Miracle-dz/UniFAR-FTUs huggingface dataset:
Methotrexate is steroid sparing in acute sarcoidosis: results of a double blind, randomized trial.

BACKGROUND AND AIM OF THE WORK Methotrexate has been steroid sparing for some patients with chronic sarcoidosis. We wished to determine whether methotrexate can be steroid sparing in the first year of corticosteroid therapy in sarcoidosis. METHODS Patients with new onset, symptomatic disease within four weeks of starting on prednisone were randomized to receive either methotrexate or placebo for the next year. They were seen monthly and prednisone dosage was tapered following a pre-determined schedule. RESULTS Of 24 patients enrolled, only 15 received at least six months of therapy. Since methotrexate appears to take six months to be effective, only patients who completed six or more months of therapy were evaluated. The amount of prednisone per day decreased for both groups: methotrexate (First 6 months: Median 26 (Range 15-37) mg/day); Second 6 months 8 (1-22) mg/day, p < 0.01) and placebo (First 6 Months 28 (24-33) mg/day; Second 6 months 16 (11-22) mg/day, p < 0.02), with less prednisone used for the methotrexate patients versus placebo in the last six months (p < 0.01). There was also less weight gain for those patients receiving methotrexate. There was no difference in toxicity between methotrexate and placebo. The difference between methotrexate versus placebo was not seen when all patients (including the dropouts) were analyzed. CONCLUSIONS Methotrexate can be a steroid sparing agent in acute sarcoidosis.
Missed appointment in adolescent clinic; perspective from tertiary care hospital, Thailand.

OBJECTIVE To determine the missed appointment rate and evaluate the factors related to appointment adherence in adolescent patients, based on the patients' characters and services provided. MATERIAL AND METHOD All medical records in adolescent clinic at Siriraj Hospital between 2004 and 2009 were reviewed Patients that visited the clinic at least twice with the follow-up visit order were recruited. Data analyses were performed by Chi-square test and Fisher's exact test wherever appropriated. RESULTS One hundred twenty six patients met the inclusion criteria. Patients'mean age were 14.3-year-old (SD = 2.7) and the majority (95%) were students. Seventy one point five percent of principle diagnosis related to behavioral problems while 90% had at least one risky behavior detected Comparing between missed and non-missed appointment, only the acute illness and the history of appointment cancellation were significant different characters between groups (p < 0.001). Of 429 visits, 409 (95.3%) got telephone reminder a few days prior the appointment date, 48 (11.2%) remained non-complying and 40 (9.7%) had rescheduled. Only 18 (4.2%) of the visits were the patients themselves made re-appointments, which all complied with the new visit. Having rescheduled after being reminded and having history of a missed previous appointment were the most significant predictors for next appointment adherence (p = 0. 01 and p = 0.02 respectively). CONCLUSION In adolescents, appointment non-compliance is a challenging issue for clinicians. Predicting factors found in this study might help foster appointment adherence. Interestingly, services provided such as telephone reminder short waiting time, appointment time did not influence adherence in this population.
Graduate medical education and physician supply in New York State.

OBJECTIVES To estimate the supply of physicians and residents in New York State and to assess the impact of state policies on the supply and distribution of physicians in the state. DESIGN A comparison of the number of residents in New York State for 1988 and 1994 (from the American Medical Association Medical Education Database) and the number of active patient care physicians in New York by specialty and age (from the 1995 New York State Physician File). MAIN OUTCOME MEASURES Changes in the number of residents in New York State between 1988 and 1994 by specialty and medical school location; estimates of the numbers of physicians by age and specialty in New York for 1995; the migration of new physicians into and out of the state. RESULTS The number of residents in New York State grew by nearly 21% between 1988 and 1994, despite a number of policies and programs encouraging maintenance of production levels. This growth is attributed to increases in the number of international medical graduates (IMGs) entering residency training through a widening "IMG window. " Projection models show that, if production of new physicians continues as current levels, the supply of physicians will grow substantially during the next 2 decades. CONCLUSIONS Past policies to influence the supply, production, and distribution of physicians in New York State have not had their desired effects. Future policies and incentives must be carefully framed and coordinated to avoid similar failures.
Three‐dimensional fine‐scale genetic structure of the neotropical epiphytic orchid, Laelia rubescens

Epiphytic plants occupy three‐dimensional space, which allows more individuals to be closely clustered spatially than is possible for populations occupying two dimensions. The unique characteristics of epiphytes can act in concert to influence the fine‐scale genetic structure of their populations which can, in turn, influence mating patterns and other population phenomena. Three large populations of Laelia rubescens (Orchidaceae) in the Costa Rican seasonal dry forest were sampled at two levels of intensity to determine: (i) whether individual clusters contain more than one genotype, and (ii) the spatial distribution and fine‐scale genetic structure of genotypes within populations. Samples were assayed for their multilocus allozyme genotypes and spatial autocorrelation analyses were performed. High levels of genetic diversity, high genotypic diversity and low among‐population variation were found. In the larger clusters, multiple genets per cluster were common with discrete clusters containing up to nine genotypes. Spatial autocorrelation analyses indicated significant positive genetic structure at distances of ≤ 45 cm. This result is likely due to the formation of discrete clusters by vegetative reproduction, as well as the establishment of sexually derived progeny within and near maternal clusters.
Effect of ozone on algal organic matters as precursors for disinfection by-products production

The effect of ozone dose on algae (Microcystic aeruginosa), algal extracellular organic matters (EOM), humic acids (HA) and four model compounds: bovine serum albumin (BSA), starch, deoxyribonucleic acid (DNA) and fish oil as precursors for disinfection by-products (DBPs) production was investigated. Algae showed the highest DBPs formation (71.8 μg mg−1 total organic carbon (TOC)) than other samples. Only BSA showed lower chloroform yield (5.9 μg mg−1 TOC) than haloacetic acids, HAAs (11.2 μg mg−1 TOC). Algae, EOM, starch, DNA, fish oil and HA all showed higher chloroform yields (46.1, 23.8, 8.9, 37.1, 44.0 and 33.7 μg mg−1 TOC, respectively) than HAAs (25.7, 20.2, 6.3, 10.0, 13.1 and 18.4 μg mg−1 TOC, respectively). Pre-ozonation increased DBPs, especially chloroform, formation from algae and DNA significantly. With the increase in ozone doses, DBPs yields of algae and DNA increased 19.0 and 34.5 μg mg−1 TOC, chloroform yields of algae and DNA increased 15.3 and 30.4 μg mg−1 TOC, respectively. However, pre-ozonation decreased DBPs formation from starch, fish oil and HA, and the corresponding decrease amount was 2.4, 26.9 and 9.5 μg mg−1 TOC, respectively. There are no regular change trends of DBPs formation from EOM and BSA with the increase in ozone doses.
Clinical and prognostic utility of cardiovascular magnetic resonance imaging in myeloma patients with suspected cardiac amyloidosis.

OBJECTIVES AL amyloidosis affects up to 30% of patients with multiple myeloma (MM), and cardiac involvement is associated with worse outcomes. Traditional screening modalities including EKG, echocardiography and biomarkers have limited value. The aim of this study was to evaluate the clinical and prognostic value of late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR) imaging in patients with plasma cell dyscrasias and suspected cardiac amyloidosis (CA). METHODS A total of 251 consecutive patients with plasma cell dyscrasias who underwent CMR were enrolled in this study. Primary endpoint was all cause mortality. Clinical, ECG, echocardiographic, biomarker and CMR predictors of mortality were analyzed. RESULTS Mean age of population was 63 ± 10 years, 36% females and 19% African Americans. During a median follow-up duration of 28 months (IQR 5-56), there were 97 deaths (39%). Patients who died were more likely to have diabetes (28% vs. 14%; P = 0.03), CAD (28% vs. 16%; P = 0.04) and CKD (33% vs. 21%; P = 0.04). With endomyocardial biopsy as the gold standard (42 (17%) patients), amyloid pattern on CMR (LGE+) had sensitivity and negative predictive values of 100%; specificity and positive predictive values of 80 and 81% with an AUC 0.9 for CA. History of CAD (HR 1.64, 95% CI 1.01-2.6; P = 0.04), brain natriuretic peptide (HR 1.0003 95% CI 1.0001-1.0006; P = 0.004) and LGE + (HR 1.72, 95% CI 1.05-2.8; P = 0.02) were independent predictors of mortality. LGE+ possessed incremental prognostic value over clinical, laboratory and echocardiographic variables for mortality prediction. CONCLUSIONS CMR is a clinically useful tool for diagnosis and prognostication in myeloma patients with suspected CA.
Optic Nerve Alterations in Apolipoprotein E Deficient Mice

Purpose To study the morphologic characteristics of the optic nerve (ON) by using an experimental model of knockout mice for expression of the ApoE gene Methods Eyeballs with the retrobulbar ON attached were obtained from 24-week-old mice. Using morphologic and morphometric techniques and light and transmission electron microscopy, the ON characteristics were determined in three groups of mice: 1) wild type mice as the controls (CG; n=15), 2) knockout mice for the ApoE gene (ApoE-G; n=15), and 3) knockout mice for the ApoE gene that were fed a cholesterol-supplemented diet (ApoED-G; n=15). Results The ON cross-sectional area was significantly higher in the ApoE-G than in the CG (p<0.001) mice, whereas no significant changes were noticed between the ApoE-G and ApoED-G mice. Significant differences were noticed between those groups regarding the myelination index. Higher density of intraaxonal degeneration and myelin sheath alterations were found in both ApoE groups in respect to the CG. Conclusions These results suggest that ApoE knockout mice have changes in ON morphology and myelination.
Oncogenic BRAFV600E inhibits BIM expression to promote melanoma cell survival

Somatic activating mutations of BRAF are the earliest and most common genetic abnormality detected in the genesis of human melanoma. However, the mechanism(s) by which activated BRAF promotes melanoma cell cycle progression and/or survival remain unclear. Here we demonstrate that expression of BIM, a pro‐apoptotic member of the BCL‐2 family, is inhibited by BRAF→MEK→ERK signaling in mouse and human melanocytes and in human melanoma cells. Trophic factor deprivation of melanocytes leads to elevated BIM expression. However, re‐addition of trophic factors or activation of a conditional form of BRAFV600E leads to rapid inhibition of BIM expression. In both cases, inhibition of BIM expression was dependent on the activity of MEK1/2 and the proteasome. Consistent with these observations, pharmacological inhibition of BRAFV600E or MEK1/2 in human melanoma cells (using PLX4720 and CI‐1040 respectively) led to a striking elevation of BIM expression. Re‐activation of BRAF→MEK→ERK signaling led to phosphorylation of BIM‐EL on serine 69 and its subsequent degradation. Interestingly, endogenous expression of BIM in melanoma cells was insufficient to induce apoptosis unless combined with serum deprivation. Under these circumstances, inhibition of BIM expression by RNA interference provided partial protection from apoptosis. These data suggest that regulation of BIM expression by BRAF→MEK→ERK signaling is one mechanism by which oncogenic BRAFV600E can influence the aberrant physiology of melanoma cells.
Qualitative Plasma PCR Assay (AMPLICOR CMV Test) versus pp65 Antigenemia Assay for Monitoring Cytomegalovirus Viremia and Guiding Preemptive Ganciclovir Therapy in Allogeneic Stem Cell Transplantation

ABSTRACT The performances of a commercially available qualitative plasma PCR assay (AMPLICOR CMV test; Roche Diagnostics) and the pp65 antigenemia assay (AG) were evaluated for the monitoring of cytomegalovirus (CMV) viremia in 43 allogeneic stem cell transplant recipients. In addition, the suitabilities of both assays for triggering the initiation of preemptive ganciclovir therapy were assessed. A total of 37 CMV viremic episodes were detected in 28 patients. Positivity of plasma PCR testing in one or more consecutive specimens was the only marker of CMV viremia in 18 of the 37 episodes (PCR positive and AG negative,n = 50 specimens). Five episodes were diagnosed on the basis of a single positive AG result (AG positive and PCR negative,n = 5 specimens); both assays were eventually positive (PCR positive and AG positive, n = 27 specimens) for 14 viremic episodes; for these episodes, conversion of the PCR assay result to a positive result occurred an average of 1 week before conversion of the AG result. Overall, the concordance between the two methods was 90%, and the sensitivities of the plasma PCR assay and AG for the detection of CMV viremic episodes were 86.5 and 51.3%, respectively. Two patients who tested positive by both assays simultaneously progressed to CMV end-stage organ disease, despite the initiation of preemptive ganciclovir therapy. Conversion of the AG result to a negative result upon administration of preemptive ganciclovir therapy occurred a median of 7.5 days earlier than conversion of the plasma PCR assay result. Nineteen of the 28 patients with CMV viremia received AG-guided preemptive ganciclovir therapy; had the positivity of the plasma PCR assay triggered the initiation of preemptive therapy, 9 additional patients would have been unnecessarily treated since none of them developed CMV end-stage organ disease. Although the AMPLICOR CMV assay is more sensitive than AG, the latter appears to be more suitable both for guiding the initiation of preemptive therapy and for monitoring a patient's response to antiviral therapy.
Depression trajectories, inflammation, and lifestyle factors in adolescence: The TRacking Adolescents' Individual Lives Survey.

OBJECTIVE In adults, depression and inflammation are bidirectionally related. This association is less clear in adolescents. Moreover, somatic and cognitive depressive symptoms might be differentially related to inflammation. Lifestyle factors, as in adults, may play an important mediating role in adolescents. For the current study we evaluated trajectories of depressive symptoms in adolescence over a 5-year course and their relation with subsequent high-sensitivity C-reactive protein (hsCRP) levels, and examined lifestyle factors as mediators. METHOD Participants of the TRacking Adolescents' Individual Lives' Survey (TRAILS; N = 1166) were followed from 2001 until 2008. Three biennial youth self-report (YSR) assessments of depressive symptoms were taken. Demographics, health, and lifestyle factors and levels of hsCRP were assessed at Wave 3. Latent-class analysis was used to determine trajectories of depression and general linear models to determine the association between depression trajectories and hsCRP. Finally, mediation analysis was performed to test mediation of lifestyle factors. RESULTS Persistently moderate to high depressive symptoms were associated with higher hsCRP levels. Results were unaltered when we adjusted for demographics and health variables. Smoking mediated the association between depressive symptoms total score and hsCRP, in large part. Persistently higher scores on somatic and cognitive symptom subscales were associated with higher levels of hsCRP than persistently low scores. These results were rendered nonsignificant after covariate adjustment. CONCLUSION Persistent depressive symptoms were associated with subsequent higher levels of hsCRP, with somatic and cognitive symptoms contributing equally. The association was mediated by smoking behavior. These findings suggest that reducing adolescent depression and smoking are important starting points in the prevention of inflammatory diseases.
The effect of androgen treatment on bone metabolism in female‐to‐male transsexuals

Histomorphometry was performed in iliac crest biopsies from 15 female‐to‐male (F‐M) transsexuals with a mean age of 30 ± 6.1 (SD) years. At the time of study, they had been treated with parenteral testosterone esters (250 mg/2 weeks) or oral testosterone undecanoate (160 mg/day). The median androgen treatment duration was 39 months. The patients had undergone hysterectomy and bilateral ovariectomy. The bone biopsy was obtained after double tetracycline labeling. Histomorphometric results were compared with data from 8 postmenopausal women and with data from 11 healthy men who had died suddenly. Dynamic parameters were compared with data from the literature. The biochemical picture was characterized by serum testosterone concentrations lower than in eugo‐nadal men and estradiol concentrations lower than in eugonadal women and elevated gonadotrophin levels. The bone mineral density in the F‐M transsexuals was as expected for age (Z‐score −0.31 ± 1.49). Cortical thickness was significantly higher in F‐M transsexuals than in both control groups. Trabecular bone structure was similar in F‐M transsexuals and both control groups. The bone formation parameters were generally lower in F‐M transsexuals than in the control groups. The eroded surface was lower in F‐M transsexuals than in postmenopausal women. The low bone turnover and preservation of trabecular bone is consistent with the assumption that testosterone treatment protects the bone in these F‐M transsexuals from the deleterious effects of estrogen deficiency. The increased cortical thickness suggests an anabolic effect of the testosterone treatment. (J Bone Miner Res 1996;11:1769–1773)
Injectable Form of Cross-Linked Hyaluronan is Effective for Middle Ear Wound Healing

Objectives: Two studies were designed to investigate a hyaluronan (HA) gel for middle ear (ME) wound healing. Methods: We used a guinea pig model of ME wound healing. In a long-term study, we performed a comparison of hearing and ME inflammation in 3 groups. Group 1 (n = 8) underwent bilateral wounding of ME mucosa and unilateral packing of the ME with HA gel (Sepragel). Group 2 (n = 6) was the same as group 1 except that the packing was absorbable bovine collagen sponges (Gelfoam). Group 3, the control group (n = 14), had operated, unpacked ears. In a short-term study, we investigated ME retention of HA gel at 1 and 2 weeks (n = 16). Results: At 1 week, all ears showed decreased distortion product otoacoustic emissions (DPOAEs) and auditory brain stem responses (ABRs) secondary to ME packing and postsurgical inflammation. The controls recovered preoperative DPOAEs and ABRs by week 2. Group 1 had decreased low-frequency DPOAEs at weeks 2 and 6, but their high-frequency DPOAEs and ABRs recovered to preoperative values by week 6. Group 2 had hearing losses that persisted throughout the study. Group 1 showed normal ME and inner ear histologic characteristics. Group 2 showed inflammatory cells within the ME and cochleas. Group 1 showed less packing retention than did group 2 at week 6 (p = 016). Eighty-five percent of the HA packing remained at 1 week, and 73% at 2 weeks. Conclusions: Hyaluronan gel was a relatively safe and effective ME packing material in our animal model.
Effect of amantadine on the sleep–wake cycle of an inpatient with brain injury

Background: A previous study suggested that the routine use of drugs intended to improve attention and arousal, such as methylphenidate, tend to have a variable but not significant effect on sleep–wake cycles. As amantadine is a frequently employed drug in brain injury rehabilitation, with known effects on fatigue and motor processing speed, this study examined the effect of amantadine on the sleep–wake behaviour of patients with brain injury undergoing rehabilitation. Method: This was a naturalistic observation using an observationally defined sleep–wake distribution for a total of 43 subjects with brain injury. Identified patients were observed for a full 24 hours a day 2 weeks before and 2 weeks after starting amantadine. Some of these patients (n = 12) had been administered amantadine on clinical grounds and, for this paper, served as the experimental group, while the drug naïve (n = 31) served as a control. Three outcome measures were operationalized: hours of sleep in 24 hours, hours of sleep during daytime and hours of sleep during night-time. Result: The average number of hours of sleep during a 24-hour period was not significantly different for the two cohorts. Similarly hours of sleep during daytime and hours of sleep during night-time were on average the same for the two groups. The data suggest that amantadine has no direct bearing on sleep/wake cycles using these parameters. Conclusion: This study fails to demonstrate that the use of amantadine on an inpatient brain injury population will affect sleep/wake quantity.
The economic cost of return to work: an employer's perspective.

BACKGROUND Although return-to-work (RTW) interventions have been shown to be cost-effective, most previous economic analyses have focused on the insurer's perspective. Employers can also incur costs when supporting the RTW of their employees. OBJECTIVE To identify a key set of items for estimating the costs of RTW interventions from the employer's perspective, and to identify and value the costs and consequences of a RTW intervention. PARTICIPANTS Employers with knowledge of the economic costs of RTW. METHODS A survey of 10 workplaces with RTW programs was conducted. The survey consisted of semi-structured interviews with a human resources or occupational health and safety representative from each enrolled workplace. RESULTS The interviews were reviewed and from them key items were identified for estimating the costs of RTW interventions from the employer's perspective. Employers identified the following costs: medical, equipment, training and education, wage replacement and productivity, and claims administration when assisting an employee's RTW. CONCLUSIONS Even in a jurisdiction with workers' compensation insurance, employers incur costs associated with RTW programs. It is important to consider these costs, from the perspective of the employer, when studying the cost-effectiveness of RTW interventions or programs.
Automatic generation of inexact digital circuits by gate-level pruning

Inexact or approximate circuits show great ability to reduce power consumption at the cost of occasional errors in comparison to their conventional counterparts. Even though the benefits of such circuits have been proven for many applications, they are not wide spread owing to the absence of a clear design methodology and the required CAD tools. In this regard, this paper presents a methodology to automatically generate inexact circuits starting from a conventional design by adding only one small step in the digital design flow. Further, this paper also demonstrates that achieving pruning at gate-level can lead to substantial savings in terms of power consumption, critical path delay and silicon area. An order of magnitude area and power savings is demonstrated for a 64-bit gate level pruned high-speed adder for a 10% relative error magnitude.