Miracle-dz/UniFAR-FTUs huggingface dataset:
Defining endpoints in clinical trials on atrial fibrillation

The major factors influencing the choice of the primary endpoint in any clinical trial in patients with atrial fibrillation (AF) are the purpose of the trial, the specific characteristics of the study population in terms of the class and aetiology of AF concerned, co-morbidities, risk factors, symptom status, and whether the trial is designed for regulatory purposes. Clinically, symptom relief and improvement in quality of life are major therapeutic goals, but they are difficult to measure objectively and an effect of treatment on these parameters is currently insufficient to support drug registration. Hard endpoints such as mortality, stroke, and hospitalization are most relevant to patients with persistent AF and other concomitant morbidities resulting in a high risk of these outcomes; however, their inclusion in an appropriately weighted composite primary endpoint may be necessary in trials including less severely ill patient populations to demonstrate treatment efficacy in a regulatory context. A therapy that reduced AF and improved quality of life but increased mortality, heart failure, or other major morbid events would not be approved in the current era. Time to first AF recurrence has practical advantages as a primary endpoint, but does not accurately reflect clinically important parameters such as the frequency, type, and duration of AF recurrence and the overall AF burden. The clinical relevance of asymptomatic recurrence of AF with regard to prognosis, quality of life, and patient care, including the need for anticoagulation, is increasingly recognized. Improvement in devices enabling more continuous monitoring of cardiac rhythm now permits more accurate assessment of the effect of treatment on asymptomatic AF, representing the majority of episodes recorded in studies employing intensive monitoring procedures. An intention-to-treat analysis is always preferred, but this may not always be possible in clinical trials in patients with AF. Irrespective of the efficacy endpoint chosen, this should ideally be assessed starting from the time steady state is achieved, for drug therapy, or maturation of the lesions in the case of ablation. These time-points may be days to months after randomization. Events occurring during the period from randomization to the pre-defined start of endpoint assessment, known as the blanking period, are not taken into account in the primary efficacy analysis. The longer the blanking period, the further on-therapy analysis departs from true intention-to-treat analysis. However, on-therapy analysis is as essential as intention-to-treat analysis, especially when comparing drug vs. non-drug therapies, as it also takes into account both the frequently high crossover rates and the poor compliance with drug therapy commonly encountered in antiarrhythmic drug (AAD) trials.
Relocation for specialist treatment for Indigenous people: Escort Issues

To date, although there is some literature on the experience of relocation, there are no research papers that focus exclusively on the Indigenous relocation experience. As a first step to address this hiatus, the present article provides findings from an Australian National Health and Medical Research Council two year study on Indigenous palliative care conducted in the Northern Territory that focus on escort issues. The methodology was qualitative, based on open-ended interviews, audio-recorded, transcribed verbatim, thematically analysed. There were a total of seventy-two (n=72) interviews completed with Indigenous patients (n=10), Indigenous caregivers (n=19), Indigenous and non-Indigenous health care workers (n=41), and Interpreters (n=2). The findings indicate that relocation for special treatment is a process fraught with difficulties and challenges for Australian Aboriginal people. Many of these problems such as loneliness, the emotional distress of separation from family, financial distress and the practical problems associated with travel and accommodation resonate with previous research on the tribulations of relocation. However, in addition to these issues, the findings indicate that there are many other specific problems associated with Aboriginal culture that negatively impact on the relocation experience. In view of the quite serious problems associated with relocation for Aboriginal people, there are strong indications from the findings that relocation for Indigenous people should not only be carried out in a culturally appropriate way, but, should be avoided whenever possible.
Access to Nonstatin Lipid-Lowering Therapies in Patients at High Risk of Atherosclerotic Cardiovascular Disease.

High-intensity statins are recommended for all patients with familial hypercholesterolemia (FH) and non-statin lipid lowering therapies (LLTs) are indicated when there is an inadequate response to statins 1, 2 . In the pre-PCSK9 inhibitor (PCSK9i) era only about 40% of FH patients achieved an LDL-C level 3 . Partly based on the need for additional therapeutic options in high-risk FH patients, PCSK9 inhibitors were approved for treatment of heterozygous and homozygous FH in 2015. Nevertheless, emerging anecdotal data suggest that access to non-statin LLTs has been a challenge for FH patients though this has not been systematically evaluated. The FH Optimal Care of the US (FOCUS) study was designed by The FH Foundation to assess current treatment patterns of FH patients, and allowed us to assess rejection rates of PCSK9 inhibitors in those with FH or ASCVD.
The influence of parent–adolescent relationship quality, parental monitoring, and peer substance use on substance use in South Korean high school students: Using latent growth curve modelling

Objective: Substance use, such as alcohol and tobacco, is becoming a critical problem in the area of health promotion and preventive programme. Furthermore, the onset of alcohol use has been becoming increasingly earlier. This study examined developmental trajectories of substance use among high school students in South Korea and effects of peer substance on such trajectories, and also examined the moderating effects of parent–adolescent relationship quality and parental monitoring in the link between peer substance use and adolescents’ own substance use. Methods: This study used the Korea Youth Panel Survey (KYPS), a nationally-representative sample of 3,125 high school students. The participants were in the 10th grade when first recruited and assessed annually from 2005 to 2007. A latent growth curve model was used for the analysis Results: Substance use in Korean high school students increased over time. Peer substance use was associated more strongly with the initial level of adolescent substance uses than parenting. Parent–adolescent relationship quality moderated the association between peer and adolescent substance use. Conclusion: The effect of peer substance use was most strongly associated with the initial level and growth of adolescents’ own substance use.
Reward Acts on the pFC to Enhance Distractor Resistance of Working Memory Representations

Working memory and reward processing are often thought to be separate, unrelated processes. However, most daily activities involve integrating these two types of information, and the two processes rarely, if ever, occur in isolation. Here, we show that working memory and reward interact in a task-dependent manner and that this task-dependent interaction involves modulation of the pFC by the ventral striatum. Specifically, BOLD signal during gains relative to losses in the ventral striatum and pFC was associated not only with enhanced distractor resistance but also with impairment in the ability to update working memory representations. Furthermore, the effect of reward on working memory was accompanied by differential coupling between the ventral striatum and ignore-related regions in the pFC. Together, these data demonstrate that reward-related signals modulate the balance between cognitive stability and cognitive flexibility by altering functional coupling between the ventral striatum and the pFC.
Improving Identification of Child Maltreatment Fatalities Through Public Health Surveillance

Estimated fatalities due to child maltreatment may underestimate the true extent of fatal child maltreatment. Public health surveillance of child maltreatment fatalities can help identify previously undetected cases and inform research, policy, and prevention efforts. A pilot effort in three states offers potentially useful insights for state-level child welfare leaders considering a similar collaboration. Key findings include the added value of using multiple data sources to identify child maltreatment fatalities, the challenges and benefits of engaging multiple disciplines in the surveillance process, and the feasibility of incorporating a common definition of child maltreatment for surveillance purposes.
The search for mRNA biomarkers: global quantification of transcriptional and translational responses to ionising radiation

Since the discovery of X-rays and the subsequent realisation that ionising radiation (IR) can provide a curative mode of therapy to treat tumours, there has been a concerted effort to discover the mechanisms by which IR induces cells to die or to become resistant to radiotherapy. Classical genetic analyses and biochemical techniques have been used to identify an ever-expanding number of genes whose activation directly or indirectly influences DNA repair, cell cycle progression and apoptosis. The advent of cDNA microarrays provides an opportunity to explore further the biological processes fundamental to the radiation response by permitting a comprehensive assessment of a cell's transcriptional landscape. The capacity to study the expression patterns of thousands of genes simultaneously may lead to (i) an increased understanding of how IR-responsive genes from seemingly mutually exclusive pathways (i.e. DNA repair and apoptosis) interact to determine the fate of irradiated cells and (ii) the discovery of n.
Dealing with dystocia in the ewe

THE lambing ewe in difficulty represents the most common ovine patient, although the numbers seen by practices may range from one or two animals from the local city farm to the queues of patients commonly presented to farm practices in areas with high sheep populations. Shepherds' skills vary markedly. Many are very experienced (often more so than the veterinarian who sees only a few lambings each year) and their cases will tend to be those requiring a caesarean section. Others are totally inexperienced and may call for help with the simplest lambing. In some instances attempts by one or more people will have gone on for far too long, risking the lives of the ewe and lamb(s). Whatever the circumstances, management of dystocia in the ewe depends vitally on making a quick and accurate assessment of the case.
Risk Factors for Two Consecutive Preterm Births in Southern Thailand

Objective: To identify the r isk factors for two consecutive preterm births in southern Thailand . Materials and Methods: A case-control study was conducted at Songklanagarind Hospital, the tertiary care hospital in the South of Thailand. Medical records of all women who had had a second live birth from 1997 to 2006 were reviewed. Term and preterm birth in both pregnancy were identified. The women having two preterm births were classified as the case group, and the women having preterm/term, term/preterm or term/term births were the control group. Socio-demographic characteristics, obstetric information and pregnancy complications were analyzed using univariate and multivariate analysis with a p-value of 0.05. Results: During the study period, 94 women with two preterm births were included in the cases, and 385 controls were randomly selected from all eligible records. Women aged <20 years had an increased risk of two preterm births compared to those aged 20-34 years. An interpregnancy interval of <12 months was also more frequent in double preterm birth cases in univariate analysis, but not in multivariate analysis. Premature rupture of membranes (adjusted OR 2.1, 95%CI 1.2-3.6), urinary tract infection (adjusted OR 8.7, 95%CI 2.3-33.5) and pregnancy-induced hypertension (adjusted OR 4.0, 95%CI 1.7-9.2) were independent factors in both univariate and multivariate analyses. Conclusions: Maternal age, premature rupture of membranes, urinary tract infection and pregnancy-induced hypertension were the significant factors in women having two consecutive preterm births . It is important for obstetricians to be aware of these risk factors in women who become pregnant after a previous preterm birth.
Low Bodyweight Type 2 Diabetes Mellitus

Non-insulin dependent diabetes mellitus (NIDDM) is the most prevalent form of diabetes mellitus (DM) in India. Currently the nomenclature is Type 2 diabetes mellitus (Type 2 DM). About one fourth of these diabetics have a body mass index (BMI) below 19, i.e. low bodyweight Type 2 DM (LB Type 2 DM). They are neither protein deficient nor belong to a poor socio-economic class. LB Type 2 DM more often presents with peripheral neuropathy and infections than coronary artery disease (CAD), hypertension or nephropathy. They achieve good glycemic control with sulphonylurea therapy. The leading causes of death are infection, coma, renal failure and cerebrovascular accident. LB Type 2 DM patients have severe basal hyperglycemia with low circulating levels of insulin while C-peptide levels are similar to those of patients with classic Type 2 DM. Studies on hepatic glucokinase levels and hepatic-microsomal enzyme systems (mixed function oxidase and cytochrome P450) using antipyrine and lidocaine as in vivo probes rev.
Risk of myocardial infarction associated with Gln/Arg 192 polymorphism in the human paraoxonase gene and diabetes mellitus. The REGICOR Investigators.

AIMS There is increasing evidence that paraoxonase, an HDL-linked enzyme, exerts its effect by removing lipid-peroxidation products. We have conducted a case-control study in Gerona, Spain, to find out whether paraoxonase1 polymorphism at codon 192 (Q and R alleles) is associated with increased risk of coronary heart disease, and how diabetes mellitus, associated with high oxidative risk, influences such an association. METHODS AND RESULTS One hundred and fifty six consecutive myocardial infarction patients and 310 age- and sex-matched control subjects were studied. There were no differences in the distribution of genotype and allele frequencies between patients and controls. The odds ratios for diabetes and dyslipaemia in control and patients stratified by genotype group were compared. Whereas dyslipaemic status was significantly related to myocardial infarction in QQ homozygotes and R carriers, diabetes mellitus was significantly associated with myocardial infarction only in R-carrier subjects. In logistic regression analysis, diabetic R carriers demonstrated a more than two and a half-fold increase in myocardial infarction risk compared with non-diabetic R carriers (OR: 2.65, P<0.05). CONCLUSION These data indicate that the R allele of the paraoxonase1-192 polymorphism is not an independent risk factor for myocardial infarction in our population. However, the interaction between this polymorphism and diabetes mellitus leads to increased myocardial infarction risk in diabetic patients with the R allele.
Orbilia ultrastructure, character evolution and phylogeny of Pezizomycotina

Molecular phylogenetic analyses indicate that the monophyletic classes Orbiliomycetes and Pezizomycetes are among the earliest diverging branches of Pezizomycotina, the largest subphylum of the Ascomycota. Although Orbiliomycetes is resolved as the most basal lineage in some analyses, molecular support for the node resolving the relationships between the two classes is low and topologies are unstable. We provide ultrastructural evidence to inform the placement of Orbiliomycetes by studying an Orbilia, a member of the only order (Orbiliales) of the class. The truncate ascus apex in the Orbilia is thin-walled except at the margin, and an irregular wall rupture of the apex permits ascospore discharge. Ascus, ascogenous and non-ascogenous hyphae were simple septate, with septal pores plugged by unelaborated electron-dense, non-membranous occlusions. Globose Woronin bodies were located on both sides of the septum. Nuclear division was characterized by the retention of an intact nuclear envelope, and a two-layered disk-shaped spindle pole body. The less differentiated nature of the spore discharge apparatus and septal pore organization supports an earliest diverging position of Orbiliomycetes within the subphylum, while the closed nuclear division and disk-shaped spindle pole body are interpreted as ancestral state characters for Ascomycota.
Serum Ferritin Is an Independent Prognostic Factor in Chinese with Myelodysplastic Syndromes Classified as IPSS Intermediate-1

Background: The International Prognostic Staging System (IPSS) for myelodysplastic syndromes (MDS) was developed predominately in patients of European ancestry and is not validated in Asians. In a recently revised IPSS (IPSS-R), several new prognostic variables are included, i.e. age, Eastern Cooperative Oncology Group performance score (ECOG PS), serum ferritin and lactate dehydrogenase. Chinese with MDS offer a unique opportunity to distinguish the prognostic impacts of haemoglobin (HGB) concentration, red blood cell (RBC) transfusions and serum ferritin because in China, patients rarely receive RBC transfusions unless the HGB concentration is <6.0 g/dl. Methods: We studied prognostic variables in 191 untreated Chinese primary patients with MDS intermediate-1 (INT-1) in the IPSS. Results: Serum ferritin level ≥500 µg/l at diagnosis was a strong independent predictor of survival. Although baseline serum ferritin level was inversely correlated with baseline HGB, it was the serum ferritin, not the baseline HGB level, that was significantly correlated with survival in Chinese patients. A new prognostic scoring system including the ECOG PS, absolute neutrophil level, serum ferritin, percentage of bone marrow blasts and poor karyotype was developed for Chinese with IPSS INT-1 MDS. Conclusions: This revised scoring system identified a subgroup of Chinese with MDS and INT-1 IPPS who have a poor prognosis and may benefit from more intensive therapy.
Efficacy of a nerve stimulator in regional analgesia; experience in a resident training programme

Forty interscalene brachial plexus regional blocks and twenty sciatic-femoral lower limb blocks were performed by 1st and 2nd year anaesthesia residents. Nerve trunk location was equally but randomly divided between use of a peripheral nerve stimulator and reliance on paraesthesiae. The stimulator group were sedated prior to nerve block while the non-stimulator group were similarly sedated after nerve block. There was no significant difference either in the number of needle insertions required for nerve location, or in the success rate, between stimulator and non-stimulator techniques. It is concluded that the stimulator is not a useful adjunct for nerve location, except in those patients who are unable to co-operate in eliciting paraesthesia. In such patients the stimulator permits a comparable success rate.
Clinicopathological characteristics and therapeutic outcomes in thyrotropin-secreting pituitary adenomas: a single-center study of 90 cases.

OBJECT The aim of this study was to analyze clinicopathological characteristics and treatment outcomes in a large single-center clinical series of cases of thyrotropin (TSH)-secreting pituitary adenomas. METHODS The authors retrospectively reviewed clinical, pathological, and treatment characteristics of 90 consecutive cases of TSH-secreting pituitary adenomas treated with transsphenoidal surgery between December 1991 and May 2013. The patient group included 47 females and 43 males (median age 42 years, range 11-74 years). RESULTS Sixteen tumors (18%) were microadenomas and 74 (82%) were macroadenomas. Microadenomas were significantly more frequent in the more recent half of our case series (12 of 45 cases) (p = 0.0274). Cavernous sinus invasion was confirmed in 21 patients (23%). In 67 cases (74%), the tumors were firm elastic or hard in consistency. Acromegaly and hyperprolactinemia were observed, respectively, in 14 (16%) and 11 (12%) of the 90 cases. Euthyroidism was achieved in 40 (83%) of 48 patients and tumor shrinkage was found in 24 (55%) of 44 patients following preoperative somatostatin analog treatment. Conventional transsphenoidal surgery, extended transsphenoidal surgery, and a simultaneous combined supra- and infrasellar approach were performed in 85, 2, and 3 patients, respectively. Total removal with endocrinological remission was achieved in 76 (84%) of 90 patients, including all 16 (100%) patients with microadenomas, 60 (81%) of the 74 with macroadenomas, and 8 (38%) of the 21 with cavernous sinus invasion. None of these 76 patients experienced tumor recurrence during a median follow-up period of 2.8 years. Stratifying by Knosp grade, total removal with endocrinological remission was achieved in 34 of 36 patients with Knosp Grade 0 tumors, all 24 of those with Grade 1 tumors, 12 of the 14 with Grade 2 tumors, 6 of the 8 with Grade 3 tumors, and none of the 8 with Grade 4 tumors. Cavernous sinus invasion and tumor size were significant independent predictors of surgical outcome. Immunoreactivity for growth hormone, prolactin, or both hormones was present in 32, 9, and 24 patients, respectively. The Ki-67 labeling index was less than 3% in 71 (97%) of 73 tumors for which it was obtained and 3% or more in 2. Postsurgery pituitary dysfunction was found in 15 patients (17%) and delayed hyponatremia was seen in 9. CONCLUSIONS TSH-secreting adenomas, particularly those in the microadenoma stage, have increased in frequency over the past 5 years. The high surgical success rate achieved in this series is due to relatively early diagnosis and relatively small tumor size. In addition, the surgical strategies used, such as extracapsular removal of hard or solid adenomas, aggressive resction of tumors with cavernous sinus invasion, or extended transsphenoidal surgery or a simultaneous combined approach for large/giant multilobulated adenomas, also may improve remission rate with a minimal incidence of complications.
Persuasion, Influence, and Value: Perspectives from Communication and Social Neuroscience

&NA; Opportunities to persuade and be persuaded are ubiquitous. What determines whether influence spreads and takes hold? This review provides an overview of evidence for the central role of subjective valuation in persuasion and social influence for both propagators and receivers of influence. We first review evidence that decisions to communicate information are determined by the subjective value a communicator expects to gain from sharing. We next review evidence that the effects of social influence and persuasion on receivers, in turn, arise from changes in the receiver's subjective valuation of objects, ideas, and behaviors. We then review evidence that self‐related and social considerations are two key inputs to the value calculation in both communicators and receivers. Finally, we highlight biological coupling between communicators and receivers as a mechanism through which perceptions of value can be transmitted.