What is the best way to diagnose polycystic ovarian syndrome?

Polycystic ovarian syndrome (PCOS) is diagnosed for women of childbearing age presenting with 2 of the following: 1)oligo- or anovulatory menstrual irregularities, 2) evidence of hyperandrogenism in the absence of secondary cause; 3) enlarged ovaries with multiple small follicular cysts on transvaginal ultrasound (strength of recommendation [SOR]: C, based on expert opinion). Depending on the clinical presentation, secondary causes should be excluded (SOR: C, expert opinion). While not among the diagnostic criteria, insulin resistance is common, and patients with PCOS should be evaluated for metabolic abnormalities, particularly hyperlipidemia and glucose intolerance or diabetes (SOR: B, based on prospective cohort studies)

Ethical dilemmas and reflexivity in qualitative research.

Context: For medical education researchers, a key concern may be the practicalities of gaining ethical approval where this is a national or local requirement. However, in qualitative studies, where the dynamics of human interaction pervade, ethical considerations are an ongoing process which continues long after approval has been granted. Responding to ethical dilemmas arising ‘in the moment’ requires a reflexive approach whereby the researcher questions his/her own motivations, assumptions and interests. Drawing on empirical studies and their experiences in academic and clinical research practice, the authors share their reflections on adhering to ethical principles throughout the research process to illustrate the complexities and nuances involved. Objectives and findings: These reflections offer critical insights into dilemmas arising in view of the ethical principles driving good conduct, and through domains which distinguish between procedural ethics, situational ethics, ethical relationships and ethical issues in exiting the study. The accounts consider integrity and altruism in research, gatekeeping and negotiating access, consent and confidentiality, power dynamics and role conflict, and challenges in dissemination of findings. The experiences are based on a range of examples of research in a UK context from managing difficult conversations in the classroom to video-ethnography in the operating theatre. Discussion and conclusions: These critical reflections make visible the challenges encountered and decisions that must be taken in the moment and on reflection after the event. Through sharing our experiences and debating the decisions we made, we offer insights into reflexivity in qualitative research which will be of value to others

A validation study of two wrist worn wearable devices for remote assessment of exercise capacity

We determined wearable device errors in assessing a 6- Minute Walk Test (6MWT). 16 healthy adults (male 7(44%), mean age±SD 27±4 years) performed a standard (6MWT-S) and modified, ‘free range’, (6MWT-FR) protocols with a Garmin and Fitbit smartwatch to measure three parameters: distance, step count and heart rate (HR). Distance during the 6MWT-FR was measured with smaller errors during 6MWT-S for both Garmin (Mean Absolute Percentage Error, MAPE=9.8% [4.6%,12.6%] vs 18.5%[13.0%,27.4%], p<0.001) and Fitbit (MAPE=9.4%[4.5%,13.3%] vs 22.7%[18.3%,29.3%], p<0.001). Steps were measured with smaller errors with Garmin (MAPE=2.3%[1.1%,2.9%]; r=0.96) than Fitbit (Fitbit: MAPE=8.1%[5.0%,12.9%]; r=0.24). Heart rate at rest, peak exercise and recovery was measured with median MAPE ranging between 1.2% and 2.9%, with no evidence of difference between the two devices. Wearable measurements of the 6MWT provide insights about exercise capacity which could be monitored and evaluated remotely

Timescales of Massive Human Entrainment

The past two decades have seen an upsurge of interest in the collective behaviors of complex systems composed of many agents entrained to each other and to external events. In this paper, we extend concepts of entrainment to the dynamics of human collective attention. We conducted a detailed investigation of the unfolding of human entrainment - as expressed by the content and patterns of hundreds of thousands of messages on Twitter - during the 2012 US presidential debates. By time locking these data sources, we quantify the impact of the unfolding debate on human attention. We show that collective social behavior covaries second-by-second to the interactional dynamics of the debates: A candidate speaking induces rapid increases in mentions of his name on social media and decreases in mentions of the other candidate. Moreover, interruptions by an interlocutor increase the attention received. We also highlight a distinct time scale for the impact of salient moments in the debate: Mentions in social media start within 5-10 seconds after the moment; peak at approximately one minute; and slowly decay in a consistent fashion across well-known events during the debates. Finally, we show that public attention after an initial burst slowly decays through the course of the debates. Thus we demonstrate that large-scale human entrainment may hold across a number of distinct scales, in an exquisitely time-locked fashion. The methods and results pave the way for careful study of the dynamics and mechanisms of large-scale human entrainment.Comment: 20 pages, 7 figures, 6 tables, 4 supplementary figures. 2nd version revised according to peer reviewers' comments: more detailed explanation of the methods, and grounding of the hypothese

Association between genetic variants in the Coenzyme Q10 metabolism and Coenzyme Q10 status in humans

<p>Abstract</p> <p>Background</p> <p>Coenzyme Q₁₀(CoQ₁₀) is essential for mitochondrial energy production and serves as an antioxidants in extra mitochondrial membranes. The genetics of primary CoQ₁₀deficiency has been described in several studies, whereas the influence of common genetic variants on CoQ₁₀status is largely unknown. Here we tested for non-synonymous single-nucleotidepolymorphisms (SNP) in genes involved in the biosynthesis (CoQ3^G272S, CoQ6^M406V, CoQ7^M103T), reduction (NQO1^P187S, NQO2^L47F) and metabolism (apoE3/4) of CoQ₁₀and their association with CoQ₁₀status. For this purpose, CoQ₁₀serum levels of 54 healthy male volunteers were determined before (T₀) and after a 14 days supplementation (T₁₄) with 150 mg/d of the reduced form of CoQ₁₀.</p> <p>Findings</p> <p>At T₀, the CoQ₁₀level of heterozygous NQO1^P187Scarriers were significantly lower than homozygous S/S carriers (0.93 ± 0.25 μM versus 1.34 ± 0.42 μM, p = 0.044). For this polymorphism a structure homology-based method (PolyPhen) revealed a possibly damaging effect on NQO1 protein activity. Furthermore, CoQ₁₀plasma levels were significantly increased in apoE4/E4 genotype after supplementation in comparison to apoE2/E3 genotype (5.93 ± 0.151 μM versus 4.38 ± 0.792 μM, p = 0.034). Likewise heterozygous CoQ3^G272Scarriers had higher CoQ₁₀plasma levels at T₁₄compared to G/G carriers but this difference did not reach significance (5.30 ± 0.96 μM versus 4.42 ± 1.67 μM, p = 0.082).</p> <p>Conclusions</p> <p>In conclusion, our pilot study provides evidence that NQO1^P187Sand apoE polymorphisms influence CoQ₁₀status in humans.</p

Palaeogenomic analysis of black rat (Rattus rattus) reveals multiple European introductions associated with human economic history

The distribution of the black rat (Rattus rattus) has been heavily influenced by its association with humans. The dispersal history of this non-native commensal rodent across Europe, however, remains poorly understood, and different introductions may have occurred during the Roman and medieval periods. Here, in order to reconstruct the population history of European black rats, we first generate a de novo genome assembly of the black rat. We then sequence 67 ancient and three modern black rat mitogenomes, and 36 ancient and three modern nuclear genomes from archaeological sites spanning the 1st-17th centuries CE in Europe and North Africa. Analyses of our newly reported sequences, together with published mitochondrial DNA sequences, confirm that black rats were introduced into the Mediterranean and Europe from Southwest Asia. Genomic analyses of the ancient rats reveal a population turnover in temperate Europe between the 6th and 10th centuries CE, coincident with an archaeologically attested decline in the black rat population. The near disappearance and re-emergence of black rats in Europe may have been the result of the breakdown of the Roman Empire, the First Plague Pandemic, and/or post-Roman climatic cooling.Peer reviewe

Multichannel Silicon Probes for Awake Hippocampal Recordings in Large Animals

Decoding laminar information across deep brain structures and cortical regions is necessary in order to understand the neuronal ensembles that represent cognition and memory. Large animal models are essential for translational research due to their gyrencephalic neuroanatomy and significant white matter composition. A lack of long-length probes with appropriate stiffness allowing penetration to deeper structures with minimal damage to the neural interface is one of the major technical limitations to applying the approaches currently utilized in lower order animals to large animals. We therefore tested the performance of multichannel silicon probes of various solutions and designs that were developed specifically for large animal electrophysiology. Neurophysiological signals from dorsal hippocampus were recorded in chronically implanted awake behaving Yucatan pigs. Single units and local field potentials were analyzed to evaluate performance of given silicon probes over time. EDGE-style probes had the highest yields during intra-hippocampal recordings in pigs, making them the most suitable for chronic implantations and awake behavioral experimentation. In addition, the cross-sectional area of silicon probes was found to be a crucial determinant of silicon probe performance over time, potentially due to reduction of damage to the neural interface. Novel 64-channel EDGE-style probes tested acutely produced an optimal single unit separation and a denser sampling of the laminar structure, identifying these research silicon probes as potential candidates for chronic implantations. This study provides an analysis of multichannel silicon probes designed for large animal electrophysiology of deep laminar brain structures, and suggests that current designs are reaching the physical thresholds necessary for long-term (∼1 month) recordings with single-unit resolution

Oncogenic BRAF mutation induces DNA methylation changes in a murine model for human serrated colorectal neoplasia

Colorectal cancer is a major cause of cancer death and approximately 20% arises within serrated polyps, which are under-recognized and poorly understood. Human serrated colorectal polyps frequently exhibit both oncogenic BRAF mutation and widespread DNA methylation changes, which are important in silencing genes restraining neoplastic progression. Here, we investigated whether in vivo induction of mutant Braf is sufficient to result in coordinated promoter methylation changes for multiple cancer-related genes. The BrafV637E mutation was induced in murine intestine on an FVB;C57BL/6J background and assessed for morphological and DNA methylation changes at multiple time points from 10 days to 14 months. Extensive intestinal hyperplasia developed by 10 days post-induction of the mutation. By 8 months, most mice had murine serrated adenomas with dysplasia and invasive cancer developed in 40% of mice by 14 months. From 5 months onwards, Braf mutant mice showed extensive, gene-specific increases in DNA methylation even in hyperplastic mucosa without lesions. This demonstrates that persistent oncogenic Braf signaling is sufficient to induce widespread DNA methylation changes. This occurs over an extended period of time, mimicking the long latency followed by rapid progression of human serrated neoplasia. This study establishes for the first time that DNA methylation arises slowly in direct response to prolonged oncogenic Braf signaling in serrated polyps; this finding has implications both for chemoprevention and for understanding the origin of DNA hypermethylation in cancer generally.Catherine E. Bond, Cheng Liu, Futoshi Kawamata, Diane M. McKeone, Winnie Fernando, Saara Jamieson, Sally-Ann Pearson, Alexandra Kane, Susan L. Woods, Tamsin R.M. Lannagan, Roshini Somashekar, Young Lee, Troy Dumenil, Gunter Hartel, Kevin J. Spring, Jennifer Borowsky, Lochlan Fennell, Mark Bettington, Jason Lee, Daniel L. Worthley, Barbara A. Leggett and Vicki L.J. Whitehal