bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of Positive Airway Pressure Following Middle Ear Surgery: A Practice Survey of Otologists
Authors: Ruhl Douglas S. , Tolisano Anthony M. , Kesser Bradley W. , Hashisaki George T. , Camacho Macario
Published: May 2017

Background:

Positive airway pressure (PAP) devices are used as treatment for obstructive sleep apnea (OSA). PAP may increase middle ear pressure which is of interest to otologic surgeons. There is a lack of data to guide management of PAP therapy after middle ear surgery.

Objective:

To elucidate how otologic surgeons manage PAP in their patients after ear surgery.

Study Design:

A survey e-mailed to practicing members of the American Neurotology Society.

Results:

Among 60 respondents, the most common recommendations to patients were to avoid PAP use for 1 week (40%), return to normal use immediately (23.3%), avoid PAP for 1 month (13.3%), or avoid PAP for 1 day (13.3%) after surgery. Twenty percent of providers reported that they change their advice on the basis of the PAP pressure settings (i.e., shorter hiatus for higher settings). Among respondents, 47% think that they have patients with middle ear issues because of PAP and 13% attributed surgical failures to PAP use. One-third of providers routinely pack the Eustachian tube during surgery. Providers who attributed a negative surgical outcome to PAP use were more likely to routinely pack/plug the Eustachian tube during otologic surgery (p = 0.001).

Conclusion:

Treatment recommendations regarding postoperative PAP treatment for obstructive sleep apnea vary greatly among practicing otologists. Providers who think that an adverse outcome was attributed to PAP use were more likely to prophylactically plug the Eustachian tube during surgery. Future research will provide additional information which will allow a better understanding of the effect of PAP on the middle ear, especially after otologic surgery.
Unsedated In‐office Transgastrostomy Esophagoscopy to Monitor Therapy in Pediatric Esophageal Disease
Authors: Hall Caroline H.T. , Nguyen Nathalie , Furuta Glenn T. , Prager Jeremy , Deboer Emily , Deterding Robin , Menard‐Katcher Calies , Capocelli Kelley E. , Kramer Robert E. , Friedlander Joel A.
Published: May 2017

Monitoring therapy in esophageal inflammatory disorders such as eosinophilic esophagitis and reflux esophagitis often requires frequent endoscopic evaluation. We recently reported the effective use of unsedated in‐office transnasal esophagoscopy that significantly decreased costs and anesthetic exposure associated with pediatric esophagoscopy in eosinophilic esophagitis. Here we report a series of pediatric patients with esophagitis with gastrostomy tubes who underwent unsedated transgastrostomy esophagoscopy (TGE) in an office setting. Nine patients (ages 16 months–21 years) tolerated TGE without significant adverse events. Biopsy specimens were adequate for evaluation. This series confirms that unsedated in‐office TGE can be used to successfully obtain mucosal biopsies to monitor esophageal inflammatory conditions in children without the use of sedation.
Long‐term Follow‐up of Adolescents Treated for Rumination Syndrome in an Inpatient Setting
Authors: Alioto Anthony , Di Lorenzo Carlo
Published: May 2017

Objectives:

Although several studies have demonstrated the short‐term benefit of the behavioral treatment of rumination syndrome, few have investigated the long‐term outcomes. Studies reporting long‐term benefit have involved combined pediatric and adult samples or have examined outcomes of patients involved in various types of treatment. The purpose of the present study was to examine several aspects of long‐term outcome in adolescent patients who took part in the same intensive, interdisciplinary, inpatient behavioral treatment approach.

Methods:

Self‐report measures were completed by 47 adolescent patients (mean age = 15.9) around 1 year or more from discharge from our inpatient program. Measures indexed changes in rumination, medical outcomes (eg, use of supplemental nutrition), somatic symptoms, and quality of life.

Results:

Most patients reported continued improvement in their rumination over time, with 20% reporting cessation of rumination for at least 6 months. The majority of patients no longer required supplemental nutrition and reported improvements in somatic symptoms and quality of life. Patients who reported greater improvement in rumination also reported more significant improvements in their somatic symptoms and quality of life.

Conclusions:

Intensive behavioral treatment of rumination syndrome leads to long‐term improvement in rumination as well as other related factors, including somatic symptoms and quality of life.
Undifferentiated and Dedifferentiated Endometrial Carcinomas With POLE Exonuclease Domain Mutations Have a Favorable Prognosis
Authors: Espinosa Iñigo , Lee Cheng-Han , D’Angelo Emanuela , Palacios José , Prat Jaime
Published: May 2017

POLE exonuclease domain mutations have recently been described in undifferentiated endometrial carcinoma but, because of the rarity of this aggressive type of endometrial cancer, their prognostic significance is unknown. We have analyzed the immunophenotype (ARID1A, MLH1, PMS2, MSH2, MSH6, p53, β-catenin, and SMARCB1) and mutational status (POLE, PIK3CA, and PTEN) of 21 undifferentiated carcinomas (8 undifferentiated and 13 dedifferentiated carcinomas). Loss of ARID1A expression was observed in 9 of 19 cases (47%), loss of expression of at least 1 DNA mismatch repair protein in 7 (7/21; 33%), and p53 immunoreaction was aberrant (mutated/inactivated) in 11 cases (11/21; 52%). All tumors were negative for β-catenin. Normal nuclear SMARCB1 (INI1) staining was found in all but 1 dedifferentiated case. Two undifferentiated and 7 dedifferentiated carcinomas showed POLE exonuclease domain mutations (9/21; 42%). PIK3CA mutations occurred in six tumors (6/21; 28%) (2 undifferentiated and 4 dedifferentiated carcinomas). PTEN mutations were found in 7 of 15 cases (47%) (4 undifferentiated and 3 dedifferentiated carcinomas). POLE-mutated undifferentiated and dedifferentiated endometrial carcinomas were more frequently stage I tumors than similar carcinomas lacking exonuclease domain mutations (7/9; 78% vs. 3/12; 25%; P=0.023) and patients had significantly better outcome (disease-specific survival) than those without POLE exonuclease domain mutations (P=0.02). Determination of the POLE mutation status is important for the management of these patients.
High Frequency of Neuroimaging Abnormalities Among Pediatric Patients With Sepsis Who Undergo Neuroimaging*
Authors: Sandquist Mary K. , Clee Mark S. , Patel Smruti K. , Howard Kelli A. , Yunger Toni , Nagaraj Usha D. , Jones Blaise V. , Fei Lin , Vadivelu Sudhakar , Wong Hector R.
Published: May 2017

Objectives:

This study was intended to describe and correlate the neuroimaging findings in pediatric patients after sepsis.

Design:

Retrospective chart review.

Setting:

Single tertiary care PICU.

Patients:

Patients admitted to Cincinnati Children’s Hospital Medical Center with a discharge diagnosis of sepsis or septic shock between 2004 and 2013 were crossmatched with patients who underwent neuroimaging during the same time period.

Interventions:

All neuroimaging studies that occurred during or subsequent to a septic event were reviewed, and all new imaging findings were recorded and classified. As many patients experienced multiple septic events and/or had multiple neuroimaging studies after sepsis, our statistical analysis utilized the most recent or “final” imaging study available for each patient so that only brain imaging findings that persisted were included.

Measurements and Main Results:

A total of 389 children with sepsis and 1,705 concurrent or subsequent neuroimaging studies were included in the study. Median age at first septic event was 3.4 years (interquartile range, 0.7–11.5). Median time from first sepsis event to final neuroimaging was 157 days (interquartile range, 10–1,054). The most common indications for final imaging were follow-up (21%), altered mental status (18%), and fever/concern for infection (15%). Sixty-three percentage (n = 243) of final imaging studies demonstrated abnormal findings, the most common of which were volume loss (39%) and MRI signal and/or CT attenuation abnormalities (21%). On multivariable logistic regression, highest Pediatric Risk of Mortality score and presence of oncologic diagnosis/organ transplantation were independently associated with any abnormal final neuroimaging study findings (odds ratio, 1.032; p = 0.048 and odds ratio, 1.632; p = 0.041), although early timing of neuroimaging demonstrated a negative association (odds ratio, 0.606; p = 0.039). The most common abnormal finding of volume loss was independently associated with highest Pediatric Risk of Mortality score (odds ratio, 1.037; p = 0.016) and oncologic diagnosis/organ transplantation (odds ratio, 2.207; p = 0.001) and was negatively associated with early timing of neuroimaging (odds ratio, 0.575; p = 0.037).

Conclusions:

The majority of pediatric patients with sepsis and concurrent or subsequent neuroimaging have abnormal neuroimaging findings. The implications of this high incidence for long-term neurologic outcomes and follow-up require further exploration.
Beyond “Option B+”: Understanding Antiretroviral Therapy (ART) Adherence, Retention in Care and Engagement in ART Services Among Pregnant and Postpartum Women Initiating Therapy in Sub-Saharan Africa
Authors: Myer Landon , Phillips Tamsin K.
Published: May 2017

Background:

Several studies from sub-Saharan Africa have highlighted significant challenges in providing antiretroviral therapy (ART) to pregnant and postpartum women, with specific concerns around maintaining optimal levels of adherence to ART and/or retaining women in long-term services. However, there are few conceptual frameworks to help understand nonadherence and nonretention, as well as the drivers of these, among HIV-infected women, particularly in the postpartum period.

Methods:

This review provides an overview of the key issues involved in thinking about ART adherence, retention in care and engagement in ART services among pregnant and postpartum women.

Results:

The related behaviors of adherence and retention may be understood as components of effective engagement of patients in ART services, which share the goal of achieving and maintaining suppressed maternal viral load on ART. Under this framework, the existing literature indicates that disengagement from care is widespread among postpartum women, with strikingly similar data emerging from ART services around the globe and indications that similar challenges may be encountered by postpartum care services outside the context of HIV. However, the drivers of disengagement require further research, and evidence-based intervention strategies are limited.

Conclusions:

The challenges of engaging women in ART services during pregnancy and the postpartum period seem pervasive, although the determinants of these are poorly understood. Looking forward, a host of innovative intervention approaches are needed to help improve women's engagement, and in turn, promote maternal and child health in the context of HIV.
Patterns of HIV Care Clinic Attendance and Adherence to Antiretroviral Therapy Among Pregnant and Breastfeeding Women Living With HIV in the Context of Option B+ in Zimbabwe
Authors: Erlwanger Alison S. , Joseph Jessica , Gotora Tendai , Muzunze Blandina , Orne-Gliemann Joanna , Mukungunugwa Solomon , Farley Tim , Mangwiro Alexio-Zambezi
Published: May 2017

Background:

Consistent use of antiretroviral therapy (ART) during pregnancy and breastfeeding reduces the likelihood of mother-to-child HIV transmission. All pregnant and breastfeeding women living with HIV in Zimbabwe are offered ART with same-day initiation regardless of CD4 count (Option B+). We investigated patterns of clinic attendance and adherence to ART among HIV-infected pregnant women in Zimbabwe.

Methods:

The Evidence for Elimination cluster-randomized trial evaluating point-of-care CD4 testing included 1150 HIV-infected ART-naive women attending antenatal care between January 2014 and June 2015. Thirty-two primary care facilities were randomized between 2 arms. In this secondary analysis of Evidence for Elimination data collected from routine clinic records, we classified women by number of pills dispensed, and estimated adherence from the ratio of pills to days since ART initiation (Medication Possession Ratio, adherent if ≥95%) or the period when they stopped receiving medication.

Results:

Two-thirds (67.7%) were still receiving medication 1 year after initiation; less than half of the cohort (39.1%) were adherent. Younger women, newly diagnosed with HIV, and/or first presenting to antenatal care in their third trimester were more likely to drop from care or be nonadherent 360 days after ART initiation.

Conclusion:

Adherence to ART is suboptimal particularly among young, newly diagnosed, and/or late presenting patients. Interventions that target these groups, as well as provide additional support to all women who are newly diagnosed, may improve Option B+ ART care. More information is needed about the barriers to ART care among late presenters and teenagers.
Integrating HIV and Maternal, Neonatal and Child Health Services in Rural Malawi: An Evaluation of the Implementation Processes and Challenges
Authors: Gunda Andrews , Jousset Aurelie , Tchereni Timothy , Joseph Jessica , Mwapasa Victor
Published: May 2017

Introduction:

Introducing Option B+ in Malawi increased antiretroviral therapy coverage among pregnant and breastfeeding women 3 fold. The Promoting Retention among Infants and Mothers Effectively (PRIME) study integrated care of Maternal, Neonatal and Child Health services through a mother–infant pair (MIP) clinic. This article evaluates the implementation processes and challenges health care workers' experienced in implementing these MIP clinics.

Methods:

Between May 2013 and August 2016, 20 health facilities implemented MIP clinics. Health care workers' performance implementing MIP clinics was assessed through a mentorship score from 0 to 5 and supplemented with qualitative data from mentorship reports. Visit alignment of participants' appointment and attendance dates with MIP clinic dates were calculated and summarized by overall proportions among all patient visits.

Results:

The average mentorship score was 3.8, improving from 3.0 to 4.2 from quarter one 2015 to quarter one 2016. Proportions of maternal and infant appointment dates that aligned with MIP clinic dates were 47.0% and 5.9%, with greatest improvement between 2013 and 2015. Proportions of maternal and infant attendance dates that aligned with MIP clinic dates were 41.7% and 51.2% and improved over time.

Discussion:

Despite improvement in staff mentorship scores, many MIPs were not exposed to integrated HIV and Maternal, Neonatal and Child Health services offered through MIP clinics primarily because of clinic scheduling challenges. To improve utilization of integrated MIP clinics, careful design of a delivery approach is needed that is acceptable to clinic staff, addresses local realities, and includes appropriate investment and oversight.
Machine Learning for Predicting Outcomes in Trauma
Authors: Liu Nehemiah T. , Salinas Jose
Published: May 2017

To date, there are no reviews on machine learning (ML) for predicting outcomes in trauma. Consequently, it remains unclear as to how ML-based prediction models compare in the triage and assessment of trauma patients. The objective of this review was to survey and identify studies involving ML for predicting outcomes in trauma, with the hypothesis that models predicting similar outcomes may share common features but the performance of ML in these studies will differ greatly. MEDLINE and other databases were searched for studies involving trauma and ML. Sixty-five observational studies involving ML for the prediction of trauma outcomes met inclusion criteria. In total 2,433,180 patients were included in the studies. The studies focused on prediction of the following outcome measures: survival/mortality (n = 34), morbidity/shock/hemorrhage (n = 12), hospital length of stay (n = 7), hospital admission/triage (n = 6), traumatic brain injury (n = 4), life-saving interventions (n = 5), post-traumatic stress disorder (n = 4), and transfusion (n = 1). Six studies were prospective observational studies. Of the 65 studies, 33 used artificial neural networks for prediction. Importantly, most studies demonstrated the benefits of ML models. However, algorithm performance was assessed differently by different authors. Sensitivity-specificity gap values varied greatly from 0.035 to 0.927. Notably, studies shared many features for model development. A common ML feature base may be determined for predicting outcomes in trauma. However, the impact of ML will require further validation in prospective observational studies and randomized clinical trials, establishment of common performance criteria, and high-quality evidence about clinical and economic impacts before ML can be widely accepted in practice.
Epidemiology of Anaphylactic Shock and its Related Mortality in Hospital Patients in Taiwan: A Nationwide Population-Based Study
Authors: Liu Fu-Chao , Chiou Hung-Jr , Kuo Chang-Fu , Chung Ting-Ting , Yu Huang-Ping
Published: May 2017

Anaphylactic shock is potentially life-threatening. However, there is a paucity of data about its incidence and associated mortality, particularly in Asian populations. We aimed to investigate the epidemiology of anaphylactic shock and its related mortality after the hospitalization of patients in the general population of Taiwan. The National Health Insurance Research Database was used to identify patients with anaphylactic shock and estimate its incidence for inpatients sampled from 2005 to 2012. The pattern of anaphylactic shock and anaphylactic shock-related mortality rate was also examined. Of 22,080,199 patients who were admitted to hospitals from 2005 to 2012, there were 2,289 incident cases of anaphylactic shock and 2,219 people were included. Incidence of hospitalizations due to anaphylactic shock ranged from 12.71 to 13.23 per million of the population between 2005 and 2012. The incidence of anaphylactic shock in our study was substantially lower than other western countries, including the United States. There were 24 deaths due to drug-induced anaphylactic shock among the hospitalizations; overall mortality rate was 1.08%. Eighteen (0.81%) patients died within 30 days; 22 (0.99%) died within 2 months following the anaphylactic shock. The highest incidence occurred in patients aged 70–79 years. Conversely, food-induced anaphylactic shock was not influenced by age. In conclusion, drug-induced anaphylactic shock was a major cause of death due to anaphylactic shock in hospitalized patients. Most cases of anaphylactic shock occurred in the older population, and the mortality rate was lower in females than in males, though the difference was not significant.
Wearable Sensor Technology Efficacy in Peripheral Vascular Disease (wSTEP)
Authors: Normahani Pasha , Kwasnicki Richard , Bicknell Colin , Allen Louise , Jenkins Mike P. , Gibbs Richard , Cheshire Nicholas , Darzi Ara , Riga Celia
Published: May 2017

Objective:

To evaluate the effect of using wearable activity monitors (WAMs) in patients with intermittent claudication (IC) within a single-center randomized controlled trial.

Background:

WAMs allow users to set daily activity targets and monitor their progress. They may offer an alternative treatment to supervised exercise programs (SEPs) for patients with IC.

Methods:

Thirty-seven patients with IC were recruited and randomized into intervention or control group. The intervention consisted of a feedback-enabled, wrist-worn activity monitor (WAM) in addition to access to SEP. The control group was given access to SEP only. The outcome measures were maximum walking distance (MWD), claudication distance (CD), and quality of life as measured by the VascuQol questionnaire. Participants were assessed upon recruitment, and at 3, 6, and 12 months.

Results:

Patients in the WAM group showed significant improvement in MWD at 3 and 6 months (80–112 m, to 178 m; P < 0.001), which was sustained at 12 months. The WAM group also increased CD (40 vs 110 m; P < 0.001) and VascuQol score (4.7 vs 5.8; P = 0.004). The control group saw a temporary increase in VascuQol score at 6 months (4.5 vs 4.7; P = 0.028), but no other improvements in MWD or CD were observed. Significantly higher improvements in MWD were seen in the WAM group compared with that in the control group at 6 months (82 vs −5 m; P = 0.009, r = 0.47) and 12 months (69 vs 7.5 m; P = 0.011, r = 0.52).

Conclusions:

The study demonstrates the significant, sustained benefit of WAM-led technologies for patients with IC. This potentially resource-sparing intervention is likely to provide a valuable adjunct or alternative to SEP.
Hospital Minimally Invasive Surgery Utilization for Gastrointestinal Cancer
Authors: Mason Meredith C. , Tran Cao Hop S. , Awad Samir S. , Farjah Farhood , Chang George J. , Massarweh Nader N.
Published: May 2017

Objective:

The aim of the study was to evaluate the impact of receiving care at high minimally invasive surgery (MIS)-utilizing hospitals

Background:

MIS techniques are used across surgical specialties. The extent of MIS utilization for gastrointestinal (GI) cancer resection and impact of receiving care at high utilizing hospitals is unclear.

Methods:

This is a retrospective cohort study of 137,581 surgically resected esophageal, gastric, pancreatic, hepatobiliary, colon, and rectal cancer patients within the National Cancer Data Base (2010–2013). Disease-specific, hospital-level, reliability-adjusted MIS utilization rates were calculated to evaluate perioperative outcomes. Among patients for whom adjuvant chemotherapy (AC) was indicated, the association between days to AC and hospital MIS utilization was examined using generalized estimating equations. Association with risk of death was evaluated using multivariable Cox regression.

Results:

Disease-specific MIS use increased significantly [42.0%–68.3% increase; trend test, P < 0.001 for all except hepatobiliary (P = 0.007)] over time. Most hospitals [range—30.3% (colon); 92.9% (pancreatic)] were low utilizers (≤30% of cases). Higher MIS utilization is associated with increased lymph nodes examined (P < 0.001, all) and shorter length of stay (P < 0.001, all). Each 10% increase in MIS utilization is associated with fewer days to AC [3.3 (95% confidence interval, 1.2–5.3) for MIS gastric; 3.3 ([0.7–5.8) for open gastric; 1.1 (0.3–2.0) days for open colon]. An association between MIS utilization and risk of death was observed for colon [Q2—hazard ratio (HR) 0.96 (0.89–1.02); Q3—HR 0.91 (0.86–0.98); Q4—HR 0.87 (0.82–0.93)] and rectal cancer [Q2—HR 0.89 (0.76–1.05); Q3—HR 0.84 (0.82–0.97); Q4—HR 0.86 (0.74–0.98)].

Conclusions:

Most hospitals treating GI malignancies are low MIS utilizers. Our findings may reflect real-world MIS effectiveness for oncologic resection and could be useful for identifying hospitals with infrastructure and/or processes beneficial for multimodality cancer care.
A note on the self-similar solutions to the spontaneous fragmentation equation
Authors: Breschi Giancarlo , Fontelos Marco A.
Published: May 2017

We provide a method to compute self-similar solutions for various fragmentation equations and use it to compute their asymptotic behaviours. Our procedure is applied to specific cases: (i) the case of mitosis, where fragmentation results into two identical fragments, (ii) fragmentation limited to the formation of sufficiently large fragments, and (iii) processes with fragmentation kernel presenting a power-like behaviour.
An integral equation method for the homogenization of unidirectional fibre-reinforced media; antiplane elasticity and other potential problems
Authors: Joyce Duncan , Parnell William J. , Assier Raphaël C. , Abrahams I. David
Published: May 2017

In Parnell & Abrahams (2008
Proc. R. Soc. A
464
, 1461–1482. (
doi:10.1098/rspa.2007.0254
)), a homogenization scheme was developed that gave rise to explicit forms for the effective antiplane shear moduli of a periodic unidirectional fibre-reinforced medium where fibres have non-circular cross section. The explicit expressions are rational functions in the volume fraction. In that scheme, a (non-dilute) approximation was invoked to determine leading-order expressions. Agreement with existing methods was shown to be good except at very high volume fractions. Here, the theory is extended in order to determine higher-order terms in the expansion. Explicit expressions for effective properties can be derived for fibres with non-circular cross section, without recourse to numerical methods. Terms appearing in the expressions are identified as being associated with the lattice geometry of the periodic fibre distribution, fibre cross-sectional shape and host/fibre material properties. Results are derived in the context of antiplane elasticity but the analogy with the potential problem illustrates the broad applicability of the method to, e.g. thermal, electrostatic and magnetostatic problems. The efficacy of the scheme is illustrated by comparison with the well-established method of asymptotic homogenization where for fibres of general cross section, the associated cell problem must be solved by some computational scheme.
Mutualistic strategies minimize coextinction in plant–disperser networks
Authors: Fricke Evan C. , Tewksbury Joshua J. , Wandrag Elizabeth M. , Rogers Haldre S.
Published: May 2017

The global decline of mutualists such as pollinators and seed dispersers may cause negative direct and indirect impacts on biodiversity. Mutualistic network models used to understand the stability of mutualistic systems indicate that species with low partner diversity are most vulnerable to coextinction following mutualism disruption. However, existing models have not considered how species vary in their dependence on mutualistic interactions for reproduction or survival, overlooking the potential influence of this variation on species' coextinction vulnerability and on network stability. Using global databases and field experiments focused on the seed dispersal mutualism, we found that plants and animals that depend heavily on mutualistic interactions have higher partner diversity. Under simulated network disruption, this empirical relationship strongly reduced coextinction because the species most likely to lose mutualists depend least on their mutualists. The pattern also reduced the importance of network structure for stability; nested network structure had little effect on coextinction after simulations incorporated the empirically derived relationship between partner diversity and mutualistic dependence. Our results highlight a previously unknown source of stability in mutualistic networks and suggest that differences among species in their mutualistic strategy, rather than network structure, primarily accounts for stability in mutualistic communities.
Minimal variation in eutherian brain growth rates during fetal neurogenesis
Authors: Halley Andrew C.
Published: May 2017

A central question in the evolution of brain development is whether species differ in rates of brain growth during fetal neurogenesis. Studies of neonatal data have found allometric evidence for brain growth rate differences according to physiological variables such as relative metabolism and placental invasiveness, but these findings have not been tested against fetal data directly. Here, we measure rates of exponential brain growth acceleration in 10 eutherian mammals, two marsupials, and two birds. Eutherian brain acceleration exhibits minimal variation relative to body and visceral organ growth, varies independently of correlated growth patterns in other organs, and is unrelated to proposed physiological constraints such as metabolic rate or placental invasiveness. Brain growth rates in two birds overlap with eutherian variation, while marsupial brain growth is exceptionally slow. Peak brain growth velocity is linked in time with forebrain myelination and eye opening, reliably separates altricial species born before it from precocial species born afterwards, and is an excellent predictor of adult brain size (
r
2
= 0.98). Species with faster body growth exhibit larger relative brain size in early ontogeny, while brain growth is unrelated to allometric measures. These findings indicate a surprising conservation of brain growth rates during fetal neurogenesis in eutherian mammals, clarify sources of variation in neonatal brain size, and suggest that slow body growth rates cause species to be more encephalized at birth.
Nonlinear trade-offs allow the cooperation game to evolve from Prisoner's Dilemma to Snowdrift
Authors: Chao Lin , Elena Santiago F.
Published: May 2017

The existence of cooperation, or the production of public goods, is an evolutionary problem. Cooperation is not favoured because the Prisoner's Dilemma (PD) game drives cooperators to extinction. We have re-analysed this problem by using RNA viruses to motivate a model for the evolution of cooperation. Gene products are the public goods and group size is the number of virions co-infecting the same host cell. Our results show that if the trade-off between replication and production of gene products is linear, PD is observed. However, if the trade-off is nonlinear, the viruses evolve into separate lineages of ultra-defectors and ultra-cooperators as group size is increased. The nonlinearity was justified by the existence of real viral ultra-defectors, known as defective interfering particles, which gain a nonlinear advantage by being smaller. The evolution of ultra-defectors and ultra-cooperators creates the Snowdrift game, which promotes high-level production of public goods.
Specific hypersensitive response-associated recognition of new apoplastic effectors fromCladosporium fulvumin wild tomato
Authors: Mesarich Carl H. , Ökmen Bilal , Rovenich Hanna , Griffiths Scott A. , Wang Changchun , Karimi Jashni Mansoor , Mihajlovski Aleksandar , Collemare Jérôme , Hunziker Lukas , Deng Cecilia H. , Burgt Ate van der , Beenen Henriek G. , Templeton Matthew D. , Bradshaw Rosie E. , de Wit Pierre J.G.M.
Published: May 2017

Tomato leaf mould disease is caused by the biotrophic fungusCladosporium fulvum. During infection,C. fulvumproduces extracellular small secreted protein (SSP) effectors that function to promote colonization of the leaf apoplast. Resistance to the disease is governed byCfimmune receptor genes that encode receptor-like proteins (RLPs). These RLPs recognize specific SSP effectors to initiate a hypersensitive response (HR) that renders the pathogen avirulent.C. fulvumstrains capable of overcoming one or more of all clonedCfgenes have now emerged. To combat these strains, newCfgenes are required. An effectoromics approach was employed to identify wild tomato accessions carrying newCfgenes. Proteomics and transcriptome sequencing were first used to identify 70 apoplasticin planta-inducedC. fulvumSSPs. Based on sequence homology, 61 of these SSPs were novel or lacked known functional domains. Seven, however, had predicted structural homology to antimicrobial proteins, suggesting a possible role in mediating antagonistic microbe−microbe interactionsin planta. Wild tomato accessions were then screened for HR-associated recognition of 41 SSPs using thePotato virus X-based transient expression system. Nine SSPs were recognized by one or more accessions, suggesting that these plants carry newCfgenes available for incorporation into cultivated tomato.
Torque and buckling in stretched intertwined double-helix DNAs
Authors: Brahmachari Sumitabha , Marko John F.
Published: May 2017

We present a statistical-mechanical model for the behavior of intertwined DNAs, with a focus on their torque and extension as a function of their catenation (linking) number and applied force, as studied in magnetic tweezers experiments. Our model produces results in good agreement with available experimental data, and predicts a catenation-dependent effective twist modulus distinct from what is observed for twisted individual double-helix DNAs. We find that buckling occurs near to the point where experiments have observed a kink in the extension versus linking number, and that the subsequent “supercoiled braid” state corresponds to a proliferation of multiple small plectoneme structures. We predict a discontinuity in extension at the buckling transition corresponding to nucleation of the first plectoneme domain. We also find that buckling occurs for lower linking number at lower salt; the opposite trend is observed for supercoiled single DNAs.
Contrast thresholds reveal different visual masking functions in humans and praying mantises
Authors: Tarawneh Ghaith , Nityananda Vivek , Rosner Ronny , Errington Steven , Herbert William , Arranz-Paraíso Sandra , Busby Natalie , Tampin Jimmy , Read Jenny , Serrano-Pedraza Ignacio
Published: May 2017

Recently, we showed a novel property of the Hassenstein-Reichardt detector: namely, that insect motion detection can be masked by “invisible” noise, i.e. visual noise presented at spatial frequencies to which the animals do not respond when presented as a signal. While this study compared the effect of noise on human and insect motion perception, it used different ways of quantifying masking in two species. This was because the human studies measured contrast thresholds, which were too time-consuming to acquire in the insect given the large number of stimulus parameters examined. Here, we run longer experiments in which we obtained contrast thresholds at just two signal and two noise frequencies. We examine the increase in threshold produced by noise at either the same frequency as the signal, or a different frequency. We do this in both humans and praying mantises (Sphodromantis lineola), enabling us to compare these species directly in the same paradigm. Our results confirm our earlier finding: whereas in humans, visual noise masks much more effectively when presented at the signal spatial frequency, in insects, noise is roughly equivalently effective whether presented at the same frequency or a lower frequency. In both species, visual noise presented at a higher spatial frequency is a less effective mask.

Summary Statement

We here show that despite having similar motion detection systems, insects and humans differ in the effect of low and high spatial frequency noise on their contrast thresholds.
CRISPR-Cas9 genome editing in human cells works via the Fanconi Anemia pathway
Authors: Richardson Chris D , Kazane Katelynn R , Feng Sharon J , Bray Nicholas L , Schäfer Axel J , Floor Stephen , Corn Jacob E
Published: May 2017

CRISPR-Cas9 genome editing creates targeted double strand breaks (DSBs) in eukaryotic cells that are processed by cellular DNA repair pathways. Co-administration of single stranded oligonucleotide donor DNA (ssODN) during editing can result in high-efficiency (>20%) incorporation of ssODN sequences into the break site. This process is commonly referred to as homology directed repair (HDR) and here referred to as single stranded template repair (SSTR) to distinguish it from repair using a double stranded DNA donor (dsDonor). The high efficacy of SSTR makes it a promising avenue for the treatment of genetic diseases1,2, but the genetic basis of SSTR editing is still unclear, leaving its use a mostly empiric process. To determine the pathways underlying SSTR in human cells, we developed a coupled knockdown-editing screening system capable of interrogating multiple editing outcomes in the context of thousands of individual gene knockdowns. Unexpectedly, we found that SSTR requires multiple components of the Fanconi Anemia (FA) repair pathway, but does not require Rad51-mediated homologous recombination, distinguishing SSTR from repair using dsDonors. Knockdown of FA genes impacts SSTR without altering break repair by non-homologous end joining (NHEJ) in multiple human cell lines and in neonatal dermal fibroblasts. Our results establish an unanticipated and central role for the FA pathway in templated repair from single stranded DNA by human cells. Therapeutic genome editing has been proposed to treat genetic disorders caused by deficiencies in DNA repair, including Fanconi Anemia. Our data imply that patient genotype and/or transcriptome profoundly impact the effectiveness of gene editing treatments and that adjuvant treatments to bias cells towards FA repair pathways could have considerable therapeutic value.
Evolution of pre-copulatory and post-copulatory strategies of inbreeding avoidance and associated polyandry
Authors: Bradley Duthie A. , Bocedi Greta , Germain Ryan R. , Reid Jane M.
Published: May 2017

Inbreeding depression is widely hypothesised to drive adaptive evolution of pre-copulatory and post-copulatory mechanisms of inbreeding avoidance, which in turn are hypothesised to affect evolution of polyandry (i.e., female multiple mating). However, surprisingly little theory or modelling critically examines selection for pre-copulatory or post-copulatory inbreeding avoidance, or both strategies, given evolutionary constraints and direct costs, or examines how evolution of inbreeding avoidance strategies might feed back to affect evolution of polyandry. Selection for post-copulatory inbreeding avoidance, but not for pre-copulatory inbreeding avoidance, requires polyandry, while interactions between pre-copulatory and post-copulatory inbreeding avoidance might cause functional redundancy (i.e., ‘degeneracy’) potentially generating complex evolutionary dynamics among inbreeding strategies and polyandry. We used individual-based modelling to quantify evolution of interacting pre-copulatory and post-copulatory inbreeding avoidance and associated polyandry given strong inbreeding depression and different evolutionary constraints and direct costs. We found that evolution of post-copulatory inbreeding avoidance increased selection for initially rare polyandry, and that evolution of a costly inbreeding avoidance strategy became negligible over time given a lower cost alternative strategy. Further, fixed pre-copulatory inbreeding avoidance often completely precluded evolution of polyandry and hence post-copulatory inbreeding avoidance, but fixed post-copulatory inbreeding avoidance did not preclude evolution of pre-copulatory inbreeding avoidance. Evolution of inbreeding avoidance phenotypes and associated polyandry are therefore affected by evolutionary feedbacks and degeneracy. All else being equal, evolution of pre-copulatory inbreeding avoidance and resulting low polyandry is more likely when post-copulatory inbreeding avoidance is precluded or costly, and evolution of post-copulatory inbreeding avoidance greatly facilitates evolution of costly polyandry.
The dental calculus metabolome in modern and historic samples
Authors: Velsko Irina M. , Overmyer Katherine A. , Speller Camilla , Collins Matthew , Loe Louise , Frantz Laurent A. F. , Martinez Juan Bautista Rodriguez , Chaves Eros , Klaus Lauren , Sankaranarayanan Krithivasan , Lewis Cecil M. , Coon Joshua J. , Larson Greger , Warinner Christina
Published: May 2017

Introduction

Dental calculus is a mineralized microbial dental plaque biofilm that forms throughout life by precipitation of salivary calcium salts. Successive cycles of dental plaque growth and calcification make it an unusually well-preserved, long-term record of host-microbial interaction in the archaeological record. Recent studies have confirmed the survival of authentic ancient DNA and proteins within historic and prehistoric dental calculus, making it a promising substrate for investigating oral microbiome evolution via direct measurement and comparison of modern and ancient specimens.

Objective

We present the first comprehensive characterization of the human dental calculus metabolome using a multi-platform approach.

Methods

Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) quantified 285 metabolites in modern and historic (200 years old) dental calculus, including metabolites of drug and dietary origin. A subset of historic samples was additionally analyzed by high-resolution gas chromatography-MS (GC-MS) and UPLC- MS/MS for further characterization of polar metabolites and lipids, respectively. Metabolite profiles of modern and historic calculus were compared to identify patterns of persistence and loss.

Results

Dipeptides, free amino acids, free nucleotides, and carbohydrates substantially decrease in abundance and ubiquity in archaeological samples, with some exceptions. Lipids generally persist, and saturated and mono-unsaturated medium and long chain fatty acids appear to be well-preserved, while metabolic derivatives related to oxidation and chemical degradation are found at higher levels in archaeological dental calculus than fresh samples.

Conclusions

The results of this study indicate that certain metabolite classes have higher potential for recovery over long time scales and may serve as appropriate targets for oral microbiome evolutionary studies.
Ketogenic diet or BHB improves epileptiform spikes, memory, survival in Alzheimer’s model
Authors: Newman John C , Kroll François , Ulrich Scott , Palop Jorge J. , Verdin Eric
Published: May 2017

Links between epilepsy and Alzheimer’s disease (AD) are seen in both human patients and mouse models. Human patients with AD may commonly have subclinical epileptiform spikes (EP spikes)1, and overt epilepsy is associated with more rapid cognitive decline2. Mechanistic studies in mouse models of Alzheimer’s disease (AD) have shown that altered network activity and epileptiform spikes stem from dysfunctional inhibitory interneurons3, which are key elements of cortical circuits underlying cognition4. Treatments that reduce epileptiform spikes improve cognition in these models5,6. Thus, targeting subclinical epileptiform activity may be a promising new therapeutic approach to AD7. Ketogenic diet (KD) has long been used to treat forms of epilepsy8, including Dravet syndrome, a childhood epilepsy caused by mutations in a gene that is critical for inhibitory interneuron function in mouse AD models5,9. However, the concurrent effects of a ketogenic diet on brain electrical activity, cognitive decline, and survival have not been tested, and the translational rationale and feasibility of such an intervention remain uncertain. Here we show that a ketogenic diet reduces epileptiform spikes in the hAPPJ20 mouse model of AD. Similar reduction of EP spikes is observed using a β-hydroxybutyrate (BHB) ester in both AD and Dravet mice. A ketogenic diet improves context-dependent and visuo-spatial learning in hAPPJ20 mice. It also reduces the high seizure-related mortality observed in male mice of this model. Therapies derived from β-hydroxybutyrate may have potential application in ameliorating cognitive dysfunction in AD through reducing subclinical epileptiform activity.
Growth, crystal structure, Hirshfeld surface, optical, piezoelectric, dielectric and mechanical properties of bis(L-asparaginium hydrogensquarate) single crystal
Authors: Yadav Harsh , Sinha Nidhi , Goel Sahil , Singh Budhendra , Bdikin Igor , Saini Anupama , Gopalaiah Kovuru , Kumar Binay
Published: May 2017

Molecular organic single crystals of bis(L-asparaginium hydrogensquarate) monohydrate [BASQ; (C8H10N2O7)2·H2O] have been grown by solution technique. Crystallographic information was investigated by single-crystal X-ray diffraction (SCXRD) analysis. Hirshfeld surface and fingerprint plot studies were performed to understand the intermolecular interactions of the BASQ crystal in graphical representation. Functional group identification was studied with FT–IR (Fourier transform–IR) spectroscopy. The positions of proton and carbon atoms in the BASQ compound were analyzed using NMR spectroscopy. High transparency and a wide band gap of 3.49 eV were observed in the linear optical study by UV–vis–NIR spectroscopy. Intense and broad photoluminescence emissions at room temperature were observed in blue and blue–green regions. The frontier molecular orbitals of the BASQ molecule were obtained by the DFT/B3LYP method employing 6-311G** as the basis set. The dielectric study was carried out with temperature at various frequency ranges. The piezoelectric charge coefficient (d33) value of BASQ crystal was found to be 2 pC/N, which leads to its application in energy harvesting, mechanical sensors and actuators applications. In the non-linear optical study, the BASQ crystal showed promising SHG conversion efficiency. Mechanical properties of the BASQ crystal were studied experimentally by Vicker's microhardness technique, which revealed that the grown crystal belonged to the softer category. BASQ crystal void estimation reveals the mechanical strength and porosity of the material.
A dihydro-β-agarofuran sesquiterpene from Maytenus boaria
Authors: Paz Cristian , von Dossow Daniela , Tiznado Victor , Suarez Sebastián , Cukiernik Fabio D. , Baggio Ricardo
Published: May 2017

The natural compound (1S,4S,5S,6R,7R,8R,9R,10S)-6-acetoxy-4,9,10-trihydroxy-2,2,5a,9-tetramethyloctahydro-2H-3,9a-methanobenzo[b]oxepin-5-yl furan-3-carboxylate, C22H30O9, (I), is a β-agarofuran sesquiterpene isolated from the seeds of Maytenus boaria as part of a study of the secondary metabolites from Chilean flora. The compound presents a central structure formed by a decalin system esterified with acetate at site 1 and furan-3-carboxylate at site 9. The chirality of the skeleton can be described as 1S,4S,5S,6R,7R,8R,9R,10S, which is consistent with that suggested by NMR studies. Unlike previously reported structures of sesquiterpenes containing a pure dihydro-β-agarofuran skeleton, (I) exhibits a three-dimensional hydrogen-bonded network.
Diphenylalanine in tetrahydrofuran: a highly potent candidate for the development of novel nanomaterials
Authors: Georgilis Evangelos , Gessmann Renate , Mitraki Anna , Petratos Kyriacos
Published: May 2017

The peptide di-L-phenylalanine (FF) has emerged as a highly potent candidate for the development of novel nanomaterials. The unprotected peptide was dissolved in 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) mixed with tetrahydrofuran (THF) and single crystals of the THF monosolvate, C18H20N2O3·C4H8O, were grown by slow evaporation in a `vial-in-closed-bottle' system. THF is a molecule that can only act as a hydrogen-bond acceptor. Thus, the hydrogen-bond patterns observed in the crystal structures at 100 and 299 K are different compared to that of crystals grown from water and methanol [Mason et al. (2014). ACS Nano.
8, 1243–1253].