bluuebunny/crossref_metadata_2025 huggingface dataset:
Transitioning From Volume to Value: One Academic Medical Center’s Approach to Improving Population Health
Authors: Halvorson Stephanie A.C. , Tanski Mary E. , Yackel Thomas R.
Published: December 2016

Problem

The U.S. health care system is undergoing a major transformation. Clinical delivery systems are now being paid according to the value of the care they provide, in accordance with the Triple Aim, which incorporates improving the quality and cost of care and the patient experience. Increasingly, financial risk is being transferred from insurers to clinical delivery systems that become responsible for both episode-based clinical care and the longitudinal care of patients. Thus, these delivery systems need to develop strategies to manage the health of populations. Academic medical centers (AMCs) serve a unique role in many markets yet may be ill prepared for this transformation.

Approach

In 2013, Oregon Health & Science University (OHSU) partnered with a large health insurer and six other hospitals across the state to form Propel Health, a collaborative partnership designed to deliver the tools, methods, and support necessary for population health management. OHSU also developed new internal structures and transformed its business model to embrace this value-based care model.

Outcomes

Each Propel Health partner included the employees and dependents enrolled in its employee medical plan, for approximately 55,000 covered individuals initially. By 2017, Propel Health is expected to cover 110,000 individuals. Other outcomes to measure in the future include the quality and cost of care provided under this partnership.

Next Steps

Anticipated challenges to overcome include insufficient primary care networks, conflicting incentives, local competition, and the magnitude of the transformation. Still, the time is right for AMCs to commit to improving the health of populations.
Trends in net survival from kidney cancer in six European Latin countries: results from the SUDCAN population-based study
Authors: Mangone Lucia , Bossard Nadine , Marcos-Gragera Rafael , Pezzarossi Annamaria , Roncaglia Francesca , Giorgi Rossi Paolo
Published: December 2016

Kidney cancer is a frequent malignant disease. To date, there is no evidence on the effectiveness of early detection and, in most cases, surgery represents the only standard treatment. So far, there is no standardized therapy for localized and locally advanced renal tumors; however, the recent introduction of target therapy has significantly improved the prognosis of metastatic disease. Therefore, survival differences in Europe are deemed to involve differences in diagnostic and therapeutic approaches. The aim of the SUDCAN collaborative study was to compare the net survival from kidney cancer between six European Latin countries (Belgium, France, Italy, Portugal, Spain, and Switzerland) and provide trends in net survival and dynamics of excess mortality rates up to 5 years after diagnosis. The data were extracted from the EUROCARE-5 database. First, net survival was studied over the 2000–2004 period using the Pohar-Perme estimator. For trend analysis, the study period was specific to each country. The results are reported from 1992 to 2004 in France, Italy, Spain, and Switzerland, and from 2000 to 2004 in Belgium and Portugal. These analyses were carried out using a flexible excess rate modeling strategy. In 2000–2004, the 5-year net survival ranged between 59% (Spain) and 67% (France and Italy) in men and between 60% (Spain) and 73% (Portugal) in women. There was an increase in the age-standardized net survival between 1992 and 2004 at 1 year, as well as at 5 years, in all age groups and countries. Irrespective of the year of diagnosis, the excess mortality rate decreased with time elapsed since diagnosis. There are some differences in survival from kidney cancer between European Latin countries, but a considerable improvement was observed in most countries.
Development of a Limited Sampling Strategy for the Estimation of Exposure to High-Dose Etoposide After Intravenous Infusion in Pediatric Patients
Authors: Danielak Dorota , Sobiak Joanna , Wachowiak Jacek , Główka Franciszek , Chrzanowska Maria
Published: December 2016

Background:

Etoposide (VP-16), a podophyllotoxin derivative, is used in conditioning regimens before allogeneic hematopoietic stem cell transplantation in children with acute lymphoblastic leukemia. The aim of this study was to develop a limited sampling strategy (LSS) suitable for the prediction of exposure to VP-16 defined as area under time–concentration curve (AUC).

Methods:

The study included 28 pediatric patients with acute lymphoblastic leukemia, who were administered a 4-hour infusion of 60 mg/kg VP-16. VP-16 concentrations were determined in samples collected 4–124 hours after the beginning of infusion. On obtaining the pharmacokinetic (PK) profiles, a population PK model was developed in NONMEM (ICON Development Solutions, Hanover, MD) with first-order conditional estimation with interaction algorithm. LSSs were chosen by means of a multivariate regression analysis and cross-validated with a leave-one-out approach. Predictive performance of LSSs was assessed by calculating relative prediction error (PE), mean PE, mean absolute PE, and root mean squared PE for model-predicted and observed AUC.

Results:

VP-16 PKs was best described by a 2-compartment first-order model, and a large variability in the PK parameters was observed. A 3-sample strategy allowed the estimation of VP-16 with highest accuracy and precision (mean relative PE = 0.18%, 95% confidence interval, 1.73%–2.09%; mean absolute relative PE = 3.47%, 95% confidence interval, 2.28%–4.66%; root mean squared PE = 4.43%). The final equation was AUC = 6.85 × C6 h + 3.88 × C12 h + 46.11 × C28 h + 282.0 (adjusted R2 = 0.9540).

Conclusions:

In conclusion, developed LSS allows accurate and precise estimation of VP-16 AUC and might be useful for therapeutic drug monitoring.
An Easy Method for Drainage of Fluid in Cases of Continuous Irrigation of the Hand
Authors: Makhijani Sumeet , Fredenberg David A.
Published: December 2016

Description of a novel method to perform continuous irrigation for flexor tenosynovitis in a way that is comfortable for the patient and convenient for nursing staff by placing the hand in the suction pouch of a lithotomy style drape attached to wall suction.
The Normal Female Pelvis
Authors: ROACH MICHELLE K. , ANDREOTTI ROCHELLE F.
Published: December 2016

This article provides an overview of ultrasonographic evaluation of the normal female pelvis. Pertinent pelvic anatomy is reviewed, and there is an in-depth discussion of the normal appearance of the uterus and ovaries. In addition, the indications and technique for performing 3-dimensional imaging and saline-infused sonohysterography are covered.
REPRODUCIBILITY AND RELIABILITY OF OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FOR FOVEAL AVASCULAR ZONE EVALUATION AND MEASUREMENT IN DIFFERENT SETTINGS
Authors: La Spina Carlo , Carnevali Adriano , Marchese Alessandro , Querques Giuseppe , Bandello Francesco
Published: December 2016

Purpose:

Optical coherence tomography angiography (OCTA) allows delineating the foveal avascular zone (FAZ) easily and noninvasively. The present study aims to test reproducibility and reliability of FAZ evaluation by means of OCTA in different settings.

Methods:

Twenty-four eyes of 24 normal subjects were investigated using AngioVue OCTA Imaging System. A series of OCTA acquisitions were taken both in basal and in different experimental settings after vasoactive stimuli. Images were evaluated separately by two operators and FAZ area was measured both manually and using the built-in automated measurement tool.

Results:

No differences for FAZ area were found in the repetition of basal acquisitions, neither in manual nor in automated measurement (0.215 ± 0.06 vs. 0.216 ± 0.07, and 0.268 ± 0.05 vs. 0.264 ± 0.09, first vs. second basal measurement in square millimetres for manual and automated evaluation, P = 0.25 and P = 0.35, respectively). Interoperators correlation was optimal (r2 = 0.978 [95% CI 0.981–0.976]). No differences were found among the other settings, which included first basal and then repeated (second) in the morning, after flickering light stimulus, after a Bruce treadmill stress test, after 30 minutes dark adaptation, and basal in the evening, neither in automated nor in manual measurements. Automated measurements for nonflow areas provided significantly larger diameters than manual ones.

Conclusion:

AngioVue OCTA Imaging System produces highly reproducible FAZ images with a high interoperators concordance level. Optical coherence tomography angiography capability to detect FAZ area seems not to be influenced by any of the vasoactive stimuli considered in the current study. Nonflow areas seem to be larger when measured automatically than manually.
CHOROIDAL THICKNESS AS A PROGNOSTIC FACTOR OF PHOTODYNAMIC THERAPY WITH AFLIBERCEPT OR RANIBIZUMAB FOR POLYPOIDAL CHOROIDAL VASCULOPATHY
Authors: Sakurada Yoichi , Sugiyama Atsushi , Tanabe Naohiko , Kikushima Wataru , Kume Atsuki , Iijima Hiroyuki
Published: December 2016

Purpose:

To investigate factors associated with visual improvement and retreatment 12 months after a combination therapy of intravitreal injection of ranibizumab or aflibercept followed by photodynamic therapy for polypoidal choroidal vasculopathy.

Methods:

Changes in the best-corrected visual acuity and the subfoveal thickness of the retina and choroid were studied in 56 consecutive eyes with polypoidal choroidal vasculopathy treated initially with a combination therapy of either intravitreal ranibizumab injection (n = 23) or intravitreal aflibercept injection (n = 33) followed by photodynamic therapy. Factors associated with visual improvement and retreatment were investigated.

Results:

Best-corrected visual acuity significantly improved with significant reduction in central macular thickness and subfoveal choroidal thickness at all points irrespective of treatment modalities (P < 0.001). Better best-corrected visual acuity and improvement of best-corrected visual acuity at 12 months were associated with baseline greater subfoveal choroidal thickness (P = 0.028 and P = 0.028) and baseline smaller greatest linear dimension (P = 0.0077 and P = 0.0077). Retreatment during 12-month follow-up was associated with baseline lesser subfoveal choroidal thickness (P = 0.036).

Conclusion:

Irrespective of treatment modalities, the visual outcome at 12 months is favorable in eyes with polypoidal choroidal vasculopathy treated by photodynamic therapy combined with intravitreal ranibizumab or aflibercept. Baseline greater subfoveal choroidal thickness was associated with a better visual outcome and with reduction in the need for retreatment.
Corneal Biomechanical Properties After Penetrating Keratoplasty or Deep Anterior Lamellar Keratoplasty Using the Ocular Response Analyzer: A Meta-Analysis
Authors: Jiang Min-Shan , Zhu Jing-Yuan , Li Xue , Zhang Nan-Nan , Zhang Xue-Dian
Published: December 2016

Purpose:

To evaluate the corneal biomechanical properties of patients who have undergone penetrating keratoplasty (PK) or deep anterior lamellar keratoplasty (DALK) using the ocular response analyzer.

Methods:

Stata 13.0 SE was used for this meta-analysis. Studies in the literature that focused on corneal hysteresis (CH) or corneal resistance factor (CRF) after PK or DALK were retrieved by searching PubMed, Embase, Ovid, and Cochrane databases. We present the results as weighted mean difference (WMD) with a corresponding 95% confidence interval (CI).

Results:

Eight studies with a total of 750 eyes were included in the post-PK versus control group, and 4 studies with a total of 218 eyes were included in the post-DALK versus control group. The pooled results showed that CH and CRF were significantly reduced (P < 0.00001) for patients who have undergone PK (WMD = −1.16, 95% CI: −1.73 to −0.60 and WMD = −1.00, 95% CI: −1.61 to −0.40). No significant differences were found in both CH and CRF for patients who have undergone DALK (WMD = −0.27, 95% CI: −0.64 to −0.09 and WMD = −0.15, 95% CI: −0.53 to 0.23).

Conclusions:

This meta-analysis suggested that both CH and CRF had better recovery after corneal transplantation with DALK than PK.
Total Corneal Astigmatism Measurements: Agreement Between 2 Rotating Scheimpflug Cameras
Authors: Savini Giacomo , Næser Kristian , Schiano-Lomoriello Domenico , Ducoli Pietro
Published: December 2016

Purpose:

To investigate agreement between rotating Scheimpflug camera (Pentacam HR, Oculus) and rotating Scheimpflug camera combined with Placido disc corneal topography (Sirius, CSO) in measuring total corneal astigmatism (TCA).

Methods:

In this observational study, all patients undergoing cataract surgery with preoperative measurement of TCA by both devices and a validated corneal topographer (Keratron, Optikon 2000) were retrospectively evaluated. Astigmatism analysis was performed with and without vector analysis separately in eyes with with-the-rule, against-the-rule, and oblique astigmatism. Vector analysis was performed using the Næser polar system.

Results:

In 130 eyes of 130 subjects, nonvectorial analysis revealed that the mean TCA values obtained with the Sirius were higher than the corresponding values given by the Pentacam HR in all subgroups, although the difference was statistically significant only in eyes with against-the-rule astigmatism (P = 0.0009). This finding was confirmed by vector analysis. A TCA magnitude difference greater than 0.5 diopters was observed in 20.8% of cases, and a TCA axis difference greater than 10 degrees was observed in 45.4% of cases. Axis differences dropped to 18.5% when only eyes with astigmatism >0.75 diopters were analyzed and 3 measurements were averaged. The mean difference in the meridional and torsional power of TCA was close to zero in all subgroups, but with relatively large standard deviations (approximately 0.5 D).

Conclusions:

Agreement between both devices in measuring TCA is only moderate with respect to both magnitude and axis orientation.
Neonatal Bacterial Conjunctivitis in Korea in the 21st Century
Authors: Pak Kang Yeun , Kim Sung Il , Lee Jong Soo
Published: December 2016

Purpose:

To investigate the microbial cause and antibiotic susceptibility of neonatal bacterial conjunctivitis in Korean patients in the 21st century.

Methods:

We retrospectively reviewed the medical records of patients diagnosed with neonatal bacterial conjunctivitis between January 2000 and December 2015. We recorded the organism, antibiotic susceptibility, and antibiotics used.

Results:

A total of 82 neonates were included in the study (53 males and 29 females), with a mean age of 17.5 ± 7.1 days. The most commonly isolated organisms were Staphylococcus aureus (43 cases, 52.4%), coagulase-negative staphylococci (11 cases, 13.4%), Staphylococcus epidermidis (11 cases, 13.4%), Serratia marcescens (4 cases, 4.9%), Pseudomonas aeruginosa (4 cases, 4.9%), and Enterobacter cloacae (3 cases, 3.7%). We found no cases of Neisseria gonorrhoeae or Chlamydia trachomatis infection. Resistance to methicillin (83.7%), macrolide (81.4%), and aminoglycoside (23.3%) was observed in patients with S. aureus infection. Conjunctivitis that did not improve with erythromycin or tobramycin generally improved with the additional use of tosufloxacin.

Conclusions:

The prevalence of neonatal gonococcal or chlamydial conjunctivitis has decreased in the 21st century. However, methicillin-resistant S. aureus has been increasing, but these cases are responsive to tosufloxacin.
Presenting Features and Prognosis of Ischemic and Nonischemic Neonatal Liver Failure
Authors: Zozaya Nieto Carlos , Fernández Caamaño Beatriz , Muñoz Bartolo Gema , Menéndez Suso Juan J. , Frauca Remacha Esteban , Valverde Núñez Eva
Published: December 2016

Objectives:

To describe the epidemiological features, clinical characteristics and outcomes of neonates diagnosed with liver failure, as well as determine prognostic factors.

Methods:

Cohort study conducted at a single tertiary referral and university‐affiliated pediatric center. Hospital records of all neonates diagnosed with liver failure between January 2003 and December 2015 were retrospectively reviewed, and data on clinical and laboratory findings, treatment, and outcomes were collected. Survival analysis (Kaplan‐Meier) and Cox regression were performed to identify prognostic factors at diagnosis. Liver failure diagnosis was established using the pediatric acute liver failure study group's diagnostic criteria for every patient with coagulopathy and biochemical pattern of liver disease.

Results:

Forty‐five patients were included. In our series, most cases were secondary to ischemia (28.9%). Other causes were neonatal hemochromatosis (17.8%), viral infections (13.3%), and inborn errors of metabolism (13.3%). A total 55.6% (25/45) of the patients died (median age: 16 days; range 1–235 days). Alanine aminotransferase (ALT) at diagnosis was associated with higher mortality or the need for liver transplantation on day 21 after diagnosis (P = .006). For every 500 IU/L increase in ALT serum levels, the mortality/liver transplantation rate increased 1.3 times (hazard ratio 95% confidence interval: 1.1–1.6). Although ischemic neonatal acute liver failure presents with higher ALT levels, these cases appear to have better outcomes. Higher international normalized ratio tended to increase mortality/transplantation (hazard ratio 1.02; 95% confidence interval 0.91–1.2).

Conclusions:

Neonatal liver failure should perhaps be considered in the differential diagnoses of any coagulopathy. ALT and international normalized ratio levels at diagnosis could predict prognosis in the short term. Ischemic liver failure appears to have a better prognosis.
Granulosa Cell Tumors: Novel Predictors of Recurrence in Early-stage Patients
Authors: Sakr Sharif , Abdulfatah Eman , Thomas Sumi , Al-wahab Zaid , Beydoun Rafic , Morris Robert , Ali-Fehmi Rouba , Bandyopadhyay Sudeshna
Published: December 2016

Granulosa cell tumors (GCTs) comprise 2% to 5% of ovarian neoplasms, with unpredictable patterns of recurrence. The HER family, GATA4, and SMAD3 genes are reportedly involved in GCT proliferation and apoptosis and may serve as new predictors of recurrence. The aim of the study was to evaluate novel predictors of recurrence in GCT from a large single institution cohort. Patients diagnosed with GCTs (n=125) between 1975 and 2014 were identified. Clinicopathologic parameters were obtained and immunohistochemical evaluation was performed of calretinin, inhibin, HER2, CD56, SMAD3, and GATA4. Statistical analyses were conducted using Fisher exact test and Kaplan-Meier survival curves and Cox regression analysis. The median follow-up period was 120 months (range, 1–465 mo). Recurrence was noted in 12/125 (9.6%) patients. Kaplan-Meier analysis showed a shorter mean disease-free interval in whites versus blacks (P=0.001), stage III-IV versus stage I-II (P=0.0001), patients treated with surgery+chemotherapy versus surgery (P=0.0001), mitotic rate ≥4 (P=0.005), severe nuclear pleomorphism (P=0.013), high HER2 expression (P=0.001), high CD56 expression (P=0.001), and high SMAD3 expression (P=0.001). On Cox regression analysis, SMAD3 and type of treatment received were the only 2 independent prognostic factors for disease-free interval (P=0.03 and P=0.007, respectively). On subanalysis for early-stage (stage I) GCTs, the need for adjuvant chemotherapy and high expression of SMAD3 continued to be independent predictors of recurrence (HR=10.2, P=0.01 and HR=8.9, P=0.001, respectively).
Primary Vaginal Melanoma With Rhabdoid Features: A Case Report and Literature Review
Authors: Lee Chien-Kuan , Lin Ho , Su Chi-Feng , Kok Victor C.
Published: December 2016

Primary vaginal melanoma is a rare mucosal neoplasm, which is more aggressive than cutaneous melanoma. Information regarding its morphologic patterns is limited. In particular, the rhabdoid phenotype, mostly observed in metastatic or recurrent cutaneous melanomas, has yet to be reported at this anatomic location. Hence, a potential diagnostic difficulty may arise because of the inability to recognize this unusual histologic variant and its immunohistochemical aberrance. In this report, we describe the case of a primary vaginal melanoma in a 62-year-old woman, who exhibited both rhabdoid and small blue round cell morphologies, absence of S100 protein, and aberrant expression of desmin, CD56, and FLI-1. This report can facilitate the task of expanding the morphologic spectrum of vaginal melanoma, and prevent misdiagnosis and inadequate medical treatment.
Relationship Between Time to Initiation of Antiretroviral Therapy and Treatment Outcomes: A Cohort Analysis of ART Eligible Adolescents in Zimbabwe
Authors: Vogt Florian , Rehman Andrea M. , Kranzer Katharina , Nyathi Mary , Van Griensven Johan , Dixon Mark , Ndebele Wedu , Gunguwo Hilary , Colebunders Robert , Ndlovu Mbongeni , Apollo Tsitsi , Ferrand Rashida A.
Published: December 2016

Background:

Age-specific retention challenges make antiretroviral therapy (ART) initiation in adolescents difficult, often requiring a lengthy preparation process. This needs to be balanced against the benefits of starting treatment quickly. The optimal time to initiation duration in adolescents is currently unknown.

Objective:

To assess the effect of time to ART initiation on mortality and loss to follow-up (LTFU) among treatment eligible adolescents.

Methods:

We conducted a retrospective cohort analysis among 1499 ART eligible adolescents aged ≥10 to <19 years registered in a public sector HIV program in Bulawayo, Zimbabwe, between 2004 and 2011. Hazard ratios (HR) for mortality and LTFU were calculated for different time to ART durations using multivariate Cox regression models.

Results:

Median follow-up duration was 1.6 years. Mortality HRs of patients who initiated at 0 to ≤7 days, >14 days to ≤1 month, >1 to ≤2 months, >2 months, and before initiation were 1.59, 1.19, 1.56, 1.08, and 0.94, respectively, compared with the reference group of >7 to ≤14 days. LTFU HRs were 1.02, 1.07, 0.85, 0.97, and 3.96, respectively. Among patients not on ART, 88% of deaths and 85% of LTFU occurred during the first 3 months after becoming ART eligible, but only 37% and 29% among adolescents on ART, respectively.

Conclusions:

Neither mortality or LTFU was associated with varying time to ART. The initiation process can be tailored to the adolescents' needs and individual life situations without risking to increase poor treatment outcomes. Early mortality was high despite rapid ART initiation, calling for earlier rather than faster initiation through HIV testing scale-up.
Independent natural genetic variation of punishment- versus relief-memory
Authors: Appel Mirjam , Scholz Claus-Jürgen , Kocabey Samet , Savage Sinead , König Christian , Yarali Ayse
Published: December 2016

A painful event establishes two opponent memories: cues that are associated with pain onset are remembered negatively, whereas cues that coincide with the relief at pain offset acquire positive valence. Such punishment- versus relief-memories are conserved across species, including humans, and the balance between them is critical for adaptive behaviour with respect to pain and trauma. In the fruit fly,
Drosophila melanogaster
as a study case, we found that both punishment- and relief-memories display natural variation across wild-derived inbred strains, but they do not covary, suggesting a considerable level of dissociation in their genetic effectors. This provokes the question whether there may be heritable inter-individual differences in the balance between these opponent memories in man, with potential psycho-clinical implications.
Primate-specific oestrogen-responsive long non-coding RNAs regulate proliferation and viability of human breast cancer cells
Authors: Lin Chin-Yo , Kleinbrink Erica L. , Dachet Fabien , Cai Juan , Ju Donghong , Goldstone Amanda , Wood Emily J. , Liu Ka , Jia Hui , Goustin Anton-Scott , Kosir Mary A. , Thepsuwan Pattaraporn , Lipovich Leonard
Published: December 2016

Long non-coding RNAs (lncRNAs) are transcripts of a recently discovered class of genes which do not code for proteins. LncRNA genes are approximately as numerous as protein-coding genes in the human genome. However, comparatively little remains known about lncRNA functions. We globally interrogated changes in the lncRNA transcriptome of oestrogen receptor positive human breast cancer cells following treatment with oestrogen, and identified 127 oestrogen-responsive lncRNAs. Consistent with the emerging evidence that most human lncRNA genes lack homologues outside of primates, our evolutionary analysis revealed primate-specific lncRNAs downstream of oestrogen signalling. We demonstrate, using multiple functional assays to probe gain- and loss-of-function phenotypes in two oestrogen receptor positive human breast cancer cell lines, that two primate-specific oestrogen-responsive lncRNAs identified in this study (the oestrogen-repressed lncRNA BC041455, which reduces cell viability, and the oestrogen-induced lncRNA CR593775, which increases cell viability) exert previously unrecognized functions in cell proliferation and growth factor signalling pathways. The results suggest that oestrogen-responsive lncRNAs are capable of altering the proliferation and viability of human breast cancer cells. No effects on cellular phenotypes were associated with control transfections. As heretofore unappreciated components of key signalling pathways in cancers, including the MAP kinase pathway, lncRNAs hence represent a novel mechanism of action for oestrogen effects on cellular proliferation and viability phenotypes. This finding warrants further investigation in basic and translational studies of breast and potentially other types of cancers, has broad relevance to lncRNAs in other nuclear hormone receptor pathways, and should facilitate exploiting and targeting these cell viability modulating lncRNAs in post-genomic therapeutics.
Accurate recapture identification for genetic mark–recapture studies with error-tolerant likelihood-based match calling and sample clustering
Authors: Sethi Suresh A. , Linden Daniel , Wenburg John , Lewis Cara , Lemons Patrick , Fuller Angela , Hare Matthew P.
Published: December 2016

Error-tolerant likelihood-based match calling presents a promising technique to accurately identify recapture events in genetic mark–recapture studies by combining probabilities of latent genotypes and probabilities of observed genotypes, which may contain genotyping errors. Combined with clustering algorithms to group samples into sets of recaptures based upon pairwise match calls, these tools can be used to reconstruct accurate capture histories for mark–recapture modelling. Here, we assess the performance of a recently introduced error-tolerant likelihood-based match-calling model and sample clustering algorithm for genetic mark–recapture studies. We assessed both biallelic (i.e. single nucleotide polymorphisms; SNP) and multiallelic (i.e. microsatellite; MSAT) markers using a combination of simulation analyses and case study data on Pacific walrus (
Odobenus rosmarus divergens
) and fishers (
Pekania pennanti
). A novel two-stage clustering approach is demonstrated for genetic mark–recapture applications. First, repeat captures within a sampling occasion are identified. Subsequently, recaptures across sampling occasions are identified. The likelihood-based matching protocol performed well in simulation trials, demonstrating utility for use in a wide range of genetic mark–recapture studies. Moderately sized SNP (64+) and MSAT (10–15) panels produced accurate match calls for recaptures and accurate non-match calls for samples from closely related individuals in the face of low to moderate genotyping error. Furthermore, matching performance remained stable or increased as the number of genetic markers increased, genotyping error notwithstanding.
Food provisioning increases the risk of injury in a long-lived marine top predator
Authors: Christiansen Fredrik , McHugh Katherine A. , Bejder Lars , Siegal Eilidh M. , Lusseau David , McCabe Elizabeth Berens , Lovewell Gretchen , Wells Randall S.
Published: December 2016

Food provisioning of wildlife is a major concern for management and conservation agencies worldwide because it encourages unnatural behaviours in wild animals and increases each individual's risk for injury and death. Here we investigate the contributing factors and potential fitness consequences of a recent increase in the frequency of human interactions with common bottlenose dolphins (Tursiops truncatus) in Sarasota Bay, Florida. A rising proportion of the local long-term resident dolphin community is becoming conditioned to human interactions through direct and indirect food provisioning. We investigate variables that are affecting conditioning and if the presence of human-induced injuries is higher for conditioned versus unconditioned dolphins. Using the most comprehensive long-term dataset available for a free-ranging bottlenose dolphin population (more than 45 years; more than 32 000 dolphin group sightings; more than 1100 individuals), we found that the association with already conditioned animals strongly affected the probability of dolphins becoming conditioned to human interactions, confirming earlier findings that conditioning is partly a learned behaviour. More importantly, we found that conditioned dolphins were more likely to be injured by human interactions when compared with unconditioned animals. This is alarming, as conditioning could lead to a decrease in survival, which could have population-level consequences. We did not find a significant relationship between human exposure or natural prey availability and the probability of dolphins becoming conditioned. This could be due to low sample size or insufficient spatio-temporal resolution in the available data. Our findings show that wildlife provisioning may lead to a decrease in survival, which could ultimately affect population dynamics.
Morbillivirus-associated unusual mortality event in South Australian bottlenose dolphins is largest reported for the Southern Hemisphere
Authors: Kemper C. M. , Tomo I. , Bingham J. , Bastianello S. S. , Wang J. , Gibbs S. E. , Woolford L. , Dickason C. , Kelly D.
Published: December 2016

Cases of morbillivirus have been recorded in the Southern Hemisphere but have not been linked to significant marine mammal mortality. Post-mortems were conducted on 58 carcasses (44 Indo-Pacific bottlenose dolphins, two common bottlenose dolphins, 12 short-beaked common dolphins) from South Australia during 2005–2013, including an unusual mortality event (UME) in St Vincent Gulf Bioregion (SVG) during 2013. Diagnostic pathology, circumstance of death, body condition, age and stomach contents were documented for Indo-Pacific bottlenose dolphins. At least 50 dolphins died during the UME, 41 were Indo-Pacific bottlenose dolphins and most were young. The UME lasted about seven months and had two peaks, the first being the largest. Effect on the population is unknown. Diagnostic testing for morbillivirus was conducted on 57 carcasses, with evidence for infection in all species during 2011–2013. All tested UME bottlenose dolphins were positive for cetacean morbillivirus (CeMV), and the pathology included interstitial pneumonia, lymphoid depletion and syncytia. Concurrent pathologies, including lung parasite and fungal infections, and severe cutaneous bruising were observed in many dolphins. The event coincided with elevated water temperatures, a diatom bloom and significant fish die-offs. We conclude that the cause for the UME was multifactorial and that CeMV was a major contributor.
Does the stress response predict the ability of wild birds to adjust to short-term captivity? A study of the rock pigeon (
Columbia livia
)
Authors: Angelier Frédéric , Parenteau Charline , Trouvé Colette , Angelier Nicole
Published: December 2016

Although the transfer of wild animals to captivity is crucial for conservation purposes, this process is often challenging because some species or individuals do not adjust well to captive conditions. Chronic stress has been identified as a major concern for animals held on long-term captivity. Surprisingly, the first hours or days of captivity have been relatively overlooked. However, they are certainly very stressful, because individuals are being transferred to a totally novel and confined environment. To ensure the success of conservation programmes, it appears crucial to better understand the proximate causes of interspecific and interindividual variability in the sensitivity to these first hours of captivity. In that respect, the study of stress hormones is relevant, because the hormonal stress response may help to assess whether specific individuals or species adjust, or not, to such captive conditions (‘the stress response-adjustment to captivity hypothesis’). We tested this hypothesis in rock pigeons by measuring their corticosterone stress response and their ability to adjust to short-term captivity (body mass loss and circulating corticosterone levels after a day of captivity). We showed that an increased corticosterone stress response is associated with a lower ability to adjust to short-term captivity (i.e. higher body mass loss and circulating corticosterone levels). Our study suggests, therefore, that a low physiological sensitivity to stress may be beneficial for adjusting to captivity. Future studies should now explore whether the stress response can be useful to predict the ability of individuals from different populations or species to not only adjust to short-term but also long-term captivity.
Integrated deep learned transcriptomic and structure-based predictor of clinical trials outcomes
Authors: Artemov Artem V. , Putin Evgeny , Vanhaelen Quentin , Aliper Alexander , Ozerov Ivan V. , Zhavoronkov Alex
Published: December 2016

Despite many recent advances in systems biology and a marked increase in the availability of high-throughput biological data, the productivity of research and development in the pharmaceutical industry is on the decline. This is primarily due to clinical trial failure rates reaching up to 95% in oncology and other disease areas. We have developed a comprehensive analytical and computational pipeline utilizing deep learning techniques and novel systems biology analytical tools to predict the outcomes of phase I/II clinical trials. The pipeline predicts the side effects of a drug using deep neural networks and estimates drug-induced pathway activation. It then uses the predicted side effect probabilities and pathway activation scores as an input to train a classifier which predicts clinical trial outcomes. This classifier was trained on 577 transcriptomic datasets and has achieved a cross-validated accuracy of 0.83. When compared to a direct gene-based classifier, our multi-stage approach dramatically improves the accuracy of the predictions. The classifier was applied to a set of compounds currently present in the pipelines of several major pharmaceutical companies to highlight potential risks in their portfolios and estimate the fraction of clinical trials that were likely to fail in phase I and II.
Genomes of all known members of aPlasmodiumsubgenus reveal paths to virulent human malaria
Authors: Otto Thomas D. , Gilabert Aude , Crellen Thomas , Böhme Ulrike , Arnathau Céline , Sanders Mandy , Oyola Samuel , Okouga Alain Prince , Boundenga Larson , Willaume Eric , Ngoubangoye Barthélémy , Moukodoum Nancy Diamella , Paupy Christophe , Durand Patrick , Rougeron Virginie , Ollomo Benjamin , Renaud François , Newbold Chris , Berriman Matthew , Prugnolle Franck
Published: December 2016

Plasmodium falciparum,the most virulent agent of human malaria, shares a recent common ancestor with the gorilla parasiteP. praefalciparum.Little is known about the other gorilla and chimpanzee-infecting species in the same (Laverania) subgenus asP. falciparumbut none of them are capable of establishing repeated infection and transmission in humans. To elucidate underlying mechanisms and the evolutionary history of this subgenus, we have generated multiple genomes from all knownLaveraniaspecies. The completeness of our dataset allows us to conclude that interspecific gene transfers as well as convergent evolution were important in the evolution of these species. Striking copy number and structural variations were observed within gene families and one,stevorshows a host specific sequence pattern. The complete genome sequence of the closest ancestor ofP. falciparumenables us to estimate confidently for the first time the timing of the beginning of speciation to be 40,000-60,000 years ago followed by a population bottleneck around 4,000-6,000 years ago. Our data allow us also to search in detail for the features ofP. falciparumthat made it the only member of theLaveraniaable to infect and spread in humans.
Functional Analysis of All Salmonid Genomes (FAASG): an international initiative supporting future salmonid research, conservation and aquaculture
Authors: Macqueen Daniel J. , Primmer Craig R. , Houston Ross D. , Nowak Barbara F. , Bernatchez Louis , Bergseth Steinar , Davidson William S. , Gallardo-Escárate Cristian , Goldammer Tom , Guiguen Yann , Iturra Patricia , Kijas James W. , Koop Ben F. , Lien Sigbjørn , Maass Alejandro , Martin Samuel A.M. , McGinnity Philip , Montecino Martin , Naish Kerry A. , Nichols Krista M. , Ólafsson Kristinn , Omholt Stig W. , Palti Yniv , Plastow Graham S. , Rexroad Caird E. , Rise Matthew L. , Ritchie Rachael J. , Sandve Simen R. , Schulte Patricia M. , Tello Alfredo , Vidal Rodrigo , Vik Jon Olav , Wargelius Anna , Yáñez José Manuel
Published: December 2016

We describe an emerging initiative - the ‘Functional Analysis of All Salmonid Genomes’ (FAASG), which will leverage the extensive trait diversity that has evolved since a whole genome duplication event in the salmonid ancestor, to develop an integrative understanding of the functional genomic basis of phenotypic variation. The outcomes of FAASG will have diverse applications, ranging from improved understanding of genome evolution, through to improving the efficiency and sustainability of aquaculture production, supporting the future of fundamental and applied research in an iconic fish lineage of major societal importance.
The interplay of stiffness and force anisotropies drive embryo elongation
Authors: Vuong-Brender Thanh TK , Ben Amar Martine , Pontabry Julien , Labouesse Michel
Published: December 2016

The morphogenesis of tissues, like the deformation of an object, results from the interplay between their material properties and the mechanical forces exerted on them. Whereas the importance of mechanical forces in influencing cell behaviour is widely recognized, the importance of tissue material properties, in particular stiffness, has received much less attention. UsingC. elegansas a model, we examine how both aspects contribute to embryonic elongation. Measuring the opening shape of the epidermal actin cortex after laser nano-ablation, we assess the spatiotemporal changes of actomyosin-dependent force and stiffness along the antero-posterior and dorso-ventral axis. Experimental data and analytical modelling show that myosin II-dependent force anisotropy within the lateral epidermis, and stiffness anisotropy within the fiber-reinforced dorso-ventral epidermis are critical to drive embryonic elongation. Together, our results establish a quantitative link between cortical tension, material properties and morphogenesis of an entire embryo.
The epigenetic landscape of Alu repeats delineates the structural and functional genomic architecture of colon cancer cells
Authors: Jordà Mireia , Díez-Villanueva Anna , Mallona Izaskun , Martín Berta , Lois Sergi , Barrera Víctor , Esteller Manel , Vavouri Tanya , Peinado Miguel A.
Published: December 2016

Cancer cells exhibit multiple epigenetic changes with prominent local DNA hypermethylation and widespread hypomethylation affecting large chromosomal domains. Epigenome studies often disregard the study of repeat elements owing to technical complexity and their undefined role in genome regulation. We have developed NSUMA (Next-generation Sequencing of UnMethylated Alu), a cost-effective approach allowing the unambiguous interrogation of DNA methylation in more than 130,000 individual Alu elements, the most abundant retrotransposon in the human genome. DNA methylation profiles of Alu repeats have been analyzed in colon cancers and normal tissues using NSUMA and whole-genome bisulfite sequencing. Normal cells show a low proportion of unmethylated Alu (1%–4%) that may increase up to 10-fold in cancer cells. In normal cells, unmethylated Alu elements tend to locate in the vicinity of functionally rich regions and display epigenetic features consistent with a direct impact on genome regulation. In cancer cells, Alu repeats are more resistant to hypomethylation than other retroelements. Genome segmentation based on high/low rates of Alu hypomethylation allows the identification of genomic compartments with differential genetic, epigenetic, and transcriptomic features. Alu hypomethylated regions show low transcriptional activity, late DNA replication, and its extent is associated with higher chromosomal instability. Our analysis demonstrates that Alu retroelements contribute to define the epigenetic landscape of normal and cancer cells and provides a unique resource on the epigenetic dynamics of a principal, but largely unexplored, component of the primate genome.
About and on Behalf of Scriptum Est by Vesa Suominen
Authors: Laporte Steven
Published: December 2016

Purpose

This book review aims to draw attention to the often disregarded philosophical foundations of the library. Both the library as an institution and the science that studies its workings, are critically analyzed and put into an epistemological and even ideological perspective.

Design/methodology/approach

The original work by Vesa Suominen is explored in detail and its key findings subjected to criticism.

Findings

The book displays great originality and questions a number of long held beliefs regarding the library. Moving away from the more usual pragmatic and instrumentalist view of the library, the author proposes an approach that values the content of a library independant of its user. This approach, however, raises a number of questions.

Originality/value

Literature on the philosophical aspects of libraries and library science is scarce. Through this review we try to kindle a discussion that involves the basic mission statement of the modern library.
Locomotor endurance predicts differences in realized dispersal between sympatric sexual and unisexual salamanders
Authors: Denton Robert D. , Greenwald Katherine R. , Gibbs H. Lisle
Published: December 2016

Dispersal is the central mechanism that determines connectivity between populations yet few studies connect the mechanisms of movement with realized dispersal in natural populations. To make such a link, we assessed how physiological variation among individuals predicted dispersal in natural populations of unisexual (all‐female) and sexual Ambystoma salamanders on the same fragmented landscape in Ohio.

Specifically, we assessed variation in a trait that influences long‐distance animal movement (locomotor endurance) and determined whether variation in endurance matched patterns of realized dispersal assessed using genetic assignment tests. A possible mechanism for why unisexuals would have lower locomotor endurance than a sympatric sexual species (Ambystoma texanum) is the potential energetic cost of evolutionarily mismatched mitochondrial and nuclear genomes within polyploid unisexuals.

We found that sexuals walked four times farther than unisexuals during treadmill endurance trials that mimic the locomotor endurance required for dispersal.

We then applied landscape genetic methods to identify dispersed adults and quantify realized dispersal. We show that the differences in locomotor endurance between unisexual and sexual salamanders scale to realized dispersal: dispersing sexual individuals travelled approximately twice the distance between presumed natal wetlands and the site of capture compared to dispersing unisexuals.

This study links variation in individual performance in terms of endurance with realized dispersal in the field and suggests a potential mechanism (physiological limitation due to mitonuclear mismatch) for the reduced endurance of unisexual individuals relative to sexual individuals although we discuss other possible explanations.

The differences in dispersal between these two types of salamanders also informs our understanding of sexual/unisexual coexistence by suggesting that unisexuals are at a competitive disadvantage in terms of colonization ability under a extinction‐colonization model of coexistence.

A lay summary is available for this article.
Trait–demography relationships underlying small mammal population fluctuations
Authors: van Benthem Koen J. , Froy Hannah , Coulson Tim , Getz Lowell L. , Oli Madan K. , Ozgul Arpat
Published: December 2016

Large‐scale fluctuations in abundance are a common feature of small mammal populations and have been the subject of extensive research. These demographic fluctuations are often associated with concurrent changes in the average body mass of individuals, sometimes referred to as the ‘Chitty effect’. Despite the long‐standing recognition of this phenomenon, an empirical investigation of the underlying coupled dynamics of body mass and population growth has been lacking.

Using long‐term life‐history data combined with a trait‐based demographic approach, we examined the relationship between body mass and demography in a small mammal population that exhibits non‐cyclic, large‐scale fluctuations in abundance. We used data from the male segment of a 25‐year study of the monogamous prairie vole, Microtus ochrogaster, in Illinois, USA. Specifically, we investigated how trait–demography relationships and trait distributions changed between different phases of population fluctuations, and the consequences of these changes for both trait and population dynamics.

We observed phase‐specific changes in male adult body mass distribution in this population of prairie voles. Our analyses revealed that these changes were driven by variation in ontogenetic growth, rather than selection acting on the trait. The resulting changes in body mass influenced most life‐history processes, and these effects varied among phases of population fluctuation. However, these changes did not propagate to affect the population growth rate due to the small effect of body mass on vital rates, compared to the overall differences in vital rates between phases. The increase phase of the fluctuations was initiated by enhanced survival, particularly of juveniles and fecundity, whereas the decline phase was driven by an overall reduction in fecundity, survival and maturation rates.

Our study provides empirical support, as well as a potential mechanism, underlying the observed trait changes accompanying population fluctuations. Body size dynamics and population fluctuations resulted from different life‐history processes. Therefore, we conclude that body size dynamics in our population do not drive the observed population dynamics. This more in‐depth understanding of different components of small mammal population fluctuations will help us to better identify the mechanistic drivers of this interesting phenomenon.
Neoliberalism, Nationalism and the Decline of Political Traditions
Authors: Crouch Colin
Published: December 2016

The three great Western political traditions (conservatism, liberalism, social democracy) incorporate three of the four possible combinations of the core political axes: traditional, unchanging authority versus the challenge of change, and egalitarianism versus inegalitarianism. The fourth possibility—egalitarian conservatism—has appeared in various guises, but has usually become submerged within the right, including its most authoritarian forms. Current xenophobic movements claiming to represent those suffering from excessive change—for example, those involved in the UK's EU referendum and Donald Trump's victory in the USA—are seeing an apparent resurgence of this neglected tradition. What are its implications for politics in general?