The nature of emotional support and counselling provision for people with sight loss in the United Kingdom

People with sight loss in the United Kingdom are known to have lower levels of emotional wellbeing and to be at higher risk of depression. Consequently ‘having someone to talk to’ is an important priority for people with visual impairment. An on-line survey of the provision of emotional support and counselling for people affected by sight loss across the UK was undertaken. The survey was distributed widely and received 182 responses. There were more services offering ‘emotional support’, in the form of listening and information and advice giving, than offered ‘counselling’. Services were delivered by providers with differing qualifications in a variety of formats. Waiting times were fairly short and clients presented with a wide range of issues. Funding came from a range of sources, but many felt their funding was vulnerable. Conclusions have been drawn about the need for a national standardised framework for the provision of emotional support and counselling services for blind and partially sighted people in the UK

Polski Hamlet

Chapter is an attempt at reconstruction of the culminating moment of the first stage of the Polish reception of Shakespeare's "Hamlet". It has been entirely devoted to J. Słowacki's "Horsztyński". There is no doubt that "Horsztyński" should be viewed as the fullest and deepest interpretation of Shakespearean elements in the literary output of Juliusz Słowacki. Numerous citations and references to the works of the Elizabethan dramatist reach deeply into the structure of the world and human's life. Thanks to many adductions (citations) to Shakespeare, Słowacki approached the so much important problem for the Romantic period in Polish literature, namely the problem of individual tragedy of existence of the main character of a play and a clash with historical dilemmas of the community. The analysis of the text is aimed at showing all references to Shakespearean masterpiece with a particular emphasis on the hamletism of the charactwe of Szczęsny Kossakowski. The author describes the motif of betrayal, ever-present on different levels of the text structure, which in the most complete way describes the organisation of space between humans and their interaction in "Horsztyński". The author focuses his attention on detailed description and analysis of the recurrent themes frequently repeated in Szczęsny's statements, namely motifs of "man-harp", "man-actor in the theatre of the world", and "man-puppet", harlequin, clown. These motifs prove the sensibility of Szczęsny's to the theatrical aspect of the surrounding reality. The motif of darkness and of a blind man groping his way in the darkness so frequent in Szczęsny's statements can be interpreted as a manifestation of utter lack of hope and the feeling of uselessness of one's existence in the world.

A Self-Organizing Neural Network Model for Redundant Sensory-Motor Control, Motor Equivalence, and Tool Use

A neural network is introduced which provides a solution of the classical motor equivalence problem, whereby many different joint configurations of a redundant manipulator can all be used to realize a desired trajectory in 3-D space. To do this, the network self-organizes a mapping from motion directions in 3-D space to velocity commands in joint space. Computer simulations demonstrate that, without any additional learning, the network can generate accurate movement commands that compensate for variable tool lengths, clamping of joints, distortions of visual input by a prism, and unexpected limb perturbations. Blind reaches have also been simulated.

A Self-Organizing Neural Model of Motor Equivalent Reaching and Tool Use by a Multijoint Arm

This paper describes a self-organizing neural model for eye-hand coordination. Called the DIRECT model, it embodies a solution of the classical motor equivalence problem. Motor equivalence computations allow humans and other animals to flexibly employ an arm with more degrees of freedom than the space in which it moves to carry out spatially defined tasks under conditions that may require novel joint configurations. During a motor babbling phase, the model endogenously generates movement commands that activate the correlated visual, spatial, and motor information that are used to learn its internal coordinate transformations. After learning occurs, the model is capable of controlling reaching movements of the arm to prescribed spatial targets using many different combinations of joints. When allowed visual feedback, the model can automatically perform, without additional learning, reaches with tools of variable lengths, with clamped joints, with distortions of visual input by a prism, and with unexpected perturbations. These compensatory computations occur within a single accurate reaching movement. No corrective movements are needed. Blind reaches using internal feedback have also been simulated. The model achieves its competence by transforming visual information about target position and end effector position in 3-D space into a body-centered spatial representation of the direction in 3-D space that the end effector must move to contact the target. The spatial direction vector is adaptively transformed into a motor direction vector, which represents the joint rotations that move the end effector in the desired spatial direction from the present arm configuration. Properties of the model are compared with psychophysical data on human reaching movements, neurophysiological data on the tuning curves of neurons in the monkey motor cortex, and alternative models of movement control.

Variations in total and differential milk somatic cell counts and plasmin levels and their role in proteolysis and quality of milk and cheese

Increased plasmin and plasminogen levels and elevated somatic cell counts (SCC) and polymorphonuclear leucocyte levels (PMN) were evident in late lactation milk. Compositional changes in these milks were associated with increased SCC. The quality of late lactation milks was related to nutritional status of herds, with milks from herds on a high plane of nutrition having composition and clotting properties similar to, or superior to, early-mid lactation milks. Nutritionally-deficient cows had elevated numbers of polymorphonuclear leucocytes (PMNs) in their milk, elevated plasmin levels and increased overall proteolytic activity. The dominant effect of plasmin on proteolysis in milks of low SCC was established. When present in elevated numbers, somatic cells and PMNs in particular had a more significant influence on the proteolysis of both raw and pasteurised milks than plasmin. PMN protease action on the caseins showed proteolysis products of two specific enzymes, cathepsin B and elastase, which were also shown in high SCC milk. Crude extracts of somatic cells had a high specificity on αs1-casein. Cheeses made from late lactation milks had increased breakdown of αs1-casein, suggestive of the action of somatic cell proteinases, which may be linked to textural defects in cheese. Late lactation cheeses also showed decreased production of small peptides and amino acids, the reason for which is unknown. Plasmin, which is elevated in activity in late lactation milk, accelerated the ripening of Gouda-type cheese, but was not associated with defects of texture or flavour. The retention of somatic cell enzymes in cheese curd was confirmed, and a potential role in production of bitter peptides identified. Cheeses made from milks containing high levels of PMNs had accelerated αs1-casein breakdown relative to cheeses made from low PMN milk of the same total SCC, consistent with the demonstrated action of PMN proteinases. The two types of cheese were determined significantly different by blind triangle testing.

Artefact detection and removal algorithms for EEG diagnostic systems

The electroencephalogram (EEG) is a medical technology that is used in the monitoring of the brain and in the diagnosis of many neurological illnesses. Although coarse in its precision, the EEG is a non-invasive tool that requires minimal set-up times, and is suitably unobtrusive and mobile to allow continuous monitoring of the patient, either in clinical or domestic environments. Consequently, the EEG is the current tool-of-choice with which to continuously monitor the brain where temporal resolution, ease-of- use and mobility are important. Traditionally, EEG data are examined by a trained clinician who identifies neurological events of interest. However, recent advances in signal processing and machine learning techniques have allowed the automated detection of neurological events for many medical applications. In doing so, the burden of work on the clinician has been significantly reduced, improving the response time to illness, and allowing the relevant medical treatment to be administered within minutes rather than hours. However, as typical EEG signals are of the order of microvolts (μV ), contamination by signals arising from sources other than the brain is frequent. These extra-cerebral sources, known as artefacts, can significantly distort the EEG signal, making its interpretation difficult, and can dramatically disimprove automatic neurological event detection classification performance. This thesis therefore, contributes to the further improvement of auto- mated neurological event detection systems, by identifying some of the major obstacles in deploying these EEG systems in ambulatory and clinical environments so that the EEG technologies can emerge from the laboratory towards real-world settings, where they can have a real-impact on the lives of patients. In this context, the thesis tackles three major problems in EEG monitoring, namely: (i) the problem of head-movement artefacts in ambulatory EEG, (ii) the high numbers of false detections in state-of-the-art, automated, epileptiform activity detection systems and (iii) false detections in state-of-the-art, automated neonatal seizure detection systems. To accomplish this, the thesis employs a wide range of statistical, signal processing and machine learning techniques drawn from mathematics, engineering and computer science. The first body of work outlined in this thesis proposes a system to automatically detect head-movement artefacts in ambulatory EEG and utilises supervised machine learning classifiers to do so. The resulting head-movement artefact detection system is the first of its kind and offers accurate detection of head-movement artefacts in ambulatory EEG. Subsequently, addtional physiological signals, in the form of gyroscopes, are used to detect head-movements and in doing so, bring additional information to the head- movement artefact detection task. A framework for combining EEG and gyroscope signals is then developed, offering improved head-movement arte- fact detection. The artefact detection methods developed for ambulatory EEG are subsequently adapted for use in an automated epileptiform activity detection system. Information from support vector machines classifiers used to detect epileptiform activity is fused with information from artefact-specific detection classifiers in order to significantly reduce the number of false detections in the epileptiform activity detection system. By this means, epileptiform activity detection which compares favourably with other state-of-the-art systems is achieved. Finally, the problem of false detections in automated neonatal seizure detection is approached in an alternative manner; blind source separation techniques, complimented with information from additional physiological signals are used to remove respiration artefact from the EEG. In utilising these methods, some encouraging advances have been made in detecting and removing respiration artefacts from the neonatal EEG, and in doing so, the performance of the underlying diagnostic technology is improved, bringing its deployment in the real-world, clinical domain one step closer.

Reflections on the transformation of my meaning making to support the organic growth of a firm

The objective of my Portfolio is to explore the working hypothesis that the organic growth of a firm is governed by the perspectives of individuals and such perspectives are governed by their meaning-making. The Portfolio presents explorations of the transformation of my meaning making and in adopting new practices to support the organic growth of a firm. I use the work of other theorists to transition my understanding of how the world works. This transition process is an essential tool to engage with and understand the perspectives of others and develop a mental capacity to “train one’s imagination to go visiting” (Arendt, 1982; p.43). The Portfolio, therefore, is primarily located in reflective research. Using Kegan’s (1994) approach to Adult Mental Development, and Sowell’s (2007) understanding of the visions which silently shape our thoughts I organise the developments of my meaning making around three transformation pillars of change. In pillar one I seek to transform an unthinking respect for authority and break down a blind pervasiveness of thought within my reasoning process arising from an instinct for attachment and support from others whom I trust. In pillar two I seek to discontinue using autocratic leadership and learn to use the thoughts and contributions of a wider team to make improved choices about uncertain future events. In pillar three I explore the use of a more reflective thinking framework to test the accuracy of my perceptions and apply a high level of integrity in my reasoning process. The transformation of my meaning making has changed my perspectives and in turn my preferred practices to support the organic growth of a firm. I identify from practice that a transformative form of leadership is far more effective that a transactional form of leadership to stimulate the trust and teamwork required to sustain the growth a firm. Creating an environment where one feels free to share thoughts and feelings with others is an essential tool to build a team to critique the thoughts of one other. Furthermore, the entrepreneurial wisdom to grow a firm must come from a wider team, located both inside and outside the boundaries of a firm. No individual or small team has the mental capacity to provide the entrepreneurship required to drive the organic growth of a firm. I address my Portfolio to leaders in organisations who have no considered framework on the best practices required to lead a social organisation. These individuals may have no sense of what they implicitly believe drives social causation and they may have no understanding if their meaning making supports or curtails the practices required to grow a firm. They may have a very limited capacity to think in a logical manner, with the result they are using guesses from their ‘gut’ to make poor judgements in the management of a firm.

Interleukin 10 reduces the incidence of pancreatitis after therapeutic endoscopic retrograde cholangiopancreatography.

BACKGROUND & AIMS: Prophylactic administration of interleukin (IL)-10 decreases the severity of experimental pancreatitis. Prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis in humans is a unique model to study the potential role of IL-10 in this setting. METHODS: In a single-center, double-blind, randomized, placebo-controlled study, the effect of a single injection of 4 microg/kg (group 1) or 20 microg/kg (group 2) IL-10 was compared with that of placebo (group 0), all administered 30 minutes before therapeutic ERCP. The primary endpoint was the effect of IL-10 on serum levels of amylases and lipases measured 4, 24, and 48 hours after ERCP. The secondary objective was to evaluate changes in plasma cytokines (IL-6, IL-8, tumor necrosis factor) at the same time points and the incidence of acute pancreatitis in the 3 groups. Subjects undergoing a first therapeutic ERCP were eligible for inclusion. RESULTS: A total of 144 patients were included. Seven were excluded based on intention to treat (n = 1) or per protocol (n = 6). Forty-five, 48, and 44 patients remained in groups 0, 1, and 2, respectively. The 3 groups were comparable for age, sex, underlying disease, indication for treatment, type of treatment, and plasma levels of C-reactive protein (CRP), cytokines, and hydrolases at baseline. No significant difference was observed in CRP, cytokine, and hydrolase plasma levels after ERCP. Forty-three patients developed hyperhydrolasemia (18 in group 0, 14 in group 1, and 11 in group 2; P = 0.297), and 19 patients developed acute clinical pancreatitis (11 in group 0, 5 in group 1, 3 in group 2; P = 0.038). Two severe cases were observed in the placebo group. No mortality related to ERCP was observed. Logistic regression identified 3 independent risk factors for post-therapeutic ERCP pancreatitis: IL-10 administration (odds ratio [OR], 0.46; 95% confidence interval [95% CI], 0.22-0.96; P = 0.039), pancreatic sphincterotomy (OR, 5.04; 95% CI, 1.53-16.61; P = 0.008), and acinarization (OR, 8.19; 95% CI, 1.83-36.57; P = 0.006). CONCLUSIONS: A single intravenous dose of IL-10, given 30 minutes before the start of the procedure, independently reduces the incidence of post-therapeutic ERCP pancreatitis.

Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial.

To compare the incidence and timing of bone fractures in postmenopausal women treated with 5 years of adjuvant tamoxifen or letrozole for endocrine-responsive early breast cancer in the Breast International Group (BIG) 1-98 trial.

Communication practices in physician decision-making for an unstable critically ill patient with end-stage cancer.

BACKGROUND: Shared decision-making has become the standard of care for most medical treatments. However, little is known about physician communication practices in the decision making for unstable critically ill patients with known end-stage disease. OBJECTIVE: To describe communication practices of physicians making treatment decisions for unstable critically ill patients with end-stage cancer, using the framework of shared decision-making. DESIGN: Analysis of audiotaped encounters between physicians and a standardized patient, in a high-fidelity simulation scenario, to identify best practice communication behaviors. The simulation depicted a 78-year-old man with metastatic gastric cancer, life-threatening hypoxia, and stable preferences to avoid intensive care unit (ICU) admission and intubation. Blinded coders assessed the encounters for verbal communication behaviors associated with handling emotions and discussion of end-of-life goals. We calculated a score for skill at handling emotions (0-6) and at discussing end of life goals (0-16). SUBJECTS: Twenty-seven hospital-based physicians. RESULTS: Independent variables included physician demographics and communication behaviors. We used treatment decisions (ICU admission and initiation of palliation) as a proxy for accurate identification of patient preferences. Eight physicians admitted the patient to the ICU, and 16 initiated palliation. Physicians varied, but on average demonstrated low skill at handling emotions (mean, 0.7) and moderate skill at discussing end-of-life goals (mean, 7.4). We found that skill at discussing end-of-life goals was associated with initiation of palliation (p = 0.04). CONCLUSIONS: It is possible to analyze the decision making of physicians managing unstable critically ill patients with end-stage cancer using the framework of shared decision-making.

Safety and immunogenicity of a replication-defective adenovirus type 5 HIV vaccine in Ad5-seronegative persons: a randomized clinical trial (HVTN 054).

BACKGROUND: Individuals without prior immunity to a vaccine vector may be more sensitive to reactions following injection, but may also show optimal immune responses to vaccine antigens. To assess safety and maximal tolerated dose of an adenoviral vaccine vector in volunteers without prior immunity, we evaluated a recombinant replication-defective adenovirus type 5 (rAd5) vaccine expressing HIV-1 Gag, Pol, and multiclade Env proteins, VRC-HIVADV014-00-VP, in a randomized, double-blind, dose-escalation, multicenter trial (HVTN study 054) in HIV-1-seronegative participants without detectable neutralizing antibodies (nAb) to the vector. As secondary outcomes, we also assessed T-cell and antibody responses. METHODOLOGY/PRINCIPAL FINDINGS: Volunteers received one dose of vaccine at either 10(10) or 10(11) adenovector particle units, or placebo. T-cell responses were measured against pools of global potential T-cell epitope peptides. HIV-1 binding and neutralizing antibodies were assessed. Systemic reactogenicity was greater at the higher dose, but the vaccine was well tolerated at both doses. Although no HIV infections occurred, commercial diagnostic assays were positive in 87% of vaccinees one year after vaccination. More than 85% of vaccinees developed HIV-1-specific T-cell responses detected by IFN-γ ELISpot and ICS assays at day 28. T-cell responses were: CD8-biased; evenly distributed across the three HIV-1 antigens; not substantially increased at the higher dose; and detected at similar frequencies one year following injection. The vaccine induced binding antibodies against at least one HIV-1 Env antigen in all recipients. CONCLUSIONS/SIGNIFICANCE: This vaccine appeared safe and was highly immunogenic following a single dose in human volunteers without prior nAb against the vector. TRIAL REGISTRATION: ClinicalTrials.gov NCT00119873.

Experimental manipulations of the phenomenology of memory.

We investigated the effects of visual input at encoding and retrieval on the phenomenology of memory. In Experiment 1, participants took part in events with and without wearing blindfolds, and later were shown a video of the events. Blindfolding, as well as later viewing of the video, both tended to decrease recollection. In Experiment 2, participants were played videos, with and without the visual component, of events involving other people. Events listened to without visual input were recalled with less recollection; later adding of the visual component increased recollection. In Experiment 3, participants were provided with progressively more information about events that they had experienced, either in the form of photographs that they had taken of the events or narrative descriptions of those photographs. In comparison with manipulations at encoding, the addition of more visual or narrative cues at recall had similar but smaller effects on recollection.

Nurse-led behavioral management of diabetes and hypertension in community practices: a randomized trial.

BACKGROUND: Several trials have demonstrated the efficacy of nurse telephone case management for diabetes (DM) and hypertension (HTN) in academic or vertically integrated systems. Little is known about the real-world potency of these interventions. OBJECTIVE: To assess the effectiveness of nurse behavioral management of DM and HTN in community practices among patients with both diseases. DESIGN: The study was designed as a patient-level randomized controlled trial. PARTICIPANTS: Participants included adult patients with both type 2 DM and HTN who were receiving care at one of nine community fee-for-service practices. Subjects were required to have inadequately controlled DM (hemoglobin A1c [A1c] ≥ 7.5%) but could have well-controlled HTN. INTERVENTIONS: All patients received a call from a nurse experienced in DM and HTN management once every two months over a period of two years, for a total of 12 calls. Intervention patients received tailored DM- and HTN- focused behavioral content; control patients received non-tailored, non-interactive information regarding health issues unrelated to DM and HTN (e.g., skin cancer prevention). MAIN OUTCOMES AND MEASURES: Systolic blood pressure (SBP) and A1c were co-primary outcomes, measured at 6, 12, and 24 months; 24 months was the primary time point. RESULTS: Three hundred seventy-seven subjects were enrolled; 193 were randomized to intervention, 184 to control. Subjects were 55% female and 50% white; the mean baseline A1c was 9.1% (SD = 1%) and mean SBP was 142 mmHg (SD = 20). Eighty-two percent of scheduled interviews were conducted; 69% of intervention patients and 70% of control patients reached the 24-month time point. Expressing model estimated differences as (intervention--control), at 24 months, intervention patients had similar A1c [diff = 0.1 %, 95 % CI (-0.3, 0.5), p = 0.51] and SBP [diff = -0.9 mmHg, 95% CI (-5.4, 3.5), p = 0.68] values compared to control patients. Likewise, DBP (diff = 0.4 mmHg, p = 0.76), weight (diff = 0.3 kg, p = 0.80), and physical activity levels (diff = 153 MET-min/week, p = 0.41) were similar between control and intervention patients. Results were also similar at the 6- and 12-month time points. CONCLUSIONS: In nine community fee-for-service practices, telephonic nurse case management did not lead to improvement in A1c or SBP. Gains seen in telephonic behavioral self-management interventions in optimal settings may not translate to the wider range of primary care settings.

The role of stimulus salience and attentional capture across the neural hierarchy in a stop-signal task.

Inhibitory motor control is a core function of cognitive control. Evidence from diverse experimental approaches has linked this function to a mostly right-lateralized network of cortical and subcortical areas, wherein a signal from the frontal cortex to the basal ganglia is believed to trigger motor-response cancellation. Recently, however, it has been recognized that in the context of typical motor-control paradigms those processes related to actual response inhibition and those related to the attentional processing of the relevant stimuli are highly interrelated and thus difficult to distinguish. Here, we used fMRI and a modified Stop-signal task to specifically examine the role of perceptual and attentional processes triggered by the different stimuli in such tasks, thus seeking to further distinguish other cognitive processes that may precede or otherwise accompany the implementation of response inhibition. In order to establish which brain areas respond to sensory stimulation differences by rare Stop-stimuli, as well as to the associated attentional capture that these may trigger irrespective of their task-relevance, we compared brain activity evoked by Stop-trials to that evoked by Go-trials in task blocks where Stop-stimuli were to be ignored. In addition, region-of-interest analyses comparing the responses to these task-irrelevant Stop-trials, with those to typical relevant Stop-trials, identified separable activity profiles as a function of the task-relevance of the Stop-signal. While occipital areas were mostly blind to the task-relevance of Stop-stimuli, activity in temporo-parietal areas dissociated between task-irrelevant and task-relevant ones. Activity profiles in frontal areas, in turn, were activated mainly by task-relevant Stop-trials, presumably reflecting a combination of triggered top-down attentional influences and inhibitory motor-control processes.

Potent functional antibody responses elicited by HIV-I DNA priming and boosting with heterologous HIV-1 recombinant MVA in healthy Tanzanian adults.

UNLABELLED: Vaccine-induced HIV antibodies were evaluated in serum samples collected from healthy Tanzanian volunteers participating in a phase I/II placebo-controlled double blind trial using multi-clade, multigene HIV-DNA priming and recombinant modified vaccinia Ankara (HIV-MVA) virus boosting (HIVIS03). The HIV-DNA vaccine contained plasmids expressing HIV-1 gp160 subtypes A, B, C, Rev B, Gag A, B and RTmut B, and the recombinant HIV-MVA boost expressed CRF01_AE HIV-1 Env subtype E and Gag-Pol subtype A. While no neutralizing antibodies were detected using pseudoviruses in the TZM-bl cell assay, this prime-boost vaccination induced neutralizing antibodies in 83% of HIVIS03 vaccinees when a peripheral blood mononuclear cell (PBMC) assay using luciferase reporter-infectious molecular clones (LucR-IMC) was employed. The serum neutralizing activity was significantly (but not completely) reduced upon depletion of natural killer (NK) cells from PBMC (p=0.006), indicating a role for antibody-mediated Fcγ-receptor function. High levels of antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies against CRF01_AE and/or subtype B were subsequently demonstrated in 97% of the sera of vaccinees. The magnitude of ADCC-mediating antibodies against CM235 CRF01_AE IMC-infected cells correlated with neutralizing antibodies against CM235 in the IMC/PBMC assay. In conclusion, HIV-DNA priming, followed by two HIV-MVA boosts elicited potent ADCC responses in a high proportion of Tanzanian vaccinees. Our findings highlight the potential of HIV-DNA prime HIV-MVA boost vaccines for induction of functional antibody responses and suggest this vaccine regimen and ADCC studies as potentially important new avenues in HIV vaccine development. TRIAL REGISTRATION: Controlled-Trials ISRCTN90053831 The Pan African Clinical Trials Registry ATMR2009040001075080 (currently PACTR2009040001075080).