Eye position signal modulates a human parietal pointing region during memory-guided movements.

Using functional magnetic resonance imaging, we examined the signal in parietal regions that were selectively activated during delayed pointing to flashed visual targets and determined whether this signal was dependent on the fixation position of the eyes. Delayed pointing activated a bilateral parietal area in the intraparietal sulcus (rIPS), rostral/anterior to areas activated by saccades. During right-hand pointing to centrally located targets, the left rIPS region showed a significant increase in activation when the eye position was rightward compared with leftward. As expected, activation in motor cortex showed no modulation when only eye position changed. During pointing to retinotopically identical targets, the left rIPS region again showed a significant increased signal when the eye position was rightward compared with leftward. Conversely, when pointing with the left arm, the right rIPS showed an increase in signal when eye position was leftward compared with rightward. The results suggest that the human parietal hand/arm movement region (rIPS), like monkey parietal areas (Andersen et al., 1985), exhibits an eye position modulation of its activity; modulation that may be used to transform the coordinates of the retinotopically coded target position into a motor error command appropriate for the wrist

Deprescribing in multi-morbid older people with polypharmacy: agreement between STOPPFrail explicit criteria and gold standard deprescribing using 100 standardized clinical cases

Purpose: Older people with advanced frailty are among the highest consumers of medications. When life expectancy is limited, some of these medications are likely to be inappropriate. The aim of this study was to compare STOPPFrail, a concise, easy-to-use, deprescribing tool based on explicit criteria, with gold standard, systematic geriatrician-led deprescribing. Methods: One hundred standardized clinical cases involving 1024 medications were prepared. Clinical cases were based on anonymized hospitalized patients aged ≥ 65 years, with advanced frailty (Clinical Frailty Scale ≥ 6), receiving ≥ 5 regular medications, who were selected from a recent observational study. Level of agreement between deprescribing methods was measured by Cohen’s kappa coefficient. Sensitivity and positive predictive value of STOPPFrail-guided deprescribing relative to gold standard deprescribing was also measured. Results: Overall, 524 medications (51.2%) of medications prescribed to this frail, elderly cohort were potentially inappropriate by gold standard criteria. STOPPFrail-guided deprescribing led to the identification of 70.2% of the potentially inappropriate medications. Cohen’s kappa was 0.60 (95% confidence interval 0.55–0.65; p < 0.001) indicating moderate agreement between STOPPFrail-guided and gold standard deprescribing. The positive predictive value of STOPPFrail was 89.3% indicating that the great majority of deprescribing decisions aligned with gold standard care. Conclusions: STOPPFrail removes an important barrier to deprescribing by explicitly highlighting circumstances where commonly used medications can be safely deprescribed in older people with advanced frailty. Our results suggest that in multi-morbid older patients with advanced frailty, the use of STOPPFrail criteria to address inappropriate polypharmacy may be reasonable alternative to specialist medication review

Discipline, debt and coercive commodification:Post-crisis neoliberalism and the welfare state in Ireland, the UK and the USA

Ireland, the UK and the USA are heterogeneous examples of liberal worlds of welfare capitalism yet all three countries were deeply implicated in the 2008 global financial crisis. Examining these three countries together provides the opportunity to further develop an international comparative political economy of instability in the context of the globalised and financialised dimensions of Anglo-liberal capitalism and disciplinary governance. Our analysis is guided by the concept of disciplinary neoliberalism (Gill, 1995) through which we explore: (i) the dynamics that have shaped the impacts of and responses to the Great Recession; (ii) the ways in which state-market relations, shaped by differentiated accommodations to market imperative or market discipline, have been used as disciplinary tools and how these have interacted with existing social divisions and iii) the implications for shaping conditions for resistance. We suggest that the neoliberal pathways of each country, whilst not uniform, mark a ‘step-change’ and acceleration in the operation of disciplinary neoliberalism, and is particularly evident in what we identify as the coercive commodification of social policy

Mapping the Organization of Axis of Motion Selective Features in Human Area MT Using High-Field fMRI

Functional magnetic resonance imaging (fMRI) at high magnetic fields has made it possible to investigate the columnar organization of the human brain in vivo with high degrees of accuracy and sensitivity. Until now, these results have been limited to the organization principles of early visual cortex (V1). While the middle temporal area (MT) has been the first identified extra-striate visual area shown to exhibit a columnar organization in monkeys, evidence of MT's columnar response properties and topographic layout in humans has remained elusive. Research using various approaches suggests similar response properties as in monkeys but failed to provide direct evidence for direction or axis of motion selectivity in human area MT. By combining state of the art pulse sequence design, high spatial resolution in all three dimensions (0.8 mm isotropic), optimized coil design, ultrahigh field magnets (7 Tesla) and novel high resolution cortical grid sampling analysis tools, we provide the first direct evidence for large-scale axis of motion selective feature organization in human area MT closely matching predictions from topographic columnar-level simulations

Economic crisis and youth unemployment: Comparing Greece and Ireland

Both Greece and Ireland have long suffered high youth unemployment rates and have been pressured to restructure their employment and social systems under the European Employment Strategy. Problems were aggravated by the harsh conditions imposed by the Troika following bail-outs. Yet there was significant divergence in youth employment outcomes between Greece and Ireland despite a convergence of policies. In Ireland, tighter conditionality of benefits and stronger ‘activation’ were already on the agenda of the social actors, so their implementation was not forcefully contested. In Greece, the lack of effective social protection made it difficult for successive governments to build support for flexibilization, and the escalating insecurity of young Greeks and their families gave rise to social unrest and political instability. This contrast leads to a reappraisal of the convergence–divergence debat

Origem e distribuição do plexo braquial de Saimiri sciureus

Os autores descreveram a origem e composição do plexo braquial de quatro Saimiri sciureus, pertencentes ao Centro Nacional de Primatas (Cenp), Ananindeua/PA, os quais foram fixados com formaldeído e dissecados. Os achados revelaram que o plexo braquial desta espécie é constituído por fibras neurais provenientes da união das raízes dorsais e ventrais das vértebras cervicais C4 a C8 e torácica T1, e organizado em quatro troncos. Cada tronco formou um nervo ou um grupo de nervos, cuja origem variou entre os animais; na maioria, foi encontrado o tronco cranial originando o nervo subclávio, o tronco médio-cranial dando origem aos nervos supraescapular, subescapular, parte do radial, e em alguns casos ao nervo axilar, nervo musculocutâneo e ao nervo mediano; o tronco médio-caudal formou parte do nervo radial, e em alguns casos os nervos axilar, nervo musculocutâneo, nervo mediano, nervo toracodorsal, nervo ulnar e nervo cutâneo medial do antebraço, sendo os dois últimos também originados no tronco caudal

Nitrated α–Synuclein Immunity Accelerates Degeneration of Nigral Dopaminergic Neurons

The neuropathology of Parkinson's disease (PD) includes loss of dopaminergic neurons in the substantia nigra, nitrated alpha-synuclein (N-alpha-Syn) enriched intraneuronal inclusions or Lewy bodies and neuroinflammation. While the contribution of innate microglial inflammatory activities to disease are known, evidence for how adaptive immune mechanisms may affect the course of PD remains obscure. We reasoned that PD-associated oxidative protein modifications create novel antigenic epitopes capable of peripheral adaptive T cell responses that could affect nigrostriatal degeneration.Nitrotyrosine (NT)-modified alpha-Syn was detected readily in cervical lymph nodes (CLN) from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice. Antigen-presenting cells within the CLN showed increased surface expression of major histocompatibility complex class II, initiating the molecular machinery necessary for efficient antigen presentation. MPTP-treated mice produced antibodies to native and nitrated alpha-Syn. Mice immunized with the NT-modified C-terminal tail fragment of alpha-Syn, but not native protein, generated robust T cell proliferative and pro-inflammatory secretory responses specific only for the modified antigen. T cells generated against the nitrated epitope do not respond to the unmodified protein. Mice deficient in T and B lymphocytes were resistant to MPTP-induced neurodegeneration. Transfer of T cells from mice immunized with N-alpha-Syn led to a robust neuroinflammatory response with accelerated dopaminergic cell loss.These data show that NT modifications within alpha-Syn, can bypass or break immunological tolerance and activate peripheral leukocytes in draining lymphoid tissue. A novel mechanism for disease is made in that NT modifications in alpha-Syn induce adaptive immune responses that exacerbate PD pathobiology. These results have implications for both the pathogenesis and treatment of this disabling neurodegenerative disease

Proteomic characterization of HIV-modulated membrane receptors, kinases and signaling proteins involved in novel angiogenic pathways

<p>Abstract</p> <p>Background</p> <p>Kaposi's sarcoma (KS), hemangioma, and other angioproliferative diseases are highly prevalent in HIV-infected individuals. While KS is etiologically linked to the human herpesvirus-8 (HHV8) infection, HIV-patients without HHV-8 and those infected with unrelated viruses also develop angiopathies. Further, HIV-Tat can activate protein-tyrosine-kinase (PTK-activity) of the vascular endothelial growth factor receptor involved in stimulating angiogenic processes. However, Tat by itself or HHV8-genes alone cannot induce angiogenesis <it>in vivo </it>unless specific proteins/enzymes are produced synchronously by different cell-types. We therefore tested a hypothesis that <it>chronic </it>HIV-<it>replication in non-endothelial cells </it>may produce novel factors that provoke angiogenic pathways.</p> <p>Methods</p> <p>Genome-wide proteins from HIV-infected and uninfected T-lymphocytes were tested by subtractive proteomics analyses at various stages of virus and cell growth <it>in vitro </it>over a period of two years. Several thousand differentially regulated proteins were identified by mass spectrometry (MS) and >200 proteins were confirmed in multiple gels. Each protein was scrutinized extensively by protein-interaction-pathways, bioinformatics, and statistical analyses.</p> <p>Results</p> <p>By functional categorization, 31 proteins were identified to be associated with various signaling events involved in angiogenesis. 88% proteins were located in the plasma membrane or extracellular matrix and >90% were found to be essential for regeneration, neovascularization and angiogenic processes during embryonic development.</p> <p>Conclusion</p> <p>Chronic HIV-infection of T-cells produces membrane receptor-PTKs, serine-threonine kinases, growth factors, adhesion molecules and many diffusible signaling proteins that have not been previously reported in HIV-infected cells. Each protein has been associated with endothelial cell-growth, morphogenesis, sprouting, microvessel-formation and other biological processes involved in angiogenesis (p = 10^-4to 10^-12). Bioinformatics analyses suggest that overproduction of PTKs and other kinases in HIV-infected cells has <it>suppressed </it>VEGF/VEGFR-PTK expression and promoted <it>VEGFR-independent </it>pathways. This unique mechanism is similar to that observed in neovascularization and angiogenesis during embryogenesis. Validation of clinically relevant proteins by gene-silencing and translational studies <it>in vivo </it>would identify specific targets that can be used for early diagnosis of angiogenic disorders and future development of inhibitors of angiopathies. This is the first comprehensive study to demonstrate that HIV-infection alone, without any co-infection or treatment, can induce numerous "embryonic" proteins and kinases capable of generating novel <it>VEGF-independent </it>angiogenic pathways.</p