Choosing the lesser of two evils, the better of two goods: Specifying the roles of ventromedial prefrontal cortex and dorsal anterior cingulate in object choice

The ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate cortices (ACd) are considered important for reward-based decision making. However, work distinguishing their individual functional contributions has only begun. One aspect of decision making that has received little attention is that making the right choice often translates to making the better choice. Thus, response choice often occurs in situations where both options are desirable (e.g., choosing between mousse au chocolat or crème caramel cheesecake from a menu) or, alternatively, in situations where both options are undesirable. Moreover, response choice is easier when the reinforcements associated with the objects are far apart, rather than close together, in value. We used functional magnetic resonance imaging to delineate the functional roles of the vmPFC and ACd by investigating these two aspects of decision making: (1) decision form (i.e., choosing between two objects to gain the greater reward or the lesser punishment), and (2) between-object reinforcement distance (i.e., the difference in reinforcements associated with the two objects). Blood oxygen level-dependent (BOLD) responses within the ACd and vmPFC were both related to decision form but differentially. Whereas ACd showed greater responses when deciding between objects to gain the lesser punishment, vmPFC showed greater responses when deciding between objects to gain the greater reward. Moreover, vmPFC was sensitive to reinforcement expectations associated with both the chosen and the forgone choice. In contrast, BOLD responses within ACd, but not vmPFC, related to between-object reinforcement distance, increasing as the distance between the reinforcements of the two objects decreased. These data are interpreted with reference to models of ACd and vmPFC functioning

A pragmatic randomised controlled trial of hydrotherapy and land exercises on overall well being and quality of life in rheumatoid arthritis

Background \ud Hydrotherapy is highly valued by people with rheumatoid arthritis yet few studies have compared the benefits of exercises in heated water against exercises on land. In particular, data on quality of life is rarely reported. This is especially important because patients treated with hydrotherapy often report an enhanced sense of well-being. We report a randomised controlled trial in which we compared the effects of hydrotherapy with exercises on land on overall response to treatment, physical function and quality of life in patients with rheumatoid arthritis. \ud \ud Methods \ud One hundred and fifteen patients with RA were randomised to receive a weekly 30-minute session of hydrotherapy or similar exercises on land for 6 weeks. Our primary outcome was a self-rated global impression of change – a measure of treatment effect on a 7-point scale ranging from 1(very much worse) to 7 (very much better) assessed immediately on completion of treatment. Secondary outcomes including EuroQol health related quality of life, EuroQol health status valuation, HAQ, 10 metre walk time and pain scores were collected at baseline, after treatment and 3 months later. Binary outcomes were analysed by Fisher's exact test and continuous variables by Wilcoxon or Mann-Whitney tests. \ud \ud Results \ud Baseline characteristics of the two groups were comparable. Significantly more patients treated with hydrotherapy (40/46, 87%) were much better or very much better than the patients treated with land exercise (19/40, 47.5%), p < 0.001 Fisher's exact test. Eleven patients allocated land exercise failed to complete treatment compared with 4 patients allocated hydrotherapy (p = 0.09). Sensitivity analyses confirmed an advantage for hydrotherapy if we assumed non-completers would all not have responded (response rates 70% versus 38%; p < 0.001) or if we assumed that non-completers would have had the same response as completers (response rates 82% versus 55% p = 0.002). Ten metre walk time improved after treatment in both cases (median pre-treatment time for both groups combined 10.9 seconds, post-treatment 9.1 s, and 3 months later 9.6 s). There was however no difference between treatment groups. Similarly there were no significant differences between groups in terms of changes to HAQ, EQ-5D utility score, EQ VAS and pain VAS. \ud \ud Conclusion \ud Patients with RA treated with hydrotherapy are more likely to report feeling much better or very much better than those treated with land exercises immediately on completion of the treatment programme. This perceived benefit was not reflected by differences between groups in 10-metre walk times, functional scores, quality of life measures and pain scores

Classification of non-Riemannian doubled-yet-gauged spacetime

Assuming $\mathbf{O}(D,D)$ covariant fields as the `fundamental' variables, Double Field Theory can accommodate novel geometries where a Riemannian metric cannot be defined, even locally. Here we present a complete classification of such non-Riemannian spacetimes in terms of two non-negative integers, $(n,\bar{n})$, $0\leq n+\bar{n}\leq D$. Upon these backgrounds, strings become chiral and anti-chiral over $n$ and $\bar{n}$ directions respectively, while particles and strings are frozen over the $n+\bar{n}$ directions. In particular, we identify $(0,0)$ as Riemannian manifolds, $(1,0)$ as non-relativistic spacetime, $(1,1)$ as Gomis-Ooguri non-relativistic string, $(D{-1},0)$ as ultra-relativistic Carroll geometry, and $(D,0)$ as Siegel's chiral string. Combined with a covariant Kaluza-Klein ansatz which we further spell, $(0,1)$ leads to Newton-Cartan gravity. Alternative to the conventional string compactifications on small manifolds, non-Riemannian spacetime such as $D=10$, $(3,3)$ may open a new scheme of the dimensional reduction from ten to four.Comment: 1+41 pages; v2) Refs added; v3) Published version; v4) Sign error in (2.51) correcte

Comparison of self-reported health & healthcare utilisation between asylum seekers and refugees: an observational study

<p>Abstract</p> <p>Background</p> <p>Adult refugees and asylum seekers living in Western countries experience a high prevalence of mental health problems, especially post traumatic stress disorder (PTSD), depression and anxiety. This study compares and contrasts the prevalence of health problems, and potential risk factors as well as the utilisation of health services by asylum seekers and refugees in the Irish context.</p> <p>Methods</p> <p>Cross sectional study using validated self reported health status questionnaires of adult asylum seekers (n = 60) and refugees (n = 28) from 30 countries, living in Ireland. Outcome measures included: general health status (SF-36), presence of PTSD symptoms and anxiety/depression symptoms. Data on chronic conditions and pre or post migration stressors are also reported. The two groups are compared for utilisation of the health care system and the use of over the counter medications.</p> <p>Results</p> <p>Asylum seekers were significantly more likely than refugees to report symptoms of PTSD (OR 6.3, 95% CI: 2.2–17.9) and depression/anxiety (OR 5.8, 95% CI: 2.2–15.4), while no significant difference was found in self-reported general health. When adjusted by multivariable regression, the presence of more than one chronic disease (OR 4.0, 95%CI: 1.3–12.7; OR 3.4, 95% CI: 1.2–10.1), high levels of pre migration stressors (OR 3.6, 95% CI: 1.1–11.9; OR 3.3, 95% CI: 1.0–10.4) or post migration stressors (OR 17.3, 95% CI: 4.9–60.8; OR 3.9, 95% CI: 1.2–12.3) were independent predictors of self reported PTSD or depression/anxiety symptoms respectively, however, residence status was no longer significantly associated with PTSD or depression/anxiety. Residence status may act as a marker for other explanatory variables; our results show it has a strong relationship with post migration stressors (χ²= 19.74, df = 1, P < 0.001).</p> <p>In terms of health care utilisation, asylum seekers use GP services more often than refugees, while no significant difference was found between these groups for use of dentists, medication, hospitalisation or mental health services.</p> <p>Conclusion</p> <p>Asylum seekers have a higher level of self reported PTSD and depression/anxiety symptoms compared to refugees. However, residence status appears to act as a marker for post migration stressors. Compared to refugees, asylum seekers utilise GP services more often, but not mental health services.</p

Sideband Cooling Micromechanical Motion to the Quantum Ground State

The advent of laser cooling techniques revolutionized the study of many atomic-scale systems. This has fueled progress towards quantum computers by preparing trapped ions in their motional ground state, and generating new states of matter by achieving Bose-Einstein condensation of atomic vapors. Analogous cooling techniques provide a general and flexible method for preparing macroscopic objects in their motional ground state, bringing the powerful technology of micromechanics into the quantum regime. Cavity opto- or electro-mechanical systems achieve sideband cooling through the strong interaction between light and motion. However, entering the quantum regime, less than a single quantum of motion, has been elusive because sideband cooling has not sufficiently overwhelmed the coupling of mechanical systems to their hot environments. Here, we demonstrate sideband cooling of the motion of a micromechanical oscillator to the quantum ground state. Entering the quantum regime requires a large electromechanical interaction, which is achieved by embedding a micromechanical membrane into a superconducting microwave resonant circuit. In order to verify the cooling of the membrane motion into the quantum regime, we perform a near quantum-limited measurement of the microwave field, resolving this motion a factor of 5.1 from the Heisenberg limit. Furthermore, our device exhibits strong-coupling allowing coherent exchange of microwave photons and mechanical phonons. Simultaneously achieving strong coupling, ground state preparation and efficient measurement sets the stage for rapid advances in the control and detection of non-classical states of motion, possibly even testing quantum theory itself in the unexplored region of larger size and mass.Comment: 13 pages, 7 figure

Association between Changes in Muscle Quality with Exercise Training and Changes in Cardiorespiratory Fitness Measures in Individuals with Type 2 Diabetes Mellitus: Results from the HART-D Study

Introduction: Type 2 diabetes mellitus (T2DM) is associated with a reduction in muscle quality. However, there is inadequate empirical evidence to determine whether changes in muscle quality following exercise are associated with improvement in cardiorespiratory fitness (CRF) in individuals with T2DM. The objective of this study was to investigate the association between change in muscle quality following a 9-month intervention of aerobic training (AT), resistance training (RT) or a combination of both (ATRT) and cardiorespiratory fitness (CRF) in individuals with T2DM. Material and Methods A total of 196 participants were randomly assigned to a control, AT, RT, or combined ATRT for a 9-months intervention. The exposure variable was change in muscle quality [(Post: leg muscle strength/leg muscle mass)-[(Pre: leg muscle strength/leg muscle mass)]. Dependent variables were change in CRF measures including absolute and relative VO2peak, and treadmill time to exhaustion (TTE) and estimated metabolic equivalent task (METs). Results Continuous change in muscle quality was independently associated with change in absolute (β = 0.015; p = 0.019) and relative (β = 0.200; p = 0.005) VO2peak, and TTE (β = 0.170; p = 0.043), but not with estimated METs (p > 0.05). A significant trend was observed across tertiles of change in muscle quality for changes in absolute (β = 0.050; p = 0.005) and relative (β = 0.624; p = 0.002) VO2peak following 9 months of exercise training. No such association was observed for change in TTE and estimated METs (p > 0.05). Discussion: The results from this ancillary study suggest that change in muscle quality following exercise training is associated with a greater improvement in CRF in individuals with T2DM. Given the effect RT has on increasing muscle quality, especially as part of a recommended training program (ATRT), individuals with T2DM should incorporate RT into their AT regimens to optimize CRF improvement

Susceptibility to corticosteroid-induced adrenal suppression: a genome-wide association study

\ua9 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: A serious adverse effect of corticosteroid therapy is adrenal suppression. Our aim was to identify genetic variants affecting susceptibility to corticosteroid-induced adrenal suppression. Methods: We enrolled children with asthma who used inhaled corticosteroids as part of their treatment from 25 sites across the UK (discovery cohort), as part of the Pharmacogenetics of Adrenal Suppression with Inhaled Steroids (PASS) study. We included two validation cohorts, one comprising children with asthma (PASS study) and the other consisting of adults with chronic obstructive pulmonary disorder (COPD) who were recruited from two UK centres for the Pharmacogenomics of Adrenal Suppression in COPD (PASIC) study. Participants underwent a low-dose short synacthen test. Adrenal suppression was defined as peak cortisol less than 350 nmol/L (in children) and less than 500 nmol/L (in adults). A case-control genome-wide association study was done with the control subset augmented by Wellcome Trust Case Control Consortium 2 (WTCCC2) participants. Single nucleotide polymorphisms (SNPs) that fulfilled criteria to be advanced to replication were tested by a random-effects inverse variance meta-analysis. This report presents the primary analysis. The PASS study is registered in the European Genome-phenome Archive (EGA). The PASS study is complete whereas the PASIC study is ongoing. Findings: Between November, 2008, and September, 2011, 499 children were enrolled to the discovery cohort. Between October, 2011, and December, 2012, 81 children were enrolled to the paediatric validation cohort, and from February, 2010, to June, 2015, 78 adults were enrolled to the adult validation cohort. Adrenal suppression was present in 35 (7%) children in the discovery cohort and six (7%) children and 17 (22%) adults in the validation cohorts. In the discovery cohort, 40 SNPs were found to be associated with adrenal suppression (genome-wide significance p&lt;1 7 10−6), including an intronic SNP within the PDGFD gene locus (rs591118; odds ratio [OR] 7\ub732, 95% CI 3\ub715–16\ub799; p=5\ub78 7 10−8). This finding for rs591118 was validated successfully in both the paediatric asthma (OR 3\ub786, 95% CI 1\ub719–12\ub750; p=0\ub702) and adult COPD (2\ub741, 1\ub710–5\ub728; p=0\ub703) cohorts. The proportions of patients with adrenal suppression by rs591118 genotype were six (3%) of 214 patients with the GG genotype, 15 (6%) of 244 with the AG genotype, and 22 (25%) of 87 with the AA genotype. Meta-analysis of the paediatric cohorts (discovery and validation) and all three cohorts showed genome-wide significance of rs591118 (respectively, OR 5\ub789, 95% CI 2\ub797–11\ub768; p=4\ub73 7 10−9; and 4\ub705, 2\ub700–8\ub721; p=3\ub75 7 10−10). Interpretation: Our findings suggest that genetic variation in the PDGFD gene locus increases the risk of adrenal suppression in children and adults who use corticosteroids to treat asthma and COPD, respectively. Funding: Department of Health Chair in Pharmacogenetics

Neural responses to others’ pain vary with psychopathic traits in healthy adult males

Disrupted empathic processing is a core feature of psychopathy. Neuroimaging data have suggested that individuals with high levels of psychopathic traits show atypical responses to others' pain in a network of brain regions typically recruited during empathic processing (anterior insula, inferior frontal gyrus, and mid- and anterior cingulate cortex). Here, we investigated whether neural responses to others' pain vary with psychopathic traits within the general population in a similar manner to that found in individuals at the extreme end of the continuum. As predicted, variation in psychopathic traits was associated with variation in neural responses to others' pain in the network of brain regions typically engaged during empathic processing. Consistent with previous research, our findings indicated the presence of suppressor effects in the association of levels of the affective-interpersonal and lifestyle-antisocial dimensions of psychopathy with neural responses to others' pain. That is, after controlling for the influence of the other dimension, higher affective-interpersonal psychopathic traits were associated with reduced neural responses to others' pain, whilst higher lifestyle-antisocial psychopathic traits were associated with increased neural responses to others' pain. Our findings provide further evidence that atypical function in this network might represent neural markers of disrupted emotional and empathic processing; that the two dimensions of psychopathy might tap into distinct underlying vulnerabilities; and, most importantly, that the relationships observed at the extreme end of the psychopathy spectrum apply to the nonclinical distribution of these traits, providing further evidence for continuities in the mechanisms underlying psychopathic traits across the general population