bluuebunny/crossref_metadata_2025 huggingface dataset:
Host–parasite oscillation dynamics and evolution in a compartmentalized RNA replication system
Authors: Bansho Yohsuke , Furubayashi Taro , Ichihashi Norikazu , Yomo Tetsuya
Published: March 2016

Significance

We reconstituted a simple in vitro molecular ecosystem using two self-replicating RNA molecules. The host RNA species produces an RNA-dependent RNA polymerase for their replication, and the parasitic RNA relies on the same enzyme for its replication as well. We found that only when compartmentalized into microscale droplets did the ecosystem show a typical host–parasite oscillatory dynamics. Furthermore, after a long cultivation, the ecosystem evolved to allow the coexistence of the two species. These results demonstrate that cell-size compartmentalization is essential for the ecological dynamics and evolution of host and parasite species.
Stokes trap for multiplexed particle manipulation and assembly using fluidics
Authors: Shenoy Anish , Rao Christopher V. , Schroeder Charles M.
Published: March 2016

Significance

In recent years, techniques for trapping and manipulating small particles and single molecules have catalyzed major advances in several fields of science. Here, we describe a new method for confining, manipulating, and assembling multiple particles in free solution using the sole action of fluid flow. The Stokes trap provides a fundamentally new method for particle manipulation and assembly using a simple microfluidic device and nonlinear feedback control in the absence of optical, electric, or magnetic fields. This method holds strong potential to enable fundamental studies in soft materials, colloidal science, and biophysics.
Markedly enhanced absorption and direct radiative forcing of black carbon under polluted urban environments
Authors: Peng Jianfei , Hu Min , Guo Song , Du Zhuofei , Zheng Jing , Shang Dongjie , Levy Zamora Misti , Zeng Limin , Shao Min , Wu Yu-Sheng , Zheng Jun , Wang Yuan , Glen Crystal R. , Collins Donald R. , Molina Mario J. , Zhang Renyi
Published: March 2016

Significance

Although black carbon (BC) represents a key short-lived climate forcer, its direct radiative forcing remains highly uncertain. The available results from available studies of absorption enhancement of BC particles during atmospheric aging are conflicting. Using a novel environmental chamber method, we have, for the first time to our knowledge, quantified the aging and variation in the optical properties of BC particles under ambient urban conditions representative of developed and developing countries. Our results indicate that BC under polluted urban environments could contribute significantly to both pollution development and large positive radiative forcing, implying that reduction of BC emissions under polluted environments achieves a cobenefit in simultaneously controlling air pollution and protecting climate, especially for developing countries.
Surface force measurements and simulations of mussel-derived peptide adhesives on wet organic surfaces
Authors: Levine Zachary A. , Rapp Michael V. , Wei Wei , Mullen Ryan Gotchy , Wu Chun , Zerze Gül H. , Mittal Jeetain , Waite J. Herbert , Israelachvili Jacob N. , Shea Joan-Emma
Published: March 2016

Significance

The need for bio-inspired wet adhesives has significantly increased in the past few decades (e.g., for dental and medical transplants, coronary artery coatings, cell encapsulants, etc.). However, the molecular basis behind catechol-facilitated adhesion to organic surfaces remains unclear, thus hindering synthesis and optimization of novel underwater adhesives. The present combined experimental and theoretical study reconciles bioadhesion measurements of novel catechol-containing peptides to self-assembled monolayers (SAMs) with all-atom molecular dynamics simulations, yielding a comprehensive framework that explicitly identifies the basis for underwater adhesion. Simulations and surface forces apparatus measurements agree with one another, and both approaches show strong peptide adhesion to hydrophobic SAMs, and weak peptide adhesion to hydrophilic SAMs, providing a starting point for the development of next-generation underwater glues.
Interventionist applied conversation analysis
Authors: Tuccio William A. , Esser David A. , Driscoll Gillian , McAndrew Ian R. , Smith MaryJo O.
Published: March 2016

Pragmatic language competence plays a central role in how aviation flight crews perform crew resource management (CRM); this competence significantly affects aviation safety. This paper contributes to existing literature on interventionist applications of conversation analysis (CA) by defining and evaluating a novel collaborative transcription and repair based learning (CTRBL) method for aviation CRM learning. CTRBL was evaluated using a quantitative quasi-­experimental repeated-measure design with 42 novice, university pilots. Results support that CTRBL is an effective, low-resource CRM learning method that will benefit from exploratory applications and further study in pragmatics, aviation, and other sociotechnical domains.
The views in this article were the result of independent research of the authors. Views herein do not necessarily represent the views of the National Transportation Safety Board (NTSB) or the United States.
Branding the nation
Authors: Del Percio Alfonso
Published: March 2016

This paper discusses how Switzerland is branded by the Swiss state under late capitalism. Drawing on discursive data collected in the framework of a research project investigating the international promotion of Switzerland, I particularly focus on how multilingualism and cultural diversity are constructed by the Swiss government as a capital belonging to Switzerland and its history and on how and why this imagined historical capital is reframed in promotional terms. In doing so, I question the function of the historicity of Swiss multilingualism and cultural diversity in nation branding practices and analyze the logics causing specific tokens of multilingualism and cultural diversity to emerge as desirable promotional features. Finally, I research how the promotional investment in Swiss multilingualism and cultural diversity affects the status and value of its historical capital and how this has consequences for what can be said (or not) about Switzerland and its history.
PI3K regulates BMAL1/CLOCK-mediated circadian transcription from the Dbp promoter
Authors: Morishita Yoshikazu , Miura Daiki , Kida Satoshi
Published: March 2016

The circadian rhythm generated by circadian clock underlies a molecular mechanism of rhythmic transcriptional regulation by transcription factor BMAL1/CLOCK. Importantly, the circadian clock is coordinated by exogenous cues to accommodate to changes in the external environment. However, the molecular mechanisms by which intracellular-signaling pathways mediate the adjustments of the circadian transcriptional rhythms remain unclear. In this study, we found that pharmacological inhibition or shRNA-mediated knockdown of phosphatidylinositol 3-kinase (PI3K) blocked upregulation of Dbp mRNA induced by serum shock in NIH 3T3 cells. Moreover, the inhibition of PI3K significantly reduced the promoter activity of the Dbp gene, as well as decreased the recruitment of BMAL1/CLOCK to the E-box in the Dbp promoter. Interestingly, the inhibition of PI3K blocked heterodimerization of BMAL1 and CLOCK. Our findings suggest that PI3K signaling plays a modulatory role in the regulation of the transcriptional rhythm of the Dbp gene by targeting BMAL1 and CLOCK.
Screening of biologically active monosaccharides: growth inhibitory effects of d-allose, d-talose, and l-idose against the nematode Caenorhabditis elegans
Authors: Sakoguchi Hirofumi , Yoshihara Akihide , Izumori Ken , Sato Masashi
Published: March 2016

We compared the growth inhibitory effects of all aldohexose stereoisomers against the model animal Caenorhabditis elegans. Among the tested compounds, the rare sugars d-allose (d-All), d-talose (d-Tal), and l-idose (l-Ido) showed considerable growth inhibition under both monoxenic and axenic culture conditions. 6-Deoxy-d-All had no effect on growth, which suggests that C6-phosphorylation by hexokinase is essential for inhibition by d-All.
Genetic basis of hyperuricaemia and gout
Authors: Dalbeth Nicola
Published: March 2016

Owing to the different means of ascertaining prevalence between studies, it is difficult to compare prevalence across countries. Country-specific studies that collect data with the same methodology show that the prevalence of gout is increasing. Factors that influence the prevalence of gout are inherited genetic factors and environmental exposures. Some foods that increase serum urate levels and trigger acute gouty arthritis are risk factors—red meat and beer are the best established, but seafood and sugar-sweetened beverages also increase serum urate levels and are strong anecdotal triggers of flares. Diuretics associate with increased serum urate and the risk of gout. Hyperuricaemia and gout are co-morbid with other metabolic conditions, the most prominent being heart disease, renal disease, and type 2 diabetes. Collectively the evidence does not suggest that increased serum urate levels are clinically detrimental, except in gout, nephrolithiasis, and perhaps progression of heart and kidney disease.
Imaging in gout
Authors: Dalbeth Nicola
Published: March 2016

Identification of monosodium urate (MSU) crystals is the gold standard for gout diagnosis. Serum urate is an important test for both gout diagnosis and effective management. For all people with gout on urate-lowering therapy, the target urate concentration is less than 0.36 mmol/L (6 mg/dL). Blood tests may also assist with screening for co-morbid conditions in gout. Spot urine tests may assist in determining the basis for hyperuricaemia in people with gout. Microscopically, the tophus represents a chronic inflammatory granulomatous response to MSU crystal aggregates.
A recent strong X-ray flaring activity of 1ES 1959+650 with possibly less efficient stochastic acceleration
Authors: Kapanadze B. , Dorner D. , Vercellone S. , Romano P. , Kapanadze S. , Mdzinarishvili T.
Published: March 2016

We present an X-ray flaring activity of 1ES 1959+650 in 2015 August–2016 January, which was the most powerful and prolonged during the 10.75 yr period since the start of its monitoring with X-ray Telescope onboard Swift. A new highest historical 0.3–10 keV count rate was recorded three times that makes this object the third BL Lacertae source exceeding the level of 20 counts s−1. Along with the overall variability by a factor of 5.7, this epoch was characterized by fast X-ray flares by a factor of 2.0–3.1, accompanied with an extreme spectral variability. The source also shows a simultaneous flaring activity in the optical – UV and 0.3–100 GeV bands, although a fast γ-ray flare without significant optical – X-ray counterparts is also found. In contrast to the X-ray flares in the previous years, the stochastic acceleration seems be less important for the electrons responsible for producing X-ray emission during this flare that challenges the earlier suggestion that the electrons in the jets of TeV-detected BL Lacertae objects should undergo an efficient stochastic acceleration resulting in a lower X-ray spectral curvature.
Long-Term Effects in Models with Temporal Dependence
Authors: Williams Laron K.
Published: March 2016

A dominant trend in models with binary outcomes is to control for unmodeled duration dependence by including temporal dependence variables. A second, distinct trend is to interpret both the short- and long-term effects of explanatory variables in autoregressive models. While the first trend is nearly ubiquitous in models with binary outcomes, the second trend has yet to be applied consistently beyond models with continuous outcomes. While scholars use temporal splines and cubic polynomials to model the underlying hazard rate, they have neglected the fact that this causes the explanatory variables to have a long-term effect (LTE) by modifying the future values of the temporal dependence variables. In this article, I propose a simple technique that estimates a wide range of probabilistic LTEs in models with temporal dependence variables. These effects can range from simple LTEs for a one-time change in an explanatory variable to more complex scenarios where effects change in magnitude with time and compound across repeated events. I then replicate Clare's (2010, Ideological fractionalization and the international conflict behavior of parliamentary democracies.International Studies Quarterly54:965–87) examination of the influence of government fractionalization on conflict behavior to show that failing to interpret the results within the context of temporal dependence underestimates the total impact of fractionalization by neglecting LTEs.
Acupuncture in Menopause (AIM) study: a pragmatic, randomized controlled trial
Authors: Avis Nancy E. , Coeytaux Remy R. , Isom Scott , Prevette Kristen , Morgan Timothy
Published: March 2016

Objective:

The aim of the study was to evaluate the short and long-term effects of acupuncture on vasomotor symptoms (VMS) and quality of life-related measures.

Methods:

A total of 209 perimenopausal and postmenopausal women aged 45 to 60 years, experiencing four or more VMS per day, were recruited from the community and randomized to receive up to 20 acupuncture treatments within the first 6 months (acupuncture group) or the second 6 months (waitlist control group) of the 12-month study period. The primary outcome was mean daily frequency of VMS. Secondary outcomes were VMS interference with daily life, sleep quality, depressive symptoms, somatic and other symptoms, anxiety, and quality of life.

Results:

The VMS frequency declined by 36.7% at 6 months in the acupuncture group and increased by 6.0% in the control group (P < 0.001 for between-group comparison). At 12 months, the reduction from baseline in the acupuncture group was 29.4% (P < 0.001 for within-group comparison from baseline to 12 months), suggesting that the reduction was largely maintained after treatment. Statistically significant clinical improvement was observed after three acupuncture treatments, and maximal clinical effects occurred after a median of eight treatments. Persistent improvements were seen in many quality of life-related outcomes in the acupuncture group relative to the control group.

Conclusions:

We found that a course of acupuncture treatments was associated with significant reduction in VMS, and several quality-of-life measures, compared with no acupuncture, and that clinical benefit persisted for at least 6 months beyond the end of treatment.
Flexible parametric survival models built on age-specific antimüllerian hormone percentiles are better predictors of menopause
Authors: Ramezani Tehrani Fahimeh , Mansournia Mohammad Ali , Solaymani-Dodaran Masoud , Steyerberg Ewout , Azizi Fereidoun
Published: March 2016

Objective:

This study aimed to improve existing prediction models for age at menopause.

Methods:

We identified all reproductive aged women with regular menstrual cycles who met our eligibility criteria (n = 1,015) in the Tehran Lipid and Glucose Study—an ongoing population-based cohort study initiated in 1998. Participants were examined every 3 years and their reproductive histories were recorded. Blood levels of antimüllerian hormone (AMH) were measured at the time of recruitment. Age at menopause was estimated based on serum concentrations of AMH using flexible parametric survival models. The optimum model was selected according to Akaike Information Criteria and the realness of the range of predicted median menopause age.

Results:

We followed study participants for a median of 9.8 years during which 277 women reached menopause and found that a spline-based proportional odds model including age-specific AMH percentiles as the covariate performed well in terms of statistical criteria and provided the most clinically relevant and realistic predictions. The range of predicted median age at menopause for this model was 47.1 to 55.9 years. For those who reached menopause, the median of the absolute mean difference between actual and predicted age at menopause was 1.9 years (interquartile range 2.9).

Conclusions:

The model including the age-specific AMH percentiles as the covariate and using proportional odds as its covariate metrics meets all the statistical criteria for the best model and provides the most clinically relevant and realistic predictions for age at menopause for reproductive-aged women.
Risk of Stroke Among Older Medicare Antidepressant Users With Traumatic Brain Injury
Authors: Khokhar Bilal , Simoni-Wastila Linda , Albrecht Jennifer S.
Published: March 2016

Objective:

To estimate the risk of stroke associated with new antidepressant use among older adults with traumatic brain injury (TBI).

Participants:

A total of 64 214 Medicare beneficiaries aged 65 years or older meeting inclusion criteria and hospitalized with a TBI during 2006 to 2010.

Design:

New user design. Generalized estimating equations were used to estimate the relative risks (RRs) of stroke.

Main Measures:

Primary exposure was new antidepressant use following TBI identified through Medicare part D claims. The primary outcome was stroke following TBI. Ischemic and hemorrhagic strokes were secondary outcomes.

Results:

A total of 20 859 (32%) beneficiaries used an antidepressant at least once following TBI. Selective serotonin reuptake inhibitors accounted for the majority of antidepressant use. Selective serotonin reuptake inhibitor use was associated with an increased risk of hemorrhagic stroke (RR, 1.26; 95% confidence interval [CI], 1.06-1.50) but not ischemic stroke (RR, 1.04; 95% CI, 0.94-1.15). The selective serotonin reuptake inhibitors escitalopram (RR, 1.33; 95% CI, 1.02-1.74) and sertraline (RR, 1.46; 95% CI, 1.10-1.94) were associated with an increase in the risk of hemorrhagic stroke.

Conclusion:

Findings from this study will aid prescribers in choosing appropriate antidepressants to treat depression in older adults with TBI.
Renal Splenosis: Renal Mass Biopsy Diagnosis of a Tumor Clinically Mimicking Renal Cell Carcinoma
Authors: Williamson Sean R.
Published: March 2016

Renal mass biopsy is increasingly used to guide conservative tumor management, placing increasing importance on pathologists’ ability to diagnose small tumor samples. A 66-year-old man with a history of prior splenectomy for trauma presented for urologic evaluation after identification of a left 5.8 cm renal mass. Partial envelopment of the mass by renal parenchyma and equivocal enhancement on computed tomography raised concern for renal cell carcinoma. Needle-core biopsy revealed blood, subtle vasculature, few aggregates of lymphocytes, and rare renal tubules. Immunohistochemical staining revealed CD8-positive sinusoids but negative reactivity for epithelial antigens (PAX8, keratin, epithelial membrane antigen, carbonic anhydrase IX), supporting diagnosis of renal splenosis. Renal splenosis is a rare phenomenon that can form a sizeable intrarenal mass, mimicking renal cell carcinoma. Pathologists’ awareness of this uncommon occurrence may avoid unnecessary surgery. CD8-positive sinusoids and negative epithelial markers are helpful confirmatory features in the biopsy setting.
Application of MDM2 Fluorescence In Situ Hybridization and Immunohistochemistry in Distinguishing Dedifferentiated Liposarcoma From Other High-grade Sarcomas
Authors: Song Min Jeong , Cho Kyung-Ja , Lee Jong-Seok , Song Joon Seon
Published: March 2016

Distinguishing dedifferentiated liposarcoma (DDLPS) from other high-grade spindle and pleomorphic sarcomas is important because of better prognosis in case of DDLPS. MDM2 amplification, a genetic abnormality of well-differentiated liposarcoma, is known to be present not only in DDLPS, but also in some other sarcomas. To differentiate DDLPS, we investigated MDM2 amplification and expression in high-grade spindle sarcomas. Eighty-five cases of nonlipogenic high-grade sarcomas, diagnosed between 2008 and 2011, were investigated. Tissue microarray, immunohistochemistry, and fluorescence in situ hybridization for MDM2 were performed. Forty-one of 85 cases (48.2%) showed MDM2 amplification and expression. Cases of MDM2 amplification were reclassified based on histology, immunophenotype, and clinical data. Thirty-nine of 41 cases, including those originally diagnosed as DDLPS (n=30), undifferentiated pleomorphic sarcoma (n=7), myxofibrosarcoma (n=1), and pleomorphic liposarcoma (n=1) could be reclassified as DDLPS. In addition, MDM2 immunohistochemistry and MDM2 fluorescence in situ hybridization showed an excellent correlation (P<0.001, sensitivity 92.7%, specificity 100%). MDM2 amplification and expression are potentially very useful in distinguishing between DDLPS and other undifferentiated high-grade spindle and pleomorphic sarcomas, even though a few other sarcomas also showed MDM2 amplification and expression.
Improvement of Fat Graft Survival with Autologous Bone Marrow Aspirate and Bone Marrow Concentrate: A One-Step Method
Authors: Xing Wenshan , Mu Dali , Wang Qian , Fu Su , Xin Minqiang , Luan Jie
Published: March 2016

Background:

Stem cells have proven to be beneficial to fat graft survival, but a one-step method of cell-assisted lipotransfer is still missing. In the present work, the authors improved the fat graft survival using bone marrow aspirate and bone marrow concentrate, to ensure that both liposuction and cell-assisted lipotransfer were included in the same procedure.

Methods:

Bone marrow aspirate was collected from the iliac crest of the rabbits. Bone marrow concentrate was obtained using density gradient centrifugation and labeled with PKH26 fluorescent cell linker. Rabbits were divided into three groups: group A, bone marrow aspirate; group B, bone marrow concentrate; and group C, phosphate-buffered saline buffer as a blank control. The implanted mixture contained 1.5 ml of adipose granule and 1 ml of bone marrow aspirate or bone marrow concentrate. The rabbits were subjected to fluorescence imaging in vivo at four time points. Grafts were harvested and analyzed at 4 weeks and 12 weeks after fat grafting.

Results:

Bone marrow cell fluorescence signals were observed in the rabbits’ injection regions during a follow-up of 12 weeks. The fat grafts of group A and B showed a better weight and volume retention, living quality, adipocyte viability, and angiogenesis after transplantation. The results of living tissue imaging also showed that the implanted bone marrow cells could contribute to fat graft survival by multilineage differentiation and could also contribute to adipogenesis and angiogenesis.

Conclusion:

Both bone marrow aspirate and bone marrow concentrate improved the survival and angiogenesis of grafted fat tissue.
A Comparative Assessment of Three Formulations of Botulinum Toxin Type A for Facial Rhytides: A Systematic Review with Meta-Analyses
Authors: Bonaparte James P. , Ellis David , Quinn Jason G. , Rabski Jessica , Hutton Brian
Published: March 2016

Background:

Three formulations of botulinum toxin are available for facial rhytides. It is unclear which formulation offers the greatest balance of benefits and harms. The objective of this study was to conduct a systematic review with meta-analyses to compare formulations of botulinum toxin for reduction of facial rhytides at the glabella.

Methods:

The authors’ protocol was registered with the International Prospective Register of Systematic Reviews (CRD4201200377). A systematic literature search was performed identifying double-blind studies. The authors assessed 1-, 3-, and 4-month follow-up. The authors performed pairwise meta-analyses using random effects models to compare response rates among the three botulinum formulations and a network meta-analysis.

Results:

A total of 18 studies (3082 patients) were included. At 30-, 90-, and 120-day follow-up, all medications with available data showed statistically significantly increased treatment response versus placebo. Only high-dose onabotulinum toxin (compared to standard-dose onabotulinum toxin) offered additional benefit at 30 days. Exploratory analysis using network meta-analysis mostly suggested insufficient evidence of incremental benefits when comparing specific formulations.

Conclusions:

Evidence supporting benefits versus placebo of the different formulations was clear over time. Comparisons between active formulations were rare and typically based on single trials of small to moderate sample size. The data suggest some gains with high-dose onabotulinum toxin (relative to standard dose), whereas exploratory indirect comparisons between active formulations were largely associated with inconclusive findings. Future studies should undertake head-to-head comparisons of the different formulations and ensure longer follow-up to best inform the accumulating evidence base.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
Transcription Profile in Sporadic Multiple Symmetric Lipomatosis Reveals Differential Expression at the Level of Adipose Tissue–Derived Stem Cells
Authors: Prantl Lukas , Schreml Julia , Gehmert Sebastian , Klein Silvan , Bai Xiaowen , Zeitler Katharina , Schreml Stephan , Alt Eckhard , Gehmert Sanga , Felthaus Oliver
Published: March 2016

Background:

The cause of the rare fat distribution disorder multiple symmetric lipomatosis is unknown. Independent reports suggest a higher proliferative activity, hormone resistance, and involvement of mitochondrial function in the disease.

Methods:

The authors performed morphologic comparison of affected and unaffected tissues in five unrelated patients and generated adipose-derived stem cell cultures from the tissue samples and characterized them as a possible cellular model of multiple symmetric lipomatosis evolution. The authors investigated proliferative activity and the expression of genes relevant to disease processes.

Results:

There was no difference in the morphologic appearance and the surface marker profile. Stem cells from lipomatous tissue showed significantly higher proliferative activity. Polymerase chain reaction arrays showed marked changes in genes associated with proliferation, hormonal regulation, and mitochondria. The authors show that multiple symmetric lipomatosis tissue is morphologically and histologically different from regular subcutaneous fat.

Conclusions:

This study indicates an involvement of mesenchymal stem cells in the pathogenesis of multiple symmetric lipomatosis and that the evolution of multiple symmetric lipomatosis tissue is a process driven by an inherent defect of the respective cell clone(s). Further molecular genetics and functional analysis will be required to unravel the pathogenetic mechanism underlying the derailment in fat cell metabolism and proliferation. Here, the authors show for the first time that adipose-derived stem cells exhibit many characteristics previously described for native multiple symmetric lipomatosis fat tissue and propose that they are therefore an excellent tool for further functional investigations in multiple symmetric lipomatosis and other disorders of the fat tissue.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, V.
Ibuprofen May Not Increase Bleeding Risk in Plastic Surgery: A Systematic Review and Meta-Analysis
Authors: Kelley Brian P. , Bennett Katelyn G. , Chung Kevin C. , Kozlow Jeffrey H.
Published: March 2016

Background:

Nonsteroidal antiinflammatory drugs such as ibuprofen are common medications with multiple useful effects, including pain relief and reduction of inflammation. However, surgeons commonly withhold all nonsteroidal antiinflammatory drugs perioperatively because of bleeding concerns. However, not all nonsteroidal antiinflammatory drugs irreversibly block platelet function. The authors hypothesized that the use of ibuprofen would have no effect on postoperative bleeding in plastic surgery patients.

Methods:

A literature review was performed using MEDLINE (PubMed), EMBASE, and the Cochrane Collaboration Library for primary research articles on ibuprofen and bleeding. Inclusion criteria were primary journal articles examining treatment of acute postoperative pain based on any modality. Data related to pain assessment, postoperative recovery, and complications were extracted. Bias assessment and meta-analysis were performed.

Results:

A total of 881 publications were reviewed. Four primary randomized controlled trials were selected for full analysis. Articles were of high quality by bias assessment. No significant difference was noted regarding bleeding events (p = 0.32), and pain control was noted to be equivalent.

Conclusions:

Ibuprofen is a useful medication in the setting of surgery, with multiple beneficial effects. This meta-analysis represents a small set of high-quality studies suggesting that ibuprofen provides pain control equivalent to narcotics. Importantly, ibuprofen was not associated with an increased risk of bleeding. Further large studies will be necessary to elucidate this issue further, but ibuprofen is a safe postoperative analgesic in patients undergoing common plastic surgery soft-tissue procedures.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
Away Rotations and Matching in Integrated Plastic Surgery Residency: Applicant and Program Director Perspectives
Authors: Drolet Brian C. , Brower Jonathan P. , Lifchez Scott D. , Janis Jeffrey E. , Liu Paul Y.
Published: March 2016

Background:

Although nearly all medical students pursuing integrated plastic surgery residency participate in elective rotations away from their home medical school, the value and costs of these “away” rotations have not been well studied.

Methods:

The authors surveyed all integrated plastic surgery program directors and all applicants in the 2015 National Residency Matching Program.

Results:

Forty-two program directors and 149 applicants (64 percent and 70 percent response rate, respectively) completed the survey. Applicants reported 13.7 weeks spent on plastic surgery rotations during medical school, including a mean of 9.2 weeks on away rotations. Average reported cost for away rotations was $3591 per applicant. Both applicants and program directors most commonly reported “making a good impression” (44.6 percent and 36.6 percent, respectively) or finding a “good-fit” program (27.7 percent and 48.8 percent, respectively) as the primary goal for away rotations. Almost all applicants (91.1 percent) believed an away rotation made them more competitive for matching to a program at which they rotated. Program directors ranked a strong away rotation performance as the most important residency selection criterion. Twenty-seven percent of postgraduate year–1 positions were filled by an away rotatorm and an additional 17 percent were filled by a home medical student.

Conclusions:

Away rotations appear to be mutually beneficial for applicants and programs in helping to establish a good fit between students and training programs through an extended interaction with the students, residents, and faculty. In addition, making a good impression on a senior elective rotation (home or away) may improve an applicant’s chance of matching to a residency program.
Validated Assessment Tools and Maintenance of Certification in Plastic Surgery: Current Status, Challenges, and Future Possibilities
Authors: Janis Jeffrey E. , Vedder Nicholas B. , Reid Christopher M. , Gosman Amanda , Mann Karen
Published: March 2016

Background:

The transition to the Next Accreditation System is well underway, and a shift toward competency-based assessment in the form of milestones is now the standard. A significant effort has been completed by the Plastic Surgery Milestones Working Group to develop specific milestones and assessment tools for plastic surgery training.

Methods:

The history of the development toward competency-based assessment was reviewed. Data regarding the trends and regulations associated with board certification and the role of maintenance of certification were reviewed.

Results:

The work of the Plastic Surgery Milestones Working Group has sparked interest in assessment and created an opportunity for further development. The efforts toward validating assessment tools by our colleagues working in other surgical specialties serve as a suitable roadmap for further progress. Board certification is an integral part of successful practice and should be regarded as an expectation. Despite the burdens associated with maintenance of certification, it serves a valuable function in ensuring optimal patient care and is often retrospectively seen as an important component of practice.

Conclusions:

The competency-based milestones are the new standard, and work on this new methodology of assessing plastic surgery trainees is expected to continue. Accurate assessment is critical to the pathways for board certification and maintenance of certification, which serve important roles for all parties involved in the delivery of medical care.
The Evolution of Free Vascularized Bone Transfer: A 40-Year Experience
Authors: Taylor G. Ian , Corlett Russell J. , Ashton Mark W.
Published: March 2016

Background:

The first successful free vascularized bone flap was performed on June 1, 1974 (and reported in 1975), using the fibula. This was followed by the iliac crest based on the superficial circumflex iliac artery in 1975 and then the deep circumflex iliac artery in 1978.

Methods:

A total of 384 transfers using fibula (n = 198), iliac crest (n = 180), radius (n = 4), rib (n = 1), and metatarsal (n = 1) were used between June of 1974 and June of 2014 for reconstruction of the mandible (n = 267), maxilla (n = 20), clavicle (n = 1), humerus (n = 8), radius and ulna (n = 21), carpus (n = 3), pelvis (n = 2), femur (n = 11), tibia (n = 47), and foot bones (n = 4). Indications were tumor ablation (n = 286), trauma (n = 84), osteomyelitis (n = 2), and the congenital deformities hemifacial microsomia (n = 2) and pseudarthrosis of the tibia (n = 9) and ulna (n = 1).

Results:

Successful transfer was achieved in 95 percent of patients. Union varied with the recipient bone, from 6 to 8 weeks in the jaw, 2 to 3 months in the upper limb, and 3 to 4 months in the femur and tibia. Union was fastest with iliac crest. The fibula provided easier dissection; it could be raised on either peroneal or anterior tibial vessels; the skin flap could be designed distally; it could be placed centrally in the medullary cavity of long bones; and hairline stress fracture in the lower limb frequently preceded rapid subperiosteal hypertrophy. The fibula lacks sufficient height for osseointegration, whereas iliac crest is ideal. Osteotomies of either bone are possible to straighten or increase curvature.

Conclusions:

The fibula is best for long bone or angle-to-angle jaw reconstruction, especially in edentulous patients. Iliac crest is best for hemimandible, curved bones (pelvis, carpus, and metacarpus), and as an alternative for short, straight, 6- to 8-cm-long bone defects.
Violence in the prehistoric period of Japan: the spatio-temporal pattern of skeletal evidence for violence in the Jomon period
Authors: Nakao Hisashi , Tamura Kohei , Arimatsu Yui , Nakagawa Tomomi , Matsumoto Naoko , Matsugi Takehiko
Published: March 2016

Whether man is predisposed to lethal violence, ranging from homicide to warfare, and how that may have impacted human evolution, are among the most controversial topics of debate on human evolution. Although recent studies on the evolution of warfare have been based on various archaeological and ethnographic data, they have reported mixed results: it is unclear whether or not warfare among prehistoric hunter–gatherers was common enough to be a component of human nature and a selective pressure for the evolution of human behaviour. This paper reports the mortality attributable to violence, and the spatio-temporal pattern of violence thus shown among ancient hunter–gatherers using skeletal evidence in prehistoric Japan (the Jomon period: 13 000 cal BC–800 cal BC). Our results suggest that the mortality due to violence was low and spatio-temporally highly restricted in the Jomon period, which implies that violence including warfare in prehistoric Japan was not common.
Climate change surpasses land-use change in the contracting range boundary of a winter-adapted mammal
Authors: Sultaire Sean M. , Pauli Jonathan N. , Martin Karl J. , Meyer Michael W. , Notaro Michael , Zuckerberg Benjamin
Published: March 2016

The effects of climate change on biodiversity have emerged as a dominant theme in conservation biology, possibly eclipsing concern over habitat loss in recent years. The extent to which this shifting focus has tracked the most eminent threats to biodiversity is not well documented. We investigated the mechanisms driving shifts in the southern range boundary of a forest and snow cover specialist, the snowshoe hare, to explore how its range boundary has responded to shifting rates of climate and land cover change over time. We found that although both forest and snow cover contributed to the historical range boundary, the current duration of snow cover best explains the most recent northward shift, while forest cover has declined in relative importance. In this respect, the southern range boundary of snowshoe hares has mirrored the focus of conservation research; first habitat loss and fragmentation was the stronger environmental constraint, but climate change has now become the main threat. Projections of future range shifts show that climate change, and associated snow cover loss, will continue to be the major driver of this species' range loss into the future.
Understanding variation in human fertility: what can we learn from evolutionary demography?
Authors: Sear Rebecca , Lawson David W. , Kaplan Hillard , Shenk Mary K.
Published: March 2016

Decades of research on human fertility has presented a clear picture ofhowfertility varies, including its dramatic decline over the last two centuries in most parts of the world.Whyfertility varies, both between and within populations, is not nearly so well understood. Fertility is a complex phenomenon, partly physiologically and partly behaviourally determined, thus an interdisciplinary approach is required to understand it. Evolutionary demographers have focused on human fertility since the 1980s. The first wave of evolutionary demographic research made major theoretical and empirical advances, investigating variation in fertility primarily in terms of fitness maximization. Research focused particularly on variation within high-fertility populations and small-scale subsistence societies and also yielded a number of hypotheses for why fitness maximization seems to break down as fertility declines during the demographic transition. A second wave of evolutionary demography research on fertility is now underway, paying much more attention to the cultural and psychological mechanisms underpinning fertility. It is also engaging with the complex, multi-causal nature of fertility variation, and with understanding fertility in complex modern and transitioning societies. Here, we summarize the history of evolutionary demographic work on human fertility, describe the current state of the field, and suggest future directions.
Status competition, inequality, and fertility: implications for the demographic transition
Authors: Shenk Mary K. , Kaplan Hillard S. , Hooper Paul L.
Published: March 2016

The role that social status plays in small-scale societies suggests that status may be important for understanding the evolution of human fertility decisions, and for understanding how such decisions play out in modern contexts. This paper explores whether modelling competition for status—in the sense of relative rank within a society—can help shed light on fertility decline and the demographic transition. We develop a model of how levels of inequality and status competition affect optimal investment by parents in the embodied capital (health, strength, and skills) and social status of offspring, focusing on feedbacks between individual decisions and socio-ecological conditions. We find that conditions similar to those in demographic transition societies yield increased investment in both embodied capital and social status, generating substantial decreases in fertility, particularly under conditions of high inequality and intense status competition. We suggest that a complete explanation for both fertility variation in small-scale societies and modern fertility decline will take into account the effects of status competition and inequality.
The evolved psychological mechanisms of fertility motivation: hunting for causation in a sea of correlation
Authors: McAllister Lisa S. , Pepper Gillian V. , Virgo Sandra , Coall David A.
Published: March 2016

Cultural, ecological, familial and physiological factors consistently influence fertility behaviours, however, the proximate psychological mechanisms underlying fertility decisions in humans are poorly understood. Understanding the psychological mechanisms underlying human fertility may illuminate the final processes by which some of these known predictors have their influence. To date, research into the psychological mechanisms underlying fertility has been fragmented. Aspects of reproductive psychology have been examined by researchers in a range of fields, but the findings have not been systematically integrated in one review. We provide such a review, examining current theories and research on psychological mechanisms of fertility. We examine the methods and populations used in the research, as well as the disciplines and theoretical perspectives from which the work has come. Much of the work that has been done to date is methodologically limited to examining correlations between ecological, social and economic factors and fertility. We propose, and support with examples, the use of experimental methods to differentiate causal factors from correlates. We also discuss weaknesses in the experimental research, including limited work with non-WEIRD (western, educated, industrialized, rich and democratic) populations.
Has the time come for preprints in biology?
Authors: Bhalla Needhi
Published: March 2016

Preprints, non-peer reviewed drafts of manuscripts available on the internet, have been used in conjunction with peer review and publication in journals in the physical sciences for almost 25 years. Recently, more scientists have been discussing whether preprints can play a similar role in biological and biomedical research. Here, I discuss my excitement and concerns about the role that preprints can play in disseminating research findings in the life sciences.
Multi-site internal modification of long DNA substrates for single-molecule studies
Authors: de la Torre Armando , Kim Yoori , Leal Andrew A. , Finkelstein Ilya J.
Published: March 2016

Single-molecule studies of protein-nucleic acid interactions frequently require site-specific modification of long DNA substrates. DNA isolated from bacteriophage λ (λ-DNA) is a convenient source of high quality long (48.5 kb) DNA. However, introducing specific DNA sequences, tertiary structures, and chemical modifications into λ-DNA remains technically challenging. Most current approaches rely on multi-step ligations with low yields and incomplete products. Here, we describe a molecular toolkit for rapid preparation of modified λ-DNA. A set of PCR cassettes facilitates the introduction of recombinant DNA sequences into λ-DNA with 90-100% yield. Furthermore, various DNA structures and chemical modifications can be inserted at user-defined sites via an improved nicking enzyme-based strategy. As a proof-of-principle, we explore the interactions of Proliferating Cell Nuclear Antigen (PCNA) with modified DNA sequences and structures incorporated within λ-DNA. Our results demonstrate that PCNA can load on both 5’-ssDNA flaps and a 13xCAG triplet repeat. However, PCNA remains trapped on the 13xCAG structure, confirming a proposed mechanism for triplet repeat expansion. Although we focus on λ-DNA, this method is applicable to all long DNA substrates. We anticipate that this molecular toolbox will be broadly useful for both ensemble‐ and single-molecule studies that require site-specific modification of long DNA substrates.
Association of NQO1 C609T (Pro187Ser) with risk of Oral Submucous Fibrosis in Eastern Indian population
Authors: Mukherjee Sanjit , Mohanty Sweta , Katarkar Atul , Dhariwal Richa , Mahato Basudev , Ray Jay Gopal , Chaudhuri Keya
Published: March 2016

Oral submucous fibrosis (OSF) is a debilitating disease mainly attributed to chewing areca nut with a 7.4-13% malignant transformation rate. Present study explores the role of NADPH quinone oxidoreductase 1 (NQO1) C609T (Pro187Ser) polymorphism in susceptibility to OSF among habitual areca nut chewers in an eastern Indian population. Overall, about 18% of the total OSF cases were detected carrying minor TT allele (Ser/Ser) p=0.026. When categorized by age, both CT (Pro/Ser) and TT (Ser/Ser) alleles were significantly higher (p= 0.003 & 0.004 respectively) in cases above 40years of age. NQO1 protein was 42% reduced in buccal tissues of heterozygous (Pro/Ser) carriers, whereas a 70% reduction was observed in TT (Ser/Ser) OSF cases. Our study suggests that the NQO1 C609T polymorphism confers increased risk for OSF in habitual chewers.
Nanocall: An Open Source Basecaller for Oxford Nanopore Sequencing Data
Authors: David Matei , Dursi L.J. , Yao Delia , Boutros Paul C. , Simpson Jared T.
Published: March 2016

Motivation

The highly portable Oxford Nanopore MinlON sequencer has enabled new applications of genome sequencing directly in the field. However, the MinlON currently relies on a cloud computing platform, Metrichor (metrichor.com), for translating locally generated sequencing data into basecalls.

Results

To allow offline and private analysis of MinlON data, we created Nanocall. Nanocall is the first freely-available, open-source basecaller for Oxford Nanopore sequencing data and does not require an internet connection. On twoE.coliand two human samples, with natural as well as PCR-amplified DNA, Nanocall reads have ~68% identity, directly comparable to Metrichor ”1D” data. Further, Nanocall is efficient, processing ~500Kbp of sequence per core hour, and fully parallelized. Using 8 cores, Nanocall could basecall a MinlON sequencing run in real time. Metrichor provides the ability to integrate the ”1D” sequencing of template and complement strands of a single DNA molecule, and create a ”2D” read. Nanocall does not currently integrate this technology, and addition of this capability will be an important future development. In summary, Nanocall is the first open-source, freely available, off-line basecaller for Oxford Nanopore sequencing data.

Availability

Nanocall is available atgithub.com/mateidavid/nanocall, released under the MIT license.

Contact

matei.david at oicr.on.ca
Syndecan functions to regulate Wnt-dependent axon guidance inC. elegans
Authors: Hartin Samantha N. , Kurland Meagan , Ackley Brian D.
Published: March 2016

Cell adhesion molecules are key to axon guidance during development, for example specific cues can instruct axons to terminate in a specific area, or to continue growth. Syndecans are conserved cell-surface receptors that function in multiple developmental contexts.Caenorhabditis eleganswith mutations in the single syndecan gene,sdn-1,exhibited errors in anterior-posterior guidance, with axons that stopped short of, or grew past their stereotypical termination point. Syndecan function was cell non-autonomous for GABAergic axon outgrowth during early development, but was likely cell autonomous to inhibit growth later in development.sdn-1appeared to regulate the inhibitory activity of theegl-20/Wntligand. Removingegl-20fromsdn-1mutants resulted in fewer animals with prematurely terminating axons. The proteoglycan modifying enzymeshse-5andhst-2, but nothst-6, had similar effects, suggesting specific heparan sulfate modifications regulated EGL-20 axon-terminating activity.sdn-1functioned withlin-17/Frizzled,bar-1/β-catenin and theegl-5Hox-like transcription factor in EGL-20-depedent axon outgrowth.bar-1was required foregl-5expression in the most posterior GABAergic neurons.sdn-1mutations did not eliminateegl-5expression, but over-expression ofegl-5rescuedsdn-1phenotypes. Our results suggest syndecan is a component of Wnt-signaling events that are necessary for axons to recognize appropriate termination points.