bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing pain in critically ill brain-injured patients: a psychometric comparison of 3 pain scales and videopupillometry
Authors: Bernard Christine , Delmas Valentine , Duflos Claire , Molinari Nicolas , Garnier Océane , Chalard Kévin , Jaber Samir , Perrigault Pierre-François , Chanques Gérald
Published: June 2019

Three clinical scales (the Nociception Coma Scale adapted for Intubated patients [NCS-I], its Revised version [NCS-R-I], and the Behavioral Pain Scale [BPS]) and videopupillometry were compared for measuring pain in intubated, noncommunicating, critically ill, brain-injured patients. Pain assessment was performed before, during, just after, and 5 minutes after 3 procedures: the reference non-nociceptive procedure (assessment of the Richmond Agitation Sedation Scale) and 2 nociceptive procedures (turning and tracheal suctioning). The primary endpoint was construct validity (discriminant and criterion validation), determined by comparing pain measurements between different times/procedures. Secondary endpoints were internal consistency, inter-rater reliability, and feasibility. Fifty patients (54% women, median age 63 years [56-68]) were included 13 [7-24] days after brain injury (76% hemorrhagic or ischemic strokes). All tools increased significantly more (P < 0.001) during the nociceptive procedures vs the non-nociceptive procedure. The BPS was the only pain tool that did not increase significantly during the non-nociceptive procedure (P = 0.41), suggesting that it was the most discriminant tool. The BPS, NCS-I, and NCS-R-I were good predictors of nociception with areas under the curves ≥0.96, contrary to videopupillometry (area under the curve = 0.67). The BPS, NCS-I, and NCS-I-R had high inter-rater reliabilities (weighted kappa = 0.86, 0.82 and 0.84, respectively). Internal consistency was moderate (>0.60) for all pain scales. Factor analysis represented a majority of information on a first dimension, with motor domains represented on a second dimension. Scale feasibility was better for the NCS-I and NCS-R-I than for the BPS. In conclusion, the BPS, NCS-I, and NCS-R-I are valid, reliable, and acceptable pain scales for use in intubated critically ill, brain-injured patients, unlike videopupillometry. Future research requires tool design centered on domains of observation adapted to this very specific population.
Adverse Drug Reactions Related to Mood and Emotion in Pediatric Patients Treated for Attention Deficit/Hyperactivity Disorder
Authors: Pozzi Marco , Carnovale Carla , Mazhar Faizan , Peeters Gabriëlla G.A.M. , Gentili Marta , Nobile Maria , Radice Sonia , Clementi Emilio
Published: June 2019

Background

Attention deficit/hyperactivity disorder (ADHD) can be comorbid with frequent anxiety and mood disorders, as well as emotional symptoms (anxiety, irritability, mood lability). These may also be triggered by drugs and appear as adverse drug reactions (ADRs).

Methods

We mined data from the US Food and Drug Administration Adverse Event Reporting System pharmacovigilance database, focused on methylphenidate, atomoxetine, amphetamine, lisdexamfetamine, and their derivatives. We collected reports of ADRs connected with mood or emotional symptoms in pediatric patients, excluding drug abuse/accidents. Reporting odds ratios (RORs) were calculated and compared between drug classes and children/adolescents.

Results

We collected 6176 ADRs of interest of which 59% occurred in children. Atomoxetine accounted for 50.7% of reports, methylphenidate for 32.5%, lisdexamfetamine for 14.2%, and amphetamine for 2.6%. Irritability, anxiety, obsessive thoughts, depressed mood, and euphoria scored significant RORs for all drugs, overall with an increasing risk from methylphenidate to atomoxetine, lisdexamfetamine, and amphetamine. Apathy regarded mostly atomoxetine, and crying regarded all drugs except methylphenidate. Several age-based differences were found. Notably, affect lability hit only adolescents. All drugs scored significant self-injury RORs, except lisdexamfetamine in adolescents, with an increasing risk from methylphenidate to lisdexamfetamine, atomoxetine, and amphetamine. For suicidality, all drugs had significant RORs in children, and methylphenidate was better than atomoxetine and lisdexamfetamine. In adolescents, only methylphenidate and atomoxetine scored significant RORs.

Conclusions

We conclude that real-world data from the US Food and Drug Administration Adverse Event Reporting System are consistent with previous evidence from meta-analyses. They support a hierarchy of drug safety for several ADRs (except self-injury/suicidality) with methylphenidate as safest, followed by atomoxetine, lisdexamfetamine, and amphetamine last. Self-injury and suicidality RORs were overall higher in children.
A Single Center Experience of Feasibility of a Novel Self-Expanding Metallic Airway Stent (Bonastent): A Case Series
Authors: Makkar Priyanka , Revelo Alberto , Lee Robert , Chawla Mohit
Published: June 2019

Background:

Central airway obstruction (CAO) is defined as obstruction of the airway lumen in the trachea or mainstem bronchi, most commonly due to primary or metastatic malignancy; and is classified as extraluminal, endoluminal, or mixed. The majority of malignant CAO are advanced stage and require a multimodality palliative approach, including stent placement. We describe a retrospective review of a novel self-expandable metallic stent, the Bonastent; a fully covered, nitinol-braided airway stent which conforms to airway tortuosity without loss of diameter in the management of CAO.

Methods:

We performed a retrospective chart review of patients with CAO who underwent Bonastent placement at a single center between February 2017 and March 2018. Ease of stent placement, short-term complications (within 24 h of stent placement) and long-term complications (within 3 mo of stent placement) were recorded.

Results:

Eleven patients were identified, reviewed and included in the study. Thirteen stents in 11 patients were placed for predominantly malignant CAO. One patient had a short-term complication of stent migration. Four patients had long-term complications; of which 3 patients had in-stent mucus impaction requiring bronchoscopy. In our study, the stent-related complication rates were comparable to the reported literature.

Conclusion:

In our experience, Bonastent is an easy to use option which adds to the armamentarium of the self-expandable metallic stent to treat malignant CAO.
Any news from the prokinetic front?
Authors: Deane Adam M. , Chapman Marianne J. , Abdelhamid Yasmine Ali
Published: June 2019

Purpose of review

This review provides an update of recently conducted studies and randomized controlled trials evaluating prokinetic drugs.

Recent findings

Prokinetic drugs accelerate gastric emptying and, particularly in patients with gastric dysmotility and enteral feed intolerance, their use increases the delivery of enteral nutrition. However, prokinetic drugs have not been shown to improve patient-centered outcomes in trials but benefit is assumed on the basis of observational studies, which report close associations between gastric dysmotility, enteral feed intolerance and poor outcomes, and improvement in surrogate physiological outcomes when prokinetic drugs are administered.

It may not be feasible to establish superiority of a prokinetic drug within a randomized controlled trial with a patient-centered event as the primary outcome. The use of metoclopramide and erythromycin as prokinetic drugs is based on observations from trials measuring surrogate physiological outcomes. Randomized controlled trials of alternative drug regimens and novel prokinetic drugs have recently been completed and results outlined.
Sexually Transmitted Disease Partner Services Costs, Other Resources, and Strategies Across Jurisdictions to Address Unique Epidemic Characteristics and Increased Incidence
Authors: Silverman Rachel A. , Katz David A. , Levin Carol , Bell Teal R. , Spellman Dawn , St. John Lisa , Manley Rodriguez Evelyn , Golden Matthew R. , Barnabas Ruanne V.
Published: June 2019

Background

Sexually transmitted disease (STD) partner services (PS) are a core component of STD programs. Data on costs are needed to support PS programming.

Methods

In Washington State STD PS programs, disease intervention specialists (DIS) conduct telephone-based interviews and occasional field visits, offer expedited partner therapy to heterosexuals with gonorrhea or chlamydia, and promote human immunodeficiency virus (HIV) testing, preexposure prophylaxis, and HIV care. We conducted activity-based microcosting of PS, including: observational and self-reported time studies and interviews. We analyzed cost, surveillance, and service delivery data to determine costs per program outcomes.

Results

In King, Pierce, and Spokane counties, respectively, DIS allocated 6.5, 6.4, and 28.8 hours per syphilis case and 1.5, 1.6, and 2.9 hours per gonorrhea/chlamydia case, on average. In 2016, each full-time DIS investigated 270, 268, and 61 syphilis and 1177, 1105, and 769 gonorrhea/chlamydia cases. Greater than 80% of syphilis cases in King and Pierce were among men who have sex with men versus 38% in Spokane. Disease intervention specialists spent 12% to 39% of their time actively interviewing cases and notifying partners (clients), and the remaining time locating clients, coordinating and verifying care, and managing case reports. Time spent on expedited partner therapy, HIV testing, and referrals to HIV treatment or preexposure prophylaxis, was minimal (<5 minutes per interview) at locations with resources outside PS staff. Program cost-per-interview ranged from US $527 to US $2210 for syphilis, US $219 to US $484 for gonorrhea, and US $164 to US $547 for chlamydia.

Discussion

The STD PS resource needs depended on epidemic characteristics and program models. Integrating HIV prevention objectives minimally impacted PS-specific program costs. Results can inform program planning, future budget impact, and cost-effectiveness analyses.
Lifestyle Risk Behaviors Among Stroke Survivors With and Without Diabetes
Authors: Bailey Ryan R. , Phad Allison , McGrath Ryan , Ford Andria L. , Tabak Rachel , Haire-Joshu Debra
Published: June 2019

Objective

History of stroke and diabetes increases risk for cardiometabolic disease, which can be mitigated through lifestyle management. To evaluate lifestyle risk behaviors among stroke survivors, we compared the prevalence of three lifestyle risk behaviors—physical inactivity, consuming one or less fruit and one or less vegetable daily, and overweight/obesity—between stroke survivors with and without diabetes.

Design

Data from the 2013 and 2015 Behavioral Risk Factor Surveillance System were examined. Weighted and age-adjusted prevalence estimates as well as crude and adjusted odds ratios (adjusted for sociodemographic characteristics) were calculated to compare lifestyle risk behaviors between US stroke survivors with and without diabetes.

Results

Prevalence and adjusted odds ratios for lifestyle risk behaviors were higher in respondents with diabetes compared with those without diabetes for consuming one or less fruit and one or less vegetable daily (58.8% vs. 53.7%, adjusted odds ratio = 1.14), physical inactivity (65.7% vs. 54.6%, adjusted odds ratio = 1.41), and overweight/obesity (87.2% vs. 63.1%, adjusted odds ratio = 2.42).

Conclusions

Prevalence of select lifestyle risk behaviors exceeds 50% in adults with stroke but is higher in adults with diabetes compared with adults without diabetes. Effective interventions, community programs, and healthcare policy are needed to promote lifestyle management in adults with stroke, particularly among those with diabetes.
A Randomized Control Trial of Comparing Ultrasound-Guided Ozone (O2-O3) vs Corticosteroid Injection in Patients With Shoulder Impingement
Authors: Babaei-Ghazani Arash , Fadavi Hamid Reza , Eftekharsadat Bina , Ebadi Safoora , Ahadi Tannaz , Ghazaei Fatemeh , Khabbaz Mohamad Sadegh
Published: June 2019

Introduction

Ozone has been recently used as a safe alternative treatment in musculoskeletal disorders with fewer adverse effects than corticosteroids. The aim of this study was to compare the efficacy of a single injection of ozone with that of a corticosteroid in the treatment of shoulder impingement.

Design

Thirty patients with shoulder pain and clinical signs and symptoms of impingement were randomly assigned into two groups: ultrasound-guided injection with ozone or corticosteroid. Patients’ symptoms were evaluated by visual analog scale, constant score, shoulder pain and disability scale, shoulder range of motion, and ultrasonographic measures before treatment, 2 wks, and 2 mos after injections.

Results

Patients’ visual analog scale, shoulder pain and disability scale and constant score improved significantly in both groups (P < 0.001), but the benefits were in favor of corticosteroid group (P < 0.001). At intervals between the two follow-ups, an improvement was observed in the visual analog scale score among patients receiving ozone, whereas during the same interval, patients’ pain slightly worsened in the corticosteroid group. The range of motion and ultrasonographic measures did not show statistical differences between the two groups.

Conclusions

Corticosteroid injection improves the pain and disability scores more significantly than a one-time ozone injection. Ozone may serve as an alternative modality in treating shoulder impingement when the use of steroids is contraindicated.
A Growing Epidemic: Plastic Surgeons and Burnout—A Literature Review
Authors: Khansa Ibrahim , Janis Jeffrey E.
Published: June 2019

Background:

The prevalence of burnout is increasing among all physicians, including plastic surgeons. Burnout is not simply synonymous with being overworked. It is a complex physical, intellectual, and psychological entity that arises when the expectation and reality of the job do not match. In this article, the authors’ goal is to define burnout, summarize its causes and consequences, and offer the plastic surgeons methods to prevent and address it.

Methods:

A literature search of articles on burnout in medicine was performed. Articles that were relevant were selected, and were qualitatively analyzed to answer our questions on the definition, prevalence, causes, consequences, and treatments of burnout.

Results:

Sixty-five relevant articles were included. The prevalence of burnout among physicians ranges between 29 and 55 percent. Risk factors for physician burnout include increased workload and call, junior academic rank, and fair physician health. There is significant overlap among burnout, depression, and substance abuse, and suicide is much more common among physicians than among the general population. Preventing burnout involves a multiprong approach that addresses the physical, intellectual, and psychological dimensions of the physician.

Conclusions:

In this article, concrete steps to prevent and address burnout are presented to plastic surgeons. For physicians, the most important elements for burnout avoidance are the prevention of emotional exhaustion, and the development of professional autonomy and control.
The Use of a Three-Dimensional Printed Model for Surgical Excision of a Vascular Lesion in the Head and Neck
Authors: Paul Marek A. , Opyrchał Jakub , Witowski Jan , Ibrahim Ahmed M.S. , Knakiewicz Michał , Jaremków Paweł
Published: June 2019

Facial vascular lesions are considered a great therapeutic challenge due to the considerable variability of clinical presentations. Surgical removal requires precise planning and advanced visualization to understand the three-dimensional anatomical relationships better.

The aim of the study was to evaluate the feasibility of three-dimensional printed models, based on computed tomography angiography (CTA), in planning and guiding surgical excision of vascular lesions.

A patient with a suspected vascular malformation in the face was recruited for participation in this feasibility study. Two personalized three-dimensional models were printed based off 2 separate CTA examinations. These constructs were used in preoperative planning and navigating surgical excision. The three-dimensional constructs identified the vicinity of the lesion and highlighted significant anatomical structures including the infraorbital nerve and vessels supplying the area of vascular anomaly. On postoperative follow-up the patient reported no recurrence of swelling and no sensory deficits.

A personalized three-dimensional printed model of a facial vascular lesion was developed based on CTA images and used in preoperative planning and navigating surgical excision. It was most useful in establishing dangerous areas during the dissection process, including critical anatomical structures such as the infraorbital nerve. Combining conventional imaging techniques with three-dimensional printing may lead to improved diagnosis of vascular malformations and should be considered a useful adjunct to surgical management.
Algorithm for Resecting Hepatocellular Carcinoma in the Caudate Lobe
Authors: Takayama Tadatoshi , Midorikawa Yutaka , Higaki Tokio , Nakayama Hisashi , Moriguchi Masamichi , Aramaki Osamu , Yamazaki Shintaro , Aoki Masaru , Kogure Kimitaka , Makuuchi Masatoshi
Published: June 2019

Objective:

To propose an algorithm for resecting hepatocellular carcinoma (HCC) in the caudate lobe.

Background:

Owing to a deep location, resection of HCC originating in the caudate lobe is challenging, but a plausible guideline enabling safe, curable resection remains unknown.

Methods:

We developed an algorithm based on sublocation or size of the tumor and liver function to guide the optimal procedure for resecting HCC in the caudate lobe, consisting of 3 portions (Spiegel, process, and caval). Partial resection was prioritized to remove Spiegel or process HCC, while total resection was aimed to remove caval HCC depending on liver function.

Results:

According to the algorithm, we performed total (n = 43) or partial (n = 158) resections of the caudate lobe for HCC in 174 of 201 patients (compliance rate, 86.6%), with a median blood loss of 400 (10–4530) mL. Postoperative morbidity (Clavien grade ≥III b) and mortality rates were 3.0% and 0%, respectively. After a median follow-up of 2.6 years (range, 0.5–14.3), the 5-year overall and recurrence-free survival rates were 57.3% and 15.3%, respectively. Total and partial resection showed no significant difference in overall survival (71.2% vs 54.0% at 5 yr; P = 0.213), but a significant factor in survival was surgical margin (58.0% vs 45.6%, P = 0.034). The major determinant for survival was vascular invasion (hazard ratio 1.7, 95% CI 1.0–3.1, P = 0.026).

Conclusions:

Our algorithm-oriented strategy is appropriate for the resection of HCC originating in the caudate lobe because of the acceptable surgical safety and curability.
Opioid Fills in Children Undergoing Surgery From 2011 to 2014
Authors: Wetzel Martha , Hockenberry Jason M. , Raval Mehul V.
Published: June 2019

Objective:

The primary objective is to describe the relationship between the days supplied of postsurgical filled opioid prescriptions and refills.

Background:

The American College of Surgeons (ACS) has called for surgeons to alter opioid prescribing to counteract the opioid epidemic while simultaneously providing pain relief. However, there is insufficient evidence to inform perioperative prescribing guidelines and quality metrics in children.

Methods:

We performed a secondary data analysis of nationwide commercial claims from the Health Care Cost Institute (HCCI) data spanning 2010 and 2014. Based on initial opioid fill and refill rates for 11 common pediatric procedures, the refill analysis focused on anterior cruciate ligament repair, humerus fracture repair, cholecystectomy, posterior spinal fusion, and tonsillectomy.

Results:

There were 178,990 cases with a median age of 6. Overall, 48.5% of patients filled an opioid prescription between 30 days before surgery through 7 days after surgery, and 14.2% filled a second opioid prescription within 30 days. There was a significant negative relationship between days supplied in the initial prescription and probability of a refill for humerus fracture, spinal fusion, and tonsillectomy. The largest effect was seen for tonsillectomy, with the odds of having a refill decreasing by approximately 12% for each day supplied in the initial prescription (odds ratio 0.88, 95% confidence interval 0.87–0.89, P < 0.001).

Conclusions:

Pediatric postoperative opioid-prescribing guidelines need to be procedure-specific and based on patient age. We provide the days supplied associated with a 20% probability of a refill by age to further guideline development.
Decreasing Trends in Intestinal Resection and Re-Resection in Crohn's Disease
Authors: Beelen Evelien M. J. , van der Woude C. Janneke , Pierik Marie J. , Hoentjen Frank , de Boer Nanne K. , Oldenburg Bas , van der Meulen Andrea E. , Ponsioen Cyriel I. J. , Dijkstra Gerard , Bruggink Annette H. , Erler Nicole S. , Schouten W. Rudolph , de Vries Annemarie C.
Published: June 2019

Objective:

To assess time trends in intestinal resection and re-resection in Crohn's disease (CD) patients.

Summary of Background Data:

CD treatment has changed considerably over the past decades. The effect of these advances on the necessity of intestinal resections and the risk of re-resection is unclear.

Methods:

In this nationwide cohort study, adult CD patients with ileocolonic, small bowel, colon, or rectum resections between 1991 and 2015 were included. Data were retrieved from the Dutch nationwide network and registry of histopathology and cytopathology (PALGA). Time trends were analyzed with a broken stick model and Cox proportional hazard model with smoothing splines.

Results:

The identified cohort comprised 8172 CD patients (3293/4879 male/female) in whom 10,315 intestinal resections were performed. The annual intestinal resection rate decreased nonlinearly from 22.7/100,000 CD patients (1991) to 2.5/100,000 (2015). A significantly steeper decrease was observed before 1999 (slope −1.56) as compared to subsequent years (slope −0.41) (P < 0.001). Analogous trends were observed for ileocolonic, small bowel, and colon resections. Overall cumulative risk of re-resection was 10.9% at 5 years, 18.6% at 10 years, and 28.3% at 20 years after intestinal resection. The hazard for intestinal re-resection showed a nonlinear decreasing trend, with hazard ratio 0.39 (95% confidence interval 0.36–0.44) in 2000 and hazard ratio 0.25 (95% confidence interval 0.18–0.34) in 2015 as compared to 1991.

Conclusion:

Over the past 25 years, intestinal resection rate has decreased significantly for ileocolonic, small bowel, and colonic CD. In addition, current postoperative CD patients are at 75% lower risk of intestinal re-resection.
Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA)
Authors: Eliason Jonathan L. , Myers Daniel D. , Ghosh Abhijit , Morrison Jonathan J. , Mathues Angela R. , Durham Laura , Dunivant Veronica , Gonzalez Andrew A. , Rasmussen Todd E.
Published: June 2019

Objectives:

Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) has been used clinically to limit torso bleeding and restore central perfusion. The objective of this study was to determine the sequelae of prolonged REBOA in a nonhuman primate animal model.

Summary Background Data:

Prolonged duration of REBOA is associated with adverse clinical outcomes. Threshold occlusion values tied to relative risk have yet to be determined.

Methods:

Juvenile baboons were subjected to 40% to 55% total blood volume hemorrhage to achieve profound hypotension and shock. Zone I REBOA was performed for 60 minutes to assess acute injury and survival at 4 hours (group 1; n = 7). Post-REBOA 10-day survival and complications were then compared between 60 minutes (group 2; n = 8) and 30 minutes (group 3; n = 6) REBOA animals.

Results:

Overall survival was 20/21 (95%). IL-6 and IL-8 were elevated at 1 and 4 hours in group 1 (P = 0.005; P = 0.001). Comparing 60-minute REBOA with 30-minute REBOA, there was (1) hypertension compared with normotension (P = 0.005), (2) increased base deficit (P = 0.003), (3) elevated Troponin I (P = 0.04), and histological evidence of kidney injury (P = 0.004). In addition, group 2 demonstrated paralysis with histopathologic changes of spinal cord ischemia (SCI) in 4/8 (50%), with no SCI in group 3 (P = 0.033).

Conclusions:

REBOA limits mortality in the primate model of severe hemorrhagic shock. However, unopposed balloon inflation in the distal thoracic aorta for 60 minutes results in high rates of spinal cord ischemia, an effect mitigated by limiting balloon inflation to 30 minutes.
Kenneth Joseph Arrow. 23 August 1921—21 February 2017
Authors: Velupillai K. Vela
Published: June 2019

Kenneth Arrow was a mathematical economist and political scientist who made many ground-breaking contributions to the theory of economics and social values. His great mathematical ability led him to introduce new approaches to theoretical economics and in particular to a series of fundamental theorems in the discipline. These included the Arrow Impossibility Theorem, the two fundamental theorems of welfare economics and the existence of a competitive equilibrium. For these and many other contributions he was awarded the 1972 Nobel Prize in Economics shared with Sir John Hicks. He took a particular interest in computation and computability in economics. He was active and very productive as a researcher for over seven decades and was renowned as a generous and inspiring teacher and colleague.
J. Murdoch Mitchison. 11 June 1922—17 March 2011
Authors: Fantes Peter , Mitchison Sally
Published: June 2019

John Murdoch Mitchison, known as Murdoch, was elected FRS in recognition of his work on the cell cycle. This emerged from a lifelong interest in the natural sciences, interrupted by war-time work in Operational Research which developed his critical appraisal of research technique. Post-war, he completed a PhD at Cambridge, then worked with Sir Michael Swann FRS (1962) on mitotic membrane changes in sea urchins. In 1953 Murdoch joined the University of Edinburgh Zoology Department and in time switched his interest to the fission yeastSchizosaccharomyces pombe. Over the next 30 years he investigated cell growth and division, employing a meticulous approach to experiments. He considered there to be a ‘growth cycle’ in cells, independent of the DNA-division cycle. There is experimental evidence to support this idea, but further investigations of it have been limited.

Actively fostering a relaxed but industrious and enquiring ethos in the lab, Murdoch ran the department jointly with Aubrey Manning. The Mitchison group's work at Edinburgh attracted students including Paul Nurse (later Sir Paul Nurse; FRS 1989, PRS 2010–2015), Béla Novak, Kim Nasmyth (FRS 1989) and Peter Fantes as well as many visiting academics. Murdoch's work onS. pombecame to both national and international recognition, forming a foundation for the current thriving community of researchers in cell physiology, cell genetics and molecular biology.

Murdoch is remembered for his single-minded commitment to cell biology research and his generous, fair-minded support of younger colleagues and students. He was, additionally, an expert landscape gardener, a convivial host and phenomenally well-informed on most subjects.
Sir John Edward Sulston CH. 27 March 1942—6 March 2018
Authors: Waterston Robert H. , Ferry Georgina
Published: June 2019

In 2002 Sir John Sulston shared the Nobel Prize for Physiology or Medicine for his contribution to understanding the genetic control of cell fate during the development of the roundwormCaenorhabditis elegans. However, it was his position as one of the leaders of the international and publicly funded Human Genome Project that brought him to public prominence. Both his work on the worm cell lineage and his later commitment to genome sequencing as founding director of the Wellcome Trust Sanger Institute stemmed from his conviction that investing in large-scale data collection would have long-term benefits for future scientific discovery. He was a key figure in promoting the principle, now widely accepted, that genomic data should be universally and freely shared. After retiring from his post at the Sanger Institute he engaged with organizations with interests in biomedical ethics and global equality. He was a loyal and supportive colleague to many, delighting in the international collegiality of the ‘worm community’, of which he was a founding member.
Of manuscripts and men: the editorial history of Isaac Newton's
Chronology
and
Observations
Authors: Schilt Cornelis J.
Published: June 2019

This article introduces the editorial history of the most important of Isaac Newton's posthumously published scholarly writings, a history so far unwritten. Often attributed solely to Newton's executor, John Conduitt, the
Chronology of Ancient Kingdoms Amended
(1728) was in fact co-edited with the antiquarian Martin Folkes, who would eventually follow in Newton's footsteps and become President of the Royal Society. Likewise, the
Observations upon the Prophecies of Daniel and the Apocalypse of St John
(1733) was edited by at least half a dozen of Newton's closest friends and colleagues. During the eighteenth and nineteenth centuries, but in particular during the twentieth, these publications were treated as solely Newton's, and analysed as such by both contemporaries and modern historians. However, as this paper shows, the
Chronology
and in particular the
Observations
were as much the product of their editors as of their author, and should be considered as such. Reconstructing the editorial history of Newton's posthumous publications reveals a fascinating tale of how his friends, relatives and colleagues tried to piece together meaning from the thousands of manuscripts with which they were confronted, a challenge that continues to this day.
When spring ephemerals fail to meet pollinators: mechanism of phenological mismatch and its impact on plant reproduction
Authors: Kudo Gaku , Cooper Elisabeth J.
Published: June 2019

The flowering phenology of early-blooming plants is largely determined by snowmelt timing in high-latitude and high-altitude ecosystems. When the synchrony of flowering and pollinator emergence is disturbed by climate change, seed production may be restricted due to insufficient pollination success. We revealed the mechanism of phenological mismatch between a spring ephemeral (
Corydalis ambigua
) and its pollinator (overwintered bumblebees), and its impact on plant reproduction, based on 19 years of monitoring and a snow removal experiment in a cool-temperate forest in northern Japan. Early snowmelt increased the risk of phenological mismatch under natural conditions. Seed production was limited by pollination success over the 3 years of the pollination experiment and decreased when flowering occurred prior to bee emergence. Similar trends were detected on modification of flowering phenology through snow removal. Following snowmelt, the length of the pre-flowering period strongly depended on the ambient surface temperature, ranging from 4 days (at greater than 7°C) to 26 days (at 2.5°C). Flowering onset was explained with an accumulated surface degree-day model. Bumblebees emerged when soil temperature reached 6°C, which was predictable by an accumulated soil degree-day model, although foraging activity after emergence might depend on air temperature. These results indicate that phenological mismatch tends to occur when snow melts early but subsequent soil warming progresses slowly. Thus, modification of the snowmelt regime could be a major driver disturbing spring phenology in northern ecosystems.
Male competition and the evolution of mating and life-history traits in experimental populations of
Aedes aegypti
Authors: Qureshi Alima , Aldersley Andrew , Hollis Brian , Ponlawat Alongkot , Cator Lauren J.
Published: June 2019

Aedes aegypti
is an important disease vector and a major target of reproductive control efforts. We manipulated the opportunity for sexual selection in populations of
Ae
.
aegypti
by controlling the number of males competing for a single female. Populations exposed to higher levels of male competition rapidly evolved higher male competitive mating success relative to populations evolved in the absence of competition, with an evolutionary response visible after only five generations. We also detected correlated evolution in other important mating and life-history traits, such as acoustic signalling, fecundity and body size. Our results indicate that there is ample segregating variation for determinants of male mating competitiveness in wild populations and that increased male mating success trades-off with other important life-history traits. The mating conditions imposed on laboratory-reared mosquitoes are likely a significant determinant of male mating success in populations destined for release.
Adaptive phenotypic plasticity for life-history and less fitness-related traits
Authors: Acasuso-Rivero Cristina , Murren Courtney J. , Schlichting Carl D. , Steiner Ulrich K.
Published: June 2019

Organisms are faced with variable environments and one of the most common solutions to cope with such variability is phenotypic plasticity, a modification of the phenotype to the environment. These modifications are commonly modelled in evolutionary theories as adaptive, influencing ecological and evolutionary processes. If plasticity is adaptive, we would predict that the closer to fitness a trait is, the less plastic it would be. To test this hypothesis, we conducted a meta-analysis of 213 studies and measured the plasticity of each reported trait as a coefficient of variation. Traits were categorized as closer to fitness—life-history traits including reproduction and survival related traits, and farther from fitness—non-life-history traits including traits related to development, metabolism and physiology, morphology and behaviour. Our results showed, unexpectedly, that although traits differed in their amounts of plasticity, trait plasticity was not related to its proximity to fitness. These findings were independent of taxonomic groups or environmental types assessed. We caution against general expectations that plasticity is adaptive, as assumed by many models of its evolution. More studies are needed that test the adaptive nature of plasticity, and additional theoretical explorations on adaptive and non-adaptive plasticity are encouraged.
Rare genetic variation and balanced polymorphisms are important for survival in global change conditions
Authors: Brennan Reid S. , Garrett April D. , Huber Kaitlin E. , Hargarten Heidi , Pespeni Melissa H.
Published: June 2019

Standing genetic variation is important for population persistence in extreme environmental conditions. While some species may have the capacity to adapt to predicted average future global change conditions, the ability to survive extreme events is largely unknown. We used single-generation selection experiments on hundreds of thousands ofStrongylocentrotus purpuratussea urchin larvae generated from wild-caught adults to identify adaptive genetic variation responsive to moderate (pH 8.0) and extreme (pH 7.5) low-pH conditions. Sequencing genomic DNA from pools of larvae, we identified consistent changes in allele frequencies across replicate cultures for each pH condition and observed increased linkage disequilibrium around selected loci, revealing selection on recombined standing genetic variation. We found that loci responding uniquely to either selection regime were at low starting allele frequencies while variants that responded to both pH conditions (11.6% of selected variants) started at high frequencies. Loci under selection performed functions related to energetics, pH tolerance, cell growth and actin/cytoskeleton dynamics. These results highlight that persistence in future conditions will require two classes of genetic variation: common, pH-responsive variants maintained by balancing selection in a heterogeneous environment, and rare variants, particularly for extreme conditions, that must be maintained by large population sizes.
Functional classification of noncoding RNAs associated with distinct histone modifications by PIRCh-seq
Authors: Fang Jingwen , Ma Qing , Chu Ci , Huang Beibei , Li Lingjie , Cai Pengfei , Batista Pedro J. , Tolentino Karen Erisse Martin , Xu Jin , Li Rui , Du Pengcheng , Qu Kun , Chang Howard Y.
Published: June 2019

Many long noncoding RNAs (lncRNAs) regulate gene transcription through binding to histone modification complexes. Therefore, a comprehensive study of nuclear RNAs in a histone modification-specific manner is critical to understand their regulatory mechanisms. Here we develop a method named Profiling Interacting RNAs on Chromatin by deep sequencing (PIRCh-seq), in which we profile chromatin-associated transcriptome in 5 different cell types using antibodies recognizing histone H3 and 6 distinct histone modifications associated with active or repressive chromatin states. PIRCh-seq identified chromatin-associated RNAs with substantially less contamination by nascent transcripts, as compared to existing methods. We classified chromatin-enriched lncRNAs into 6 functional groups based on the patterns of their association with specific histone modifications. LncRNAs were enriched with different chromatin modifications in different cell types, suggesting lncRNAs’ regulation may also be cell type-specific. By integrating profiles of RNA secondary structure and RNA m6A modification, we found that RNA bases which bind to chromatin tend to be more single stranded. We discovered hundreds of allele-specific RNA-chromatin interactions, nominating specific single nucleotide variants that alter RNA association with chromatin. These results provide a unique resource to globally study the functions of chromatin-associated lncRNAs and elucidate the basic mechanisms of chromatin-RNA interaction.
Single-cell whole-genome sequencing reveals mutational landscapes of DNA mismatch repair deficiency in mouse primary fibroblasts
Authors: Zhang Lei , Dong Xiao , Hao Xiaoxiao , Lee Moonsook , Chi Zhongxuan , Jin Bo , Maslov Alexander Y. , Edelmann Winfried , Vijg Jan
Published: June 2019

DNA Mismatch repair (MMR) deficiency is a major cause of hereditary non-polyposis colorectal cancer, and is also associated with increased risk of several other cancers. This is generally ascribed to the role of MMR in avoiding mutations by correcting DNA replication errors. In MMR knockout mice very high frequencies of somatic mutations, up until 100-fold of background, have been reported. However, these results have been obtained using bacterial reporter transgenes, which are not representative for the genome overall, and mutational patterns of MMR deficiency remain largely unknown. To fill this knowledge gap, we performed single-cell whole-genome sequencing of lung fibroblasts of Msh2−/− and wild-type mice. We observed a 4-fold increase of somatic single nucleotide variants (SNVs) in the fibroblasts of Msh2−/− mice compared to those of wild-type mice. The SNV signature of Msh2 deficiency was found to be driven by C>T and T>C transitions. By comparing it to human cancer signatures, we not only confirmed the inferred MMR-deficiency-related etiology of several cancer signatures but also suggested that MMR deficiency is likely the cause of a cancer signature with its etiology previously unknown. We also observed a 7-fold increase of somatic small insertions and deletions (INDELs) in the Msh2−/− mice. An elevated INDEL frequency has also been found in human MMR-related cancers. INDELs and SNVs distributed differently across genomic features in the Msh2−/− and control cells, with evidence of selection pressure and repair preference. These results provide insights into the landscape of somatic mutations in normal somatic cells caused by MMR deficiency.

Significance

Our results show that MMR deficiency in the mouse is associated with a much lower elevation of somatic mutation rates than previously reported and provides the first MMR whole-genome mutational landscapes in normal somatic cells in vivo.
A theoretical model of neural maturation in the developing spinal cord
Authors: Joshi Piyush , Skromne Isaac
Published: June 2019

Cellular differentiation is a tightly regulated process under the control of intricate signaling and transcription factors interaction network working in coordination. These interactions make the systems dynamic, robust and stable but also difficult to dissect. In the spinal cord, recent work has shown that a network of FGF, WNT and Retinoic Acid (RA) signaling factors regulate neural maturation by directing the activity of a transcription factor network that contains CDX at its core. Here we have used partial and ordinary (Hill) differential equation based models to understand the spatiotemporal dynamics of the FGF/WNT/RA and the CDX/transcription factor networks, alone and in combination. We show that in both networks, the strength of interaction among network partners impacts the dynamics, behavior and output of the system. In the signaling network, interaction strength determine the position and size of discrete regions of cell differentiation and small changes in the strength of the interactions among networking partners can result in a signal overriding, balancing or oscillating with another signal. We also show that the spatiotemporal information generated by the signaling network can be conveyed to the CDX/transcription network to produces a transition zone that separates regions of high cell potency from regions of cell differentiation, in agreement with mostin vivoobservations. Importantly, both networks have built in robustness to extrinsic disturbances. This analysis provides a model for the interaction conditions underlying spinal cord cell maturation during embryonic axial elongation.
Screening topological materials with a CsCl-type structure in crystallographic databases
Authors: Jin L. , Zhang X. M. , Dai X. F. , Wang L. Y. , Liu H. Y. , Liu G. D.
Published: June 2019

CsCl-type materials have many outstanding characteristics, i.e. simple in structure, ease of synthesis and good stability at room temperature, thus are an excellent choice for designing functional materials. Using high-throughput first-principles calculations, a large number of topological semimetals/metals (TMs) were designed from CsCl-type materials found in crystallographic databases and their crystal and electronic structures have been studied. The CsCl-type TMs in this work show rich topological character, ranging from triple nodal points, type-I nodal lines and critical-type nodal lines, to hybrid nodal lines. The TMs identified show clean topological band structures near the Fermi level, which are suitable for experimental investigations and future applications. This work provides a rich data set of TMs with a CsCl-type structure.
Classification, representation and automatic extraction of adhesively bonded assembly features
Authors: Das Shantanu Kumar , Swain Abinash Kumar
Published: June 2019

Purpose

This paper aims to present the classification, representation and extraction of adhesively bonded assembly features (ABAFs) from the computer-aided design (CAD) model.

Design/methodology/approach

The ABAFs are represented as a set of faces with a characteristic arrangement among the faces among parts in proximity suitable for adhesive bonding. The characteristics combination of the faying surfaces and their topological relationships help in classification of ABAFs. The ABAFs are classified into elementary and compound types based on the number of assembly features exist at the joint location.

Findings

A set of algorithms is developed to extract and identify the ABAFs from CAD model. Typical automotive and aerospace CAD assembly models have been used to illustrate and validate the proposed approach.

Originality/value

New classification and extraction methods for ABAFs are proposed, which are useful for variant design.
Integrated design environment for reusable modular assembly systems
Authors: Ferreira Pedro , Anandan Paul Danny , Pereira Ivo , Hiwarkar Vikrant , Sayed Mohmed , Lohse Niels , Aguiar Susana , Gonçalves Gil , Gonçalves Joana , Bottinger Fabian
Published: June 2019

Purpose

This paper aims to provide a service-based integrated prototype framework for the design of reusable modular assembly systems (RMAS) incorporating reusability of equipment into the process. It extends AutomationML (AML) developments for an engineering data exchange to integrate and standardize the data formats that support the design of RMAS.

Design/methodology/approach

The approach provides a set of systematic procedures and support tools for the design of RMAS. This includes enhanced domain knowledge models that facilitate the interpretation and integration of information across the design phases.

Findings

The inclusion of reusability aspects in the design phase improves the sustainability of future assembly systems, by ensuring equipment use until its end-of-life. Moreover, the integrated support tools reduce the design time, while improving the quality/performance of the system design solution, as it enables the exploration of a larger solution space. This will result in a better response to dynamic and rapidly changing system requirements.

Social implications

This work provides a sustainable approach for the design of modular assembly systems (MAS), which will ensure better resource utilization. Additionally, the standardization of the data and the support of low cost tools is expected to benefit industrial companies, particularly the small- and medium-sized enterprises.

Originality/value

This approach offers a service-based platform which uses production data to incorporate reusability aspects into the design process of modular assembly system. Moreover, it provides a framework for modular assembly system design by extending the current design processes and interactions between stakeholders. To support this, a standardized method for information representation and exchange across the several phases of the RMAS design activity is briefly illustrated with an industrial case study.
The changing role of convenience stores in South Korea
Authors: Kim So-young , Choi Ji Yu
Published: June 2019

Purpose

The purpose of this paper is to develop policy recommendations for creating a healthy food environment around convenience stores which has been recently extending beyond the retail to the food retail and even to the foodservice market in South Korea.

Design/methodology/approach

This study was based on case studies of evaluating the nutritional quality of lunch box products sold by the Korean big 3 convenience store brands (CU, GS25 and 7-Eleven) as meal replacements. Samples of all lunch box products sold during October 2016 in Asan city, South Korea were collected for nutritional quality evaluation.

Findings

The amount of food items in the “Meats/Fish/Eggs/Legume” food group was 2.4 times the recommended intake, while that in the “Vegetables” food group was even less than one serving size. The most frequent cooking method both for the animal- and plant-based food groups was stir-frying. The average calories fell short of the reference value for men but exceeded it for women. The percentage energy contribution from fats exceeded the reference range. The average amounts of protein, saturated fat, cholesterol and sodium were higher than recommended.

Originality/value

This study calls attention to the necessity and importance of establishing a healthy food environment around convenience stores, given the ever-growing reliance on these establishments as a go-to spot for a convenient meal. The results may also provide useful insights for developing countries in Asia, which are being spotlighted as the emerging markets for convenience stores.