What did Hadropithecus eat, and why should paleoanthropologists care?

Over 40 years ago, Clifford Jolly noted different ways in which Hadropithecus stenognathus converged in its craniodental anatomy with basal hominins and with geladas. The Malagasy subfossil lemur Hadropithecus departs from its sister taxon, Archaeolemur, in that it displays comparatively large molars, reduced incisors and canines, a shortened rostrum, and thickened mandibular corpus. Its molars, however, look nothing like those of basal hominins; rather, they much more closely resemble molars of grazers such as Theropithecus. A number of tools have been used to interpret these traits, including dental microwear and texture analysis, molar internal and external morphology, and finite element analysis of crania. These tools, however, have failed to provide support for a simple dietary interpretation; whereas there is some consistency in the inferences they support, dietary inferences (e.g., that it was graminivorous, or that it specialized on hard objects) have been downright contradictory. Cranial shape may correlate poorly with diet. But a fundamental question remains unresolved: why do the various cranial and dental convergences exemplified by Hadropithecus, basal hominins, and Theropithecus exist? In this paper we review prior hypotheses regarding the diet of Hadropithecus. We then use stable carbon and nitrogen isotope data to elucidate this species' diet, summarizing earlier stable isotope analyses and presenting new data for lemurs from the central highlands of Madagascar, where Hadropithecus exhibits an isotopic signature strikingly different from that seen in other parts of the island. We offer a dietary explanation for these differences. Hadropithecus likely specialized neither on grasses nor hard objects; its staples were probably the succulent leaves of CAM plants. Nevertheless, aspects of prior hypotheses regarding the ecological significance of its morphology can be supported. This is the peer reviewed version of the following article: Godfrey, L. R., Crowley, B. E., Muldoon, K. M., Kelley, E. A., King, S. J., Best, A. W. and Berthaume, M. A. (2016), What did Hadropithecus eat, and why should paleoanthropologists care?. Am. J. Primatol. , 78: 1098-1112. , which has been published in final form at 10.1002/ajp.22506. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions

Measuring health-related quality of life in chronic headache: A comparative evaluation of the Chronic Headache Quality of Life Questionnaire and Headache Impact Test (HIT-6).

OBJECTIVE: To compare the quality and acceptability of a new headache-specific patient-reported measure, the Chronic Headache Quality of Life Questionnaire (CHQLQ) with the six-item Headache Impact Test (HIT-6), in people meeting an epidemiological definition of chronic headaches. METHODS: Participants in the feasibility stage of the Chronic Headache Education and Self-management Study (CHESS) (n = 130) completed measures three times during a 12-week prospective cohort study. Data quality, measurement acceptability, reliability, validity, responsiveness to change, and score interpretation were determined. Semi-structured cognitive interviews explored measurement relevance, acceptability, clarity, and comprehensiveness. RESULTS: Both measures were well completed with few missing items. The CHQLQ's inclusion of emotional wellbeing items increased its relevance to participant's experience of chronic headache. End effects were present at item level only for both measures. Structural assessment supported the three and one-factor solutions of the CHQLQ and HIT-6, respectively. Both the CHQLQ (range 0.87 to 0.94) and HIT-6 (0.90) were internally consistent, with acceptable temporal stability over 2 weeks (CHQLQ range 0.74 to 0.80; HIT-6 0.86). Both measures responded to change in headache-specific health at 12 weeks (CHQLQ smallest detectable change (improvement) range 3 to 5; HIT-6 2.1). CONCLUSIONS: While both measures are structurally valid, internally consistent, temporally stable, and responsive to change, the CHQLQ has greater relevance to the patient experience of chronic headache.Trial registration number: ISRCTN79708100. Registered 16th December 2015, http://www.isrctn.com/ISRCTN79708100

Measuring health-related quality of life in chronic headache:a comparative evaluation of the Chronic Headache Quality of Life Questionnaire and Headache Impact Test (HIT-6)

Objective: To compare the quality and acceptability of a new headache-specific patient-reported measure the Chronic Headache Quality of Life Questionnaire (CHQLQ), with the Headache Impact Test–6 item (HIT-6), in people meeting an epidemiological definition of chronic headaches.Methods: Participants in the feasibility stage of the Chronic Headache Education and Self-management Study (CHESS) (N=130) completed measures three times during a 12-week prospective cohort study. Data quality, measurement acceptability, reliability, validity, responsiveness to change, and score interpretation were determined. Semi-structured cognitive interviews explored measurement relevance, acceptability, clarity, and comprehensiveness.Results: Both measures were well completed with few missing items. The CHQLQ’s inclusion of emotional wellbeing items increased its relevance to participant’s experience of chronic headache. End effects were present at item level only for both measures. Structural assessment supported the three and one-factor solutions of the CHQLQ and HIT-6, respectively. Both the CHQLQ (range 0.87 to 0.94) and HIT-6 (0.90) were internally consistent, with acceptable temporal stability over 2-weeks (CHQLQ range 0.74 to 0.80; HIT-6 0.86). Both measures responded to change in headache-specific health at 12-weeks (CHQLQ smallest detectable change (improvement) range 3 to 5; HIT-6 2.1). Conclusions: While both measures are structurally valid, internally consistent, temporally stable and responsive to change, the CHQLQ has greater relevance to the patient experience of chronic headache. <br/

A Core Outcome Set for Preventive Intervention Trials in Chronic and Episodic Migraine (COSMIG):an international, consensus-derived and multistakeholder initiative

Objective Typically, migraine prevention trials focus on reducing migraine days. This narrow focus may not capture all that is important to people with migraine. Inconsistency in outcome selection across trials limits the potential for data pooling and evidence synthesis. In response, we describe the development of core outcome set for migraine (COSMIG). Design A two-stage approach sought to achieve international, multistakeholder consensus on both the core domain set and core measurement set. Following construction of a comprehensive list of outcomes, expert panellists (patients, healthcare professionals and researchers) completed a three-round electronic-Delphi study to support a reduction and prioritisation of core domains and outcomes. Participants in a consensus meeting finalised the core domains and methods of assessment. All stages were overseen by an international core team, including patient research partners. Results There was a good representation of patients (episodic migraine (n=34) and chronic migraine (n=42)) and healthcare professionals (n=33) with high response and retention rates. The initial list of domains and outcomes was reduced from >50 to 7 core domains for consideration in the consensus meeting, during which a 2-domain core outcome set was agreed. Conclusion International and multistakeholder consensus emerged to describe a two-domain core outcome set for reporting research on preventive interventions for chronic and episodic migraine: migraine-specific pain and migraine-specific quality of life. Intensity of migraine pain assessed with an 11-point Numerical Rating Scale and the frequency as the number of headache/migraine days over a specified time period. Migraine-specific quality of life assessed using the Migraine Functional Impact Questionnaire

Elimination of Arctic Variant Rabies in Red Foxes, Metropolitan Toronto

To control the arctic variant of rabies virus in red foxes, 332,257 bait doses containing live, attenuated Evelyn-Rokitnicki-Abelseth rabies vaccine were distributed in greater metropolitan Toronto during 1989–1999. Human and pet contact with bait was minimal, and no adverse reactions to the vaccine were noted. Significantly fewer rabid foxes were found during the 17 years after fox baiting (5 cases during 1990–2006) than in the 17 years before (96 cases during 1973–1989). The last report of a rabid fox in metropolitan Toronto was in 1996 (reporting period through September 2006), which confirms that distributing oral rabies vaccine bait is a feasible tactic for the control of rabies in foxes in urban environments

Core outcome set for preventive intervention trials in chronic and episodic migraine (COSMIG): an international, consensus-derived and multistakeholder initiative

OBJECTIVE: Typically, migraine prevention trials focus on reducing migraine days. This narrow focus may not capture all that is important to people with migraine. Inconsistency in outcome selection across trials limits the potential for data pooling and evidence synthesis. In response, we describe the development of core outcome set for migraine (COSMIG). DESIGN: A two-stage approach sought to achieve international, multistakeholder consensus on both the core domain set and core measurement set. Following construction of a comprehensive list of outcomes, expert panellists (patients, healthcare professionals and researchers) completed a three-round electronic-Delphi study to support a reduction and prioritisation of core domains and outcomes. Participants in a consensus meeting finalised the core domains and methods of assessment. All stages were overseen by an international core team, including patient research partners. RESULTS: There was a good representation of patients (episodic migraine (n=34) and chronic migraine (n=42)) and healthcare professionals (n=33) with high response and retention rates. The initial list of domains and outcomes was reduced from >50 to 7 core domains for consideration in the consensus meeting, during which a 2-domain core outcome set was agreed. CONCLUSION: International and multistakeholder consensus emerged to describe a two-domain core outcome set for reporting research on preventive interventions for chronic and episodic migraine: migraine-specific pain and migraine-specific quality of life. Intensity of migraine pain assessed with an 11-point Numerical Rating Scale and the frequency as the number of headache/migraine days over a specified time period. Migraine-specific quality of life assessed using the Migraine Functional Impact Questionnaire

Trait positive and negative emotionality differentially associate withdiurnal cortisol activity

Inter-individual variability in metrics of hypothalamic-pituitary-adrenocortical (HPA) activity, such asthe slope of the diurnal decline in cortisol, cortisol awakening response (CAR), and total cortisol out-put, have been found to associate inversely with trait ratings of extraversion and positive affect (E/PA)and positively with neuroticism and negative affect (N/NA) in some, but not all, investigations. Theseinconsistencies may partly reflect varied intensity of cortisol sampling among studies and reliance onself-rated traits, which are subject to reporting biases and limitations of introspection. Here, we furtherexamined dispositional correlates of HPA activity in 490 healthy, employed midlife volunteers (M age = 43years; 54% Female; 86% white). Trait ratings were requested from participants and 2 participant-electedinformants using the Positive and Negative Affect Schedule (PANAS) and Extraversion and Neuroticismdimensions of NEO personality inventories. CAR was assessed as percent increase in cortisol levels fromawakening to 30 min after awakening; and the diurnal slope and total output of cortisol [Area Underthe Curve (AUC)] were determined from cortisol measurements taken at awakening, +4 and +9 h later,and bedtime, across 3 workdays. Structural equation modeling was used to estimate multi-informantE/PA and N/NA factors. We used 3 days of measurement as indicators to model each of the three latentcortisol factors (slope, CAR, and AUC). With the two latent emotionality and three latent cortisol indicesincluded there was good fit to the data ( 2(200)= 278.38, p = 0.0002; RMSEA = 0.028, 90% CI = 0.02–0.04;CFI/TLI = 0.97/0.96; SRMR = 0.04). After controlling for covariates (age, sex, race), results showed higherlatent E/PA associated with a steeper diurnal slope (Standardized ˇ = −0.19, p = 0.02) and smaller CAR(Standardized ˇ = −0.26, p = 0.004), whereas N/NA did not associate with any cortisol metric (Standard-ized ˇ’s = −0.12 to 0.13, p’s = 0.10 to 0.53). These findings suggest that positive emotionality may be moreclosely associated with indices of diurnal cortisol release than negative emotionality

Neuromuscular Blockade with Rocuronium Bromide Increases the Tolerance of Acute Normovolemic Anemia in Anesthetized Pigs

Background: The patient's individual anemia tolerance is pivotal when blood transfusions become necessary, but are not feasible for some reason. To date, the effects of neuromuscular blockade (NMB) on anemia tolerance have not been investigated. Methods: 14 anesthetized and mechanically ventilated pigs were randomly assigned to the Roc group (3.78 mg/kg rocuronium bromide followed by continuous infusion of 1 mg/kg/min, n = 7) or to the Sal group (administration of the corresponding volume of normal saline, n = 7). Subsequently, acute normovolemic anemia was induced by simultaneous exchange of whole blood for a 6% hydroxyethyl starch solution (130/0.4) until a sudden decrease of total body O-2 consumption (VO2) indicated a critical limitation of O-2 transport capacity. The Hb concentration quantified at this time point (Hb(crit)) was the primary end-point of the protocol. Secondary endpoints were parameters of hemodynamics, O-2 transport and tissue oxygenation. Results: Hb(crit) was significantly lower in the Roc group (2.4 +/- 0.5 vs. 3.2 +/- 0.7 g/dl) reflecting increased anemia tolerance. NMB with rocuronium bromide reduced skeletal muscular VO2 and total body O-2 extraction rate. As the cardiac index increased simultaneously, total body VO2 only decreased marginally in the Roc group (change of VO2 relative to baseline -1.7 +/- 0.8 vs. 3.2 +/- 1.9% in the Sal group, p < 0.05). Conclusion: Deep NMB with rocuronium bromide increases the tolerance of acute normovolemic anemia. The underlying mechanism most likely involves a reduction of skeletal muscular VO2. During acellular treatment of an acute blood loss, NMB might play an adjuvant role in situations where profound stages of normovolemic anemia have to be tolerated (e.g. bridging an unexpected blood loss until blood products become available for transfusion). Copyright (C) 2011 S. Karger AG, Base

Functional interaction between Lypd6 and nicotinic acetylcholine receptors

Nicotinic acetylcholine receptors (nAChRs) affect multiple physiological functions in the brain and their functions are modulated by regulatory proteins of the Lynx family. Here, we report for the first time a direct interaction of the Lynx protein LY6/PLAUR domain‐containing 6 (Lypd6) with nAChRs in human brain extracts, identifying Lypd6 as a novel regulator of nAChR function. Using protein cross‐linking and affinity purification from human temporal cortical extracts, we demonstrate that Lypd6 is a synaptically enriched membrane‐bound protein that binds to multiple nAChR subtypes in the human brain. Additionally, soluble recombinant Lypd6 protein attenuates nicotine‐induced hippocampal inward currents in rat brain slices and decreases nicotine‐induced extracellular signal‐regulated kinase phosphorylation in PC12 cells, suggesting that binding of Lypd6 is sufficient to inhibit nAChR‐mediated intracellular signaling. We further show that perinatal nicotine exposure in rats (4 mg/kg/day through minipumps to dams from embryonic day 7 to post‐natal day 21) significantly increases Lypd6 protein levels in the hippocampus in adulthood, which did not occur after exposure to nicotine in adulthood only. Our findings suggest that Lypd6 is a versatile inhibitor of cholinergic signaling in the brain, and that Lypd6 is dysregulated by nicotine exposure during early development. [Image: see text] Regulatory proteins of the Lynx family modulate the function of nicotinic receptors (nAChRs). We report for the first time that the Lynx protein Lypd6 binds to nAChRs in human brain extracts, and that recombinant Lypd6 decreases nicotine‐induced ERK phosphorylation and attenuates nicotine‐induced hippocampal inward currents. Our findings suggest that Lypd6 is a versatile inhibitor of cholinergic signaling in the brain

Exploring children’s perspectives on the welfare needs of pet animals

This work was supported by the Department for Environment, Food and Rural Affairs (grant number AW1404).Children are increasingly viewed as important recipients of eduational interventions to improve animal welfare, yet research examining their perspectives is lacking, particularly within the UK. Helping children to care appropriately for animals depends, not least, on an ability to understand the needs of different species and correctly identify cues given by the animal that indicate its welfare state. This study began to explore: (a) children’s perceptions of welfare needs, focusing on four common pet animals; (b) influences on the development of knowledge; (c) beliefs about whether or not (all) animals are sentient, and (d) their confidence in identifying when their own pets are in need. Fourteen focus groups were carried out with 53 children aged 7 to 13 years. Findings highlighted an affirmative response that animals have feelings (dogs especially), albeit with doubts about this applying universally. There was wide variation in children’s knowledge of welfare needs, even among owners of the animal in question. Conversely, some children lacked confidence in spite of the extensive knowledge they had developed through direct experience. An important finding was a perceived difficulty in identifying the needs of particular species or specific types of need in their own pets. Fitting well with a recent emphasis on “positive welfare,” children felt that many animals need demonstrative love and attention, especially cats and dogs. While there is clearly scope for educating children about common needs and cues that indicate animals’ welfare state, other areas pose a greater challenge. Emotional connection seems important in the development of extensive knowledge and concern for welfare. Accordingly, animals that do not possess the kind of behavioral repertoire that is easy to interpret or allows for a perceived sense of reciprocity are possibly at risk of negative welfare experiences.PostprintPeer reviewe