The Real Combination Problem : Panpsychism, Micro-Subjects, and Emergence

Panpsychism harbors an unresolved tension, the seriousness of which has yet to be fully appreciated. I capture this tension as a dilemma, and offer panpsychists advice on how to resolve it. The dilemma, briefly, is as follows. Panpsychists are committed to the perspicuous explanation of macro-mentality in terms of micro-mentality. But panpsychists take the micro-material realm to feature not just mental properties, but also micro-subjects to whom these properties belong. Yet it is impossible to explain the constitution of a macro-subject (like one of us) in terms of the assembly of micro-subjects, for, I show, subjects cannot combine. Therefore the panpsychist explanatory project is derailed by the insistence that the world’s ultimate material constituents (ultimates) are subjects of experience. The panpsychist faces a choice of abandoning her explanatory project, or recanting the claim that the ultimates are subjects. This is the dilemma. I argue that the latter option is to be preferred. This needn’t constitute a wholesale abandonment of panpsychism, however, since panpsychists can maintain that the ultimates possess phenomenal qualities, despite not being subjects of those qualities. This proposal requires us to make sense of phenomenal qualities existing independently of experiencing subjects, a challenge I tackle in the penultimate section. The position eventually reached is a form of neutral monism, so another way to express the overall argument is to say that, keeping true to their philosophical motivations, panpsychists should really be neutral monists.Peer reviewedFinal Accepted Versio

Statistical methodologies to pool across multiple intervention studies

Combining and analyzing data from heterogeneous randomized controlled trials of complex multiple-component intervention studies, or discussing them in a systematic review, is not straightforward. The present article describes certain issues to be considered when combining data across studies, based on discussions in an NIH-sponsored workshop on pooling issues across studies in consortia (see Belle et al. in Psychol Aging, 18(3):396–405, 2003). Several statistical methodologies are described and their advantages and limitations are explored. Whether weighting the different studies data differently, or via employing random effects, one must recognize that different pooling methodologies may yield different results. Pooling can be used for comprehensive exploratory analyses of data from RCTs and should not be viewed as replacing the standard analysis plan for each study. Pooling may help to identify intervention components that may be more effective especially for subsets of participants with certain behavioral characteristics. Pooling, when supported by statistical tests, can allow exploratory investigation of potential hypotheses and for the design of future interventions

Free Recall Learning of Hierarchically Organised Lists by Adults with Asperger's Syndrome: Additional Evidence for Diminished Relational Processing

The Task Support Hypothesis (TSH, Bowler et al. Neuropsychologia 35:65–70 1997) states that individuals with autism spectrum disorder (ASD) show better memory when test procedures provide support for retrieval. The present study aimed to see whether this principle also applied at encoding. Twenty participants with high-functioning ASD and 20 matched comparison participants studied arrays of 112 words over four trials. Words were arranged either under hierarchically embedded category headings (e.g. Instruments—String—Plucked—Violin) or randomly. Both groups showed similar overall recall and better recall for the hierarchically organised words. However, the ASD participants made less use of information about relations between words and more use of item-specific information in their recall, confirming earlier reports of relational difficulties in this population

Tau accumulation in autosomal dominant Alzheimer’s disease: a longitudinal [18F]flortaucipir study

Cortical tau accumulation is a key pathological event that partly defines Alzheimer’s disease (AD) onset and is associated with cognitive decline and future disease progression. However, an improved understanding of the timing and pattern of early tau deposition in AD and how this may be tracked in vivo is needed. Data from 59 participants involved in two longitudinal cohort studies of autosomal dominant AD (ADAD) were used to investigate whether tau PET can detect and track presymptomatic change; seven participants were symptomatic, and 52 were asymptomatic but at a 50% risk of carrying a pathogenic mutation. All had baseline flortaucipir (FTP) PET, MRI and clinical assessments; 26 individuals had more than one FTP PET scan. Standardised uptake value ratios (SUVRs) in prespecified regions of interest (ROIs) were obtained using inferior cerebellar grey matter as the reference region. We compared the changes in FTP SUVRs between presymptomatic carriers, symptomatic carriers and non-carriers, adjusting for age, sex and study site. We also investigated the relationship between regional FTP SUVRs and estimated years to/from symptom onset (EYO). Compared to both non-carriers and presymptomatic carriers, FTP SUVRs were significantly higher in symptomatic carriers in all ROIs tested (p 0.05), although increased FTP signal uptake was seen posteriorly in some individuals around the time of expected symptom onset. When we examined the relationship of FTP SUVR with respect to EYO, the earliest significant regional difference between mutation carriers and non-carriers was detected within the precuneus prior to estimated symptom onset in some cases. This study supports preliminary studies suggesting that presymptomatic tau tracer uptake is rare in ADAD. In cases where early uptake was seen, there was often a predilection for posterior regions (the precuneus and post-cingulate) as opposed to the medial temporal lobe, highlighting the importance of examining in vivo tau uptake beyond the confines of traditional Braak staging

Sensory Electrical Stimulation Improves Foot Placement during Targeted Stepping Post-Stroke

Proper foot placement is vital for maintaining balance during walking, requiring the integration of multiple sensory signals with motor commands. Disruption of brain structures post-stroke likely alters the processing of sensory information by motor centers, interfering with precision control of foot placement and walking function for stroke survivors. In this study, we examined whether somatosensory stimulation, which improves functional movements of the paretic hand, could be used to improve foot placement of the paretic limb. Foot placement was evaluated before, during, and after application of somatosensory electrical stimulation to the paretic foot during a targeted stepping task. Starting from standing, twelve chronic stroke participants initiated movement with the non-paretic limb and stepped to one of five target locations projected onto the floor with distances normalized to the paretic stride length. Targeting error and lower extremity kinematics were used to assess changes in foot placement and limb control due to somatosensory stimulation. Significant reductions in placement error in the medial–lateral direction (p = 0.008) were observed during the stimulation and post-stimulation blocks. Seven participants, presenting with a hip circumduction walking pattern, had reductions (p = 0.008) in the magnitude and duration of hip abduction during swing with somatosensory stimulation. Reductions in circumduction correlated with both functional and clinical measures, with larger improvements observed in participants with greater impairment. The results of this study suggest that somatosensory stimulation of the paretic foot applied during movement can improve the precision control of foot placement

Trump vs. Hillary: What went Viral during the 2016 US Presidential Election

In this paper, we present quantitative and qualitative analysis of the top retweeted tweets (viral tweets) pertaining to the US presidential elections from September 1, 2016 to Election Day on November 8, 2016. For everyday, we tagged the top 50 most retweeted tweets as supporting or attacking either candidate or as neutral/irrelevant. Then we analyzed the tweets in each class for: general trends and statistics; the most frequently used hashtags, terms, and locations; the most retweeted accounts and tweets; and the most shared news and links. In all we analyzed the 3,450 most viral tweets that grabbed the most attention during the US election and were retweeted in total 26.3 million times accounting over 40% of the total tweet volume pertaining to the US election in the aforementioned period. Our analysis of the tweets highlights some of the differences between the social media strategies of both candidates, the penetration of their messages, and the potential effect of attacks on bothComment: Paper to appear in Springer SocInfo 201

Patient Satisfaction with Primary Care Office-Based Buprenorphine/Naloxone Treatment

BACKGROUND: Factors associated with satisfaction among patients receiving primary care–based buprenorphine/naloxone are unknown. OBJECTIVE: To identify factors related to patient satisfaction in patients receiving primary care–based buprenorphine/naloxone that varied in counseling intensity (20 vs 45 minutes) and office visit frequency (weekly vs thrice weekly). DESIGN AND PARTICIPANTS: One hundred and forty-two opioid-dependent subjects. MEASUREMENTS: Demographics, drug treatment history, and substance use status at baseline and during treatment were collected. The primary outcome was patient satisfaction at 12 weeks. RESULTS: Patients’ mean overall satisfaction score was 4.4 (out of 5). Patients were most satisfied with the medication and ancillary services and indicated strong willingness to refer a substance-abusing friend for the same treatment. Patients were least satisfied with their interactions with other opioid-dependent patients, referrals to Narcotics Anonymous, and the inconvenience of the treatment location. Female gender (β = .17, P = .04) and non-White ethnicity/race (β = .17, P = .04) independently predicted patient satisfaction. Patients who received briefer counseling and buprenorphine/naloxone dispensed weekly had greater satisfaction than those whose medication was dispensed thrice weekly (mean difference 4.9, 95% confidence interval 0.08 to 9.80, P = .03). CONCLUSIONS: Patients are satisfied with primary care office-based buprenorphine/naloxone. Providers should consider the identified barriers to patient satisfaction

An Intact Kidney Slice Model to Investigate Vasa Recta Properties and Function in situ

Background: Medullary blood flow is via vasa recta capillaries, which possess contractile pericytes. In vitro studies using isolated descending vasa recta show that pericytes can constrict/dilate descending vasa recta when vasoactive substances are present. We describe a live kidney slice model in which pericyte-mediated vasa recta constriction/dilation can be visualized in situ. Methods: Confocal microscopy was used to image calcein, propidium iodide and Hoechst labelling in ‘live’ kidney slices, to determine tubular and vascular cell viability and morphology. DIC video-imaging of live kidney slices was employed to investigate pericyte-mediated real-time changes in vasa recta diameter. Results: Pericytes were identified on vasa recta and their morphology and density were characterized in the medulla. Pericyte-mediated changes in vasa recta diameter (10–30%) were evoked in response to bath application of vasoactive agents (norepinephrine, endothelin-1, angiotensin-II and prostaglandin E2) or by manipulating endogenous vasoactive signalling pathways (using tyramine, L-NAME, a cyclo-oxygenase (COX-1) inhibitor indomethacin, and ATP release). Conclusions: The live kidney slice model is a valid complementary technique for investigating vasa recta function in situ and the role of pericytes as regulators of vasa recta diameter. This technique may also be useful in exploring the role of tubulovascular crosstalk in regulation of medullary blood flow

Critical research gaps and translational priorities for the successful prevention and treatment of breast cancer

INTRODUCTION Breast cancer remains a significant scientific, clinical and societal challenge. This gap analysis has reviewed and critically assessed enduring issues and new challenges emerging from recent research, and proposes strategies for translating solutions into practice. METHODS More than 100 internationally recognised specialist breast cancer scientists, clinicians and healthcare professionals collaborated to address nine thematic areas: genetics, epigenetics and epidemiology; molecular pathology and cell biology; hormonal influences and endocrine therapy; imaging, detection and screening; current/novel therapies and biomarkers; drug resistance; metastasis, angiogenesis, circulating tumour cells, cancer 'stem' cells; risk and prevention; living with and managing breast cancer and its treatment. The groups developed summary papers through an iterative process which, following further appraisal from experts and patients, were melded into this summary account. RESULTS The 10 major gaps identified were: (1) understanding the functions and contextual interactions of genetic and epigenetic changes in normal breast development and during malignant transformation; (2) how to implement sustainable lifestyle changes (diet, exercise and weight) and chemopreventive strategies; (3) the need for tailored screening approaches including clinically actionable tests; (4) enhancing knowledge of molecular drivers behind breast cancer subtypes, progression and metastasis; (5) understanding the molecular mechanisms of tumour heterogeneity, dormancy, de novo or acquired resistance and how to target key nodes in these dynamic processes; (6) developing validated markers for chemosensitivity and radiosensitivity; (7) understanding the optimal duration, sequencing and rational combinations of treatment for improved personalised therapy; (8) validating multimodality imaging biomarkers for minimally invasive diagnosis and monitoring of responses in primary and metastatic disease; (9) developing interventions and support to improve the survivorship experience; (10) a continuing need for clinical material for translational research derived from normal breast, blood, primary, relapsed, metastatic and drug-resistant cancers with expert bioinformatics support to maximise its utility. The proposed infrastructural enablers include enhanced resources to support clinically relevant in vitro and in vivo tumour models; improved access to appropriate, fully annotated clinical samples; extended biomarker discovery, validation and standardisation; and facilitated cross-discipline working. CONCLUSIONS With resources to conduct further high-quality targeted research focusing on the gaps identified, increased knowledge translating into improved clinical care should be achievable within five years

The influence of gravimetric moisture content on studded shoe–surface interactions in soccer

It is desirable for the studs of a soccer shoe to penetrate the sport surface and provide the player with sufficient traction when accelerating. Mechanical tests are often used to measure the traction of shoe–surface combinations. Mechanical testing offers a repeatable measure of shoe–surface traction, eliminating the inherent uncertainties that exist when human participant testing is employed, and are hence used to directly compare the performance of shoe–surface combinations. However, the influence specific surface characteristics has on traction is often overlooked. Examining the influence of surface characteristics on mechanical test results improves the understanding of the traction mechanisms at the shoe–surface interface. This allows footwear developers to make informed decisions on the design of studded outsoles. The aim of this paper is to understand the effect gravimetric moisture content has on the tribological mechanisms at play during stud–surface interaction. This study investigates the relationships between: the gravimetric moisture content of a natural sand-based soccer surface; surface stiffness measured via a bespoke impact test device; and surface traction measured via a bespoke mechanical test device. Regression analysis revealed that surface stiffness decreases linearly with increased gravimetric moisture content (p = 0.04). Traction was found to initially increase and then decrease with gravimetric moisture content. It was observed that: a surface of low moisture content provides low stud penetration and therefore reduced traction; a surface of high moisture content provides high stud penetration but also reduced traction due to a lubricating effect; and surfaces with moisture content in between the two extremes provide increased traction. In this study a standard commercially available stud was used and other studs may provide slightly different results. The results provide insight into the traction mechanisms at the stud–surface interface which are described in the paper. The variation between traction measurements shows the influence gravimetric moisture content will have on player performance. This highlights the requirement to understand surface conditions prior to making comparative shoe–surface traction studies and the importance of using a studded outsole that is appropriate to the surface condition during play