bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated parasite management improves control of gastrointestinal nematodes in lamb production systems in a high summer-rainfall region, on the Northern Tablelands, New South Wales
Authors: Dever M. L. , Kahn L. P. , Doyle E. K.
Published: August 2016

This experiment tested the hypothesis that integrated parasite management (IPM) programs would reduce the effects of gastrointestinal nematodes (GIN) in meat-breed lamb production systems on the Northern Tablelands of New South Wales. The experiment was a longitudinal experiment using twin-bearing Border Leicester × Merino ewes on farms managed in accordance to either regional WormBoss IPM programs (n = 3 farms) or typical (TYP) regional GIN control (n = 2 farms). Ewes on each farm were either GIN-suppressed (SUP; n = 120 ewes) or not (NSUP; n = 120 ewes) and were managed in two groups (n = 120/group) balanced for GIN control. Ewes lambed in September and at lamb marking, 120 lambs (Dorset sires) from each ewe GIN control group were enrolled in the experiment to investigate the effect of ewe GIN control on lamb performance up to weaning. Overall mean worm egg count (WEC) of ewes (P = 0.004) was lower with IPM (IPM 766 vs TYP 931 epg) and was achieved with fewer drenches (IPM 4.5 vs TYP 5.5/year). Despite lower WEC, GIN infection reduced liveweight (IPM –2.1 kg vs TYP –1.1 kg, P = 0.0006) and clean fleece weight (IPM –0.11 kg vs TYP –0.01 kg, P = 0.03) of ewes to a greater extent on IPM farms. The annual rate of apparent ewe mortality was 6.5% and this was unaffected by GIN infection. WEC of lambs at weaning was lower on IPM farms (IPM 159 epg vs TYP 322, P < 0.0001) but the difference in weaning weights of lambs reared by NSUP and SUP ewes was greater on IPM farms (IPM –1.1 kg vs TYP 0.2 kg, P < 0.0001). Overall, the production loss due to GIN infection in these sheep-meat production systems, on the Northern Tablelands of New South Wales, was small and treatment frequency can be reduced by IPM programs.
Rab5 and its effector FHF contribute to neuronal polarity through dynein-dependent retrieval of somatodendritic proteins from the axon
Authors: Guo Xiaoli , Farías Ginny G. , Mattera Rafael , Bonifacino Juan S.
Published: August 2016

Significance

Ras-related proteins in brain (Rab) GTPases are general regulators of intracellular traffic in eukaryotic cells, but their specialized roles in neurons are poorly understood. Here we report that Rab5 contributes to the somatodendritic polarity of various surface receptors by mediating their retrieval from the axon. This retrieval is dependent on the Rab5 effector Fused Toes (FTS)–Hook–FTS and Hook-interacting protein (FHIP) (FHF), which in turn interacts with the minus-end–directed microtubule motor dynein–dynactin to drive retrograde transport of receptor-containing carriers from the axon to the soma. These findings reveal a mechanism for coupling axonal retrograde carriers to dynein–dynactin and demonstrate that the somatodendritic polarity of various receptors results from a combination of biosynthetic sorting, the barrier function of the axon initial segment, and retrieval from the axon.
Combination therapy with BPTES nanoparticles and metformin targets the metabolic heterogeneity of pancreatic cancer
Authors: Elgogary Amira , Xu Qingguo , Poore Brad , Alt Jesse , Zimmermann Sarah C. , Zhao Liang , Fu Jie , Chen Baiwei , Xia Shiyu , Liu Yanfei , Neisser Marc , Nguyen Christopher , Lee Ramon , Park Joshua K. , Reyes Juvenal , Hartung Thomas , Rojas Camilo , Rais Rana , Tsukamoto Takashi , Semenza Gregg L. , Hanes Justin , Slusher Barbara S. , Le Anne
Published: August 2016

Significance

There are no effective therapies currently available for advanced pancreatic cancer. We show that there are two populations of cancer cells within a pancreatic tumor that require targeting by different metabolic inhibitors for effective tumor control. Rapidly dividing cells use glutamine, and can be effectively killed by administration of a nanoparticle containing an inhibitor of glutamine metabolism. Hypoxic cells, which are slowly dividing cells, metabolize glucose and can be targeted by metformin, a drug used for the treatment of diabetes. Clinical trials are needed to determine whether combination therapy, with drugs that effectively block the metabolism of glutamine and glucose, improves the survival of patients with pancreatic cancer.
Biallelic hypomorphic mutations in a linear deubiquitinase define otulipenia, an early-onset autoinflammatory disease
Authors: Zhou Qing , Yu Xiaomin , Demirkaya Erkan , Deuitch Natalie , Stone Deborah , Tsai Wanxia Li , Kuehn Hye Sun , Wang Hongying , Yang Dan , Park Yong Hwan , Ombrello Amanda K. , Blake Mary , Romeo Tina , Remmers Elaine F. , Chae Jae Jin , Mullikin James C. , Güzel Ferhat , Milner Joshua D. , Boehm Manfred , Rosenzweig Sergio D. , Gadina Massimo , Welch Steven B. , Özen Seza , Topaloglu Rezan , Abinun Mario , Kastner Daniel L. , Aksentijevich Ivona
Published: August 2016

Significance

We describe a human disease linked to mutations in the linear deubiquitinase (DUB) OTULIN, which functions as a Met1-specific DUB to remove linear polyubiquitin chains that are assembled by the linear ubiquitin assembly complex (LUBAC). OTULIN has a role in regulating Wnt and innate immune signaling complexes. Hydrolysis of Met1-linked ubiquitin chains attenuates inflammatory signals in the NF-κB and ASC-mediated pathways. OTULIN-deficient patients have excessive linear ubiquitination of target proteins, such as NEMO, RIPK1, TNFR1, and ASC, leading to severe inflammation. Cytokine inhibitors have been efficient in suppressing constitutive inflammation in these patients. This study, together with the identification of haploinsufficiency of A20 (HA20), suggests a category of human inflammatory diseases, diseases of dysregulated ubiquitination.
Population Characteristics and the Suppression of Nonnative Burbot
Authors: Klein Zachary B. , Quist Michael C. , Rhea Darren T. , Senecal Anna C.
Published: August 2016

Burbot Lota lota were illegally introduced into the Green River, Wyoming, drainage and have since proliferated throughout the system. Burbot in the Green River pose a threat to native species and to socially, economically, and ecologically important recreational fisheries. Therefore, managers of the Green River are interested in implementing a suppression program for Burbot. We collected demographic data on Burbot in the Green River (summer and autumn 2013) and used the information to construct an age-based population model (female-based Leslie matrix) to simulate the population-level response of Burbot to the selective removal of different age-classes. Burbot in the Green River grew faster, matured at relatively young ages, and were highly fecund compared with other Burbot populations within the species’ native distribution. The age-structured population model, in conjunction with demographic information, indicated that the Burbot population in the Green River could be expected to increase under current conditions. The model also indicated that the Burbot population in the Green River would decline once total annual mortality reached 58%. The population growth of Burbot in the Green River was most sensitive to age-0 and age-1 mortality. The age-structured population model indicated that an increase in mortality, particularly for younger age-classes, would result in the effective suppression of the Burbot population in the Green River.

Received May 27, 2015; accepted March 20, 2016 Published online August 24, 2016
Energetic variational approaches for incompressible fluid systems on an evolving surface
Authors: Koba Hajime , Liu Chun , Giga Yoshikazu
Published: August 2016

This paper considers the equations governing incompressible fluid-flow on an evolving surface. We employ an energetic variational approach to derive the dynamical system for the motion of incompressible fluid on such an evolving surface. The focus is to understand the coupling of an incompressible fluid-flow and the evolution of a moving surface, involving both the curvature and the motion of the surface.
Actin filaments as dynamic reservoirs for Drp1 recruitment
Authors: Hatch Anna L. , Ji Wei-Ke , Merrill Ronald A. , Strack Stefan , Higgs Henry N.
Published: August 2016

Drp1 is a dynamin-family GTPase recruited to mitochondria and peroxisomes, where it oligomerizes and drives membrane fission. Regulation of mitochondrial Drp1 recruitment is not fully understood. We previously showed that Drp1 binds actin filaments directly, and actin polymerization is necessary for mitochondrial Drp1 oligomerization in mammals. Here we show the Drp1/actin interaction displays unusual properties that are influenced by several factors. At saturation, only a fraction Drp1 binds actin filaments, and the off-rate of actin-bound Drp1 is significantly increased by unbound Drp1. GDP and GTP accelerate and decelerate Drp1/actin binding dynamics, respectively. Actin has a biphasic effect on Drp1 GTP hydrolysis, increasing at low actin:Drp1 ratio but returning to baseline at high ratio. Drp1 also bundles filaments. Bundles have reduced dynamics but follow the same trends as single filaments. Drp1 preferentially incorporates into bundles at higher ionic strength. We measure Drp1 concentration to be ∼0.5 μM in U2OS cell cytosol, suggesting the actin-binding affinity measured here (Kd= 0.6 μM) is in the physiologically relevant range. The ability of Drp1 to bind actin filaments in a highly dynamic manner provides potential for actin filaments to serve as reservoirs of oligomerization-competent Drp1 that can be accessed for mitochondrial fission.
Baseline and Change in Uric Acid Concentration Over Time Are Associated With Incident Hypertension in Large Korean Cohort
Authors: Sung Ki-Chul , Byrne Christopher D. , Ryu Seungho , Lee Jong-Young , Lee Sung Ho , Kim Jang-Young , Kim Seong Hwan , Wild Sarah H. , Guallar Eliseo
Published: August 2016

BACKGROUND

It is uncertain whether high-baseline uric acid (UA) or change in UA concentration over time is related to development of incident hypertension. To investigate relationships between: (i) baseline serum UA concentration and (ii) change in UA concentration and incident hypertension.

METHODS

About 96,606 Korean individuals (with follow-up UA data available for 56,085 people) participating in a health check program was undertaken. Cox regression models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for incident hypertension according to UA quartiles regarding the lowest UA quartile as the reference, and also according to change in UA concentration comparing individuals with an increase in UA to those with a decrease in UA concentration over time.

RESULTS

Total follow up time was 8 years (median follow-up 3.3 years; interquartile range, 1.9–5.1). About 10,405 cases of incident hypertension occurred. In the fully adjusted regression models, the HRs (95% CI) for incident hypertension comparing the highest vs. the lowest quartiles of UA were 1.29 (1.19–1.38) in men and 1.24 (1.09–1.42) in women, with statistically significant P for trend for both gender. Additionally, stable or increasing UA concentration over time was associated with increased risk of incident hypertension, particularly in participants with baseline UA concentration ≥median (aHRs 1.14; 95% CI (1.03–1.26) and 1.18; 95% CI (0.98–1.40) in men and women, respectively).

CONCLUSIONS

High initial UA concentration and increases in UA concentration over time should be considered independent risk factors for hypertension.
Fast-SNP: a fast matrix pre-processing algorithm for efficient loopless flux optimization of metabolic models
Authors: Saa Pedro A. , Nielsen Lars K.
Published: August 2016

Motivation: Computation of steady-state flux solutions in large metabolic models is routinely performed using flux balance analysis based on a simple LP (Linear Programming) formulation. A minimal requirement for thermodynamic feasibility of the flux solution is the absence of internal loops, which are enforced using ‘loopless constraints’. The resulting loopless flux problem is a substantially harder MILP (Mixed Integer Linear Programming) problem, which is computationally expensive for large metabolic models.

Results: We developed a pre-processing algorithm that significantly reduces the size of the original loopless problem into an easier and equivalent MILP problem. The pre-processing step employs a fast matrix sparsification algorithm—Fast- sparse null-space pursuit (SNP)—inspired by recent results on SNP. By finding a reduced feasible ‘loop-law’ matrix subject to known directionalities, Fast-SNP considerably improves the computational efficiency in several metabolic models running different loopless optimization problems. Furthermore, analysis of the topology encoded in the reduced loop matrix enabled identification of key directional constraints for the potential permanent elimination of infeasible loops in the underlying model. Overall, Fast-SNP is an effective and simple algorithm for efficient formulation of loop-law constraints, making loopless flux optimization feasible and numerically tractable at large scale.

Availability and Implementation: Source code for MATLAB including examples is freely available for download at http://www.aibn.uq.edu.au/cssb-resources under Software. Optimization uses Gurobi, CPLEX or GLPK (the latter is included with the algorithm).

Contact:  lars.nielsen@uq.edu.au

Supplementary information:  Supplementary data are available at Bioinformatics online.
Discoal: flexible coalescent simulations with selection
Authors: Kern Andrew D. , Schrider Daniel R.
Published: August 2016

Summary: Here we describe discoal, a coalescent simulator able to generate population samples that include selective sweeps in a feature-rich, flexible manner. discoal can perform simulations conditioning on the fixation of an allele due to drift or either hard or soft sweeps—even those occurring a large genetic distance away from the simulated locus. discoal can simulate sweeps with recurrent mutation to the adaptive allele, recombination, and gene conversion, under non-equilibrium demographic histories and without specifying an allele frequency trajectory in advance.

Availability and Implementation: discoal is implemented in the C programming language. Source code is freely available on GitHub (https://github.com/kern-lab/discoal) under a GNU General Public License.

Contact:  kern@dls.rutgers.edu or dan.schrider@rutgers.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
AlmostSignificant: simplifying quality control of high-throughput sequencing data
Authors: Ward Joseph , Cole Christian , Febrer Melanie , Barton Geoffrey J.
Published: August 2016

Motivation: The current generation of DNA sequencing technologies produce a large amount of data quickly. All of these data need to pass some form of quality control (QC) processing and checking before they can be used for any analysis. The large number of samples that are run through Illumina sequencing machines makes the process of QC an onerous and time-consuming task that requires multiple pieces of information from several sources.

Results: AlmostSignificant is an open-source platform for aggregating multiple sources of quality metrics as well as run and sample meta-data associated with DNA sequencing runs from Illumina sequencing machines. AlmostSignificant is a graphical platform to streamline the QC of DNA sequencing data, to store these data for future reference together with extra meta-data associated with the sequencing runs not typically retained. This simplifies the challenge of monitoring the volume of data produced by Illumina sequencers. AlmostSignificant has been used to track the quality of over 80 sequencing runs covering over 2500 samples produced over the last three years.

Availability and Implementation: The code and documentation for AlmostSignificant is freely available at https://github.com/bartongroup/AlmostSignificant.

Contacts:  c.cole@dundee.ac.uk or g.j.barton@dundee.ac.uk

Supplementary information:  Supplementary data are available at Bioinformatics online.
Cas-analyzer: an online tool for assessing genome editing results using NGS data
Authors: Park Jeongbin , Lim Kayeong , Kim Jin-Soo , Bae Sangsu
Published: August 2016

Genome editing with programmable nucleases has been widely adopted in research and medicine. Next generation sequencing (NGS) platforms are now widely used for measuring the frequencies of mutations induced by CRISPR-Cas9 and other programmable nucleases. Here, we present an online tool, Cas-Analyzer, a JavaScript-based implementation for NGS data analysis. Because Cas-Analyzer is completely used at a client-side web browser on-the-fly, there is no need to upload very large NGS datasets to a server, a time-consuming step in genome editing analysis. Currently, Cas-Analyzer supports various programmable nucleases, including single nucleases and paired nucleases.

Availability and Implementation

Free access at http://www.rgenome.net/cas-analyzer/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Patients learning to read their doctors’ notes: the importance of reminders
Authors: Mafi John N , Mejilla Roanne , Feldman Henry , Ngo Long , Delbanco Tom , Darer Jonathan , Wee Christina , Walker Jan
Published: August 2016

Objective To examine whether patients invited to review their clinicians’ notes continue to access them and to assess the impact of reminders on whether patients continued to view notes.

Materials and methods We followed OpenNotes trial participants for 2 years at Beth Israel Deaconess Medical Center (BIDMC) and Geisinger Health System (GHS). Electronic invitations alerting patients to signed notes stopped at GHS after year 1, creating a natural experiment to assess the impact of reminders. We used generalized linear models to measure whether notes were viewed within 30 days of availability.

Results We identified 14 360 patients (49 271 visits); mean age 52.2; 57.8% female. In year 1, patients viewed 57.5% of their notes, and their interest in viewing notes persisted over time. In year 2, BIDMC patients viewed notes with similar frequency. In contrast, GHS patients viewed notes far less frequently, a change starting when invitations ceased (RR 0.29 [0.26–0.32]) and persisting to the end of the study (RR 0.20 [0.17–0.23]). A subanalysis of BIDMC patients revealed that black and other/multiracial patients also continued to view notes, although they were overall less likely to view notes compared with whites (RR 0.75 [0.67–0.83] and 0.93 [0.89–0.98], respectively).

Discussion As millions of patients nationwide increasingly gain access to clinicians’ notes, explicit email invitations to review notes may be important for fostering patient engagement and patient-doctor communication.

Conclusion Note viewing persists when accompanied by email alerts, but may decline substantially in their absence. Non-white patients at BIDMC viewed notes less frequently than whites, although their interest also persisted.
Human Immunodeficiency Virus-1 Sequence Changes and Drug Resistance Mutation Among Virologic Failures of Lopinavir/Ritonavir Monotherapy: AIDS Clinical Trials Group Protocol A5230
Authors: Vardhanabhuti Saran , Katzenstein David , Bartlett John , Kumarasamy Nagalingeswaran , Wallis Carole L.
Published: August 2016

Background.  The mechanism of virologic failure (VF) of lopinavir/ritonavir (LPV/r) monotherapy is not well understood. We assessed sequence changes in human immunodeficiency virus-1 reverse-transcriptase (RT) and protease (PR) regions.

Methods.  Human immunodeficiency virus-1 pol sequences from 34 participants who failed second-line LPV/r monotherapy were obtained at study entry (SE) and VF. Sequence changes were evaluated using phylogenetic analysis and hamming distance.

Results.  Human immunodeficiency virus-1 sequence change was higher over drug resistance mutation (DRM) sites (median genetic distance, 2.2%; Q1 to Q3, 2.1%–2.5%) from SE to VF compared with non-DRM sites (median genetic distance, 1.3%; Q1 to Q3, 1.0%–1.4%; P < .0001). Evolution over DRM sites was mainly driven by changes in the RT (median genetic distance, 2.7%; Q1 to Q3, 2.2%–3.2%) compared with PR (median genetic distance, 1.1%; Q1 to Q3, 0.0%–1.1%; P < .0001). Most RT DRMs present at SE were lost at VF. At VF, 19 (56%) and 26 (76%) were susceptible to efavirenz/nevirapine and etravirine (ETV)/rilpivirine (RPV), respectively, compared with 1 (3%) and 12 (35%) at SE. Participants who retained nonnucleoside reverse-transcriptase inhibitor (NNRTI) DRMs and those without evolution of LPV/r DRMs had significantly shorter time to VF.

Conclusions.  The selection of LPV/r DRMs in participants with longer time to VF suggests better adherence and more selective pressure. Fading NNRTI mutations and an increase in genotypic susceptibility to ETV and RPV could allow for the reuse of NNRTI. Further studies are warranted to understand mechanisms of PR failure.
Characterization of Low-Strigolactone Germplasm in Pea (Pisum sativum L.) Resistant to Crenate Broomrape (Orobanche crenata Forsk.)
Authors: Pavan Stefano , Schiavulli Adalgisa , Marcotrigiano Angelo Raffaele , Bardaro Nicoletta , Bracuto Valentina , Ricciardi Francesca , Charnikhova Tatsiana , Lotti Concetta , Bouwmeester Harro , Ricciardi Luigi
Published: August 2016

Crenate broomrape (Orobanche crenata Forsk.) is a devastating parasitic weed threatening the cultivation of legumes around the Mediterranean and in the Middle East. So far, only moderate levels of resistance were reported to occur in pea (Pisum sativum L.) natural germplasm, and most commercial cultivars are prone to severe infestation. Here, we describe the selection of a pea line highly resistant to O. crenata, following the screening of local genetic resources. Time series observations show that delayed emergence of the parasite is an important parameter associated with broomrape resistance. High performance liquid chromatography connected to tandem mass spectrometry analysis and in vitro broomrape germination bioassays suggest that the resistance mechanism might involve the reduced secretion of strigolactones, plant hormones exuded by roots and acting as signaling molecules for the germination of parasitic weeds. Two years of replicated trials in noninfested fields indicate that the resistance is devoid of pleiotropic effects on yield, in contrast to pea experimental mutants impaired in strigolactone biosynthesis and, thus, is suitable for use in breeding programs.
Binaural Hearing Ability With Bilateral Bone Conduction Stimulation in Subjects With Normal Hearing: Implications for Bone Conduction Hearing Aids
Authors: Zeitooni Mehrnaz , Mäki-Torkko Elina , Stenfelt Stefan
Published: August 2016

Objectives:

The purpose of this study is to evaluate binaural hearing ability in adults with normal hearing when bone conduction (BC) stimulation is bilaterally applied at the bone conduction hearing aid (BCHA) implant position as well as at the audiometric position on the mastoid. The results with BC stimulation are compared with bilateral air conduction (AC) stimulation through earphones.

Design:

Binaural hearing ability is investigated with tests of spatial release from masking and binaural intelligibility level difference using sentence material, binaural masking level difference with tonal chirp stimulation, and precedence effect using noise stimulus.

Results:

In all tests, results with bilateral BC stimulation at the BCHA position illustrate an ability to extract binaural cues similar to BC stimulation at the mastoid position. The binaural benefit is overall greater with AC stimulation than BC stimulation at both positions. The binaural benefit for BC stimulation at the mastoid and BCHA position is approximately half in terms of decibels compared with AC stimulation in the speech based tests (spatial release from masking and binaural intelligibility level difference). For binaural masking level difference, the binaural benefit for the two BC positions with chirp signal phase inversion is approximately twice the benefit with inverted phase of the noise. The precedence effect results with BC stimulation at the mastoid and BCHA position are similar for low frequency noise stimulation but differ with high-frequency noise stimulation.

Conclusions:

The results confirm that binaural hearing processing with bilateral BC stimulation at the mastoid position is also present at the BCHA implant position. This indicates the ability for binaural hearing in patients with good cochlear function when using bilateral BCHAs.
Extensive Postradiation Ocular and Diffuse Cranial Neuromyotonia Mimicking Myasthenia Gravis
Authors: Hardy Todd A. , Lee Andrew W. , Yiannikas Con , Chen Celia S. , Reddel Stephen W.
Published: August 2016

Background:

Ocular neuromyotonia is a rare, but well-recognized, complication of cranial irradiation.

Case Report:

Using figures and videos, we report a 52-year-old man with extensive ocular, brainstem, and lower cranial nerve neuromyotonia postradiation therapy for a fourth ventricle glioma who, in the context of an apparently positive edrophonium test, was initially misdiagnosed with myasthenia gravis.

Conclusions:

This is the first case of postirradiation neuromyotonia to be reported with such extensive cranial nerve and brainstem involvement.
Palatal and Oromandibular Tremor Secondary to Degenerative Olivary Hypertrophy After Ependymoma Surgery
Authors: Lozano-Ros Alberto , Miranda-Acuña Jahir A. , Hidalgo-de la Cruz Milagros , Fernández-García Pilar , Massot-Tarrús Andreu , García-Domínguez José M.
Published: August 2016

Palatal tremor (PT) is a rare movement disorder that involves pharynx, tongue, and other facial muscles. Symptomatic PT is due to lesions on the dentate-rubro-olivary pathways. We present an illustrative case of PT due to degenerative olivary hypertrophy after ependymoma surgery.
Is Single-Stage Prosthetic Reconstruction Cost Effective? A Cost-Utility Analysis for the Use of Direct-to-Implant Breast Reconstruction Relative to Expander-Implant Reconstruction in Postmastectomy Patients
Authors: Krishnan Naveen M. , Fischer John P. , Basta Marten N. , Nahabedian Maurice Y.
Published: August 2016

Background:

Prosthetic breast reconstruction is most commonly performed using the two-stage (expander-implant) technique. However, with the advent of skin-sparing mastectomy and the use of acellular dermal matrices, one-stage prosthetic reconstruction has become more feasible. Prior studies have suggested that one-stage reconstruction has economic advantages relative to two-stage reconstruction despite a higher revision rate. This is the first cost-utility analysis to compare the cost and quality of life of both procedures to guide patient care.

Methods:

A comprehensive literature review was conducted using the MEDLINE, EMBASE, and Cochrane databases to include studies directly comparing matched patient cohorts undergoing single-stage or staged prosthetic reconstruction. Six studies were selected examining 791 direct-to-implant reconstructions and 1142 expander-implant reconstructions. Costs were derived adopting both patient and third-party payer perspectives. Utilities were derived by surveying an expert panel. Probabilities of clinically relevant complications were combined with cost and utility estimates to fit into a decision tree analysis.

Results:

The overall complication rate was 35 percent for single-stage reconstruction and 34 percent for expander-implant reconstruction. The authors’ baseline analysis using Medicare reimbursement revealed a cost decrease of $525.25 and a clinical benefit of 0.89 quality-adjusted life-year when performing single-stage reconstructions, yielding a negative incremental cost-utility ratio. When using national billing, the incremental cost-utility further decreased, indicating that direct-to-implant breast reconstruction was the dominant strategy. Sensitivity analysis confirmed the robustness of the authors’ conclusions.

Conclusions:

Direct-to-implant breast reconstruction is the dominant strategy when used appropriately. Surgeons are encouraged to consider single-stage reconstruction when feasible in properly selected patients.
Fat Grafting for Gluteal Augmentation: A Systematic Review of the Literature and Meta-Analysis
Authors: Condé-Green Alexandra , Kotamarti Vasanth , Nini Kevin T. , Wey Philip D. , Ahuja Naveen K. , Granick Mark S. , Lee Edward S.
Published: August 2016

Background:

With the increasing demand for gluteal fat augmentation, reports of fatal complications have surfaced. Therefore, the authors proposed to analyze the published techniques and compare different protocols, to identify those of potential concern.

Methods:

A systematic review of the literature was performed with a search of 21 terms on the PubMed, MEDLINE, Cochrane, and Scientific Electronic Library Online databases. Nineteen articles meeting our predetermined criteria were analyzed, and data from the different steps of the procedure were classified, allowing evaluation and comparison of techniques. Independent-samples t test and one-way analysis of variance were used for statistical analysis.

Results:

Seventeen case series and two retrospective studies including 4105 patients were reviewed. Most articles were authored in Colombia, Mexico, and Brazil. Most procedures were performed on adult female patients under general anesthesia. Fat was harvested using a tumescent technique from the lower extremities and the back, with machine-vacuum suction. A mean of 400 ml of decanted lipoaspirate was injected into each gluteal region, mostly subcutaneously and intramuscularly with 60-ml syringes. Most patients rated their results as “excellent.” The mean complication rate was 7 percent (6.7 percent minor, 0.32 percent major), with no significant relation to the planes of injection.

Conclusions:

Fat grafting is an effective and predictable way to remodel the gluteal region; however, the procedure is not without risks. Avoiding gluteal vessel damage may prevent most feared complications, such as fat embolism. Accurate analysis, systematization of the procedure, and reporting cases in the fat grafting registry may provide the foundation for optimization of outcomes.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
In-Depth Review of Symptoms, Triggers, and Surgical Deactivation of Frontal Migraine Headaches (Site I)
Authors: Kurlander David E. , Ascha Mona , Sattar Abdus , Guyuron Bahman
Published: August 2016

Background:

This study reports details of the technique and assesses efficacy of surgical deactivation of frontal migraine headaches. In addition, this study examines the effect of surgical deactivation of frontal migraine headaches on migraine triggers and associated symptoms besides the pain.

Methods:

Charts of 270 patients undergoing surgery performed by a single surgeon for frontal migraine headaches, who were followed for at least 1 year, were analyzed. Median regression adjusted for age, sex, and follow-up time was used to determine postoperative reduction in frontal-specific Migraine Headache Index, which is the product of duration, frequency, and severity. Reduction in migraine-days, which is the product of duration and frequency, was also measured. The association between individual symptom or trigger resolution and frontal-specific Migraine Headache Index reduction was studied by logistic regression. Details of the surgical treatment are discussed and complication rates are reported.

Results:

Eighty-six percent of patients reported a successful operation (≥50 percent improvement of frontal-specific Migraine Headache Index) at least 12 months after surgery (mean follow-up, 3 years). Eighty-four percent of patients had a successful operation as measured by migraine-days. Fifty-seven percent of patients reported complete elimination of frontal migraine headaches. Symptoms resolving with successful site I surgery beyond the headaches include visual aura and blurred or double vision (p < 0.05). Triggers resolving with successful site I surgery include fatigue, weather change, and missed meals (p < 0.05).

Conclusions:

Surgical deactivation of frontal migraine headaches provides long-lasting migraine relief. Successful site I surgery is associated with changes in specific symptoms and triggers. This information can assist in trigger avoidance and contribute to constellations used for frontal migraine headache trigger-site identification.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Current Uses of Botulinum Neurotoxins in Plastic Surgery
Authors: Noland Marie E. , Lalonde Donald H. , Yee G. Jackie , Rohrich Rod J.
Published: August 2016

Learning Objectives:

After reading this article, the participant should be able to: 1. Recognize the various types of botulinum toxins and their differences. 2. Identify current indications, both approved and off-label. 3. Inject botulinum toxin to counteract various natural aging processes, including facial descent and rhytides.

Botulinum neurotoxin is a naturally synthesized microbial protein that has been applied in the management of various disorders. In particular, its application within the realm of plastic surgery is addressed in this article. After evaluating the medical literature, the seven indications with the highest quality trials for the use of botulinum neurotoxin in plastic surgery were as follows: rhytides, facial dystonias, facial nerve palsy and aberrant regeneration, hand tremor, palmar hyperhidrosis, neuropathic pain, and upper limb spasticity.
The Deep Temporal Nerve Transfer: An Anatomical Feasibility Study and Implications for Upper Facial Reanimation
Authors: Dauwe Phillip B. , Hembd Austin , De La Concha-Blankenagel Erika , Saba Salim , White Charles , Cardenas-Mejia Alexander , Rozen Shai M.
Published: August 2016

Background:

Facial paralysis has a profound impact on the brow, and currently static procedures are the mainstay of treatment. The deep temporal branches of the trigeminal nerve, given their proximity to the brow, may serve as possible donor nerves for both potential innervation of a free muscle transfer in patients with prolonged facial palsy or nerve transfers in acute or subacute palsy. As such, the authors present the detailed surgical anatomy of the deep temporal nerve, assessing feasibility for both functional muscle and nerve transfers, including a proposed surgical technique.

Methods:

Thirty cadaver hemifaces were dissected to establish deep temporal nerve anatomy and perform axonal analysis.

Results:

Two (53 percent) or three (47 percent) divisions of the deep temporal nerve were noted, with the most consistent division being the middle division (30 of 30 specimens). This division was consistently found approximately 4.1 cm (range, 3.7 to 4.5 cm) anterior to the tragus at the level of the zygomatic arch. For each 1 cm cranial to the arch, the nerve courses approximately 1 mm posteriorly. The number of axons in the proposed temporal branch is 1469 as it emerges from behind the zygomatic arch, 889 at 1 cm, 682 at 2 cm, 534 at 3 cm, 355 at 4 cm, 377 at 5 cm, and 256 at 6 cm.

Conclusion:

Given its anatomical consistency, and expendability, the middle division of the deep temporal nerve is a viable donor nerve for dynamic upper facial reanimation with either nerve transfer or functional muscle transfer, depending on the length of facial palsy.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
The Medical Mission and Modern Core Competency Training: A 10-Year Follow-Up of Resident Experiences in Global Plastic Surgery
Authors: Yao Caroline A. , Swanson Jordan , McCullough Meghan , Taro Trisa B. , Gutierrez Ricardo , Bradshaw Allison , Campbell Alex , Magee William P. , Magee William P.
Published: August 2016

Background:

The emphasis on cultural competency for physicians and surgeons is increasingly important, as communication with both patients and other providers significantly affects individual and system-wide outcomes. International surgical training has been shown to improve leadership skills, cultural competency, and technical proficiency of participants in short-term follow-up. This study explores the long-term impact of international surgical mission experiences on developing participants’ core competencies, professional outcomes, and commitment to global health.

Methods:

All 208 plastic and reconstructive surgeons who completed the Operation Smile Regan/Stryker fellowship programs between 2006 and 2015 were surveyed electronically.

Results:

One hundred sixty-five surveys were returned, for an overall response rate of 79.3 percent. The majority of participants reported that the fellowship positively impacted all six Accreditation Council for Graduate Medical Education core competencies. Most participants who were attending physicians at the time of the survey were practicing general plastic surgery, with 42 percent in an academic/teaching environment, 32 percent in assistant/associate professor positions, and 6 percent in either a program director or department chairman position. The majority currently volunteer on local or international missions, and all respondents would consider volunteering again.

Conclusions:

Carefully structured and rigorously proctored programs such as the Regan/Stryker Fellowship offer plastic surgery residents the opportunity to gain valuable professional and personal experiences that benefit them long after their service experience. Programs of this nature can not only effectively improve cultural competency of physicians, but also positively influence their attitudes toward leadership and direct that potential to meet the growing need for surgical care in low- and middle-income countries.
Liposuction-Assisted Short-Scar Brachioplasty: Technical Highlights
Authors: Hill Sean , Small Kevin H. , Pezeshk Ronnie A. , Rohrich Rod J.
Published: August 2016

Upper arm contouring is based on the location and amount of excess skin and fat. The short-scar brachioplasty addresses minimal to moderate skin laxity and lipodystrophy in the proximal arm in patients with appropriate skin tone and quality. This article highlights technical refinements of the senior author’s (R.J.R.) approach to short-scar medial liposuction-assisted brachioplasty to maximize results and minimize incision length. To highlight this simple and safe approach with high patient/surgeon satisfaction, the authors discuss the following in this Video Plus article: patient examination, preoperative assessment, surgical pearls, and postoperative outcomes.
Lengthening Temporalis Myoplasty: Virtual Animation-Assisted Technical Video
Authors: Aljudaibi Nawaf , Bennis Yasmine , Duquennoy-Martinot Veronique , Labbé Daniel , Guerreschi Pierre
Published: August 2016

Lengthening temporalis myoplasty is a well-established procedure for dynamic palliative reanimation of the lip in facial palsy sequelae. The particularity of this technique is that the entire temporal muscle is transferred from the coronoid process to the upper half of the lip without interposition of aponeurotic tissue. To date, no video describing the technique was available. This is the first video describing the entire procedure, from preoperative markings through postoperative rehabilitation. In the video presented herein, the authors craft virtual three-dimensional animations in addition to a live operation on a patient performed by Daniel Labbé, who first described this technique 20 years ago.
HLA-MA: Simple yet powerful matching of samples using HLA typing results
Authors: Messerschmidt Clemens , Holtgrewe Manuel , Beule Dieter
Published: August 2016

We propose the simple method HLA-MA for consistency checking in pipelines operating on human HTS data. The method is based on the HLA typing result of the state-of-the-art method Opti-Type. Provided that there is sufficient coverage of the HLA loci, comparing HLA types allows for simple, fast, and robust matching of samples from whole genome, exome, and RNA-seq data. This approach is reliable for sample re-identification even for samples with high mutational loads, e.g., caused by microsatellite instability or POLE1 defects.

Availability and Implementation

The software is implemented In Python 3 and freely available under the MIT license athttps://github.com/bihealth/hlamaand via Bioconda.

Contact

dieter.beule@bihealth.de
Inference of direction, diversity, and frequency of HIV-1 transmission using approximate Bayesian computation
Authors: Romero-Severson Ethan O. , Bulla Ingo , Hengartner Nick , Bártolo Inês , Abecasis Ana , Azevedo-Pereira José M. , Taveira Nuno , Leitner Thomas
Published: August 2016

Diversity of the founding population of Human Immunodeficiency Virus Type 1 (HIV-1) transmissions raises many important biological, clinical, and epidemiological issues. In up to 40% of sexual infections there is clear evidence for multiple founding variants, which can influence the efficacy of putative prevention methods and the reconstruction of epidemiologic histories. To measure the diversity of the founding population and to compute the probability of alternative transmission scenarios, while explicitly taking phylogenetic uncertainty into account, we created an Approximate Bayesian Computation (ABC) method based on a set of statistics measuring phylogenetic topology, branch lengths, and genetic diversity. We applied our method to a heterosexual transmission pair showing a complex paraphyletic-polyphyletic donor-recipient phylogenetic topology. We found evidence identifying the donor that was consistent with the known facts of the case (Bayes factor >20). We also found that while the evidence for ongoing transmission between the pair was as good or better than the singular transmission event model, it was only viable when the rate of ongoing transmission was implausibly high (~1/day). We concluded that the singular transmission model, which was able to estimate the diversity of the founding population (mean 7% substitutions/site), was more biologically plausible. Our study provides a formal inference framework to investigate HIV-1 direction, diversity, and frequency of transmission. The ability to measure the diversity of founding populations in both simple and complex transmission situations is essential to understanding the relationship between the phylogeny and epidemiology of HIV-1 as well as in efforts developing new prevention technologies.
RNA-Dependent Synthesis of Mammalian mRNA: Identification of Chimeric Intermediate and Putative End Product
Authors: Rits Sophia , Olsen Bjorn R. , Volloch Vladimir
Published: August 2016

Our initial understanding of the flow of protein-encoding genetic information, DNA to RNA to protein, a process defined as the “central dogma of molecular biology”, was eventually amended to account for the information back-flow from RNA to DNA (reverse transcription), and for its “side-flow” from RNA to RNA (RNA-dependent RNA synthesis, RdRs). These processes, both potentially leading to protein production, were described only in viral systems, and although putative RNA-dependent RNA polymerase (RdRp) was shown to be present, and RdRs to occur, in most, if not all, mammalian cells, its function was presumed to be restricted to regulatory. Here we report the occurrence of protein-encoding RNA to RNA information transfer in mammalian cells. We describe below the detection, by next generation sequencing (NGS), of a chimeric doublestranded/pinhead intermediate containing both sense and antisense globin RNA strands covalently joined in a predicted and uniquely defined manner, whose cleavage at the pinhead would result in the generation of an endproduct containing the intact coding region of the original mRNA. We also describe the identification of the putative end product of RNA-dependent globin mRNA amplification. It is heavily modified, uniformly truncated at both untranslated regions (UTRs), terminates with the OH group at the 5’ end, consistent with a cleavagegenerated 5’ terminus, and its massive cellular amount is unprecedented for a conventional mRNA transcription product. It also translates in a cell-free system into polypeptides indistinguishable from the translation product of conventional globin mRNA. The physiological significance of the mammalian mRNA amplification, which might operate during terminal differentiation and in the production of highly abundant rapidly generated proteins such as some collagens or other components of extracellular matrix, with every genome-originated mRNA molecule acting as a potential template, as well as possible implications, including physiologically occurring intracellular PCR process, iPCR, are discussed in the paper.
Modeling time-series data from microbial communities
Authors: Ridenhour Benjamin J , Brooker Sarah L , Williams Janet E , Van Leuven James T , Miller Aaron W , Dearing M Denise , Remien Christopher H
Published: August 2016

As sequencing technologies have advanced, the amount of information regarding the composition of bacterial communities from various environments (e.g. skin, soil) has grown exponentially. To date, most work has focused on cataloging taxa present in samples and determining whether the distribution of taxa shifts with exogenous covariates. However, important questions regarding how taxa interact with each other and their environment remain open, thus preventing in-depth ecological understanding of microbiomes. Time-series data from 16S rDNA amplicon sequencing are becoming more common within microbial ecology, but given the ‘big data’ nature of these studies, there are currently no methods capable of utilizing the breadth of the data to infer ecological interactions from these longitudinal data. We address this gap by presenting a method of analysis using Poisson regression fit with an elastic-net penalty that 1) takes advantage of the fact that the data are time series; 2) constrains estimates to allow for the possibility of many more interactions than data; and 3) is scalable enough to handle data consisting of thousands of taxa. We test the method on gut microbiome data from white-throated woodrats (Neotoma albigula) that were fed varying amounts of the plant secondary compound oxalate over a period of 22 days to estimate interactions between OTUs and their environment.
Newborn chicks show inherited variability in early social predispositions for hen-like stimuli
Authors: Versace Elisabetta , Fracasso Ilaria , Baldan Gabriele , Zotte Antonella Dalle , Vallortigara Giorgio
Published: August 2016

Predispositions of newborn vertebrates to preferentially attend to living beings and learn about them are pervasive. Their disturbance (e.g. in human neonates at risk for autism), may compromise the proper development of a social brain. The genetic bases of such predispositions are unknown. Here we take advantage of well-known visual preferences exhibited by newly-hatched domestic chicks (Gallus gallus) for the head/neck region of their mother hen, to investigate the presence of segregating variation in the predispositions to approach a stuffed henvs.a scrambled version of it. We compared the spontaneous preferences of three different breeds that have been maintained genetically isolated for at least eighteen years and identically raised in the same farm. Visually-naïve chicks of all the three tested breeds (Padovana, Polverara and Robusta maculata) showed the same initial preference for the predisposed stimulus, suggesting that the direction of the initial preference might be genetically fixed. A few minutes later though, striking differences emerged between breeds, which could indicate early different strategies of dealing with affiliative objects: while the Polverara breed maintained a constant preference across the entire test, the Padovana and Robusta breeds progressively explored the alternative stimulus more. We argue that exploration of novelty might help chicks to look for responsive parental objects and to form a more structured representation of the mother hen. We hence documented the presence of inherited genetic variability for early social predisposition in interaction with environmental stimuli.