Miracle-dz/UniFAR-FTUs huggingface dataset:
The Need for a More Stringent LDL-C Goal in Patients with Diabetes

Objective: To review relevant literature supporting the need for intensive lipid management in patients with diabetes mellitus. Data Sources: A literature search using MEDLINE (1975–March 2005) was conducted. The search terms coronary disease, diabetes mellitus, hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins), lipoproteins, and low-density lipoprotein cholesterol (LDL-C) were used to identify published trials comparing the effects of intensive LDL-C lowering and cardiovascular morbidity and mortality. Study Selection and Data Extraction: Primary literature was evaluated and included in this review if the study was a large randomized trial containing a significant number of diabetic patients receiving primary prevention. For trials including patients without diabetes, an available sub-analysis of the diabetic population in that trial must have been available. Data Synthesis: The incidence of diabetes mellitus is rising in dramatic proportions throughout the nation. In addition to the diagnosis of diabetes, many of these patients also have preexisting risk factors that increase their risk for cardiovascular morbidity and mortality. In 2004, the National Cholesterol Education Program issued a scientific statement proposing a newer and lower optimal LDL-C goal for high-risk populations. This article reviews pertinent findings from recent clinical trials and guidelines discussing the need to integrate more stringent LDL-C goals into clinical practice. Conclusions: Although data are limited, all patients with diabetes mellitus, regardless of cardiovascular status, may benefit from lipid-lowering therapy with an optimal LDL-C goal of < 70 mg/dL.
A phase II survival comparison of patients with adenocarcinoma of the pancreas treated with 5-fluorouracil and calcium leucovorin versus a matched tumor registry control population.

Carcinoma of the pancreas is a virulent malignancy. We performed a Phase II survival study by treating 30 patients with pancreatic cancer with leucovorin, 200 mg/m2 x 5 days immediately followed by 5-fluorouracil, 370 mg/m2 every 4 weeks. We examined the survival of our 30 study patients with patients drawn from the Manitoba Tumor Registry, matched for important prognostic criteria. Classical response rates were also evaluated in those patients who had measurable tumors. The response rate was 13% with two complete remissions and one partial remission, with 40 patients (7.8%) demonstrating stable disease for 2 months, and 39% of patients demonstrating progressive disease while on treatment. The mean survival of the Phase II-treated group was 16 weeks, compared to 12 weeks in the matched controls, which indicated an increase in survival of 30%. This was significant at the p = . 001 level. Toxicity was not as great as expected. This trial demonstrates that there may be marginal survival benefit with 5FU leucovorin in pancreatic cancer, but more profound prolongation needs to be seen with chemotherapy regimens before instituting randomized trials.
In vitro studies of a bispecific monoclonal antibody antithrombotic conjugate [ATC(3)]

We assessed whether chemical conjugation of a monoclonal antibody (M735) against platelet glycoprotein IIb/IIIa receptors to urokinase and to a monoclonal antibody which binds to damaged endothelium (P14G11) resulted in enhanced inhibition of platelet aggregation with maintenance of localizing features (to damaged endothelium). Conjugation of M735 (an IgM monoclonal antibody) to urokinase and P14G11 (an IgG2a monoclonal antibody) was carried out using SPDP [N-Succinimidyl-3-(2-pyridyldithio)-propionate] as the cross-linking reagent. The resulting triple conjugate [ATC(3)] had fibrinolytic activity and retained platelet and damaged endothelium localizing features. Enhanced inhibition of platelet aggregation (induced by either adenosine diphosphate (ADP), collagen, or thrombin) was observed compared with both an unconjugated mixture of the three individual components and to the M735-urokinase conjugate. We conclude that it is possible to produce a bimonoclonal antibody-urokinase agent which has both potent antiplatelet aggregatory effects and additional targeting or localizing features.
Generalizability

Clinical and epidemiologic investigations are paying increasing attention to the critical constructs of “representativeness” of study samples and “generalizability” of study results. This is a laudable trend and yet, these key concepts are often misconstrued and conflated, masking the central issues of internal and external validity. The authors define these issues and demonstrate how they are related to one another and to generalizability. Providing examples, they identify threats to validity from different forms of bias and confounding. They also lay out relevant practical issues in study design, from sample selection to assessment of exposures, in both clinic-based and population-based settings.
In-home walking speeds and variability trajectories associated with mild cognitive impairment

Objective: To determine whether unobtrusive long-term in-home assessment of walking speed and its variability can distinguish those with mild cognitive impairment (MCI) from those with intact cognition. Methods: Walking speed was assessed using passive infrared sensors fixed in series on the ceiling of the homes of elderly individuals participating in the Intelligent Systems for Assessing Aging Change (ISAAC) cohort study. Latent trajectory models were used to analyze weekly mean speed and walking speed variability (coefficient of variation [COV]). Results: ISAAC participants living alone included 54 participants with intact cognition, 31 participants with nonamnestic MCI (naMCI), and 8 participants with amnestic MCI at baseline, with a mean follow-up of 2.6 ± 1.0 years. Trajectory models identified 3 distinct trajectories (fast, moderate, and slow) of mean weekly walking speed. Participants with naMCI were more likely to be in the slow speed group than in the fast (p = 0.01) or moderate (p = 0.04) speed groups. For COV, 4 distinct trajectories were identified: group 1, the highest baseline and increasing COV followed by a sharply declining COV; groups 2 and 3, relatively stable COV; and group 4, the lowest baseline and decreasing COV. Participants with naMCI were more likely to be members of either highest or lowest baseline COV groups (groups 1 or 4), possibly representing the trajectory of walking speed variability for early- and late-stage MCI, respectively. Conclusion: Walking speed and its daily variability may be an early marker of the development of MCI. These and other real-time measures of function may offer novel ways of detecting transition phases leading to dementia.
Importance of SPP1 genotype as a covariate in clinical trials in Duchenne muscular dystrophy

Objective: To test the effect of the single nucleotide polymorphism −66 T>G (rs28357094) in the osteopontin gene (SPP1) on functional measures over 12 months in Duchenne muscular dystrophy (DMD). Methods: This study was conducted on a cohort of ambulatory patients with DMD from a network of Italian neuromuscular centers, evaluated longitudinally with the North Star Ambulatory Assessment (NSAA) and the 6-Minute Walk Test (6MWT) at study entry and after 12 months. Genotype at rs28357094 was determined after completion of the clinical evaluations. Patients were stratified in 2 groups according to a dominant model (TT homozygotes vs TG heterozygotes and GG homozygotes) and clinical data were retrospectively compared between groups. Results: Eighty patients were selected (age 4.1–19.3 years; mean 8.3 ± 2.7 SD). There were no differences in age or steroid treatment between the 2 subgroups. Paired t test showed a significant difference in both NSAA (p = 0.013) and 6MWT (p = 0.03) between baseline and follow-up after 12 months in patients with DMD carrying the G allele. The difference was not significant in the T subgroup. The analysis of covariance using age and baseline values as covariate and SPP1 genotype as fixed effect showed that these parameters are significantly correlated with the 12-month values. Conclusions: These data provide evidence of the role of SPP1 genotype as a disease modifier in DMD and support its relevance in the selection of homogeneous groups of patients for future clinical trials.
Networks involved in seizure initiation

Objective: To define the ictal cortical/subcortical network of reading-induced seizures. Methods: We analyzed ictal magnetoencephalography (MEG) and EEG-correlated fMRI (EEG-fMRI) data in a unique patient with reading epilepsy (RE) affected by frequent perioral reflex myocloni triggered by reading silently. Results: Ictal MEG corroborated EEG localization and revealed activity extending precentrally into Brodmann area (BA) 6. fMRI blood oxygen level−dependent (BOLD) signal changes in the left deep piriform cortex (PFC) and left BA6 preceded seizures and occurred before BOLD changes were observed in thalamus and right inferior frontal gyrus (BA44). Dynamic causal modeling provided evidence of a causal link between hemodynamic changes in the left PFC and reading-evoked seizures. Conclusion: Our findings support the important role of deep cortical and subcortical structures, in particular the frontal PFC, as key regions in initiating and modulating seizure activity. In our patient with RE, BA6 appeared to be the area linking cognitive activation and seizure activity.
Power-Area Trade-Offs in Divided Word Line Memory Arrays

Since on-chip caches account for a significant portion of the power budget of modern microprocessors, low power caches are needed in microprocessors destined for portable electronic applications. A significant portion of the power consumption of caches comes from accessing the cache memory array and most of the power consumption of the memory array comes from driving the bit line pairs (i.e., the column current). Various memory array architectures have been proposed to improve the word line delay and the column current. For example, in a divided word line memory array memory cells in each row are organized into blocks. Only the memory cells which are in the activated block have their bit line pairs driven, thus both improving the speed (by decreasing the word line delay) and lowering the power consumption (by decreasing the column current). In this paper we analyze the power-area tradeoffs of divided word line memories with different size blocks. We compare the area and power consumption of 16 Kbit and 64 Kbit memory arrays with 2, 4, 8, and 16 memory cells per block. Our experiments show that a divided word line memory array can lower the power consumption by 50% to 90% over a nondivided word line memory array. However, they consume more area; the area of a divided word line memory array can be 15% to 27% larger than the area of a comparable nondivided word line array. Our experiments also showed that divided word line memory arrays with two or four memory cells in a block have better power-area product than those with more than four cells per block.
Ginkgo biloba does not improve cognitive function in MS

Objective: To determine whether Ginkgo biloba extract (ginkgo) improves cognitive function in persons with multiple sclerosis (MS). Methods: Persons with MS from the Seattle and Portland VA clinics and adjacent communities who scored 1 SD or more below the mean on one of 4 neuropsychological tests (Stroop Test, California Verbal Learning Test II [CVLT-II], Controlled Oral Word Association Test [COWAT], and Paced Auditory Serial Addition Task [PASAT]) were randomly assigned to receive either one 120-mg tablet of ginkgo (EGb-761; Willmar Schwabe GmbH & Co, Germany) or one placebo tablet twice a day for 12 weeks. As the primary outcome, we compared the performance of the 2 groups on the 4 tests at exit after adjusting for baseline performance. Results: Fifty-nine subjects received placebo and 61 received ginkgo; 1 participant receiving placebo and 3 receiving ginkgo were lost to follow-up. Two serious adverse events (AEs) (myocardial infarction and severe depression) believed to be unrelated to the treatment occurred in the ginkgo group; otherwise, there were no significant differences in AEs. The differences (ginkgo − placebo) at exit in the z scores for the cognitive tests were as follows: PASAT −0.2 (95% confidence interval [CI] −0.5 to 0.1); Stroop Test −0.5 (95% CI −0.9 to −0.1); COWAT 0.0 (95% CI −0.2 to 0.3); and CVLT-II 0.0 (95% CI −0.3 to 0.3); none was statistically significant. Conclusions: Treatment with ginkgo 120 mg twice a day did not improve cognitive performance in persons with MS. Classification of evidence: This study provides Class I evidence that treatment with ginkgo 120 mg twice a day for 12 weeks does not improve cognitive performance in people with MS.
Bifurcations on Elliptic Functions

In this paper we are dealing with the dynamical properties of the Jacobian elliptic functions, cosine-amplitude and sine-amplitude. Seen as one parameter dynamical systems, they present a flip type bifurcation at the origin. In fact they are particular cases of some general families of functions holding sufficient conditions we call degenerate.
Retinopathy of prematurity: a review

Retinopathy of prematurity [ROP], previously called retrolental fibroplasia, is a vasoproliferative retinopathy that occurs principally, but not exclusively in premature and low-birth-weight infants. It occurs in two overlapping phases, namely, (a) an acute phase in which normal vasculogenesis is interrupted and a response to injury is observable in the retina and (b) a chronic or late proliferation of membranes into the vitreous during which tractional detachment of the retina, scarring of the macula and significant visual loss occur. More than 90 percent of cases of acute ROP regress spontaneously, healing with minimal scarring and little or no visual loss. Less than 10 percent of the involved eyes go on to significant cicatrisation. Nigerian Journal of Paediatrics Vol. 31(3) 2004: 61-66
Chaotic attractors in One-Dimension Generated by a singular Shilnikov Orbit

Chaotic attractors containing Shilnikov's saddle-focus homoclinic orbits have been observed in many physical systems. Past and current researches of this type of Shilnikov homoclinic phenomena have focused on the orbit and nearby structures only. In this paper we will look at the role such orbits play in a type of attractor, which arises from one-dimensional return maps at the singular limits of some singularly perturbed systems. Results on symbolic dynamics, natural measures, and Lyapunov exponents are obtained for a sequence of a one-parameter caricature family of such attractors.
Author's reply: Managing the combination of non-alcoholic fatty liver disease and metabolic syndrome

We thank our colleagues for the timely letter, giving us the opportunity to underline a point which was not considered in our review [1], i.e., the tight control of cholesterol levels and cardiovascular risk by statins. Several recent studies suggested that elevated liver enzymes (namely alanine aminotransferase and particularly g-glutamyl-transpeptidase levels [2]) are significantly associated with cardiovascular risk, independent of established risk factors and the features of the metabolic syndrome. This evidence fits with the results of the GREACE study, where atorvastatin treatment in subjects with coronary disease and abnormal liver tests reduced both cardiovascular events and liver enzymes [3]. Unfortunately, when statins were used to reduce fatty liver, the results were disappointing. In a comprehensive meta-analysis, Musso et al. identified 4 RCT of statin use in NAFLD [4]. In the only study based on repeated liver biopsies, simvastatin did not improve histological outcomes; in the remaining studies atorvastatin improved the ultrasonographic imaging of the liver and/or liver enzymes, as biochemical markers of steatosis. In the large St. Francis Heart Study, atorvastatin combined with vitamin E and C significantly reduced the odds of NAFLD in a 3.6-year follow-up [5]. Ezetimibe was evaluated in 2 uncontrolled trials and 2 RCTs, consistently improving liver histology and plasma lipids [4]. Notably all studies reported that statins were well-tolerated [6], confirming the results of Chalasani et al. that patients with elevated liver enzymes are not at higher risk for statin hepatotoxicity [7]. Triglyceride accumulation in the liver should no longer be considered a mere epiphenomenon of the dyslipidemia associated with insulin resistance, but steatosis probably participates in the metabolic imbalance and drives an additional cardiovascular risk. A comprehensive management of NAFLD must include an effective drug treatment of hyperlipidemia to reduce both liver disease progression and cardiovascular-related outcomes, and statins may be a valuable opportunity.
tPA and warfarin

The appropriate use of IV tissue plasminogen activator (tPA) for patients with acute ischemic stroke remains an area of active discussion among health care professionals. Since its approval in the United States by the Food and Drug Administration in 1996, the medical community has continued to review and discuss the risks vs benefits of this important therapy. Two recent publications1,2 and accompanying editorials have refocused attention on the vexing issue of using IV tPA in patients taking warfarin. The Xian et al.1 study found a 1.1% absolute increase in the risk of intracranial hemorrhage (ICH) with warfarin use (5.7% vs 4.6%), but this difference was no longer present once the analysis was adjusted for various risk factors. The Ruecker et al.2 study reported a 20% risk of ICH, but the difference was barely significant (p = 0.044) once proper adjustments were made. It is important to consider that successful recanalization or reperfusion of the stroke is likely to have precipitated a hemorrhage in some of these cases.3 Therefore the reported measure (cerebral hemorrhage) might actually be consequent (in part) to the therapeutic intervention, and not solely related to therapy with warfarin.
Short-term aromatase inhibition: effects on glucose metabolism and serum leptin levels in young and elderly men.

OBJECTIVE To assess and compare the effects of short-term aromatase inhibition on glucose metabolism, lipid profile, and adipocytokine levels in young and elderly men. DESIGN AND METHODS Ten elderly and nine young healthy men were randomized to receive letrozole 2.5 mg daily or placebo for 28 days in a crossover design. RESULTS Both in young and elderly men, active treatment significantly increased serum testosterone (+128 and +99%, respectively) and decreased estradiol levels (-41 and -62%, respectively). Fasting glucose and insulin levels decreased in young men after active intervention (-7 and -37%, respectively) compared with placebo. Leptin levels fell markedly in both age groups (-24 and -25%, respectively), while adiponectin levels were not affected by the intervention. Lipid profile was slightly impaired in both groups, with increasing low density lipoprotein-cholesterol levels (+14%) in the younger age group and 10% lower levels of APOA1 in the elderly. A decline in IGF1 levels (-15%) was observed in the younger age group. No changes in weight or body mass index were observed in either young or old men. CONCLUSIONS Short-term aromatase inhibition appears to affect glucose metabolism in young men, and lipid metabolism, including leptin secretion, in young and elderly men. Furthermore, the short period of exposure suggests that these changes might be mediated by direct effects of sex steroids rather than by changes in body composition.
Stochastic Resonance in alpha oscillators in the Human Brain

We experimentally study stochastic resonance (SR) in the human brain through a noise effect for entrainment dynamics of the alpha (α) wave. The measurement has been carried out under the following conditions in order to obtain clear evidence of the SR phenomenon in the central nervous system. The periodic and noisy stimuli are respectively applied to the right and the left eyes of the subject independently. When only periodic and constant (but weak enough) stimulus is applied to the right eye, it does not induce any global entrainment of α-oscillators to the stimulus frequency. In this situation increasing the amplitude of the noise stimulus (frequency bandwidth from 15 to 60 Hz), harmonic entrainment occurs for a certain range of the noise amplitude and shows a sharp peak in the power spectrum of brain waves. Plotting the amplitude of the peak against the noise amplitude, a bell-type shape is seen, i.e. the maximum signal amplitude at an optimum noise. It clearly indicates the SR phenomenon. Taking account of our experimental conditions and set-up, the present SR phenomenon occurs not on the retina but on the visual processing area in the central nervous systems beyond the optic chiasma.
Fasting insulin has a stronger association with an adverse cardiometabolic risk profile than insulin resistance: the RISC study.

OBJECTIVE Fasting insulin concentrations are often used as a surrogate measure of insulin resistance. We investigated the relative contributions of fasting insulin and insulin resistance to cardiometabolic risk and preclinical atherosclerosis. DESIGN AND METHODS The Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) cohort consists of 1326 European non-diabetic, overall healthy men and women aged 30-60 years. We performed standard oral glucose tolerance tests and hyperinsulinemic euglycemic clamps. As a general measure of cardiovascular risk, we assessed the prevalence of the metabolic syndrome in 1177 participants. Carotid artery intima media thickness (IMT) was measured by ultrasound to assess preclinical atherosclerosis. RESULTS Fasting insulin was correlated with all elements of the metabolic syndrome. Insulin sensitivity (M/I) was correlated with most elements. The odds ratio for the metabolic syndrome of those in the highest quartile of fasting insulin compared with those in the lower quartiles was 5.4 (95% confidence interval (CI) 2.8-10.3, adjusted for insulin sensitivity) in men and 5.1 (2.6-9.9) in women. The odds ratio for metabolic syndrome of those with insulin sensitivity in the lowest quartile of the cohort compared with those in the higher quartiles was 2.4 (95% CI 1.3-4.7, adjusted for fasting insulin) in men and 1.6 (0.8-3.1) in women. Carotid IMT was only statistically significantly associated with fasting insulin in both men and women. CONCLUSIONS Fasting insulin, a simple and practical measure, may be a stronger and independent contributor to cardiometabolic risk and atherosclerosis in a healthy population than hyperinsulinemic euglycemic clamp-derived insulin sensitivity.
Bifurcation of Equilibrium in Micromachined Elastic Structures with Liquid Interface

The determination of bifurcation of equilibrium in micromachined elastic structures with liquid interface is posed as nonlinear boundary-value problems associated with spatially distributed models involving fluid forces. Explicit nonlinear algebraic equations for determining the bifurcation points associated with micromachined cantilever beam and membrane are derived. These equations permit bifurcation analysis involving any system parameter. It is shown that bifurcation of equilibrium in these structures is of the fold type. Numerical results are obtained for typical cantilever beam and membrane.