Palliative care for patients with motor neurone disease: current challenges

Motor neurone disease is a progressive disease, and the patient and his/her family face many challenges during the disease progression, with increasing weakness and multiple losses of function. The provision of care for these patients and their families is equally challenging, anticipating and responding to the person's needs. There are increasing challenges as more is understood about the disease and its management, including the genetic basis, cognitive change, the use of interventions such as ventilatory support, and gastrostomy. There is also an increasing need to ensure that the later stages are recognized so that all can be more prepared for the end of life, including recognition of deterioration and end of life, advance care planning, symptom management and psychosocial care at the end of life, and coping with requests for assisted dying. Careful assessment and good multidisciplinary team (MDT) work can enable patients and their families to have as good a quality of life as possible, and allow a peaceful death of the patient

A study of event traffic during the shared manipulation of objects within a collaborative virtual environment

Event management must balance consistency and responsiveness above the requirements of shared object interaction within a Collaborative Virtual Environment (CVE) system. An understanding of the event traffic during collaborative tasks helps in the design of all aspects of a CVE system. The application, user activity, the display interface, and the network resources, all play a part in determining the characteristics of event management. Linked cubic displays lend themselves well to supporting natural social human communication between remote users. To allow users to communicate naturally and subconsciously, continuous and detailed tracking is necessary. This, however, is hard to balance with the real-time consistency constraints of general shared object interaction. This paper aims to explain these issues through a detailed examination of event traffic produced by a typical CVE, using both immersive and desktop displays, while supporting a variety of collaborative activities. We analyze event traffic during a highly collaborative task requiring various forms of shared object manipulation, including the concurrent manipulation of a shared object. Event sources are categorized and the influence of the form of object sharing as well as the display device interface are detailed. With the presented findings the paper wishes to aid the design of future systems

The expression of stlA in Photorhabdus luminescens is controlled by nutrient limitation

Photorhabdus is a genus of Gram-negative entomopathogenic bacteria that also maintain a mutualistic association with nematodes from the family Heterorhabditis. Photorhabdus has an extensive secondary metabolism that is required for the interaction between the bacteria and the nematode. A major component of this secondary metabolism is a stilbene molecule, called ST. The first step in ST biosynthesis is the non-oxidative deamination of phenylalanine resulting in the production of cinnamic acid. This reaction is catalyzed by phenylalanine-ammonium lyase, an enzyme encoded by the stlA gene. In this study we show, using a stlA-gfp transcriptional fusion, that the expression of stlA is regulated by nutrient limitation through a regulatory network that involves at least 3 regulators. We show that TyrR, a LysR-type transcriptional regulator that regulates gene expression in response to aromatic amino acids in E. coli, is absolutely required for stlA expression. We also show that stlA expression is modulated by σS and Lrp, regulators that are implicated in the regulation of the response to nutrient limitation in other bacteria. This work is the first that describes pathway-specific regulation of secondary metabolism in Photorhabdus and, therefore, our study provides an initial insight into the complex regulatory network that controls secondary metabolism, and therefore mutualism, in this model organism

On a strong form of Oliver’s p-group conjecture.

We introduce a stronger and more tractable form of Olivers p-group conjecture, and derive a reformulation in terms of the modular representation theory of a quotient group. The Sylow p-subgroups of the symmetric group Sn and of the general linear group satisfy both the strong conjecture and its reformulation

Stress-Induced Cocaine Seeking Requires a Beta-2 Adrenergic Receptor-Regulated Pathway from the Ventral Bed Nucleus of the Stria Terminalis That Regulates CRF Actions in the Ventral Tegmental Area

The ventral bed nucleus of the stria terminalis (vBNST) has been implicated in stress-induced cocaine use. Here we demonstrate that, in the vBNST, corticotropin releasing factor (CRF) is expressed in neurons that innervate the ventral tegmental area (VTA), a site where the CRF receptor antagonist antalarmin prevents the reinstatement of cocaine seeking by a stressor, intermittent footshock, following intravenous self-administration in rats. The vBNST receives dense noradrenergic innervation and expresses β adrenergic receptors (ARs). Footshock-induced reinstatement was prevented by bilateral intra-vBNST injection of the β-2 AR antagonist, ICI-118,551, but not the β-1 AR antagonist, betaxolol. Moreover, bilateral intra-vBNST injection of the β-2 AR agonist, clenbuterol, but not the β-1 agonist, dobutamine, reinstated cocaine seeking, suggesting that activation of vBNST β-2 AR is both necessary for stress-induced reinstatement and sufficient to induce cocaine seeking. The contribution of a β-2 AR-regulated vBNST-to-VTA pathway that releases CRF was investigated using a disconnection approach. Injection of ICI-118,551 into the vBNST in one hemisphere and antalarmin into the VTA of the contralateral hemisphere prevented footshock-induced reinstatement, whereas ipsilateral manipulations failed to attenuate stress-induced cocaine seeking, suggesting that β-2 AR regulate vBNST efferents that release CRF into the VTA, activating CRF receptors, and promoting cocaine use. Last, reinstatement by clenbuterol delivered bilaterally into the vBNST was prevented by bilateral vBNST pretreatment with antalarmin, indicating that β-2 AR-mediated actions in the vBNST also require local CRF receptor activation. Understanding the processes through which stress induces cocaine seeking should guide the development of new treatments for addiction

Giant pop-ins and amorphization in germanium during indentation

Sudden excursions of unusually large magnitude (>1 μm), “giant pop-ins,” have been observed in the force-displacement curve for high load indentation of crystalline germanium(Ge). A range of techniques including Raman microspectroscopy, focused ion-beam cross sectioning, and transmission electron microscopy, are applied to study this phenomenon. Amorphous material is observed in residual indents following the giant pop-in. The giant pop-in is shown to be a material removal event, triggered by the development of shallow lateral cracks adjacent to the indent. Enhanced depth recovery, or “elbowing,” observed in the force-displacement curve following the giant pop-in is explained in terms of a compliant response of plates of material around the indent detached by lateral cracking. The possible causes of amorphization are discussed, and the implications in light of earlier indentation studies of Ge are considered

Photopatterned Multidomain Gels : Multi-Component Self-Assembled Hydrogels Based on Partially Self-Sorting 1,3:2,4-Dibenzylidene-d-sorbitol Derivatives

We report a multicomponent self-assembling system based on 1,3:2,4-dibenzyldene-d-sorbitol (DBS) derivatives which form gels as the pH is lowered in a controlled way. The two DBS gelators are functionalized with carboxylic acids: the first in the 4-position of the aromatic rings (DBS-CO2H), the second having glycine connected through an amide bond and displaying a terminal carboxylic acid (DBS-Gly). Importantly, these two self-assembling DBS-acids have different pKa values, and as such, their self-assembly is triggered at different pHs. Slowly lowering the pH of a mixture of gelators using glucono-d-lactone (GdL) initially triggers assembly of DBS-CO2H, followed by DBS-Gly; a good degree of kinetic self-sorting is achieved. Gel formation can also be triggered in the presence of diphenyliodonium nitrate (DPIN) as a photoacid under UV irradiation. Two-step acidification of a mixture of gelators using (a) GdL and (b) DPIN assembles the two networks sequentially. By combining this approach with a mask during step b, multidomain gels are formed, in which the network based on DBS-Gly is positively patterned into a pre-existing network based on DBS-CO2H. This innovative approach yields spatially resolved multidomain multicomponent gels based on programmable low-molecular-weight gelators, with one network being positively 'written' into another

Supporting a Closely Coupled Task between a Distributed Team: Using Immersive Virtual Reality Technology

Collaboration and teamwork is important in many areas of our lives. People come together to share and discuss ideas, split and distribute work or help and support each other. The sharing of information and artefacts is a central part of collaboration. This often involves the manipulation of shared objects, both sequentially as well as concurrently. For coordinating an efficient collaboration, communication between the team members is necessary. This can happen verbally in form of speech or text and non-verbally through gesturing, pointing, gaze or facial expressions and the referencing and manipulation of shared objects. Collaborative Virtual Environments (CVE) allow remote users to come together and interact with each other and virtual objects within a computer simulated environment. Immersive display interfaces, such as a walk-in display (e.g. CAVE), that place a human physically into the synthetic environment, lend themselves well to support a natural manipulation of objects as well a set of natural non-verbal human communication, as they can both capture and display human movement. Communication of tracking data, however, can saturate the network and result in delay or loss of messages vital to the manipulation of shared objects. This paper investigates the reality of shared object manipulation between remote users collaborating through linked walk-in displays and extends our research in [27]. Various forms of shared interaction are examined through a set of structured sub tasks within a representative construction task. We report on extensive user-trials between three walk-in displays in the UK and Austria linked over the Internet using a CVE, and demonstrate such effects on a naive implementation of a benchmark application, the Gazebo building task. We then present and evaluate application-level workarounds and conclude by suggesting solutions that may be implemented within next-generation CVE infrastructures