Hypoxia-inducible transcription factor 1 (HIF-1) and HIF-2alpha regulate the expression of an expansive array of genes associated with cellular responses to hypoxia. Although HIF-regulated genes mediate crucial beneficial short-term biological adaptations, we hypothesized that chronic activation of the HIF pathway in cardiac muscle, as occurs in advanced ischemic heart disease, is detrimental. We generated mice with cardiac myocyte-specific deletion of the von Hippel-Lindau protein (VHL), an essential component of an E3 ubiquitin ligase responsible for suppressing HIF levels during normoxia. These mice were born at expected frequency and thrived until after 3 months postbirth, when they developed severe progressive heart failure and premature death. VHL-null hearts developed lipid accumulation, myofibril rarefaction, altered nuclear morphology, myocyte loss, and fibrosis, features seen for various forms of human heart failure. Further, nearly 50% of VHL(-/-) hearts developed malignant cardiac tumors with features of rhabdomyosarcoma and the capacity to metastasize. As compelling evidence for the mechanistic contribution of HIF-1alpha, the concomitant deletion of VHL and HIF-1alpha in the heart prevented this phenotype and restored normal longevity. These findings strongly suggest that chronic activation of the HIF pathway in ischemic hearts is maladaptive and contributes to cardiac degeneration and progression to heart failure.

The concept of self-paced control has recently emerged from within the general field of brain-computer interface research. The use of assistive devices in real-world environments is best served by interfaces operated in an asynchronous manner. This self-paced or asynchronous mode of device control is more natural than the more commonly studied synchronized control mode whereby the system dictates the control of the user. The Neil Squire Society develops asynchronous, direct brain-switches for self-paced control applications. Our latest switch design operated with a mean activation rate of 73 percent and false positive error rates of 2 percent. This report provides an introduction to asynchronous control, summarizes our results to date, and details some key issues that specifically relate to brain interface design for asynchronous control.

Direct brain interface (BI) systems provide an alternative communication and control solution for individuals with severe motor disabilities, bypassing impaired interface pathways. Most BI systems are aimed to be operated by individuals with severe disabilities. With these individuals, there is no observable indicator of their intent to control or communicate with the BI system. In contrast, able-bodied subjects can perform the desired physical movements such as finger flexion and one can observe the movement as the indicator of intent. Since no external knowledge of intention is available for individuals with severe motor disabilities, generating the data for system training is problematic. This paper introduces three methods for generating training-data for self-paced BI systems and compares their performances with four alternative methods of training-data generation. Results of the offline analysis on the electroencephalogram data of eight subjects during self-paced BI experiments show that two of the proposed methods increase true positive rates (at fixed false positive rate of 2%) over that of the four alternative methods from 50.8%-58.4% to about 62% which corresponds to 3.6%-11.2% improvement.

Purpose - Scholars in the field of performance measurement tend to use the term business performance measurement (BPM) systems without explaining exactly what they mean by it. This lack of clarity creates confusion and comparability issues, and makes it difficult for researchers to build on one an each other's work. The purpose of this paper is to identify the key characteristics of a BPM system, by reviewing the different definitions of a BPM system that exist in the literature. This work aims to open a debate on what are the necessary and sufficient conditions of a BPM system. It is also hoped that a greater level of clarity in the performance measurement research arena will be encouraged.Design/methodology/approach - The performance measurement literature is reviewed using a systematic approach. Findings - Based on this research, a set of conditions of a BPM system has been proposed from which researchers can choose those which are necessary and sufficient conditions for their studies.Research limitations/implications - The analysis in this paper provides a structure and set of characteristics that researchers could use as a reference framework to define a BPM system for their work, and as a way to define the specific focus of their investigations. More clarity and precision around the use of the BPM systems phrase will improve the generalisability and comparability of research in this area.Originality/value - By reviewing the different definitions of a BPM system that exist in the literature this paper will hopefully stimulate a debate on the necessary and sufficient conditions of a BPM system and encourage a greater level of clarity in the performance measurement research arena.

China National Offshore Oil Corporation (CNOOC), Chevron, and ENI, the field operator, are partners in the development of the HZ oil and gas fields, operating as the CACT Operators Group (CACT) in the South China Sea. The HZ fields are stacked, thin, high-permeability sandstone reservoirs interlayered with low-permeability layers. The shallower layers generally have better permeability and were developed first while the deeper, lower-permeability reservoirs have been developed more recently. The lower-permeability reservoirs are generally of lower porosity and higher compressive strength. Drilling-mud- filtrate invasion also tends to be deeper. Deep-penetration perforating charges are required to perforate past the damaged zone. Experience indicates that underbalance perforation provides better productivity compared to overbalance perforation. Although conventional underbalance perforation can be performed using pipe-conveyed or tubing-conveyed perforation (TCP), depth uncertainties and the time requirement for TCP service in thin reservoir zones makes wireline-conveyed perforation an attractive method. However, where multiple zones must be perforated, the conventional wireline approach can only perforate the first zone underbalance (with the completion fluid weighted accordingly) while subsequent zones could only be perforated balanced at best. A new perforating system, designed to generate a large dynamic underbalance with a static overbalance, was used to perforate new wells for the development project to maximize well productivity per well expenditure. A multilayer production evaluation of one of the wells perforated with the dynamic underbalance method produced a zero skin value in the 9-md layer and a -0.97 skin value in the 1600-md layer. Conventional underbalanced perforation, employing multiple wireline runs, could not achieve these low skin values over this wide range of permeabilities.

The low-frequency asynchronous switch design (LF-ASD) has been introduced as a direct brain interface (BI) for asynchronous control applications. Asynchronous interfaces, as opposed to synchronous interfaces, have the advantage of being operational at all times and not only at specific system-defined periods. This paper modifies the LF-ASD design by incorporating into the system more knowledge about the attempted movements. Specifically, the history of feature values extracted from the EEG signal is used to detect a right index finger movement attempt. Using data collected from individuals with high-level spinal cord injuries and able-bodied subjects, it is shown that the e ' rror characteristics of the modified design are significantly better than the previous LF-ASD design. The true positive rate percentage increased by up to 15 which corresponds to 50% improvement when the system is operating with false positive rates in the 1-2% range.

China National Offshore Oil Corporation (CNOOC), Chevron, and ENI, the field operator, are partners in the development of the HZ oil and gas fields, operating as the CACT Operators Group (CACT) in the South China Sea. The HZ fields are stacked, thin, high-permeability sandstone reservoirs interlayered with low-permeability layers. The shallower layers generally have better permeability and were developed first while the deeper, lower-permeability reservoirs have been developed more recently.The lower-permeability reservoirs are generally of lower porosity and higher compressive strength. Drilling-mud-filtrate invasion also tends to be deeper. Deep-penetration perforating charges are required to perforate past the damaged zone. Experience indicates that underbalance perforation provides better productivity compared to overbalance perforation.Although conventional underbalance perforation can be performed using pipe-conveyed or tubing-conveyed perforation (TCP), depth uncertainties and the time requirement for TCP service in thin reservoir zones makes wireline-conveyed perforation an attractive method. However, where multiple zones must be perforated, the conventional wireline approach can only perforate the first zone underbalance (with the completion fluid weighted accordingly) while subsequent zones could only be perforated balanced at best.A new perforating system, designed to generate a large dynamic underbalance with a static overbalance, was used to perforate new wells for the development project to maximize well productivity per well expenditure.A multilayer production evaluation of one of the wells perforated with the dynamic underbalance method produced a zero skin value in the 9-md layer and a −0.97 skin value in the 1600-md layer. Conventional underbalanced perforation, employing multiple wireline runs, could not achieve these low skin values over this wide range of permeabilities.

An animatronic robot was designed and constructed for the 2003 Annual Student Robotic Technology and Engineering Challenge organized by the Robotics International (RI) association of the Society of Manufacturing Engineers (SME). It was also the senior capstone design project for two of the design team members. After a thorough study of body and biomechanics of polar bears, the skeleton and limbs of a polar bear robot were designed to scale. The design was complemented with the drive train and DC electric motors as actuators. A microcontroller, a LEGO controller, was utilized to control the motions of the bear. Design experience included artistic design of the bear and its shell for placement of fur, mechanism design for the body and its limbs, the design of power train, selection of the electric actuators and control circuit design, and programming of the microcontroller. Most mechanical and electrical components were obtained through recycling of old robots and equipment from laboratories.

However much of this debate has been based on performance information reported in performance league tables and performance targets against which public sector organisations are assessed. These targets and league tables, which are regularly debated by politicians and the media, are often criticised. Analysis of three recent reports regarding the measurement and reporting of the performance of public service delivery (The Gershon Review; The Office of National Statistics Report “Public Service Productivity: Health” and The Atkinson Review) suggest that published performance information causes problems when debating the performance of public service delivery. Specifically they highlight the following major problems:

The Brain-Computer Interface (BCI) research community has acknowledged that researchers are experiencing difficulties when they try to compare the BCI techniques described in the literature. In response to this situation, the community has stressed the need for objective methods to compare BCI technologies. Suggested improvements have included the development and use of benchmark applications and standard data sets. However, as a young, multidisciplinary research field, the BCI community lacks a common vocabulary. As a result, this deficiency leads to poor intergroup communication, which hinders the development of the desired methods of comparison. One of the principle reasons for the lack of common vocabulary is the absence of a common functional model of a BCI System. This paper proposes a new functional model for BCI System design. The model supports many features that facilitate the comparison of BCI technologies with other BCI and non-BCI user interface technologies. From this model, taxonomy for BCI System design is developed. Together the model and taxonomy are considered a general framework for BCI System design. The representational power of the proposed framework was evaluated by applying it to a set of existing BCI technologies. The framework could effectively describe all of the BCI System designs tested.

The Neil Squire Foundation (NSF) is a Canadian nonprofit organization whose purpose is to create opportunities for independence for individuals who have significant physical disabilities. Over the last ten years, our team in partnership with researchers at the Electrical and Computer Engineering Department, the University of British Columbia, has been working to develop a direct brain-controlled switch for individuals with significant physical disabilities. The NSF Brain Interface Project primarily focuses on the development of brain-computer interface switch technologies for intermittent (or asynchronous) control in natural environments. That is, technologies that will work when the User intends control but also remains in a stable off state when there is no intent to control. A prototype of such a switch has successfully been developed. This switch has demonstrated classification accuracies greater than 94%. The initial results are promising, but further research is required to improve switch accuracies and reliability and to test these switch technologies over a larger population of users and operating conditions. This paper provides an overview of the NSF brain-switch technologies and details our approach to future work in this area.

A 77-year-old woman was seen to walk into her local church alone in the late morning. Immediately prior to sitting down in a pew, the patient was noted to collapse without prior complaint. She was believed to be apneic and pulseless by bystanders, and emergency medical services (EMS) were summoned. No bystander cardiopulmonary resuscitation (CPR) was performed. Responders included fire department personnel with a semi-automatic external defibrillator and basic life support (BLS) capabilities, and municipal EMS personnel equipped with advanced life support (ALS) capabilities. These units arrived simultaneously, 4 minutes after the call was dispatched. The patient was assessed, and found to be in cardiopulmonary arrest. An apparently organized rhythm was seen on “quick-look” using manual paddles. The patient was noted on three-lead electrocardiogram (ECG) to be in slow pulseless electrical activity (PEA), with a narrow-complex rhythm of approximately 10 beats/min. The patient was successfully intubated 7 minutes after the call was dispatched. A peripheral intravenous line was established, and 1 mg of epinephrine and 1 mg of atropine were administered intravenously 9 minutes after the call was dispatched. Rhythm strips are shown in Figure 1, detailing a progressively more rapid PEA rhythm without any return of spontaneous circulation and with interpolated chest compressions. This rhythm converted into a ventricular tachycardia (VT), spontaneously converted back into a PEA, back into a VT, and was then followed by apparent degradation to ventricular fibrillation (VF). Without electrical countershock or defibrillatory medication administration, this VF converted spontaneously into an organized narrow-complex rhythm (Figs. 2 and 3). Following a subsequent second episode of VF, a single countershock was delivered at 200 joules with successful cardioversion to a narrow-complex rhythm. This rhythm accelerated and was noted to result in spontaneous perfusion, with a palpable systolic blood pressure of 100 mm Hg. The patient evidenced spontaneous respiratory effort and extremity movement with stable vital signs throughout transport to the hospital. Following emergency department evaluation and stabilization, the patient was admitted to the medical intensive care unit. Her cardiac enzymes had elevations consistent with myocardial injury, and her 12-lead ECG demonstrated left ventricular hypertrophy, and S-T depressions and deep symmetric T-wave inversions in leads V2 through V5. Heparin and nitroglycerin intravenous therapy were initiated. Although the patient showed some signs of neurologic progress through the first week of her stay (responses to verbal stimuli and continued movement of all extremities), support was withdrawn five days after admission upon request from the family and in keeping with a previously signed document expressing the patient’s wishes not to be mechanically ventilated. The patient died six days after admission.

Previous research has focused on developing a brain-controlled switch named the low frequency asynchronous switch design (LF-ASD) that is suitable for intermittent control of devices such as environmental control systems, computers, and neural prostheses. On-line implementations of the LF-ASD have shown promising results in response to actual index finger flexions with able-bodied subjects. This paper reports the results of initial on-line evaluations of the LF-ASD brain-controlled switch with both able-bodied subjects and subjects with high-level spinal-cord injuries. This paper has demonstrated that users can activate the LF-ASD switch by imagining movement. In this paper, two able-bodied subjects were able to control the LF-ASD with imagined voluntary movements with hit (true positive) rates above 70% and false positive rates below 3% while two subjects with high-level spinal-cord injuries demonstrated hit rates ranging from 45-48% and false positive rates below 1%.

OBJECTIVE:Evaluation of a short latency component (SLC) observed in profoundly deaf young children during recordings of the auditory brain stem response (ABR) before cochlear implantation. DESIGN:Seventy young children (ages 2 to 11 yr) were investigated as part of their routine audiologic and diagnostic assessment, before cochlear implantation. The ABR was evoked using click stimuli and tone pips (500 Hz and 1 kHz) at intensity levels up to 105 dB nHL. The incidence of the SLC arising at a latency of 3 msec with high level click stimuli, in addition to residual ABR waves, was assessed. RESULTS:An SLC was observed in a total of 18 of the 70 children investigated. It was present in 15 out of 31 congenitally deaf children (48%) compared with only 2 out of 33 children deafened after meningitis (6%). A chi-squared test employing a 2 x 2 contingency table shows that this dependency on etiology of deafness is highly statistically significant (p < 0.001). The presence of the SLC in the congenitally deaf children is related to age at the time of the Electric Response Audiometry test and is more likely to be observed in the younger child (p < 0.01). CONCLUSIONS:Interpretation of the ABR in profoundly deaf children should take into consideration the possible presence of the SLC. An evoked potential arising from stimulation of the vestibular system, particularly the vestibular nuclei, is proposed as a likely origin for this component. Damage to sensory cells in the vestibular portion of the labyrinth might explain why an SLC is seen rarely in cases of deafness after meningitis.