bluuebunny/crossref_metadata_2025 huggingface dataset:
Prescriptions Written for Opioid Pain Medication in the Veterans Health Administration Between 2000 and 2016
Authors: Grasso Michael A. , Grasso Clare T. , Jerrard David A.
Published: August 2017

Objectives:

The purpose of this study was to identify national opioid pain medication (OPM) prescribing trends within the Veterans Health Administration (VA), and assess the impact of educational campaigns introduced in 2010 and 2013.

Methods:

We created a national cohort that documents more than 21 million patient records and 97 million outpatient OPM prescriptions covering a 17-year period. We examined OPM prescriptions in emergency departments, outpatient clinics, and inpatient settings.

Results:

The cohort accounted for 2.5 billion outpatient clinic visits, 18.9 million emergency department visits, and 12.4 million hospital admissions. The number of OPM prescriptions peaked in 2011, when they were provided during 5% of all outpatient visits and 15% of all emergency department visits. The morphine milligram equivalents (MMEs) peaked in 2014 at almost 17 billion in outpatient clinics and at 137 million in emergency departments. In 2016, OPM prescriptions were down 37% in outpatient clinics and 23% in emergency departments, and MMEs were down 30% in both settings. Prescriptions for hydrocodone and tramadol increased markedly between 2011 and 2015. OPM doses in inpatient settings continued to rise until 2015.

Conclusions:

We used a large national cohort to study trends in OPM prescriptions within the VA. Educational efforts to reduce the number of OPM prescriptions coincided with these reductions, but were initially associated with an increase in OPM dosage, an increase in the use of tramadol and hydrocodone, and an increase in the use of OPMs in inpatient settings.
Cracking the case: should orthopaedic case carts be subjected to more stringent regulations?
Authors: Darnley James , Denham Zachary , Phieffer Laura S. , Scharschmidt Thomas J. , Mayerson Joel L. , Glassman Andrew H. , Moffatt-Bruce Susan D. , Quatman Carmen E.
Published: August 2017

Background:

Long periods of time with opened, uncovered sterile case carts and high rates of operating room (OR) traffic are correlated with contamination risk. We studied the length of time the case cart was open before incision and compared room traffic frequency before and after surgical incision.

Methods:

Thirty-three orthopaedic implant cases were observed at three hospitals over an 8-week period. Observation began at the opening of the implant case cart and concluded when the final dressing was placed. The length of time the sterile case cart was open before the patient was in the room and before an incision was made was recorded. Traffic was counted any time a surgical door opened and stratified on a per-hour basis. The traffic rate was counted before and after incision.

Results:

The average length that the case cart was open prior to the patient being in the room was 43.2 (±29.7) mins, (range, 0-153). On average the case cart was open 91.5 (±31.2) mins, (range, 45-189) prior to the incision. The room traffic was significantly greater during preincision period (45.0±12.8), than during postincision period (26.6±12.8) (P<0.0001). The average number of people in the operating room was 6.9 (±2.7).

Conclusions:

Room traffic during orthopaedic implant cases is high, with more than one door opening every 2 min. The highest frequencies of traffic occurred before incision but after case carts were opened. Case carts usually were opened more than 1 hr before incision for orthopaedic implant cases.
Colonoscopy in Patients With Postmyocardial Infarction Gastrointestinal Bleeding
Authors: Modi Rohan M. , Li Feng , Mumtaz Khalid , Hinton Alice , Lilly Scott M. , Hussan Hisham , Levine Edward , Zhang Cheng , Conwell Darwin L. , Krishna Somashekar G. , Stanich Peter P.
Published: August 2017

Goals:

The goal of this study was to evaluate outcomes of colonoscopy in the setting of post myocardial infarction (MI) gastrointestinal bleeding (GIB) in a large population-based data set.

Background:

The literature to substantiate the proposed safety of colonoscopy following an acute MI is limited.

Study:

The Nationwide Inpatient Sample (2007 to 2013) was utilized to identify all adult patients (age, 18 y or above) hospitalized with a primary diagnosis of ST-elevation MI and receiving left heart catheterization (STEMI-C). The outcomes of patients with concomitant diagnosis of GIB receiving endoscopic intervention with esophagogastroduodenoscopy (EGD) or colonoscopy postcatheterization were compared with those who did not. Primary outcomes including mortality, length of stay, and hospital costs were evaluated with univariate and multivariate analysis.

Results:

There were 131,752 patients with post-STEMI-C GIB (5.35% of all STEMI-C patients) and same admission colonoscopy was performed in 1599 patients (1.21%). Although the prevalence of post-STEMI-C GIB increased from 4.27% in 2007 to 5.87% in 2013 (P<0.001), patients receiving colonoscopy decreased from 1.42% to 1.09% (P<0.001) over the course of the study period. Multivariate analysis revealed that patients receiving no endoscopic intervention [odds ratio, 3.61; 95% confidence interval: 1.57, 8.31] or EGD alone (OR, 2.70; 95% confidence interval: 1.12, 6.49) have higher mortality compared with those receiving colonoscopy.

Conclusions:

Same admission colonoscopy performed for post-STEMI-C GIB was associated with lower mortality. However, despite increased incidence of GIB in these patients during the study period, a lower percentage of patients received colonoscopy. These results suggest that colonoscopy is safe but underutilized in this setting.
Six Weeks Versus 3 Months of Anticoagulant Treatment for Pediatric Central Venous Catheter-related Venous Thromboembolism
Authors: Smith Rowenne , Jones Sophie , Newall Fiona
Published: August 2017

Objective:

Central venous catheters (CVCs) are the single most important predisposing factor for the development of pediatric venous thromboembolism (VTE). Treatment recommendations suggest anticoagulation for the duration of 6 weeks to 3 months. This project investigated clinical outcomes associated with 6 weeks compared with 3 months of enoxaparin therapy following diagnosis of a CVC-related VTE.

Methods:

This retrospective cohort study enrolled patients aged 18 years and below treated with enoxaparin with/without unfractionated heparin for a radiologically confirmed CVC-related VTE. Patients were identified using the pharmacy database, radiologic imaging, and medical records. Patients were divided into 2 groups based on the duration of anticoagulation (6+1 or 12±2 wk) and data were analyzed using descriptive statistics.

Results:

Seventy-four patients were included. Higher rates of complete thrombosis resolution were observed in children treated for 6 weeks at treatment cessation (39.4%) and long-term follow-up (61.5%), compared with 3 months (11.8% and 9.0%, respectively).

Conclusions:

Six weeks of treatment for CVC-related VTE may provide noninferior clinical outcomes compared with 3 months of anticoagulation. An international randomized-controlled trial (Kids-DOTT) is underway to explore the optimal duration of anticoagulation for acute-provoked VTE in children. This manuscript highlights that data from such studies is urgently needed.
Vincristine, Irinotecan, and Bevacizumab in Relapsed Wilms Tumor With Diffuse Anaplasia
Authors: Schiavetti Amalia , Varrasso Giulia , Collini Paola , Clerico Anna
Published: August 2017

The prognosis of relapsed Wilms tumor (WT) with diffuse anaplasia is dismal, therefore, novel therapeutic strategies need to be explored. We reported on 2 consecutive cases with relapsed anaplastic WT who presented a partial response after 2 courses of vincristine, irinotecan, and bevacizumab association. This regimen may have a role in the treatment of patients with anaplastic advanced WT.
Case Report: Clinical Variation in Children With Thrombopoietin Receptor (C-MPL) Mutations: Report of 2 Cases
Authors: Lo Clara , Alvarez Elysia , Ohgami Robert S. , Jeng Michael
Published: August 2017

Congenital amegakaryocytic thrombocytopenia (CAMT, MIM# 604498) is a rare congenital bone marrow failure syndrome which presents early in life with abnormal bleeding because of thrombocytopenia. Classically, megakaryocytes are decreased to absent in the bone marrow. The development of aplastic anemia early in childhood has led to the recommendation for early stem cell transplantation. Quantitative or loss-of-function mutations in the myeloproliferative leukemia gene (c-mpl), whose gene product functions as the thrombopoietin receptor, have been identified as causative for CAMT. Approximately 100 cases of CAMT are published in the medical literature. We describe 2 cases of CAMT who demonstrate disparate clinical courses, thereby highlighting phenotypic differences and increasing awareness of this clinical entity.
Childhood Blastic Plasmacytoid Dendritic Cell Neoplasm Mimicking Acute Rheumatic Fever: Report of an Unusual Clinical Presentation and Review of Literature
Authors: Rajkumari Banashree Devi , Munikoty Vinay , Sreedharanunni Sreejesh , Jain Richa , Sachdeva Man Updesh Singh , Varma Neelam
Published: August 2017

Background:

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is very rarely diagnosed in children with less than 50 cases in the literature.

Observation:

We report a case of childhood BPDCN who mimicked acute rheumatic fever at presentation. Majority of the reported childhood BPDCN received acute lymphoblastic leukemia–like chemotherapy with/without stem cell therapy, whereas those who received acute myeloid leukemia–like therapy predominantly succumbed to disease or sepsis. Overall 68% of the patients were alive and achieved complete remission with an overall prognosis slightly better in children compared with adults.

Conclusions:

The case is reported due to its unique unusual clinical presentation and its rarity in pediatric population.
Successful Treatment of Recurrent Li-Fraumeni Syndrome-related Choroid Plexus Carcinoma
Authors: McEvoy Matthew , Robison Nathan , Manley Peter , Yock Torunn , Konopka Kristine , Brown Robert E. , Wolff Johannes , Green Adam L.
Published: August 2017

The management of choroid plexus carcinoma (CPC) is challenging and multifaceted. Here, we discuss a 3-year-old girl with CPC and Li-Fraumeni syndrome who achieved full remission after surgery and chemotherapy, with radiation therapy spared. At recurrence, we used a novel, standard-dose cytotoxic chemotherapy regimen, focal proton radiation therapy, and targeted agents based on morphoproteomic analysis to achieve long-term survival. We highlight the rationale for our therapy at recurrence, as well as the risk-benefit analyses necessary in decision making for these patients. Our strategy may be effective in managing other patients with recurrent CPC and Li-Fraumeni syndrome.
Developing Professional Practice and Ethics Engagement
Authors: Reilly Karen M. , Jurchak Martha
Published: August 2017

Nurse leaders are responsible for a practice environment that fosters safe, quality patient outcomes through excellence in nursing practice. This article describes a reflective practice intervention in the Cardiac Intensive Care Unit of an urban academic medical center led by the unit nursing director and the hospital's nurse ethicist. The twice monthly case-based discussions, called “Nursing Practice and Ethics Rounds,” were attended by staff and unit managers (nurse director, assistant nurse director, and clinical educator) and were facilitated by the nurse ethicist. The purpose of this descriptive qualitative study was to identify nurses' perceptions of the rounds on individual practice, unit practice, and the practice of their peers. Two focus groups were conducted with nurses who attended 3 or more sessions. Staff reported that they felt valued; experienced a decrease in moral distress; and improved empathy with patients, families, and other staff members after the intervention. They also reported better understanding of ethical issues and language to better talk about them. The presence of nurse leaders was valued as affirming the importance of practice development and of witnessing the experience of staff nurses. Finally, the process of reflection was valued for the opportunity it provided to process emotional and intellectual aspects of challenging cases.
Nurses to Their Nurse Leaders
Authors: Bacon Cynthia Thornton
Published: August 2017

The purpose of this study was to describe nurses' needs and how they are being met and not met after caring for surgical patients who died after a failure to rescue (FTR). A qualitative, phenomenologic approach was used for the interview and analysis framework. Methods to ensure rigor and trustworthiness were incorporated into the design. The investigator conducted semistructured 1:1 interviews with 14 nurses. Data were analyzed using Colaizzi's methods. Four themes were identified: (1) coping mechanisms are important; (2) immediate peer and supervisor feedback and support are needed for successful coping; (3) subsequent supervisor support is crucial to moving on; and (4) nurses desire both immediate support and subsequent follow-up from their nurse leaders after every FTR death. Nurses' needs after experiencing an FTR patient death across multiple practice areas and specialties were remarkably similar and clearly identified and articulated. Coping mechanisms vary and are not uniformly effective across different groups. Although most nurses in this study received support from their peers after the FTR event, many nurses did not receive the feedback and support that they needed from their nurse leaders. Immediate nurse leader support and follow-up debriefings should be mandatory after patient FTR deaths. Developing an understanding of nurses' needs after experiencing an FTR event can assist nurse leaders to better support nurses who experience FTR deaths. Insight into the environment surrounding FTR deaths also provides a foundation for future research aimed at improving patient safety and quality through an improved working environment for nurses.
Substance Use Education in Schools of Nursing
Authors: Smothers Zachary , Reynolds Victoria , McEachern Mark , Derouin Anne L. , Carter Brigit M. , Muzyk Andrew
Published: August 2017

The authors systematically reviewed the nursing literature for articles describing substance use disorders (SUDs) education in schools of nursing. Five literature databases were searched, producing 3107 retrieved articles, of which 12 were included in this review. A Medical Education Research Study Quality Instrument score was calculated for each study. The included studies demonstrated that teaching nursing students about SUDs produced a positive impact on their attitudes, knowledge, and skills.
Seizures Induced by Exiting Water
Authors: Appavu Brian , Fox Jordana , Little Robert , Kerrigan John F. , Obeid Makram
Published: August 2017

Introduction:

Reflex epilepsies represent a form of epilepsy in which unique modes of seizure precipitation are characterized by endogenous or exogenous stimuli. Hot water epilepsy represents a subtype of reflex epilepsy in which seizure precipitation arises from the act of immersing the head with hot water. Bathing epilepsy represents another subtype of reflex epilepsy in which seizure precipitation arises from the immersion with water at lukewarm temperatures.

Case Series:

We report on 2 boys with a unique form of bathing epilepsy characterized by the act of exiting out of water. The first patient had a family history significant for a brother with frontal lobe epilepsy. He underwent an evaluation in the epilepsy monitoring unit in which a reflex seizure was recorded while exiting the shower. This seizure was characterized by an ictal onset in the left frontal lobe and subsequent secondary generalization. The second patient initially had nonreflex seizures arising from the left temporal lobe and went on to develop reflex seizures upon exiting water. For both patients, the precipitation of seizures was independent of water or environmental temperature, exposure of specific body parts, or duration of water immersion. Both children experienced a sensation of coldness, followed by convulsive or atonic activity.

Conclusions:

Our cases represent a unique form of bathing epilepsy in which seizure precipitation is dependent upon exiting water.
Development and Psychometric Evaluation of the Speaking Up About Patient Safety Questionnaire
Authors: Richard Aline , Pfeiffer Yvonne , Schwappach David D.L.
Published: August 2017

Objective

Speaking up about safety concerns by staff is important to prevent medical errors. Knowledge about healthcare workers’ speaking up behaviors and perceived speaking up climate is useful for healthcare organizations (HCOs) to identify areas for improvement. The aim of this study was to develop a short questionnaire allowing HCOs to assess different aspects of speaking up among healthcare staff.

Methods

Healthcare workers (n = 523) from 2 Swiss hospitals completed a questionnaire covering various aspects of speak up–related behaviors and climate. Psychometric testing included descriptive statistics, correlations, reliabilities (Cronbach α), principal component analysis, and t tests for assessing differences in hierarchical groups.

Results

Principal component analysis confirmed the structure of 3 speaking up behavior-related scales, that is, frequency of perceived concerns (concern scale, α = 0.73), withholding voice (silence scale, α = 0.76), and speaking up (speak up scale, α = 0.85). Concerning speak up climate, principal component analysis revealed 3 scales (psychological safety, α = 0.84; encouraging environment, α = 0.74; resignation, α = 0.73). The final survey instrument also included items covering speaking up barriers and a vignette to assess simulated behavior. A higher hierarchical level was mostly associated with a more positive speak up–related behavior and climate.

Conclusions

Patient safety concerns, speaking up, and withholding voice were frequently reported. With this questionnaire, we present a tool to systematically assess and evaluate important aspects of speaking up in HCOs. This allows for identifying areas for improvement, and because it is a short survey, to monitor changes in speaking up—for example, before and after an improvement project.
The Theory is Out There: The Use of ALPHA-2 Agonists in Treatment of Septic Shock
Authors: Ferreira Jason
Published: August 2017

The sympathetic nervous system plays an important role in the initial response to sepsis. This response enables the host to respond to invading pathogens; however, prolonged activation can become pathological. The potential for unregulated sympathetic tone to become detrimental in the septic patient has fueled interest in the role and impact of sympathetic manipulation, including the selective inhibition of sympathetic tone to return and augment vascular reactivity. While conventional understanding of alpha 2 agonists activity is depletion of sympathetic outflow, novel evidence suggests mitigation rather than depletion. The mechanism by which these agents exert these properties remains controversial and appears to be condition-specific. The hypothesis by which alpha agonists affect the pathology of sepsis is multifactorial, but includes influence on inflammatory regulation, coagulopathy, dynamic flow, as well as vascular responsiveness and integrity. Theory and basic science evidence supports the use of α agonists in the septic population. The clinical evidence shedding light on this topic is limited and confounded by intention or trial design. Future evidence should focus on adjuvant therapy in patients progressing to or at high risk of shock development.
Neutrophil Activation During Septic Shock
Authors: Stiel Laure , Meziani Ferhat , Helms Julie
Published: August 2017

In addition to their well-known role as the cellular mediators of immunity, key other roles have been identified for neutrophils during septic shock. Importantly, neutrophils indeed play a critical role in the recently described immunothrombosis concept and in septic shock-induced coagulopathy. Septic shock is one of the most severe forms of infection, characterized by an inadequate host response to the pathogenic organism. This host response involves numerous defense mechanisms with an intense cellular activation, including neutrophil activation. Neutrophils are key cells of innate immunity through complex interactions with vascular cells and their activation may participate in systemic tissue damages. Their activation also leads to the emission of neutrophil extracellular traps, which take part in both pathogen circumscription and phagocytosis, but also in coagulation activation. Neutrophils thus stand at the interface between hemostasis and immunity, called immunothrombosis.

The present review will develop a cellular approach of septic shock pathophysiology focusing on neutrophils as key players of septic shock-induced vascular cell dysfunction and of the host response, associating immunity and hemostasis. We will therefore first develop the role of neutrophils in the interplay between innate and adaptive immunity, and will then highlight recent advances in our understanding of immunothrombosis septic shock-induced coagulopathy.
Liver Enzymes and the Development of Posttransplantation Diabetes Mellitus in Renal Transplant Recipients
Authors: Klaassen Gerald , Corpeleijn Eva , Deetman Nicole P.E. , Navis Gerjan J. , Bakker Stephan J.L. , Zelle Dorien M.
Published: August 2017

Background

Posttransplantation diabetes mellitus (PTDM) is common in renal transplant recipients (RTR), increasing the risk of graft failure, cardiovascular disease, and mortality. Early detection of a high risk for PTDM is warranted. Because liver function and liver fat are involved, we investigated whether serum liver markers are associated with future PTDM in RTR.

Methods

Between 2001 and 2003, 606 RTR with a functioning allograft beyond the first year after transplantation were included of which 500 participants (56% men; age, 50 ± 12 years) were free of diabetes at baseline and had liver enzyme values (1 missing) available. Serum concentrations of alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase were measured at baseline at 6.0 (6.2-11.5) years posttransplantation. PTDM cases were recorded until April 2012.

Results

During median follow-up for 9.6 years (interquartile range [IQR], 6.2-10.2) beyond baseline, 76 (15.2%) patients developed PTDM. Comparing the highest to the lower tertiles, higher liver enzyme activities were significantly related to incident PTDM for ALT (hazard ratio [HR], 2.22; IQR, 1.42-3.48), for GGT (HR, 2.93; IQR, 1.87-4.61), and for alkaline phosphatase (HR, 1.78; IQR, 1.13-2.80). The associations of ALT and GGT with development of PTDM were independent of potential confounders and risk factors, including age, sex, renal function, medication use, lifestyle factors, adiposity, presence of the metabolic syndrome, fasting glucose, HbA1c, proinsulin, and cytomegalovirus status.

Conclusions

Markers for liver function and liver fat in the subclinical range are potential markers for future PTDM, independent of other known risk factors. This may allow for early detection and management of PTDM development.
Predation, metabolic priming and early life-history rearing environment affect the swimming capabilities of growth hormone transgenic rainbow trout
Authors: Crossin Glenn T. , Devlin Robert H.
Published: August 2017

The period of first feeding, when young salmonid fishes emerge from natal stream beds, is one fraught with predation risk. Experiments conducted in semi-natural stream mesocosms have shown that growth hormone transgenic salmonids are at greater risk of predation than their non-transgenic siblings, due partly to the higher metabolic demands associated with transgenesis, which force risky foraging behaviours. This raises questions as to whether there are differences in the swim-performance of transgenic and non-transgenic fishes surviving predation experiments. We tested this hypothesis in wild-origin rainbow trout (
Oncorhynchus mykiss
) that were reared from first feeding in semi-natural stream mesocosms characterized by complex hydrodynamics, the presence of predators and oligotrophic conditions. Using an open-flume raceway, we swam fish and measured their capacity for burst-swimming against a sustained flow. We found a significant genotype effect on burst-performance, with transgenic fish sustaining performance longer than their wild-type siblings, both in predator and predator-free stream segments. Importantly, this effect occurred before differences in growth were discernable. We also found that mesocosm-reared fish had greater burst-performance than fish reared in the controlled hatchery environment, despite the latter being unexposed to predators and having abundant food. Our results suggest a potential interaction between predation and metabolic priming, which leads to greater burst capacity in transgenic trout.
Vladimir Igorevich Arnold. 12 June 1937—3 June 2010
Authors: Khesin Boris , Tabachnikov Sergei
Published: August 2017

Vladimir Arnold was a pre-eminent mathematician of the second half of the twentieth and early twenty-first century. Kolmogorov–Arnold–Moser (KAM) theory, Arnold diffusion, Arnold tongues in bifurcation theory, Liouville–Arnold theorem in completely integrable systems, Arnold conjectures in symplectic topology—this is a very incomplete list of notions and results named after him. Arnold was a charismatic leader of a mathematical school, a prolific writer, a flamboyant speaker and a tremendously erudite person. Our biographical sketch describes his extraordinary personality and his major contributions to mathematics.
David Parker Craig AO FAA. 23 December 1919—1 July 2015
Authors: Hush Noel S. , Radom Leo
Published: August 2017

David Craig was an outstanding Australian theoretical chemist whose academic life oscillated between Australia (University of Sydney and Australian National University (ANU)) and the UK (University College London). The Craig Building of the Research School of Chemistry of the ANU was named in his honour in 1995. He was President of the Australian Academy of Science from 1990 to 1994, and the Academy's David Craig Medal, which recognizes outstanding contributions to chemistry research, was inaugurated in his honour. His best-known research is in the fields of quantum theory and spectroscopy of aromatic molecules, molecular crystals, quantum electrodynamics and chirality.
Anin vivogenetic screen inDrosophilaidentifies the orthologue of human cancer/testis geneSPO11among a network of targets to inhibitlethal(3)malignant brain tumourgrowth
Authors: Rossi Fabrizio , Molnar Cristina , Hashiyama Kazuya , Heinen Jan P. , Pampalona Judit , Llamazares Salud , Reina José , Hashiyama Tomomi , Rai Madhulika , Pollarolo Giulia , Fernández-Hernández Ismael , Gonzalez Cayetano
Published: August 2017

Using transgenic RNAi technology, we have screened over 4000 genes to identify targets to inhibit malignant growth caused by the loss of function oflethal(3)malignant brain tumourinDrosophila in vivo. We have identified 131 targets, which belong to a wide range of gene ontologies. Most of these target genes are not significantly overexpressed in mbt tumours hence showing that, rather counterintuitively, tumour-linked overexpression is not a good predictor of functional requirement. Moreover, we have found that most of the genes upregulated in mbt tumours remain overexpressed in tumour-suppressed double-mutant conditions, hence revealing that most of the tumour transcriptome signature is not necessarily correlated with malignant growth. One of the identified target genes ismeiotic W68(mei-W68), theDrosophilaorthologue of the human cancer/testis geneSporulation-specific protein 11(SPO11), the enzyme that catalyses the formation of meiotic double-strand breaks. We show thatDrosophila mei-W68/SPO11drives oncogenesis by causing DNA damage in a somatic tissue, hence providing the first instance in which aSPO11orthologue is unequivocally shown to have a pro-tumoural role. Altogether, the results from this screen point to the possibility of investigating the function of human cancer relevant genes in a tractable experimental model organism likeDrosophila.
Effective potentials in nonlinear polycrystals and quadrature formulae
Authors: Michel Jean-Claude , Suquet Pierre
Published: August 2017

This study presents a family of estimates for effective potentials in nonlinear polycrystals. Noting that these potentials are given as averages, several quadrature formulae are investigated to express these integrals of nonlinear functions of local fields in terms of the moments of these fields. Two of these quadrature formulae reduce to known schemes, including a recent proposition (Ponte Castañeda 2015
Proc. R. Soc. A
471
, 20150665 (
doi:10.1098/rspa.2015.0665
)) obtained by completely different means. Other formulae are also reviewed that make use of statistical information on the fields beyond their first and second moments. These quadrature formulae are applied to the estimation of effective potentials in polycrystals governed by two potentials, by means of a reduced-order model proposed by the authors (non-uniform transformation field analysis). It is shown how the quadrature formulae improve on the tangent second-order approximation in porous crystals at high stress triaxiality. It is found that, in order to retrieve a satisfactory accuracy for highly nonlinear porous crystals under high stress triaxiality, a quadrature formula of higher order is required.
Quaternary vertebrate faunas from Sumba, Indonesia: implications for Wallacean biogeography and evolution
Authors: Turvey Samuel T. , Crees Jennifer J. , Hansford James , Jeffree Timothy E. , Crumpton Nick , Kurniawan Iwan , Setiyabudi Erick , Guillerme Thomas , Paranggarimu Umbu , Dosseto Anthony , van den Bergh Gerrit D.
Published: August 2017

Historical patterns of diversity, biogeography and faunal turnover remain poorly understood for Wallacea, the biologically and geologically complex island region between the Asian and Australian continental shelves. A distinctive Quaternary vertebrate fauna containing the small-bodied homininHomo floresiensis, pygmyStegodonproboscideans, varanids and giant murids has been described from Flores, but Quaternary faunas are poorly known from most other Lesser Sunda Islands. We report the discovery of extensive new fossil vertebrate collections from Pleistocene and Holocene deposits on Sumba, a large Wallacean island situated less than 50 km south of Flores. A fossil assemblage recovered from a Pleistocene deposit at Lewapaku in the interior highlands of Sumba, which may be close to 1 million years old, contains a series of skeletal elements of a very smallStegodonreferable toS. sumbaensis, a tooth attributable toVaranus komodoensis, and fragmentary remains of unidentified giant murids. Holocene cave deposits at Mahaniwa dated to approximately 2000–3500 BP yielded extensive material of two new genera of endemic large-bodied murids, as well as fossils of an extinct frugivorous varanid. This new baseline for reconstructing Wallacean faunal histories reveals that Sumba's Quaternary vertebrate fauna, although phylogenetically distinctive, was comparable in diversity and composition to the Quaternary fauna of Flores, suggesting that similar assemblages may have characterized Quaternary terrestrial ecosystems on many or all of the larger Lesser Sunda Islands.
Social transmission of information about a mutualist via trophallaxis in ant colonies
Authors: Hayashi Masayuki , Hojo Masaru K. , Nomura Masashi , Tsuji Kazuki
Published: August 2017

Partner discrimination is crucial in mutualistic interactions between organisms to counteract cheating by the partner. Trophobiosis between ants and aphids is a model system of such mutualistic interaction. To establish and maintain the mutualistic association, ants need to correctly discriminate mutualistic aphids. However, the mechanism by which ants recognize aphids as their partners is poorly understood, despite its ecological and evolutionary importance. Here, we show for the first time the evidence that interaction with nest-mates that have tended aphids (
Aphis craccivora
) allows ants (
Tetramorium tsushimae
) to learn to recognize the aphid species as their partner. When ants had previously tended aphids, they moderated their aggressiveness towards aphids. More importantly, ants that had interacted with aphid-experienced nest-mates also reduced their aggressiveness towards aphids, even though they had never directly experienced them, indicating that aphid information was transmitted from aphid-experienced ants to inexperienced ants. Furthermore, inhibition of mouth-to-mouth contact (trophallaxis) from aphid-experienced ants to inexperienced ants by providing the inexperienced ants with artificial honeydew solution caused the inexperienced ants to become aggressive towards aphids. These results, with further supporting data, strongly suggest that ants transfer information on their mutualists during trophallactic interactions.
Socially cued seminal fluid gene expression mediates responses in ejaculate quality to sperm competition risk
Authors: Simmons Leigh W. , Lovegrove Maxine
Published: August 2017

There is considerable evidence that males will increase the number of sperm ejaculated in response to sperm competition risk. However, whether they have the capacity to adjust seminal fluid components of the ejaculate has received less attention. Male crickets (Teleogryllus oceanicus) have been shown to adjust the viability of sperm in their ejaculate in response to sperm competition risk. Here we show that socially mediated plasticity in sperm viability is probably due, at least in part, to male adjustments in the protein composition of the seminal fluid. Seven seminal fluid protein genes were found to have an increased expression in males exposed to rival calls. Increased expression of these genes was correlated with increased sperm viability in whole ejaculates, and gene knockdown confirmed that at least one of these proteins promotes sperm viability. Our results lend support for recent theoretical models that predict complex responses in male allocation to seminal fluid composition in response to sperm competition risk.
Mechanical mapping of spinal cord development and repair in living zebrafish larvae using Brillouin microscopy
Authors: Schlüßler Raimund , Möllmert Stephanie , Abuhattum Shada , Cojoc Gheorghe , Müller Paul , Kim Kyoohyun , Möckel Conrad , Zimmermann Conrad , Czarske Jürgen , Guck Jochen
Published: August 2017

The mechanical properties of biological tissues are increasingly recognized as important factors in developmental and pathological processes. Most existing mechanical measurement techniques either necessitate destruction of the tissue for access or provide insufficient spatial resolution. Here, we show for the first time a systematic application of confocal Brillouin microscopy to quantitatively map the mechanical properties of spinal cord tissues during biologically relevant processes in a contact-free and non-destructive manner. Living zebrafish larvae were mechanically imaged in all anatomical planes, during development and after spinal cord injury. These experiments revealed that Brillouin microscopy is capable of detecting the mechanical properties of distinct anatomical structures without interfering with the animal’s natural development. The Brillouin shift within the spinal cord increased during development and transiently decreased during the repair processes following spinal cord transection. By taking into account the refractive index distribution, we explicitly determined the apparent longitudinal modulus and viscosity of different larval zebrafish tissues. Importantly, mechanical properties differed between tissuesin situand in excised slices. The presented work constitutes the first step towards anin vivoassessment of spinal cord tissue mechanics during regeneration, provides a methodical basis to identify key determinants of mechanical tissue properties and allows to test their relative importance in combination with biochemical and genetic factors during developmental and regenerative processes.
BITE: an R package for biodiversity analyses
Authors: Milanesi Marco , Capomaccio Stefano , Vajana Elia , Bomba Lorenzo , Garcia José Fernando , Ajmone-Marsan Paolo , Colli Licia
Published: August 2017

Nowadays, molecular data analyses for biodiversity studies often require advanced bioinformatics skills, preventing many life scientists from analyzing their own data autonomously. BITE R package provides complete and user-friendly functions to handle SNP data and third-party software results (i.e. Admixture, TreeMix), facilitating their visualization, interpretation and use. Furthermore, BITE implements additional useful procedures, such as representative sampling and bootstrap for TreeMix, filling the gap in existing biodiversity data analysis tools.

Availability:

https://github.com/marcomilanesi/BITE
Mitochondrial sirtuinssir-2.2andsir-2.3regulate lifespan in C.elegans
Authors: Chang Sarah M. , McReynolds Melanie R. , Hanna-Rose Wendy
Published: August 2017

Mitochondrial sirtuins regulate biochemical pathways and are emerging drug targets for metabolic and age-related diseases such as cancer, diabetes, and neurodegeneration. Yet, their functions remain unclear. Here, we uncover a novel physiological role for theC. elegansmitochondrial sirtuins,sir-2.2andsir-2.3,in lifespan regulation. Using a genetic approach, we demonstrate thatsir-2.2andsir-2.3mutants live 28-30% longer than controls when fed the normal lab diet ofE. coliOP50. Interestingly, this effect is diet specific and is not observed when animals are fed the strain HT115, which is typically used for RNAi experiments. While decreased consumption of food is a known mechanism for lifespan extension, this does not account for the increased lifespan in the mitochondrial sirtuin mutants.sir-2.2andsir-2.3mutants display altered expression of genes involved in oxidative stress response, including increased expression of the mitochondrial superoxide dismutasesod-3and decreased levels of catalasesctl-1andctl-2. Like their extended lifespan phenotype, these alterations in oxidative stress gene expression are diet dependent. The mitochondrial sirtuin mutants are more resistant to the lifespan extending effects of low levels of superoxide, suggesting that their increased lifespan involves a hormetic response. Our data suggest thatsir-2.2andsir-2.3are not completely redundant in function and may possess overlapping yet distinct mechanisms for regulating oxidative stress response and lifespan.
Covert Shift of Attention Modulates the Value Encoding in the Orbitofrontal Cortex
Authors: Xie Yang , Nie Chechang , Yang Tianming
Published: August 2017

During value-based decision making, we often evaluate the value of each option sequentially by shifting our attention, even when the options are presented simultaneously. The orbitofrontal cortex (OFC) has been suggested to encode value during value-based decision making. Yet it is not known how its activity is modulated by attention shifts. We investigated this question by employing a passive viewing task that allowed us to disentangle effects of attention, value, choice and eye movement. We found that the attention modulated OFC activity through a winner-take-all mechanism. When we attracted the monkeys’ attention covertly, the OFC neuronal activity reflected the reward value of the newly attended cue. The shift of attention could be explained by a normalization model. Our results strongly argue for the hypothesis that the OFC neuronal activity represents the value of covertly attended item. They provide important insights toward the neural mechanism of value-based decision making.
Network structure of the human musculoskeletal system shapes neural interactions on multiple timescales
Authors: Kerkman Jennifer N. , Daffertshofer Andreas , Gollo Leonardo L. , Breakspear Michael , Boonstra Tjeerd W.
Published: August 2017

Human motor control requires the coordination of muscle activity under the anatomical constraints imposed by the musculoskeletal system. Interactions within the central nervous system are fundamental to motor coordination, but the principles governing functional integration remain poorly understood. We used network analysis to investigate the relationship between anatomical and functional connectivity amongst 36 muscles. Anatomical networks were defined by the physical connections between muscles and functional networks were based on intermuscular coherence assessed during postural tasks. We found a modular structure of functional networks that was strongly shaped by the anatomical constraints of the musculoskeletal system. Changes in postural tasks were associated with a frequency-dependent reconfiguration of the coupling between functional modules. These findings reveal distinct patterns of functional interactions between muscles involved in flexibly organising muscle activity during postural control. Our network approach to the motor system offers a unique window into the neural circuitry driving the musculoskeletal system.
Peptide Pattern Recognition for high-throughput protein sequence analysis and clustering
Authors: Busk Peter Kamp
Published: August 2017

Large collections of protein sequences with divergent sequences are tedious to analyze for understanding their phylogenetic or structure-function relation. Peptide Pattern Recognition is an algorithm that was developed to facilitate this task but the previous version does only allow a limited number of sequences as input.

I implemented Peptide Pattern Recognition as a multithread software designed to handle large numbers of sequences and perform analysis in a reasonable time frame. Benchmarking showed that the new implementation of Peptide Pattern Recognition is twenty times faster than the previous implementation on a small protein collection with 673 MAP kinase sequences. In addition, the new implementation could analyze a large protein collection with 48,570 Glycosyl Transferase family 20 sequences without reaching its upper limit on a desktop computer.

Peptide Pattern Recognition is a useful software for providing comprehensive groups of related sequences from large protein sequence collections.
Topology and cooperative stability: the two master regulators of protein half-life in the cell
Authors: Mallik Saurav , Kundu Sudip
Published: August 2017

In a quest for finding additional structural constraints, apart from disordered segments, regulating protein half-life in the cell (and during evolution), here we recognize and assess the influence of native topology of biological proteins and their sequestration into multimeric complexes. Native topology acts as a molecular marker of protein’s mechanical resistance and consequently captures their half-life variations on genome-scale, irrespective of the enormous sequence, structural and functional diversity of the proteins. Cooperative stability (slower degradation upon sequestration into complexes) is a master regulator of oligomeric protein half-life that involves at least three mechanisms. (i) Association with multiple complexes results longer protein half-life; (ii) hierarchy of complex self-assembly involves short-living proteins binding late in the assembly order and (iii) binding with larger buried surface area leads to slower subunit dissociation and thereby longer half-life. Altered half-lives of paralog proteins refer to their structural divergence and oligomerization with non-identical set of complexes.
Taxon sampling unequally affects individual nodes in a phylogenetic tree: consequences for model gene tree construction in SwissTree
Authors: Boeckmann Brigitte , Dylus David , Moretti Sebastien , Altenhoff Adrian , Train Clément-Marie , Kriventseva Evgenia , Bougueleret Lydie , Xenarios Ioannis , Privman Eyal , Gabaldon Toni , Dessimoz Christophe
Published: August 2017

Medium to large phylogenetic gene trees constructed from datasets of different species density and taxonomic range are rarely topologically consistent because of missing phylogenetic signal, non-phylogenetic signal and error. In this study, we first use simulations to show that taxon sampling unequally affects nodes in a gene tree, which likely contributes to controversial conclusions from taxon sampling experiments and contradicting species phylogenies such as for the boreoeutherians. Hence, because it is unlikely that a large gene tree can be reconstructed correctly based on a single optimized dataset, we take a two-step approach for the construction of model gene trees. First, stable and unstable clades are identified by comparing phylogenetic trees inferred from multiple datasets and data types (nucleotide, amino acid, codon) from the same gene family. Subsequently, data subsets are optimized for the analysis of individual uncertain clades. Results are summarized in form of a model tree that illustrates the evolutionary relationship of gene loci. A case study shows how a seemingly complex gene phylogeny becomes increasingly consistent with the reference species tree by attentive taxon sampling and subtree analysis. The procedure is progressively introduced to SwissTree (http://swisstree.vital-it.ch), a resource of high confidence model gene (locus) trees. Finally we demonstrate the usefulness of SwissTree for orthology benchmarking.
The impact of persistent bacterial bronchitis on the pulmonary microbiome of children
Authors: Cuthbertson Leah , Craven Vanessa , Bingle Lynne , Cookson William O.C.M. , Everard Mark L. , Moffatt Miriam F.
Published: August 2017

Abstract

Persistent bacterial bronchitis is a leading cause of chronic wet cough in young children. This study aimed to characterise the respiratory bacterial microbiota of healthy children and to assess the impact of the changes associated with the development of persistent bacterial bronchitis.

Blind, protected brushings were obtained from 20 healthy controls and 24 children with persistent bacterial bronchitis, with an additional directed sample obtained from persistent bacterial bronchitis patients. DNA was extracted, quantified using a 16S rRNA gene quantitative PCR assay prior to microbial community analysis by 16S rRNA gene sequencing.

No significant difference in bacterial diversity or community composition (R2= 0.01,P= 0.36) was observed between paired blind and non-blind brushes, showing that blind brushings are a valid means of accessing the airway microbiota. This has important implications for collecting lower respiratory samples from healthy children. A significant decrease in bacterial diversity (P< 0.001) and change in community composition (R2= 0.08,P= 0.004) was observed between controls and patients. Bacterial communities within patients with PBB were dominated byProteobacteria, and indicator species analysis showed thatHaemophilusandNeisseriawere significantly associated with the patient group. In 15 (52.9%) cases the dominant organism by sequencing was not identified by standard routine clinical culture.

The bacteria present in the lungs of patients with persistent bacterial bronchitis were less diverse in terms of richness and evenness. The results validate the clinical diagnosis, and suggest that more attention to bacterial communities in children with chronic cough may lead to more rapid recognition of this condition with earlier treatment and reduction in disease burden.
Single-shot super-resolution total internal reflection fluorescence microscopy
Authors: Guo Min , Chandris Panagiotis , Giannini John Paul , Trexler Adam J. , Fischer Robert , Chen Jiji , Vishwasrao Harshad D. , Rey-Suarez Ivan , Wu Yicong , Waterman Clare M. , Patterson George H. , Upadhyaya Arpita , Taraska Justin , Shroff Hari
Published: August 2017

We demonstrate a simple method for combining instant structured illumination microscopy (SIM) with total internal reflection fluorescence microscopy (TIRF), doubling the spatial resolution of TIRF (down to 115 +/-13 nm) and enabling imaging frame rates up to 100 Hz over hundreds of time points. We apply instant TIRF-SIM to multiple live samples, achieving rapid, high contrast super-resolution imaging in close proximity to the coverslip surface.