Empirical results on scheduling and dynamic backtracking

At the Honeywell Technology Center (HTC), we have been working on a scheduling problem related to commercial avionics. This application is large, complex, and hard to solve. To be a little more concrete: 'large' means almost 20,000 activities, 'complex' means several activity types, periodic behavior, and assorted types of temporal constraints, and 'hard to solve' means that we have been unable to eliminate backtracking through the use of search heuristics. At this point, we can generate solutions, where solutions exist, or report failure and sometimes why the system failed. To the best of our knowledge, this is among the largest and most complex scheduling problems to have been solved as a constraint satisfaction problem, at least that has appeared in the published literature. This abstract is a preliminary report on what we have done and how. In the next section, we present our approach to treating scheduling as a constraint satisfaction problem. The following sections present the application in more detail and describe how we solve scheduling problems in the application domain. The implemented system makes use of Ginsberg's Dynamic Backtracking algorithm, with some minor extensions to improve its utility for scheduling. We describe those extensions and the performance of the resulting system. The paper concludes with some general remarks, open questions and plans for future work

Global affordability of fluoride toothpaste

<p>Abstract</p> <p>Objective</p> <p>Dental caries remains the most common disease worldwide and the use of fluoride toothpaste is a most effective preventive public health measure to prevent it. Changes in diets following globalization contribute to the development of dental caries in emerging economies. The aim of this paper is to compare the cost and relative affordability of fluoride toothpaste in high-, middle- and low-income countries. The hypothesis is that fluoride toothpaste is not equally affordable in high-, middle- and low-income countries.</p> <p>Methods</p> <p>Data on consumer prices of fluoride toothpastes were obtained from a self-completion questionnaire from 48 countries. The cost of fluoride toothpaste in high-, middle- and low-income countries was compared and related to annual household expenditure as well as to days of work needed to purchase the average annual usage of toothpaste per head.</p> <p>Results</p> <p>The general trend seems to be that the proportion of household expenditure required to purchase the annual dosage of toothpaste increases as the country's per capita household expenditure decreases. While in the UK for the poorest 30% of the population only 0.037 days of household expenditure is needed to purchase the annual average dosage (182.5 g) of the lowest cost toothpaste, 10.75 days are needed in Kenya. The proportion of annual household expenditure ranged from 0.02% in the UK to 4% in Zambia to buy the annual average amount of lowest cost toothpaste per head.</p> <p>Conclusion</p> <p>Significant inequalities in the affordability of this essential preventive care product indicate the necessity for action to make it more affordable. Various measures to improve affordability based on experiences from essential pharmaceuticals are proposed.</p

Fragile antiferromagnetism in the heavy-fermion compound YbBiPt

We report results from neutron scattering experiments on single crystals of YbBiPt that demonstrate antiferromagnetic order characterized by a propagation vector, $\tau_{\rm{AFM}}$ = ($\frac{1}{2} \frac{1}{2} \frac{1}{2}$), and ordered moments that align along the [1 1 1] direction of the cubic unit cell. We describe the scattering in terms of a two-Gaussian peak fit, which consists of a narrower component that appears below $T_{\rm{N}}~\approx 0.4$ K and corresponds to a magnetic correlation length of $\xi_{\rm{n}} \approx$ 80 $\rm{\AA}$, and a broad component that persists up to $T^*\approx$ 0.7 K and corresponds to antiferromagnetic correlations extending over $\xi_{\rm{b}} \approx$ 20 $\rm{\AA}$. Our results illustrate the fragile magnetic order present in YbBiPt and provide a path forward for microscopic investigations of the ground states and fluctuations associated with the purported quantum critical point in this heavy-fermion compound.Comment: 5 pages, 3 figure

BUMC Annual Report

Annual report of the Boston University Medical Center

Bostonia: v. 64, no. 1

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

Negative symptoms, neuropsychological findings, and ventricular enlargement in schizophrenia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29357/1/0000425.pd

Bioactivation of Trimethoprim to Protein-Reactive Metabolites in Human Liver Microsomes

The formation of drug-protein adducts via metabolic activation and covalent binding may stimulate an immune response or may result in direct cell toxicity. Protein covalent binding is a potentially pivotal step in the development of idiosyncratic adverse drug reactions (IADRs). Trimethoprim (TMP)-sulfamethoxazole (SMX) is a combination antibiotic that commonly causes IADRs. Recent data suggest that the contribution of the TMP component of TMP-SMX to IADRs may be underappreciated. We previously demonstrated that TMP is bioactivated to chemically reactive intermediates that can be trapped in vitro by N-acetyl cysteine (NAC), and we have detected TMP-NAC adducts (i.e., mercapturic acids) in the urine of patients taking TMP-SMX. However, the occurrence and extent of TMP covalent binding to proteins was unknown. To determine the ability of TMP to form protein adducts, we incubated [14C]TMP with human liver microsomes in the presence and absence of NADPH. We observed protein covalent binding that was NADPH dependent and increased with incubation time and concentration of both protein and TMP. The estimated covalent binding was 0.8 nmol Eq TMP/mg protein, which is comparable to the level of covalent binding for several other drugs that have been associated with covalent binding–induced toxicity and/or IADRs. NAC and selective inhibitors of CYP2B6 and CYP3A4 significantly reduced TMP covalent binding. These results demonstrate for the first time that TMP bioactivation can lead directly to protein adduct formation, suggesting that TMP has been overlooked as a potential contributor of TMP-SMX IADRs

Safety and effectiveness of ulotaront (SEP-363856) in schizophrenia: results of a 6-month, open-label extension study

Ulotaront, a trace amine-associated receptor 1 (TAAR1) and serotonin 5-HT1A receptors agonist, has demonstrated efficacy in the treatment of patients with an acute exacerbation of schizophrenia in a 4-week, double-blind, placebo-controlled study. The aim of this 26-week open-label extension study was to evaluate the safety and effectiveness of ulotaront (25/50/75 mg/d) in patients who completed the initial 4-week study. Of the 193 4-week completers, 157 patients (81.3%) continued into the open-label extension study; 66.9% were completers. Among all extension phase patients, treatment with ulotaront was associated with minimal changes in body weight (mean [SD] change from double-blind baseline: -0.3 [3.7] kg), cholesterol (median change, -2.0 mg/dL), triglycerides (median, -5.0 mg/dL), and prolactin (female, median, -3.4 ng/mL; male, median, -2.7 ng/mL). Movement disorder scales showed no extrapyramidal effects. Twenty-six weeks of extension phase treatment was associated with a mean (95% CI) observed change from open-label baseline in the PANSS total score of -22.6 (-25.6, -19.6; effect size, 1.46), and a mean (95% CI) change in the CGI-Severity score of -1.0 (-1.2, -0.8; effect size, 1.07). Long-term treatment with the TAAR1 agonist ulotaront, in the daily dose range of 25-75 mg, was characterized by a relatively high completion rate, an adverse event profile notable for the absence of extrapyramidal-related adverse effects, a low liability for adverse weight and metabolic effects, and no effect on prolactin levels. Additional studies are needed to further confirm the long-term efficacy and safety of ulotaront