bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Patient Reported Outcome Measurement Information System With Neck Disability Index and Visual Analog Scale in Patients With Neck Pain
Authors: Moses Michael J. , Tishelman Jared C. , Stekas Nicholas , Jevotovsky David S. , Vasquez-Montes Dennis , Karia Raj , Errico Thomas , Buckland Aaron , Protopsaltis Themistocles S.
Published: July 2018

Study Design.

A retrospective analysis of a patient-reported outcomes database from a single institution from December 2016 to April 2017.

Objective.

To validate the association of Patient Reported Outcome Measurement Information System (PROMIS) with Neck Disability Index (NDI) in patients with neck pain and examine each instruments ability to capture concomitant arm pain and concomitant back pain.

Summary of Background Data.

PROMIS has been increasingly utilized and its computer adapted testing methodology improves assessment of pain and disability. However, literature is lacking regarding how these instruments perform in neck pain patients with concomitant arm pain or back pain.

Methods.

Inclusion criteria were age >18 years and a primary complaint of neck pain. The NDI; Visual Analog Scale (VAS) back, neck, arm, and leg; and PROMIS physical function, pain intensity, and pain interference questionnaires were administered. Propensity score matching was performed to compare patients with high and low back and arm pain by controlling for neck pain. Bivariate correlations and independent samples t tests were performed to assess linear relationships and compare back and arm pain groups with PROMIS.

Results.

Approximately, 130 patients were included. NDI correlated strongly to PROMIS physical function (r = −0.771, P < 0.001), pain intensity (r = 0.605, P < 0.001), and pain interference (r = 0.786, P < 0.001). VAS neck and arm pain also correlated to the PROMIS pain intensity instrument (VAS neck: r = 0.642, P < 0.001; VAS arm: r = 0.376, P < 0.001).

After matching for neck pain, the high and low back pain groups each included 32 patients. There were significant differences in PROMIS physical function when high and low back pain groups were compared (39.07 vs. 43.68, P = 0.031). No significant difference was found for any outcome metric for high and low arm pain groups.

Conclusion.

PROMIS instruments are capable of characterizing pain and disability in patients with neck pain and are sensitive to disability in regions adjacent to the neck.

Level of Evidence: 3
Real-World Effectiveness of Physical Therapy for Common Neck Pain Diagnoses
Authors: Divi Srikanth N. , Eleswarapu Ananth S. , Stout Christopher E. , Lee Michael J.
Published: July 2018

Study Design:

Retrospective cohort study (Level of evidence—3).

Objective:

The objective of this study was to investigate the real-life effectiveness of physical therapy (PT) for patients initially presenting with common neck pain diagnoses.

Summary of Background Data:

Neck pain is a common cause of morbidity and a leading cause of disability in the United States. PT is prescribed as a first-line treatment for the vast majority of patients with neck pain; however, there is limited literature supporting the effectiveness of these treatments.

Methods:

A total of 1554 patients enrolled in PT for the nonoperative treatment of neck pain were included in the study. Three primary patient-reported outcome (PRO) measures [neck disability index (NDI), resting numeric pain rating scale (NPRS), and activity NPRS] were recorded before and at conclusion of therapy. Improvement was noted if patients met a threshold value for a minimal clinically important difference (MCID). Bivariate analysis using a χ2 test and multiple logistic regression analysis were performed to determine risk factors predictive of treatment failure.

Results:

About 40.5% of patients achieved MCID for NDI with an average change of −6.31 points. For resting NPRS and activity NPRS scores, 50.6% and 52.1% of patients achieved MCID with an average change of −1.93 and −2.36, respectively. After multiple logistic regression analysis, worker’s compensation status was found to be an independent predictor for treatment failure in all groups; whereas, Medicare status was found predictive of achieving MCID in the activity NPRS group.

Conclusions:

We observed that up to half of the patients analyzed met the minimum criteria for improvement in neck pain with respect to the PRO measures, suggesting that real-life effectiveness of PT for common neck pain diagnoses may approach 50%.
Inspiratory Muscle Training in Patients With Prolonged Mechanical Ventilation: Narrative Review
Authors: Ahmed Shakeel , Martin A Anatole. Daniel , Smith Barbara K.
Published: July 2018

Patients with impending respiratory failure often require mechanical ventilation (MV) to optimize gas exchange. Although this form of assisted ventilation is required for survival, its persistent use results in diaphragm weakness and muscle fiber atrophy. There is strong evidence that MV alters the structure and function of the diaphragm, resulting in prolonged dependence on assisted ventilation and long-term consequences such as a delayed functional recovery, reduced quality of life, and increased risk of mortality. This review summarizes the mechanisms underlying diaphragm dysfunction due to prolonged MV, highlights the role of inspiratory muscle exercise as a strategy to counter diaphragm weakness, and identifies the parameters of an evidence-supported exercise prescription for difficult to wean patients.
REVERSIBLE RETINAL TOXICITY IN A PATIENT TAKING AXITINIB
Authors: Jenkins Thomas L. , Aderman Christopher M. , Ho Allen C.
Published: July 2018

Purpose:

Axitinib (Inlyta, New York, NY) is a kinase inhibitor indicated for the treatment of advanced renal cell carcinoma after failure of one previous systemic therapy. A case of bilateral retinal hemorrhages and cotton wool spots associated with axitinib is reported.

Methods:

A 62-year-old woman with a 4-year history of renal cell carcinoma with metastases was treated with axitinib at a maximum oral daily dose of 8 mg. Soon after beginning higher dose therapy, she developed blurred vision, floaters, and photopsias.

Results:

Funduscopic examination of both eyes revealed cotton wool spots and retinal hemorrhages that improved with cessation of therapy.

Conclusion:

Axitinib may be associated with microangiopathic retinal toxicity.
Macular Vessel Density and Ganglion Cell/Inner Plexiform Layer Thickness and Their Combinational Index Using Artificial Intelligence
Authors: Park Keunheung , Kim Jinmi , Lee Jiwoong
Published: July 2018

Purpose:

To evaluate the relationship between macular vessel density and ganglion cell to inner plexiform layer thickness (GCIPLT) and to compare their diagnostic performance. We attempted to develop a new combined parameter using an artificial neural network.

Methods:

A total of 173 subjects: 100 for the test and 73 for neural net training. The test group consisted of 32 healthy, 33 early, and 35 advanced glaucoma subjects. Macular GCIPLT and vessel density were measured using Spectralis optical coherence tomography and Topcon swept-source optical coherence tomography, respectively. Various regression models were used to investigate the relationships between macular vessel density and GCIPLT. A multilayer neural network with one hidden layer was used to determine a single combined parameter. To compare diagnostic performance, we used the area under the receiver operating characteristic curve (AUROC).

Results:

Correlation analyses in all subjects showed a significant correlation between macular vessel density and GCIPLT in all sectors (r=0.27 to 0.56; allPs≤0.006). The fitness of linear, quadratic, and exponential regression models showed clinically negligible differences (Akaike’s information criterion=714.6, 713.8, and 713.3, respectively) and were almost linear. In differentiating normal and early glaucoma, the diagnostic power of macular GCIPLT (AUROC=0.67 to 0.81) was much better than that of macular vessel density (AUROC=0.50 to 0.60). However, when vessel density information was incorporated into GCIPLT using the neural network, the combined parameter (AUROC=0.87) showed significantly enhanced diagnostic performance than all sectors of macular vessel density and GCIPLT (allPs≤0.043).

Conclusions:

Macular vessel density was significantly decreased in glaucoma patients and showed an almost linear correlation with macular GCIPLT. The diagnostic performance of macular vessel density was much lower than that of macular GCIPLT. However, when incorporated into macular GCIPLT using an artificial neural network, the combined parameter showed better performance than macular GCIPLT alone.
Contextual influences in decoding pain expressions: effects of patient age, informational priming, and observer characteristics
Authors: Hampton Amy J. D. , Hadjistavropoulos Thomas , Gagnon Michelle M.
Published: July 2018

We aimed to examine the effects of contextual factors (ie, observers' training background and priming texts) on decoding facial pain expressions of younger and older adults. A total of 165 participants (82 nursing students and 83 nonhealth professionals) were randomly assigned to one of 3 priming conditions: (1) information about the possibility of secondary gain (misuse); (2) information about the frequency and undertreatment of pain in the older adult (undertreatment); or (3) neutral information (control). Subsequently, participants viewed 8 videos of older adults and 8 videos of younger adults undergoing a discomforting physical therapy examination. Participants rated their perception of each patient's pain intensity, unpleasantness, and condition severity. They also rated their willingness to help, sympathy level, patient deservingness of financial compensation, and how negatively/positively they feel towards the patient (ie, valence). Results demonstrated that observers ascribed greater levels of pain and other indicators (eg, sympathy and help) to older compared with younger patients. An interaction between observer type and patient age demonstrated that nursing students endorsed higher ratings of younger adults' pain compared with other students. In addition, observers in the undertreatment priming condition reported more positive valence towards older patients. By contrast, priming observers with the misuse text attenuated their valence ratings towards younger patients. Finally, the undertreatment prime influenced observers' pain estimates indirectly through observers' valence towards patients. In summary, results add specificity to the theoretical formulations of pain by demonstrating the influence of patient and observer characteristics, as well as informational primes, on decoding pain expressions.
Genetic predisposition in pancreatitis
Authors: Gonska Tanja
Published: July 2018

Purpose of review

Genetic mutations are the primary cause for acute recurrent (ARP) and chronic pancreatitis in children. Further, our medical approach for many diseases is changing from a one-drug therapy to more individualized therapeutic strategies. In respect to the therapeutic management of ARP/chronic pancreatitis, this entails an understanding of the individual, mainly genetic, risk factors that led to pancreatitis disease.

Recent findings

New pancreatitis-associated genes are continuously emerging from increasingly large genetic cohort studies. Furthermore, newer research findings demonstrate that multiple genetic and nongenetic factors are required to increase the individual risk for developing ARP/chronic pancreatitis. Last, there is new exciting development towards targeted pancreatitis therapy in the future.

This review introduces the current concept of ARP/chronic pancreatitis as a complex disease caused by multiple genetic and nongenetic factors. This warrants careful evaluation of these patients and ideally consultation of a pancreas expert to help understand individual genetic risk profiles and to provide more effective patient consultation.
Effectiveness of Video-Assisted Debriefing in Simulation-Based Health Professions Education
Authors: Zhang Hui , Mörelius Evalotte , Goh Sam Hong Li , Wang Wenru
Published: July 2018

Background

Debriefing helps learners to gain knowledge through guided reflection and discussion. Video-assisted debriefing (VAD) refers to adding video review during the debriefing process.

Purpose

This review evaluated the effectiveness of VAD on learners' reactions, learning, and behavior compared with verbal debriefing (if possible) and identified its effective elements.

Methods

A structured search was conducted in PubMed, MEDLINE, CINAHL, ScienceDirect, Scopus, Web of Science, and PsycINFO. The quality of the included studies was evaluated using the Medical Education Research Study Quality Instrument.

Results

Twenty-three studies published between 2002 and 2017 were selected. Results showed that VAD improved learners' experience, attitude, and performance, but it did not show its advantage over verbal debriefing on knowledge acquisition. Effective elements included using experienced debriefers, curriculum-embedded simulation, a structured debriefing, and the time between 10 and 90 minutes.

Conclusions

VAD improved learning outcomes and offered comparable benefits as verbal debriefing.
The Accuracy of Left Ventricular and Left Atrial Volumetry Using 64-Slice Computed Tomography: In Vitro Validation Study With Human Cardiac Cadaveric Casts
Authors: Järvinen Vesa , Uusitalo Valtteri , Tolvanen Tuula , Saraste Antti , Kuusisto Jouni , Sinisalo Juha , Knuuti Juhani
Published: July 2018

Objective

We aimed to validate the accuracy of imaging of left atrial and ventricular volumes using cardiac cadaveric silicone casts.

Methods

Left atrial (n = 14) and ventricular (n = 15) casts were imaged using 64-slice computed tomography (CT). Water displacement (WD) of cardiac casts was used as the gold standard for volume measurements.

Results

Compared with WD, CT resulted in slightly higher left atrial and ventricular volumes (54 ± 25 vs 56 ± 26 mL [P = 0.003] and 57 ± 47 vs 66 ± 47 mL [P = 0.0001]). Variability between left atrial and ventricular volumes by CT and WD was low (coefficients of variation [CVs], 4% [intraclass correlation coefficient {ICC}, 0.99] and 12% [ICC, 0.97]). Intraobserver variability of CT was low for both the left atrium and the left ventricle (CVs, 1% [ICC, 1.00] and 4% [ICC, 1.00]).

Conclusions

Cardiac CT is both accurate and reproducible in assessment of left ventricular and atrial chamber volumes.
Accelerated Internal Auditory Canal Screening Magnetic Resonance Imaging Protocol With Compressed Sensing 3-Dimensional T2-Weighted Sequence
Authors: Yuhasz Mikell , Hoch Michael J. , Hagiwara Mari , Bruno Mary T. , Babb James S. , Raithel Esther , Forman Christoph , Anwar Abbas , Thomas Roland J. , Shepherd Timothy M.
Published: July 2018

Background and Purpose

High-resolution T2-weighted sequences are frequently used in magnetic resonance imaging (MRI) studies to assess the cerebellopontine angle and internal auditory canal (IAC) in sensorineural hearing loss patients but have low yield and lengthened examinations. Because image content in the Wavelet domain is sparse, compressed sensing (CS) that uses incoherent undersampling ofk-space and iterative reconstruction can accelerate MRI acquisitions. We hypothesized that an accelerated CS T2 Sampling Perfection with Application optimized Contrasts using different flip angle Evolution (SPACE) sequence would produce acceptable diagnostic quality for IAC screening protocols.

Material and Methods

Seventy-six patients underwent 3 T MRI using conventional SPACE and a CS T2 SPACE prototype sequence for screening the IACs were identified retrospectively. Unilateral reconstructions for each sequence were separated, then placed into mixed folders for independent, blinded review by 3 neuroradiologists during 2 sessions 4+weeks apart. Radiologists reported if a lesion was present. Motion and visualization of specific structures were rated using ordinal scales. McNemar, Wilcoxon, Cohen κ, and Mann-WhitneyUtests were performed for accuracy, equivalence, and interrater and intrarater reliability.

Results

T2 SPACE using CS reconstruction reduced scan time by 80% to 50 seconds and provided 98.7% accuracy for IAC mass detection by 3 raters. Radiologists preferred conventional images (0.7–1.0 reduction on 5-point scale,P< 0.001), but rated CS SPACE acceptable. The 95% confidence for reduction in any cerebellopontine angle, IAC, or fluid-filled inner ear structure assessment with CS SPACE did not exceed 0.5.

Conclusions

Internal auditory canal screening MRI protocols can be performed using a 5-fold accelerated T2 SPACE sequence with compressed sensing while preserving diagnostic image quality and acceptable lesion detection rate.
FDG PET-CT in Adrenal Multiple Myeloma
Authors: Choudhury Sayak , Purandare Nilendu , Agrawal Archi , Shah Sneha , Rangarajan Venkatesh
Published: July 2018

Extramedullary involvement in multiple myeloma is rare, but carries poor prognosis. We describe the FDG PET-CT findings of rare adrenal involvement in a case of multiple myeloma.
Frontal Sinus Osteoplastic Flap Surgery Using a Surgical Navigation System
Authors: Bang Yu Jin , Lim Byeong Woo , Ha Ryun , Woo Joo Hyun , Kim Seon Tae , Jung Joo Hyun , Cha Heung Eog , Chang Jin Soon , Han Ji Hye , Choi Ji Yun , Kang Il Gyu
Published: July 2018

Objective:

To report the case of a 38-year-old woman who underwent osteoplastic flap surgery for recurrent frontal sinus mucocele. During surgery, the exact shape of the frontal sinus was duplicated using a surgical navigation system.

Methods:

In this case report, the authors suggest intraoperative surgical navigation systems are useful for accurately determining the dimensions of the frontal sinus for osteoplastic flap surgery.

Results:

The patient underwent successful and safe osteoplastic flap surgery using a surgical navigation system.

Conclusion:

Surgical navigation is useful and safe for frontal sinus osteoplastic flap surgery.
A Cost Analysis of Icon Reusable Underwear Versus Disposable Pads for Mild to Moderate Urinary Incontinence
Authors: Alam Pakeeza A. , Huang Jim C. , Clark Brett A. , Burkett Linda S. , Richter Lee A.
Published: July 2018

Objective

The objective of this study was to perform a cost analysis assessing the economic feasibility of reusable underwear as alternative for disposable pads for women with mild to moderate urinary incontinence.

Methods

A consumer-perspective cost analysis was performed with the following assumptions: (1) consumers have mild to moderate urinary incontinence and use 2 pads per day (PPD); (2) consumers have a 2-week supply of underwear; (3) there is no difference in laundering cost between 2 incontinence options; (4) there is no difference in use of labor/other accessories of care; (5) there is no difference in skin complaints/associated cost; (6) cost of products are nonfluctuant with time; and (7) all incontinence products were purchased online. Sensitivity analyses were performed varying the longevity of underwear, price of regular underwear, price of pads, pads used per day, and shipping and handling.

Results

The total cost of disposable pads with regular underwear was US $392.40, whereas the cost of Icon underwear was US $380.80 over the course of 2 years. Icon costs less than using regular underwear with disposable pads as long as the cost of the regular underwear is at least US $2.17. Icon is economically inferior if the cost per pad is US $0.15 when using 3 PPD or if the cost per pad is US $0.24 when using less than 2 PPD.

Conclusions

Reusable incontinence underwear can be an economically feasible alternative to disposable pads for light to moderate urinary incontinence after 2 years of use assuming underwear has a 2-year longevity and the consumer is using 2 PPD with regular underwear.
Poor Cardiorespiratory Fitness Is a Risk Factor for Sepsis in Patients Awaiting Liver Transplantation
Authors: Wallen Matthew P. , Woodward Aidan J. , Hall Adrian , Skinner Tina L. , Coombes Jeff S. , Macdonald Graeme A.
Published: July 2018

Background.

Patients with advanced liver disease are at increased risk of infection and other complications. A significant proportion of patients also have poor fitness and low muscle mass. The primary aim of this study was to investigate if cardiorespiratory fitness and body composition are risk factors for sepsis and other complications of advanced liver disease.

Methods.

Patients being listed for liver transplantation underwent cardiopulmonary exercise testing to determine ventilatory threshold (VT). Computed tomography was used to measure skeletal muscle and subcutaneous and visceral adipose tissue indexes. All unplanned hospital admissions, deaths or delistings before transplantation were recorded.

Results.

Eighty-two patients (aged 55.1 [50.6–59.4] years, median (interquartile range); male 87%] achieved a median VT of 11.7 (9.7–13.4) mL·kg−1·min−1. Their median model of end-stage liver disease, incorporating serum sodium score was 18 (14–22); and 37 had hepatocellular carcinoma. There were 50 admissions in 31 patients; with 16 admissions for sepsis in 13 patients. Patients with sepsis had a significantly lower VT (sepsis, 9.5 [7.8–11.9]; no sepsis, 11.8 [10.5–13.8] mL·kg−1·min−1; P = 0.003]. No body composition variables correlated with sepsis, nor were there any significant associations between VT and unplanned admissions for other indications. Multivariate logistic regression demonstrated that VT was independently associated with a diagnosis of sepsis (P = 0.03). Poisson regression revealed that VT was a significant predictor for the number of septic episodes (P = 0.02); independent of age, model of end-stage liver disease, incorporating serum sodium score, hepatocellular carcinoma diagnosis, presence of ascites, and β-blocker use.

Conclusions.

Poor cardiorespiratory fitness is an independent risk factor for the development of sepsis in advanced liver disease.
No Evidence for Cross-reactivity of Virus-specific Antibodies With HLA Alloantigens
Authors: Heidt Sebastiaan , Feltkamp Mariet C. , Karahan Gonca E , de Brouwer Caroline S. , Langerak-Langerak Janneke , Mulder Arend , Claas Frans H.J.
Published: July 2018

Background

Antibodies directed against HLA can develop through pregnancy, blood transfusions, or organ transplants. Anecdotal evidence suggests that virus-specific antibodies may have the capacity to cross-react with HLA, a phenomenon called heterologous immunity, which is well described for T-cell alloreactivity.

Methods

To determine whether antibody cross-reactivity between viral antigens and HLA is common, we tested 51 virus-specific human monoclonal antibodies (mAbs) specific for human immunodeficiency virus, varicella zoster virus, cytomegalovirus, and parvovirus, for reactivity against HLA class I and class II in single-antigen bead assays. In addition, we tested the reactivity of 41 HLA-specific human mAbs against common viral antigens of cytomegalovirus, varicella zoster virus, human immunodeficiency virus, Epstein-Barr virus, and BK polyomavirus.

Results

No cross-reactivity of any of the virus-specific mAbs with either HLA class I or class II molecules, as well as no cross-reactivity of any of the HLA-specific mAbs with any of the viral antigens was observed.

Conclusions

These findings indicate that the frequency of cross-reactivity on the antibody level between viral antigens and HLA, if present at all, is low. The emergence of HLA antibodies upon viral infection or vaccination is therefore probably due to bystander activation of dormant HLA-specific memory B cells.
Occurrence and variability of tactile interactions between wild American crows and dead conspecifics
Authors: Swift Kaeli , Marzluff John M.
Published: July 2018

Observations of some mammals and birds touching their dead provoke questions about the motivation and adaptive value of this potentially risky behaviour. Here, we use controlled experiments to determine if tactile interactions are characteristic of wild American crow responses to dead crows, and what the prevalence and nature of tactile interactions suggests about their motivations. In Experiment 1, we test if food or information acquisition motivates contact by presenting crows with taxidermy-prepared dead crows, and two species crows are known to scavenge: dead pigeons and dead squirrels. In Experiment 2, we test if territoriality motivates tactile interactions by presenting crows with taxidermy crows prepared to look either dead or upright and life-like. In Experiment 1, we find that crows are significantly less likely to make contact but more likely to alarm call and recruit other birds in response to dead crows than to dead pigeons and squirrels. In addition, we find that aggressive and sexual encounters with dead crows are seasonally biased. These findings are inconsistent with feeding or information acquisition-based motivation. In Experiment 2, we find that crows rarely dive-bomb and more often alarm call and recruit other crows to dead than to life-like crows, behaviours inconsistent with responses given to live intruders. Consistent with a danger response hypothesis, our results show that alarm calling and neighbour recruitment occur more frequently in response to dead crows than other stimuli, and that touching dead crows is atypical. Occasional contacts, which take a variety of aggressive and sexual forms, may result from an inability to mediate conflicting stimuli.

This article is part of the theme issue ‘Evolutionary thanatology: impacts of the dead on the living in humans and other animals’.
Comparative thanatology, an integrative approach: exploring sensory/cognitive aspects of death recognition in vertebrates and invertebrates
Authors: Gonçalves André , Biro Dora
Published: July 2018

Evolutionary thanatology benefits from broad taxonomic comparisons of non-human animals' responses to death. Furthermore, exploring the sensory and cognitive bases of these responses promises to allow classification of the underlying mechanisms on a spectrum from phylogenetically ancient to more derived traits. We draw on studies of perception and cognition in invertebrate and vertebrate taxa (with a focus on arthropods, corvids, proboscids, cetaceans and primates) to explore the cues that these animals use to detect life and death in others, and discuss proximate and ultimate drivers behind their capacities to do so. Parallels in thanatological behaviour exhibited by the last four taxa suggest similar sensory–cognitive processing rules for dealing with corpses, the evolution of which may have been driven by complex social environments. Uniting these responses is a phenomenon we term ‘animacy detection malfunction’, whereupon the corpse, having both animate and inanimate attributes, creates states of fear/curiosity manifested as approach/avoidance behaviours in observers. We suggest that integrating diverse lines of evidence (including the ‘uncanny valley’ effect originating from the field of robotics) provides a promising way to advance the field, and conclude by proposing avenues for future research.

This article is part of the theme issue ‘Evolutionary thanatology: impacts of the dead on the living in humans and other animals’.
The Late Upper Palaeolithic and earliest Mesolithic evidence of burials in Europe
Authors: Orschiedt Jörg
Published: July 2018

Burials of the Late Palaeolithic (14 000–11 600 cal years before present, henceforth BP) are a rare phenomenon in Europe. Several sites possess burials of single and double individuals. As with the preceding Magdalenian, the burial of more than two individuals in the same grave cutting seems to be unusual, but does occur occasionally. The deposition of isolated and disarticulated human remains with or without cut marks seems additionally to belong to the Magdalenian context. In the final Palaeolithic phase (13 000–11 600 cal years BP) there is evidence for cemetery-like clusters of burials, which contrast to the Magdalenian evidence, instead showing some similarities with the succeeding Mesolithic. The earliest Mesolithic burials 11 600–10 500 cal BP) are a very rare phenomenon, covering a short time span between the beginning of the Preboreal and the beginning of the Boreal phase of the early Holocene. Here the evidence includes single inhumations, cemetery-like structures and a number of isolated human remains. Caves and rock shelters were the most common places for inhumations in both the final Palaeolithic and the early Mesolithic. Although the number of sites with a chronological continuity from the LUP to the Early Mesolithic burial is low, several aspects indicate a general continuity in burial patterns over this period. Apart from this continuity, the Mesolithic burials in general seem to represent a new level of diversity in burial practices.

This article is part of the theme issue ‘Evolutionary thanatology: impacts of the dead on the living in humans and other animals’.
Children's understanding of death: from biology to religion
Authors: Harris Paul L.
Published: July 2018

Young children construct a biological conception of death, recognizing that death terminates mental and bodily processes. Despite this recognition, many children are receptive to an alternative conception of death, which affirms that the deceased has an afterlife elsewhere. A plausible interpretation of children's receptivity to this alternative conception is that human beings, including young children, are naturally disposed to remember and keep in mind individuals to whom they are attached even when those individuals leave and are absent for extended periods. This disposition is reflected in the pervasive tendency to talk about death as a departure rather than a terminus. It also enables the living to sustain their ties to the dead, even if, in the case of death, the departure is permanent rather than temporary. Linguistic and developmental evidence for these claims is reviewed. Possible biological origins and implications for archaeological research are also discussed.

This article is part of the theme issue ‘Evolutionary thanatology: impacts of the dead on the living in humans and other animals’.
Complicated grief: recent developments in diagnostic criteria and treatment
Authors: Nakajima Satomi
Published: July 2018

Although grief is a natural response to loss among human beings, some people have a severe and prolonged course of grief. In the 1990s, unusual grief persisting with a high level of acute symptoms became known as ‘complicated grief (CG)’. Many studies have shown that people who suffer from CG are at risk of long-term mental and physical health impairments and suicidal behaviours; it is considered a pathological state, which requires clinical intervention and treatment. DSM-5 (2013
Diagnostic and statistical manual of mental disorders
, 5th edn) proposed ‘persistent complex bereavement disorder’ as a psychiatric disorder; it is similar to CG in that it is a trauma- and stress-related disorder. In recent years, there has been considerable research on the treatment of CG. Randomized controlled trials have suggested the efficacy of cognitive behavioural therapy including an exposure component that is targeted for CG. However, experts disagree about the terminology and diagnostic criteria for CG. The ICD-11 (
International classification of diseases
, 11th revision) beta draft proposed prolonged grief disorder as a condition that differs from persistent complex bereavement disorder with respect to terminology and the duration of symptoms. This divergence has arisen from insufficient evidence for a set of core symptoms and the biological basis of CG. Future studies including biological studies are needed to reach consensus about the diagnostic criteria for CG.

This article is part of the theme issue ‘Evolutionary thanatology: impacts of the dead on the living in humans and other animals’.
Hominin evolutionary thanatology from the mortuary to funerary realm: the palaeoanthropological bridge between chemistry and culture
Authors: Pettitt Paul
Published: July 2018

Palaeoanthropology, or more precisely Palaeolithic archaeology, offers the possibility of bridging the gap between mortuary activities that can be observed in the wider animal community and which relate to chemistry and emotion; to the often-elaborate systems of rationalization and symbolic contextualisation that are characteristic of recently observable societies. I draw on ethological studies to provide a core set of mortuary behaviours one might expect hominoids to inherit, and on anthropological observations to explore funerary activity represented in the Middle and Upper Palaeolithic, in order to examine how a distinctly human set of funerary behaviours arose from a more widespread set of mortuary behaviours. I suggest that the most profound innovation of the hominins was the incorporation of places into the commemoration of the dead, and propose a falsifiable mechanism for why this came about; and I suggest that the pattern of the earliest burials fits with modern hunter–gatherer belief systems about death, and how these vary by social complexity. Finally, I propose several research questions pertaining to the social context of funerary practices, suggesting how a hominin evolutionary thanatology may contribute not only to our understanding of human behavioural evolution, but to a wider thanatology of the animal kingdom.

This article is part of the theme issue ‘Evolutionary thanatology: impacts of the dead on the living in humans and other animals’.
Saccharomyces cerevisiae adapted to grow in the presence of low-dose rapamycin exhibit altered amino acid metabolism
Authors: Dikicioglu Duygu , Eke Elif Dereli , Eraslan Serpil , Oliver Stephen G , Kirdar Betul
Published: July 2018

Rapamycin is a potent inhibitor of the highly conserved TOR kinase, the nutrient-sensitive controller of growth and aging. It has been utilised as a chemotherapeutic agent due to its anti-proliferative properties and as an immunosuppressive drug, and is also known to extend lifespan in a range of eukaryotes from yeast to mammals. However, the mechanisms through which eukaryotic cells adapt to sustained exposure to rapamycin have not yet been thoroughly investigated. Here, S. cerevisiae response to long-term rapamycin exposure was investigated by identifying the physiological, transcriptomic and metabolic differences observed for yeast populations inoculated into low-dose rapamycin-containing environment. The effect of oxygen availability and acidity of extracellular environment on this response was further deliberated by controlling or monitoring the dissolved oxygen level and pH of the culture. Yeast populations grown in the presence of rapamycin reached higher cell densities complemented by an increase in their chronological lifespan, and these physiological adaptations were associated with a rewiring of the amino acid metabolism, particularly that of arginine. The ability to synthesise amino acids emerges as the key factor leading to the major mechanistic differences between mammalian and microbial TOR signalling pathways in relation to nutrient recognition. Furthermore, oxygen levels and extracellular acidity of the culture were observed to conjointly affect yeast populations, virtually acting as coupled physiological effectors; cells were best adapted when maximal oxygenation of the culture was maintained in slightly acidic pH, any deviation necessitated more extensive readjustment to additional stress factors.
Theta-frequency resonance as the scale of input-output mapping in the medial entorhinal cortex
Authors: Katyare Nupur , Sikdar Sujit
Published: July 2018

Grid cell spatial period is thought to be dictated by a mapping between the speed-direction modulated excitatory inputs, and consequent modulation of the firing rate, yet, the exact underlying mechanisms are not known. Here, through experiments on the medial entorhinal cortex stellate cells, subjected to in-vivo like stochastic synaptic activity through the dynamic clamp, we show that such mapping can emerge from a theta-frequency resonance in the signal gain, which is HCN sensitive, robust to noise, and is potent enough to modulate the synaptic responses in the theta frequency. This modulation also extends to the corresponding theta-gamma modulation of the firing rate, the slope of whose excitation mediated increase is steeper in the presence of HCN channels. We also show that in the cells devoid of HCN channels, inhibition can emulate their role. Considering the dorso-ventral gradients of HCN and inhibition, which are present aligned to the grid spacing gradient in the medial entorhinal cortex, these findings should be noteworthy.
How do your genetics compare to the world’s elite marathoners?
Authors: Sims Gregory E. , Zeng Xiang-pei , Falk Jeffrey , Nova Michael
Published: July 2018

Pathway OME (Formerly Pathway Genomics, http://www.pathway.com) has identified a unique set of genetic traits associated with endurance, anxiety and likelihood of hamstring/Achilles injuries in an elite set of marathon runners. To date, this is the largest database of elite marathon athletes to ever have their exomes sequenced. Proprietary SportIQ Artificial Intelligence (AI) algorithms were developed and used to compare genetic traits in these 1,119 elite marathon runners to a normal population enabling us to develop a ‘Marathon Runner’ profile to assist athletes in training to compete and achieve their athletic goals. Athlete’s whose genetic profiles differ significantly from the “Marathon Runner” profile will gain additional insights on the specific training necessary to prepare their muscles for the demanding conditions of long distance running.
Early life stress impairs postnatal oligodendrogenesis and adult emotional behaviour through activity-dependent mechanisms
Authors: Teissier A. , Le Magueresse C. , Olusakin J. , Andrade da Costa B. L. S. , De Stasi A. M. , Bacci A. , Kawasawa Y. , Vaidya V. A. , Gaspar P.
Published: July 2018

Exposure to stress during early life (infancy/childhood) has long-term effects on the structure and function of the prefrontal cortex (PFC) and increases the risk for adult depression and anxiety disorders. However, little is known about the molecular and cellular mechanisms of these effects. Here we focused on changes induced by chronic maternal separation during the first two weeks of postnatal life. Unbiased mRNA expression profiling in the medial PFC (mPFC) of maternally separated (MS) pups identified an increased expression of myelin-related genes and a decreased expression of immediate early genes. Oligodendrocyte lineage markers and birthdating experiments indicated a precocious oligodendrocyte differentiation in the mPFC at P15, leading to a depletion of the oligodendrocyte progenitor pool in MS adults. We tested the role of neuronal activity in oligodendrogenesis, using designed receptors exclusively activated by designed drugs (DREADDs) techniques. hM4Di or hM3Dq constructs were transfected into mPFC neurons using fast-acting AAV8 viruses. Reduction of mPFC neuron excitability during the first two postnatal weeks caused a premature differentiation of oligodendrocytes similar to the MS pups, while chemogenetic activation normalized it in the MS animals. Bidirectional manipulation of neuron excitability in the mPFC during the P2-P14 period had long lasting effects on adult emotional behaviours and on temporal object recognition: hM4Di mimicked MS effects, while hM3Dq prevented the pro-depressive effects and short term memory impairment of MS. Thus, our results identify neuronal activity as a critical target of early life stress and demonstrate its function in controlling both postnatal oligodendrogenesis and adult mPFC-related behaviors.
Simultaneous production of diverse neuronal subtypes during early corticogenesis
Authors: Magrinelli E. , Wagener R. J. , Jabaudon D.
Published: July 2018

The circuits of the neocortex are composed of a broad diversity of neuronal cell types, which can be distinguished by their laminar location, molecular identity, and connectivity. During embryogenesis, successive generations of glutamatergic neurons are sequentially born from progenitors located in germinal zones below the cortex. In this process, the earliest-born generations of neurons differentiate to reside in deep layers, while later-born daughter neurons reside in more superficial layers. Although the aggregate competence of progenitors to produce successive subtypes of neurons progresses as corticogenesis proceeds, a fine-grained temporal understanding of how neuronal subtypes are sequentially produced is still missing. Here, we use FlashTag, a high temporal resolution labeling approach, to follow the fate of the simultaneously-born daughter neurons of ventricular zone progenitors at multiple stages of corticogenesis. Our findings reveal a bimodal regulation in the diversity of neurons being produced at single time points of corticogenesis. Initially, distinct subtypes of deep-layer neurons are simultaneously produced, as defined by their laminar location, molecular identity and connectivity. Later on, instead, instantaneous neuronal production is homogeneous and the distinct superficial-layer neurons subtypes are sequentially produced. These findings suggest that early-born, deep-layer neurons have a less determined fate potential than later-born superficial layer neurons, which may reflect the progressive implementation of pre-and/or post-mitotic mechanisms controlling neuronal fate reliability.
The trichotomy of pneumococcal infection outcomes
Authors: Almocera Alexis Erich S. , Hernandez-Mejia Gustavo , Parra-Rojas César , Hernandez-Vargas Esteban A.
Published: July 2018

The successful elimination of bacteria such as Streptococcus pneumoniae from a host involves the coordination between different parts of the immune system. Previous studies have explored the effects of the initial pneumococcal load (bacterial dose) on different representations of innate immunity, finding that pathogenic outcomes can vary with the size of the bacterial dose. However, others yield support to the notion of dose-independent factors contributing to bacterial clearance. In this paper, we seek to provide a deeper understanding of the immune responses associated to the pneumococcus. To this end, we formulate a model that realizes an abstraction of the innate-regulatory immune host response. Stability and bifurcation analyses of the model reveal the following trichotomy of pneumococcal outcomes determined by the bifurcation parameters: (i) dose-independent clearance; (ii) dose-independent persistence; and (iii) dose-limited clearance. Bistability, where the bacteria-free equilibrium co-stabilizes with the most substantial steady-state bacterial load is the specific result behind dose-limited clearance. The trichotomy of pneumococcal outcomes here described integrates all previously observed bacterial fates into a unified framework.
Novel cytonuclear combinations modify Arabidopsis seed physiology and vigor
Authors: Boussardon Clément , Martin-Magniette Marie-Laure , Godin Béatrice , Benamar Abdelilah , Vittrant Benjamin , Citerne Sylvie , Mary-Huard Tristan , Macherel David , Rajjou Loïc , Budar Françoise
Published: July 2018

The influence of intraspecific variation in cytoplasmic genomes and cytonuclear interactions on key seed traits that can impact adaptation and agriculture has not been thoroughly explored, so far. Here, dormancy, germination performance and longevity of seeds have been assessed in Arabidopsis plants with novel cytonuclear combinations that disrupt coadaptation between natural variants of nuclear and cytoplasmic genomes. Although all three traits were affected by cytonuclear reshuffling, the sensitivity of seed traits to cytoplasmic change was dependent on the nuclear background. Both deleterious and, more surprisingly, favorable effects of novel cytonuclear combinations (in comparison with the nuclear parent) were observed, suggesting suboptimal genetic combinations exist in natural populations for these traits. Significant changes on dormancy and germination performance due to specific cytonuclear interacting combinations mainly occurred in opposite directions, in accordance with the previously proposed ‘dormancy continuum’. Consistently, reduced sensitivity to exogenous ABA and faster endogenous ABA decay during germination were observed in a novel cytonuclear combination that also exhibited enhanced longevity and better germination performance, compared to its natural nuclear parent. Cytoplasmic genomes, therefore, represent an additional resource of natural variation for breeding seed vigor traits.

Issue section

Growth and development

Highlight

Natural variation in Arabidopsis organelles and cytonuclear interactions influence seed dormancy, longevity and germination performance. Enhanced seed vigor was obtained through the creation of novel cytonuclear combinations.
ATG13 dynamics in non-selective autophagy and mitophagy: insights from live imaging studies and mathematical modelling
Authors: Pezze Piero Dalle , Karanasios Eleftherios , Kandia Varvara , Manifava Maria , Walker Simon A. , Le Novère Nicolas Gambardella , Ktistakis Nicholas T.
Published: July 2018

During autophagy, the ULK complex nucleates autophagic precursors which give rise to autophagosomes. We analysed by live imaging and mathematical modelling translocation of ATG13 (part of ULK complex) to autophagic puncta in starvation-induced autophagy and ivermectin-induced mitophagy. In non-selective autophagy, the intensity and duration of ATG13 translocation approximated a normal distribution whereas wortmannin reduced this and shifted to a log-normal distribution. During mitophagy, multiple translocations of ATG13, with increasing time between peaks were observed. We hypothesised that these multiple translocations arise because engulfment of mitochondrial fragments requires successive nucleations of multiple phagophores on the same target, and a mathematical model based on this idea reproduced the oscillatory behaviour. Significantly, model and experimental data were also in agreement that the number of ATG13 translocations is directly proportional to the diameter of the targeted mitochondrial fragments. Our data provide novel insights into the early dynamics of selective and non-selective autophagy.
MuSCA: a multi-scale model to explore carbon allocation in plants
Authors: Reyes F. , Pallas B. , Pradal C. , Vaggi F. , Zanotelli D. , Tagliavini M. , Gianelle D. , Costes E.
Published: July 2018

Background and aims

Carbon allocation in plants is usually represented at a specific spatial scale, peculiar to each model. This makes the results obtained by different models, and the impact of their scale of representation, difficult to compare. In this work we developed a Multi Scale Carbon Allocation model (MuSCA) that can be applied at different, user-defined, topological scales of a plant, and used to assess the impact of each spatial scale on simulated results and computation time.

Methods

Model multi-scale consistency and behavior were tested by applications on three realistic apple tree structures. Carbon allocation was computed at five spatial scales, spanning from the metamer (the finest scale, used as a reference) up to 1st order branches, and for different values of a sap friction coefficient. Fruit dry mass increments were compared across spatial scales and with field data.

Key Results

The model showed physiological coherence in representing competition for carbon assimilates. Results from intermediate values of the friction parameter best fitted the field data. For these, fruit growth simulated at the metamer scale (considered as a reference) differed from about 1% at growth unit scale up to 35% at first order branch scale. Generally, the coarser the spatial scale the more fruit growth diverged from the reference and the lower the obtained within-tree fruit growth variability. Coherence in the carbon allocated across scales was also differently impacted, depending on the tree structure considered. Decreasing the topological resolution reduced computation time up to four orders of magnitude.

Conclusions

MuSCA revealed that the topological scale has a major influence on the simulation of carbon allocation, suggesting that this factor should be carefully evaluated when using different carbon allocation models or comparing their results. Trades-off between computation time and prediction accuracy can be evaluated by changing topological scales.