bluuebunny/crossref_metadata_2025 huggingface dataset:
Current concepts in rheumatology
Authors: Helliwell Philip
Published: May 2019

Musculoskeletal disorders contribute significantly to the global burden of disease and rank alongside mental health disorders in their impact on society. Nevertheless, there are large gaps in our knowledge of prevalence and impact of these disorders worldwide. The majority of musculoskeletal disorders are non-inflammatory (osteoarthritis and low back pain), yet inflammatory disorders receive a disproportionate share of the attention, possibly because of their wider impact within the patient. Major advances in the understanding and treatment of inflammatory diseases have occurred in the past 20 years and these are now being echoed in other fields, such as the management of foot health conditions. New paradigms of treatment are emerging, with the emphasis on early intervention, and the evidence base for non-pharmacological treatments is improving. This chapter will reflect on these changes and the likely future delivery of care for rheumatic and musculoskeletal disorders.
Autoimmune connective tissue diseases
Authors: Alcacer-Pitarch Begonya , Vital Edward , Buch Maya
Published: May 2019

This chapter will briefly cover the epidemiology and pathophysiology of systemic sclerosis and systemic lupus erythematosus, and, to a larger extent, their pathological effect on the lower limb. It will also discuss current evidence for foot pathology management with reference to potential risks and imaging strategies.
Soft-tissue disorders
Authors: Landorf Karl B. , Keenan Anne-Maree , Kearney Rebecca
Published: May 2019

This chapter covers soft-tissue disorders, a common occurrence in rheumatology. There is a brief overview of 10 of the most common soft-tissue disorders of the foot in rheumatology, including Achilles tendinopathy, ankle sprains, retrocalcaneal bursitis, tarsal tunnel syndrome, peroneal tendinopathy, tibialis posterior tendinopathy, plantar heel pain, and more. For each disorder, presentation, signs, and management are discussed.
Identification, measurement, and valuation of resource use in economic evaluations of public health interventions
Authors: Jones Carys , Charles Joanna M. , Edwards Rhiannon T.
Published: May 2019

Chapter 5 provides a practical guide to the types of costs relevant to an economic evaluation of a public health intervention, perspective of analysis, and sources of unit costs spanning a range of sectors including health, social care, education, and transport. The chapter covers the important issues of time horizon and discounting in the economic evaluation of public health interventions. Taking account of sources of uncertainty, the chapter sets out good practice in reporting cost information in published economic studies. The chapter concludes with a worked example of a micro-costing of a parenting programme delivered in the community.
Cost–consequence analysis of public health interventions
Authors: Hartfiel Ned , Edwards Rhiannon T.
Published: May 2019

This chapter opens with a discussion around cost–consequence analysis (CCA) and the UK’s NICE recommendation to use CCA in addition to cost–utility analysis for evaluating public health interventions. CCA is sometimes referred to as a disaggregated approach, because the benefits and costs are not combined in a single ratio such as incremental cost-effectiveness ratios (ICERs) in cost–utility analysis. CCA provides a clear descriptive summary for decision-makers that is often easier to interpret than cost-effectiveness, cost–utility, and cost–benefit analysis. The reader or the decision-maker has to form their own opinion concerning the relative importance of costs and outcomes. The chapter offers a case study of CCA by comparing a yoga-based intervention with self-care for managing musculoskeletal conditions in the workplace. The chapter ends with a summary of the principle benefits and major drawbacks of CCA.
The role of multi-criteria decision analysis (MCDA) in public health economic evaluation
Authors: Lloyd-Williams Huw
Published: May 2019

Decision making regarding implementation of public health interventions (PHIs) can sometimes be heuristic (i.e. ad hoc) and it can be argued that decisions based only on a single criterion disregards important information about other relevant related outcomes. Multi-criteria decision analysis (MCDA) can help decision-makers make decisions based on multiple, sometimes conflicting criteria. This chapter looks at the definition and history of decision analysis as a field of study and at its application in various disciplines. It describes the different approaches used in MCDA and how these approaches help generate information a decision-maker can use to make decisions regarding resource allocation in public health. A case study is presented which shows a practical example of MCDA being conducted to evaluate healthcare policy issues in public health in The Netherlands.
To disinvest or invest? The role of programme budgeting and marginal analysis (PBMA) for economic evaluation and prioritization between public health interventions
Authors: Charles Joanna M. , Edwards Rhiannon T.
Published: May 2019

This chapter describes the application of programme budgeting and marginal analysis (PBMA) as an evidence-based framework to make resource allocation decisions such as whether to invest or disinvest in certain services, products, or interventions. This evidence-based eight-step decision-making process can help decision-makers to maximize the impact of healthcare resources on the health needs of a local population. Programme budgeting is an appraisal of past resource allocation in specified programmes or services with a view to tracking future resource allocation in those same programmes or services. Marginal analysis is the appraisal of the added benefits and added costs of a proposed investment or the lost benefits and lower costs of a proposed disinvestment. This chapter pays particular attention to the use of the PBMA framework to appraise a national health improvement budget as a case study to illustrate the methods practical application in public health.
Early pregnancy and pelvic ultrasound
Authors: Henneberry Ryan , Cox Chris , Hoffmann Beatrice , Atkinson Paul
Published: May 2019

Point-of-care ultrasound (PoCUS) has an important role in the management of vaginal bleeding and/or abdominal pain in early pregnancy. When combined with other clinical parameters, PoCUS enables the treating physician to accurately confirm the presence of an early intrauterine pregnancy (IUP). This chapter provides a suggested algorithm for the use of bedside ultrasound and clinical findings to safely assess patients with first-trimester pregnancy pain or bleeding and rule out an ectopic pregnancy. Both trans-abdominal and trans-vaginal approaches are described in detail.
Pre-hospital point-of-care ultrasound
Authors: Oveland Nils Petter , Connolly Jim
Published: May 2019

Over the last two decades, ultrasound has evolved from a modality reserved to certain medical specialties into its current state, with a diversity in both the operator background and clinical applications. This has, in large part, been due to the increasing portability and image quality of ultrasound machines, combined with decreased cost of systems, as well as the fact that physicians from different specialties can become very adept at using ultrasound for diagnostic and procedural applications relevant to their medical field. These characteristics add the aspect for operators to make bedside diagnostic and therapeutic decisions in real time, without having to take the patients out of their environment. Point-of-care ultrasound is therefore a particularly attractive modality in pre-hospital settings as an extension of the comprehensive Airway, Breathing, Circulation, Disability, and Exposure/Extremities (ABCDE) resuscitation.
DNA repair after oncological therapy (radiotherapy and chemotherapy)
Authors: Dikomey Ekkehard , Borgmann Kerstin , Kriegs Malte , Mansour Wael Y. , Petersen Cordula , Rieckmann Thorsten
Published: May 2019

The lethal effect of ionizing irradiation on tumour cells is mostly determined by the repair of DNA double-strand breaks (DSBs). Cells are able to repair most of the DSBs, but 1% to 3 % are either non- or mis-repaired, which will then give rise to lethal chromosomal aberrations. Cells have evolved complex DSB repair mechanisms with a stringent hierarchy to guarantee the genomic stability. However, in tumour cells both mechanisms as well as hierarchy are often disturbed. This knowledge is important for an understanding of the radiation response of tumours, but—most of all—for the establishment of new and specific targets for therapy.
Sarcomas of soft tissues and bone and gastrointestinal stromal tumour
Authors: Gronchi Alessandro , Dei Tos Angelo P. , Casali Paolo G.
Published: May 2019

Sarcomas are rare tumours that can arise from bone or a variety of soft tissues in a variety of body sites. Surgery is the treatment mainstay for localized disease. Margins of resection are contingent on accurate histologic diagnosis. Adjuvant chemotherapy is routinely employed in osteosarcoma and Ewing Sarcomas, while it is used only on an individualized basis in high-risk soft tissue sarcoma. Isolated lung metastases from either bone or soft tissue sarcoma are primarily treated by surgery, especially if the disease-free interval is long and the number limited. Otherwise chemotherapy is the first-line therapy and subsequent treatments are decided according to response and disease evolution. Treatment planning should include multidisciplinary consultation to determine optimal therapy, taking into consideration tumour histology, site, and extent of the disease, its natural history and sensitivity to available treatments, surgical challenges and, of course, quality of life.
Pacemaker complications
Authors: Timperley Jonathan
Published: May 2019

This chapter acknowledges that although pacemaker implantation is a relatively simple technique, there are significant complications that can occur at different times. Peri-procedural complications, such as failed venous access, air embolus, and cardiac perforation are described, including early warning signs and management methods. Intermediate complications such as haematoma and dislodgement of the lead tip are covered. Late complications, including thrombosis, ‘Twiddler’s syndrome’, and the appearance of manufacturing defects are also described, along with management techniques.
Pacemaker programming and device interrogation
Authors: Betts Timothy , Ormerod Julian
Published: May 2019

This chapter covers all areas of pacemaker programming and choices related to pacing. Methods of choosing rate limits, and related programming features are described for the lower rate interval, the upper rate interval, the atrioventricular interval, and refractory and blanking periods are described in detail. The anatomical and signal changes for each period are defined, and all descriptions are illustrated with example ECGs to show different programme outcomes. Rate response, programming rate response, and mode switching are covered. Automated functions and stored information are described, and algorithms to prevent atrial arrhythmias are explained. Finally, pacemaker-mediated tachycardia is outlined, including detection and methods of terminating the pacemaker-mediated tachycardia (PMT).
Temporary cardiac pacing
Authors: Timperley Jonathan
Published: May 2019

This chapter describes the recommendations for temporary cardiac pacing. Indications for emergency and semi-elective temporary pacing are discussed, and American College of Cardiology (ACC) and American Heart Association (AHA) guidelines are summarized. Preparations for transvenous temporary pacing, including equipment, patient preparation, and choice of access are outlined. Internal jugular vein cannulation, subclavian vein cannulation, and femoral vein cannulation are described and compared. Different approaches to the insertion of a rigid pacing electrode and a flotation electrode are discussed, including tips for difficult electrode positioning. The method for setting up pacing is described, and complications with solutions are featured.
Implantable cardioverter defibrillator programming
Authors: Chelliah Rajesh , Timperley Jonathan
Published: May 2019

Programming is often performed on an individual patient basis, tailoring therapies and detection criteria to clinical history and documented arrhythmias. This chapter describes detection zones and therapies, including important questions to ask yourself before programming. Programming for specific syndromes is described, and case studies based on the MADIT-RIT study are included. Bradycardia and post-shock pacing are discussed in view of the DAVID trial.
Device clinic and follow-up
Authors: Meldrum Nicola , Mitchell Andrew
Published: May 2019

This chapter describes the device clinic. Requirements for a suitable facility, including maintaining patient dignity, are covered, and the development of remote follow-up is defined, including advantages and disadvantages. The follow-up schedule is covered, and history taking and examination are covered. Pacemaker testing and interrogation are shown, to aid the physician in management, diagnosis, and optimization of programming. Implantable cardioverter defibrillator (ICD) follow-up is also described, with all additional information required for follow-up described. Finally, cardiac resynchronization therapy (CRT) follow-up differences from standard pacemaker checks are covered.
SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules
Authors: Daina Antoine , Michielin Olivier , Zoete Vincent
Published: May 2019

SwissTargetPrediction is a web tool, on-line since 2014, that aims to predict the most probable protein targets of small molecules. Predictions are based on the similarity principle, through reverse screening. Here, we describe the 2019 version, which represents a major update in terms of underlying data, backend and web interface. The bioactivity data were updated, the model retrained and similarity thresholds redefined. In the new version, the predictions are performed by searching for similar molecules, in 2D and 3D, within a larger collection of 376 342 compounds known to be experimentally active on an extended set of 3068 macromolecular targets. An efficient backend implementation allows to speed up the process that returns results for a druglike molecule on human proteins in 15–20 s. The refreshed web interface enhances user experience with new features for easy input and improved analysis. Interoperability capacity enables straightforward submission of any input or output molecule to other on-line computer-aided drug design tools, developed by the SIB Swiss Institute of Bioinformatics. High levels of predictive performance were maintained despite more extended biological and chemical spaces to be explored, e.g. achieving at least one correct human target in the top 15 predictions for >70% of external compounds. The new SwissTargetPrediction is available free of charge (www.swisstargetprediction.ch).
PubTator central: automated concept annotation for biomedical full text articles
Authors: Wei Chih-Hsuan , Allot Alexis , Leaman Robert , Lu Zhiyong
Published: May 2019

PubTator Central (https://www.ncbi.nlm.nih.gov/research/pubtator/) is a web service for viewing and retrieving bioconcept annotations in full text biomedical articles. PubTator Central (PTC) provides automated annotations from state-of-the-art text mining systems for genes/proteins, genetic variants, diseases, chemicals, species and cell lines, all available for immediate download. PTC annotates PubMed (29 million abstracts) and the PMC Text Mining subset (3 million full text articles). The new PTC web interface allows users to build full text document collections and visualize concept annotations in each document. Annotations are downloadable in multiple formats (XML, JSON and tab delimited) via the online interface, a RESTful web service and bulk FTP. Improved concept identification systems and a new disambiguation module based on deep learning increase annotation accuracy, and the new server-side architecture is significantly faster. PTC is synchronized with PubMed and PubMed Central, with new articles added daily. The original PubTator service has served annotated abstracts for ∼300 million requests, enabling third-party research in use cases such as biocuration support, gene prioritization, genetic disease analysis, and literature-based knowledge discovery. We demonstrate the full text results in PTC significantly increase biomedical concept coverage and anticipate this expansion will both enhance existing downstream applications and enable new use cases.
Variations in VA and Medicare Use Among Veterans With Diabetes
Authors: Rose Danielle E. , Rowneki Mazhgan , Sambamoorthi Usha , Fried Dennis , Dwibedi Nilanjana , Tseng Chin-Lin , Jani Nisha , Yano Elizabeth M. , Helmer Drew A.
Published: May 2019

Introduction:

VA and Medicare use among older Veterans has been considered fragmented care, however, it may represent access to needed care.

Methods:

The population studied were Veterans with diabetes, age 66 years and older, dually enrolled in VA and Medicare.

Data Source/Study Setting:

We conducted a dynamic retrospective cohort study with 2008, 2009, and 2010 as the outcome years (Ambulatory Care Sensitive Conditions Hospitalization (ACSC-H) or not). We analyzed administrative data to identify comorbidities; ambulatory care utilization to identify variations in use before hospitalization. We linked 2007 primary care (PC) survey data to assess if organizational factors were associated with ACSC-H.

Measures and Analysis:

We identified ACSC-Hs using a validated definition. We categorized VA/Medicare use as: single system; dual system: supplemental specialty care use; or primary care use. Using hierarchical logistic regression models, we tested for associations between VA/Medicare use, organizational characteristics, and ACSC-H controlling for patient-level, organizational-level, and area-level characteristics.

Results:

Our analytic population was comprised of 210,726 Medicare-eligible Veterans; more than one quarter had an ACSC-H. We found that single system users had higher odds of ACSC-H compared with dual system specialty supplemental care use (odds ratio, 1.14; 95% confidence interval, 1.09–1.20), and no significant difference between dual-system users. Veterans obtaining care at sites where PC leaders reported greater autonomy (eg, authority over personnel issues) had lower odds of ACSC-H (odds ratio, 0.74; 95% confidence interval, 0.59–0.92).

Discussion:

Our findings suggest that earlier assumptions about VA/Medicare use should be weighed against the possibility that neither VA nor Medicare may address complex Veterans’ health needs. Greater PC leader autonomy may allow for tailoring of care to match local clinical contexts.
Addressing Loneliness in Complex PTSD
Authors: Dagan Yael , Yager Joel
Published: May 2019

Loneliness impacts both physical and psychological health and is associated with increases of all-cause mortality and suicidal behavior. Because loneliness may result from a variety of developmental, interpersonal, and intrapersonal factors, distinguishing its components, origins, and sustaining factors as it manifests in various psychopathological states are important steps in formulating interventions to alleviate these conditions. To date, loneliness has not been widely studied in relation to complex posttraumatic stress disorder (PTSD), which is newly delineated in the International Classification of Diseases, characterized by PTSD symptoms in the context of significant early trauma, as well as “disturbances in self-organization” marked by affective dysregulation, negative self-concept, and disturbances in relationships. In this article, illustrating with case material, we suggest that loneliness plays a major role in the development of complex PTSD and in the preservation of its symptoms. Consequently, therapies for complex PTSD should include interventions that address loneliness.
Heart Rate Variability in Individual Psychotherapy
Authors: Blanck Paul , Stoffel Martin , Bents Hinrich , Ditzen Beate , Mander Johannes
Published: May 2019

Heart rate variability (HRV) can be conceptualized as a marker of an individual's capability to adaptively respond to its environment and has been linked with mental health. Although conceptually and empirically linked to social behavior and thus relevant in the therapeutic setting, HRV is seldom investigated directly within therapy sessions. In the present examination, we aimed at addressing this research gap by assessing patients' and therapists' HRVs both ambulatory within therapy sessions and under resting conditions. Drawing on polyvagal theory, we hypothesized that higher in-session HRV is accompanied with higher therapeutic alliance ratings. Further, we expected baseline HRV to predict symptomatic outcome and to increase over the course of therapy. In a sample of 53 outpatients receiving 25 sessions of cognitive behavioral therapy, we measured HRV, therapeutic alliance and depressive symptoms on four occasions. Multilevel modeling analyses demonstrated that patients with higher in-session high-frequency HRV rated the therapeutic alliance higher. Baseline HRV predicted symptomatic outcome and increased over the course of therapy. Possible explanations involve a link between in-session HRV and in-session behavior and should be investigated in future studies. The results highlight the usefulness of in-session HRV as a promising process variable in psychotherapy research.
WAIS-IV Performance in Patients With Schizophrenia
Authors: Fuentes-Durá Inmaculada , Ruiz Juan Carlos , Dasí Carmen , Navarro Marisa , Blasco Pilar , Tomás Pilar
Published: May 2019

Wechsler Adult Intelligence Scale (WAIS) is one of the most widely used instruments to measure cognitive functioning. The aims of this study were 1) to obtain the cognitive profile of Spanish patients with schizophrenia on the WAIS-IV; 2) to compare their profile to the profile of a healthy control group; and 3) to compare the cognitive profile of patients with schizophrenia to the performance observed in two separate previous studies in Canada and China. A sample of 99 outpatients and 99 healthy control participants, matched on age, sex, and educational level, were measured using the WAIS-IV, including 10 core subtests, 4 indices, and 2 general intelligence scores, to obtain their cognitive profile. Results showed that only the performance on the Verbal Comprehension Index and its subtests was similar in the patient and control groups. This pattern of cognitive impairment was similar to the pattern reported in the Canadian and Chinese studies.
Unplanned readmission after traumatic injury: A long-term nationwide analysis
Authors: Lunardi Nicole , Mehta Ambar , Ezzeddine Hiba , Varma Sanskriti , Winfield Robert D. , Kent Alistair , Canner Joseph K. , Nathens Avery B. , Joseph Bellal A. , Efron David T. , Sakran Joseph V.
Published: May 2019

BACKGROUND

Long-term outcomes after trauma admissions remain understudied. We analyzed the characteristics of inpatient readmissions within 6 months of an index hospitalization for traumatic injury.

METHODS

Using the 2010 to 2015 Nationwide Readmissions Database, which captures data from up to 27 US states, we identified patients at least 15 years old admitted to a hospital through an emergency department for blunt trauma, penetrating trauma, or burns. Exclusion criteria included hospital transfers, patients who died during their index hospitalizations, and hospitals with fewer than 100 trauma patients annually. After calculating the incidences of all-cause, unplanned inpatient readmissions within 1 month, 3 months, and 6 months, we used multivariable logistic regression models to identify predictors of readmissions. Analyses adjusted for patient, clinical, and hospital factors.

RESULTS

Among 2,763,890 trauma patients, the majority had blunt injuries (92.5%), followed by penetrating injuries (6.2%) and burns (1.5%). Overall, rates of inpatient readmissions were 11.1% within 1 month, 21.6% within 6 months, and 29.8% within 6 months, with limited variability by year. After adjustment, the following were associated with all-cause 6 months inpatient readmissions: male sex (adjusted odds ratio [aOR], 1.10; 95% confidence interval [95% CI], 1.09–1.10), comorbidities (aOR, 1.21; 95% CI, 1.21–1.22), low-income quartiles (first and second) (aOR, 1.08; 95% CI, 1.07–1.10 and aOR, 1.04; 95% CI, 1.03–1.06, respectively), Medicare (aOR, 1.65; 95% CI, 1.62–1.69), Medicaid (aOR, 1.51; 95% CI, 1.48–1.53), being treated at private, investor-owned hospitals (aOR, 1.15; 95% CI, 1.12–1.18), longer hospital length of stay (aOR, 1.01; 95% CI, 1.01–1.01) and patient disposition to short-term hospital (aOR, 1.55; 95% CI, 1.49–1.62), skilled nursing facility (aOR, 1.43; 95% CI, 1.42–1.45), home health care (aOR, 1.27; 95% CI, 1.25–1.28), or leaving against medical advice (aOR, 1.85; 95% CI, 1.78–1.92).

CONCLUSION

Unplanned readmission after trauma is high and remains this way 6 months after discharge. Understanding the factors that increase the odds of readmissions within 1 month, 3 months, and 6 months offer a focus for quality improvement and have important implications for hospital benchmarking.

LEVEL OF EVIDENCE

Epidemiological study, level III.
A descriptive study of US Special Operations Command fatalities, 2001 to 2018
Authors: Kotwal Russ S. , Mazuchowski Edward L. , Stern Caryn A. , Montgomery Harold R. , Janak Jud C. , Howard Jeffrey T. , Butler Frank K. , Holcomb John B. , Eastridge Brian J. , Gurney Jennifer M. , Shackelford Stacy A.
Published: May 2019

BACKGROUND

Studies of fatalities from injury and disease guide prevention and treatment efforts for populations at risk. Findings can inform leadership and direct clinical practice guidelines, research, and personnel, training, and equipment requirements.

METHODS

A retrospective review and descriptive analysis was conducted of United States Special Operations Command (USSOCOM) fatalities who died while performing duties from September 11, 2001, to September 10, 2018. Characteristics analyzed included subcommand, military activity, operational posture, and manner of death.

RESULTS

Of 614 USSOCOM fatalities (median age, 30 years; male, 98.5%) the leading cause of death was injury (97.7%); specifically, multiple/blunt force injury (34.5%), blast injury (30.7%), gunshot wound (GSW; 30.3%), and other (4.5%). Most died outside the United States (87.1%), during combat operations (85.3%), in the prehospital environment (91.5%), and the same day of insult (90.4%). Most fatalities were with the US Army Special Operations Command (67.6%), followed by the Naval Special Warfare Command (16.0%), Air Force Special Operations Command (9.3%), and Marine Corps Forces Special Operations Command (7.2%). Of 54.6% who died of injuries incurred during mounted operations, most were on ground vehicles (53.7%), followed by rotary-wing (37.3%) and fixed-wing (9.0%) aircrafts. The manner of death was primarily homicide (66.0%) and accident (30.5%), followed by natural (2.1%), suicide (0.8%), and undetermined (0.7%). Specific homicide causes of death were GSW (43.7%), blast injury (42.2%), multiple/blunt force injury (13.8%), and other (0.2%). Specific accident causes of death were multiple/blunt force injury (80.7%), blast injury (6.4%), GSW (0.5%), and other (12.3%). Of accident fatalities with multiple/blunt force injury, the mechanism was mostly aircraft mishaps (62.9%), particularly rotary wing (68.4%).

CONCLUSION

Most USSOCOM fatalities died abroad from injury in the prehospital setting. To improve survival from military activities worldwide, leaders must continue to optimize prehospital capability and develop strategies that rapidly connect patients to advanced resuscitative and surgical care.

LEVEL OF EVIDENCE

Epidemiological, level IV; Therapeutic level IV.
Rapid point-of-care detection and classification of direct-acting oral anticoagulants with the TEG 6s: Implications for trauma and acute care surgery
Authors: Dias João D. , Lopez-Espina Carlos G. , Ippolito Jeffrey , Hsiao L. Hsiuyin , Zaman Fowzia , Muresan Adina A. , Thomas Scott G. , Walsh Mark , Jones Alexander Joseph , Grisoli Anne , Thurston Brian C. , Artang Ramin , Bilden Kevin P. , Hartmann Jan , Achneck Hardean E.
Published: May 2019

BACKGROUND

The trauma patient on direct oral anticoagulant (DOAC) therapy preinjury presents a challenge in trauma and acute care surgery. Our understanding of these patients is extrapolated from vitamin K antagonists. However, DOACs have different mechanisms of action, effects on laboratory coagulation assays, and reversal strategies. Rapid identification of DOACs in the blood will allow timely reversal of factor Xa inhibitors and direct thrombin inhibitors when necessary. The present study evaluated viscoelastic testing to detect and classify DOACs in patient blood samples.

METHODS

This observational, prospective, open-label, multicenter study used point-of-care viscoelastic testing to analyze blood samples taken from patients with and without DOAC treatment, and healthy volunteers. Antifactor Xa and direct thrombin inhibition (DTI) assays were used to establish reference ranges for viscoelastic testing parameters on the TEG 6s system. These ranges were applied to produce a DOAC identification algorithm for patient blood samples. Internal consistency of the measurements, as well as algorithm sensitivity and specificity, was evaluated.

RESULTS

Using the TEG 6s system, the R parameter reference range was 0.6 minutes to 1.5 minutes for the Antifactor Xa assay and 1.6 minutes to 2.5 minutes for the DTI assay. Our identification algorithm using these ranges for 2.5 minutes or less has sensitives of 98.3% and 100% for factor Xa inhibitor and direct thrombin inhibitor detection, respectively. Specificity was 100%. Both classes of DOAC were detectable, even when samples were collected during the “trough” between doses of medication.

CONCLUSION

Point-of-care viscoelastic testing with TEG 6s can detect and classify DOACs with high sensitivity and specificity. This tool can be used to better determine the need for reversal in trauma and acute care surgery patients and guide optimal surgical timing in the acute setting.

LEVEL OF EVIDENCE

Prognostic and epidemiological study, level II.
Women Travellers, Romantic-era science and the Banksian empire
Authors: Thompson Carl
Published: May 2019

This article explores the contributions to science made by three women travellers in the Romantic period: Maria Riddell (1772–1808), who visited the Caribbean between 1788 and 1791; Maria Graham (later Callcott, 1785–1842), who visited South America between 1821 and 1825; and Sarah Bowdich (later Lee, 1791–1856), who visited Madeira and West Africa in the late 1810s and early 1820s. As well as mapping their scientific accomplishments, the article explores their integration into contemporary scientific networks and circuits of knowledge production, paying particular attention to their connections with the so-called ‘Banksian empire’ of Sir Joseph Banks (1743–1820). Simultaneously, it addresses the diverse strategies adopted by Riddell, Graham and Bowdich as they sought to negotiate the constraints undoubtedly faced in this period by women seeking to participate in scientific endeavours; however, the article also argues that such constraints did not ultimately prevent Riddell, Graham and Bowdich from attaining scientific authority and influence, both within the contemporary scientific community and with the wider public.
Where and what? Frugivory is associated with more efficient foraging in three semi-free ranging primate species
Authors: Trapanese Cinzia , Robira Benjamin , Tonachella Giordana , di Gristina Silvia , Meunier Hélène , Masi Shelly
Published: May 2019

Foraging in seasonal environments can be cognitively challenging. Comparative studies have associated brain size with a frugivorous diet. We investigated how fruit distribution (where) and preference (what) affect foraging decisions in three semi-free ranging primate species with different degrees of frugivory:Macaca tonkeana(Nindiv= 5;Ntrials= 430),M. fascicularis(Nindiv= 3;Ntrials= 168) andSapajus apella(Nindiv= 6;Ntrials= 288). We used 36 boxes fixed on trees and filled with highly and less preferred fruits with different (weekly) spatio-temporal distributions. Individuals were tested in two conditions: (1) same fruit provided concurrently in the same quantity but in a scattered and in a clumped distribution, (2) highly preferred fruit was scattered while the less preferred was clumped. Generally, primates preferred feeding first on the boxes of the clumped distribution in both conditions, with the more frugivorous species at a higher degree than the less frugivorous species in condition (1), but not (2). Therefore,whatfruit was available changed the foraging decisions of the more frugivorous species who also engaged more in goal-directed travel. When feeding on preferred fruit, primates probably maximized foraging efficiency regardless of their degree of frugivory. Our findings emphasize that the food type and distribution may be a preponderant driver in cognitive evolution.
Gentamicin-loaded silk/nanosilver composite scaffolds for MRSA-induced chronic osteomyelitis
Authors: Zhang Peng , Qin Jianzhong , Zhang Bo , Zheng Yi , Yang Lingyan , Shen Yixin , Zuo Baoqi , Zhang Feng
Published: May 2019

Methicillin-resistant
Staphylococcus aureus
(MRSA) often induces chronic osteomyelitis and then bone defects. Here, gentamicin-loaded silk/nanosilver composite scaffolds were developed to treat MRSA-induced chronic osteomyelitis. AgNO
3
was reduced with silk as a reducing agent in formic acid, forming silver nanoparticles
in situ
that were distributed uniformly in the composite scaffolds. Superior antibacterial properties against MRSA were achieved for the composite scaffolds, without the compromise of osteogenesis capacity. Then gentamicin was loaded on the scaffolds for better treatment of osteomyelitis.
In vivo
results showed effective inhibition of the growth of MRSA bacteria, confirming the promising future in the treatment of chronic osteomyelitis.
Synthesis and characterization of silver nanoparticle-decorated cobalt nanocomposites (Co@AgNPs) and their density-dependent antibacterial activity
Authors: Kanwal Zakia , Raza Muhammad Akram , Riaz Saira , Manzoor Saher , Tayyeb Asima , Sajid Imran , Naseem Shahzad
Published: May 2019

Magnetic cores loaded with metallic nanoparticles can be promising nano-carriers for successful drug delivery at infectious sites. We report fabrication, characteristic analysis and
in vitro
antibacterial performance of nanocomposites comprising cobalt cores (Co-cores) functionalized with a varied concentration of silver nanoparticles (AgNPs). A two-step polyol process synchronized with the transmetalation reduction method was used. Co-cores were synthesized with cobalt acetate, and decoration of AgNPs was carried out with silver acetate. The density of AgNPs was varied by changing the amount of silver content as 0.01, 0.1 and 0.2 g in the synthesis solution. Both AgNPs and Co-cores were spherical having a size range of 30–80 nm and 200 nm to more than 1 µm, respectively, as determined by scanning electron microscopy. The metallic nature and face-centred cubic crystalline phase of prepared nanocomposites were confirmed by X-ray diffraction. Biocompatibility analysis confirmed high cell viability of MCF7 at low concentrations of tested particles. The antibacterial performance of nanocomposites (Co@AgNPs) against
Escherichia coli
and
Bacillus subtilis
was found to be AgNPs density-dependent, and nanocomposites with the highest AgNPs density exhibited the maximum bactericidal efficacy. We therefore propose that Co@AgNPs as effective drug containers for various biomedical applications.
Fake science and the knowledge crisis: ignorance can be fatal
Authors: Hopf Henning , Krief Alain , Mehta Goverdhan , Matlin Stephen A.
Published: May 2019

Computers, the Internet and social media enable every individual to be a publisher, communicating true or false information instantly and globally. In the ‘post-truth’ era, deception is commonplace at all levels of contemporary life. Fakery affects science and social information and the two have become highly interactive globally, undermining trust in science and the capacity of individuals and society to make evidence-informed choices, including on life-or-death issues. Ironically, drivers of fake science are embedded in the current science publishing system intended to disseminate evidenced knowledge, in which the intersection of science advancement and reputational and financial rewards for scientists and publishers incentivize gaming and, in the extreme, creation and promotion of falsified results. In the battle for truth, individual scientists, professional associations, academic institutions and funding bodies must act to put their own house in order by promoting ethics and integrity and de-incentivizing the production and publishing of false data and results. They must speak out against false information and fake science in circulation and forcefully contradict public figures who promote it. They must contribute to research that helps understand and counter false information, to education that builds knowledge and skills in assessing information and to strengthening science literacy in society.
Neural arbors are Pareto optimal
Authors: Chandrasekhar Arjun , Navlakha Saket
Published: May 2019

Neural arbors (dendrites and axons) can be viewed as graphs connecting the cell body of a neuron to various pre- and post-synaptic partners. Several constraints have been proposed on the topology of these graphs, such as minimizing the amount of wire needed to construct the arbor (wiring cost), and minimizing the graph distances between the cell body and synaptic partners (conduction delay). These two objectives compete with each other—optimizing one results in poorer performance on the other. Here, we describe how well neural arbors resolve this network design trade-off using the theory of Pareto optimality. We develop an algorithm to generate arbors that near-optimally balance between these two objectives, and demonstrate that this algorithm improves over previous algorithms. We then use this algorithm to study how close neural arbors are to being Pareto optimal. Analysing 14 145 arbors across numerous brain regions, species and cell types, we find that neural arbors are much closer to being Pareto optimal than would be expected by chance and other reasonable baselines. We also investigate how the location of the arbor on the Pareto front, and the distance from the arbor to the Pareto front, can be used to classify between some arbor types (e.g. axons versus dendrites, or different cell types), highlighting a new potential connection between arbor structure and function. Finally, using this framework, we find that another biological branching structure—plant shoot architectures used to collect and distribute nutrients—are also Pareto optimal, suggesting shared principles of network design between two systems separated by millions of years of evolution.
Personality and gonadal development as sources of individual variation in response to GnRH challenge in female great tits
Authors: Caro Samuel P. , Cornil Charlotte A. , van Oers Kees , Visser Marcel E.
Published: May 2019

Seasonal timing of reproduction is a key life-history trait, but we know little about the mechanisms underlying individual variation in female endocrine profiles associated with reproduction. In birds, 17β-oestradiol is a key reproductive hormone that links brain neuroendocrine mechanisms, involved in information processing and decision-making, to downstream mechanisms in the liver, where egg-yolk is produced. Here, we test, using a simulated induction of the reproductive system through a Gonadotropin-Releasing Hormone (GnRH) challenge, whether the ovary of pre-breeding female great tits responds to brain stimulation by increasing oestradiol. We also assess how this response is modified by individual-specific traits like age, ovarian follicle size, and personality, using females from lines artificially selected for divergent levels of exploratory behaviour. We show that a GnRH injection leads to a rapid increase in circulating concentrations of oestradiol, but responses varied among individuals. Females with more developed ovarian follicles showed stronger responses and females from lines selected for fast exploratory behaviour showed stronger increases compared to females from the slow line, indicating a heritable component. This study shows that the response of the ovary to reproductive stimulation from the brain greatly varies among individuals and that this variation can be attributed to several commonly measured individual traits, which sheds light on the mechanisms shaping heritable endocrine phenotypes.
Competition and resource breadth shape niche variation and overlap in multiple trophic dimensions
Authors: Costa-Pereira Raul , Araújo Márcio S. , Souza Franco L. , Ingram Travis
Published: May 2019

Competition plays a central role in the maintenance of biodiversity. A backbone of classic niche theory is that local coexistence of competitors is favoured by the contraction or divergence of species' niches. However, this effect should depend on the diversity of resources available in the local environment, particularly when resources vary in multiple ecological dimensions. Here, we investigated how available resource breadth (i.e. prey diversity) and competition together shape multidimensional niche variation (between and within individuals) and interspecific niche overlap in 42 populations of congeneric tropical frog species. We modelled realized niches in two key trophic dimensions (prey size and carbon stable isotopes) and sampled available food resources to quantify two-dimensional resource breadth. We found a 14-fold variation in multidimensional population niche width across populations, most of which was accounted for by within-individual diet variation. This striking variation was predicted by an interaction whereby individual niche breadth increased with resource breadth and decreased with the number of congeneric competitors. These ecological gradients also interact to influence the degree of niche overlap between species, which surprisingly decreased with population total niche width, providing novel insights on how similar species can coexist in local communities. Together, our results emphasize that patterns of exploitation of resources in multiple dimensions are driven by both competitive interactions and extrinsic factors such as local resource breadth.
Testing for dependence on tree structures
Authors: Behr Merle , Ansari M. Azim , Munk Axel , Holmes Chris
Published: May 2019

Tree structures, showing hierarchical relationships and the latent structures between samples, are ubiquitous in genomic and biomedical sciences. A common question in many studies is whether there is an association between a response variable measured on each sample and the latent group structure represented by some given tree. Currently this is addressed on an ad hoc basis, usually requiring the user to decide on an appropriate number of clusters to prune out of the tree to be tested against the response variable. Here we present a statistical method with statistical guarantees that tests for association between the response variable and a fixed tree structure across all levels of the tree hierarchy with high power, while accounting for the overall false positive error rate. This enhances the robustness and reproducibility of such findings.

Significance Statement

Tree like structures are abundant in the empirical sciences as they can summarize high dimensional data and show latent structure among many samples in a single framework. Prominent examples include phylogenetic trees or hierarchical clustering derived from genetic data. Currently users employ ad hoc methods to test for association between a given tree and a response variable, which reduces reproducibility and robustness. In this paper, we introduce treeSeg, a simple to use and widely applicable methodology with high power for testing between all levels of hierarchy for a given tree and the response while accounting for the overall false positive rate. Our method allows for precise uncertainty quantification and therefore increases interpretability and reproducibility of such studies across many fields of science.
Understanding the dynamics of physical activity practice in the health context through Regulatory Focus and Self-Determination theories
Authors: Laroche Manon , Roussel Peggy , Cury François , Boiche Julie
Published: May 2019

This research aimed to associate for the first time in the literature the Regulatory Focus and Self-Determination theories to understand the dynamics of physical activity practice in the health context. Two cross-sectional studies were conducted with 603 (Study 1) and 395 (Study 2) French volunteer participants aged from 18 to 69 and 19 to 71 respectively, and healthy or concerned by a health condition. The main results of structural equation modeling analyses demonstrated that across the two studies, health promotion focus was positively associated with intrinsic motivation (.44 < β < .74, p < .001), integrated regulation (.47 < β < .72, p < .001), identified regulation (.40 < β < .69, p < .001) and introjected regulation (.41 < β < .53, p < .001), whereas health prevention focus was positively related with external regulation (.31 < β < .45, p < .001) and amotivation (.32 < β < .38, p < .001). Bootstrapping analyses main results in Study 2 showed that health promotion focus was indirectly associated with physical activity through intrinsic motivation (95% CI [.02 to .11]), integrated regulation (95% CI [.00 to .08]), identified regulation (95% CI [.00 to .09]) and introjected regulation (95% CI [.04 to .12]), whereas health prevention focus was indirectly associated with physical activity through external regulation (95% CI [.00 to .12]). These studies reveal meaningful associations between Regulatory Focus and Self-Determination theories’ variables which support the relevance of associating these two models to understand the processes underlying the physical activity practice.
IL-1RA controls the development of esophageal cancer by inhibition of VEGF via PI3K/NF-κB signaling pathway
Authors: Shen Zhimin , Yu Shaobin , Gao Lei , Liu Zhun , Zhang Peipei , Chai Tianci , Chen Sui , Kang Mingqiang
Published: May 2019

IL-1RA has been reported to function as tumor suppressor in a variety of tumors, but its function and mechanism in esophageal cancer remains largely unknown. Our previous studies have shown that IL-1RA is downregulated in primary esophageal cancer(EC), and this downregulation of IL-1RA is closely related to TNM staging and survival prognosis. In this study, we observed that over-expression of IL-1RA inhibits proliferation, migration, and tumor growth in esophageal cancer cells(ESCC), inhibits the expression and secretion of VEGF, and inhibits tumor angiogenesis. Further studies have shown the overexpression of IL-1RA inhibits the transmission of PI3K/NF-kappaB. Taken together, this study shows that IL-1RA can regulating the development of esophageal cancer by inhibiting VEGF expression and secretion via inhibiting PI3K/NF-kappaB signaling, and it may serve as a potential prognostic marker and therapeutic target for EC.