LLukas22/scidocs huggingface dataset:
Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation: results on health-related quality of life and symptom burden. The MANTRA-PAF trial.

AIMS
The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial assessed the long-term efficacy of an initial strategy of radiofrequency ablation (RFA) vs. antiarrhythmic drug therapy (AAD) as first-line treatment for patients with PAF. In this substudy, we evaluated the effect of these treatment modalities on the Health-Related Quality of Life (HRQoL) and symptom burden of patients at 12 and 24 months.


METHODS AND RESULTS
During the study period, 294 patients were enrolled in the MANTRA-PAF trial and randomized to receive AAD (N = 148) or RFA (N = 146). Two generic questionnaires were used to assess the HRQoL [Short Form-36 (SF-36) and EuroQol-five dimensions (EQ-5D)], and the Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia (ASTA) was used to evaluate the symptoms appearing during the trial. All comparisons were made on an intention-to-treat basis. Both randomization groups showed significant improvements in assessments with both SF-36 and EQ-5D, at 24 months. Patients randomized to RFA showed significantly greater improvement in four physically related scales of the SF-36. The three most frequently reported symptoms were breathlessness during activity, pronounced tiredness, and worry/anxiety. In both groups, there was a significant reduction in ASTA symptom index and in the severity of seven of the eight symptoms over time.


CONCLUSION
Both AAD and RFA as first-line treatment resulted in substantial improvement of HRQoL and symptom burden in patients with PAF. Patients randomized to RFA showed greater improvement in physical scales (SF-36) and the EQ-visual analogue scale.


CLINICAL TRIAL REGISTRATION
URL http://www.clinicaltrials.gov. Unique identifier: NCT00133211.
An unusual presentation of a customs importation seizure containing amphetamine, possibly synthesized by the APAAN-P2P-Leuckart route.

During the analysis of an Irish customs seizure (14 packages each containing approximately one kilogram of a white wet paste) were analysed for the suspected presence of controlled drugs. The samples were found to contain amphetamine and also characteristic by-products including benzyl cyanide, phenylacetone (P2P), methyl-phenyl-pyrimidines, N-formylamphetamine, naphthalene derivatives and amphetamine dimers. The analytical results corresponded with the impurity profile observed and recently reported for the synthesis of 4-methylamphetamine from 4-methylphenylacetoacetonitrile [1]. The synthesis of amphetamine from alpha-phenylacetoacetonitrile (APAAN) was performed (via an acid hydrolysis and subsequent Leuckart reaction) and the impurity profile of the product obtained was compared to those observed in the customs seizure. Observations are made regarding the route specificity of these by-products.
Influence of early enteral nutrition (EEN) on insulin resistance in gastric cancer patients after surgery.

OBJECTIVE
To evaluate the benefits of reducing insulin resistance by early enteral nutrition (EEN) in gastric cancer patients after surgery.


METHODS
Gastric cancer patients were managed to randomly accept traditional total parenteral nutrition (group A) or EEN (group B) after surgical treatment. The patients in group B were fed by tubes with 250-500 mL 5% sodium chloride and glucose injection at 24 h post-surgery, and were fed enteral nutritional emulsion with constant infusion by pump slowly increasing from 20 mL/h to 100 mL/h from 48 h, and then transiting to total enteral nutrition. Insulin sensitivity of patients was detected by Quicki method before operation and at 24 h, 48 h, 72 h, 120 h and 168 h post-surgery.


RESULTS
A total of 77 patients were enrolled, with 42 patients in group A, and 35 patients in group B. Baseline characteristics, biochemical indexes and operational characteristics were well balanced between two groups. The time-insulin sensitivity curves of the two groups indicated that IR was present early (day 1 to day 7) in gastric cancer patients and was significantly different between patients who had undergone surgical treatment and those who had not. Insulin sensitivity (SI) of patients in group B were higher than patients in group A with adjusting BMI, age and SI preoperative at 72 h, 120 h and 168 h post-surgery.


CONCLUSIONS
The management of EEN can alleviate insulin resistance in gastric cancer patients with surgical treatment.
Total pineal endocrine substitution therapy (TPEST) as a new neuroendocrine palliative treatment of untreatable metastatic solid tumor patients: a phase II study.

OBJECTIVES
It is known since many years that the pineal gland plays an anticancer role, and melatonin (MLT), the most investigated pineal hormone, has been proven to exert antitumor activity. However, MLT would not be the only hormone responsible for the antitumor action of the pineal gland. In fact, recent advances in the pineal investigations have shown that pineal indoles other than MLT may also exert anticancer activity, namely the three main indoles, consisting of 5-methoxytriptamine (5-MTT), 5-methoxytryptophol (5-MTP) and 5-methoxy-indole acetic acid (5-MIA). Cancer progression has appeared to be associated with a concomitant decline in the pineal endocrine function. Therefore, the replacement of a complete pineal function in the advanced cancer patients would require the exogenous administration of the overall four pineal indoles. Several clinical studies have shown that MLT alone at pharmacological doses may induce a control of the neoplastic progression in about 30% of untreatable metastatic solid tumor patients. The present study was performed in an attempt to evaluate the therapeutic of a total pineal endocrine substitution therapy with its four indole hormones in cancer patients, for whom no other conventional therapy was available.


METHODS
The study included 14 metastatic solid tumor patients, who had failed to respond to the conventional anticancer therapies. The pineal indoles were given orally according to a schedule elaborated in an attempt to reproduce their physiological circadian secretion during the daily photoperiod. MLT was given at 20 mg/day during the night, whereas the other indoles were given at 1 mg/day, by administering 5-MIA in the morning, 5-MTP at noon and 5-MTT in the afternoon.


RESULTS
A disease-control was achieved in 9/14 (64%) patients, consisting of partial response (PR) in one patient and stable disease (SD) in the other 8 patients. The median time of disease-control (PR + SD) was 6 months (range: 4-10).


CONCLUSIONS
This preliminary study shows that a total pineal endocrine replacement therapy by an exogenous administration of the overall four pineal indoles may induce a disease-control in about 60% of untreatable metastatic solid tumor patients. Then, these results would be clearly superior with respect to those described with MLT alone, by confirming in humans that MLT is not the only hormone responsible for the anticancer property of the pineal gland. Since Cartesius was the first author who suggested the fundamental role of the pineal in the connection between consciousness and biological life, this therapy could be defined as a Cartesian therapy.
Acetyl-L-carnitine (ALC) in attention-deficit/hyperactivity disorder: a multi-site, placebo-controlled pilot trial.

OBJECTIVE
To determine whether acetyl-L-carnitine (ALC), a metabolite necessary for energy metabolism and essential fatty acid anabolism, might help attention-deficit/hyperactivity disorder (ADHD). Trials in Down's syndrome, migraine, and Alzheimer's disease showed benefit for attention. A preliminary trial in ADHD using L-carnitine reported significant benefit.


METHOD
A multi-site 16-week pilot study randomized 112 children (83 boys, 29 girls) age 5-12 with systematically diagnosed ADHD to placebo or ALC in weight-based doses from 500 to 1500 mg b.i.d. The 2001 revisions of the Conners' parent and teacher scales (including DSM-IV ADHD symptoms) were administered at baseline, 8, 12, and 16 weeks. Analyses were ANOVA of change from baseline to 16 weeks with treatment, center, and treatment-by-center interaction as independent variables.


RESULTS
The primary intent-to-treat analysis, of 9 DSM-IV teacher-rated inattentive symptoms, was not significant. However, secondary analyses were interesting. There was significant (p = 0.02) moderation by subtype: superiority of ALC over placebo in the inattentive type, with an opposite tendency in combined type. There was also a geographic effect (p = 0.047). Side effects were negligible; electrocardiograms, lab work, and physical exam unremarkable.


CONCLUSION
ALC appears safe, but with no effect on the overall ADHD population (especially combined type). It deserves further exploration for possible benefit specifically in the inattentive type.
Administration of an intravenous perfluorocarbon contrast agent improves echocardiographic determination of left ventricular volumes and ejection fraction: comparison with cine magnetic resonance imaging.

OBJECTIVES
The purpose of this study was to determine whether contrast-enhanced transthoracic echocardiography improves the evaluation of left ventricular (LV) volumes and ejection fraction (EF).


BACKGROUND
Echocardiographic assessment of LV volumes and EF is widely used but may be inaccurate when the endocardium is not completely visualized. Recently the intravenous (i.v.) administration of perfluorocarbon microbubbles has been shown to enhance opacification of the LV cavity, but the utility of these agents to improve the echocardiographic assessment of LV systolic function is unknown.


METHODS
In 40 subjects (29 men and 11 women, aged 24 to 81 years) an assessment of LV volumes and EF was performed with a magnetic resonance imaging examination, followed immediately by a transthoracic echocardiogram before and after the intravenous administration of 2% dodecafluoropentane emulsion (EchoGen; Sonus Pharmaceuticals, Bothell, Washington).


RESULTS
Contrast enhanced the echocardiographic assessment of LV end diastolic volume (p < 0.02), end systolic volume (p < 0.01) and LVEF (p < 0.03). The percentage of subjects in whom the correct echocardiographic classification EF was normal, mild to moderately depressed or severely reduced improved significantly after contrast enhancement (from 71% before contrast to 94% after, p < 0.03). These findings were most striking in the subjects with two or more adjacent endocardial segments not visualized at baseline.


CONCLUSIONS
Administration of an intravenous contrast agent improves the ability to accurately assess LV volumes and EF in humans. Contrast enhancement is most useful in subjects with two or more adjacent endocardial segments not seen at baseline.
Challenges for co-morbid chronic illness care and policy in Australia: a qualitative study

BACKGROUND
In response to the escalating burden of chronic illness in Australia, recent health policies have emphasised the promotion of patient self-management and better preventive care. A notable omission from these policies is the acknowledgment that patients with chronic illness tend to have co-morbid conditions. Our objectives were: to identify the common challenges co-morbidity poses to patients and carers in their experiences of self-management; to detail the views and perceptions of health professionals about these challenges; and to discuss policy options to improve health care for people with co-morbid chronic illness. The method included semi-structured interviews and focus groups with 129 purposively sampled participants. Participants were people with Type 2 diabetes, chronic obstructive pulmonary disease and/or chronic heart failure as well as carers and health care professionals. Content analysis of the interview data was conducted using NVivo7 software.


RESULTS
Patients and their carers found co-morbidity influenced their capacity to manage chronic illness in three ways. First, co-morbidity created barriers to patients acting on risk factors; second, it complicated the process of recognising the early symptoms of deterioration of each condition, and third, it complicated their capacity to manage medication.


CONCLUSION
Findings highlight challenges that patients with multiple chronic conditions face in relation to preventive care and self-management. Future clinical policy initiatives need to move away from single illness orientation toward strategies that meet the needs of people with co-morbid conditions and strengthen their capacity to self-manage. These patients will benefit directly from specialised education and services that cater to the needs of people with clusters of co-morbidities.
The hypertriglyceridemic-waist phenotype and the risk of coronary artery disease: results from the EPIC-Norfolk prospective population study.

BACKGROUND
Screening for increased waist circumference and hypertriglyceridemia (the hypertriglyceridemic-waist phenotype) has been proposed as an inexpensive approach to identify patients with excess intra-abdominal adiposity and associated metabolic abnormalities. We examined the relationship between the hypertriglyceridemic-waist phenotype to the risk of coronary artery disease in apparently healthy individuals.


METHODS
A total of 21,787 participants aged 45-79 years were followed for a mean of 9.8 (standard deviation 1.7) years. Coronary artery disease developed in 2109 of them during follow-up. The hypertriglyceridemic-waist phenotype was defined as a waist circumference of 90 cm or more and a triglyceride level of 2.0 mmol/L or more in men, and a waist circumference of 85 cm or more and a triglyceride level of 1.5 mmol/L or more in women.


RESULTS
Compared with participants who had a waist circumference and triglyceride level below the threshold, those with the hypertriglyceridemic-waist phenotype had higher blood pressure indices, higher levels of apolipoprotein B and C-reactive protein, lower levels of high-density lipoprotein cholesterol and apolipoprotein A-I, and smaller low-density lipoprotein particles. Among men, those with the hypertriglyceridemic-waist phenotype had an unadjusted hazard ratio for future coronary artery disease of 2.40 (95% confidence interval [CI] 2.02-2.87) compared with men who did not have the phenotype. Women with the phenotype had an unadjusted hazard ratio of 3.84 (95% CI 3.20-4.62) compared with women who did not have the phenotype.


INTERPRETATION
Among participants from a European cohort representative of a contemporary Western population, the hypertriglyceridemic-waist phenotype was associated with a deteriorated cardiometabolic risk profile and an increased risk for coronary artery disease.
Instant effects of peppermint essential oil on the physiological parameters and exercise performance

OBJECTIVE
Effect of peppermint on exercise performance was previously investigated but equivocal findings exist. This study aimed to investigate the effects of peppermint ingestion on the physiological parameters and exercise performance after 5 min and 1 h.


MATERIALS AND METHODS
Thirty healthy male university students were randomly divided into experimental (n=15) and control (n=15) groups. Maximum isometric grip force, vertical and long jumps, spirometric parameters, visual and audio reaction times, blood pressure, heart rate, and breath rate were recorded three times: before, five minutes, and one hour after single dose oral administration of peppermint essential oil (50 µl). Data were analyzed using repeated measures ANOVA.


RESULTS
Our results revealed significant improvement in all of the variables after oral administration of peppermint essential oil. Experimental group compared with control group showed an incremental and a significant increase in the grip force (36.1%), standing vertical jump (7.0%), and standing long jump (6.4%). Data obtained from the experimental group after five minutes exhibited a significant increase in the forced vital capacity in first second (FVC1)(35.1%), peak inspiratory flow rate (PIF) (66.4%), and peak expiratory flow rate (PEF) (65.1%), whereas after one hour, only PIF shown a significant increase as compare with the baseline and control group. At both times, visual and audio reaction times were significantly decreased. Physiological parameters were also significantly improved after five minutes. A considerable enhancement in the grip force, spiromery, and other parameters were the important findings of this study. Conclusion : An improvement in the spirometric measurements (FVC1, PEF, and PIF) might be due to the peppermint effects on the bronchial smooth muscle tonicity with or without affecting the lung surfactant. Yet, no scientific evidence exists regarding isometric force enhancement in this novel study.
Soy isoflavones sensitize cancer cells to radiotherapy.

Soy isoflavones are dietary compounds isolated from soybeans, which are safe for human use and have mild anti-cancer properties. Soy isoflavones inhibit the activity of transcription factors and genes essential for tumor cell proliferation, invasion, and neovascularization, and it appears that soy isoflavones may enhance the effectiveness of conventional therapies against cancer. Soy isoflavones could be an effective complementary treatment given that they inhibit the survival signaling pathways of various cancer cells through altered activation of APE1/Ref-1, NF-κB, and HIF-1α, which are genes essential for tumor cell survival, tumor growth, and angiogenesis, thus making such cells more sensitive to radiotherapy. Studies in which soy isoflavones were given in conjunction with radiotherapy to prostate cancer patients suggest that soy isoflavones might also mitigate the adverse effects of radiation on normal tissues, probably by acting as antioxidants. These observations open new avenues for exploiting soy isoflavones as supplements to conventional therapies.
On-line learning and stochastic approximations

The convergence of online learning algorithms is analyzed using the tools of the stochastic approximation theory, and proved under very weak conditions. A general framework for online learning algorithms is first presented. This framework encompasses the most common online learning algorithms in use today, as illustrated by several examples. The stochastic approximation theory then provides general results describing the convergence of all these learning algorithms at once. Revised version, May 2018.
An Expressive Model for the Web Infrastructure: Definition and Application to the Browser ID SSO System

The web constitutes a complex infrastructure and, as demonstrated by numerous attacks, rigorous analysis of standards and web applications is indispensable. Inspired by successful prior work, in particular the work by Akhawe et al. as well as Bansal et al., in this work we propose a formal model for the web infrastructure. While unlike prior works, which aim at automatic analysis, our model so far is not directly amenable to automation, it is much more comprehensive and accurate with respect to the standards and specifications. As such, it can serve as a solid basis for the analysis of a broad range of standards and applications. As a case study and another important contribution of our work, we use our model to carry out the first rigorous analysis of the Browser ID system (a.k.a. Mozilla Persona), a recently developed complex real-world single sign-on system that employs technologies such as AJAX, cross-document messaging, and HTML5 web storage. Our analysis revealed a number of very critical flaws that could not have been captured in prior models. We propose fixes for the flaws, formally state relevant security properties, and prove that the fixed system in a setting with a so-called secondary identity provider satisfies these security properties in our model. The fixes for the most critical flaws have already been adopted by Mozilla and our findings have been rewarded by the Mozilla Security Bug Bounty Program.
Replication of association of the D-repeat polymorphism in asporin with osteoarthristis

Rodriguez-Lopez and colleagues [1] describe a replication study of our previous association between osteoarthritis (OA) and asporin [2]. The authors were unable to find this association in the Spanish population and question the association we found in the Japanese population. Their report also contains an interpretation of two previous papers on the same topic [3,4] that differs from those of the original study authors. We have concerns about their interpretation of data and about the conclusions drawn.
Evaluation of the Family Integrated Care model of neonatal intensive care: a cluster randomized controlled trial in Canada and Australia

BACKGROUND
Admission to the neonatal intensive care unit (NICU) may disrupt parent-infant interaction with adverse consequences for infants and their families. Several family-centered care programs promote parent-infant interaction in the NICU; however, all of these retain the premise that health-care professionals should provide most of the infant's care. Parents play a mainly supportive role in the NICU and continue to feel anxious and unprepared to care for their infant after discharge. In the Family Integrated Care (FICare) model, parents provide all except the most advanced medical care for their infants with support from the medical team. Our hypothesis is that infants whose families complete the FICare program will have greater weight gain and better clinical and parental outcomes compared with infants provided with standard NICU care.


METHODS/DESIGN
FICare is being evaluated in a cluster randomized controlled trial among infants born at ≤ 33 weeks' gestation admitted to 19 Canadian, 6 Australian, and 1 New Zealand tertiary-level NICU. Trial enrollment began in April, 2013, with a target sample size of 675 infants in each arm, to be completed by August, 2015. Participating sites were stratified by country, and by NICU size within Canada, for randomization to either the FICare intervention or control arm. In intervention sites, parents are taught how to provide most of their infant's care and supported by nursing staff, veteran parents, a program coordinator, and education sessions. In control sites standard NICU care is provided. The primary outcome is infants' weight gain at 21 days after enrollment, which will be compared between the FICare and control groups using Student's t-test adjusted for site-level clustering, and multi-level hierarchical models accounting for both clustering and potential confounders. Similar analyses will examine secondary outcomes including breastfeeding, clinical outcomes, safety, parental stress and anxiety, and resource use. The trial was designed, is being conducted, and will be reported according to the CONSORT 2010 guidelines for cluster randomized controlled trials.


DISCUSSION
By evaluating the impact of integrating parents into the care of their infant in the NICU, this trial may transform the delivery of neonatal care.


TRIAL REGISTRATION
NCT01852695 , registered December 19, 2012.
Rates and indications for surgical breast biopsies in a community-based health system.

BACKGROUND
High rates of surgical breast biopsies in community hospitals have been reported but may misrepresent actual practice.


METHODS
Patient-level data from 5,757 women who underwent breast biopsies in a large integrated health system were evaluated to determine biopsy types, rates, indications, and diagnoses.


RESULTS
Between 2008 and 2010, 6,047 breast biopsies were performed on 5,757 women. Surgical biopsy was the initial diagnostic procedure in 16% (n = 942) of women overall and in 6% (72 of 1,236) of women with newly diagnosed invasive breast cancer. Invasive breast cancer was diagnosed in 72 women (8%) undergoing surgical biopsy compared with 1,164 (24%) undergoing core needle biopsy (P < .001, age adjusted). Main indications for surgical biopsies included symptomatic abnormalities, technical challenges, and patient choice.


CONCLUSIONS
Surgical biopsy was the initial diagnostic procedure in 16% of women with breast abnormalities, comparable with rates at academic centers. Rates could be improved by more careful consideration of indications.