bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal Development of Distortion Product Otoacoustic Emissions in Infants With Normal Hearing
Authors: Hunter Lisa L. , Blankenship Chelsea M. , Keefe Douglas H. , Feeney M. Patrick , Brown David K. , McCune Annie , Fitzpatrick Denis F. , Lin Li
Published: January 2018

Objectives:

The purpose of this study was to describe normal characteristics of distortion product otoacoustic emission (DPOAE) signal and noise level in a group of newborns and infants with normal hearing followed longitudinally from birth to 15 months of age.

Design:

This is a prospective, longitudinal study of 231 infants who passed newborn hearing screening and were verified to have normal hearing. Infants were enrolled from a well-baby nursery and two neonatal intensive care units (NICUs) in Cincinnati, OH. Normal hearing was confirmed with threshold auditory brainstem response and visual reinforcement audiometry. DPOAEs were measured in up to four study visits over the first year after birth. Stimulus frequencies f
1 and f
2 were used with f
2/f
1 = 1.22, and the DPOAE was recorded at frequency 2f
1–f
2. A longitudinal repeated-measure linear mixed model design was used to study changes in DPOAE level and noise level as related to age, middle ear transfer, race, and NICU history.

Results:

Significant changes in the DPOAE and noise levels occurred from birth to 12 months of age. DPOAE levels were the highest at 1 month of age. The largest decrease in DPOAE level occurred between 1 and 5 months of age in the mid to high frequencies (2 to 8 kHz) with minimal changes occurring between 6, 9, and 12 months of age. The decrease in DPOAE level was significantly related to a decrease in wideband absorbance at the same f
2 frequencies. DPOAE noise level increased only slightly with age over the first year with the highest noise levels in the 12-month-old age range. Minor, nonsystematic effects for NICU history, race, and gestational age at birth were found, thus these results were generalizable to commonly seen clinical populations.

Conclusions:

DPOAE levels were related to wideband middle ear absorbance changes in this large sample of infants confirmed to have normal hearing at auditory brainstem response and visual reinforcement audiometry testing. This normative database can be used to evaluate clinical results from birth to 1 year of age. The distributions of DPOAE level and signal to noise ratio data reported herein across frequency and age in normal-hearing infants who were healthy or had NICU histories may be helpful to detect the presence of hearing loss in infants.
Is the “Appropriate Use Criteria” for Type II Supracondylar Humerus Fractures Really Appropriate?
Authors: Silva Mauricio , Delfosse Erin M. , Park Howard , Panchal Hemali , Ebramzadeh Edward
Published: January 2018

Introduction:

The Appropriate Use Criteria for the treatment of supracondylar humerus fractures (SCHFs), developed by American Academy of Orthopaedic Surgeons, recommends pinning for all type II SCHFs. However, previous studies have suggested that, with close follow-up some of the less severe type II SCHF’s can be successfully treated without surgery. Our purpose was to analyze data collected prospectively on a large cohort of type II SCHF’s.

Methods:

We reviewed clinical and radiographic information on all type II pediatric SCHF (n=1120) that were enrolled in a prospective registry and were followed for a minimum of 8 weeks. The characteristics of the patients who were treated without surgery were compared with those of patients who were ultimately treated surgically. Treatment outcomes, as assessed by the final clinical and radiographic alignment, range of motion of the elbow, and complications were compared between the groups to define clinical and radiographic features that related to success or failure of nonoperative management.

Results:

Ultimately, 812 fractures (72%) were treated nonoperatively, and 309 fractures (28%) were treated surgically. At final follow-up, outcome measures of change in carrying angle, range of motion, and complications did not show clinically significant differences between treatment groups. Binary logistic regression analysis indicated that initial radiographic features, specifically rotational deformity, varus malalignment, valgus malalignment, and a shaft-condylar angle of <30 degrees were strongly related to selection for surgery. Patients with isolated extension deformity, but none of the other features, were more likely to complete successful nonoperative management.

Conclusions:

Pinning all type II SCHF, as recommended by the Appropriate Use Criteria, would have resulted in unnecessary surgery in 72% of patients in this series. Given the wide range of injury severity within the type II category of SCHF, better discrimination of factors commonly associated with successful nonoperative treatment is required. In this particular series, fractures with an isolated extension deformity (without rotational or coronal malalignment) were more likely to complete successful nonoperative management.
The Role of Ankle Arthroscopy in Ankle Fractures
Authors: Diefenbach Christopher , Nguyen Kevin , Kreulen Christopher , Giza Eric
Published: January 2018

The purpose of this chapter is to review the available literature and describe the technique when utilizing arthroscopy in the treatment of ankle fractures. The high incidence of acute cartilage injuries and the difficulty diagnosing syndesmotic instability in ankle fractures have led to the adjunctive use of arthroscopy in their treatment since the 1990s. Although this remains a controversial topic, multiple studies have demonstrated the potential of ankle arthroscopy to help confirm anatomic reduction, limit the surgical exposure and soft tissue trauma, and to diagnose and treat associated intra-articular pathology in displaced ankle fractures.

Level of Evidence:Diagnostic Level 4. See Instructions for Authors for a complete description of levels of evidence.
Prompt Administration of Antibiotics and Fluids in the Treatment of Sepsis: A Murine Trial*
Authors: Lewis Anthony J. , Griepentrog John E. , Zhang Xianghong , Angus Derek C. , Seymour Christopher W. , Rosengart Matthew R.
Published: January 2018

Objectives:

Sepsis, the acute organ dysfunction caused by a dysregulated host response to infection, poses a serious public health burden. Current management includes early detection, initiation of antibiotics and fluids, and source control as necessary. Although observational data suggest that delays of even a few hours in the initiation of antibiotics or IV fluids is associated with survival, these findings are controversial. There are no randomized data in humans, and prior animal studies studied time from experimental manipulation, not from the onset of clinical features of sepsis. Using a recently developed murine cecal ligation and puncture model that precisely monitors physiologic deterioration, we hypothesize that incremental hourly delays in the first dose of antibiotics, in the first bolus of fluid resuscitation, or a combination of the two at a clinically relevant point of physiologic deterioration during polymicrobial sepsis will shorten survival.

Design:

Randomized laboratory animal experimental trial.

Setting:

University basic science laboratory.

Subjects:

Male C57BL/6J, female C57BL/6J, aged (40–50 wk old) male C57BL/6J, and BALB/C mice.

Interventions:

Mice (n = 200) underwent biotelemetry-enhanced cecal ligation and puncture and were randomized after meeting validated criteria for acute physiologic deterioration. Treatment groups consisted of a single dose of imipenem/cilastatin, a single bolus of 30 mL/kg fluid resuscitation, or a combination of the two. Mice were allocated to receive treatment at the time of meeting deterioration criteria, after a 2-hour delay or after a 4-hour delay.

Measurements and Main Results:

Hourly delays in the initiation of antibiotic therapy led to progressively shortened survival in our model (p < 0.001). The addition of fluid resuscitation was unable to rescue animals, which received treatment 4 hours after meeting enrollment criteria. Systemic inflammation was increased, and host physiology was increasingly deranged with hourly delays to antibiotics.

Conclusions:

We conclude that antibiotic therapy is highly time sensitive, and efforts should be made to deliver this critical therapy as early as possible in sepsis, perhaps extending into the first point of medical contact outside the hospital.
Effects of a Kundalini Yoga Program on Elementary and Middle School Students' Stress, Affect, and Resilience
Authors: Sarkissian Meliné , Trent Natalie L. , Huchting Karen , Singh Khalsa Sat Bir
Published: January 2018

Objective:

The Your Own Greatness Affirmed (YOGA) for Youth program delivers yoga to urban inner-city schools with the goal of providing practical benefits that support underserved children at high risk of behavioral and emotional problems. A 10-week YOGA for Youth program delivered 1 to 2 times per week was implemented in 3 schools in urban neighborhoods to examine the effect of the program on student stress, affect, and resilience.

Methods:

Thirty children were administered the Perceived Stress Scale, the Positive and Negative Affect Schedule, and the Resilience Scale before and after the yoga program. After the program, informal qualitative interviews were conducted with school teachers, yoga teachers, and students to determine the overall impact of the yoga program.

Results:

The quantitative results of this study indicated that the yoga program significantly improved students stress (p < 0.05), positive affect (p < 0.05), and resilience (p < 0.001). The qualitative results indicated that students, school teachers, and yoga teachers all found the program to be beneficial for students' well-being.

Conclusion:

Taken together, these data suggest that the YOGA for Youth program may provide students in low-income urban schools with behavioral skills that will protect against risk factors associated with the development of behavioral and emotional problems.
BETA-D-GLUCAN TESTING IN PATIENTS WITH FUNGAL ENDOPHTHALMITIS
Authors: Kolomeyer Anton M. , Murphy Kathleen M. , Traband Anastasia , Frank Ian , Kim Benjamin J.
Published: January 2018

Purpose:

To review the literature on beta-D-glucan (BDG) testing in fungal endophthalmitis.

Methods:

Review of primary literature using PubMed through April 2017 and presentation of an illustrative case report. A total of 231 articles were identified and 43 were ultimately chosen for review based on relevance and presence of ophthalmologic examination and objective data.

Results:

Beta-D-glucan is a major component of fungal cell walls. It is quantified using a calorimetry-based Fungitell assay based on modification of the limulus amebocyte lysate. Serum BDG levels are commonly used clinically in conjunction with other tests for early surveillance and diagnosis of invasive fungal infections. In the ophthalmic literature, elevated levels of BDG have been detected in vitreous fluid of patients undergoing vitrectomy for fungal endophthalmitis, tear fluid of patients with mycotic keratitis, and serum of a patient with bilateral endogenous subretinal abscesses. Elevated serum BDG levels appear to be highly associated with fungal endophthalmitis. Potential uses and considerations with regards to test limitations are discussed.

Conclusion:

Beta-D-glucan testing may be used as an adjunct to support a diagnosis, initiate pharmacologic therapy or surgical intervention, and optimize overall clinical management in patients diagnosed with or under clinical suspicion for invasive fungal infections, including endophthalmitis. Additional clinical studies are necessary to fully characterize the utility of BDG testing in patients with fungal endophthalmitis.
Paracanthal “One-Snip” Decompression in a Cadaver Model of Retrobulbar Hemorrhage
Authors: Blandford Alexander D. , Young Jason M. , Arepalli Sruthi , Li Ang , Hwang Catherine J. , Perry Julian D.
Published: January 2018

Purpose:

The authors assess the effectiveness of a modified paracanthal or “one-snip” procedure compared with the traditional lateral canthotomy and inferior cantholysis in the reduction of intraocular pressure (IOP) and proptosis in a human cadaveric model of retrobulbar hemorrhage.

Methods:

This study comprised a comparative interventional study in a cadaveric model of retrobulbar hemorrhage. Six orbits of 3 fresh cadavers were included in the study. Baseline measurements of IOP and proptosis were recorded for all 6 orbits before and after simulation of retrobulbar hemorrhage as previously described. Right orbits (n = 3) underwent traditional lateral canthotomy and inferior cantholysis. Left orbits (n = 3) underwent modified paracanthal or “one-snip” procedure. The primary outcome measures were reduction in IOP and proptosis between the 2 techniques.

Results:

Following lateral canthotomy and inferior cantholysis of each right orbit, the average IOP dropped to 14 mm Hg (range of 11–18 mm Hg), corresponding to a mean decrease of 32 mm Hg. Following the “one-snip” procedure of each left orbit, the average IOP dropped to 19 mm Hg with a range of 16 to 23 mm Hg, corresponding to a mean decrease of 22 mm Hg. There was no statistically significant difference in IOP reduction (p = 0.36) or proptosis reduction (p = 0.23) between the 2 treatment groups.

Conclusions:

Compared with traditional lateral canthotomy xand inferior cantholysis, the modified paracanthal or “one-snip” procedure is effective for IOP reduction and led to mild improvement of proptosis in a cadaveric model of retrobulbar hemorrhage. The authors hope this study helps improve orbital compartment syndrome outcomes by providing an option that more providers will feel comfortable performing and therefore decreasing time to surgical decompression.
Analysis of Complications After Button Battery Ingestion in Children
Authors: Varga Ágnes , Kovács Tamás , Saxena Amulya K.
Published: January 2018

Aim

Button battery ingestion (BBI) in children may cause severe complications. This analysis is a literature review of complications after pediatric BBI.

Methods

Literature was searched on PubMed (1995–2015) using the terms “button battery,” “ingestion,” and “children.” End points were age, type and diameter of battery, complications, affected organ, and fatality.

Results

A total of 31 publications were analyzed. Patients from 4 months to 19 years old were included (n = 136,191, with n = 102,143 or 75% aged <6 y). In 6262, the diameter of the battery was documented. Batteries of 20 mm or greater in size were more prone to complications (n = 226). With regard to the anatomy, BBI caused complications mainly in the esophagus (n = 88, 38.94%). Sixty-one fatal outcomes were reported.

Conclusions

Children younger than 6 years are the most prone to BBI, with lithium batteries of 20 mm or greater in size associated with complications. Complications have been estimated at 0.165%, with lethality of 0.04%. The esophagus is the most affected organ, but vascular involvement is often fatal.
Patient-Reported Dental Safety Events: A South African Perspective
Authors: Obadan-Udoh Enihomo , Van der Berg-Cloete Sophy , Ramoni Rachel , Kalenderian Elsbeth , White John George
Published: January 2018

Objectives

In recent years, there has been an increase in research studies highlighting patients’ experiences of adverse events (AEs) as well as the role of patients in promoting safety. The primary goal of the study was to assess the prevalence of dental AEs (DAEs) among dental patients in South Africa and its associated factors. The integration of the patient perspective into dental patient safety research will enhance our collective understanding of DAEs.

Methods

We conducted a cross-sectional study of adult patients at a large dental academic institution in South Africa from May to June 2015, evaluating their previous experiences of DAEs at any dental clinic in South Africa. Descriptive statistics and bivariate and multivariate analyses were performed to identify the factors associated with an increased likelihood of experiencing a DAE.

Results

A total of 440 questionnaires were returned during the 6-week study period (response rate = 97.8%). Overall, 45.5% of participants reported experiencing one or more DAEs. Two hundred participants reported a total of 717 DAEs giving us a lifetime prevalence of 1.6 DAEs per respondent. Our results suggest that respondents who were younger (18–24 y), from high-income families (>R150,000 or US $9200), dissatisfied with their last dental visit and oral health had an increased likelihood of reporting a previous experience of a DAE.

Conclusions

This study provides an insight into the nature of information that can be gleaned from dental patients regarding safety and helps lay the foundation for patient involvement in patient safety reporting.
Gastric Lipoma
Authors: Chagarlamudi Kaushik , Devita Robert , Barr Richard G.
Published: January 2018

Gastric lipoma is a rare benign tumor of the stomach. The imaging characteristics are diagnostic because the lesion has fat attenuation on computed tomography and demonstrates characteristics of fat on magnetic resonance images. On ultrasound, the lesion can be identified as a lesion hypoechoic to the gastric mucosa that is soft, but the mass cannot be displaced with compression. Identifying these imaging characteristics can prevent biopsy or surgery in asymptomatic patients. Although this lesion is benign, it can cause gastric obstruction.
Does Brow Lift Add Risk to Blepharoplasty? Answers From a Multicenter Analysis of 6126 Patients Undergoing Aesthetic Eye Surgery
Authors: Wormer Blair A. , Rankin Timothy M. , Kaoutzanis Christodoulos , Al Kassis Salam , Gupta Varun , Grotting James C. , Higdon Kent K.
Published: January 2018

Background

Browlift is frequently combinedwith blepharoplasty; however, the literature is lacking on their combined effect on complication rates.

Objectives

This study aims to evaluate major complication rates after blepharoplasty and brow lift and to determine if complication rates increase when blepharoplasty and brow lift were performed simultaneously.

Methods

A prospective cohort of patients who underwent cosmetic blepharoplasty, brow lift, or a combination of the 2 procedures between 2008 and 2013 was identified from the CosmetAssure Insurance database. The primary outcome was a postoperative major complication requiring emergency room evaluation, hospital admission, or reoperation within 30 days. Groups were compared with univariate analysis (significance, P < 0.05).

Results

A total of 6126 patients underwent aesthetic eye surgery, of which, 4879 (79.6%) underwent blepharoplasty, 441 (7.2%) brow lift, and 806 (13.2%) a combination the 2 procedures. Patients who underwent a combined procedure were older than patients who underwent isolated blepharoplasty or brow lift (55.5 ± 9.4 vs 54.6 ± 11.1 vs 53.3 ± 12.0 years; P < 0.01). In males, blepharoplasty was the most commonly performed procedure, followed by a combined procedure and brow lift (17.6% vs 12.9% vs 10.7%; P < 0.01). There were similar rates of smokers between the 3 groups (5.7% vs 8.0% vs 6.6%; P = 0.06). Between combined procedures, blepharoplasty, and brow lift there, were similar rates of major complications (0.4% vs 0.4% vs 0.7%; P = 0.65) and hematoma (0.2% vs 0.2% vs 0.5%; P = 0.49), which was the most common complication.

Conclusions

Aesthetic eye surgery has a very low overall major complication rate (0.4%). When brow lift is combined with blepharoplasty, it poses no additional risk of major complications compared with either procedure alone.
Is Food Insecurity Associated With Lipid Profile and Atherogenic Indices in Iranian Adults? A Population-Based Study
Authors: Nikniaz Leila , Tabrizi Jafar Sadegh , Sadeghi-Bazargani Homayoun , Farahbakhsh Mostafa , Nikniaz Zeinab
Published: January 2018

The associations between food insecurity and lipid profile and atherogenic indices were assessed. Food insecurity data were collected through the short form of the Household Food Security Scale. The serum levels of triglyceride (TG), total cholesterol (TC), and high-density lipoprotein (HDL) were measured and low-density lipoprotein (LDL) level, TC/HDL, and log (TG/HDL) were calculated. The analysis of variance and logistic regression were used for statistical analysis. There was a significant difference in the mean TC/HDL and log (TG/HDL) ratios between men in different categories of food security. The mean TC/HDL cholesterol level was significantly higher in men in the low food secure group (P = .03). Among women, the mean level of TC/HDL in the very low food secure group was significantly higher than that in 2 other categories (P = .04). According to the results of logistic regression, very low food secure men compared with food secure men were more likely to have lower level of HDL cholesterol (2.75, 95% confidence interval [CI]: 1.06–7.12) and higher ratio of log (TG/HDL) (3.03, 95% CI: 1.17–7.58). Compared with the food secure group, very low food secure women were more likely to have higher level of TG values (2.55, 95% CI: 1.01–6.45). The association observed between food insecurity and dyslipidemia strengthens the growing evidence that food insecurity may be a marker of poor overall health.
Towards personalized computational oncology: from spatial models of tumour spheroids, to organoids, to tissues
Authors: Karolak Aleksandra , Markov Dmitry A. , McCawley Lisa J. , Rejniak Katarzyna A.
Published: January 2018

A main goal of mathematical and computational oncology is to develop quantitative tools to determine the most effective therapies for each individual patient. This involves predicting the right drug to be administered at the right time and at the right dose. Such an approach is known as precision medicine. Mathematical modelling can play an invaluable role in the development of such therapeutic strategies, since it allows for relatively fast, efficient and inexpensive simulations of a large number of treatment schedules in order to find the most effective. This review is a survey of mathematical models that explicitly take into account the spatial architecture of three-dimensional tumours and address tumour development, progression and response to treatments. In particular, we discuss models of epithelial acini, multicellular spheroids, normal and tumour spheroids and organoids, and multi-component tissues. Our intent is to showcase how these
in silico
models can be applied to patient-specific data to assess which therapeutic strategies will be the most efficient. We also present the concept of virtual clinical trials that integrate standard-of-care patient data, medical imaging, organ-on-chip experiments and computational models to determine personalized medical treatment strategies.
Quantitative approaches to energy and glucose homeostasis: machine learning and modelling for precision understanding and prediction
Authors: McGrath Thomas , Murphy Kevin G. , Jones Nick S.
Published: January 2018

Obesity is a major global public health problem. Understanding how energy homeostasis is regulated, and can become dysregulated, is crucial for developing new treatments for obesity. Detailed recording of individual behaviour and new imaging modalities offer the prospect of medically relevant models of energy homeostasis that are both understandable and individually predictive. The profusion of data from these sources has led to an interest in applying machine learning techniques to gain insight from these large, relatively unstructured datasets. We review both physiological models and machine learning results across a diverse range of applications in energy homeostasis, and highlight how modelling and machine learning can work together to improve predictive ability. We collect quantitative details in a comprehensive mathematical supplement. We also discuss the prospects of forecasting homeostatic behaviour and stress the importance of characterizing stochasticity within and between individuals in order to provide practical, tailored forecasts and guidance to combat the spread of obesity.
Overcoming hydrodynamic challenges in suspension feeding by juvenile
Mya arenaria
clams
Authors: Du Clos Kevin T. , Jiang Houshuo
Published: January 2018

We present some of the few suspension-feeding measurements and to our knowledge the first velocity-field measurements for early post-settlement juvenile bivalve clams. We verify and extend our experimental results with numerical simulations. For 1.8–2.8 mm shell length
Mya arenaria
clams, pumping rates ranged 0.03–0.22 μl s
−1
, inhalant siphon Reynolds numbers (
Re
) ranged 0.16–0.79 and mean inhalant velocities ranged 0.8–3.2 mm s
−1
. Owing to the low
Re
at which they pump and the small diameters of their siphons, juvenile clams are subject to unique hydrodynamic challenges, including high siphon resistance and susceptibility to refiltration. At least three features of juvenile clam siphons differentiate them from those of adults–shorter inhalant siphon length, a more rapid increase in inhalant siphon diameter with shell length, and the presence of a prominent exhalant siphon extension. These features are probably adaptations to the challenges of suspension feeding at low
Re
.
Quantification of plasma cell dynamics using mathematical modelling
Authors: Mohr Marcel , Hose Dirk , Seckinger Anja , Marciniak-Czochra Anna
Published: January 2018

Plasma cells (PCs) are the main antibody-producing cells in humans. They are long-lived so that specific antibodies against either pathogens or vaccines are produced for decades. PC longevity is attributed to specific areas within the bone marrow micro-environment, the so-called ‘niche’, providing the cells with required growth and survival factors. With antigen encounters, e.g. infection or vaccination, new PCs are generated and home to the bone marrow where they compete with resident PCs for the niche. We propose a parametrized mathematical model describing healthy PC dynamics in the bone marrow. The model accounts for competition for the niche between newly produced PCs owing to vaccination and resident PCs. Mathematical analysis and numerical simulations of the model allow explanation of the recovery of PC homoeostasis after a vaccine-induced perturbation, and the fraction of vaccine-specific PCs inside the niche. The model enables quantification of the niche-related dynamics of PCs, i.e. the duration of PC transition into the niche and the impact of different rates for PC transitions into and out of the niche on the observed cell dynamics. Ultimately, it provides a potential basis for further investigations in health and disease.
Rapid and sensitive biomarker detection using molecular imprinting polymer hydrogel and surface-enhanced Raman scattering
Authors: Chen Shaona , Dong Lijing , Yan Min , Dai Zhongxu , Sun Chenghua , Li Xin
Published: January 2018

Biomarkers are important biochemical indicators, which could be used for identification, early diagnosis and monitoring of diseases during the course of treatment. However, biomarker diagnosis has some shortcomings such as requiring a large amount of samples, long test time and high cost, which seriously influences the correctness and timely treatment to patients. Here, a relatively fast and efficient plasmonic hot spot-localized surface imprinting of Ag spheres using biomarker template immobilization and hydrogel copolymerization is described. The technique takes a fine control of the imprinting process at the nanometre scale and provides a biosensor with high sensitivity. Proof of the opinion is established by detection of biomarker using surface-enhanced Raman scattering (SERS) spectroscopy. This work represents a valuable step towards SERS with biomarkers for cost-saving and time-saving diagnostic assay. It is expected that the new surface imprinted hydrogel plasmonic material can drive possibilities in advancing application of biomarkers in plasmonic biosensors.
Synthesis of gypsogenin derivatives with capabilities to arrest cell cycle and induce apoptosis in human cancer cells
Authors: Zhang Haochao , Mu Yanling , Wang Fengling , Song Leling , Sun Jie , Liu Yongjun , Sun Jingyong
Published: January 2018

Thirty-two gypsogenin derivatives were synthesized and screened for their cytotoxic activities. Their structures were established using IR,
1
H NMR,
13
C NMR, and LC-MS spectroscopic data. In MTT assays nearly all the compounds displayed good cytotoxicity in the low μM range for several human tumour cell lines (A549, LOVO, SKOV3 and HepG2). Low IC
50
values were obtained especially for the carboxamides
7a
–
7j
, for an oxime derivative
3
and a (2,4-dinitrophenyl)hydrazono derivative
4
. In particular, the IC
50
values of compounds
4
(IC
50
 = 2.97 ± 1.13 µΜ) and
7 g
(IC
50
 = 3.59 ± 2.04 µΜ) against LOVO cells were found to be much lower than those of the other derivatives and parent compound. These compounds were submitted to an extensive biological testing and proved compounds
4
and
7 g
to act mainly by an arrest of the tumour cells in the S phase of the cell cycle. In addition, compounds
4
and
7 g
triggered the apoptotic pathway in cancer cells, showing high apoptosis ratios.
Trophic interactions between larger crocodylians and giant tortoises on Aldabra Atoll, Western Indian Ocean, during the Late Pleistocene
Authors: Scheyer Torsten M. , Delfino Massimo , Klein Nicole , Bunbury Nancy , Fleischer-Dogley Frauke , Hansen Dennis M.
Published: January 2018

Today, the UNESCO World Heritage Site of Aldabra Atoll is home to about 100 000 giant tortoises,
Aldabrachelys gigantea
, whose fossil record goes back to the Late Pleistocene. New Late Pleistocene fossils (age
ca
. 90–125 000 years) from the atoll revealed some appendicular bones and numerous shell fragments of giant tortoises and cranial and postcranial elements of crocodylians. Several tortoise bones show circular holes, pits and scratch marks that are interpreted as bite marks of crocodylians. The presence of a Late Pleistocene crocodylian species,
Aldabrachampsus dilophus
, has been known for some time, but the recently found crocodylian remains presented herein are distinctly larger than those previously described. This indicates the presence of at least some larger crocodylians, either of the same or of a different species, on the atoll. These larger crocodylians, likely the apex predators in the Aldabra ecosystem at the time, were well capable of inflicting damage on even very large giant tortoises. We thus propose an extinct predator–prey interaction between crocodylians and giant tortoises during the Late Pleistocene, when both groups were living sympatrically on Aldabra, and we discuss scenarios for the crocodylians directly attacking the tortoises or scavenging on recently deceased animals.
Assessing the features of extreme smog in China and the differentiated treatment strategy
Authors: Deng Lu , Zhang Zhengjun
Published: January 2018

Extreme smog can have potentially harmful effects on human health, the economy and daily life. However, the average (mean) values do not provide strategically useful information on the hazard analysis and control of extreme smog. This article investigates China's smog extremes by applying extreme value analysis to hourly PM2.5 data from 2014 to 2016 obtained from monitoring stations across China. By fitting a generalized extreme value (GEV) distribution to exceedances over a station-specific extreme smog level at each monitoring location, all study stations are grouped into eight different categories based on the estimated mean and shape parameter values of fitted GEV distributions. The extreme features characterized by the mean of the fitted extreme value distribution, the maximum frequency and the tail index of extreme smog at each location are analysed. These features can provide useful information for central/local government to conduct differentiated treatments in cities within different categories and conduct similar prevention goals and control strategies among those cities belonging to the same category in a range of areas. Furthermore, hazardous hours, breaking probability and the 1-year return level of each station are demonstrated by category, based on which the future control and reduction targets of extreme smog are proposed for the cities of Beijing, Tianjin and Hebei as an example.
Brain size affects performance in a reversal-learning test
Authors: Buechel Séverine D. , Boussard Annika , Kotrschal Alexander , van der Bijl Wouter , Kolm Niclas
Published: January 2018

It has become increasingly clear that a larger brain can confer cognitive benefits. Yet not all of the numerous aspects of cognition seem to be affected by brain size. Recent evidence suggests that some more basic forms of cognition, for instance colour vision, are not influenced by brain size. We therefore hypothesize that a larger brain is especially beneficial for distinct and gradually more complex aspects of cognition. To test this hypothesis, we assessed the performance of brain size selected female guppies (
Poecilia reticulata
) in two distinct aspects of cognition that differ in cognitive complexity. In a standard reversal-learning test we first investigated basic learning ability with a colour discrimination test, then reversed the reward contingency to specifically test for cognitive flexibility. We found that large-brained females outperformed small-brained females in the reversed-learning part of the test but not in the colour discrimination part of the test. Large-brained individuals are hence cognitively more flexible, which probably yields fitness benefits, as they may adapt more quickly to social and/or ecological cognitive challenges. Our results also suggest that a larger brain becomes especially advantageous with increasing cognitive complexity. These findings corroborate the significance of brain size for cognitive evolution.
Evidence that fertility trades off with early offspring fitness as males age
Authors: Johnson Sheri L. , Zellhuber-McMillan Sylvia , Gillum Joanne , Dunleavy Jessica , Evans Jonathan P. , Nakagawa Shinichi , Gemmell Neil J.
Published: January 2018

Models of ageing predict that sperm function and fertility should decline with age as sperm are exposed to free radical damage and mutation accumulation. However, theory also suggests that mating with older males should be beneficial for females because survival to old age is a demonstration of a male's high genetic and/or phenotypic quality. Consequently, declines in sperm fitness may be offset by indirect fitness benefits exhibited in offspring. While numerous studies have investigated age-based declines in male fertility, none has taken the integrated approach of studying age-based effects on both male fertility and offspring fitness. Here, using a cohort-based longitudinal study of zebrafish (Danio rerio), we report a decline in male mating success and fertility with male age but also compensating indirect benefits. Usingin vitrofertilization, we show that offspring from older males exhibit superior early survival compared to those from their youngest counterparts. These findings suggest that the high offspring fitness observed for the subset of males that survive to an old age (approx. 51% in this study) may represent compensating benefits for declining fertility with age, thus challenging widely held views about the fitness costs of mating with older males.
Trust your gut: using physiological states as a source of information is almost as effective as optimal Bayesian learning
Authors: Higginson Andrew D. , Fawcett Tim W. , Houston Alasdair I. , McNamara John M.
Published: January 2018

Approaches to understanding adaptive behaviour often assume that animals have perfect information about environmental conditions or are capable of sophisticated learning. If such learning abilities are costly, however, natural selection will favour simpler mechanisms for controlling behaviour when faced with uncertain conditions. Here, we show that, in a foraging context, a strategy based only on current energy reserves often performs almost as well as a Bayesian learning strategy that integrates all previous experiences to form an optimal estimate of environmental conditions. We find that Bayesian learning gives a strong advantage only if fluctuations in the food supply are very strong and reasonably frequent. The performance of both the Bayesian and the reserve-based strategy are more robust to inaccurate knowledge of the temporal pattern of environmental conditions than a strategy that has perfect knowledge about current conditions. Studies assuming Bayesian learning are often accused of being unrealistic; our results suggest that animals can achieve a similar level of performance to Bayesians using much simpler mechanisms based on their physiological state. More broadly, our work suggests that the ability to use internal states as a source of information about recent environmental conditions will have weakened selection for sophisticated learning and decision-making systems.
Simple decision rules underlie collaborative hunting in yellow saddle goatfish
Authors: Steinegger Marc , Roche Dominique G. , Bshary Redouan
Published: January 2018

Collaborative hunting, the coordination of animal behaviour in space and time to capture prey, is reported in several vertebrate species. However, previous studies are observational, hampering our ability to identify individual decision rules that result in collaboration. We experimentally investigated collaborative hunting in yellow saddle goatfish (
Parupeneus cyclostomus
) by exposing pairs to a mock prey that fled to an artificial shelter with multiple entrances. The first fish to initiate the chase (the ‘initiator’) was always closest to the prey and pursued it directly in its path. Conversely, the behaviour of the second goatfish (the ‘follower’) depended on its spatial position relative to the initiator. When the follower was less than one body length behind the initiator, it also accelerated directly towards the prey in over 95% of cases. However, if the two goatfish were separated by a distance of one body length or more, the follower chose a less direct route to reach the prey in 87% of cases. In this scenario, the follower often reached the prey's more distant refuge first, which might increase its hunting success or block the prey's escape path under natural conditions. Our findings suggest that coordinated hunting behaviour can result from simple, self-serving decisions.
PhanerozoicpO2and the early evolution of terrestrial animals
Authors: Schachat Sandra R. , Labandeira Conrad C. , Saltzman Matthew R. , Cramer Bradley D. , Payne Jonathan L. , Boyce C. Kevin
Published: January 2018

Concurrent gaps in the Late Devonian/Mississippian fossil records of insects and tetrapods (i.e. Romer's Gap) have been attributed to physiological suppression by low atmosphericpO2. Here, updated stable isotope inputs inform a reconstruction of Phanerozoic oxygen levels that contradicts the low oxygen hypothesis (and contradicts the purported role of oxygen in the evolution of gigantic insects during the late Palaeozoic), but reconciles isotope-based calculations with other proxies, like charcoal. Furthermore, statistical analysis demonstrates that the gap between the first Devonian insect and earliest diverse insect assemblages of the Pennsylvanian (Bashkirian Stage) requires no special explanation if insects were neither diverse nor abundant prior to the evolution of wings. Rather than tracking physiological constraint, the fossil record may accurately record the transformative evolutionary impact of insect flight.
Social brain volume is associated with in-degree social network size among older adults
Authors: Kwak Seyul , Joo Won-tak , Youm Yoosik , Chey Jeanyung
Published: January 2018

The social brain hypothesis proposes that large neocortex size evolved to support cognitively demanding social interactions. Accordingly, previous studies have observed that larger orbitofrontal and amygdala structures predict the size of an individual's social network. However, it remains uncertain how an individual's social connectedness reported by other people is associated with the social brain volume. In this study, we found that a greater in-degree network size, a measure of social ties identified by a subject's social connections rather than by the subject, significantly correlated with a larger regional volume of the orbitofrontal cortex, dorsomedial prefrontal cortex and lingual gyrus. By contrast, out-degree size, which is based on an individual's self-perceived connectedness, showed no associations. Meta-analytic reverse inference further revealed that regional volume pattern of in-degree size was specifically involved in social inference ability. These findings were possible because our dataset contained the social networks of an entire village, i.e. a global network. The results suggest that the in-degree aspect of social network size not only confirms the previously reported brain correlates of the social network but also shows an association in brain regions involved in the ability to infer other people's minds. This study provides insight into understanding how the social brain is uniquely associated with sociocentric measures derived from a global network.
Male mice with large inversions or deletions of X-palindrome arms are fertile and express their associated genes post-meiosis
Authors: Kruger Alyssa N. , Ellison Quinn , Brogley Michele A. , Gerlinger Emma R. , Mueller Jacob L.
Published: January 2018

Large (>10 kb) palindromic sequences are enriched on mammalian sex chromosomes. In mice, these palindromes harbor gene families (≥2 gene copies) expressed exclusively in post-meiotic testicular germ cells, at a time when most single-copy sex-linked genes are transcriptionally repressed. This distinct expression pattern led to the hypothesis that containment within palindrome structures or having ≥2 gene enables post-meiotic gene expression. We tested these two hypotheses by using CRISPR to precisely engineer large (10’s of kb) inversions and deletions of X chromosome palindrome arms for two regions carrying the mouse 4930567H17Rik and Mageb5 gene families. We found that 4930567H17Rik and Mageb5 gene expression is unaffected in mice carrying palindrome arm inversions, suggesting that palindromic structure is not important for mediating palindrome-associated gene expression. We also found that 4930567H17Rik and Mageb5 gene expression is reduced by half in mice carrying palindrome arm deletions, allowing us to test whether palindrome-associated genes are sensitive to reduced expression levels resulting in spermatogenic defects. Male mice carrying palindrome arm deletions of 4930567H17Rik or Mageb5, however, are fertile, have normal testis histology, and show no aberrations in spermatogenic cell population frequencies via FACS quantification. Together, these findings suggest that large palindromic structures on the sex chromosomes are not necessary for their associated genes to evade post-meiotic transcriptional repression and that these genes are not sensitive to reduced expression levels. Large sex chromosome palindromes may thus be important for other reasons, such as the long-term evolutionary stability of their associated gene families.
NRSF–mediated repression of neuronal genes in developing brain persists in the absence of NRSF-Sin3 interaction
Authors: Hall Alicia M. , Short Annabel K. , Singh-Taylor Akanksha , Daglian Jennifer , Mishina Tadashi , Schmidt William K. , Kouji Hiroyuki , Baram Tallie Z.
Published: January 2018

Repression of target genes by the transcriptional repressor neuronal restrictive silencing factor (NRSF)/repressor element 1 silencing transcription factor (REST) contributes to enduring plasticity in the developing brain. However, the cofactor(s) interacting with NRSF to enable target gene repressor are not well understood, and may vary among neuronal populations and brain regions as well as with different contexts. Here we employed the novel designer drug mS-11 to block the interactions of the cofactor Sin3 with NRSF. We tested if NRSF-Sin3 interaction is required for repression of NRSF target genes in developing hypothalamus after activity-dependent modulation of NRSF function. In the hypothalamus in vitro, blocking glutamatergic neurotransmission robustly increased NRSF binding to the target gene Crh, resulting in its repression. Blocking the binding of NRSF to the chromatin with decoy NRSE-oligodeoxynucleotides abrogated this repression. In contrast, mS-11 at several concentrations did not impede Crh repression. NRSF-mediated repression may underlie disease processes such as the onset of epilepsy. Therefore, identifying small-molecule antagonists of NRSF is crucial for the development of disease-preventing or modifying interventions.
Enzyme-based synthesis of single molecule RNA FISH probes
Authors: Lanctôt Christian
Published: January 2018

Single molecule RNA fluorescence in situ hybridization (smRNA FISH) allows the quantitative analysis of gene expression in single cells. The technique relies on the use of pools of end-labeled fluorescent oligonucleotides to detect specific cellular RNA sequences. These fluorescent probes are currently chemically synthesized. Here I describe a novel technique based on the use of routine molecular biology enzymes to generate smRNA FISH probes without the need for chemical synthesis of pools of oligonucleotides. The protocol comprises 3 main steps: purification of phagemid-derived single stranded DNA molecules comprising a segment complementary to a target RNA sequence; fragmentation of these molecules by limited DNase I digestion; and end-labeling of the resulting oligonucleotides with terminal deoxynucleotide transferase and fluorescent dideoxynucleotides. smRNA FISH probes that are obtained using the technique presented here are shown to perform as well as conventional probes. The main advantages of the method are the low cost of probes and the flexibility it affords in the choice of labels. Enzyme-based synthesis of probes should further increase the popularity of smRNA FISH as a tool to investigate gene expression at the cellular or subcellular level.
The Effect of Dissociation between Proprioception and Vision on Perception and Grip Force Control in a Stiffness Judgment Task
Authors: Hu Stephanie , Leib Raz , Nisky Ilana
Published: January 2018

Our sensorimotor system estimates stiffness to form stiffness perception, such as for choosing a ripe fruit, and to generate actions, such as to adjust grip force to avoid slippage of a scalpel during surgery. We examined how temporal manipulation of the haptic and visual feedback affect stiffness perception and grip force adjustment during a stiffness discrimination task. We used delayed force feedback and delayed visual feedback to break the natural relations between these modalities when participants tried to choose the harder spring between pairs of springs. We found that visual delay caused participants to slightly overestimate stiffness while force feedback delay caused a mixed effect on perception; for some it caused underestimation and for some overestimation of stiffness. Interestingly and in contrast to previous findings without vision, we found that participants increased the magnitude of their applied grip force for all conditions. We propose a model that suggests that this increase was a result of coupling the grip force adjustment to their proprioceptive hand position, which was the only modality which we could not delay. Our findings shed light on how the sensorimotor system combines information from different sensory modalities for perception and action. These results are important for the design of improved teleoperation systems that suffer from unavoidable delays.