Posterior cortical atrophy : impact on daily living activities and exploration of a cognitive rehabilitation approach

Posterior cortical atrophy (PCA) is a neurodegenerative disease affecting the posterior region of the brain. Little is known about both the impact of PCA on functioning and how to support patients on a daily basis. The purpose of this study was to describe the functional profile of DD, a woman diagnosed with PCA, as well as to explore a pilot cognitive rehabilitation program designed to optimize functioning in daily living. The ADL Profile was used to assess the daily tasks that DD chose to undertake. Four operations, i.e. formulate a goal, plan, carry out and verify goal attainment, were scored for each task. Difficulties were observed during the execution of all tasks, as she struggled to find items or showed unsafe behaviors. Impairments were also seen in formulating a goal and planning, especially for less routine tasks. DD identified two tasks to be addressed in rehabilitation: setting the table and dealing cards. Learning was optimized using errorless learning and compensatory aids when setting the table, while dealing cards received no intervention. Only setting the table improved significantly with time. Further studies should be conducted to portray a wider functional profile of people living with PCA and develop effective rehabilitation programs

Synthesis of spiroacetals using functionalised titanium carbenoids

Alkylidenation of lactones with functionalised titanium carbenoid reagents (Schrock carbenes) followed by acid-induced cyclisation of the resulting enol ethers constitutes a new method for the preparation of [4.4], [4.5] and [5.5] spiroacetals (1,6-dioxaspiro[4.4]nonanes, 1,6-dioxaspiro[4.5]decanes and 1,7-dioxaspiro[5.5]undecanes, respectively, sometimes termed 5,5-, 5,6- and 6,6-spiroketals). The titanium carbenoids are easily generated from readily available thioacetals

The <i>Rosetta</i> Mission and the Chemistry of Organic Species in Comet 67P/Churyumov–Gerasimenko

Comets are regarded as probably the most primitive of solar system objects, preserving a record of the materials from which the solar system aggregated. Key amongst their components are organic compounds – molecules that may trace their heritage to the interstellar medium from which the protosolar nebula eventually emerged. The most recent cometary space mission, Rosetta, carried instruments designed to characterize, in unprecedented detail, the organic species in comet 67P/Churyumov–Gerasimenko (67P). Rosetta was the first mission to match orbits with a comet and follow its evolution over time, and also the first mission to land scientific instruments on a comet surface. Results from the mission revealed a greater variety of molecules than previously identified and indicated that 67P contained both primitive and processed organic entities

Impact of simulated brain interstitial fluid flow on the chemokine CXCL12 release from an alginate-based hydrogel in a new 3D in vitro model

ABSTRACT: Introduction: Extensive investigation has been undertaken regarding drug delivery systems for the management of glioblastoma multiforme (GBM). The infiltrative behavior of GBM cells within the brain tissue is primarily attributed to their heterogeneity, the movement of interstitial fluid (IFF), and the presence of chemokines. These factors contribute to the limited effectiveness of current conventional treatments. To address the dissemination of GBM cells, a proposed therapeutic approach involves utilizing a controlled release gradient of CXC-chemokine-ligand-12 (CXCL12). However, the impact of IFF on GBM cell migration within the brain underscores its critical importance as a significant parameter, which, surprisingly, has not been extensively studied in the context of localized drug delivery targeting the brain. Methods: Hydrogels are known for their inherent capacity to entrap various agents and exert precise control over their subsequent release. In the present investigation, we aimed to elucidate the release kinetics of CXCL12, whether in its free form or encapsulated within nanoparticles, from alginate-based hydrogels, both under static and dynamic conditions. To investigate the impact of convective forces mimicking the interstitial fluid flow (IFF) within the peritumoral environment of the brain, a three-dimensional in vitro model was developed. This model enabled the evaluation of CXCL12 release as a function of time and position, specifically accounting for the contribution of simulated IFF on the release behavior. Results: We first demonstrated that the release kinetic profiles under static culture conditions were independent of the initial mass loading and the predominant phenomenon occurring was diffusion. Subsequently, we investigated the release of CXCL12, which was loaded into Alginate/Chitosan-Nanoparticles (Alg/Chit-NPs) and embedded within an alginate hydrogel matrix. Mathematical modeling results also indicated the presence of electrostatic interactions between alginate and CXCL12. The Alg/Chit-NPs effectively slowed down the initial burst release, leading to a reduction in the diffusion coefficient of CXCL12. To further study the release behavior, we developed a perfusion bioreactor with a unique culture chamber designed to recapitulate the peritumoral environment and varied the fluid flow rates at 0.5 µL/min, 3 µL/min, 6.5 µL/min, and 10 µL/min. As the flow rate increased, the cumulative amount of released CXCL12 also increased for all three initial mass loadings. Beyond 3 µL/min, convection became the dominant mechanism governing CXCL12 release, whereas below this threshold, diffusion played a more prominent role. Conclusion: The indirect perfusion flow had a crucial impact on CXCL12 release and distribution inside the hydrogel in and against its direction. This system highlights the importance of considering the IFF in brain targeting delivery system and will be used in the future to study GBM cell behaviors in response to CXCL12 gradient

The treatment experiences of people living with ileostomies: an interpretative phenomenological analysis

AIMS: To explore treatment and healthcare experiences of people living with ileostomies, so nurses can build on best practice whilst caring for these patients. Background Ileostomies, in which the small intestine is re-directed out of a stoma in the abdominal wall so waste is collected using a bag, are used to treat conditions including Inflammatory Bowel Disease. Existing research suggests that although life with a stoma can be challenging, ileostomy patients are largely supported by multi-disciplinary teams. However, more research is needed to understand the nuances of these relationships and experiences of treatment, with a view to improving clinical care. DESIGN: Participants took part in semi-structured interviews consisting of open ended questions about their experiences of life with an ileostomy and their treatments and time in hospital. Points of interest were followed up. Data were collected between July and December of 2014. METHODS: The qualitative method Interpretative Phenomenological Analysis was used to analyse interviews with 21 people living with ileostomies. FINDINGS: We present findings from two clinical themes: Issues around treatment and Relationships with multi-disciplinary teams. Surgical complications were common, and several participants reported concerns about addiction to painkillers. Varying attitudes were found around reversal surgery. Many reported experiencing distressing, dehumanising care, whilst some felt supported by excellent healthcare providers. CONCLUSION: People living with ileostomies have a very mixed experience of multi-disciplinary teams and treatments, and much could be done to support them more fully. For example, more information about ileostomies could be given to patients and more training given to nurses around stomas

Demonstration of Universal Parametric Entangling Gates on a Multi-Qubit Lattice

We show that parametric coupling techniques can be used to generate selective entangling interactions for multi-qubit processors. By inducing coherent population exchange between adjacent qubits under frequency modulation, we implement a universal gateset for a linear array of four superconducting qubits. An average process fidelity of $\mathcal{F}=93\%$ is estimated for three two-qubit gates via quantum process tomography. We establish the suitability of these techniques for computation by preparing a four-qubit maximally entangled state and comparing the estimated state fidelity against the expected performance of the individual entangling gates. In addition, we prepare an eight-qubit register in all possible bitstring permutations and monitor the fidelity of a two-qubit gate across one pair of these qubits. Across all such permutations, an average fidelity of $\mathcal{F}=91.6\pm2.6\%$ is observed. These results thus offer a path to a scalable architecture with high selectivity and low crosstalk

Age-related decline of peripheral visual processing: the role of eye movements

Earlier work suggests that the area of space from which useful visual information can be extracted (useful field of view, UFoV) shrinks in old age. We investigated whether this shrinkage, documented previously with a visual search task, extends to a bimanual tracking task. Young and elderly subjects executed two concurrent tracking tasks with their right and left arms. The separation between tracking displays varied from 3 to 35 cm. Subjects were asked to fixate straight ahead (condition FIX) or were free to move their eyes (condition FREE). Eye position was registered. In FREE, young subjects tracked equally well at all display separations. Elderly subjects produced higher tracking errors, and the difference between age groups increased with display separation. Eye movements were comparable across age groups. In FIX, elderly and young subjects tracked less well at large display separations. Seniors again produced higher tracking errors in FIX, but the difference between age groups did not increase reliably with display separation. However, older subjects produced a substantial number of illicit saccades, and when the effect of those saccades was factored out, the difference between young and older subjects’ tracking did increase significantly with display separation in FIX. We conclude that the age-related shrinkage of UFoV, previously documented with a visual search task, is observable with a manual tracking task as well. Older subjects seem to partly compensate their deficit by illicit saccades. Since the deficit is similar in both conditions, it may be located downstream from the convergence of retinal and oculomotor signals

Constraints on perception of information from obstacles during foot clearance in people with chronic stroke

The aim of this study was to examine effects of different types of task constraints on coupling of perception and action in people with chronic stroke when crossing obstacles during a walking task. Ten participants with hemiplegic chronic stroke volunteered to walk over a static obstacle under two distinct task constraints: simple and dual task. Under simple task constraints, without specific instructions, participants walked at their preferred speed and crossed over an obstacle. Under dual task constraints the same individuals were required to subtract numbers whilst walking. Under both distinct task constraints, we examined emergent values of foot distance when clearing a static obstacle in both affected and unaffected legs, measured by a 3D motion tracking system. Principal Component Analysis was used to quantify task performance and discriminant analysis was used to compare gait performance between task constraints. Results suggested that patients, regardless of affected body side, demonstrated differences in perception of distance information from the obstacle, which constrained gait differences in initial swing, mid-swing and crossing phases. Further, dual task constraints, rather than hemiplegic body side, was a significant discriminator in patients' perceptions of distance and height information to the obstacle. These findings suggested how performance of additional cognitive tasks might constrain perception of information from an obstacle in people with chronic stroke during different phases of obstacle crossing, and thus may impair their adaptive ability to successfully manoeuvre around objects

Communicating Auditory Impairments Using Electroacoustic Composition

Changes in human sensory perception can occur for a variety of reasons. In the case of distortions or transformations in the human auditory system, the aetiology may include factors such as medical conditions affecting cognition or physiology, interaction of the ears with mechanical waves, or stem from chemically induced sources, such the consumption of alcohol. These changes may be permanent, intermittent, or temporary. In order to communicate such effects to an audience in an accessible, and easily understood manner, a series of electroacoustic compositions were produced. This concept follows on from previous work on the theme of representing auditory hallucinations. Specifically, these compositions relate to auditory impairments that humans can experience due to tinnitus or through the consumption of alcohol. In the case of tinnitus, whilst much is known about the causes and symptoms, the experience of what it is like to live with tinnitus is less explored and those who have acquired the condition may often feel frustration when trying to convey the experience of ‘what it is like’ for them. In terms of impairment from alcohol consumption, whilst there is much hearsay, little research exists on the immediate and short-term effects of alcohol consumption on the human auditory system, despite over half of the UK population reported as consuming alcohol in 2017. The methodology employed to design these compositions draws upon scientific research findings, including experimental and explorative studies involving human participants, coupled with electroacoustic composition techniques. The pieces are typically constructed by mixing field recordings with synthesised materials and incorporating a range of temporal and frequency domain manipulations to the elements therein. In this way, the listener is able to experience the phenomenon in a recognisable context, where distortions of reality can be emulated to varying degrees. It is intended that these compositions can serve as easily accessible and understood examples of auditory impairments and that they might find utility in the communication of symptoms to those who have never experienced the underlying causes or conditions. This presents opportunities for pieces like these to be used in scenarios such as education and public health awareness campaigns