Overcoming resolution limits with quantum sensing.

The field of quantum sensing explores the use of quantum phenomena to measure a broad range of physical quantities, of both static and time-dependent types. While for static signals the main figure of merit is sensitivity, for time dependent signals it is spectral resolution, i.e. the ability to resolve two different frequencies. Here we study this problem, and develop new superresolution methods that rely on quantum features. We first formulate a general criterion for superresolution in quantum problems. Inspired by this, we show that quantum detectors can resolve two frequencies from incoherent segments of the signal, irrespective of their separation, in contrast to what is known about classical detection schemes. The main idea behind these methods is to overcome the vanishing distinguishability in resolution problems by nullifying the projection noise.

Oxygen supply by photosynthesis to an implantable islet cell device.

Transplantation of islet cells is an effective treatment for type 1 diabetes with critically labile metabolic control. However, during islet isolation, blood supply is disrupted, and the transport of nutrients/metabolites to and from the islet cells occurs entirely by diffusion. Adequate oxygen supply is essential for function/survival of islet cells and is the limiting factor for graft integrity. Recently, we developed an immunoisolated chamber system for transplantation of human islets without immunosuppression. This system depended on daily oxygen supply. To provide independence from this external source, we incorporated a novel approach based on photosynthetically-generated oxygen. The chamber system was packed sandwich-like with a slab of immobilized photosynthetically active microorganisms (Synechococcus lividus) on top of a flat light source (LEDs, red light at 660 nm, intensity of 8 µE/m(2)/s). Islet cells immobilized in an alginate slab (500-1,000 islet equivalents/cm(2)) were mounted on the photosynthetic slab separated by a gas permeable silicone rubber-Teflon membrane, and the complete module was sealed with a microporous polytetrafluorethylene (Teflon) membrane (pore size: 0.4 µm) to protect the contents from the host immune cells. Upon illumination, oxygen produced by photosynthesis diffused via the silicone Teflon membrane into the islet compartment. Oxygen production from implanted encapsulated microorganisms was stable for 1 month. After implantation of the device into diabetic rats, normoglycemia was achieved for 1 week. Upon retrieval of the device, blood glucose levels returned to the diabetic state. Our results demonstrate that an implanted photosynthetic bioreactor can supply oxygen to transplanted islets and thus maintain islet viability/functionality.

What is the diagnostic value of repeating a nondiagnostic video-EEG study?

Repeat video-EEG (VEEG) may increase diagnostic yield, but the test is resource intensive, time-consuming, and expensive and poses some potential risks to patients. It is also relatively common to monitor a patient for several days without capturing any clinical events. The purpose of this study was to determine the diagnostic value of repeat admissions for VEEG and to determine if the commonly available clinical information could predict the diagnostic outcome, "diagnostic" or "nondiagnostic," of a repeat study. A study was deemed diagnostic if the admission resulted in a definitive diagnosis of the patient's typical events. The authors retrospectively reviewed the charts of 3,727 patients completing scalp VEEG at the University of Alabama at Birmingham Epilepsy Center from 2002 to 2009. Minors, mentally retarded patients, and patients readmitted for surgical procedures or presurgical localization were excluded. Single and multiple regressions were used to determine if any of the parameters could predict the diagnostic outcome of a repeat VEEG study. Only younger age was independently predictive of a diagnostic readmission (P < 0.05), while longer total duration of monitoring was suggestive (P = 0.07). A repeat VEEG study was useful in 55.2% of patients, most of whom were diagnosed after only 1 additional admission. In the patient population studied, 82.4% were diagnosed on the first admission (2,622 of 3,183), 52.9% on the second (46 of 87), and 40% on the third (2 of 5). Repeat VEEG admissions are useful, and clinical expertise may be the best tool for planning potential readmissions.

A novel device for islet transplantation providing immune protection and oxygen supply.

Islet transplantation as a biological ß-cell replacement therapy has emerged as a promising option for achieving restoration of metabolic control in type 1 diabetes patients. However, partial or complete loss of islet graft function occurs in relatively short time (months to few years) after implantation. The high rate of early transplant dysfunction has been attributed to poorly viable and/or functional islets and is mediated by innate inflammatory response at the intravascular (hepatic) transplant site and critical lack of initial nutrient/oxygen supply prior to islet engraftment. In addition, the diabetogenic effect of mandatory immunosuppressive agents, limited control of alloimmunity, and the recurrence of autoimmunity limit the long-term success of islet transplantation. In order to abrogate instant blood-mediated inflammatory reaction and to provide oxygen supply for the islet graft, we have developed an extravascular (subcutaneous) transplant macrochamber (the 'ßAir' device). This device contains islets immobilized in alginate, protected from the immune system by a thin hydrophilized teflon membrane impregnated with alginate and supplied with oxygen by daily refueling with oxygen-CO (2) mixture. We have demonstrated successful utilization of the oxygen-refueling macrochamber for sustained islet viability and function as well as immunoprotection after allogeneic subcutaneous transplantation in healthy minipigs. Considering the current limitations of intraportal islet engraftment and the restricted indication for islet transplantation mainly due to necessary immunosuppressive therapy, this work could very likely lead to remarkable improvements in the procedure and moreover opens up further strategies for porcine islet cell xenotransplantation.

Effect of epilepsy magnetic source imaging on intracranial electrode placement.

OBJECTIVE: Intracranial electroencephalography (ICEEG) with chronically implanted electrodes is a costly invasive diagnostic procedure that remains necessary for a large proportion of patients who undergo evaluation for epilepsy surgery. This study was designed to evaluate whether magnetic source imaging (MSI), a noninvasive test based on magnetoencephalography source localization, can supplement ICEEG by affecting electrode placement to improve sampling of the seizure onset zone(s). METHODS: Of 298 consecutive epilepsy surgery candidates (between 2001 and 2006), 160 patients were prospectively enrolled by insufficient localization from seizure monitoring and magnetic resonance imaging results. Before presenting MSI results, decisions were made whether to proceed with ICEEG, and if so, where to place electrodes such that the hypothetical seizure-onset zone would be sampled. MSI results were then provided with allowance of changes to the original plan. RESULTS: MSI indicated additional electrode coverage in 18 of 77 (23%) ICEEG cases. In 39% (95% confidence interval, 16.4-61.4), seizure-onset ICEEG patterns involved the additional electrodes indicated by MSI. Sixty-two patients underwent surgical resection based on ICEEG recording of seizures. Highly localized MSI was significantly associated with seizure-free outcome (mean, 3.4 years; minimum, >1 year) for the entire surgical population (n = 62). INTERPRETATION: MSI spike localization increases the chance that the seizure-onset zone is sampled when patients undergo ICEEG for presurgical epilepsy evaluations. The clinical impact of this effect, improving diagnostic yield of ICEEG, should be considered in surgery candidates who do not have satisfactory indication of epilepsy localization from seizure semiology, electroencephalogram, and magnetic resonance imaging.

Functional imaging: II. Prediction of epilepsy surgery outcome.

OBJECTIVE: To gain information on the value of magnetic source imaging (MSI), 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), and ictal single photon emission computed tomography (SPECT) to predict seizure-free outcome following epilepsy surgery in patients who require intracranial electroencephalography (ICEEG). METHODS: This work was part of a prospective observation study of epilepsy surgery candidates not sufficiently localized with scalp EEG and MRI. Of 160 patients enrolled 62 completed ICEEG and subsequent surgical resection. Sixty-one percent resulted in an Engel I seizure-free outcome at a minimum of one-year follow-up (mean = 3.4 years). Sensitivity, specificity, and predictive values were computed for each modality. Multivariate logistical regression was used to identify prediction of surgical outcome by imaging test. RESULTS: MSI sensitivity for a conclusively localized study was 55% with a positive predictive value of 78%. Eliminating non-diagnostic MSI cases (no spikes captured during recording) yielded a corrected negative predictive value of 64%. With available comparison subgroups FDG-PET and ictal SPECT values were similar to MSI. The OR (adjusted for epilepsy and MRI classification) for MSI prediction of seizure-free outcome was 4.4 (p =0.01). In cases with both PET and MSI, the adjusted OR for PET was 7.1 (p <0.01) and for MSI was 6.4 (p = 0.01). In the cases with all three tests (n = 27), ictal SPECT had the highest OR of 9.1 (p = 0.05). INTERPRETATION: MSI, FDG-PET, and ictal SPECT each have clinical value in predicting seizure-free surgical outcome in epilepsy surgery candidates who typically require ICEEG.

Functional imaging: I. Relative predictive value of intracranial electroencephalography.

OBJECTIVE: To gain information on the predictive and prognostic value of magnetic source imaging (MSI), 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)FDG-PET), and ictal single-photon emission computed tomography (SPECT) as compared with intracranial electroencephalography (ICEEG) localization in epilepsy surgery. METHODS: This work was part of a cohort study of epilepsy surgery candidates not sufficiently localized with noninvasive studies. Of 160 patients enrolled over 4 years, 77 completed ICEEG seizure monitoring. Sensitivity, specificity, and predictive values relative to ICEEG were computed for each modality. RESULTS: Seizures were not captured in five patients. Of the 72 diagnostic ICEEG studies, seizure localization results were 74% localized, 10% multifocal, and 17% nonlocalized. Sixty-one percent were localized to neocortical regions. Depending on patient subgroup pairs, sensitivity ranged from 58 to 64% (MSI), 22 to 40% (PET), and 39 to 48% (SPECT); specificity ranges were 79 to 88% (MSI), 53 to 63% (PET), and 44 to 50% (SPECT). Gains in diagnostic yield were seen only with the combination of MSI and PET or MSI and ictal SPECT. Localization concordance with ICEEG was greatest with MSI, but a significant difference was demonstrated only between MSI and PET. Moderate redundancy was seen between PET and ictal SPECT (kappa = 0.452; p = 0.011). INTERPRETATION: Conclusively positive MSI has a high predictive value for seizures localized with ICEEG. Diagnostic gain may be achieved with addition of either PET or ictal SPECT to MSI. Diagnostic values for imaging tests are lower than "true values" because of the limitations of ICEEG as a gold standard.

Magnetic stimulation of curved nerves.

Magnetic stimulation of nerves is attracting increased attention recently, as it has been found to be useful in therapy of neural disorders in humans. In an effort to explain the mechanisms of magnetic stimulation, we focus in this paper on the dependence of magnetic stimulation on neuronal morphology and in particular on the importance of curvature of axonal bundles. Using the theory of passive membrane dynamics, we predict the threshold power (the minimum stimulation power required to initiate an action potential) of specific axonal morphologies. In the experimental section, we show that magnetic stimulation of the frog sciatic nerve follows our theoretical predictions. Furthermore, the voltage length constant of the nerve can be measured based on these results alone.

Identifying competencies for Australian health professionals working in international health.

A profile of the roles performed by Australian health professionals working in international health was constructed to identify the core competencies they require, and the implications for education and training of international health practitioners. The methods used included: literature review and document analysis of available training and education; an analysis of competencies required in job descriptions for international health positions; and consultations with key informants. The international health roles identified were classified in four main groups: Program Directors, Program Managers, Team Leaders and Health Specialists. Thirteen 'core' competencies were identified from the job analysis and key informant/group interviews. Contributing to international health development in resource poor countries requires high level cultural, interpersonal and teamwork competencies. Technical expertise in health disciplines is required, with flexibility to adapt to new situations. International health professionals need to combine public health competencies with high level personal maturity to respond to emerging challenges.

Improved depiction of small anatomic structures in MR images using Gaussian-weighted spirals and zero-filled interpolation.

Partial-volume artifacts reduce the contrast and continuity of small structures in magnetic resonance images. Zero-filled interpolation (ZFI) has been known for some time as a useful technique to reduce partial-volume artifacts and improve the appearance of small structures and edges. However, its use is limited by the fact that ZFI can exacerbate image artifacts. For example, it can exacerbate Gibbs ringing, also known as the truncation artifact, which manifests itself as spurious ringing around sharp edges. Currently, the most common technique to address this problem is post-acquisition filtering, which causes blurring in the image. Using ZFI in conjunction with a variable-density sampling method designed to reduce ringing is proposed as a possible solution to this problem. This approach is demonstrated with a Gaussian-weighted spiral and is compared to conventional spiral sampling both with and without the application of a filter used to reduce ringing. The two spiral sampling techniques are compared using simulations, phantom images, and in vivo brain images. The Gaussian-weighted spiral demonstrates reduced ringing without the loss of spatial resolution commonly associated with post-acquisition filtering. Additionally, this sampling technique is shown to work well in conjunction with ZFI to reduce partial-volume artifacts without the apparent increase in Gibbs ringing usually associated with zero-filled reconstruction. This approach will be most useful for imaging techniques such as MR angiography which are known to be sensitive to partial-volume effects, as well as when imaging anatomic regions associated with more severe Gibbs ringing.

A comparative biomechanical study of the strength of the bony patella following dome cut or uniplanar cut in total knee arthroplasty.

This study was designed to investigate whether there is a difference in the strength of the bony patella following preparation either with a dome configuration or with a regular uniplanar cut in total knee arthroplasty. For each test 4 cadaveric patellae were used. Two of the 4 patellae were prepared with a regular uniplanar cut and 2 were prepared into a dome shape with a circumferential wall, using a concave reamer. The thickness of each patella after preparation was [figure 1 & 2: see text] 15 mm. The tests were performed using an impact drop weight apparatus. In the first two tests, which tested the resistance of the patella to tensile force and evaluated the strength of the patella by impact load while under tension, the soft tissues were torn, with no harm to the bony patella. In the third test, which evaluated the resistance of the patella without tension against impact load, the force required to fracture the dome-shaped patella was greater than for the traditional uniplanar cut (500 Kg vs 350 Kg). Dome shape with circumferential wall preparations of the bony patella in total knee arthroplasty were stronger in resisting external impact than the conventional uniplanar cut patella. This established the rationale for our use of the dome-shaped patella implant with a concave undersurface.

From policy to action: access to essential drugs for the treatment of hypertension in the Small Island States (SIS) of the South Pacific.

The existing acquisition cost for essential drugs in the Cook Islands, Kiribati, Marshall Islands, Nauru, Niue, Tuvalu, is sufficiently high to compromise equitable access to quality drug therapy. The difficulty of access is further compounded by problems of distance from drug manufacturers and suppliers, associated with inadequate transport and communication links. In some of the Small Island States of the Pacific, internal distribution challenges further reduce access to drugs for those people who live on the outer islands. Two management processes to address these problems which have successfully been used in the past, are the establishment of an essential drug list to guarantee consistent appropriate treatment, and the introduction of pooled or bulk purchasing in order to achieve economies of scale. The major non-communicable diseases (NCDs) in the South Pacific include diabetes, hypertension and cardiovascular disease. These diseases, in association with life-style factors of obesity and smoking result in significant morbidity and mortality. This paper demonstrates that collaboration in drug purchasing of a defined list of essential drugs for hypertension would be beneficial in the South Pacific, and that the process is a model for achievement of rational drug treatment for NCDs in isolated small economies.

Vaccination with empty plasmid DNA or CpG oligonucleotide inhibits diabetes in nonobese diabetic mice: modulation of spontaneous 60-kDa heat shock protein autoimmunity.

Nonobese diabetic (NOD) mice develop insulitis and diabetes through a process involving autoimmunity to the 60-kDa heat shock protein (HSP60). Treatment of NOD mice with HSP60 or with peptides derived from HSP60 inhibits this diabetogenic process. We now report that NOD diabetes can be inhibited by vaccination with a DNA construct encoding human HSP60, with the pcDNA3 empty vector, or with an oligonucleotide containing the CpG motif. Prevention of diabetes was associated with a decrease in the degree of insulitis and with down-regulation of spontaneous proliferative T cell responses to HSP60 and its peptide p277. Moreover, both the pcDNA3 vector and the CpG oligonucleotide induced specific Abs, primarily of the IgG2b isotype, to HSP60 and p277, and not to other islet Ags (glutamic acid decarboxylase or insulin) or to an unrelated recombinant Ag expressed in bacteria (GST). The IgG2b isotype of the specific Abs together with the decrease in T cell proliferative responses indicate a shift of the autoimmune process to a Th2 type in treated mice. These results suggest that immunostimulation by bacterial DNA motifs can modulate spontaneous HSP60 autoimmunity and inhibit NOD diabetes.

G protein levels and function as an objective measure of depression in patients with functional bowel disorders.

Heterotrimeric G proteins play a pivotal role in postreceptor information transduction. These proteins have been implicated in the pathophysiology, diagnosis, and treatment of mood disorders and proposed as a state-dependent biochemical mood marker in mononuclear leukocytes. Irritable bowel syndrome (IBS) is associated with changes in mood, affecting patients' illness perceptions and behavior. We examined whether mononuclear leukocytes of patients with IBS have altered G protein measures. We undertook G protein functional measurements through agonist-enhanced [3H]Gpp(NH)p binding capacity and quantitative measures by immunoblot analysis using anti-Galpha antibodies in mononuclear leukocytes obtained from 19 IBS patients (Rome criteria) and 19 healthy matched subjects. The study groups were similar in age, gender, and years of education. Mononuclear leukocyte functions of G(s) (21.3+/-8.3%) and G(i) (22.2+/-6.7%) proteins in IBS patients were similar to healthy subjects (24.8+/-4.7 and 25.2+/-4.0%, respectively). The relative immunoreactivities of the G(sa) (98.9+/-10.2%) and the G(ia) (104.2+/-11.5%) subunit proteins in mononuclear leukocytes of IBS patients were also similar to those in healthy subjects. Two patients clinically diagnosed as depressed were detected by the G protein assay. The results lend objective support to the contention that major depression is not a causative factor in IBS, nor associated with its severity. The G protein assay may provide an objective biochemical tool for detecting depression in IBS, differentiating it from psychological distress that is commonly diagnosed by subjective tests.

Meeting the needs of medical students training in paediatrics and child health.

The way education is delivered is changing, and the type of clinical experience in paediatrics available to medical students is changing. Accordingly, the academic departments of Paediatrics and Child Health in Australia and New Zealand are revising both the content and methods of delivery of training in Paediatrics and Child Health. The educational change paradigm and the nature of the changes in training proposed are summarized.

Linking public health education and practice: the Australian experience.

The public health workforce in Australia is highly skilled, multifunctional, and drawn from a variety of backgrounds, including clinical practice and non-health areas. A wide range of activities is needed to meet the educational and training requirements of this workforce, including on the job inservice training, context specific continuing education programs and short courses, distance and self-directed learning packages, and postgraduate University level courses. The core components of public health today include: a social and political commitment to health, a shared responsibility between government and the public, and a multidisciplinary field of action. The challenge for those providing education and training for the public health workforce is to ensure graduates have the broad range of knowledge and skills needed in this climate. A system-wide approach to learning, where knowledge and skill development is related to the practices and settings of service and program delivery, will ensure strong links between education and practice.

Blood-borne virus-related discrimination in dental services.

While the risk of infection through occupational exposure to blood-borne viruses is a major concern of dental health care workers, the National HIV/AIDS Strategy and many health, AIDS and discrimination-related agencies have identified discrimination related to HIV/AIDS as a priority area for action. In 1995 the Commonwealth Department of Health and Family Services selected the School of Medical Education at the University of New South Wales to conduct a national project to reduce discrimination related to blood-borne viruses within dental services (Godwin, Meihubers & Rotem 1997). This paper provides an overview of the study and its major findings. The study focused on quality of care issues which may cause or manifest discrimination. Key stakeholders were invited to review policies, procedures, organisational arrangements and other systemic issues which influence the quality of oral health services to populations within selected geographical regions.

The clinical learning environment.

This paper presents a brief review of the attributes of effective learning environments in clinical settings. Recent studies articulate the perceived importance of social and organizational factors as determinants of learning. Differences are evident among hospitals and among departments within hospitals with regard to the quality of the learning environment they offer. These differences are reflected in the orientation towards teaching and learning, the level of autonomy, variety and workload, and the quality of supervision and social support. Differences are also evident in the type and quality of opportunities for practice of important skills and in the availability of educational resources. These factors are perceived as major determinants of the effectiveness of learning in clinical settings. The implications for clinical teachers and administrators are discussed. The authors argue that emphasis should be given to the creation of supportive and well-organized learning environments in clinical settings. This may require a great emphasis on the role of clinical teachers as designers of opportunities for learning and managers of learning resources.