Insensitivity to loss predicts apathy in Huntington's disease

Background Apathy is a deficit in goal‐directed behavior that significantly affects quality of life and function. It is common in Huntington's disease and other disorders affecting corticostriatal pathways. Deficits in processing of reward, altered effort, and executive dysfunction are associated with apathy in other disorders, but the cognitive processes leading to apathy in Huntington's disease remain largely unknown. A previously reported deficit in learning from losses in Huntington's disease raises the possibility of a hitherto unrecognized mechanism leading to apathy. This study's objective was to delineate the cognitive processes associated with apathy in HD. Methods We tested 51 Huntington's disease participants and 26 controls on a battery of novel and established measures to assess the contribution to apathy in Huntington's disease of executive function, reward value, reward‐effort calculations, instrumental learning, and response to reward and loss. Results Huntington's disase participants had deficits in instrumental learning with impaired response to loss, but no evidence to suggest altered reward‐related behavior or effort. We also saw an executive dysfunction contribution to apathy in Huntington's disease. Discussion We report the novel finding that apathy in Huntington's disease is associated with blunted responses to losses and impaired instrumental learning. This association is consistent with the known early degeneration of the indirect pathway and amygdala involvement in apathy in Huntington's disease, but is previously unreported in any disorder. In keeping with the comparative preservation of the ventral striatum and orbitofrontal cortex in Huntington's disease, reward valuation and reward‐effort calculations did not contribute to apathy

Strain-dependent and distinctive T-cell responses to HIV antigens following immunisation of mice with differing chimpanzee adenovirus vaccine vectors

In vivo vaccination studies are conventionally conducted in a single mouse strain with results, only reflecting responses to a single immunogenetic background. We decided to examine the immune response to an HIV transgene (gag, pol and nef fusion protein) in 3 strains of mice (CBA, C57BL/6 and BALB/c) to determine the spectrum of responses and in addition to determine whether the serotype of the adenoviral vector used (ChAd3 and ChAd63) impacted the outcome of response. Our results demonstrated that all three strains of mice responded to the transgene and that the magnitude of responses were different between the strains. The C57BL/6 strain showed the lowest range of responses compared to the other strains and, very few responses were seen to the same peptide pool in all three strains of mice. In CBA and BALB/c mice there were significant differences in IFNγ production dependent on the adenoviral vector used. Our results suggest that employing a single strain of mouse may underestimate the efficacy and efficiency of vaccine products

PENGARUH PENGGUNAAN ETIKET BRAILLE TERHADAP PEMAHAMAN DAN KEPATUHAN MINUM OBAT PADA PASIEN PENYANDANG TUNANETRA DI PUSKESMAS JANTI KOTA MALANG

Tunanetra adalah tidak berfungsinya indra penglihatan yaitu mata karena kecelakaan atau kecacatan. Menyebabkan tunanetra sulit memahami aturan minum obat setiap harinya ini memicu pengaruh pemahaman dan kepatuhan minum obat pasien penyandang tunanetra. Penelitian ini bertujuan untuk mengetahui pengaruh penggunaan etiket Braille terhadap tingkat kepahaman dan kepatuhan aturan minum obat. Jenis penelitian termasuk metode Pra-eskperimen dengan rancangan perbandingan kelompok statis (Static Group Comprarison),dengan pengambilan sampel Consecutive sampling, instrument penelitian dengan kuesioner kepada 30 responden. Hasil penelitian menunjukkan tingkat pemahaman pada kelompok kontrol 61,67%, sementara kelompok perlakuan sebesar 100%. Untuk kepatuhan kelompok kontrol sebesar 3,65%, dan kelompok perlakuan sebesar 7,92%. Hasil uji Mann Whitey didapat nilai p signifikansi 0,000 < 0,05 terhadap pengaruh penggunaan etiket Braille terhadap pemahaman dan kepatuhan minum obat. Kata Kunci : Pemahaman, Kepatuhan, Aturan Minum Obat, Etiket Braille, Tunanetra, Puskesma

Indicators of relative completeness of the glacial record of the Port Askaig Formation, Garvellach Islands, Scotland

The Port Askaig Formation (PAF) is a diamictite-bearing succession in the Dalradian Supergroup of Scotland that provides an excellent archive of a Cryogenian glaciation in the Garvellach Islands and Islay, Argyll. The formation is ∼1100 m thick, comprises 5 members and includes 47 diamictite beds, interbedded with siltstones, dolostones and sandstones. Here we document seven features of the PAF that indicate its relative stratigraphic completeness. There are gradual, progressive changes up-section in the lithologies of the diamictites, their interbeds, and clast lithologies. The sharp basal surfaces of the diamictites each show the same, repeated pattern of environmental change, from non-glacial to glacial. Many of the top surfaces of the diamictites show evidence of periglacial conditions. The succession in the PAF records a total of 76 climatically-related stratigraphic episodes: 28 glacial episodes, 25 periglacial episodes and 23 non-glacial episodes. Parts of Member 1 (Diamictites 1–12 and Diamictites 16–18) and Member 2 (Diamictite 31 to the base of Member 3) are most compete on the east coast of Garbh Eileach. The PAF in the Garvellach Islands occurs within a succession that is several kilometres thick, as newly revealed by sea-floor mapping. Compared with other Cryogenian and Phanerozoic glacial successions, the PAF is exceptional in its combination of formation thickness, the number of climatically-related stratigraphic episodes, and the considerable thickness of its host supergroup. Furthermore, these indicators of relative stratigraphic completeness provide evidence that the base of the PAF on the east coast of Garbh Eileach is a succession without a major break in deposition, supporting the account of the strata at and below the base of the PAF in the companion article by Fairchild et al. (2018)

Dopamine modulates dynamic decision-making during foraging

The mesolimbic dopaminergic system exerts a crucial influence on incentive processing. However, the contribution of dopamine in dynamic, ecological situations where reward rates vary, and decisions evolve over time, remains unclear. In such circumstances, current (foreground) reward accrual needs to be compared continuously with potential rewards that could be obtained by travelling elsewhere (background reward rate), in order to determine the opportunity cost of staying versus leaving. We hypothesised that dopamine specifically modulates the influence of background – but not foreground – reward information when making a dynamic comparison of these variables for optimal behaviour. On a novel foraging task based on an ecological account of animal behaviour (marginal value theorem), human participants of either sex decided when to leave locations in situations where foreground rewards depleted at different rates, either in rich or poor environments with high or low background rates. In line with theoretical accounts, people’s decisions to move from current locations were independently modulated by changes in both foreground and background reward rates. Pharmacological manipulation of dopamine D2 receptor activity using the agonist cabergoline significantly affected decisions to move on, specifically modulating the effect of background reward rates. In particular, when on cabergoline, people left patches in poor environments much earlier. These results demonstrate a role of dopamine in signalling the opportunity cost of rewards, not value per se. Using this ecologically derived framework we uncover a specific mechanism by which D2 dopamine receptor activity modulates decision-making when foreground and background reward rates are dynamically compared

New Perspectives on Glacial Geomorphology in Earth's Deep Time Record

International audienceThe deep time (pre-Quaternary) glacial record is an important means to understand the growth, development, and recession of the global cryosphere on very long timescales (10 6-10 8 Myr). Sedimentological description and interpretation of outcrops has traditionally played an important role. Whilst such data remain vital, new insights are now possible thanks to freely accessible aerial and satellite imagery, the widespread availability and affordability of Uncrewed Aerial Vehicles, and accessibility to 3D rendering software. In this paper, we showcase examples of glaciated landscapes from the Cryogenian, Ediacaran, Late Ordovician and Late Carboniferous where this approach is revolutionizing our understanding of deep time glaciation. Although some problems cannot be overcome (erosion or dissolution of the evidence), robust interpretations in terms of the evolving subglacial environment can be made. Citing examples from Australia (Cryogenian), China (Ediacaran), North and South Africa (Late Ordovician, Late Carboniferous), and Namibia (Late Carboniferous), we illustrate how the power of glacial geomorphology can be harnessed to interpret Earth's ancient glacial record