Miracle-dz/UniFAR-FTUs huggingface dataset:
Understanding Mail Survey Response Rates among Male Reserve Component Gulf War Era Veterans

In this study of current and former male Reserve and National Guard members from the State of Ohio, it was expected that veterans who were older, had more years of military service, who had participated in the Persian Gulf War, who were Euro-Americans, who were higher in rank, who had higher residential stability in Ohio who belonged to the Air Force, who had higher formal education, and who belong to the National Guard would have a greater investment in U.S. society as defined by 11 demographic variables. It was assumed that those with greater investment in society would more often have valid addresses and would be more likely to respond to a survey on military issues, thereby biasing sample outcomes in those directions. Results for male veterans were consistent with the hypothesis that investment in the society system would predict validity of addresses and response rates. In other words, results supported the idea that those veterans who might be expected to have a greater investment in U.S. society were more likely to be located and to respond (once located) to a survey concerning Desert Storm-era military service and its aftermath. Implications for future Desert Storm research are discussed.
Lack of effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of amlodipine.

AIMS To determine whether repeated once daily administration of grapefruit juice altered the pharmacokinetics or pharmacodynamics of the calcium antagonist amlodipine. METHOD S The effects of grapefruit juice on the pharmacokinetics and pharmacodynamics of oral and intravenous amlodipine were assessed in 20 healthy men in a placebo-controlled, open, randomized, four-way crossover study using single doses of amlodipine 10 mg. For 9 days beginning with the day of administration of amlodipine, grapefruit juice (or water control) was given once daily, and blood samples, blood pressure and heart rate measures were obtained. Plasma concentrations of amlodipine and its enantiomers were determined in separate assays by GC-ECD. RESULTS Oral amlodipine had high systemic availability (grapefruit juice: 88%; water: 81%). Pharmacokinetic parameters of racemic amlodipine (AUC, Cmax, tmax, and kel) were not markedly changed with grapefruit juice coadministration. Total plasma clearance and volume of distribution, calculated after intravenous amlodipine, were essentially unchanged by grapefruit juice (CL 6.65 ml min-1 kg-1, juice vs 6.93 ml min-1 kg-1, water; Vdss 22.7 l kg-1, juice vs 21.0 l kg-1, water). Grapefruit juice coadministration did not greatly alter the stereoselectivity in amlodipine oral or intravenous kinetics. The sum of S(-) and R(+) enantiomer concentrations correlated well with total racemic amlodipine concentration (r2 = 0. 957; P = 0.0001). Coadministration of grapefruit juice with either route of amlodipine administration did not significantly alter blood pressure changes vs control. CONCLUSIONS Grapefruit juice has no appreciable effect on amlodipine pharmacodynamics or pharmacokinetics, including its stereoselective kinetics. Bioavailability enhancement by grapefruit juice, noted with other dihydropyridine calcium antagonists, does not occur with amlodipine. Once daily grapefruit juice administration with usual oral doses of amlodipine is unlikely to alter the profile of response in clinical practice.
Acceptability of emergency department-based screening and brief intervention for alcohol problems.

OBJECTIVES To adapt screening and brief intervention for alcohol problems (SBI) to a high-volume emergency department (ED) setting and evaluate its acceptability to patients. METHODS Patients at a large public-hospital ED were screened with the Alcohol Use Disorders Identification Test (AUDIT). Screen-positive drinkers (AUDIT score >/= 6) were provided brief, on-site counseling and referral as needed. Three months later, project staff blinded to baseline measures reassessed alcohol intake, alcohol-related harm, alcohol dependence symptoms, and readiness to change. RESULTS Of 1, 034 patients approached, 78.3% (810) consented to participate (95% CI = 75.5% to 81.2%), and 21.2% (172) screened positive (95% CI = 18.4% to 24.0%). Of 88 patients with complete intervention data, 94.3% (83) accepted an intervention (95% CI = 89.5% to 99.2%), with acceptance rates ranging from 93% to 100% across four alcohol-problem-severity levels (p = 0.7). A majority (59.0%) set goals to decrease or stop drinking (95% CI = 48.4% to 69.6%). The group recontacted (n = 23) experienced statistically significant decreases in alcohol intake, alcohol-related harm, and dependence symptoms, with measures decreasing for 68%, 52%, and 61% of the patients. Readiness to change also showed statistically significant improvement, with scores increasing for 43% of the patients. Moreover, two-thirds of the patients (15/23) reported at follow-up that SBI was a helpful part of their ED visit. CONCLUSIONS High rates of consent and acceptance of counseling for alcohol problems by patients across a wide range of problem severity indicate that this protocol was acceptable to at-risk patients in a public-hospital ED. Improvements in alcohol-related outcome measures at follow-up were strong enough to warrant controlled studies of intervention efficacy.
T1 lesion load and cerebral atrophy as a marker for clinical progression in patients with multiple sclerosis. A prospective 18 months follow‐up study

We investigated the relationship between local tissue destruction, diffuse cerebral atrophy and clinical progression in patients with established multiple sclerosis (MS). Twenty‐nine patients with MS (13 patients with relapsing–remitting and 16 with secondary progressive disease) were included in a prospective serial study. Cerebral volumes, T1 hypointense lesion volumes, T2 hyperintense lesion volumes at baseline and at 18 months follow‐up, and the volume of monthly enhancing lesions from month 0 to month 9 were assessed on magnetic resonance imaging (MRI) brain scans using highly reproducible semi‐automated quantitative techniques. The main outcome measures were the MRI parameters and disability on Kurtzkes’ Expanded Disability Status Scale.
Tailoring the activity of restriction endonuclease PleI by PNA‐induced DNA looping

DNA looping is one of the key factors allowing proteins bound to different DNA sites to signal one another via direct contacts. We demonstrate that DNA looping can be generated in an arbitrary chosen site by sequence‐directed targeting of double‐stranded DNA with pseudocomplementary peptide‐nucleic acids (pcPNAs). We designed pcPNAs to mask the DNA from cleavage by type IIs restriction enzyme PleI while not preventing the enzyme from binding to its primary DNA recognition site. Direct interaction between two protein molecules (one bound to the original recognition site and the other to a sequence‐degenerated site) results in a totally new activity of PleI: it produces a nick near the degenerate site. The PNA‐induced nicking efficiency varies with the distance between the two protein‐binding sites in a phase with the DNA helical periodicity. Our findings imply a general approach for the fine‐tuning of proteins bound to DNA sites well separated along the DNA chain.
Is muscle–tendon unit length a valid indicator for muscle spindle output?

An important role of feedback from muscle and cutaneous receptors is to regulate the magnitude and timing of muscle activity to satisfy the mechanical demands during locomotion (Rossignol et al. 2006). Such sensory information can be used to modulate the walking system of the central nervous system, but it is also suitable to compensate for acute mechanical perturbations via rapid spinal pathways. The latter is likely to be important during walking on uneven surfaces, preventing the body from getting off balance and in the worst case falling. This hypothesis was tested in a well-designed study by af Klint et al. (2008), who assessed changes in within-step activity of the triceps surae muscles during over-ground walking. In this study, natural variations in ground surface were mimicked with small (i.e. ± 3 deg) slope changes of a robotic platform that was embedded in the walkway. Modulation of proprioceptive feedback as a result of an altered ground was assessed by changes in muscle–tendon unit (MTU) length, Achilles tendon force (ATF) and electromyography. MTU length was calculated using kinematic data of the ankle and knee joints as well as regression equations from the literature. ATF was assessed using a E-shaped buckle transducer externally clamped to the tendon. It was found that stepping on an inclined surface increased triceps surae activity as well as MTU length and ATF. The opposite occurred during steps on a negative slope. These results clearly show acute modulation of neural drive to the muscle. As the slopes were imposed in a random order, these compensatory responses most likely rely on within-step reflex pathways (through proprioceptive and/or cutaneous afferents) in contrast to feed-forward control. This significant finding opens the door for our understanding of which of the reflex pathways might be critical for maintaining stability during walking on uneven terrain.
A Minimum Discrepancy Estimator in Parameter Estimation

In statistical estimation theory, a satisfactory estimator should be able to embody a large portion of the available information, which may be known a priori or provided by the data. Hence, the loss of information is minimum when this estimator is employed. In previous work, an estimator criterion based on the discrepancy between the estimator's error covariance and its information lower bound was proposed. Conceptually, this criterion is a measure of the loss of information carried by a parameter estimator based on the Bayesian approach. A minimum discrepancy estimator (MDE) was derived under the linearity assumption. It was, however, pointed out that the minimal information loss could not be guaranteed by the linear version. Moreover, some good asymptotic properties were not obtainable. Therefore, in this paper, the existence and uniqueness conditions of the general MDE are studied under certain regularity conditions. The MDE can be obtained by solving a Fredholm equation of the second kind. Furthermore, it is shown to be consistent and asymptotically efficient. As a result, the MDE is ensured to have the minimum loss of information in finite samples and no loss of information when sample size tends to infinity. Examples indicate that if the prior information is vague, the MDE is superior to the minimum variance estimator (MVE) in terms of information loss. If the prior distribution is suitably chosen, the MDE is superior to the maximum-likelihood estimator (MLE) on the basis of deficiency.
Is there an elephant in the room?

I am a GP in Wales. My pay has been dependent upon my performance, the performance of the nursing and management team of my practice, and of my patients since April 2004. If the patients take my advice and the tablets I prescribe, if our call and recall systems run effectively, and we are careful to put all relevant data into the computer system, then the Quality and Outcomes Framework (QOF) will reward me handsomely. At the beginning of the QOF payment system, our practice team agreed to enter all blood pressure values taken on the sphygmomanometer into the patient computer records using the recommended codes. We did not wish to be vulnerable to charges of fraud or cheating or to compromise our professional values as doctors and nurses. At the end of the first year of the new payment system, our practice ranked 146th above the lowest achieving practice in Wales for blood pressure target achievement in the diabetes clinical domain. The data for 2007–2008 are now available and we are now ranked as the 25th practice …
Evidence of Gene–Environment Interactions between Common Breast Cancer Susceptibility Loci and Established Environmental Risk Factors

Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity) in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene–environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction = 2.4×10−6) and between CASP8-rs17468277 and alcohol consumption (Pinteraction = 3.1×10−4). Overall, the per-allele odds ratio (95% confidence interval) for LSP1-rs3817198 was 1.08 (1.01–1.16) in nulliparous women and ranged from 1.03 (0.96–1.10) in parous women with one birth to 1.26 (1.16–1.37) in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85–0.98) in those with an alcohol intake of <20 g/day and 1.45 (1.14–1.85) in those who drank ≥20 g/day. Additionally, interaction was found between 1p11.2-rs11249433 and ever being parous (Pinteraction = 5.3×10−5), with a per-allele OR of 1.14 (1.11–1.17) in parous women and 0.98 (0.92–1.05) in nulliparous women. These data provide first strong evidence that the risk of breast cancer associated with some common genetic variants may vary with environmental risk factors.
Should Countries Promote Foreign Direct Investment

This paper examines whether policies to promote foreign direct investment (FDI) make economic sense. The discussion focuses on whether existing academic research suggests that the benefits of FDI are sufficient to justify the kind of policy interventions seen in practice. For small open economies, efficient taxation of foreign and domestic capital depends on their relative mobility. If foreign and domestic capital are equally mobile internationally, it will be optimal for countries to subject both types of capital to equal tax treatment. If foreign capital is more mobile internationally, it will be optimal to have lower taxes on capital owned by foreign residents than on capital owned by domestic residents. Absent market failure, there is no justification for favouring FDI over foreign portfolio investment. In practice, countries appear to tax income from foreign capital at rates lower than those for domestic capital and to subject different forms of foreign investment to very different tax treatment. FDI appears to be sensitive to host-country characteristics. Higher taxes deter foreign investment, while a more educated work force and larger goods markets attract FDI. There is also some evidence that multinationals tend to agglomerate in a manner consistent with location-specific externalities. There is weak evidence that FDI generates positive spillovers for host economies. While multinationals are attracted to high-productivity countries, and to high-productivity industries within these countries, there is little evidence at the firm or plant level that FDI raises the productivity of domestic enterprises. Indeed, it appears that plants in industries with a larger multinational presence tend to enjoy lower rates of productivity growth over time. Empirical research thus provides little support for the idea that promoting FDI is warranted on welfare grounds. Subsidies to FDI are more likely to be warranted where multinationals are intensive in the use of elastically supplied factors, where the arrival of multinationals to a market does not lower the market share of domestic firms, and where FDI generates strong positive productivity spillovers for domestic agents. Empirical research suggests that the first and third conditions are unlikely to hold. In the three cases we examine, it appears that the second condition holds, but not the first or third conditions. This suggests that Brazil’s subsidies to foreign automobile manufacturers may have lowered national welfare. Costa Rica appears to have been prudent in not offering subsidies in the case of Intel. There clearly is a need for much more research on the host-economy consequences of FDI. The impression from existing academic literature is that countries should be sceptical about claims that promoting FDI will raise national welfare. A sensible approach for policy makes in host countries is to presume that subsidizing FDI is unwarranted, unless clear evidence is presented to support the argument that the social returns to FDI exceed the private returns.
Survival of patients with biopsy-proven usual interstitial pneumonia and nonspecific interstitial pneumonia

This is the first Australian study to examine survival and clinical characteristics in biopsy-proven idiopathic interstitial pneumonia. A cohort of 70 patients from a single institution between January 1990 and December 1999 was reviewed. All patients were Caucasian, 23 (33%) female. Mean age±sd at diagnosis was 60±12 yrs for males and 54±14 yrs for females. A total 24% of patients had never smoked. The histopathological diagnoses were usual interstitial pneumonia (UIP) (n=59), nonspecific interstitial pneumonia (NSIP) (n=7), desquamative interstitial pneumonia (n=3) and acute interstitial pneumonia (n=11). Clinical and functional characteristics of the two main histological subgroups of UIP and NSIP showed significantly older patients in the UIP group and a significantly lower mean forced expiratory volume in one second (FEV1) in the NSIP group. Median survival for UIP was 78 months compared with 178 months for NSIP. No survival difference between treated and untreated patients with UIP was found. Multivariate analysis revealed smoking alone to be predictive of poorer survival. This study demonstrates the best median survival for usual interstitial pneumonia of available series and confirms a survival difference between usual interstitial pneumonia and nonspecific interstitial pneumonia. Furthermore, the reported results may have implications for treatment timing using conventional protocols currently recommended.
Cholesterol-lowering effect of-glucan from oat bran in mildly hypercholesterolemic subjects may decrease when-glucan is incorporated into bread and cookies 1 – 3

Background: Findings about the effects of -glucan on serum lipoproteins are conflicting. Objective: The study investigated the effects of -glucan from oat bran in bread and cookies (study 1) and in orange juice (study 2) on serum lipoproteins in mildly hypercholesterolemic subjects. Design: In study 1, 48 subjects (21 men, 27 women) received for 3 wk control bread and cookies rich in wheat fiber. For the next 4 wk, by random assignment, 23 subjects continued to consume the control products, and 25 received bread and cookies rich in -glucan. Mean daily intake of -glucan was 5.9 g. Total dietary fiber intake did not differ significantly between the groups. In study 2, the same sources of control fiber and -glucan (5 g/d) as in study 1 were provided. For 2 wk, 25 of the original 48 subjects (10 men, 15 women) were randomly assigned to consume orange juice containing either wheat fiber (n = 13) or -glucan from oat bran (n = 12). After a washout period of 1 wk, dietary regimens were crossed over. Results: In study 1, the change in LDL cholesterol did not differ significantly ( 0.12 mmol/L; P = 0.173) between the 2 groups. In study 2, the drink rich in -glucan decreased LDL cholesterol by 0.26 ± 0.07 mmol/L (6.7 ± 1.8%; P = 0.001) and the ratio of total to HDL cholesterol by 0.26 ± 0.11 (5.4 ± 2.1%; P = 0.029) compared with the other drink. HDL-cholesterol and triacylglycerol concentrations did not change significantly. Conclusions: The food matrix or the food processing, or both, could have adverse effects on the hypocholesterolemic properties of oat -glucan. Am J Clin Nutr 2003;78:221–7.
Introduction to Special Section

This Special Section of the International Journal of Neuropsychopharmacology presents papers which review the current status of the relationship between the inflammatory response system (IRS) and major 'endogenous' and 'organic' (due to a medical condition) depression. Studies published over the last 11 years and reviewed in this Special Section begin to test the necessary conditions which are needed to accept the hypothesis that an activation of the IRS is involved in the pathophysiology and aetiology of 'endogenous' and 'organic' depression. This hypothesis suggests that some types of 'endogenous' and 'organic' depression may be related to IRS activation, such as an increased production of pro-inflammatory cytokines, such as interleukin-1beta (IL-1beta), IL-6, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN)-gamma. These cytokines are stress-sensitive, may cause depression, they have specific effects on brain systems involved in the pathogenesis of major depression, such as the serotonergic system and the hypothalamic-pituitary-adrenal (HPA) axis, and their production may be suppressed by antidepressants. Future research should examine whether anti-inflammatory drugs are effective in the treatment of depression and whether naturally occurring variants of the 'IRS' genes confer susceptibility to the development of the depressive phenotype through altered function of the respective gene products.
Cloning and Characterization of the Genes Encoding a Cytochrome P450 (PipA) Involved in Piperidine and Pyrrolidine Utilization and Its Regulatory Protein (PipR) in Mycobacterium smegmatis mc2155

ABSTRACT Transposon mutagenesis of Mycobacterium smegmatismc2155 enabled the isolation of a mutant strain (called LGM1) altered in the regulation of piperidine and pyrrolidine utilization. The complete nucleotide sequence of the gene inactivated in mutant LGM1 was determined from the wild-type strain. This gene (pipR) encoded a member of the GntR family of bacterial regulatory proteins. An insertion element (IS1096), previously described for M. smegmatis, was detected downstream of the gene pipR. Three additional open reading frames were found downstream of IS1096. The first open reading frame (pipA) appeared to encode a protein identified as a cytochrome P450 enzyme. This gene is the first member of a new family, CYP151. By a gene replacement experiment, it was demonstrated that the cytochrome P450 pipA gene is required for piperidine and pyrrolidine utilization in M. smegmatis mc2155. Genes homologous topipA were detected by hybridization in several, previously isolated, morpholine-degrading mycobacterial strains. A gene encoding a putative [3Fe-4S] ferredoxin (orf1) and a truncated gene encoding a putative glutamine synthetase (orf2′) were found downstream of pipA.