bluuebunny/crossref_metadata_2025 huggingface dataset:
POSTERIOR SCLERAL MELANOCYTOSIS: A NOVEL FUNDUS FINDING MASQUERADING AS A CHOROIDAL NEVUS
Authors: Dolz-Marco Rosa , Sebrow Dov B. , Freund K. Bailey
Published: May 2017

Purpose:

To report a case of “posterior scleral melanocytosis,” a pigmented lesion of the posterior sclera that clinically resembles a flat choroidal nevus.

Methods:

Case report of a patient with posterior scleral melanocytosis. Multimodal imaging, including swept source optical coherence tomography, was used to demonstrate the scleral location of the pigmented lesion and to distinguish its features from a typical choroidal nevus present in the same eye.

Results:

An 86-year-old woman was seen for regular follow-up for neovascular age-related macular degeneration in her right eye and 2 pigmented lesions in her left eye, both presumed to be choroidal nevi. Anterior segment examination showed no evidence of ocular or dermal melanocytosis. Optical coherence tomography of the pigmented lesion in the left eye showed two distinct patterns. One lesion showed hyperreflectivity within the choroidal tissue associated with posterior shadowing, whereas the second lesion showed normal choroidal reflectivity with hyperreflectivity confined to the inner sclera associated with marked posterior shadowing.

Conclusion:

To the authors' knowledge, this is the first report of posterior scleral melanocytosis, a pigmented fundus lesion confined to the inner sclera. The need for high-penetrance optical coherence tomography to differentiate these lesions from a typical choroidal nevus may explain why this entity has not been previously described. The true nature of this entity will ultimately require histopathologic study.
Oral Ketamine in Treatment-Resistant Depression
Authors: Al Shirawi Maryam I. , Kennedy Sidney H. , Ho Keith T. , Byrne Roisin , Downar Jonathan
Published: May 2017

Purpose

The aim of the study was to assess the effectiveness, tolerability, and safety of oral ketamine as an antidepressant treatment in adults with treatment-resistant depression.

Methods

We reviewed retrospective data on 22 patients with treatment-resistant depression, who failed at least 3 adequate antidepressant treatment trials and 1 adequate trial of repetitive transcranial magnetic stimulation; subsequently, they received open-label treatment with oral ketamine, commenced at a dose of 50 mg every 3 days, titrated up by 25 mg every 3 days, according to response and tolerability. The primary outcome measure was the Beck Depression Inventory II, which was used to rate subjective mood improvement at baseline and then at each follow-up visit. Data about adverse effects related to ketamine and a self-harm risk assessment were also obtained.

Findings

Over the course of treatment, 18% of the patients showed greater than 50% reduction in the Beck Depression Inventory II scores, 14% reported partial improvement in mood symptoms, while 45% had no response to ketamine and 23% showed a mild worsening in their depressive symptoms. The most frequent adverse effects were acute dissociation, dizziness, blurred vision, numbness and sedation. Neither serious adverse effects, nor any cases of abuse or dependence were observed.

Conclusions

Although this case series found oral ketamine to be safe and well tolerated, the findings also showed rather modest effectiveness of oral ketamine in treatment-resistant depression, with only approximately 30% reporting some benefit and approximately 70% reporting no change or worsening of mood. However, bearing in mind the limitations of this small, open-label case series, further exploration of the effectiveness of oral ketamine is warranted.
The Power of a Parent's Touch
Authors: Campbell-Yeo Marsha , Dol Justine , Disher Timothy , Benoit Britney , Chambers Christine T. , Sheffield Kaitlyn , Boates Talia , Harrison Denise , Hewitt Brenda , Jangaard Krista , Stinson Jennifer , Taddio Anna , Parker Jennifer A. , Caddell Kim
Published: May 2017

Despite strong evidence that skin-to-skin contact and breast-feeding are effective pain-relieving interventions for infants undergoing painful procedures, they remain underutilized in clinical practice. Given the important contribution of parents, there is a need to find innovative ways to assist parents to become actively involved in their infant's care. We developed a YouTube video to disseminate evidence-based information on the effectiveness of skin-to-skin contact and breast-feeding for infant pain management. The 2-minute 39-second video launched on December 2, 2014, and was promoted through Web-based and in-person communication and YouTube advertisements. Data were collected using YouTube analytics and an online survey. Post–18 months from its launch, the video had a reach of 157 938 views from 154 countries, with most viewers watching an average of 73% of the video (1 minute 56 seconds). Parents (n = 32) and healthcare providers (n = 170) completed the survey. Overall, both reported that they liked the video, found it helpful, felt more confident, and were more likely to use skin-to-skin contact (16% and 12%) and breast-feeding (3% and 11%), respectively, during future painful procedures. Despite the high-viewing patterns, alternative methods should be considered to better evaluate the impact on practice change.
Effectiveness of Intracavitary Electrocardiogram Guidance in Peripherally Inserted Central Catheter Tip Placement in Neonates
Authors: Zhou Lianjuan , Xu Hongzhen , Liang Jianfeng , Xu Meifang , Yu Jun
Published: May 2017

Correct tip location is crucial for a peripherally inserted central catheter (PICC) to maximize the effects of central venous infusion. However, it is difficult to place the tip in a correct location in neonates because of the unreliable estimated length by surface landmark. Therefore, we evaluated the feasibility and safety of an improved intracavitary electrocardiogram (IC-ECG) technique in guiding PICC placement in neonates based on the ratios of P/R wave amplitudes on IC-ECG. The results showed that all of the 32 neonates whose PICCs had been successfully placed and correct tip position verified by chest radiography acquired qualified P wave on IC-ECG. The average ratio of P/R wave amplitude was 0.6 ± 0.1, with a range of 0.4 to 0.8. The 49 neonates who received IC-ECG–guided PICC catheterization showed higher success rates of correct PICC tip position on the first attempt than traditional, predetermined length estimation on surface landmark (93.9% vs 62.5%, χ2 = 18.01, P < .001). No significant complications occurred in the studied neonates. Based on these findings, IC-ECG–guided tip placement appears to be a promising approach in improving the success rate of tip location when placing a PICC in neonates.
Ventricular Energetics in Pediatric Left Ventricular Assist Device Patients: A Retrospective Clinical Study
Authors: Di Molfetta Arianna , Ferrari Gianfranco , Iacobelli Roberta , Filippelli Sergio , Di Chiara Luca , Guccione Paolo , Amodeo Antonio
Published: May 2017

The aim of this study is to estimate the trend of right and left energetic parameters in left ventricular assist device (LVAD) pediatric patients. Echocardiographic data were retrospectively collected at the baseline, in the acute phase after and at the monthly follow-ups till the LVAD explantation to estimate left and right ventricular energetic parameters. A significant relationship between the left and right ventricular energetic parameter trends was found along all the study period. Left ventricular end-systolic pressure–volume relationship improved till the follow-up of 2 months and then progressively decreases. Left arteroventricular coupling decreases after the LVAD, and right arteroventricular coupling decreases at the short-term follow-up. Left ventricular external work, potential energy, and pressure–volume area decrease at the short-term follow-up and then increase progressively. Right ventricular external work, potential energy, and pressure–volume area increase after the LVAD implantation. Left (right) cardiac mechanical efficiency is improved (worsened) by the LVAD. Energetic variables show that the LVAD benefits could decrease over time. A continuous and patient tailored LVAD setting could contribute to prolong LVAD benefits. The introduction of energetic parameters could lead to a more complete evaluation of LVAD patients’ outcome which is a multiparametric process.
Role of tyrosine kinase inhibitors in the treatment of pituitary tumours: from bench to bedside
Authors: Ben-Shlomo Anat , Cooper Odelia
Published: May 2017

Purpose of review

Treatment of aggressive pituitary tumours often yields suboptimal control of the tumour and confers significant morbidity. Lactotroph and corticotroph-derived tumours express ErbB receptors and ligands, and mutations in ubiquitin-specific protease 8 (USP8), which alters epidermal growth factor receptor (EGFR) degradation, have been implicated in Cushing disease pathogenesis. EGFR tyrosine kinase inhibitor (TKI) therapy has emerged as a potential new therapeutic approach for patients with aggressive prolactinomas and Cushing disease.

Recent findings

Using EGFR or human epidermal growth factor receptor 2-driven prolactin (PRL) promoters, transgenic mice develop large tumours that respond to TKI inhibition. In human corticotroph primary cultures, treatment with the pan-ErbB TKI canertinib as well as the EGFR TKI gefitinib suppresses proopiomelanocortin mRNA. USP8 mutations, detected in up to two-thirds of Cushing disease, may underlie the increase in EGFR signalling in these tumours. Human prolactinomas have differential ErbB receptor expression associated with aggressive behaviour and data from an ongoing clinical trial suggest that resistant prolactinomas may respond to the EGFR TKI lapatinib.

Preclinical and clinical models substantiate the role of the EGFR pathway in corticotroph and lactotroph adenomas. Although further study is needed, results to date suggest that targeting the ErbB pathway may be an effective therapeutic approach for patients with aggressive pituitary tumours.
Stem cell therapy and its potential role in pituitary disorders
Authors: Lara-Velazquez Montserrat , Akinduro Oluwaseun O. , Reimer Ronald , Woodmansee Whitney W. , Quinones-Hinojosa Alfredo
Published: May 2017

Purpose of review

The pituitary gland is one of the key components of the endocrine system. Congenital or acquired alterations can mediate destruction of cells in the gland leading to hormonal dysfunction. Even though pharmacological treatment for pituitary disorders is available, exogenous hormone replacement is neither curative nor sustainable. Thus, alternative therapies to optimize management and improve quality of life are desired.

Recent findings

An alternative modality to re-establish pituitary function is to promote endocrine cell regeneration through stem cells that can be obtained from the pituitary parenchyma or pluripotent cells. Stem cell therapy has been successfully applied to a plethora of other disorders, and is a promising alternative to hormonal supplementation for resumption of normal hormone homeostasis.

In this review, we describe the common causes for pituitary deficiencies and the advances in cellular therapy to restore the physiological pituitary function.
Orthotopic liver transplantation changes the course of gastric antral vascular ectasia: a case series from a transplant center
Authors: Allamneni Chaitanya , Alkurdi Basem , Naseemuddin Rehan , McGuire Brendan M. , Shoreibah Mohamed G. , Eckhoff Devin E. , Peter Shajan
Published: May 2017

Background and aim

Gastric antral vascular ectasia (GAVE) is an important cause of upper gastrointestinal bleeding and anemia in patients with cirrhosis. The aim of our study was to evaluate the effect of orthotopic liver transplantation (OLT) on GAVE and associated anemia.

Patients and methods

We performed a chart review and identified all cirrhotic patients with GAVE who underwent OLT at the University Of Alabama at Birmingham between 2005 and 2013. Population’s demographics, etiology of cirrhosis, comorbidities, presentation and treatment modalities of GAVE, endoscopic and histopathologic reports, hemoglobin values before and after transplant, and immunosuppressive regimens were collected.

Results

Twelve patients were identified, mean age 52.4±4.4 years; seven were men (58.3%); 11 (91.7%) were White; and 6 of 12 patients had biopsy-proven GAVE. The most common etiology of cirrhosis in the cohort was chronic hepatitis C and obesity was the most common chronic condition in 50 and 83.3%, respectively. Anemia resolution was observed in 9/12 (75%) patients who underwent OLT with an increase in hemoglobin from 8.1±2.4 (5.7–13.1) before transplant to 12.0±1.4 (10–15) after transplant (P<0.0001). Esophagogastroduodenoscopy after transplant was performed in all 12 (100%) patients. The mean time between transplant and post-OLT esophagogastroduodenoscopy was 13.8±18.28 (2–57) months; complete resolution of GAVE was observed in 10 (83.3%) patients, with resolving GAVE in one (8.3%) patient.

Conclusion

GAVE is an important cause of anemia and upper gastrointestinal bleeding in patients with liver cirrhosis. Our findings show that liver transplantation can resolve GAVE and related anemia.
Key performance indicators’ assessment to develop best practices in an Emergency Medical Communication Centre
Authors: Penverne Yann , Leclere Brice , Labady Julien , Berthier Frederic , Jenvrin Joel , Javaudin Francois , Batard Eric , Montassier Emmanuel
Published: May 2017

Introduction

Emergency Medical Communication Centre (EMCC) represents a pivotal link in the chain of survival for those requiring rapid response for out-of-hospital medical emergencies. Assessing and grading the performance of EMCCs are warranted as it can affect the health and safety of the served population.

Objective

The aim of our work was to describe the activity on an EMCC and to explore the associations between different key performance indicators.

Methods

We carried out our prospective observational study in the EMCC of Nantes, France, from 6 June 2011 to 6 June 2015. The EMCC performance was assessed with the following key performance indicators: answered calls, Quality of Service 20 s (QS20), occupation rate and average call duration.

Results

A total of 35 073 h of dispatch activity were analysed. 1 488 998 emergency calls were answered. The emergency call incidence varied slightly from 274 to 284 calls/1000 citizens/year between 2011 and 2015. The median occupation rate was 35% (25–44). QS20 was correlated negatively with the occupation rate (Spearman’s ρ: −0.78). The structural equation model confirmed that the occupation rate was highly correlated with the QS20 (standardized coefficient: −0.89). For an occupation rate of 26%, the target value estimated by our polynomial model, the probability of achieving a QS20 superior or equal to 95% varied between 56 and 84%.

Conclusion

The occupation rate appeared to be the most important factor contributing towards the QS20. Our data will be useful to develop best practices and guidelines in the field of emergency medicine communication centres.
Eating disorders and bone metabolism in women
Authors: Robinson Lauren , Micali Nadia , Misra Madhusmita
Published: May 2017

Purpose of review

Eating Disorders are psychiatric disorders associated with a high risk for low bone mineral density (BMD) and fractures. Low BMD is a consequence of undernutrition, changes in body composition, and hormonal alterations. This review summarizes recent findings regarding novel strategies for assessing bone outcomes in patients with eating disorders, factors contributing to altered bone metabolism, and possible therapeutic strategies.

Recent findings

Emerging research in this field suggests that not only anorexia nervosa, but also bulimia nervosa results in lower BMD compared to controls. To date studies of bone structure, and all randomized controlled trials examining the impact of various therapies on bone outcomes in anorexia nervosa, have focused on adolescent girls and women. We discuss the impact of anorexia nervosa on bone structure, and associations of resting energy expenditure, marrow adipose tissue (including the ratio of saturated to unsaturated fat), and cold activated brown adipose tissue with BMD and bone structure. Promising strategies for treatment include physiological estrogen replacement (rather than oral contraceptives) in adolescent girls with anorexia nervosa, and bisphosphonates, as well as teriparatide, in adult women with anorexia nervosa.

Recent data on (i) BMD and bone structure in adolescent girls and women with eating disorders, (ii) factors that contribute to altered bone metabolism, and (iii) randomized controlled trials reporting positive effects of physiologic estrogen replacement, bisphosphonates and teriparatide on bone health, provide us with a greater understanding of the impact of eating disorders on bone and novel management strategies.
Selective Y Centromere Inactivation Triggers Chromosome Shattering in Micronuclei and Repair by Non-homologous End Joining
Authors: Ly Peter , Teitz Levi S. , Kim Dong H. , Shoshani Ofer , Skaletsky Helen , Fachinetti Daniele , Page David C. , Cleveland Don W.
Published: May 2017

(Abstracted from Nat Cell Biol 2017;19:68–75)

Evidence from plant models, human-cell models, and yeast genetics has suggested that complex and localized rearrangements termed chromothripsis can be triggered by chromosome missegregation into nuclear compartments called micronuclei. Chromothripsis is likely to arise through chromosome breakage and inaccurate reassembly.
Impact of Sexual Violence Across the Lifespan on HIV Risk Behaviors Among Transgender Women and Cisgender People Living With HIV
Authors: Smith Laramie R. , Yore Jennifer , Triplett Daniel P. , Urada Lianne , Nemoto Tooru ,   Kaiser Permanente Community-Based HIV Test and Treat Study Team, Raj Anita
Published: May 2017

Background:

To examine sexual violence across the lifespan among transgender and cisgender people living with HIV and its associations with recent risk behaviors.

Setting:

Seven community-based sites serving priority populations disproportionately affected by HIV in the United States, including major metropolitan areas in the West and East Coast, as well as the suburban Mid-Atlantic and rural Southeastern regions.

Methods:

From 2013 to 2016, baseline survey data were collected from participants (N = 583) of a multisite community-based HIV linkage to/retention in care study conducted at 7 sites across the United States. Adjusted mixed-effects logistic regression models with random effect for site-assessed associations of sexual violence and gender identity with risk outcomes including condomless sex, sex trade involvement, and substance use–related harms.

Results:

One-third of participants reported a history of sexual violence; transgender [adjusted odds ratio (AOR) = 5.1, 95% confidence interval (CI): 2.6 to 10.1] and cisgender women (AOR = 3.8, 95% CI: 2.3 to 6.4) were more likely than cisgender men to experience sexual violence. Sexual violence was associated with experiencing drug-related harms (AOR = 2.6, 95% CI: 1.2 to 5.5). Transgender women were more likely than cisgender men to have sold sex (AOR = 9.3, 95% CI: 1.7 to 50.0).

Conclusions:

A history of sexual violence is common among transgender and cisgender women PLWH, and it increases risk for drug-related harms. Transgender women are also more likely to report selling sex.
Effectiveness of an Integrated Approach to HIV and Hypertension Care in Rural South Africa: Controlled Interrupted Time-Series Analysis
Authors: Ameh Soter , Klipstein-Grobusch Kerstin , Musenge Eustasius , Kahn Kathleen , Tollman Stephen , Gómez-Olivé Francesc Xavier
Published: May 2017

Background:

South Africa faces a dual burden of HIV/AIDS and noncommunicable diseases. In 2011, a pilot integrated chronic disease management (ICDM) model was introduced by the National Health Department into selected primary health care (PHC) facilities. The objective of this study was to assess the effectiveness of the ICDM model in controlling patients' CD4 counts (>350 cells/mm3) and blood pressure [BP (<140/90 mm Hg)] in PHC facilities in the Bushbuckridge municipality, South Africa.

Methods:

A controlled interrupted time-series study was conducted using the data from patients' clinical records collected multiple times before and after the ICDM model was initiated in PHC facilities in Bushbuckridge. Patients ≥18 years were recruited by proportionate sampling from the pilot (n = 435) and comparing (n = 443) PHC facilities from 2011 to 2013. Health outcomes for patients were retrieved from facility records for 30 months. We performed controlled segmented regression to model the monthly averages of individuals' propensity scores using autoregressive moving average model at 5% significance level.

Results:

The pilot facilities had 6% greater likelihood of controlling patients' CD4 counts than the comparison facilities (coefficient = 0.057; 95% confidence interval: 0.056 to 0.058; P < 0.001). Compared with the comparison facilities, the pilot facilities had 1.0% greater likelihood of controlling patients' BP (coefficient = 0.010; 95% confidence interval: 0.003 to 0.016; P = 0.002).

Conclusions:

Application of the model had a small effect in controlling patients' CD4 counts and BP, but showed no overall clinical benefit for the patients; hence, the need to more extensively leverage the HIV program for hypertension treatment.
Balloon Dilatation of the Minor Duodenal Papilla Up to 4 mm is Safe in a Porcine Model
Authors: Müller Philip C. , Steinemann Daniel C. , Sauer Peter , Z’graggen Kaspar , Linke Georg R. , Müller-Stich Beat P.
Published: May 2017

Objectives:

Balloon dilatation of the minor duodenal papilla is a treatment option for symptomatic pancreas divisum. The histologic effects of balloon dilatation have not yet been evaluated. The aim of this study is to investigate the tolerated extent of dilatation of the minor papilla.

Materials and Methods:

A dilatation of the minor papilla was performed in freshly explanted pancreas of pigs using biliary balloon dilatators. Three organs were not dilated (control group), in each 8 organs a dilatation of 4, 6, and 8 mm, respectively, was performed. Tissue damage was assessed by microscopic evaluation. Ductal wall disruption and perforation as well as a semiquantitative inflammation score was described and compared.

Results:

Ductal wall disruption was increased by dilatation of 6 (5/8; P=0.019) and 8 mm (6/8; P=0.006) compared with 4 mm (1/8). Median inflammation score was 0 (0 to 0), 1 (0 to 2), and 1 (0 to 2) for dilatation of 4, 6, and 8 mm, respectively (4 vs. 6 mm, P=0.007; 4 vs. 8 mm, P=0.026). No perforation occurred in the 4 (0/8) and 6 mm (0/8) group, 1 perforation occurred in the 8 mm group (1/8).

Conclusions:

A dilatation of up to 4 mm seems to be safe. However, dilatation of the minor papilla from 4 mm onwards is increasingly associated with tissue damage. These findings should be considered in endoscopic procedures dilating the minor duodenal papilla.
Disruption of Brain–Heart Coupling in Sepsis
Authors: Admiraal Marjolein M. , Gilmore Emily J. , Van Putten Michel J. A. M. , Zaveri Hitten P. , Hirsch Lawrence J. , Gaspard Nicolas
Published: May 2017

Purpose:

To investigate heart rate and EEG variability and their coupling in patients with sepsis and determine their relationship to sepsis severity and severity of sepsis-associated brain dysfunction.

Methods:

Fifty-two patients with sepsis were prospectively identified, categorized as comatose (N = 30) and noncomatose (N = 22), and compared with 11 control subjects. In a 30-minute EEG and electrocardiogram recording, heart rate variability and EEG variability (measured by the variability of relative power in a modified alpha band = RAP) and their coupled oscillations were quantified using linear (least-square periodogram and magnitude square coherence) and nonlinear (Shannon entropy and mutual information) measures. These measures were compared between the three groups and correlated with outcome, adjusting for severity of sepsis.

Results:

Several measures of heart rate variability and EEG variability and of their coupled oscillations were significantly lower in patients with sepsis compared with controls and correlated with outcome. This correlation was not independent when adjusting for severity of sepsis.

Conclusions:

Sepsis is associated with lower variability of both heart rate and RAP on EEG and reduction of their coupled oscillations. This uncoupling is associated with the severity of encephalopathy. Combined EEG and electrocardiogram monitoring may be used to gain insight in underlying mechanisms of sepsis and quantify brainstem or thalamic dysfunction.
Insular Cortex Surgery for the Treatment of Refractory Epilepsy
Authors: von Lehe Marec , Parpaley Yaroslav
Published: May 2017

Focal epilepsy originating from the insular cortex is rare. One reason is the small amount of cortical tissue compared with other lobes of the brain. However, the incidence of insular epilepsy might be underestimated because of diagnostic difficulties. The semiology and the surface EEG are often not meaningful or even misleading, and elaborated imaging might be necessary. The close connections of the insular cortex with other potentially epileptogenic areas, such as the temporal lobe or frontal/central cortex, is increasingly recognized as possible reason for failure of epilepsy surgery for temporal or extratemporal seizures. Therefore, some centers consider invasive EEG recording of the insular cortex not only in case of insular epilepsy but also in other focal epilepsies with nonconclusive results from the presurgical work-up. The surgical approach to and resection of insular cortex is challenging because of its deep location and proximity to highly eloquent brain structures. Over the last decades, technical adjuncts like navigation tools, electrophysiological monitoring and intraoperative imaging have improved the outcome after surgery. Nevertheless, there is still a considerable rate of postoperative transient or permanent deficits, in some cases as unavoidable and calculated deficits. In most of the recent series, seizure outcome was favorable and comparable with extratemporal epilepsy surgery or even better. Up to now, the data volume concerning long-term follow-up is limited. This review focusses on the surgical challenges of resections to treat insular epilepsy, on prognostic factors concerning seizure outcome, on postoperative deficits and complications. Moreover, less invasive surgical techniques to treat epilepsy in this highly eloquent area are summarized.
Cannibalism by damselflies increases with rising temperature
Authors: Start Denon , Kirk Devin , Shea Dylan , Gilbert Benjamin
Published: May 2017

Trophic interactions are likely to change under climate warming. These interactions can be altered directly by changing consumption rates, or indirectly by altering growth rates and size asymmetries among individuals that in turn affect feeding. Understanding these processes is particularly important for intraspecific interactions, as direct and indirect changes may exacerbate antagonistic interactions. We examined the effect of temperature on activity rate, growth and intraspecific size asymmetries, and how these temperature dependencies affected cannibalism in
Lestes congener
, a damselfly with marked intraspecific variation in size. Temperature increased activity rates and exacerbated differences in body size by increasing growth rates. Increased activity and changes in body size interacted to increase cannibalism at higher temperatures. We argue that our results are likely to be general to species with life-history stages that vary in their temperature dependencies, and that the effects of climate change on communities may depend on the temperature dependencies of intraspecific interactions.
Francis Harry Compton Crick OM. 8 June 1916 — 28 July 2004
Authors: Bretscher Mark S. , Mitchison Graeme
Published: May 2017

The first half of the twentieth century saw a profound change in our understanding of the chemistry underlying biology. We came to learn in detail how the small molecules upon which life is based are interconverted by specific enzymes, a web which increased in complexity and became modern biochemistry. Intellectually, a quite separate development—molecular biology—arose from physicists and chemists studying the structure of proteins with X-rays, and biologists studying viruses that infect bacteria. Its intellectual thrust was to discover how information in genes is expressed and controlled. This led to a revolution in our understanding of biology, and no person was more influential in shaping and guiding this emerging field than Francis Crick.
Minimum action principle and shape dynamics
Authors: Koehl Patrice
Published: May 2017

In this paper, we propose a new method for computing a distance between two shapes embedded in three-dimensional space. Instead of comparing directly the geometric properties of the two shapes, we measure the cost of deforming one of the two shapes into the other. The deformation is computed as the geodesic between the two shapes in the space of shapes. The geodesic is found as a minimizer of the Onsager–Machlup action, based on an elastic energy for shapes that we define. Its length is set to be the integral of the action along that path; it defines an intrinsic quasi-metric on the space of shapes. We illustrate applications of our method to geometric morphometrics using three datasets representing bones and teeth of primates. Experiments on these datasets show that the variational quasi-metric we have introduced performs remarkably well both in shape recognition and in identifying evolutionary patterns, with success rates similar to, and in some cases better than, those obtained by expert observers.
Density-dependent coral recruitment displays divergent responses during distinct early life-history stages
Authors: Doropoulos Christopher , Evensen Nicolas R. , Gómez-Lemos Luis A. , Babcock Russell C.
Published: May 2017

Population growth involves demographic bottlenecks that regulate recruitment success during various early life-history stages. The success of each early life-history stage can vary in response to population density, interacting with intrinsic (e.g. behavioural) and environmental (e.g. competition, predation) factors. Here, we used the common reef-building coralAcropora milleporato investigate how density-dependence influences larval survival and settlement in laboratory experiments that isolated intrinsic effects, and post-settlement survival in a field experiment that examined interactions with environmental factors. Larval survival was exceptionally high (greater than 80%) and density-independent from 2.5 to 12 days following spawning. By contrast, there was a weak positive effect of larval density on settlement, driven by gregarious behaviour at the highest density. When larval supply was saturated, settlement was three times higher in crevices compared with exposed microhabitats, but a negative relationship between settler density and post-settlement survival in crevices and density-independent survival on exposed surfaces resulted in similar recruit densities just one month following settlement. Moreover, a negative relationship was found between turf algae and settler survival in crevices, whereas gregarious settlement improved settler survival on exposed surfaces. Overall, our findings reveal divergent responses by coral larvae and newly settled recruits to density-dependent regulation, mediated by intrinsic and environmental interactions.
Relative geodesics in bi-invariant Lie groups
Authors: Zhang E. , Noakes L.
Published: May 2017

Motivated by registration problems, this paper deals with a curve matching problem in homogeneous spaces. Let
G
be a connected finite-dimensional bi-invariant Lie group and
K
a closed subgroup. A smooth curve
g
in
G
is said to be
admissible
if it can transform two smooth curves
f
1
and
f
2
in
G
/
K
from one to the other. An (
f
1
,
f
2
)-
relative geodesic
(Holm
et al.
2013
Proc. R. Soc. A
469
, 20130297. (
doi:10.1098/rspa.2013.0297
)) is defined as a critical point of the total energy
E
(
g
) as
g
varies in the set of all (
f
1
,
f
2
)-admissible curves. We obtain the Euler–Lagrange equation, a first-order differential equation, satisfied by a relative geodesic. Furthermore, the Euler–Lagrange equation is simplified for the case where
G
/
K
is globally symmetric. As a concrete example, relative geodesics are found for special cases where
G
is SO(3) and
K
is SO(2). As an application of discrepancy for curves in
S
2
, we construct and study a new measure of non-congruency for constant speed curves in Euclidean 3-space. Numerical examples are given to illustrate results.
Aeroacoustic catastrophes: upstream cusp beaming in Lilley's equation
Authors: Stone J. T. , Self R. H. , Howls C. J.
Published: May 2017

The downstream propagation of high-frequency acoustic waves from a point source in a subsonic jet obeying Lilley's equation is well known to be organized around the so-called ‘cone of silence’, a fold catastrophe across which the amplitude may be modelled uniformly using Airy functions. Here we show that acoustic waves not only unexpectedly propagate upstream, but also are organized at constant distance from the point source around a cusp catastrophe with amplitude modelled locally by the Pearcey function. Furthermore, the cone of silence is revealed to be a cross-section of a swallowtail catastrophe. One consequence of these discoveries is that the peak acoustic field upstream is not only structurally stable but also at a similar level to the known downstream field. The fine structure of the upstream cusp is blurred out by distributions of symmetric acoustic sources, but peak upstream acoustic beaming persists when asymmetries are introduced, from either arrays of discrete point sources or perturbed continuum ring source distributions. These results may pose interesting questions for future novel jet-aircraft engine designs where asymmetric source distributions arise.
Crossing the quasi-threshold manifold of a noise-driven excitable system
Authors: Chen Zhen , Zhu Jinjie , Liu Xianbin
Published: May 2017

We consider the noise-induced escapes in an excitable system possessing a quasi-threshold manifold, along which there exists a certain point of minimal quasi-potential. In the weak noise limit, the optimal escaping path turns out to approach this particular point asymptotically, making it analogous to an ordinary saddle. Numerical simulations are performed and an elaboration on the effect of small but finite noise is given, which shows that the ridges where the prehistory probability distribution peaks are located mainly within the region where the quasi-potential increases gently. The cases allowing anisotropic noise are discussed and we found that varying the noise term in the slow variable would dramatically raise the whole level of quasi-potentials, leading to significant changes in both patterns of optimal paths and exit locations.
Uncertainty relations on nilpotent Lie groups
Authors: Ruzhansky Michael , Suragan Durvudkhan
Published: May 2017

We give relations between main operators of quantum mechanics on one of most general classes of nilpotent Lie groups. Namely, we show relations between momentum and position operators as well as Euler and Coulomb potential operators on homogeneous groups. Homogeneous group analogues of some well-known inequalities such as Hardy's inequality, Heisenberg–Kennard type and Heisenberg–Pauli–Weyl type uncertainty inequalities, as well as Caffarelli–Kohn–Nirenberg inequality are derived, with best constants. The obtained relations yield new results already in the setting of both isotropic and anisotropicRn, and of the Heisenberg group. The proof demonstrates that the method of establishing equalities in sharper versions of such inequalities works well in both isotropic and anisotropic settings.
A genetic legacy of introgression confounds phylogeny and biogeography in oaks
Authors: McVay John D. , Hipp Andrew L. , Manos Paul S.
Published: May 2017

Oaks (QuercusL.) have long been suspected to hybridize in nature, and widespread genetic exchange between morphologically defined species is well documented in two- to six-species systems, but the phylogenetic consequences of hybridization in oaks have never been demonstrated in a phylogenetically diverse sample. Here, we present phylogenomic analyses of aca30 Myr clade that strongly support morphologically defined species and the resolution of novel clades of white oaks; however, historical hybridization across clade boundaries is detectable and, undiagnosed, would obscure the imprint of biogeographic history in the phylogeny. Phylogenetic estimation from restriction-site-associated DNA sequencing data for 156 individuals representing 81 species supports two successive intercontinental disjunctions of white oaks: an early vicariance between the Eurasian and American white oaks, and a second, independent radiation represented by two relictual species. A suite of subsampled and partitioned analyses, however, supports a more recent divergence of the Eurasian white oaks from within the American white oaks and suggests that historic introgression between the Eurasian white oaks and a now-relictual lineage biases concatenated phylogenetic estimates. We demonstrate how divergence and reticulation both influence our understanding of the timing and nature of diversification and global colonization in these ecologically and economically important taxa.
Family network size and survival across the lifespan of female macaques
Authors: Brent L. J. N. , Ruiz-Lambides A. , Platt M. L.
Published: May 2017

Two decades of research suggest social relationships have a common evolutionary basis in humans and other gregarious mammals. Critical to the support of this idea is growing evidence that mortality is influenced by social integration, but when these effects emerge and how long they last is mostly unknown. Here, we report in adult female macaques that the impact of number of close adult female relatives, a proxy for social integration, on survival is not experienced uniformly across the life course; prime-aged females with a greater number of relatives had better survival outcomes compared with prime-aged females with fewer relatives, whereas no such effect was found in older females. Group size and dominance rank did not influence this result. Older females were less frequent targets of aggression, suggesting enhanced experience navigating the social landscape may obviate the need for social relationships in old age. Only one study of humans has found age-based dependency in the association between social integration and survival. Using the largest dataset for any non-human animal to date, our study extends support for the idea that sociality promotes survival and suggests strategies employed across the life course change along with experience of the social world.
Carriage of extended-spectrum beta-lactamase-producing Enterobacteriaceae in HIV-infected children in Zimbabwe
Authors: Wilmore S. M. S , Kranzer K , Williams A , Makamure B , Nhidza A. F , Mayini J , Bandason T , Metcalfe J , Nicol M. P , Balakrishnan I , Ellington M. J , Woodford N , Hopkins S , McHugh T. D , Ferrand R. A
Published: May 2017

Background. Antimicrobial resistance is an emerging global health issue. Data on the epidemiology of multidrug-resistant organisms are scarce for Africa, especially in HIV-infected individuals who often have frequent contact with healthcare. We investigated the prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) carriage in stool among HIV-infected children attending an HIV outpatient department in Harare, Zimbabwe.

Methods. We recruited children who were stable on antiretroviral therapy (ART) attending a HIV clinic from August 2014 to June 2015. Information was collected on antibiotic use and hospitalization. Stool was tested for ESBL-E through combination disc diffusion. API20E identification and antimicrobial susceptibility was performed on the positive samples followed by whole genome sequencing.

Results. Stool was collected from 175/202 (86.6 %) children. Median age was 11 [inter-quartile range (IQR) 9–12] years. Median time on ART was 4.6 years (IQR 2.4–6.4). ESBL-Es were found in 24/175 samples (13.7 %); 50 % of all ESBL-Es were resistant to amoxicillin-clavulanate, 100 % to co-trimoxazole, 45.8 % to chloramphenicol, 91.6 % to ceftriaxone, 20.8 % to gentamicin and 62.5 % to ciprofloxacin. ESBL-Es variously encoded CTX-M, OXA, TEM and SHV enzymes. The odds of ESBL-E carriage were 8.5 times (95 % CI 2.2–32.3) higher in those on ART for less than one year (versus longer) and 8.5 times (95 % CI 1.1–32.3) higher in those recently hospitalized for a chest infection.

Conclusion. We found a 13.7 % prevalence of ESBL-E carriage in a population where ESBL-E carriage has not been described previously. Antimicrobial resistance (AMR) in Africa merits further study, particularly given the high HIV prevalence and limited diagnostic and therapeutic options available.
Temporal dynamics of gene expression in heat-stressed Caenorhabditis elegans
Authors: Jovic Katharina , Sterken Mark G. , Grilli Jacopo , Bevers Roel P. J. , Rodriguez Miriam , Riksen Joost A. G. , Allesina Stefano , Kammenga Jan E. , Snoek L. Basten
Published: May 2017

There is considerable insight into pathways and genes associated with heat-stress conditions. Most genes involved in stress response have been identified using mutant screens or gene knockdowns. Yet, there is limited understanding of the temporal dynamics of global gene expression in stressful environments. Here, we studied global gene expression profiles during 12 hours of heat stress in the nematode C. elegans. Using a high-resolution time series of increasing stress exposures, we found a distinct shift in gene expression patterns between 3-4 hours into the stress response, separating an initially highly dynamic phase from a later relatively stagnant phase. This turning point in expression dynamics coincided with a phenotypic turning point, as shown by a strong decrease in movement, survival and, progeny count in the days following the stress. Both detectable at transcriptional and phenotypic level, this study pin-points a relatively small time frame during heat stress at which enough damage is accumulated, making it impossible to recover the next few days.
Mutations in the pantothenate kinase ofPlasmodium falciparumconfer diverse sensitivity profiles to antiplasmodial pantothenate analogues
Authors: Tjhin Erick T. , Spry Christina , Sewell Alan L. , Hoegl Annabelle , Barnard Leanne , Sexton Anna E. , Howieson Vanessa M. , Maier Alexander G. , Creek Darren J. , Strauss Erick , Marquez Rodolfo , Auclair Karine , Saliba Kevin J.
Published: May 2017

The malaria-causing blood stage ofPlasmodium falciparumrequires extracellular pantothenate for proliferation. The parasite converts pantothenate into coenzyme A (CoA) via five enzymes, the first being a pantothenate kinase (PfPanK). Multiple antiplasmodial pantothenate analogues, including pantothenol and CJ-15,801, kill the parasite by targeting CoA biosynthesis/utilisation. Their mechanism of action, however, remains unknown. Here, we show that parasites pressured with pantothenol or CJ-15,801 become resistant to these analogues. Whole-genome sequencing revealed mutations in one of two putative PanK genes (Pfpank1) in each resistant line. These mutations significantly alterPfPanK activity, with two conferring a fitness cost, consistent withPfpank1coding for a functional PanK that is essential for normal growth. The mutants exhibit a different sensitivity profile to recently-described, potent, antiplasmodial pantothenate analogues, with one line beinghypersensitive. We provide evidence consistent with different pantothenate analogue classes having different mechanisms of action: some inhibit CoA biosynthesis while others inhibit CoA-utilising enzymes.
Molecular mechanisms of human papillomavirus-related carcinogenesis in head and neck cancer
Authors: Faraji Farhoud , Zaidi Munfarid , Fakhry Carole , Gaykalova Daria A.
Published: May 2017

This review examines the general cellular and molecular underpinnings of human papillomavirus (HPV)-related carcinogenesis in the context of head and neck squamous cell carcinoma (HNSCC) and focuses on HPV-positive oropharyngeal squamous cell carcinoma in areas for which specific data is available. It covers the major pathways dysregulated in HPV- positive HNSCC and the genome-wide changes associated with this disease.
Lewy pathology in Parkinson’s disease consists of a crowded organellar, membranous medley
Authors: Shahmoradian Sarah H. , Lewis Amanda J. , Genoud Christel , Hench Jürgen , Moors Tim , Navarro Paula P. , Castaño-Díez Daniel , Schweighauser Gabriel , Graff-Meyer Alexandra , Goldie Kenneth N. , Sütterlin Rosmarie , Huisman Evelien , Ingrassia Angela , de Gier Yvonne , Rozemuller Annemieke J.M. , Wang Jing , De Paepe Anne , Erny Johannes , Staempfli Andreas , Hoernschemeyer Joerg , Großerüschkamp Frederik , Niedieker Daniel , El-Mashtoly Samir F. , Quadri Marialuisa , van IJcken Wilfred F.J. , Bonifati Vincenzo , Gerwert Klaus , Bohrmann Bernd , Frank Stephan , Britschgi Markus , Stahlberg Henning , van de Berg Wilma D. J. , Lauer Matthias E.
Published: May 2017

Parkinson’s disease, the most common age-related movement disorder, is a progressive neurodegenerative disease with unclear etiology. Key neuropathological hallmarks are Lewy bodies and Lewy neurites, which are neuronal inclusions that are immunopositive for the protein α-synuclein. In-depth ultrastructural analysis of this Lewy pathology is crucial to understanding pathogenesis and progression of the disease. Using correlative light and electron microscopy/tomography on brain tissue from five Parkinson’s disease brain donors, we identified α-synuclein immunopositive Lewy pathology and could show that the majority of these features including Lewy bodies and Lewy neurites primarily consists of a crowded membranous medley of vesicular structures and dysmorphic organelles. Only a small fraction of observed Lewy bodies contained predominant proteinaceous filaments, as previously described. The crowding of organellar components was confirmed by STED- based super-resolution microscopy, and high lipid content within the α-synuclein immunopositive inclusions was corroborated by confocal imaging, CARS/FTIR imaging and lipidomics. Applying this correlative high-resolution imaging and biophysical approach, we discovered in the postmortem brain of Parkinson’s patients a subcellular protein-lipid compartmentalization not previously described in Lewy pathology.