The physiological and emotional effects of touch: Assessing a hand-massage intervention with high self-critics

Research demonstrates that highly self-critical individuals can respond negatively to the initial introduction of a range of therapeutic interventions. Yet touch as a form of therapeutic intervention in self-critical individuals has received limited prior investigation, despite documentation of its beneficial effects for well-being. Using the Forms of Self-Criticism/Self-Reassuring Scale, 15 high- and 14 low- self-critical individuals (from a sample of 139 females) were recruited to assess how self-criticism impacts upon a single instance of focused touch. All participants took part in a hand massage- and haptic control- intervention. Salivary cortisol and alpha amylase, as well as questionnaire measures of emotional responding were taken before and after the interventions. Following hand massage, analyses revealed cortisol decreased significantly across all participants; and that significant changes in emotional responding reflected well-being improvements across all participants. Supplementary analyses further revealed decreased alpha amylase responding to hand massage as compared to a compassion-focused intervention in the same (highly self-critical) individuals. Taken together, the physiological and emotional data indicate high self-critical individuals responded in a comparable manner to low self-critical individuals to a single instance of hand massage. This highlights that focused touch may be beneficial when first engaging highly self-critical individuals with specific interventions.This research was part funded by the Compassionate Mind Foundatio

A systematic review of self-report measures of negative self-referential emotions developed for non-clinical child and adolescent samples

The crisis in child and adolescent mental health and wellbeing has prompted the development of school and community-based interventions to tackle negative emotions towards the self. Providing an evidence-base for such interventions is therefore a priority for policy makers and practitioners. This paper presents the first systematic review of self-referential and self-report measures of negative emotions for use with non-clinical child/adolescent populations, and evaluation of their psychometric properties. A systematic search of electronic databases and grey literature was conducted. Peer reviewed articles that introduced a new measure or included psychometric evaluation of a negative self-referential emotion for children and/or adolescents were identified. Study characteristics were extracted, and psychometric properties rated using internationally recognised quality criteria. Initially, 98 measures designed for evaluating children and adolescents’ negative self-referential emotions were found. Measures were primarily excluded if they were intended for clinical diagnosis or did not focus on self-referential emotions. The remaining eight measures (Brief Shame and Guilt Questionnaire; Self-Consciousness Scale-Children; Shame and Guilt Scale for Adolescents; Test of Self-Conscious Affect- Adolescents; The Child-Adolescent Perfectionism Scale [CAPS]; Child and Adolescent Dysfunctional Attitudes Scale Revised; Children Automatic Thoughts Scale [CATS]; Negative Affect Self-Statement Questionnaire) were organised into domains consisting of self-conscious emotions, self-oriented perfectionism and negative self-cognitions. Psychometric quality ratings identified the CAPS (Flett et al. in J Psychoeduc Assess 34:634–652, 2016) and the CATS (Schniering and Rapee in Behav Res Ther 40:1091–1109, 2002) as having the strongest psychometric qualities. However, all reviewed measures lacked full evaluation of essential psychometric properties. Our review revealed a paucity of self-referential emotional measures suitable for assessing adverse negative self-referential emotions in general child and adolescent populations. Measures suitable for use in non-clinical samples were identified, but these require further evaluation and/or new scale developments are needed. The psychometric findings and methodological issues identified will guide researchers and practitioners to make evidence-based decisions in order to select optimal measures.N/

Characterisation and expression of SPLUNC2, the human orthologue of rodent parotid secretory protein

We recently described the Palate Lung Nasal Clone (PLUNC) family of proteins as an extended group of proteins expressed in the upper airways, nose and mouth. Little is known about these proteins, but they are secreted into the airway and nasal lining fluids and saliva where, due to their structural similarity with lipopolysaccharide-binding protein and bactericidal/permeability-increasing protein, they may play a role in the innate immune defence. We now describe the generation and characterisation of novel affinity-purified antibodies to SPLUNC2, and use them to determine the expression of this, the major salivary gland PLUNC. Western blotting showed that the antibodies identified a number of distinct protein bands in saliva, whilst immunohistochemical analysis demonstrated protein expression in serous cells of the major salivary glands and in the ductal lumens as well as in cells of minor mucosal glands. Antibodies directed against distinct epitopes of the protein yielded different staining patterns in both minor and major salivary glands. Using RT-PCR of tissues from the oral cavity, coupled with EST analysis, we showed that the gene undergoes alternative splicing using two 5' non-coding exons, suggesting that the gene is regulated by alternative promoters. Comprehensive RACE analysis using salivary gland RNA as template failed to identify any additional exons. Analysis of saliva showed that SPLUNC2 is subject to N-glycosylation. Thus, our study shows that multiple SPLUNC2 isoforms are found in the oral cavity and suggest that these proteins may be differentially regulated in distinct tissues where they may function in the innate immune response

Evolution favors protein mutational robustness in sufficiently large populations

BACKGROUND: An important question is whether evolution favors properties such as mutational robustness or evolvability that do not directly benefit any individual, but can influence the course of future evolution. Functionally similar proteins can differ substantially in their robustness to mutations and capacity to evolve new functions, but it has remained unclear whether any of these differences might be due to evolutionary selection for these properties. RESULTS: Here we use laboratory experiments to demonstrate that evolution favors protein mutational robustness if the evolving population is sufficiently large. We neutrally evolve cytochrome P450 proteins under identical selection pressures and mutation rates in populations of different sizes, and show that proteins from the larger and thus more polymorphic population tend towards higher mutational robustness. Proteins from the larger population also evolve greater stability, a biophysical property that is known to enhance both mutational robustness and evolvability. The excess mutational robustness and stability is well described by existing mathematical theories, and can be quantitatively related to the way that the proteins occupy their neutral network. CONCLUSIONS: Our work is the first experimental demonstration of the general tendency of evolution to favor mutational robustness and protein stability in highly polymorphic populations. We suggest that this phenomenon may contribute to the mutational robustness and evolvability of viruses and bacteria that exist in large populations

Anxiety and avoidance in psychogenic nonepileptic seizures: the role of implicit and explicit anxiety

This study examined implicit and explicit anxiety in individuals with epilepsy and psychogenic nonepileptic seizures (PNESs) and explored whether these constructs were related to experiential avoidance and seizure frequency. Based on recent psychological models of PNESs, it was hypothesized that nonepileptic seizures would be associated with implicit and explicit anxiety and experiential avoidance. Explicit anxiety was measured by the State-Trait Anxiety Inventory; implicit anxiety was measured by an Implicit Relational Assessment Procedure; and experiential avoidance was measured with the Multidimensional Experiential Avoidance Questionnaire. Although both groups with epilepsy and PNESs scored similarly on implicit measures of anxiety, significant implicit–explicit anxiety discrepancies were only identified in patients with PNESs (p < .001). In the group with PNESs (but not in the group with epilepsy), explicit anxiety correlated with experiential avoidance (r = .63, p < .01) and frequency of seizures (r = .67, p < .01); implicit anxiety correlated with frequency of seizures only (r = .56, p < .01). Our findings demonstrate the role of implicit anxiety in PNESs and provide additional support for the contribution of explicit anxiety and experiential avoidance to this disorder

Directed evolution of a magnetic resonance imaging contrast agent for noninvasive imaging of dopamine

The development of molecular probes that allow in vivo imaging of neural signaling processes with high temporal and spatial resolution remains challenging. Here we applied directed evolution techniques to create magnetic resonance imaging (MRI) contrast agents sensitive to the neurotransmitter dopamine. The sensors were derived from the heme domain of the bacterial cytochrome P450-BM3 (BM3h). Ligand binding to a site near BM3h's paramagnetic heme iron led to a drop in MRI signal enhancement and a shift in optical absorbance. Using an absorbance-based screen, we evolved the specificity of BM3h away from its natural ligand and toward dopamine, producing sensors with dissociation constants for dopamine of 3.3–8.9 μM. These molecules were used to image depolarization-triggered neurotransmitter release from PC12 cells and in the brains of live animals. Our results demonstrate the feasibility of molecular-level functional MRI using neural activity–dependent sensors, and our protein engineering approach can be generalized to create probes for other targets.Charles A. Dana Foundation. Brain and Immuno-ImagingRaymond and Beverley Sackler FoundationNational Institutes of Health (U.S.) (grant R01-DA28299)National Institutes of Health (U.S.) (grant DP2-OD2441)National Institutes of Health (U.S.) (grant R01-GM068664)Jacobs Institute for Molecular Engineering for Medicine. Jacobs Institute for Molecular Engineering for MedicineNational Institutes of Health (U.S.) (grant R01-DE013023

Costs and effects of a 'healthy living' approach to community development in two deprived communities: findings from a mixed methods study

Background: Inequalities in health have proved resistant to 'top down' approaches. It is increasingly recognised that health promotion initiatives are unlikely to succeed without strong local involvement at all stages of the process and many programmes now use grass roots approaches. A healthy living approach to community development (HLA) was developed as an innovative response to local concerns about a lack of appropriate services in two deprived communities in Pembrokeshire, West Wales. We sought to assess feasibility, costs, benefits and working relationships of this HLA. Methods: The HLA intervention operated through existing community forums and focused on the whole community and its relationship with statutory and voluntary sectors. Local people were trained as community researchers and gathered views about local needs though resident interviews. Forums used interview results to write action plans, disseminated to commissioning organisations. The process was supported throughout through the project. The evaluation used a multi-method before and after study design including process and outcome formative and summative evaluation; data gathered through documentary evidence, diaries and reflective accounts, semi-structured interviews, focus groups and costing proformas. Main outcome measures were processes and timelines of implementation of HLA; self reported impact on communities and participants; community-agency processes of liaison; costs. Results: Communities were able to produce and disseminate action plans based on locally-identified needs. The process was slower than anticipated: few community changes had occurred but expectations were high. Community participants gained skills and confidence. Cross-sector partnership working developed. The process had credibility within service provider organisations but mechanisms for refocusing commissioning were patchy. Intervention costs averaged £58,304 per community per annum. Conclusions: The intervention was feasible and inexpensive, with indications of potential impact at individual, community and policy planning levels. However, it is a long term process which requires sustained investment and must be embedded in planning and service delivery processes.12 page(s

Ancient Martian aeolian processes and palaeomorphology reconstructed from the Stimson formation on the lower slope of Aeolis Mons, Gale crater, Mars

Reconstruction of the palaeoenvironmental context of Martian sedimentary rocks is central to studies of ancient Martian habitability and regional palaeoclimate history. This paper reports the analysis of a distinct aeolian deposit preserved in Gale crater, Mars, and evaluates its palaeomorphology, the processes responsible for its deposition, and its implications for Gale crater geological history and regional palaeoclimate. Whilst exploring the sedimentary succession cropping out on the northern flank of Aeolis Mons, Gale crater, the Mars Science Laboratory rover Curiosity encountered a decametre‐thick sandstone succession, named the Stimson formation, unconformably overlying lacustrine deposits of the Murray formation. The sandstone contains sand grains characterized by high roundness and sphericity, and cross‐bedding on the order of 1 m in thickness, separated by sub‐horizontal bounding surfaces traceable for tens of metres across outcrops. The cross‐beds are composed of uniform thickness cross‐laminations interpreted as wind‐ripple strata. Cross‐sets are separated by sub‐horizontal bounding surfaces traceable for tens of metres across outcrops that are interpreted as dune migration surfaces. Grain characteristics and presence of wind‐ripple strata indicate deposition of the Stimson formation by aeolian processes. The absence of features characteristic of damp or wet aeolian sediment accumulation indicate deposition in a dry aeolian system. Reconstruction of the palaeogeomorphology suggests that the Stimson dune field was composed largely of simple sinuous crescentic dunes with a height of ca 10 m, and wavelengths of ca 150 m, with local development of complex dunes. Analysis of cross‐strata dip azimuths indicates that the general dune migration direction and hence net sediment transport was towards the north‐east. The juxtaposition of a dry aeolian system unconformably above the lacustrine Murray formation represents starkly contrasting palaeoenvironmental and palaeoclimatic conditions. Stratigraphic relationships indicate that this transition records a significant break in time, with the Stimson formation being deposited after the Murray formation and stratigraphically higher Mount Sharp group rocks had been buried, lithified and subsequently eroded

Ancient Martian aeolian processes and palaeomorphology reconstructed from the Stimson formation on the lower slope of Aeolis Mons, Gale crater, Mars

Reconstruction of the palaeoenvironmental context of Martian sedimentary rocks is central to studies of ancient Martian habitability and regional palaeoclimate history. This paper reports the analysis of a distinct aeolian deposit preserved in Gale crater, Mars, and evaluates its palaeomorphology, the processes responsible for its deposition, and its implications for Gale crater geological history and regional palaeoclimate. Whilst exploring the sedimentary succession cropping out on the northern flank of Aeolis Mons, Gale crater, the Mars Science Laboratory rover Curiosity encountered a decametre‐thick sandstone succession, named the Stimson formation, unconformably overlying lacustrine deposits of the Murray formation. The sandstone contains sand grains characterized by high roundness and sphericity, and cross‐bedding on the order of 1 m in thickness, separated by sub‐horizontal bounding surfaces traceable for tens of metres across outcrops. The cross‐beds are composed of uniform thickness cross‐laminations interpreted as wind‐ripple strata. Cross‐sets are separated by sub‐horizontal bounding surfaces traceable for tens of metres across outcrops that are interpreted as dune migration surfaces. Grain characteristics and presence of wind‐ripple strata indicate deposition of the Stimson formation by aeolian processes. The absence of features characteristic of damp or wet aeolian sediment accumulation indicate deposition in a dry aeolian system. Reconstruction of the palaeogeomorphology suggests that the Stimson dune field was composed largely of simple sinuous crescentic dunes with a height of ca 10 m, and wavelengths of ca 150 m, with local development of complex dunes. Analysis of cross‐strata dip azimuths indicates that the general dune migration direction and hence net sediment transport was towards the north‐east. The juxtaposition of a dry aeolian system unconformably above the lacustrine Murray formation represents starkly contrasting palaeoenvironmental and palaeoclimatic conditions. Stratigraphic relationships indicate that this transition records a significant break in time, with the Stimson formation being deposited after the Murray formation and stratigraphically higher Mount Sharp group rocks had been buried, lithified and subsequently eroded

Neonatal rotavirus vaccine (RV3-BB) immunogenicity and safety in a neonatal and infant administration schedule in Malawi: a randomised, double-blind, four-arm parallel group dose-ranging study.

BackgroundRotavirus vaccines reduce rotavirus-related deaths and hospitalisations but are less effective in high child mortality countries. The human RV3-BB neonatal G3P[6] rotavirus vaccine administered in a neonatal schedule was efficacious in reducing severe rotavirus gastroenteritis in Indonesia but had not yet been evaluated in African infants.MethodsWe did a phase 2, randomised, double-blind, parallel group dose-ranging study of three doses of oral RV3-BB rotavirus vaccine in infants in three primary health centres in Blantyre, Malawi. Healthy infants less than 6 days of age with a birthweight 2·5 to 4·0 kg were randomly assigned (1:1:1:1) into one of four treatment groups: neonatal vaccine group, which included high-titre (1·0 × 107 focus-forming unit [FFU] per mL), mid-titre (3·0 × 106 FFU per mL), or low-titre (1·0 × 106 FFU per mL); and infant vaccine group, which included high-titre (1·0 × 107 FFU per mL) using a computer generated code (block size of four), stratified by birth (singleton vs multiple). Neonates received their three doses at 0-5 days to 10 weeks and infants at 6-14 weeks. Investigators, participant families, and laboratory staff were masked to group allocation. Anti-rotavirus IgA seroconversion and vaccine take (IgA seroconversion and stool shedding) were evaluated. Safety was assessed in all participants who received at least one dose of vaccine or placebo. The primary outcome was the cumulative IgA seroconversion 4 weeks after three doses of RV3-BB in the neonatal schedule in the high-titre, mid-titre, and low-titre groups in the per protocol population, with its 95% CI. With the high-titre group as the active control group, we did a non-inferiority analysis of the proportion of participants with IgA seroconversion in the mid-titre and low-titre groups, using a non-inferiority margin of less than 20%. This trial is registered at ClinicalTrials.gov (NCT03483116).FindingsBetween Sept 17, 2018, and Jan 27, 2020, 711 participants recruited were randomly assigned into four treatment groups (neonatal schedule high titre n=178, mid titre n=179, low titre n=175, or infant schedule high titre n=179). In the neonatal schedule, cumulative IgA seroconversion 4 weeks after three doses of RV3-BB was observed in 79 (57%) of 139 participants in the high-titre group, 80 (57%) of 141 participants in the mid-titre group, and 57 (41%) of 138 participants in the low-titre group and at 18 weeks in 100 (72%) of 139 participants in the high-titre group, 96 (67%) of 143 participants in the mid-titre group, and 86 (62%) of 138 of participants in the low-titre. No difference in cumulative IgA seroconversion 4 weeks after three doses of RV3-BB was observed between high-titre and mid-titre groups in the neonatal schedule (difference in response rate 0·001 [95%CI -0·115 to 0·117]), fulfilling the criteria for non-inferiority. In the infant schedule group 82 (59%) of 139 participants had a cumulative IgA seroconversion 4 weeks after three doses of RV3-BB at 18 weeks. Cumulative vaccine take was detected in 483 (85%) of 565 participants at 18 weeks. Three doses of RV3-BB were well tolerated with no difference in adverse events among treatment groups: 67 (39%) of 170 participants had at least one adverse event in the high titre group, 68 (40%) of 172 participants had at least one adverse event in the mid titre group, and 69 (41%) of 169 participants had at least one adverse event in the low titre group.InterpretationRV3-BB was well tolerated and immunogenic when co-administered with Expanded Programme on Immunisation vaccines in a neonatal or infant schedule. A lower titre (mid-titre) vaccine generated similar IgA seroconversion to the high-titre vaccine presenting an opportunity to enhance manufacturing capacity and reduce costs. Neonatal administration of the RV3-BB vaccine has the potential to improve protection against rotavirus disease in children in a high-child mortality country in Africa.FundingBill & Melinda Gates Foundation, Australian Tropical Medicine Commercialisation Grant