Walking through volcanic mud : the 2,100 year-old Acahualina footprints (Nicaragua) II: the Acahualina people, environmental conditions and motivation

We analyzed bare human footprints in Holocene tuff preserved in two pits in the Acahualinca barrio in the northern outskirts of Managua (Nicaragua). Lithology, volcanology, and age of the deposits are discussed in a companion paper (Schmincke et al. Bull Volcanol doi: 10.1007/s00445-008-0235-9, 2008). The footprint layer occurs within a series of rapidly accumulated basaltic–andesitic tephra that is regionally correlated to the Masaya Triple Layer Tephra. The people were probably trying to escape from a powerful volcanic eruption at Masaya Caldera 20 km farther south that occurred at 2.1 ka BP. We subdivided the swath of footprints, up to 5.6 m wide, in the northern pit (Pit I) into (1) a central group of footprints made by about six individuals, the total number being difficult to determine because people walked in each other’s footsteps one behind the other and (2) two marginal groups on either side of the central group with more widely spaced tracks. The western band comprises tracks of three adjacent individuals and an isolated single footprint farther out. The eastern marginal area comprises an inner band of deep footprints made by three individuals and, farther out, three clearly separated individuals. We estimate the total number of people as 15–16. In the southern narrow and smaller pit (Pit II), we recognize tracks of ca. 12 individuals, no doubt made by the same group. The group represented in both pits probably comprised male and female adults, teenagers and children based on differences in length of footprints and of strides and depth of footprints made in the soft wet ash. The smallest footprints (probably made by children) occur in the central group, where protection was most effective. The footprint layer is composed of a lower 5–15-cm thick, coarse-grained vesicle tuff capped by a medium to fine-grained tuff up to 3 cm thick. The surface on which the people walked was muddy, and the soft ash was squeezed up on the sides of the foot imprints and between toes. Especially, deep footprints are mainly due to local thickening of the water-rich ash, multiple track use, and differences in weight of individuals. The excellent preservation of the footprints, ubiquitous mudcracks, sharp and well-preserved squeeze-ups along the margins of the tracks and toe imprints, and the absence of raindrop impressions all suggest that the eruption occurred during the dry season. The people walked at a brisk pace, as judged from the tight orientation of the swath and the length of the strides. The directions of a major erosional channel in the overlying deposits that probably debouched into Lake Managua and the band of footprints are strictly parallel, indicating that people walked together in stride along the eastern margin of a channel straight toward the lake shore, possibly a site with huts and/or boats for protection and/or escape

A sense of embodiment is reflected in people's signature size

BACKGROUND: The size of a person's signature may reveal implicit information about how the self is perceived although this has not been closely examined. METHODS/RESULTS: We conducted three experiments to test whether increases in signature size can be induced. Specifically, the aim of these experiments was to test whether changes in signature size reflect a person's current implicit sense of embodiment. Experiment 1 showed that an implicit affect task (positive subliminal evaluative conditioning) led to increases in signature size relative to an affectively neutral task, showing that implicit affective cues alter signature size. Experiments 2 and 3 demonstrated increases in signature size following experiential self-focus on sensory and affective stimuli relative to both conceptual self-focus and external (non-self-focus) in both healthy participants and patients with anorexia nervosa, a disorder associated with self-evaluation and a sense of disembodiment. In all three experiments, increases in signature size were unrelated to changes in self-reported mood and larger than manipulation unrelated variations. CONCLUSIONS: Together, these findings suggest that a person's sense of embodiment is reflected in their signature size

An observational study of once-daily modified-release methylphenidate in ADHD: the effect of previous treatment on ADHD symptoms, other externalising symptoms and quality-of-life outcomes

Methylphenidate (MPH) is the most commonly prescribed stimulant for children with ADHD. Data on the effects of different MPH formulations in real-life settings are scarce, and the role of previous therapy on treatment outcome when switching medications has not been well studied. OBSEER was an observational study designed to evaluate the effectiveness and safety of Equasym XL® in routine care. This study assessed whether the improvements reported with Equasym XL® are influenced by the degree of symptom control achieved with the previous medication. Patients enrolled in OBSEER were stratified by prior treatment (none, MPH-immediate release [IR] once daily [o.d.] [MPH-IR o.d.], MPH-IR repeated [MPH-IR >o.d.] and MPH-MR [modified release] excluding Equasym XL®), and changes in ADHD and other externalising symptoms (CGI-S, FBB-ADHD and DAYAS) and quality of life (QoL, KINDL) were evaluated during treatment with Equasym XL®. A total of 782 patients were analysed. Significant group-by-time interactions were found for all symptom variables analysed, indicating that effects varied by previous medication. For CGI-S and FBB-ADHD total scores, the greatest reductions in ADHD symptoms were observed in the treatment-naïve subgroup, followed (in order) by MPH-IR o.d., MPH-IR >o.d. and MPH-MR. A similar profile was seen for DAYAS ratings for all periods of the day except the evening, when there were no significant differences between subgroups. Similarly, the treatment-naïve and MPH-IR o.d. subgroups showed the greatest improvements in KINDL ratings. Although effects were greatest for treatment-naïve patients, improvements were also observed in the prior treatment subgroups for symptoms and QoL. This suggests that a change to Equasym XL® may be beneficial in patients with suboptimal effects on prior medication

Intraspecific Correlations of Basal and Maximal Metabolic Rates in Birds and the Aerobic Capacity Model for the Evolution of Endothermy

The underlying assumption of the aerobic capacity model for the evolution of endothermy is that basal (BMR) and maximal aerobic metabolic rates are phenotypically linked. However, because BMR is largely a function of central organs whereas maximal metabolic output is largely a function of skeletal muscles, the mechanistic underpinnings for their linkage are not obvious. Interspecific studies in birds generally support a phenotypic correlation between BMR and maximal metabolic output. If the aerobic capacity model is valid, these phenotypic correlations should also extend to intraspecific comparisons. We measured BMR, Msum (maximum thermoregulatory metabolic rate) and MMR (maximum exercise metabolic rate in a hop-flutter chamber) in winter for dark-eyed juncos (Junco hyemalis), American goldfinches (Carduelis tristis; Msum and MMR only), and black-capped chickadees (Poecile atricapillus; BMR and Msum only) and examined correlations among these variables. We also measured BMR and Msum in individual house sparrows (Passer domesticus) in both summer, winter and spring. For both raw metabolic rates and residuals from allometric regressions, BMR was not significantly correlated with either Msum or MMR in juncos. Moreover, no significant correlation between Msum and MMR or their mass-independent residuals occurred for juncos or goldfinches. Raw BMR and Msum were significantly positively correlated for black-capped chickadees and house sparrows, but mass-independent residuals of BMR and Msum were not. These data suggest that central organ and exercise organ metabolic levels are not inextricably linked and that muscular capacities for exercise and shivering do not necessarily vary in tandem in individual birds. Why intraspecific and interspecific avian studies show differing results and the significance of these differences to the aerobic capacity model are unknown, and resolution of these questions will require additional studies of potential mechanistic links between minimal and maximal metabolic output

A systematic review of the safety of lisdexamfetamine dimesylate

BACKGROUND: Here we review the safety and tolerability profile of lisdexamfetamine dimesylate (LDX), the first long-acting prodrug stimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD). METHODS: A PubMed search was conducted for English-language articles published up to 16 September 2013 using the following search terms: (lisdexamfetamine OR lisdexamphetamine OR SPD489 OR Vyvanse OR Venvanse OR NRP104 NOT review [publication type]). RESULTS: In short-term, parallel-group, placebo-controlled, phase III trials, treatment-emergent adverse events (TEAEs) in children, adolescents, and adults receiving LDX were typical for those reported for stimulants in general. Decreased appetite was reported by 25-39 % of patients and insomnia by 11-19 %. The most frequently reported TEAEs in long-term studies were similar to those reported in the short-term trials. Most TEAEs were mild or moderate in severity. Literature relating to four specific safety concerns associated with stimulant medications was evaluated in detail in patients receiving LDX. Gains in weight, height, and body mass index were smaller in children and adolescents receiving LDX than in placebo controls or untreated norms. Insomnia was a frequently reported TEAE in patients with ADHD of all ages receiving LDX, although the available data indicated no overall worsening of sleep quality in adults. Post-marketing survey data suggest that the rate of non-medical use of LDX was lower than that for short-acting stimulants and lower than or equivalent to long-acting stimulant formulations. Small mean increases were seen in blood pressure and pulse rate in patients receiving LDX. CONCLUSIONS: The safety and tolerability profile of LDX in individuals with ADHD is similar to that of other stimulants

Postcopulatory sexual selection

The female reproductive tract is where competition between the sperm of different males takes place, aided and abetted by the female herself. Intense postcopulatory sexual selection fosters inter-sexual conflict and drives rapid evolutionary change to generate a startling diversity of morphological, behavioural and physiological adaptations. We identify three main issues that should be resolved to advance our understanding of postcopulatory sexual selection. We need to determine the genetic basis of different male fertility traits and female traits that mediate sperm selection; identify the genes or genomic regions that control these traits; and establish the coevolutionary trajectory of sexes

Growth and Puberty in a 2-Year Open-Label Study of Lisdexamfetamine Dimesylate in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

BACKGROUND: Stimulant medications for the treatment of attention-deficit/hyperactivity disorder have a history of safe and effective use; however, concerns exist that they may adversely affect growth trajectories in children and adolescents. OBJECTIVE: The objective of this study was to evaluate the longer-term effects of lisdexamfetamine dimesylate on weight, height, body mass index and pubertal development in children and adolescents with attention-deficit/hyperactivity disorder. METHODS: Children and adolescents aged 6-17 years with attention-deficit/hyperactivity disorder took open-label lisdexamfetamine dimesylate (30, 50 or 70 mg/day) in this open-label 2-year safety and efficacy study. Safety evaluations included treatment-emergent adverse events, measurement of weight, height and body mass index, and self-reported pubertal status using Tanner staging. RESULTS: The safety analysis population comprised all enrolled participants (N = 314) and 191 (60.8%) completed the study. Weight decrease was reported as a treatment-emergent adverse event in 63 participants (20.1%) and two participants (0.6%) discontinued the study as a result of treatment-emergent adverse events of weight decrease. Growth retardation of moderate intensity was reported as a treatment-emergent adverse event for two participants. From baseline to the last on-treatment assessment, there were increases in mean weight of 2.1 kg (standard deviation 5.83) and height of 6.1 cm (standard deviation 4.90), and a body mass index decrease of 0.5 kg/m2 (standard deviation 1.72). Mean weight, height and body mass index z-scores decreased over the first 36 weeks of the study and then stabilised. Changes from baseline to the last on-treatment assessment in mean z-scores for weight, height and body mass index were significantly less than zero (- 0.51, - 0.24 and - 0.59, respectively; nominal p < 0.0001). The proportion of participants with a z-score of < - 1 ranged from 5.1% (baseline) to 22.1% (week 84) for weight, 8.2% (baseline) to 12.6% (week 96) for height, and 8.3% (baseline) to 28.8% (week 96) for body mass index. Thirteen participants (4.1%) shifted to a weight below the fifth percentile at the last on-treatment assessment from a higher weight category at baseline. At the last on-treatment assessment, most participants remained at their baseline Tanner stage or had shifted higher. CONCLUSIONS: Findings from this comprehensive examination of growth outcomes associated with lisdexamfetamine dimesylate treatment over 2 years were consistent with previous studies of stimulant medications. Whilst mean weight and height increased over the course of the study, there was a small but transient reduction in mean weight, height and body mass index z-scores. A small increase in the proportion of participants in the lowest weight and body mass index categories highlights the importance of the regular monitoring of weight and height. There was no evidence of delayed onset of puberty. CLINICALTRIALS. GOV IDENTIFIER: NCT01328756

An observational study of once-daily modified-release methylphenidate in ADHD: effectiveness on symptoms and impairment, and safety

ADHD affects over 5% of children worldwide. It is typically treated with stimulant medications, and methylphenidate (MPH) is the most commonly prescribed. This study investigated the effectiveness, on symptoms and impairment, and safety of Equasym XL®, a combination of 30% immediate-release and 70% modified-release MPH, in the treatment of ADHD in daily clinical practice. This open-label, observational, post-marketing surveillance study was conducted in 169 centres in Germany. Eligible patients, aged 6–17 years, were diagnosed with ADHD and about to begin treatment with Equasym XL®. Effectiveness was assessed by physicians using the clinical global impression (CGI) severity and improvement scales; teachers and parents completed questionnaires evaluating ADHD symptoms and behavioural problems (DAYAS, FBB-ADHD and SDQ-P). Assessments were carried out at baseline, after 1–3 and 6–12 weeks of treatment. Of 852 enrolled patients, 822 were evaluable; 25.30% were treatment naïve, 69.84% had previously received different MPH formulations, and 4.87% had received other medications. ADHD symptoms improved from baseline to last visit for the majority of patients for all outcome measures. According to physician ratings of core ADHD symptoms, 75.73% of patients showed improvements on the CGI-Improvement scale, 17.77% had no change, and 6.50% worsened. In teacher and parent ratings, the effectiveness of Equasym XL® was rated better than prior therapy at all measured time points across the day, particularly late morning (teachers) and early afternoon (parents). Equasym XL® was generally well tolerated; only 3.16% of patients permanently discontinued treatment due to adverse events. Equasym XL® is effective and well tolerated in daily clinical practice

Treatment response and remission in a double-blind, randomized, head-to-head study of lisdexamfetamine dimesylate and atomoxetine in children and adolescents with attention-deficit hyperactivity disorder

The Author(s) 2014. This article is published with open access at Springerlink.com Objectives A secondary objective of this head-to-head study of lisdexamfetamine dimesylate (LDX) and ato-moxetine (ATX) was to assess treatment response rates in children and adolescents with attention-deficit hyperactiv-ity disorder (ADHD) and an inadequate response to methylphenidate (MPH). The primary efficacy and safety outcomes of the study, SPD489-317 (ClinicalTrials.gov NCT01106430), have been published previously. Methods In this 9-week, double-blind, active-controlled study, patients aged 6–17 years with a previous inadequate response to MPH were randomized (1:1) to dose-optimized LDX (30, 50 or 70 mg/day) or ATX (patients \70 kg: 0.5–1.2 mg/kg/day, not to exceed 1.4 mg/kg/day; patients C70 kg: 40, 80 or 100 mg/day). Treatment response was a secondary efficacy outcome and was predefined as a reduction from baseline in ADHD Rating Scale IV (ADHD-RS-IV) total score of at least 25, 30 or 50 %. Sustained response was predefined as a reduction from baseline in ADHD-RS-IV total score (C25, C30 or C50 %) or a Clinical Global Impressions (CGI)–Improvement (CGI–I) score of 1 or 2 throughout weeks 4–9. CGI– Severity (CGI–S) scores were also assessed, as an indicator of remission. Results A total of 267 patients were enrolled (LDX, n = 133; ATX, n = 134) and 200 completed the study (LDX, n = 99; ATX, n = 101). By week 9, significantly (p \ 0.01) greater proportions of patients receiving LDX than ATX met the response criteria of a reduction from baseline in ADHD-RS-IV total score of at least 25 % (90.5 vs. 76.7 %), 30 % (88.1 vs. 73.7 %) or 50 % (73.0 vs. 50.4 %). Sustained response rates were also signifi-cantly (p \ 0.05) higher among LDX-treated patient

Focal brain trauma in the cryogenic lesion model in mice

The method to induce unilateral cryogenic lesions was first described in 1958 by Klatzo. We describe here an adaptation of this model that allows reliable measurement of lesion volume and vasogenic edema by 2, 3, 5-triphenyltetrazolium chloride-staining and Evans blue extravasation in mice. A copper or aluminium cylinder with a tip diameter of 2.5 mm is cooled with liquid nitrogen and placed on the exposed skull bone over the parietal cortex (coordinates from bregma: 1.5 mm posterior, 1.5 mm lateral). The tip diameter and the contact time between the tip and the parietal skull determine the extent of cryolesion. Due to an early damage of the blood brain barrier, the cryogenic cortical injury is characterized by vasogenic edema, marked brain swelling, and inflammation. The lesion grows during the first 24 hours, a process involving complex interactions between endothelial cells, immune cells, cerebral blood flow, and the intracranial pressure. These contribute substantially to the damage from the initial injury. The major advantage of the cryogenic lesion model is the circumscribed and highly reproducible lesion size and location