Simultaneous determination of electrical conductivity and thickness of nonmagnetic metallic foils using two-sided multifrequency eddy current techniques.

In this paper, we describe a simple method for performing multifrequency eddy current characterization of free-standing uniform-thickness metallic foils using a forked inductive coil arrangement. The method involves measuring the mutual inductance between two coils when a foil is present between the coils, and when it is not present; the ratio of these mutual inductances is compared with an analytical solution, and foil conductivity, thickness, and sheet resistance are simultaneously estimated using numerical inversion and least-squares fitting. This method was used to characterize 34 non-ferrous metallic samples with thicknesses between 50 and 640 µm and with conductivities between 0.8 × 107 and 5.8 × 107 S/m. The estimated thicknesses from eddy current characterization agreed well with those measured using confocal optical techniques; the two approaches agreed to within 1 µm for samples that were thinner than 200 µm, and to within 0.5% for samples that had a thickness of 200 µm or greater. The estimated conductivities from eddy current characterization were in close agreement with expected values, given knowledge of the materials used. A particular strength of this approach is that the instrumentation needed is broadly available in research and development laboratories and the associated fixturing is easy to manufacture and assemble. A calibration procedure is described that can be used to reduce errors from geometric uncertainties. This calibration requires a sample that has only a known conductivity or thickness; both do not need to be known. The method described herein is likely extensible to conductivities and thickness well outside the ranges measured as part of this work.

An aerosol challenge model of tuberculosis in Mauritian cynomolgus macaques.

BACKGROUND: New interventions for tuberculosis are urgently needed. Non-human primate (NHP) models provide the most relevant pre-clinical models of human disease and play a critical role in vaccine development. Models utilising Asian cynomolgus macaque populations are well established but the restricted genetic diversity of the Mauritian cynomolgus macaques may be of added value. METHODS: Mauritian cynomolgus macaques were exposed to a range of doses of M. tuberculosis delivered by aerosol, and the outcome was assessed using clinical, imaging and pathology-based measures. RESULTS: All macaques developed characteristic clinical signs and disease features of tuberculosis (TB). Disease burden and the ability to control disease were dependent on exposure dose. Mauritian cynomolgus macaques showed less variation in pulmonary disease burden and total gross pathology scores within exposure dose groups than either Indian rhesus macaques or Chinese cynomolgus macaques. CONCLUSIONS: The genetic homogeneity of Mauritian cynomolgus macaques makes them a potentially useful model of human tuberculosis.

Inconsistent reporting of minimally invasive surgery errors.

INTRODUCTION: Minimally invasive surgery (MIS) is a complex task requiring dexterity and high level cognitive function. Unlike surgical 'never events', potentially important (and frequent) manual or cognitive slips ('technical errors') are underresearched. Little is known about the occurrence of routine errors in MIS, their relationship to patient outcome, and whether they are reported accurately and/or consistently. METHODS: An electronic survey was sent to all members of the Association of Surgeons of Great Britain and Ireland, gathering demographic information, experience and reporting of MIS errors, and a rating of factors affecting error prevalence. RESULTS: Of 249 responses, 203 completed more than 80% of the questions regarding the surgery they had performed in the preceding 12 months. Of these, 47% reported a significant error in their own performance and 75% were aware of a colleague experiencing error. Technical skill, knowledge, situational awareness and decision making were all identified as particularly important for avoiding errors in MIS. Reporting of errors was variable: 15% did not necessarily report an intraoperative error to a patient while 50% did not consistently report at an institutional level. Critically, 12% of surgeons were unaware of the procedure for reporting a technical error and 59% felt guidance is needed. Overall, 40% believed a confidential reporting system would increase their likelihood of reporting an error. CONCLUSION: These data indicate inconsistent reporting of operative errors, and highlight the need to better understand how and why technical errors occur in MIS. A confidential 'no blame' reporting system might help improve patient outcomes and avoid a closed culture that can undermine public confidence.

Evaluation of the Immunogenicity of Mycobacterium bovis BCG Delivered by Aerosol to the Lungs of Macaques.

Nine million cases of tuberculosis (TB) were reported in 2013, with a further 1.5 million deaths attributed to the disease. When delivered as an intradermal (i.d.) injection, the Mycobacterium bovis BCG vaccine provides limited protection, whereas aerosol delivery has been shown to enhance efficacy in experimental models. In this study, we used the rhesus macaque model to characterize the mucosal and systemic immune response induced by aerosol-delivered BCG vaccine. Aerosol delivery of BCG induced both Th1 and Th17 cytokine responses. Polyfunctional CD4 T cells were detected in bronchoalveolar lavage (BAL) fluid and peripheral blood mononuclear cells (PBMCs) 8 weeks following vaccination in a dose-dependent manner. A similar trend was seen in peripheral gamma interferon (IFN-γ) spot-forming units measured by enzyme-linked immunosorbent spot (ELISpot) assay and serum anti-purified protein derivative (PPD) IgG levels. CD8 T cells predominantly expressed cytokines individually, with pronounced tumor necrosis factor alpha (TNF-α) production by BAL fluid cells. T-cell memory phenotype analysis revealed that CD4 and CD8 populations isolated from BAL fluid samples were polarized toward an effector memory phenotype, whereas the frequencies of peripheral central memory T cells increased significantly and remained elevated following aerosol vaccination. Expression patterns of the α4ß1 integrin lung homing markers remained consistently high on CD4 and CD8 T cells isolated from BAL fluid and varied on peripheral T cells. This characterization of aerosol BCG vaccination highlights features of the resulting mycobacterium-specific immune response that may contribute to the enhanced protection previously reported in aerosol BCG vaccination studies and will inform future studies involving vaccines delivered to the mucosal surfaces of the lung.

Outcome after liver resection in patients presenting with simultaneous hepatopulmonary colorectal metastases.

BACKGROUND: The most common sites of metastasis from colorectal cancer (CRC) are hepatic and pulmonary; they can present simultaneously (hepatic and pulmonary metastases) or sequentially (hepatic then pulmonary metastases, or vice versa). Simultaneous disease may be aggressive, and thus may be approached with caution by the clinician. The aim of this study was to determine the outcomes following hepatic and pulmonary resection for simultaneously presenting metastatic CRC. METHODS: A retrospective review was undertaken of a prospectively maintained database to identify patients presenting with simultaneous hepatopulmonary disease who underwent hepatic resection. Patients' electronic records were used to identify clinicopathological variables. The log rank test was used to determine survival, and χ(2) analysis to determine predictors of failure of intended treatment. RESULTS: Fifty-nine patients were identified and underwent hepatic resection; median survival was 45·4 months and the 5-year survival rate 38 per cent. Twenty-two patients (37 per cent) did not have the intended pulmonary intervention owing to progression or recurrence of disease. Thirty-seven patients who progressed to hepatopulmonary resection had a median survival of 54·2 months (5-year survival rate 43 per cent). Those who had hepatic resection alone had a median survival of 24·0 months (5-year survival rate 30 per cent). Failure to progress to pulmonary resection was predicted by heavy nodal burden of primary colorectal disease and bilobar hepatic metastases. Redo pulmonary surgery following pulmonary recurrence did not confer a survival benefit. CONCLUSION: Selected patients with simultaneous hepatopulmonary CRC metastases should be considered for attempted curative resection, but some patients may not receive the intended treatment owing to progression of pulmonary disease after hepatic resection.

The management of the surgical complications of HELLP syndrome.

INTRODUCTION: Complications from HELLP (Haemolysis, Elevated Liver enzymes and Low Platelet) syndrome may present as an emergency to any surgeon. We review the ten-year experience of a tertiary hepatobiliary centre managing HELLP patients. Three selected cases are described to highlight our management strategy and a systematic review of the recent literature is presented. METHODS: All patients with HELLP syndrome were identified from a prospectively maintained database and their details collated. Subsequently, a detailed search of PubMed was carried out to identify all case series of HELLP syndrome in the literature in the English language since 1999. RESULTS: On review of 1,002 cases, 10 patients were identified with surgical complications of HELLP syndrome. Seven of these patients had a significant liver injury. Only three of these required surgical intervention for liver injury although four other patients required surgical intervention for other complications. There was no maternal mortality in this series. Review of the literature identified 49 cases in 31 publications. The management approaches of these patients were compared with ours. CONCLUSIONS: We have presented a large series of patients with surgical complications resulting from HELLP syndrome managed without maternal mortality. This review has confirmed that haemodynamically stable patients with HELLP syndrome associated hepatic rupture can be conservatively treated successfully. However, in unstable patients, perihepatic packing and transfer to a specialist liver unit is recommended.

Nodular regenerative hyperplasia (NRH) complicating oxaliplatin chemotherapy in patients undergoing resection of colorectal liver metastases.

INTRODUCTION: Sinusoidal obstructive syndrome (SOS) is well associated with the use oxaliplatin-based chemotherapy, and represents a spectrum of hepatotoxicity, with nodular regenerative hyperplasia (NRH) representing the most significant degree of injury. The aim of this study was to determine the prevalence of NRH in patients undergoing resection of colorectal liver metastases (CRLM) and to determine its impact on outcome. METHODS: From January 2000 to December 2010, some 978 first primary liver resections were performed for CRLM. A prospectively maintained database was analysed to identify all patients with evidence of NRH in the non-tumour portion of their histopathology specimens. Clinical data of these patients was reviewed and outcomes assessed. RESULTS: Five patients exhibited NRH (four males, one female) with a median age of 69 years (range: 35-74). Three patients presented with synchronous hepatic metastases, and two with metachronous lesions. All received at least 6 cycles of oxaliplatin as either adjuvant or neo-adjuvant chemotherapy. Only one patient developed a post-operative complication namely transient hepatic failure that required a 4-day stay in the intensive care unit. The median hospital stay was 6 days (range: 6-14 days). There were no 90-day mortalities. One patient is alive and disease free at 55 months, the remaining 4 died of recurrent disease between 37 and 70 months following diagnosis of their primary tumours. CONCLUSIONS: NRH is not an uncommon finding amongst patients with SOS with all patients having received oxaliplatin-based chemotherapy. Data on outcome would suggest no increased morbidity and mortality associated with the presence of NRH.

Evaluation of the safety and immunogenicity of a candidate tuberculosis vaccine, MVA85A, delivered by aerosol to the lungs of macaques.

Tuberculosis (TB) is a reemerging disease. The only available vaccine, Mycobacterium bovis BCG, is delivered intradermally and confers highly variable efficacy against pulmonary disease. There is an urgent need for improved vaccination strategies. Murine studies suggest that immunizations delivered directly to the respiratory mucosa might be a more effective route of vaccination. This study compared the immunogenicity of a leading candidate tuberculosis (TB) vaccine, modified vaccinia virus Ankara expressing antigen 85A (MVA85A), in rhesus macaques, delivered either as an aerosol or as an intradermal boost immunization 12 weeks after an intradermal BCG prime vaccine. Aerosol vaccination was well tolerated. MVA85A delivered by aerosol or by intradermal injection induced antigen-specific immune responses in the periphery and the lung, with a trend toward the highest response when the compartment and route of delivery were matched. The ability of poxvirus-vectored vaccines delivered by the systemic route to induce responses in the mucosal immune compartment in macaques is in contrast to the independent compartmentalization of mucosal and systemic immune systems described in mice. Unlike intradermal vaccination, aerosol vaccination did not induce a detectable serum anti-vector antibody response. The delivery of vaccines to the lungs might provide an immunization strategy that limits the induction of systemic anti-vector immunity, which would be extremely useful in the development of improved vaccine strategies. This is the first study to show a recombinant MVA-vectored vaccine to be highly immunogenic when delivered by the aerosol route to nonhuman primates. These results provide important safety and proof-of-concept data for further evaluation of this route of immunization for use in human clinical trials.

Loss of OPA1 disturbs cellular calcium homeostasis and sensitizes for excitotoxicity.

Optic atrophy 1 (OPA1) mutations cause dominant optic atrophy (DOA) with retinal ganglion cell (RGC) and optic nerve degeneration. The mechanism for the selective degeneration of RGCs in DOA remains elusive. To address the mechanism, we reduced OPA1 protein expression in cell lines and RGCs by RNA interference. OPA1 loss results in mitochondrial fragmentation, deficiency in oxidative phosphorylation, decreased ATP levels, decreased mitochondrial Ca(2+) retention capacity, reduced mtDNA copy numbers, and sensitization to apoptotic insults. We demonstrate profound cristae depletion and loss of crista junctions in OPA1 knockdown cells, whereas the remaining crista junctions preserve their normal size. OPA1-depleted cells exhibit decreased agonist-evoked mitochondrial Ca(2+) transients and corresponding reduction of NAD(+) to NADH, but the impairment in NADH oxidation leads to an overall more reduced mitochondrial NADH pool. Although in our model OPA1 loss in RGCs has no apparent impact on mitochondrial morphology, it decreases buffering of cytosolic Ca(2+) and sensitizes RGCs to excitotoxic injury. Exposure to glutamate triggers delayed calcium deregulation (DCD), often in a reversible manner, indicating partial resistance of RGCs to this injury. However, when OPA1 is depleted, DCD becomes irreversible. Thus, our data show that whereas OPA1 is required for mitochondrial fusion, maintenance of crista morphology and oxidative phosphorylation, loss of OPA1 also results in defective Ca(2+) homeostasis.

Meta-analysis of prospective trials determining the short- and mid-term effect of elective open and endovascular repair of abdominal aortic aneurysms on quality of life.

BACKGROUND: Repair of an abdominal aortic aneurysm (AAA) is undertaken to prevent rupture. Intervention is by either open repair (OR) or a more minimally invasive endovascular repair (EVAR). Quality-of-life (QoL) analysis is an important health outcome and a number of single studies have assessed QoL following OR and EVAR. This was a meta-analysis of published studies to assess the effect of an intervention on QoL in patients with an AAA. METHODS: A systematic literature search was undertaken for studies prospectively reporting QoL analysis in patients with an AAA undergoing elective intervention. A multivariable meta-analysis model was developed in which the outcomes were mean changes in QoL scores over time, both for all AAA repairs (OR and EVAR) and comparing OR with EVAR. RESULTS: Data were collated from 16 studies (14 OR, 12 EVAR). The results suggested that treating an AAA had an effect on patient-reported QoL, evident from the statistically significant changes predominantly in domains assessing physical ability and pain. QoL was affected most within the first 3 months after any form of intervention, and was more pronounced following OR. Furthermore, a deterioration in the Physical Component Summary score following an AAA repair (either OR or EVAR) was evident at 12 months after intervention. CONCLUSION: Treating an AAA deleteriously affects patient-reported QoL over the first year following intervention.

Biliary papillomatosis in three Caucasian patients in a Western centre.

INTRODUCTION: Biliary papillomatosis (BP) is a rare condition with a strong potential for malignant transformation and cases from Western centres are sparse.(1) We discuss the presentation, investigation and management of this condition in three Caucasian patients and present a review of the existing literature on BP. PATIENTS AND METHODS: The case notes of three Caucasian patients with BP who presented to our tertiary referral centre were reviewed. Their case histories, investigations and managements are presented. A search of MEDLINE, PubMed and Cochrane databases was performed to review relevant literature around BP. DISCUSSION: BP is a rare condition characterised by multiple papillary adenomas involving the biliary tree which lead to recurrent attacks of cholangitis. It is a low-grade neoplasm with high malignant potential and should be regarded as a pre-malignant lesion.

Hindlimb response to tactile stimulation of the pastern and coronet.

REASONS FOR PERFORMING STUDY: Lightweight tactile stimulators attached to the hind pasterns increase the height of the hind hoof flight arc but details of the induced changes in swing phase kinematics and kinetics have not been investigated. HYPOTHESES: Stimulators on the hind pasterns are associated with increased hindlimb joint flexions and increased positive work performed by the hip and tarsal musculature. MATERIALS AND METHODS: Nine nonlame horses trotted 4 times with and without 55 g tactile stimulators loosely attached around the hind pasterns. Height of the flight arc and peak flexion angles of the hindlimb joints were measured and net positive and negative work performed across each joint during the swing phase were calculated using inverse dynamics analysis and compared across paired conditions. RESULTS: Speed and stride duration did not change but stimulators were associated with a reduction in hind stance duration. The flight arc was higher with stimulators due to increased flexions of the stifle, tarsal, metatarsophalangeal and distal interphalangeal joints. Positive work increased in the tarsal musculature, but not in the hip musculature, and negative work increased across the stifle, metatarsophalangeal and distal interphalangeal joints. POTENTIAL RELEVANCE: The effects of tactile stimulation of the hind pasterns on joint motion and muscle activation may be used in physiotherapy and rehabilitation to restore or increase flexion of the hindlimb joints with the exception of the hip joint. The ability to stimulate concentric activity of the tarsal musculature may have therapeutic applications in conditions such as toe dragging.

The advanced helical generator.

A high explosive pulsed power generator called the advanced helical generator (AHG) has been designed, built, and successfully tested. The AHG incorporates design principles of voltage and current management to obtain a high current and energy gain. Its design was facilitated by the use of modern modeling tools as well as high precision manufacture. The result was a first-shot success. The AHG delivered 16 MA of current and 11 MJ of energy to a quasistatic 80 nH inductive load. A current gain of 160 times was obtained with a peak exponential rise time of 20 micros. We will describe in detail the design and testing of the AHG.

Note: The full function test explosive generator.

We have conducted three tests of a new pulsed power device called the full function test. These tests represented the culmination of an effort to establish a high energy pulsed power capability based on high explosive pulsed power (HEPP) technology. This involved an extensive computational modeling, engineering, fabrication, and fielding effort. The experiments were highly successful and a new U.S. record for magnetic energy was obtained.

Short-term habituation of equine limb kinematics to tactile stimulation of the coronet.

UNLABELLED: A lightweight bracelet that provides tactile stimulation to the horse's pastern and coronet induces a higher flight arc of the hoof. This study addresses the pattern of habituation to these devices. OBJECTIVE: To evaluate short-term habituation to tactile stimulation of the pastern and coronet in trotting horses. METHODS: Tactile stimulation was provided by a lightweight (55 g) device consisting of a strap with seven chains that was attached loosely around the pastern. Reflective markers were fixed to the dorsal hoof wall, the forehead and over the tenth thoracic vertebra of eight sound horses. The horses trotted in hand 10 times at a consistent velocity along a 30 m runway under three conditions applied in random order at two-hour intervals: no stimulators, stimulators on both front hooves or stimulators on both hind hooves. One stride per trial was analyzed to determine peak hoof heights in the swing phase. Sequential trials with stimulators were compared with unstimulated trials using a nested ANCOVA and Bonferronni's post hoc test (P < 0.005). RESULTS: Peak hind hoof height increased significantly for all 10 trials when wearing hind stimulators, whereas peak fore hoof height increased during the first six trials only when wearing fore stimulators. The first trial with stimulators showed the greatest elevation, followed by a rapid decrease over the next three trials and then a more gradual decrease. CONCLUSIONS: If the goal is to facilitate a generalized muscular response, a short burst of tactile stimulation is likely to be most effective, whereas longer periods of stimulation will be more effective for strength training.

Nephrotoxicity in the elderly due to co-prescription of angiotensin converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs.

Both angiotensin converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs can lead to functional renal insufficiency. In an observational study we assessed the frequency of this adverse effect in patients aged over 75 years receiving these drugs in combination. In one year, out of 1500 patients whose records were screened, 12 were prescribed this combination. 2 developed acute renal failure, of whom one died and the other recovered after discontinuation of both drugs. 4 patients showed deterioration in renal function, which returned to normal after one of the drugs was stopped. Renal function remained stable in 6 patients: patients with deterioration in renal function were older and more likely to be on diuretics. This drug combination is commonly nephrotoxic in the elderly and should be avoided, especially in those taking diuretics.

Diagnoses in discharge communications: how far are they reliable?

To discover whether general practitioners are correctly notified of a patient's final diagnosis following hospital discharge, an observational study was undertaken in a district general hospital. The final diagnosis was compared with the diagnosis documented in the discharge summary and the take-home prescription. Two hundred discharges were studied. Only 163 (81%) discharge summaries and 138 (69%) take-home prescriptions had the correct diagnosis; 24 (12%) take-home prescriptions did not have any diagnosis at all. In some cases the diagnosis differed between the discharge summaries and the take-home prescriptions. Only in 122 (61%) cases was the final diagnosis correctly documented in both instances. Communication regarding diagnosis in discharge letters is less than adequate. Every effort should be made to improve this.

Colonic perforation associated with slow-release diclofenac sodium.

Upper gastrointestinal tract complications due to non-steroidal anti-inflammatory drugs are well recognised. However, adverse effects on large intestinal mucosa are less common and less well recognised, even though they carry a significant morbidity and mortality. Here we report a case of colonic perforation in a healthy woman without any underlying colonic pathology associated with ingestion of slow release diclofenac sodium.

Cytogenetic abnormalities in the myelodysplastic syndromes and occupational or environmental exposure.

Patients with myelodysplastic syndromes (MDS) have high frequencies of cytogenetic abnormalities and evidence is accumulating of associations between exposure history and primary MDS. The objective of this article is to examine the relationship between histories of occupational or environmental exposure and presence of cytogenetic abnormalities. A case control study of MDS patients estimated lifetime exposure to more than 90 potential hazards in 400 age, sex, and area of residence matched patient and control pairs. A parallel cytogenetics study undertaken at time of diagnosis, independently of any knowledge of exposure history, identified 75 cytogenetically abnormal and 139 normal (186 not studied). Odds ratios of MDS patients and their matched controls were compared for 3 groups: cytogenetically abnormal, normal, and not known. The odds ratios for all exposures combined were possibly higher among cytogenetically abnormal 2.0 (95% confidence interval 0.8-5.9) than among normal 1.0 (0.6-1.8). This pattern was observed for exposure to semimetals, abnormal 4.0 (0.4-195.1) and normal 0.5 (0.1-1.0) and inorganic dusts, 1.6 (0. 6-3.8) and 0.4 (0.1-1.4) respectively. The pattern was principally in abnormalities in chromosomes 5 and 7. For organic chemicals and radiation, the odds ratios for both cytogenetically abnormal and normal were marginally raised: organic 1.8 (0.6-6.0) and 1.3 (0.6-2.9), respectively, and radiation 1.7 (0.5-5.6) and 1.3 (0.4-4.7) respectively. For radiation, abnormalities were mostly in chromosome 8. This study of association between exposures and cytogenetics in primary MDS complements those previously reported in secondary MDS and may provide some insight into pathogenetic mechanisms that lead to development of MDS. (Blood. 2000;95:2093-2097)

Underutilization of antithrombotic therapy in atrial fibrillation.

Most patients with atrial fibrillation should be considered for antithrombotic therapy. In a retrospective survey we investigated practice in two hospitals. For patients at high risk, established guidelines recommend warfarin, or aspirin if anticoagulants are contraindicated; for those at medium risk, either may be used. Of 156 with atrial fibrillation (acute, chronic or paroxysmal), 119 were at high risk, mean age 79 years. According to the guidelines, 89 of these were suitable for anticoagulation but only 49 (55%) received warfarin; 27 received aspirin and 13 neither. Of 27 patients at medium risk (mean age 70 years), 6 were not prescribed any antithrombotic therapy. This survey indicates that guidelines on antithrombotic therapy are commonly disregarded and that, in particular, warfarin is underutilized in the group for whom it is most indicated.