Advances at the interface: merging information technologies with genomic methodologies

Deoxyribonucleic acid (DNA) is a molecule whose importance towers like a colossus in the sweeping field of biomedicine. The chemical structure of double stranded DNA is itself a helical tower that forms not only the backbone of medical research, but of life itself. Yet, we cannot let DNA be constrained to this role of solid, rigid building block if we wish to utilize its full potential. In its single stranded form, DNA can take on unexpected tertiary shapes that allow it to interact with polymerases, proteins, and organic molecules. This ability gives nucleic acids immense potential for molecular recognition. From monitoring a state of health to identifying toxins in drug development, using DNA as a sensing element can bring valuable information. Clinical diagnostics have benefited enormously from the sensitivity, specificity, and rapidity of nucleic acid testing (NAT). It can be easy to take blood donor screening, heritable genotyping of newborns, and other standard operating procedures for granted in the developed world. Developing nations with as few as one physician for every 100 people are lacking in the healthcare infrastructure (to say the least) to provide these molecular tests. The key to unlocking the progressions made by NAT in identifying causative agents of disease comes in the form of a ubiquitous tool: mobile phones. Almost 7B people in the world own cell phones. By combining the optical imaging capabilities and computational powers of mobile phones with a streamlined amplification platform, the ability to detect diseases becomes available to those who could truly reap its benefits.The synergistic nature of merged technologies is something that extends beyond nucleic acid amplification tests (NAATs) to analysis of recombinant DNA products. Most fields have single-use products that are essential for one purpose but otherwise hidden from view. When brought to the attention of other disciplines, nucleic acid analysis tools such as next generation sequencing (NGS) can segue from providing information on full genomes to identifying highly represented DNA affinity agents from candidate pools. Bringing the systems of particle display, high throughput sequencing (HTS), and in situ microarray synthesis to a sequence selection process enhances screening capabilities to the extent that hundreds of sequences can be identified en masse as binding to thousands of targets

What consultation resources are available to support delivery of integrated sexual and reproductive health services? A scoping review

Background: Contraceptive and sexual healthcare is increasingly delivered in an integrated setting in the UK and worldwide, requiring staff to be competent in differing styles of delivery, and to have a wide knowledge base. Objectives: We did a scoping review of the literature for evidence of the resources that exist for healthcare professionals to guide or structure the process of conducting an integrated sexual and reproductive health (SRH) consultation. Eligibility criteria: Articles were included in the review if (1) their primary focus was a consultation resource related to one or more aspects of an SRH consultation and (2) they provided details of the resource and/or its application including evaluation of use. Sources of evidence: Peer-reviewed articles published in English, published non-peer-reviewed guides, and web-based guidelines addressing the conduct of a contraception or sexual health consultation were included. Date range: 1998-December 2018. Searches were carried out in the databases AMED (Ovid), ASSIA (ProQuest), CINAHL Complete (EBSCO), Cochrane Library (Wiley), HMIC (NHS Evidence), Medline (EBSCO), PsycINFO (Proquest) and Scopus (Elsevier) on 10 February 2017, and incremental searching performed until December 2018. Results: A total of 12 peer-reviewed journal articles, two web-published guidelines from the Faculty of Sexual & Reproductive Healthcare and three published, non-peer-reviewed resources were included. Conclusion: Many resources exist to guide either the contraceptive or sexual health consultations, but there is a lack of a comprehensive consultation resource to guide the conduct of an integrated consultation

Progress and divergence in palliative care education for medical students: A comparative survey of UK course structure, content, delivery, contact with patients and assessment of learning.

BACKGROUND: Effective undergraduate education is required to enable newly qualified doctors to safely care for patients with palliative care and end-of-life needs. The status of palliative care teaching for UK medical students is unknown. AIM: To investigate palliative care training at UK medical schools and compare with data collected in 2000. DESIGN: An anonymised, web-based multifactorial questionnaire. SETTINGS/PARTICIPANTS: Results were obtained from palliative care course organisers at all 30 medical schools in 2013 and compared with 23 medical schools (24 programmes) in 2000. RESULTS: All continue to deliver mandatory teaching on 'last days of life, death and bereavement'. Time devoted to palliative care teaching time varied (2000: 6-100 h, mean 20 h; 2013: 7-98 h, mean 36 h, median 25 h). Current palliative care teaching is more integrated. There was little change in core topics and teaching methods. New features include 'involvement in clinical areas', participation of patient and carers and attendance at multidisciplinary team meetings. Hospice visits are offered (22/24 (92%) vs 27/30 (90%)) although they do not always involve patient contact. There has been an increase in students' assessments (2000: 6/24, 25% vs 2013: 25/30, 83%) using a mixture of formative and summative methods. Some course organisers lack an overview of what is delivered locally. CONCLUSION: Undergraduate palliative care training continues to evolve with greater integration, increased teaching, new delivery methods and wider assessment. There is a trend towards increased patient contact and clinical involvement. A minority of medical schools offer limited teaching and patient contact which could impact on the delivery of safe palliative care by newly qualified doctors.This is the author accepted manuscript. The final version is available from Sage Publications via http://dx.doi.org/10.1177/026921631562712

Inside the volcano : Three-dimensional magmatic architecture of a buried shield volcano

Acknowledgements: Funding from NERC (Oil and Gas CDT) and BGS is gratefully acknowledged. DAJ and SP are part-funded by the Research Council of Norway Centre of Excellence funding scheme (project No. 223272). TGS is thanked for providing seismic data to the University of Aberdeen. Seismic interpretation was undertaken using Schlumberger Petrel software and gravity modelling using ARK CLS XField software. Thanks go to Steffi Burchardt, Eric Horsman and Christian Eide for constructive reviews which greatly improved the manuscript.Peer reviewedPublisher PD

Quaternary and Neogene Reservoirs of the Norwegian Continental Shelf and the Faroe-Shetland Basin

Glaciogenic reservoirs host important hydrocarbon resources across the globe. Examples such as the Peon and Aviat discoveries in the North Sea show that Quaternary and Neogene reservoirs can be prospective in the region. In this study, we interpret 2D and 3D reflection seismic data combined with borehole information to document unconventional play models from the shallow subsurface of the Norwegian Continental Shelf and the Faroe-Shetland Basin. These plays include (i) glacial sands in ice-marginal outwash fans, sealed by stiff subglacial tills (the Peon discovery), (ii) meltwater turbidites, (iii) contouritic fine-grained glacimarine sands sealed by gas hydrates, (iv) remobilized oozes above large evacuation craters which are sealed by megaslides and glacial muds, and (v) Neogene sand injectites. The hydrocarbon reservoirs are characterized by negative-polarity reflections with anomalously high amplitudes in the reflection seismic data as well as density and velocity decreases in the borehole data. Extensive new 3D reflection seismic data are crucial to correctly interpret glacial processes and distinguish shallow reservoirs from shallow seals. These data document a variety of play models with the potential for gas in large quantities and enable the identification of optimal drilling targets at stratigraphic levels which have so far been overlooked

Schwartz Centre Rounds: a new initiative in the undergraduate curriculum — what do medical students think?

Background: Training to be a doctor and caring for patients are recognized as being stressful and demanding. The wellbeing of healthcare professionals impacts upon the wellbeing and care of patients. Schwartz Centre Rounds (SCRs), multidisciplinary meetings led by a trained facilitator and designed for hospital staff, were introduced to enhance communication and compassion, and have since been widely adopted as a way of fostering compassion. The continuum of education suggests that medical students need to develop these attributes in conjunction with resilience and maintaining empathy. The benefits of SCRs in fostering this development in medical students is unexplored. The objective of this study was to examine the potential of SCRs within the undergraduate curriculum. Methods: Two student–focused SCRs were piloted at a major medical school. The sessions were based on the current format implemented across the US and UK: a presentation of cases by a multidisciplinary panel followed by an open discussion with the audience. Participants were asked to complete an evaluative questionnaire immediately following the sessions. Seven students took part in a focus group to explore their views on the SCR. Data sets were examined using descriptive statistics and thematic analysis. Results: Feedback was obtained from 77 % (258/334) Year 5 and 37 % (126/343) Year 6 students. Mean student ratings of the session on a five-point scale, where 1 = poor and 5 = exceptional, were 3.5 (Year 5) and 3.3 (Year 6). Over 80 % of respondents either agreed or strongly agreed that the presentation of cases was helpful and gave them insight into how others feel/think about caring for patients. Eighty percent said they would attend a future SCR and 64 % believed SCRs should be integrated into the curriculum. Focus group participants felt SCRs promoted reflection and processing of emotion. Students identified smaller group sizes and timing in the curriculum as ways of improving SCRs. Conclusion: Students were positive about SCRs, preferring them to their current reflective practice assignments. Whether this results in sustained benefits to trainee doctors is yet to be explored. Consideration is given to overcoming the challenges that were encountered, such as optimal timing and participation. Staff training and costs are potential obstacles to adoption

Inpatient versus outpatient acute venous thromboembolism management: Trends and postacute healthcare utilization from 2011 to 2018

Background - Acute outpatient management of venous thromboembolism (VTE), which includes pulmonary embolism (PE) and deep vein thrombosis (DVT), is perceived to be as safe as inpatient management in some settings. How widely this strategy is used is not well documented. Methods and Results - Using MarketScan administrative claims databases for years 2011 through 2018, we identified patients with International Classification of Diseases (ICD) codes indicating incident VTE and trends in the use of acute outpatient management. We also evaluated healthcare utilization and hospitalized bleeding events in the 6 months following the incident VTE event. A total of 200 346 patients with VTE were included, of whom 50% had evidence of PE. Acute outpatient management was used for 18% of those with PE and 57% of those with DVT only, and for both DVT and PE its use increased from 2011 to 2018. Outpatient management was less prevalent among patients with cancer, higher Charlson comorbidity index scores, and whose primary treatment was warfarin as compared with a direct oral anticoagulant. Healthcare utilization in the 6 months following the incident VTE event was generally lower among patients managed acutely as outpatients, regardless of initial presentation. Acute outpatient management was associated with lower hazard ratios of incident bleeding risk for both patients who initially presented with PE (0.71 [95% CI, 0.61, 0.82]) and DVT only (0.59 [95% CI, 0.54, 0.64]). Conclusions - Outpatient management of VTE is increasing. In the present analysis, it was associated with lower subsequent healthcare utilization and fewer bleeding events. However, this may be because healthier patients were managed on an outpatient basis

Autoimmune disease and risk of postpartum venous thromboembolism

Background - The risk of pregnancy-related mortality in the United States has nearly doubled since 1990, with venous thromboembolism (VTE) accounting for approximately 10% of these deaths. Objectives - The objective of this study was to assess whether preexisting autoimmune disease is a risk factor for postpartum VTE. Methods - Using the MarketScan Commercial and Medicare Supplemental administrative databases, a retrospective cohort study analyzed whether postpartum persons with autoimmune disease had a higher risk of postpartum VTE incidence than postpartum persons without autoimmune disease. Using International Classification of Diseases codes, we identified 757,303 individuals of childbearing age who had a valid delivery date with at least 12 weeks of follow-up. Results - Individuals were, on average, 30.7 years old (SD, 5.4), and 3.7% (N = 27,997 of 757,303) of them had evidence of preexisting autoimmune disease. In covariate-adjusted models, postpartum persons with preexisting autoimmune disease had higher rates of postpartum VTE than postpartum persons without autoimmune disease (hazard ratio [HR], 1.33; 95% CI, 1.07-1.64). When analyzed by individual autoimmune disease, those with systemic lupus erythematosus (HR, 2.49; 95% CI, 1.47-4.21) and Crohn’s disease (HR, 2.49; 95% CI, 1.34-4.64) were at an elevated risk of postpartum VTE compared with those without autoimmune disease. Conclusion - Autoimmune disease was associated with a higher rate of postpartum VTE, with evidence that the association was most pronounced among individuals with systemic lupus erythematosus and Crohn’s disease. These findings suggest that postpartum persons of childbearing age with autoimmune disease may require more monitoring and prophylactic care after delivery to prevent potentially fatal VTE events

Objective assessment of blood and lymphatic vessel invasion and association with macrophage infiltration in cutaneous melanoma

The aims of this study were to investigate the role of vascular invasion (blood and lymphatic), vessel density and the presence of tumour-associated macrophages as prognostic markers in 202 cutaneous melanoma patients. Sections of primary melanoma were stained with lymphatic-specific antibody D2-40 to assess lymphatic vessel invasion and density in intratumoural and peritumoural areas; an antibody against endothelial marker CD34 was used to determine blood vessel invasion and density, and an antibody against CD68 was used to determine macrophage counts. Immunohistochemically determined vascular invasion (combined blood and lymphatic) was compared with that determined using haematoxylin and eosin (H&E) staining. The use of immunohistochemistry increased detection of vascular invasion from 8–30% of patients, and histological exam of H&E-stained tissue was associated with a false positive rate of 64%. Lymphatic vessel invasion occurred at a much higher frequency than blood vessel invasion (27 and 4% of patients, respectively). Although immunohistochemically detected vessel invasion was significantly associated with histological markers of adverse prognosis, such as increased Breslow thickness, ulceration and mitotic rate (all P<0.001), no associations with relapse-free or overall survival were observed. High macrophage counts were significantly associated with markers of aggressive disease, such as Breslow thickness, ulceration and mitotic rate (P<0.001, P<0.001, P=0.005, respectively), and lymphatic vessel invasion and high microvessel density (P=0.002 and P=0.003, respectively). These results suggest that vascular invasion is more accurately detected using immunohistochemistry and occurs predominantly via lymphatic vessels. The association of vessel characteristics with histological characteristics of the primary melanoma provides evidence for their biological importance in melanoma, but that they were not associated with clinical outcome attests to the value of existing histological prognostic biomarkers. We note that a high macrophage count may be associated with neovascularisation and primary tumour growth, and may also promote invasion through lymphatic vessels

Gravitational field and equations of motion of compact binaries to 5/2 post-Newtonian order

We derive the gravitational field and equations of motion of compact binary systems up to the 5/2 post-Newtonian approximation of general relativity (where radiation-reaction effects first appear). The approximate post-Newtonian gravitational field might be used in the problem of initial conditions for the numerical evolution of binary black-hole space-times. On the other hand we recover the Damour-Deruelle 2.5PN equations of motion of compact binary systems. Our method is based on an expression of the post-Newtonian metric valid for general (continuous) fluids. We substitute into the fluid metric the standard stress-energy tensor appropriate for a system of two point-like particles. We remove systematically the infinite self-field of each particle by means of the Hadamard partie finie regularization.Comment: 41 pages to appear in Physical Review