Does Connectionism undermine Fodor’s Language of Thought Hypothesis?

In 1975, Fodor hypothesised that thought is structured in much the same way as language. 1 Thoughts have semantics, a combinatorial syntax, and store information symbolically. In the 1980s, Connectionism looked to undermine his view. It suggested that mental information is stored non-symbolically in neural nets; it was considered a “paradigm shift” for cognitive theories. 2 In the 1990s, further work by Chalmers and Rowlands undermined Fodor’s Language of Thought Hypothesis. 345 Modern cognitive research into Deep Learning uses an inherently Connectionist framework. This paper separates Fodor’s hypothesis from his arguments in its support. It argues that Fodor’s Language of Thought Hypothesis is still a legitimate theory of cognition. However, it accepts that Fodor’s arguments in favour of his hypothesis are fallacious. The paper examines three of Fodor’s arguments for a language of thought: the only game in town argument, the argument from systematicity and productivity, and the argument from isomorphism. 6789 It shows each to be flawed. Further, this paper dismisses the dilemma Fodor and Pylyshyn present the Connectionist: that they must either merely implement his Language of Thought Hypothesis or concede that it is an inadequate theory of cognition. 10 he paper uses Chalmers’ Backpropagation Model, a system that encodes grammatical information without using symbols, to escape the dilemma. 11 Throughout, I argue that despite successfully undermining his arguments, Connectionism does not undermine Fodor’s Language of Thought Hypothesis. I provide two positive reasons to upholding the Language of Thought Hypothesis. This paper concludes that – at present – neither Connectionism nor Fodor’s Language of Thought Hypothesis has undermined the other

Topological study of bonding in aquo and bis(triazinyl)pyridine complexes of trivalent lanthanides and actinides:does covalency imply stability?

The geometrical and electronic structures of Ln[(H2O)9]3+ and [Ln(BTP)3]3+, where Ln = Ce–Lu, have been evaluated at the density functional level of theory using three related exchange-correlation (xc-)functionals. The BHLYP xc-functional was found to be most accurate, and this, along with the B3LYP functional, was used as the basis for topological studies of the electron density via the quantum theory of atoms in molecules (QTAIM). This analysis revealed that, for both sets of complexes, bonding was almost identical across the Ln series and was dominated by ionic interactions. Geometrical and electronic structures of actinide (An = Am, Cm) analogues were evaluated, and [An(H2O)9]3+ + [Ln(BTP)3]3+ → [Ln(H2O)9]3+ + [An(BTP)3]3+ exchange reaction energies were evaluated, revealing Eu ↔ Am and Gd ↔ Cm reactions to favor the An species. Detailed QTAIM analysis of Eu, Gd, Am, and Cm complexes revealed increased covalent character in M–O and M–N bonds when M = An, with this increase being more pronounced in the BTP complexes. This therefore implies a small electronic contribution to An–N bond stability and the experimentally observed selectivity of the BTP ligand for Am and Cm over lanthanides

Validation of reference tissue modelling for [11C]flumazenil positron emission tomography following head injury.

OBJECTIVE: [(11)C]Flumazenil ([(11)C]FMZ) positron emission tomography (PET) can be used as a measure of neuronal loss. The purpose of this study was to validate reference tissue kinetic modelling of [(11)C]FMZ PET within a group of patients with head injury. METHODS: Following earlier studies, the pons was used as the reference region. PET scans were performed on 16 controls and 11 patients at least 6 months following injury, each of whom also had arterial blood sampling to provide whole blood and metabolite-corrected plasma input functions. Regional non-displaceable binding potentials (BP(ND)) were calculated from five reference tissue models and compared to BP(ND) from arterial input models. For the patients, the regions included a peri-lesional region of interest (ROI). RESULTS: Total distribution volume of the pons was not significantly different between control and patient groups (P = 0.24). BP(ND) from all the reference tissue approaches correlated well with BP(ND) from the plasma input models for both controls (r (2) = 0.98-1.00; P < 0.001) and patients (r (2) = 0.99-1.00; P < 0.001). For the peri-lesional regions (n = 11 ROI values), the correlation was also high (r (2) = 0.91). CONCLUSIONS: These results indicate that reference tissue modelling with the pons as the reference region is valid for [(11)C]FMZ PET in head-injured patients at 6 months following injury within both normal appearing and peri-lesional brain regions

Oxygen Recovery Kinetics in the Forearm Flexors of Multiple Ability Groups of Rock Climbers

Fryer, SM, Stoner, L, Dickson, TG, Draper, SB, McCluskey, MJ, Hughes, JD, How, SC, and Draper, N. Oxygen recovery kinetics in the forearm flexors of multiple ability groups of rock climbers. J Strength Cond Res 29(6): 1633-1639, 2015-The purpose of this study was to determine muscle tissue oxidative capacity and recovery in intermediate, advanced, and elite rock climbers. Forty-four male participants performed (a) sustained and (b) intermittent contractions at 40% of maximal volitional contraction (MVC) on a sport-specific fingerboard until volitional fatigue. Near-infrared spectroscopy was used to assess muscle tissue oxygenation during both the exercise and the 5-minutes passive recovery period, in the flexor digitorum profundus (FDP) and flexor carpi radialis (FCR). During the sustained contraction only, muscle tissue deoxygenation (O2 debt) in the FDP and FCR was significantly greater in elite climbers compared with the control, intermediate, and advanced groups (FDP: 32 vs. 15, 19, 22%; FCR: 19 vs. 11, 8, 15%, respectively). However, elite climbers had a significantly quicker time to half recovery (T1/2) than the control and intermediate groups in the FDP (8 vs. 95 and 47 seconds, respectively) and the FCR (7 vs. 30 and 97 seconds, respectively) because the O2% recovered per second being significantly greater (FDP: 4.2 vs. 0.7 and 0.3; FCR: 4.8 vs. 0.1 and 0.2, respectively). Furthermore, during the intermittent contraction, T1/2 in elite climbers was significantly quicker compared with the control and intermediate groups in the FDP (8 vs. 93 and 83 seconds, respectively) and FCR (16 vs. 76 and 50 seconds, respectively). Consequently, lower-level climbers should focus training on specific intermittent fatigue protocols. Competition or elite climbers should make use of appropriate rests on route to aid recovery and increase the chances of reaching the next hold

[18F]AV-1451 binding in vivo mirrors the expected distribution of TDP-43 pathology in the semantic variant of primary progressive aphasia

Introduction Semantic dementia, including the semantic variant of primary progressive aphasia (svPPA), is strongly associated with TAR-DNA binding protein 43 (TDP-43) type C pathology. It provides a useful model in which to test the specificity of in vivo binding of the putative tau ligand [18F]AV-1451, which is elevated in frontotemporal lobar degeneration tauopathies. Methods and results Seven patients (five with svPPA and two with ‘right’ semantic dementia) and 12 healthy controls underwent positron emission tomography brain imaging with [18F]AV-1451. Two independent preprocessing methods were used. For both methods, all patients had clearly elevated binding potential (BPND (non-displaceable binding potential)) in temporal lobes, lateralising according to their clinical syndrome and evident in raw images. Region of interest analyses confirmed that BPND was significantly increased in temporal regions, insula and fusiform gyrus, consistent with those areas known to be most affected in semantic dementia. Hierarchical cluster analysis, based on the distribution of [18F]AV-1451 binding potential, separated semantic dementia from controls with 86% sensitivity and 100% specificity. Conclusions [18F]AV-1451 binds in vivo regions that are likely to contain TDP-43 and not significant tau pathology. While this suggests a non-tau target for [18F]AV-1451, the pathological regions in semantic dementia do not normally contain significant levels of recently proposed ‘off target’ binding sites for [18F]AV-1451, such as neuronal monoamine oxidase or neuromelanin. Postmortem and longitudinal data will be useful to assess the utility of [18F]AV-1451 to differentiate and track different types of frontotemporal lobar degeneration.This work was supported by the National Institute for Health Research Biomedical Research Centre and Biomedical Research Unit in Dementia; the Wellcome Trust (JBR 103838); the Association of British Neurologists and the Patrick Berthoud Charitable Trust (TEC)

Epigenetic and oncogenic regulation of SLC16A7 (MCT2) results in protein over-expression, impacting on signalling and cellular phenotypes in prostate cancer

Felisbino S. received a fellowship from the Sao Paulo Research Foundation (FAPESP) ref. 2013/08830-2 and 2013/06802-1. Anne Y Warren research time funded by: Cambridge Biomedical Research Centre.Monocarboxylate Transporter 2 (MCT2) is a major pyruvate transporter encoded by the SLC16A7 gene. Recent studies pointed to a consistent overexpression of MCT2 in prostate cancer (PCa) suggesting MCT2 as a putative biomarker and molecular target. Despite the importance of this observation the mechanisms involved in MCT2 regulation are unknown. Through an integrative analysis we have discovered that selective demethylation of an internal SLC16A7/MCT2 promoter is a recurrent event in independent PCa cohorts. This demethylation is associated with expression of isoforms differing only in 5'-UTR translational control motifs, providing one contributing mechanism for MCT2 protein overexpression in PCa. Genes co-expressed with SLC16A7/MCT2 also clustered in oncogenic-related pathways and effectors of these signalling pathways were found to bind at the SLC16A7/MCT2 gene locus. Finally, MCT2 knock-down attenuated the growth of PCa cells. The present study unveils an unexpected epigenetic regulation of SLC16A7/MCT2 isoforms and identifies a link between SLC16A7/MCT2, Androgen Receptor (AR), ETS-related gene (ERG) and other oncogenic pathways in PCa. These results underscore the importance of combining data from epigenetic, transcriptomic and protein level changes to allow more comprehensive insights into the mechanisms underlying protein expression, that in our case provide additional weight to MCT2 as a candidate biomarker and molecular target in PCa.Publisher PDFPeer reviewe

Doing cold smarter

Cold has been much neglected in the energy debate. Governments are developing strategies and policies to green everything from electricity to transport to heat, but the energy and environmental impacts of cooling have so far been largely ignored. This is a serious oversight, since making things cold is energy intensive and can be highly polluting, and demand for cooling in all its forms is booming worldwide – especially in developing countries. According to one projection, by the end of this century global demand for air conditioning alone could consume the equivalent of half our worldwide electricity generation today – and most of the increase will come in developing markets. The ‘greening’ of cold is clearly an urgent global problem – but it may also offer Britain a massive business opportunity. Cold may have been ignored but is vitally important to many aspects of modern life. An effective cold chain, for example, is essential for tackling problems such as food waste, food security, water conservation and public health. Cooling is also critical for many less obvious but essential functions: data centres couldn’t operate without it, nor for example MRI scanners in medicine or superconductors in power electronics. Cooling also provides modern levels of comfort in hot countries – and can make the difference between some regions being habitable or not. At the same time, vast amounts of cold are wasted – for instance during the regasification of LNG – which could in principle be recycled to satisfy some of this demand and start to reduce the environmental damage caused by cooling. Such a system-level approach – which starts by asking what energy services we need, and what is the least damaging way to provide them, rather than accepting existing practices as a fait accompli – has recently been coined the ‘Cold Economy’. It is clear the Cold Economy could unleash a wide range of innovative clean cold technologies and provide energy resilience, economic growth and environmental benefits, but there is an urgent need to develop a system-level analysis of this problem and the potential solutions to inform both industry and policymakers. The Birmingham Policy Commission: Doing Cold Smarter was convened to start this work

Delineating the topography of amyloid-associated cortical atrophy in Down syndrome

Older adults with Down syndrome (DS) often have Alzheimer's disease (AD) neuropathologies. Although positron emission tomography imaging studies of amyloid deposition (beta amyloid, Aβ) have been associated with worse clinical prognosis and cognitive impairment, their relationships with cortical thickness remain unclear in people with DS. In a sample of 44 DS adults who underwent cognitive assessments, [C]-PiB positron emission tomography, and T1-weighted magnetization-prepared rapid gradient echo, we used mixed effect models to evaluate the spatial relationships between Aβ binding with patterns of cortical thickness. Partial Spearman correlations were used to delineate the topography of local Aβ-associated cortical thinning. [C]-PiB nondisplaceable binding potential was negatively associated with decreased cortical thickness. Locally, regional [C]-PiB retention was negatively correlated with cortical thickness in widespread cortices, predominantly in temporoparietal regions. Contrary to the prevailing evidence in established AD, we propose that our findings implicate Aβ in spatial patterns of atrophy that recapitulated the “cortical signature” of neurodegeneration in AD, conferring support to recent recommendations for earlier disease-interventions

Synaptic Loss in Primary Tauopathies Revealed by [11 C]UCB-J Positron Emission Tomography.

BACKGROUND: Synaptic loss is a prominent and early feature of many neurodegenerative diseases. OBJECTIVES: We tested the hypothesis that synaptic density is reduced in the primary tauopathies of progressive supranuclear palsy (PSP) (Richardson's syndrome) and amyloid-negative corticobasal syndrome (CBS). METHODS: Forty-four participants (15 CBS, 14 PSP, and 15 age-/sex-/education-matched controls) underwent PET with the radioligand [11 C]UCB-J, which binds to synaptic vesicle glycoprotein 2A, a marker of synaptic density; participants also had 3 Tesla MRI and clinical and neuropsychological assessment. RESULTS: Nine CBS patients had negative amyloid biomarkers determined by [11 C]PiB PET and hence were deemed likely to have corticobasal degeneration (CBD). Patients with PSP-Richardson's syndrome and amyloid-negative CBS were impaired in executive, memory, and visuospatial tasks. [11 C]UCB-J binding was reduced across frontal, temporal, parietal, and occipital lobes, cingulate, hippocampus, insula, amygdala, and subcortical structures in both PSP and CBD patients compared to controls (P < 0.01), with median reductions up to 50%, consistent with postmortem data. Reductions of 20% to 30% were widespread even in areas of the brain with minimal atrophy. There was a negative correlation between global [11 C]UCB-J binding and the PSP and CBD rating scales (R = -0.61, P < 0.002; R = -0.72, P < 0.001, respectively) and a positive correlation with the revised Addenbrooke's Cognitive Examination (R = 0.52; P = 0.01). CONCLUSIONS: We confirm severe synaptic loss in PSP and CBD in proportion to disease severity, providing critical insight into the pathophysiology of primary degenerative tauopathies. [11 C]UCB-J may facilitate treatment strategies for disease-modification, synaptic maintenance, or restoration. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Effectiveness of a symptom-clinic intervention delivered by general practitioners with an extended role for people with multiple and persistent physical symptoms in England:the Multiple Symptoms Study 3 pragmatic, multicentre, parallel-group, individually randomised controlled trial

BACKGROUND: People with multiple and persistent physical symptoms have impaired quality of life and poor experiences of health care. We aimed to evaluate the effectiveness of a community-based symptom-clinic intervention in people with multiple and persistent physical symptoms, hypothesising that this symptoms clinic plus usual care would be superior to usual care only.METHODS: The Multiple Symptoms Study 3 was a pragmatic, multicentre, parallel-group, individually randomised controlled trial conducted in 108 general practices in the UK National Health Service in four regions of England between Dec 6, 2018, and June 30, 2023. Participants were individually randomised (1:1) to the symptom-clinic intervention plus usual care or to usual care only via a computer-generated, pseudo-random list stratified by trial centre. Allocation was done by the trial statistician and concealed with a centralised, web-based randomisation system; masking participants was not possible due to the nature of the intervention. The symptom-clinic intervention was a sequence of up to four medical consultations that aimed to elicit a detailed clinical history, fully hear and validate the participant, offer rational explanations for symptoms, and assist the participant to develop ways of managing their symptoms; it was delivered by general practitioners with an extended role. The primary outcome was Patient Health Questionnaire-15 (PHQ-15) score 52 weeks after randomisation, analysed by intention to treat. The trial is registered on the ISRCTN registry (ISRCTN57050216).FINDINGS: 354 participants were randomly assigned; 178 (50%) were assigned to receive the community-based symptoms clinic plus usual care and 176 (50%) were assigned to receive usual care only. At the primary-outcome point of 52 weeks, PHQ-15 scores were 14·1 (SD 3·7) in the group receiving usual care and 12·2 (4·5) in the group receiving the intervention. The adjusted between-group difference of -1·82 (95% CI -2·67 to -0·97) was statistically significantly in favour of the intervention group (p&lt;0·0001). There were 39 adverse events in the group receiving usual care and 36 adverse events in the group receiving the intervention. There were no statistically significant between-group differences in the proportion of participants who had non-serious adverse events (-0·03, 95% CI -0·11 to 0·05) or serious adverse events (0·02, -0·02 to 0·07). No serious adverse event was deemed to be related to the trial intervention.INTERPRETATION: Our symptom-clinic intervention, which focused on explaining persistent symptoms to participants in order to support self-management, led to sustained improvement in multiple and persistent physical symptoms.FUNDING: UK National Institute for Health and Care Research.</p