18, 30 and 25 mg 15N/day, in Experiments 1 to 4, respectively) for at least 14 days. In all experiments, SAB had consistently higher concentrations of organic matter (826 v. 716 g/kg DM, as average) and total lipids (192 v. 95 g/kg DM, as average) than LAB. Similar CP concentrations of both populations were observed, except a higher concentration in SAB than in LAB in Experiment 3. A consistent (in Experiment 4 only as tendency) higher AA-N/total N ratio (on average 17.5%) was observed in SAB than in LAB. The 15N enrichment in SAB was systematically lower than in LAB. On the basis of the results of all studies a close relationship was found between the 15N enrichment in SAB and LAB, which was shown irrespective of experiments. This relationship was established from Experiments 1 and 2 and the above cited previous results (n = 20; P < 0.001; R 2 = 0.996), and then confirmed from the results of Experiments 3 and 4. These relationships between SAB and LAB demonstrate that CP supply from SAB is underevaluated by, on average, 21.2% when LAB are used as the reference. This underevaluation was higher for true protein and even higher for the lipid supply (32.5% and 59.6%, respectively, as an average of the four experiments). Large differences in AA profile were observed between SAB and LAB. The prediction equation obtained using 15N as the marker may be used to correct the errors associated with the traditional use of LAB as the reference sample, and therefore to obtain more accurate estimates of the microbial nutrient supply to the ruminants. © Copyright The Animal Consortium 2011.Financial support was provided by the CICYT funded Projects AGL 2001-3662, AGL 2005-01712 and AGL 2006-08300. Analyses of 15N isotope ratios were performed at the Servicio Interdepartamental de Investigacio´ n, Universidad Auto´ noma de Madrid, Spain.González, J.; Arroyo, J.; Ouarti, M.; Guevara-González, J.; Rodríguez, C.; Alvir, M.; Moya Salvador, VJ.... (2012). Composition of free and adherent ruminal bacteria: inaccuracyof the microbial nutrient supply estimates obtained using freebacteria as reference samples and 15N as the marker. Animal. 6(3):468-475. https://doi.org/10.1017/S17517311110018074684756

Factors influencing the use of biologic therapy and adoption of treat-to-target recommendations in current european rheumatology practice

Objective: The aim of this study was to identify factors that influence treatment adjustments and adoption of a treat-to-target (T2T) strategy in patients with rheumatoid arthritis (RA) in European practices. Methods: Cross-sectional data were drawn from the Adelphi 2014 RA Disease Specific Programme. Treatment patterns and clinical characteristics were investigated in patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs) vs non-bDMARDs. For the T2T analysis, patients were subdivided into two subsets (RA diagnosis &lt;2 or 652 years) and compared according to the approach used (no target = no T2T approach; pragmatic = target different from remission; and aspirational = target set as remission). Results: Data from 2,536 patients were analyzed (mean age: 52.76 years and mean time since RA diagnosis: 6.05 years). Of the 1,438 patients eligible to receive bDMARDs, 55% did not receive them. Initiation of bDMARDs in a bDMARD-na\uefve patient was prompted by worsening of the disease. In the RA diagnosis &lt;2 years subset, a T2T approach was not adopted in 58% of the patients, whereas 8% and 34% adopted a pragmatic and aspirational approach, respectively. In the RA diagnosis 652 years subset, 45%, 19%, and 36% of the patients adopted a no target, pragmatic, and aspirational approach, respectively. Physician satisfaction with RA control was lower in the RA diagnosis &lt;2 years subset than in the RA diagnosis 652 years subset (65% vs 77% satisfied, respectively; P&lt;0.0001). Conclusion: This analysis shows that the use of bDMARDs remains suboptimal and that a T2T strategy is not universally adopted

Toward characterization and definition of fibromyalgia severity

<p>Abstract</p> <p>Background</p> <p>There are no standard criteria for defining or assessing severity of fibromyalgia (FM) as a condition as fibromyalgia is associated with multiple symptom domains. The objective of this study was to evaluate whether patient self-reported severity of FM is associated with severity of pain and sleep interference and the presence of core co-morbidities.</p> <p>Methods</p> <p>We recruited individuals ≥ 18 years of age with a clinician-confirmed diagnosis of FM ≥ 3 months and a current pain rating >2 on a 0-10 numeric rating scale (NRS). Patients completed a questionnaire by mail in which they self-rated their FM severity (very mild, mild, moderate, and severe), their current pain severity and extent of sleep interference (NRS; mild, 0-3; moderate, 4-6, severe, 7-10), and provided information (yes/no) on the presence of core comorbidities (symptoms of depression, anxiety, sleep problems, back pain, neck pain) and medication use for FM. The core symptoms of FM were stratified to assist with patient characterization. Analysis of variance (ANOVA) was used to explore the relationship between self-reported FM severity and continuous variables (pain severity and sleep interference), and Mantel-Haenszel chi-square analysis was used to evaluate the trend in the proportions of patients reporting use of medications and core symptoms of FM by severity of FM. To complement patient-reported FM severity and to understand physicians' perspectives, a survey was performed among 28 physician specialists (rheumatology, neurology, anesthesiology/pain management, family practice, internal medicine, and psychiatry) to determine what they assessed when evaluating FM severity in clinical practice.</p> <p>Results</p> <p>The population (N = 129) of FM patients was predominantly female (89.1%), with a mean age of 49.4 ± 11.0 years, and 81.4% reported duration ≥ 2 years. Self-reported FM severity was moderate/severe in 86.0% of patients; mean current pain score was 6.40 ± 2.19 (moderate), and mean sleep interference score was 7.28 ± 2.23 (severe). Greater FM severity was significantly associated with higher levels of current pain and sleep interference (p < 0.0001), the proportion of patients reporting FM medication use (p = 0.0001), and the presence of core comorbidities (p < 0.05). Pain, functional disability, and fatigue severity were ranked as the top three criteria by the highest proportion of physicians when evaluating FM severity.</p> <p>Conclusion</p> <p>With higher self-reported FM severity, patients have greater pain and sleep interference as well as increased frequency of core comorbidities. Further investigation into understanding FM severity is warranted.</p

Exploring Off-Targets and Off-Systems for Adverse Drug Reactions via Chemical-Protein Interactome — Clozapine-Induced Agranulocytosis as a Case Study

In the era of personalized medical practice, understanding the genetic basis of patient-specific adverse drug reaction (ADR) is a major challenge. Clozapine provides effective treatments for schizophrenia but its usage is limited because of life-threatening agranulocytosis. A recent high impact study showed the necessity of moving clozapine to a first line drug, thus identifying the biomarkers for drug-induced agranulocytosis has become important. Here we report a methodology termed as antithesis chemical-protein interactome (CPI), which utilizes the docking method to mimic the differences in the drug-protein interactions across a panel of human proteins. Using this method, we identified HSPA1A, a known susceptibility gene for CIA, to be the off-target of clozapine. Furthermore, the mRNA expression of HSPA1A-related genes (off-target associated systems) was also found to be differentially expressed in clozapine treated leukemia cell line. Apart from identifying the CIA causal genes we identified several novel candidate genes which could be responsible for agranulocytosis. Proteins related to reactive oxygen clearance system, such as oxidoreductases and glutathione metabolite enzymes, were significantly enriched in the antithesis CPI. This methodology conducted a multi-dimensional analysis of drugs' perturbation to the biological system, investigating both the off-targets and the associated off-systems to explore the molecular basis of an adverse event or the new uses for old drugs

Off-Target Effects of Psychoactive Drugs Revealed by Genome-Wide Assays in Yeast

To better understand off-target effects of widely prescribed psychoactive drugs, we performed a comprehensive series of chemogenomic screens using the budding yeast Saccharomyces cerevisiae as a model system. Because the known human targets of these drugs do not exist in yeast, we could employ the yeast gene deletion collections and parallel fitness profiling to explore potential off-target effects in a genome-wide manner. Among 214 tested, documented psychoactive drugs, we identified 81 compounds that inhibited wild-type yeast growth and were thus selected for genome-wide fitness profiling. Many of these drugs had a propensity to affect multiple cellular functions. The sensitivity profiles of half of the analyzed drugs were enriched for core cellular processes such as secretion, protein folding, RNA processing, and chromatin structure. Interestingly, fluoxetine (Prozac) interfered with establishment of cell polarity, cyproheptadine (Periactin) targeted essential genes with chromatin-remodeling roles, while paroxetine (Paxil) interfered with essential RNA metabolism genes, suggesting potential secondary drug targets. We also found that the more recently developed atypical antipsychotic clozapine (Clozaril) had no fewer off-target effects in yeast than the typical antipsychotics haloperidol (Haldol) and pimozide (Orap). Our results suggest that model organism pharmacogenetic studies provide a rational foundation for understanding the off-target effects of clinically important psychoactive agents and suggest a rational means both for devising compound derivatives with fewer side effects and for tailoring drug treatment to individual patient genotypes

Efectos de la relación gramíneas-leguminosas sobre la degradabilidad ruminal de las materias nitrogenadas de henos de praderas temporales

Sobre 4 corderos adultos fistulizados en rumen se ha estudiado, mediante métodos in sacco, la variación de la degradabilidad ruminal de la proteína bruta entre 6 henos obtenidos de 2 cortes (2 o y 4o) de 3 praderas polifitas temporales con una relación gramíneas: leguminosas decreciente. El nitrógeno total de los henos se fraccionó, a partir de sus cinéticas de degradación, en sus componentes soluble, potencialmente degradable por los microorganismos e indegradable en el rumen, determinándose, así mismo, la duración del tiempo de latencia previo al inicio de la degradación de la segunda fracción indicada y la velocidad de degradación de ésta. La variación observada en estos parámetros se discutió en base a la composición botánica y química de los henos. Los valores medios de degradabilidad de la proteína bruta aumentaron (P 0,05) del 60, 9 al 71, 6% con la proporción de leguminosas en la pradera, aumentando, así mismo, aparentemente del 65,1 al 68,2% entre el 2o y 4o corte. Los factores que ejercieron un mayor efecto sobre estos incrementos fueron: el aumento del contenido en materias nitrogenadas solubles del heno, la reducción del tiempo de lactancia y la elevación de las velocidades de degradación