bluuebunny/crossref_metadata_2025_split huggingface dataset:
The multiobjective multidimensional knapsack problem: a survey and a new approach
Authors: Lust Thibaut , Teghem Jacques 
Published: February 2012

AbstractThe knapsack problem (KP) and its multidimensional version (MKP) are basic problems in combinatorial optimization. In this paper, we consider their multiobjective extension (MOKP and MOMKP), for which the aim is to obtain or approximate the set of efficient solutions. In the first step, we classify and briefly describe the existing works that are essentially based on the use of metaheuristics. In the second step, we propose the adaptation of the two‐phase Pareto local search (2PPLS) to the resolution of the MOMKP. With this aim, we use a very large scale neighborhood in the second phase of the method, that is the PLS. We compare our results with state‐of‐the‐art results and show that the results we obtained were never reached before by heuristics for biobjective instances. Finally, we consider the extension to three‐objective instances.
The Effect ofHIFA Waiver Expansions on Uninsurance Rates in Adult  Populations
Authors: Atherly Adam , Dowd Bryan E. , Coulam Robert F. , Guy Gery 
Published: February 2012

Research ObjectiveTo evaluate the effect of theHealthInsuranceFlexibility andAccountability (HIFA) demonstrations on the rate of uninsured. The policy purpose of theHIFAdemonstrations is to encourage “new comprehensive state approaches” that will increase the number of insured.HIFAinterventions include changes in benefit packages, eligibility rules for public programs, and state subsidization of private health insurance premiums. Some states emphasized private insurance (premium assistance), whereas others placed greater emphasis on expanded eligibility for public insurance.Data Sources/Study SettingData were drawn from theCurrentPopulationSurvey from 2000 to 2007. The target populations for theHIFAwaiver demonstrations consisted of individuals who were eligible for theHIFAwaiver demonstrations in demonstration states.Study DesignThe estimation approach was a probit model using a difference‐in‐differences approach.Principal FindingsIn states that fully implemented theirHIFAwaiver,HIFAincreased the rate of insurance coverage by 6.4 percentage points on average in the targeted adult population, suggesting that approximately 118,848 adults gained health insurance due toHIFA. TotalHIFAadult enrollment in the six states studied was 280,739. The effect size varied by state, with Maine having the largest effect and Illinois the smallest. The results were robust to different specifications of the control group.ConclusionsOur findings suggest that public insurance initiatives that provide states with flexibility regarding eligibility and plan design are a viable policy approach to reducing uninsurance rates.
Organizational Characteristics of High‐ and Low‐Performing Anticoagulation Clinics in the Veterans Health Administration
Authors: Rose Adam J. , Petrakis Beth Ann , Callahan Patricia , Mambourg Scott , Patel Dimple , Hylek Elaine M. , Bokhour Barbara G. 
Published: February 2012

ObjectiveAnticoagulation clinics (ACCs) can improve anticoagulation control and prevent adverse events. However, ACCs vary widely in their performance on anticoagulation control. Our objective was to compare the organization and management of top‐performing with that of bottom‐performing ACCs.Data Sources/Study SettingThree high outlier and three low outlier ACCs in the Veterans Health Administration (VA).Study DesignSite visits with qualitative data collection and analysis.Data Collection/Extraction MethodsWe conducted semi‐structured interviews with ACC staff regarding work flow, staffing, organization, and quality assurance efforts. We also observed ACC operations and collected documents, such as the clinic protocol. We used grounded thematic analysis to examine site‐level factors associated with high and low outlier status.Principal FindingsHigh outlier sites were characterized by (1) adequate (pharmacist) staffing and effective use of (nonpharmacist) support personnel; (2) innovation to standardize clinical practice around evidence‐based guidelines; (3) the presence of a quality champion for the ACC; (4) higher staff qualifications; (5) a climate of ongoing group learning; and (6) internal efforts to measure performance. Although high outliers had all of these features, no low outlier had more than two of them.ConclusionsThe top‐performing ACCs in the VA system shared six relatively recognizable characteristics. Efforts to improve performance should focus on these domains.
A Comparison of Two Approaches to Increasing Access to Care: Expanding Coverage versus Increasing Physician Fees
Authors: White Chapin 
Published: February 2012

ObjectiveTo compare the effects of a coverage expansion versus a Medicaid physician fee increase on children's utilization of physician services.Primary Data SourceNational Health Interview Survey (1997–2009).Study DesignWe use the Children's Health Insurance Program, enacted in 1997, as a natural experiment, and we performed a panel data regression analysis using the state‐year as the unit of observation. Outcomes include physician visits per child per year and the following indicators of access to primary care: whether the child saw a physician, pediatrician, or visited an ER in the last year, and whether the parents reported experiencing a non‐cost‐related access problem. We analyzed these outcomes among all children, and separately among socioeconomic status (SES) quartiles defined based on family income and parents' education.Principal FindingsChildren's Health Insurance Program had a major impact on the extent and nature of children's insurance coverage. However, it is not associated with any change in the aggregate quantity of physician services, and its associations with indicators of access are mixed. Increases in physician fees are associated with broad‐based improvements in indicators of access.ConclusionsThe findings suggest that (1) coverage expansions, even if they substantially reduce patient cost sharing, do not necessarily increase physician utilization, and (2) increasing the generosity of provider payments in public programs can improve access among low‐SES children, and, through spillover effects, increase higher‐SES children as well.
Investor Information Demand: Evidence from Google Searches Around Earnings Announcements
Authors: DRAKE MICHAEL S. , ROULSTONE DARREN T. , THORNOCK JACOB R. 
Published: February 2012

ABSTRACTThe objective of this study is to investigate factors that influence investor information demand around earnings announcements and to provide insights into how variation in information demand impacts the capital market response to earnings. The Internet is one channel through which public information is disseminated to investors and we propose that one way that investors express their demand for public information is via Google searches. We find that abnormal Google search increases about two weeks prior to the earnings announcement, spikes markedly at the announcement, and continues at high levels for a period after the announcement. This finding suggests that information diffusion is not instantaneous with the release of the earnings information, but rather is spread over a period surrounding the announcement. We also find that information demand is positively associated with media attention and news, and is negatively associated with investor distraction. When investors search for more information in the days just prior to the announcement, preannouncement price and volume changes reflect more of the upcoming earnings news and there is less of a price and volume response when the news is announced. This result suggests that, when investors demand more information about a firm, the information content of the earnings announcement is partially preempted.
The Influence of Elections on the Accounting Choices of Governmental Entities
Authors: KIDO NOLAN , PETACCHI REINING , WEBER JOSEPH 
Published: February 2012

ABSTRACT This paper investigates whether gubernatorial elections affect state governments’ accounting choices. We identify two accounts, the compensated absence liability account and the unfunded pension liability account, which provide incumbent gubernatorial candidates with flexibility for manipulation. We find that, in an election year, the liability associated with compensated absences and unfunded pension liabilities are both systematically lower. We also find that the variation in these employment‐related liabilities is correlated with proxies for the incumbent's incentives and ability to manipulate their accounting reports. Jointly, these results suggest that state governments manipulate accounting numbers to present a healthier financial picture in an election year.
Regional quantification of muscarinic acetylcholine receptors and β‐adrenoceptors in human airways
Authors: Ikeda T , Anisuzzaman ASM , Yoshiki H , Sasaki M , Koshiji T , Uwada J , Nishimune A , Itoh H , Muramatsu I 
Published: February 2012

BACKGROUND AND PURPOSE Muscarinic acetylcholine receptors (mAChRs) and β‐adrenoceptors in the airways and lungs are clinically important in chronic obstructive pulmonary disease (COPD) and asthma. However, the quantitative and qualitative estimation of these receptors by radioligand binding approaches in human airways has not yet been reported because of tissue limitations.EXPERIMENTAL APPROACH The regional distribution and relative proportion of mAChR and β‐adrenoceptor subtypes were evaluated in human bronchus and lung parenchyma by a tissue segment binding method with [3H]‐N‐methylscopolamine ([3H]‐NMS) for mAChRs and [3H]‐CGP‐12,177 for β‐adrenoceptors. Functional responses to carbachol and isoprenaline were also analysed in the bronchus.KEY RESULTS The M3 subtype predominantly occurred in the bronchus, but the density decreased from the segmental to subsegmental bronchus, and was absent in lung parenchyma. On the other hand, the M1 subtype occurred in the lung only, and the M2 subtype was distributed ubiquitously in the bronchus and lungs. β2‐adrenoceptors were increased along the airways, and their densities in the subsegmental bronchus and lung parenchyma were approximately twofold higher than those of mAChRs in the same region. β1‐adrenoceptors were also detected in lung parenchyma but not in the bronchus. The muscarinic contractions and adrenoceptor relaxations in both bronchial regions were mediated through M3‐mAChRs and β2‐adrenoceptors, respectively.CONCLUSIONS AND IMPLICATIONS From the present radioligand binding approach with intact tissue segments, we constructed a distribution map of mAChRs and β‐adrenoceptors in human bronchus and lung parenchyma for the first time, providing important evidence for future pharmacotherapy and new drug development for respiratory disorders.
The omega‐3 polyunsaturated fatty acid eicosapentaenoic acid inhibits mouse MC‐26 colorectal cancer cell liver metastasis via inhibition of PGE2‐dependent cell motility
Authors: Hawcroft G , Volpato M , Marston G , Ingram N , Perry SL , Cockbain AJ , Race AD , Munarini A , Belluzzi A , Loadman PM , Coletta PL , Hull MA 
Published: February 2012

BACKGROUND AND PURPOSEThe omega‐3 polyunsaturated fatty acid (PUFA) eicosapentaenoic acid (EPA) has antineoplastic activity at early stages of colorectal carcinogenesis, relevant to chemoprevention of colorectal cancer (CRC). We tested the hypothesis that EPA also has anti‐CRC activity at later stages of colorectal carcinogenesis, relevant to treatment of metastatic CRC, via modulation of E‐type PG synthesis.EXPERIMENTAL APPROACHA BALB/c mouse model, in which intrasplenic injection of syngeneic MC‐26 mouse CRC cells leads to development of liver metastases, was used. Dietary EPA was administered in the free fatty acid (FFA) form for 2 weeks before and after ultrasound‐guided intrasplenic injection of 1 × 106 MC‐26 cells (n= 16 each group).KEY RESULTSTreatment with 5% (w w‐1) EPA‐FFA was associated with a reduced MC‐26 mouse CRC cell liver tumour burden compared with control animals (median liver weight 1.03 g vs. 1.62 g; P < 0.034). Administration of 5% EPA‐FFA was also linked to a significant increase in tumour EPA incorporation and lower intratumoural PGE2 levels (with concomitant increased production of PGE3). Liver tumours from 5% EPA‐FFA‐ treated mice demonstrated decreased 5‐bromo‐2‐deoxyuridine‐positive CRC cell proliferation and reduced phosphorylated ERK 1/2 expression at the invasive edge of tumours. A concentration‐dependent reduction in MC‐26 CRC cell Transwell® migration following EPA‐FFA treatment (50–200 µM) in vitro was rescued by exogenous PGE2 (10 µM) and PGE1‐alcohol (1 µM).CONCLUSIONS AND IMPLICATIONSEPA‐FFA inhibits MC‐26 CRC cell liver metastasis. EPA incorporation is associated with a ‘PGE2 to PGE3 switch’ in liver tumours. Inhibition of PGE2‐EP4 receptor‐dependent CRC cell motility probably contributes to the antineoplastic activity of EPA.
Pharmacokinetic interaction study of sulphasalazine in healthy subjects and the impact of curcumin as an in vivo inhibitor of BCRP
Authors: Kusuhara Hiroyuki , Furuie Hidetoshi , Inano Akihiro , Sunagawa Akihiro , Yamada Saiko , Wu Chunyong , Fukizawa Shinya , Morimoto Nozomi , Ieiri Ichiro , Morishita Mariko , Sumita Kiminobu , Mayahara Hiroshi , Fujita Takuya , Maeda Kazuya , Sugiyama Yuichi 
Published: February 2012

BACKGROUND AND PURPOSE An ATP‐binding cassette (ABC) transporter, breast cancer resistance protein (BCRP)/ABCG2, limits oral bioavailability of sulphasalazine. Here we examined the effect of curcumin, the principal curcuminoid of turmeric, on oral bioavailability of microdoses and therapeutic doses of sulphasalazine in humans.EXPERIMENTAL APPROACH Effects of curcumin were measured on the ATP‐dependent sulphasalazine uptake by hBCRP‐expressing membrane vesicles and on oral bioavailability of sulphasalazine in wild‐type and Bcrp(–/–) mice. Eight healthy Japanese subjects received an oral dose of sulphasalazine suspension (100 µg) or tablets (2 g) alone or after curcumin tablets (2 g). Uptake of sulphasalazine was studied in HEK293 cells transfected with the influx transporter (OATP)2B1.KEY RESULTS Curcumin was a potent hBCRP inhibitor in vitro (Ki 0.70 ± 0.41 µM). Curcumin increased the area under the curve (AUC)0–8 of plasma sulphasalazine eightfold in wild‐type mice at 300 and 400 mg·kg−1, but not in Bcrp(–/–) mice. Curcumin increased AUC0–24 of plasma sulphasalazine 2.0‐fold at microdoses and 3.2‐fold at therapeutic doses in humans. Non‐linearity of the dose–exposure relationship was observed between microdoses and therapeutic doses of sulphasalazine. Sulphasalazine was a substrate for OATP2B1 (Km 1.7 ± 0.3 µM). Its linear index (dose/Km) at the therapeutic dose was high and may saturate OATP2B1.CONCLUSIONS AND IMPLICATIONS Curcumin can be used to investigate effects of BCRP on oral bioavailability of drugs in humans. Besides the limited dissolution, OATP2B1 saturation is a possible mechanism underlying non‐linearity in the dose–exposure relationship of sulphasalazine.
Efficacy of the ketogenic diet: Which epilepsies respond?
Authors: Thammongkol Sasipa , Vears Danya F. , Bicknell‐Royle Jillian , Nation Judy , Draffin Kellie , Stewart Karen G. , Scheffer Ingrid E. , Mackay Mark T. 
Published: February 2012

SummaryWe report the efficacy of the ketogenic diet in refractory epilepsies focusing on outcomes with regard to epilepsy syndromes and etiology in children and adults with refractory epilepsy. Sixty‐four consecutive children and four adults were prospectively enrolled from 2002 to 2009; seven were excluded from analysis. The classical ketogenic diet was initiated on an inpatient basis with dietary ratios ranging from 2:1 to 4:1 fat to carbohydrate and protein. Patients were classified according to syndrome and etiology using the 1989 and more recent 2010 International League Against Epilepsy (ILAE) classification systems. Responders were defined as >50% reduction in seizure frequency compared to baseline. Syndromes included symptomatic generalized (52), genetic (idiopathic) generalized (7), and focal epilepsies (2) and etiologies included structural (24), genetic (18), and unknown (19). Twenty‐nine (48%) of 61 patients were responders at 3 months. Two children became seizure‐free: one with focal epilepsy of unknown etiology and another with refractory childhood absence epilepsy. Responsive syndromes included migrating partial epilepsy of infancy, childhood absence epilepsy, focal epilepsy, epilepsy with myoclonic‐atonic seizures, and Dravet syndrome. Children with lissencephaly and hypoxic ischemic encephalopathy had surprisingly good responses. The ketogenic diet is an effective treatment for children and adults with refractory epilepsy. The response is predicted by type of epilepsy syndrome. Accurate characterization of the electroclinical syndrome is an important factor in decisions about timing of initiation of the ketogenic diet.
Modulation of Somatosensory Profiles by Spinal Cord Stimulation in Primary Raynaud′s Syndrome
Authors: Münster Tino , Tiebel Nils , Seyer Hendrikus , Maihöfner Christian 
Published: February 2012

AbstractBackground and Goal: Spinal cord stimulation (SCS) is an effective antinociceptive treatment for various neuropathic pain syndromes. Apart from antinociceptive action, it may modulate overall somatosensory perception. This case report targets the question of whether SCS may alter quantitative sensory testing (QST) in a patient with primary Raynaud′s syndrome.Materials and Methods: We report on a 44‐year‐old female patient with primary Raynaud′s syndrome who had SCS via cervical and lumbar electrodes. QST was performed in a standardized manner assessing cold detection threshold (CDT) and warm detection threshold (WDT), cold pain threshold (CPT) and heat pain threshold (HPT), mechanical detection threshold (MDT) and mechanical pain threshold (MPT) thresholds, and vibration detection threshold (VDT) and pressure pain thresholds (PPT). We tested at the dorsum of the right/left hand of the patient with engaged and disengaged SCS. Test results were compared with a control group of 80 subjects.Results: Without SCS, the patient showed a sensory decrease in CDT, MDT, MPT, and VDT. SCS influenced the perception of cold, warm, and tactile detection thresholds, whereby CDT, WDT, and VDT were impaired and MDT was improved.Conclusion: SCS significantly modulated the somatosensory profile in a patient with primary Raynaud′s syndrome. These effects were pronounced in qualities involving Aβ, C, and A∂ nerve fibers. Further investigations may help to understand the mechanisms of action of SCS.
Use and Costs of Prescription Medications and Alternative Treatments in Patients with Osteoarthritis and Chronic Low Back Pain in Community‐Based Settings
Authors: Gore Mugdha , Tai Kei‐Sing , Sadosky Alesia , Leslie Douglas , Stacey Brett R. 
Published: February 2012

AbstractObjective:  To evaluate the use and direct medical costs of pharmacologic and alternative treatments for patients with osteoarthritis (OA) and chronic low back pain (CLBP).Methods:  The LifeLink™ Health Plan Claims Database was used to identify patients ≥18 years old, diagnosed with OA (N = 112,951) or CLBP (N = 101,294). Of these patients, 64,085 with OA and 47,386 with CLBP received pain‐related treatments during CY2008 and were selected for inclusion. For patients in both cohorts, pharmacologic and alternative treatments, and direct medical costs were examined during CY2008.Results:  Opioids were the most frequently prescribed medication (>70%) in both groups, followed by nonselective nonsteroidal anti‐inflammatory drugs (>50%). Over 30% received antidepressants, >20% received benzodiazepines, and 15% in each group received sedative hypnotics. Use of alternative treatments was as follows: chiropractor, OA 11%, CLBP 34%; physical therapy, 20% in both groups; transcutaneous electrical nerve stimulations (TENS), OA 14%, CLBP 22%; acupuncture, hydrotherapy, massage therapy, and biofeedback, <3% in both groups. Mean (SD) total healthcare costs among these patients were, OA: $15,638 ($22,595); CLBP: $11,829 ($20,035). Pharmacologic therapies accounted for approximately 20% of these costs, whereas alternative treatments accounted for only 3% to 4% of the total costs.Conclusions:  Patients with OA and CLBP used a variety of pain‐related and adjunctive medications. Although, alternative treatments are widely recommended, we found limited use of several of these in clinical practice, potentially due to the source of our data (commercial claims). Further research is needed to ascertain the extent to which such therapies contribute to the total costs of OA and CLBP management.
The clinical relevance of persistent recombinant immunoblot assay–indeterminate reactions: insights into the natural history of hepatitis C virus infection and implications for donor counseling
Authors: Makuria Addisalem T. , Raghuraman Sukanya , Burbelo Peter D. , Cantilena Cathy C. , Allison Robert D. , Gibble Joan , Rehermann Barbara , Alter Harvey J. 
Published: February 2012

BACKGROUND: Recombinant immunoblot assay (RIBA) is used to determine the specificity of antibody to hepatitis C virus (anti‐HCV). The RIBA result is recorded as positive, negative, or indeterminate. The interpretation and significance of RIBA‐indeterminate reactions are unclear. We addressed the clinical relevance of these reactions in the context of the natural history of HCV infection in a prospectively followed cohort of anti‐HCV–positive blood donors.STUDY DESIGN AND METHODS: Donor demographics, exposure history, and humoral and cell‐mediated immunity (CMI) were compared in 15 RIBA‐indeterminate subjects, nine chronic HCV carriers, and eight spontaneously recovered subjects. Serum samples were tested for anti‐HCV by a quantitative, liquid luciferase immunoprecipitation system (LIPS). CMI was assessed by interferon‐γ enzyme‐linked immunosorbent spot assay.RESULTS: In the LIPS assay, the sum of antibody responses to six HCV antigens showed significant (p < 0.001) stepwise diminution progressing from chronic carriers to spontaneously recovered to RIBA‐indeterminate subjects. CMI responses in RIBA‐indeterminate subjects were similar to spontaneously recovered subjects and greater than chronic carriers and controls (p < 0.008). A parenteral risk factor was identified in only 13% of RIBA‐indeterminate subjects compared to 89% of chronic carriers and 87% of spontaneously recovered subjects. RIBA‐indeterminate donors were older than the other groups.CONCLUSION: The CMI and LIPS results suggest that persistent RIBA‐indeterminate reactions represent waning anti‐HCV responses in persons who have recovered from a remote HCV infection. In such cases, detectable antibody may ultimately disappear leaving no residual serologic evidence of prior HCV infection, as reported in a minority of long‐term HCV‐recovered subjects.