Miracle-dz/UniFAR-FTUs huggingface dataset:
Further investigation on the regression method of mapping quantitative trait loci

The simple regression method of mapping quantitative trait loci (QTL) is further investigated in comparison with the mixture model maximum likelihood method under high heritabilities, dominant and missing markers. No significant difference between the two methods is detected in terms of errors of parameter estimation and statistical powers, with the exception that the estimation of residual variance provided by the regression method is confounded with part of the QTL variance. The test statistic profiles show some difference between the two methods, but the difference is only detectable at the micro level. An alternative method, referred to as iteratively reweighted least squares, is proposed, which can correct the deficiency of parameter confounding in the regression method yet retains the properties of simplicity and rapidity of the ordinary regression method. Like the existing regression method, the weighted least squares method can be useful in QTL mapping in conjunction with the permutation tests and construction of confidence intervals by bootstrapping.
Biological markers as indicators of response to primary and adjuvant chemotherapy in breast cancer

Interest in translational studies on breast cancer is presently devoted to identify biological predictors of treatment response. In patients with operable breast cancer, subjected to primary and adjuvant chemotherapy, we analyzed the predictivity on objective clinical response and relapse‐free survival of biological markers related to different cellular aspects and functions. Tumour proliferative rate (evaluated as the 3H‐thymidine‐labelling index, TLI), oestrogen and progesterone receptors (ER and PgR, evaluated by the dextran‐coated‐charcoal method), nuclear DNA ploidy and the immunocytochemical expression of p53, bcl‐2 and bax proteins were determined before primary treatment, at the time of diagnosis, and after primary chemotherapy, at surgery. Objective clinical response was significantly related only to pre‐treatment p53 expression or PgR status, with a higher rate for tumours not expressing than for those expressing p53 (94% vs. 72%), as well as for PgR‐negative (PgR−) than for PgR‐positive (PgR+) tumours (86% vs. 68%). In the overall series, 8‐year clinical outcome was significantly related only to post‐treatment steroid receptors. In particular, higher 8‐year relapse‐free survival rate was observed for patients with ER− or PgR− than for those with ER+ (64% vs. 38%) or PgR+ (53% vs. 37%) tumours. Such findings held true even within the sub‐set of patients who received adjuvant post‐operative chemotherapy, i.e., those with node‐positive (N+) or ER−/node‐negative (N−) tumours, among whom also rapid proliferation or the presence of apoptosis‐favouring markers (bcl‐2− or bax+, singly and in association) on surgical specimens identified a sub‐set of women who benefited from systemic treatment. The different biological markers were variously indicative of clinical outcome, with a predictivity on tumour shrinkage for p53 and PgR, detected before primary chemotherapy, and on long‐term follow‐up for ER, PgR and, to a lesser extent, TLI and apoptosis‐modulating markers. Int. J. Cancer (Pred. Oncol.) 84:580–586, 1999. © 1999 Wiley‐Liss, Inc.
Pentoxifylline therapy for hepatopulmonary syndrome: a pilot study.

H epatopulmonary syndrome (HPS) is characterized by a triad of liver disease, hypoxemia, and intrapulmonary vascular dilations (IPVDs). Its prevalence is 4% to 47% in patients with cirrhosis. Patients with HPS demonstrate a significant reduction in exercise capacity due to abnormal pulmonary circulation. Anatomic arteriovenous shunts in the lung are used during exercise and lead to exercise-induced impairment in gas exchange and exercise-induced arterial hypoxemia. The pathogenesis of HPS is unclear. Cytokinemediated injury is alleged to play a key role. Endothelin-1 and tumor necrosis factor (TNF) interaction, occurring in the lung vasculature, contribute to the development of experimental HPS. Overproduction of TNF, due to endotoxin stimulation of Kupffer cells, might be a major mechanism leading to HPS. Pentoxifylline, a nonspecific phosphodiesterase-4 inhibitor, blocks TNF synthesis and TNF-induced macrophagic nitric oxide production. Pentoxifylline prevented the development of HPS and attenuated HPS in cirrhotic rats. However, to our knowledge, pentoxifylline has not been used clinically for the treatment of HPS. In this study, we tried pentoxifylline therapy in patients with HPS.
Children with excessive fears.

A sample of 28 children with excessive fears, all under twelve years of age, is compared with a control group from the same outpatient psychiatric population. Demographic characteristics of the sample are discussed, as well as the nature and content of the fears, their context, and the degree of symboliza-tion and displacement. A relationship between excessive fears and bedsharing is noted.
Universal effective potential for scalar field theory in three dimensions by Monte Carlo computation.

We study the low-energy effective action for the theory of a one-component real scalar field in three Euclidean dimensions (3[ital D]), in the symmetric phase, concentrating on its static part-effective potential [ital V][sub eff]([ital cphi]). We compute it from the probability distributions of the average magnetization in the 3D Ising model in an external field, obtained by Monte Carlo computation. We find that the [ital cphi][sup 6] term in [ital V][sub [ital e][ital f][ital f]] is important in 3D, and compute the values of the universal 4-point and 6-point couplings.
Cost-effectiveness analysis of clinical smoking cessation interventions in Thailand.

AIMS Clinical smoking cessation interventions have been found typically to be highly cost-effective in many high-income countries. There is a need to extend this to low- and middle-income countries and undertake comparative analyses. This study aimed to estimate the incremental cost-effectiveness ratio of a range of clinical smoking cessation interventions available in Thailand. METHODS Using a Markov model, cost-effectiveness, in terms of cost per quality-adjusted life years (QALY) gained, from a range of interventions was estimated from a societal perspective for males and females aged 40 years who smoke at least 10 cigarettes per day. Interventions considered were: counselling in hospital, phone counselling (Quitline) and counselling plus nicotine gum, nicotine patch, bupropion, nortriptyline or varenicline. An annual discounting rate of 3% was used. Probabilistic sensitivity analyses were conducted and a cost-effectiveness acceptability curve (CEAC) plotted. Comparisons between interventions were conducted involving application of a 'decision rule' process. RESULTS Counselling with varenicline and counselling with nortriptyline were found to be cost-effective. Hospital counselling only, nicotine patch and bupropion were dominated by Quitline, nortriptyline and varenicline, respectively, according to the decision rule. When compared with unassisted cessation, probabilistic sensitivity analysis revealed that all interventions have very high probabilities (95%) of being cost-saving except for nicotine replacement therapy (NRT) patch (74%). CONCLUSION In middle-income countries such as Thailand, nortriptyline and varenicline appear to provide cost-effective clinical options for supporting smokers to quit.
Absorption and deposition of xanthophylls in broilers challenged with three dosages of Eimeria acervulina oocysts

Abstract 1. An experiment was designed to evaluate the effect of different doses of oocysts of Eimeria acervulina on intestinal absorption and skin deposition of xanthophylls (XAs) in broilers. 2. A total of 192 broiler chickens were randomly assigned to 4 groups: an uninfected control group and three groups inoculated with either 1 × 102, 1 × 104 or 1 × 105 sporulated oocysts of E. acervulina by gavaging at 21 d. There were 4 replicate pens (2 male and 2 female) per group. 3. Plasma xanthophyll (PX) and skin yellowness (SY) were measured in live birds weekly. At 42 d of age, SY was measured in the breast and abdomen after chilling and in the breast 24 h post-processing on refrigerated carcasses. 4. In general, in all challenged treatments, and for the duration of the study, the average PX decreased by 0.02 μg/ml (R2 = 61.6%) for every 1000 inoculated oocysts, whereas PX increased by 1.26 μg/ml/d in uninfected birds. 5. The average SY in live birds from 21 to 42 d of age decreased by 0.019 b*/every 1000 oocysts administered, while SY of uninfected controls increased by 0.57 b*/d. It was also noted that in all treatments females had a greater SY (6.17 b*) than males for the duration of the study. The SY of the breast and abdomen was correlated (r = 0.76) in chilled carcasses. Breast SY in 24 h refrigerated carcasses was greater in the control group and for female birds. 6. Oocyst excretion was different between inoculated treatments only on 7 d post-inoculation (PI). Coccidia lesion scores in the duodenum averaged 1+ in infected birds and 2+ in birds given the highest oocyst dose.
Cytochrome P450-Mediated Oxidative Metabolism of Abused Synthetic Cannabinoids Found in K2/Spice: Identification of Novel Cannabinoid Receptor Ligands

Abuse of synthetic cannabinoids (SCs), such as [1-naphthalenyl-(1-pentyl-1H-indol-3-yl]-methanone (JWH-018) and [1-(5-fluoropentyl)-1H-indol-3-yl]-1-naphthalenyl-methanone (AM2201), is increasing at an alarming rate. Although very little is known about the metabolism and toxicology of these popular designer drugs, mass spectrometric analysis of human urine specimens after JWH-018 and AM2201 exposure identified monohydroxylated and carboxylated derivatives as major metabolites. The present study extends these initial findings by testing the hypothesis that JWH-018 and its fluorinated counterpart AM2201 are subject to cytochrome P450 (P450)-mediated oxidation, forming potent hydroxylated metabolites that retain significant affinity and activity at the cannabinoid 1 (CB1) receptor. Kinetic analysis using human liver microsomes and recombinant human protein identified CYP2C9 and CYP1A2 as major P450s involved in the oxidation of the JWH-018 and AM2201. In vitro metabolite formation mirrored human urinary metabolic profiles, and each of the primary enzymes exhibited high affinity (Km = 0.81–7.3 μM) and low to high reaction velocities (Vmax = 0.0053–2.7 nmol of product · min−1 · nmol protein−1). The contribution of CYP2C19, 2D6, 2E1, and 3A4 in the hepatic metabolic clearance of these synthetic cannabinoids was minimal (fm = <0.2). In vitro studies demonstrated that the primary metabolites produced in humans display high affinity and intrinsic activity at the CB1 receptor, which was attenuated by the CB1 receptor antagonist (6aR,10aR)-3-(1-methanesulfonylamino-4-hexyn-6-yl)-6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo[b,d]pyran (O-2050). Results from the present study provide critical, missing data related to potential toxicological properties of “K2” parent compounds and their human metabolites, including mechanism(s) of action at cannabinoid receptors.
Doppler Ultrasound Velocimetry of Middle Cerebral Arteries of Patients With Sickle Cell Disease at Aminu Kano Teaching Hospital: A Preliminary Report

Abstract Transcranial Doppler ultrasound scan is a noninvasive method of evaluating the major intracranial vessels. It is becoming an important screening tool for predicting high-risk sickle cell patients for developing cerebrovascular disease. This study evaluates the patients’ characteristics, common indications, and findings on Doppler ultrasound of the middle cerebral arteries of sickle cell patients performed at Aminu Kano Teaching Hospital, Kano, Nigeria. This is a preliminary report of an ongoing review of the transcranial Doppler scans done at Aminu Kano Teaching Hospital. The records of all patients, the indications for Doppler examination, and major findings on the middle cerebral arteries were documented. There are 60 patients, consisting of 22 males and 38 females. Their ages ranged from 1.0 to 41.0 years, with mean of 11.58 ± 7.30 years. About a third of the patients were asymptomatic (38.3%). Those with headache constituted 20.0%, whereas those with past cerebral syndrome constituted 8.3%. Other indications include stroke (11.67%) and transient ischemic attack (3.3%). The mean peak systolic velocity of the middle cerebral artery measured 204.8 cm/s (±80 cm/s) and 208.8 (±79 cm/s) on the respective right and left side. This right-to-left difference was statistically significant (P = 0.046). Symptomatic and female patients showed higher mean peak systolic velocity values when compared with males, although the difference was not statistically significant.
Diffusion processes and growth on stepped metal surfaces.

We study the dynamics of adatoms in a model of vicinal (11m) fcc metal surfaces. We examine the role of different diffusion mechanisms and their implications to surface growth. In particular, we study the effect of steps and kinks on adatom dynamics. We show that the existence of kinks is crucially important for adatom motion along and across steps. Our results are in agreement with recent experiments on Cu(100) and Cu(1,1,19) surfaces. The results also suggest that for some metals exotic diffusion mechanisms may be important for mass transport across the steps.
Effectiveness of Antilock Braking Systems in Reducing Fatal Motorcycle Crashes

The effect of antilock braking systems (ABS) on motorcyclist fatal crash risk in 2005-06 was studied by comparing fatal crash rates per registrations of motorcycles with and without ABS. Study motorcycles included those for which ABS was optional equipment and could be identified as present by the model name. Fatal motorcycle crashes per 10,000 registered vehicle years were 38 percent lower for ABS models than for their non-ABS versions. INTRODUCTION Annual motorcyclist deaths in the United States have more than doubled, from 2,077 in 1997 to 4,697 in 2006 (Insurance Institute for Highway Safety, 2008), and motorcycle registrations have increased by about two-thirds, from 5,167,693 in 2000 (earliest year for which data are available) to 8,642,243 in 2006, according to data from R.L. Polk and Company. Many factors contribute to motorcycle crashes, but improper braking was identified as a major pre-impact factor in a study of motorcycle crash causation (Hurt et al., 1981) and again, 20 years later, in the Motorcycle Accident In-Depth Study (MAIDS) (Association of European Motorcycle Manufacturers, 2004). Operating the brakes on most motorcycles is much more complicated than on four-wheel vehicles. Most motorcycles have separate controls for the front and rear brakes, with the front brake usually controlled by a lever on the right handlebar and the rear brake controlled by a pedal operated by the rider’s right foot. During braking, a rider must decide how much force to apply to each control. As with other types of vehicles, much more deceleration can be obtained from braking the front wheel than from braking the rear wheel. Motorcycles are inherently less stable than four-wheel vehicles and rely on riders’ skills to remain upright during extreme maneuvers such as hard braking. Braking too hard and locking a wheel creates an unstable situation. Locking the front wheel is particularly dangerous, with loss of control being almost certain. A locked rear wheel is more controllable but still can lead to loss of control if the rider simultaneously tries to steer the motorcycle, as in an emergency avoidance maneuver. However, in an emergency requiring full stopping power, riders concerned about wheel lock may be reluctant to apply full force to the brakes, particularly to the front brake. Both Hurt et al. (1981) and MAIDS (Association of European Motorcycle Manufacturers, 2004) had examples of both loss of control due to wheel lock and failure to adequately brake. Although proper braking practices can be taught, rider training courses have not been shown to be effective in reducing motorcycle crashes (Mayhew and Simpson, 1996) or have provided mixed results at best (Billheimer, 1998). In an effort to address the issue of under-braking (especially the front wheel), manufacturers have developed braking systems that essentially link the front and rear brake controls. These systems, collectively referred to here as combined braking systems (CBS), apply braking force to
Experimental investigation of a moving averaging algorithm for motion perpendicular to the leaf travel direction in dynamic MLC target tracking.

PURPOSE In dynamic multileaf collimator (MLC) motion tracking with complex intensity-modulated radiation therapy (IMRT) fields, target motion perpendicular to the MLC leaf travel direction can cause beam holds, which increase beam delivery time by up to a factor of 4. As a means to balance delivery efficiency and accuracy, a moving average algorithm was incorporated into a dynamic MLC motion tracking system (i.e., moving average tracking) to account for target motion perpendicular to the MLC leaf travel direction. The experimental investigation of the moving average algorithm compared with real-time tracking and no compensation beam delivery is described. METHODS The properties of the moving average algorithm were measured and compared with those of real-time tracking (dynamic MLC motion tracking accounting for both target motion parallel and perpendicular to the leaf travel direction) and no compensation beam delivery. The algorithm was investigated using a synthetic motion trace with a baseline drift and four patient-measured 3D tumor motion traces representing regular and irregular motions with varying baseline drifts. Each motion trace was reproduced by a moving platform. The delivery efficiency, geometric accuracy, and dosimetric accuracy were evaluated for conformal, step-and-shoot IMRT, and dynamic sliding window IMRT treatment plans using the synthetic and patient motion traces. The dosimetric accuracy was quantified via a tgamma-test with a 3%/3 mm criterion. RESULTS The delivery efficiency ranged from 89 to 100% for moving average tracking, 26%-100% for real-time tracking, and 100% (by definition) for no compensation. The root-mean-square geometric error ranged from 3.2 to 4.0 mm for moving average tracking, 0.7-1.1 mm for real-time tracking, and 3.7-7.2 mm for no compensation. The percentage of dosimetric points failing the gamma-test ranged from 4 to 30% for moving average tracking, 0%-23% for real-time tracking, and 10%-47% for no compensation. CONCLUSIONS The delivery efficiency of moving average tracking was up to four times higher than that of real-time tracking and approached the efficiency of no compensation for all cases. The geometric accuracy and dosimetric accuracy of the moving average algorithm was between real-time tracking and no compensation, approximately half the percentage of dosimetric points failing the gamma-test compared with no compensation.
Some observations on the pharmacology of clofazimine (B663).

Abstract Chemical methods are described for the determination of clofazimine in serum, urine, and feces, and in homogenates of liver and spleen. Feeding clofazimine to mice resulted in a large accumulation of crystalline drug in the liver and spleen. When dosage with clofazimine was terminated tissue and serum concentrations fell extremely slowly, at rates over a period of 4 months equivalent to a half-life of about 70 days. The concentrations of clofazimine were also measured in the serum, urine, or feces of leprosy patients and a healthy volunteer. Clofazimine appeared to be incompletly absorbed in man. The relevance of these findings to the treatment of leprosy with clofazimine is discussed.
Low-velocity shocks: signatures of turbulent dissipation in diffuse irradiated gas

Context. Large-scale motions in galaxies (supernovae explosions, galaxy collisions, galactic shear etc.) generate turbulence, which allows a fraction of the available kinetic energy to cascade down to small scales before it is dissipated. Aims. We establish and quantify the diagnostics of turbulent dissipation in mildly irradiated diffuse gas in the specific context of shock structures. Methods. We incorporated the basic physics of photon-dominated regions into a state-of-the-art steady-state shock code. We examined the chemical and emission properties of mildly irradiated (G_0 = 1) magnetised shocks in diffuse media (n_H = 10^2 to 10^4 cm^(-3)) at low- to moderate velocities (from 3 to 40 km s^(-1)). Results. The formation of some molecules relies on endoergic reactions. Their abundances in J-type shocks are enhanced by several orders of magnitude for shock velocities as low as 7 km s^(-1). Otherwise most chemical properties of J-type shocks vary over less than an order of magnitude between velocities from about 7 to about 30 km s^(-1), where H_2 dissociation sets in. C-type shocks display a more gradual molecular enhancement with increasing shock velocity. We quantified the energy flux budget (fluxes of kinetic, radiated and magnetic energies) with emphasis on the main cooling lines of the cold interstellar medium. Their sensitivity to shock velocity is such that it allows observations to constrain statistical distributions of shock velocities. We fitted various probability distribution functions (PDFs) of shock velocities to spectroscopic observations of the galaxy-wide shock in Stephan’s Quintet and of a Galactic line of sight which samples diffuse molecular gas in Chamaeleon. In both cases, low velocities bear the greatest statistical weight and the PDF is consistent with a bimodal distribution. In the very low velocity shocks (below 5 km s^(-1)), dissipation is due to ion-neutral friction and it powers H_2 low-energy transitions and atomic lines. In moderate velocity shocks (20 km s^(-1) and above), the dissipation is due to viscous heating and accounts for most of the molecular emission. In our interpretation a significant fraction of the gas in the line of sight is shocked (from 4% to 66%). For example, C^+ emission may trace shocks in UV irradiated gas where C^+ is the dominant carbon species. Conclusions. Low- and moderate velocity shocks are important in shaping the chemical composition and excitation state of the interstellar gas. This allows one to probe the statistical distribution of shock velocities in interstellar turbulence.
An fMRI study of prefrontal brain activation during multiple tasks in patients with major depressive disorder

Objective: Previous research has provided conflicting information regarding the pattern of brain activation associated with cognitive performance in depressed people. We aimed to assess brain activation related to cognitive performance during planning and working memory tasks. Method: fMRI scans were conducted using a modified Tower of London task and a 2‐back task in 13 patients with major depressive disorder and a matched control group. Results: Task performance was impaired in the depressed group on the Tower of London task but there were no differences between the groups in task performance on the n‐back task. The patient group showed widespread increased brain activation in both tasks. There was considerable overlap in increased activation between the two tasks, especially in right prefrontal cortical regions. Conclusions: Patients with depression exhibit increased brain activation, especially in right prefrontal regions, across several types of cognitive task activity. Patients with depression may recruit greater brain regions to achieve similar or even poorer task performance than control subjects. Hum Brain Mapp, 2008. © 2007 Wiley‐Liss, Inc.