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Background Percutaneous nephrostomy tubes (PCN) are indicated for relief of urinary tract obstruction. These devices are prone to mechanical and infectious complications. The infection rate at 90 days is ±20%. Our objective was to determine whether discordant antimicrobial coverage provided prior to PCN exchange was associated with a higher rate of recurrent infection compared with those who received concordant therapy. Methods We retrospectively reviewed 780 patients that had undergone initial PCN placement at our institution between July 2014 and February 2017. We only included patients that had developed a definite PCN infection, subsequent PCN exchange, with a minimum 30 day post-PCN exchange follow up. We defined PCN infection as the presence of a positive urine culture (≥104 cfu/mL) plus symptoms consistent with a urinary tract infection. Recurrence was defined as a new PCN infection with the isolation of the same organism to the initial episode. Antibiotics were defined as concordant if they had activity against all organisms’ isolated based on antimicrobial susceptibilities. Results A total of 47 patients met our inclusion criteria. The median age of patients was 59, with 49% being male. The most common underlying tumors were urothelial (45%), cervical (17%) and prostate cancer (15%). Clinical characteristics included ureteral stents (17%), diabetes (19%), history of GU surgery (38%), and active chemotherapy at the time of PCN insertion (70%). The median time to onset of infection was 42 days. Infections were polymicrobial in 50% of the cases. The most common organisms encountered were Pseudomonas spp. (36%), Enterococcus spp. (23%) and Escherichia coli (18%). The median length of follow up of PCN tubes after exchange was 55 days. There were 12 (26%) recurrences occurring at a median time of 27 days. The provision of discordant antibiotics preceding PCN exchange was significantly associated with recurrence of infection (66.7% vs. 12.8%; P < 0.002). Conclusion Discordant antimicrobial therapy provided during PCN exchange, in the setting of a PCN infection is associated with a higher rate of relapse. Therefore, to decrease the high rate for PCN reinfection, we propose that prior to PCN exchange secondary to infection, patients should be receiving concordant antimicrobial therapy. Disclosures All authors: No reported disclosures.

Summary About 20 species of rapidly growing mycobacteria species that are capable of infecting human beings and causing bloodstream infections have been identified. Many more of these species are being discovered worldwide, especially in resource-poor settings. These microorganisms have been known to cause outbreaks and pseudo-outbreaks. Although rapidly growing mycobacteria are not highly virulent or life threatening, they have a high predisposition to create biofilms and to colonise and infect intravascular catheters. Early detection and identification of specific species can help to estimate predictable antimicrobial susceptibility patterns. However, because susceptibility data originate from developed countries, studies in resource-poor settings urgently need to be done. The best outcome of cure without recurrence depends on a combination of at least 4 weeks of treatment with two or more active antimicrobial agents, plus removal of the intravascular catheter. We review and discuss the epidemiology, pathogenesis, diagnosis, management, and outcomes of rapidly growing mycobacterial bloodstream infections.

The L-type Ca2+ channel is the main route for calcium entry into cardiac myocytes, and it is essential for contraction. Alterations in whole cell L-type Ca2+ channel current and Ca2+ homeostasis have been implicated in the development of cardiomyopathies. Cytoskeletal proteins can influence whole cell L-type Ca2+ current and mitochondrial function. Duchenne muscular dystrophy is a fatal X-linked disease that leads to progressive muscle weakness due to the absence of cytoskeletal protein dystrophin. This includes dilated cardiomyopathy, but the mechanisms are not well understood. We sought to identify the effect of alterations in whole cell L-type Ca2+ channel current on mitochondrial function in the murine model of Duchenne muscular dystrophy ( mdx). Activation of the L-type Ca2+ channel with the dihydropyridine agonist BayK(−) caused a significantly larger increase in cytosolic Ca2+ in mdx vs. wild-type ( wt) ventricular myocytes. Consistent with elevated cytosolic Ca2+, resting mitochondrial Ca2+, NADH, and mitochondrial superoxide were significantly greater in mdx vs. wt myocytes. Activation of the channel with BayK(−) caused a further increase in mitochondrial Ca2+, NADH, and superoxide in mdx myocytes. The ratios of the increases were similar to the ratios recorded in wt myocytes. In mitochondria isolated from 8-wk-old mdx hearts, respiration and mitochondrial electron transport chain complex activity were similar to mitochondria isolated from wt hearts. We conclude that mitochondria function at a higher level of resting calcium in the intact mdx myocyte and activation of the L-type Ca2+ channel contributes to alterations in calcium handling by the mitochondria. This perturbation may contribute to the development of cardiomyopathy.

Rationale: Regulator of G-protein signaling 5 (RGS5) modulates G-protein-coupled receptor signaling and is prominently expressed in arterial smooth muscle cells. Our group first reported that RGS5 is important in vascular remodeling during tumor angiogenesis. We hypothesized that RGS5 may play an important role in vessel wall remodeling and blood pressure regulation. Objective: To demonstrate that RGS5 has a unique and nonredundant role in the pathogenesis of hypertension and to identify crucial RGS5-regulated signaling pathways. Methods and Results: We observed that arterial RGS5 expression is downregulated with chronically elevated blood pressure after angiotensin II infusion. Using a knockout mouse model, radiotelemetry, and pharmacological inhibition, we subsequently showed that loss of RGS5 results in profound hypertension. RGS5 signaling is linked to the renin–angiotensin system and directly controls vascular resistance, vessel contractility, and remodeling. RGS5 deficiency aggravates pathophysiological features of hypertension, such as medial hypertrophy and fibrosis. Moreover, we demonstrate that protein kinase C, mitogen-activated protein kinase/extracellular signal–regulated kinase, and Rho kinase signaling pathways are major effectors of RGS5-mediated hypertension. Conclusions: Loss of RGS5 results in hypertension. Loss of RGS5 signaling also correlates with hyper-responsiveness to vasoconstrictors and vascular stiffening. This establishes a significant, distinct, and causal role of RGS5 in vascular homeostasis. RGS5 modulates signaling through the angiotensin II receptor 1 and major Gα q -coupled downstream pathways, including Rho kinase. So far, activation of RhoA/Rho kinase has not been associated with RGS molecules. Thus, RGS5 is a crucial regulator of blood pressure homeostasis with significant clinical implications for vascular pathologies, such as hypertension.

Ontario Hydro has had experience in designing and qualifying safety critical software used in the reactor shutdown systems of its nuclear generating stations. During software design, an analysis of system level hazards and potential hardware failure effects provide input to determining what safeguards will be needed. One form of safeguard, called software self checks, continually monitor the health of the computer on line. The design of self checks usually is a trade off between the amount of computing resources required, the software complexity, and the level of safeguarding provided. As part of the software verification activity, a software hazards analysis is performed, which identifies any failure modes that could lead to the software causing an unsafe state, and which recommends changes to mitigate that potential. These recommendations may involve a re-structuring of the software to be more resistant to failure, or the introduction of other safeguarding measures. This paper discusses how Ontario Hydro has implemented these aspects of software design and verification into safety critical software used in reactor shutdown systems. >

After many years of fusion research, the conditions needed for a D–T fusion reactor have been approached on the Tokamak Fusion Test Reactor (TFTR) [Fusion Technol. 21, 1324 (1992)]. For the first time the unique phenomena present in a D–T plasma are now being studied in a laboratory plasma.The first magnetic fusion experiments to study plasmas using nearly equal concentrations of deuterium and tritium have been carried out on TFTR. At present the maximum fusion power of 10.7 MW, using 39.5 MW of neutral‐beam heating, in a supershot discharge and 6.7 MW in a high‐βp discharge following a current rampdown. The fusion power density in a core of the plasma is ≊2.8 MW m−3, exceeding that expected in the International Thermonuclear Experimental Reactor (ITER) [Plasma Physics and Controlled Nuclear Fusion Research (International Atomic Energy Agency, Vienna, 1991), Vol. 3, p. 239] at 1500 MW total fusion power. The energy confinement time, τE, is observed to increase in D–T, relative to D plasmas, by 20% and the ni(0) Ti(0) τE product by 55%. The improvement in thermal confinement is caused primarily by a decrease in ion heat conductivity in both supershot and limiter‐H‐mode discharges. Extensive lithium pellet injection increased the confinement time to 0.27 s and enabled higher current operation in both supershot and high‐βp discharges. Ion cyclotron range of frequencies (ICRF) heating of a D–T plasma, using the second harmonic of tritium, has been demonstrated. First measurements of the confined alpha particles have been performed and found to be in good agreement with TRANSP [Nucl. Fusion 34, 1247 (1994)] simulations. Initial measurements of the alpha ash profile have been compared with simulations using particle transport coefficients from He gas puffing experiments. The loss of alpha particles to a detector at the bottom of the vessel is well described by the first‐orbit loss mechanism. No loss due to alpha‐particle‐driven instabilities has yet been observed. D–T experiments on TFTR will continue to explore the assumptions of the ITER design and to examine some of the physics issues associated with an advanced tokamak reactor.

The high power D-T experiments on the tokamak fusion test reactor (TFTR) at the Princeton Plasma Physics Laboratory commenced in November 1993. During initial operation of the tritium systems a number of start-up problems surfaced and had to be corrected. These were corrected through a series of system modifications and upgrades and by repair of failed or inadequate components. Even as these operational concerns were being addressed, the tritium systems continued to support D-T operations on the tokamak. During the first six months of D-T operations more than 107 kCi of tritium were processed successfully by the tritium systems. D-T experiments conducted at TFTR during this period provided significant new data. Fusion power in excess of 9 MW was achieved in May 1994. This paper describes some of the early start-up issues, and reports on the operation of the tritium system and the tritium tracking and accounting system during the early phase of TFTR D-T experiments.

Mutations in cardiac troponin I (cTnI) or β-myosin heavy chain (MHC) account for approximately 45% of genotyped families with hypertrophic cardiomyopathy (HCM). HCM is characterised by disorganisation of cytoskeletal proteins and altered energy metabolism. The L-type Ca2+ channel (LTCC) plays a critical role in cardiac excitation and contraction. We have demonstrated that activation of LTCC can also regulate mitochondrial function. HCM mouse models cTnI-G203S and αMHC403/+ exhibit a faster LTCC inactivation rate and altered mitochondrial responses after LTCC activation. This results in a “hypermetabolic” mitochondrial state. We examined the efficacy of in vitro and in vivo exposure of cTnI-G203S and αMHC403/+ mice to a peptide derived against the alpha-interacting domain (AID-TAT) on mitochondrial function by assessing alterations in mitochondrial membrane potential (Ψm, JC-1 fluorescence) and mitochondrial oxygen consumption (flavoprotein autofluorescence). In vitro exposure of cTnI-G203S cardiomyocytes to 10µM AID-TAT attenuated the increase in JC-1 fluorescence in response to activation of LTCC with channel agonist BayK(-) (cTnI-G203S+AID-TAT=4.4±0.36% increase, n=6 versus cTnI-G203S=29.2±1.8% increase, n=15, p

Implantation of cardiac implantable electronic devices (CIED) has dramatically increased over the past several years. Although several preventive measures have been implemented, there has been a disproportional increase in the number of CIED-related infections. To evaluate the adherence of bacteria to polyurethane and titanium, the 2 surfaces that coat the CIED, we proceeded with an in vitro study using the most common microorganisms responsible for CIED-related infections. Original, unused 1 × 1 centimeter titanium and polyurethane flat plates were incubated with coagulase-negative staphylococci, methicillin-resistant Staphylococcus aureus, and Pseudomonas aeruginosa. Each experiment was repeated 5 times. After incubating the titanium and polyurethane plates for 3, 6, 12, or 24 hours, all 3 organisms displayed a higher grade of bacterial adherence to the polyurethane versus titanium surfaces (p = 0.01). In conclusion, to decrease the rate of bacterial adherence, especially during the immediate postimplantation period when the CIED is at high risk for bacterial adherence, colonization, and infection, it may be prudent to consider constructing CIED surfaces with a higher proportion of titanium over polyurethane. Animal studies are warranted to explore the relevance of these laboratory findings.

Secreted frizzled-related protein 4 (sFRP4) is a Wnt signaling antagonist. Classically, sFRP4 antagonizes the canonical Wnt signaling pathway, resulting in decreased cellular proliferation and increased apoptosis. Recent research from our laboratory has established that sFRP4 inhibits angiogenesis by decreasing proliferation, migration, and tube formation of endothelial cells. The objective of this study was to examine the role of sFRP4's cysteine-rich domain (CRD) and netrin-like domain (NLD) in angiogenesis inhibition. Experiments were carried out to examine cell death and tube formation of endothelial cells after treatment with the CRD and the NLD. The CRD was seen to inhibit tube formation of endothelial cells, which suggests that this domain is important to sFRP4's antiangiogenesis property. In addition, the NLD promoted endothelial cell death and may also inhibit angiogenesis. Furthermore, treatment with the CRD and the NLD increased endothelial intracellular calcium levels. Our findings implicate a role for both the CRD and NLD in angiogenesis inhibition by sFRP4. It is suggestive of alternative antiangiogenic downstream targets of canonical Wnt signaling and a possible importance of the noncanonical Ca2+ Wnt signaling pathway in sFRP4-mediated angiogenesis inhibition.

Although no lipids were considered to be present inside the nuclear membrane (Berg, 1951), their presence in chromatin was first demonstrated cytochemically by Chayen et al (1957) in Vicia faba root apices and liver nuclei. Sphingomyelin was further demonstrated biochemically to represent some 7% of isolated calf thymus nucleohistone preparations (Chayen and Gahan, 1958), the presence of sphingomyelin being confirmed by X-ray diffraction studies (Wilkins M. H. F, personal communication). Nevertheless, the lipids and carbohydrate present in the nuclei were considered to be minor components, most of them being due to contamination during chromatin separation (Tata et al.1972). In contrast, some biochemical measurements showed the presence of neutral lipids (Song and Rebel 1987) and phospholipids in nuclei and chromosomes from a large variety of tissues (Chayen et al 1959, a, b, Gahan 1965a). The criticism linked to possible contamination cannot be applied to the cytochemical evidence that showed the presence of chromatin-associated phospholipid material in a broad range of tissues (Idelman 1957, 1958a,b, Chayen et al. 1959a,b, La Cour et al. 1958, Gahan 1965a,b, Cave and Gahan 1971, Gahan et al. 1974, Gahan et al. 1987, ViolaMagni et al. 1985a). In a combined autoradiographic and biochemical analysis, it was shown that H3 -ethalomine incorporated into Vicia faba root nuclei was localised at the level of chromatin and nucleoli rather than at the level of the nuclear membrane. Hepatocyte nuclei treated with Triton and hypotonic solutions liberate chromatin that contains 10% of the total nuclear lipids. The composition of fatty acids demonstrated an enrichment of palmitic acid and a reduction in arachidonic acid (Albi et al. 1994) thus supporting the idea that these lipids cannot be derived from the nuclear membrane. In addition, the chromatographic separation of phospholipids has demonstrated an enrichment of both sphingomyelin and phosphatidylserine with respect to the nuclear membrane composition (Albi et al. 1994). The data were also confirmed by studying the turnover of phospholipids at the level of the microsomes, nuclear membrane and chromatin from hepatocytes (Viola-Magni et al. 1986). In rats injected with radioactive phosphorus, the peak of incorporation was observed after 6 h in microsomes and nuclear membranes, but only after 9h in the chromatin. This confirmed a lack of possible chromatin contamination.

This paper describes the therapeutic components of an eclectic, intensive inpatient treatment strategy for Vietnam and Desert Storm veterans with posttraumatic stress disorder. A specific treatment model was devised by this author. The procedure was a collaborative effort: the staff and the patients participated in this preparatory phase treatment program at the Tripler Posttraumatic Stress Unit, Tripler Army Medical Center, Honolulu, Hawaii. The basic treatment is based on group therapy, utilizing educational, cognitive-behavioral therapy, gestalt therapy, and individualized psychotherapy, and eye movement desensitization strategies. The timing and sequencing of these treatments are a critical part of the model, and we have come to refer to it as the layered model because the treatments are layered, much like the delicious parfait dessert.

Recently, an Edge Localized Mode (ELM) control coil was developed for use on the DIII-D tokamak. The coil design represented a significant challenge due primarily to the requirement for the coil insulation to withstand bakeout temperatures of 400°C for extended periods. This requirement ruled out most common organic insulating systems and necessitated a significant prototyping and development effort, leading to the selection of an advanced high temperature glass/polyimide resin system. The development included developing a heating mechanism that provided the discrete temperature ramp cycles and cure cycles required by this exotic resin. To complicate matters, the resin had a limited shelf life. Additionally the coil was small and rectangular in shape with rather small corner radii. This created a corner buildup that was not previously encountered and made dimensional control difficult. Another unique design requirement was the need to apply a sufficient internal pre-load to the wound and cured coil to insure there will be no relative motion between the coil and the Inconel case due to Lorentz forces from the 4 Tesla toroidal field on the vessel center post. This led to development of very unique leaf springs and a significant research and development effort coupled with an equally arduous finite element analysis effort. A satisfactory prototype was produced. This paper will focus primarily on the manufacturing challenges and discuss the prototyping effort.

The spherical tokamak (ST) is a leading candidate for a fusion nuclear science facility (FNSF) due to its compact size and modular configuration. The National Spherical Torus eXperiment (NSTX) is a MA-class ST facility in the U.S. actively developing the physics basis for an ST-based FNSF. In plasma transport research, ST experiments exhibit a strong (nearly inverse) scaling of normalized confinement with collisionality, and if this trend holds at low collisionality, high fusion neutron fluences could be achievable in very compact ST devices. A major motivation for the NSTX Upgrade (NSTX-U) is to span the next factor of 3–6 reduction in collisionality. To achieve this collisionality reduction with equilibrated profiles, NSTX-U will double the toroidal field, plasma current, and NBI heating power and increase the pulse length from 1–1.5s to 5s. In the area of stability and advanced scenarios, plasmas with higher aspect ratio and elongation, high β N , and broad current profiles approaching those of an ST-based FNSF have been produced in NSTX using active control of the plasma β and advanced resistive wall mode control. High non-inductive current fractions of 70% have been sustained for many current diffusion times, and the more tangential injection of the 2nd NBI of the Upgrade is projected to increase the NBI current drive by up to a factor of 2 and support 100% non-inductive operation. More tangential NBI injection is also projected to provide non-solenoidal current ramp-up (from I P = 0.4MA up to 0.8–1MA) as needed for an ST-based FNSF. In boundary physics, NSTX and higher-A tokamaks measure an inverse relationship between the scrape-off layer heat-flux width and plasma current that could unfavorably impact next-step devices. Recently, NSTX has successfully demonstrated very high flux expansion and substantial heat-flux reduction using a snowflake divertor configuration, and this type of divertor is incorporated in the NSTX-U design. The physics and engineering design supporting NSTX Upgrade are described.

As life expectancy continues to increase and biotechnology advances, the use of cardiovascular implantable devices will continue to rise. Unfortunately, despite modern medical advances, the infection and mortality rates remain excessively elevated. This article reviews the pathophysiology and general concepts of cardiac device–related infections, including the physical and chemical characteristics of the medical device, host response to the medical device, and the microbiologic virulence factors. Infections of the most commonly utilized cardiovascular implantable devices, including cardiovascular implantable electronic devices, bioprosthetic and mechanical valves, ventricular assist devices, total artificial hearts, and coronary artery stents, are reviewed in detail.

Glutathionylation as a posttranslational modification of proteins is becoming increasingly recognized, but its role in many diseases has not been demonstrated. Oxidative stress and alterations in calcium homeostasis are associated with the development of cardiac hypertrophy. Because the cardiac L-type Ca(2+) channel can be persistently activated after exposure to H(2)O(2), the aim of this study was to determine whether alterations in channel function were associated with glutathionylation of the α(1C) subunit (Ca(v)1.2) channel protein. Immunoblot analysis indicated that Ca(v)1.2 protein is significantly glutathionylated after exposure to H(2)O(2) and glutathione in vitro and after ischemia-reperfusion injury. L-type Ca(2+) channel macroscopic current and intracellular calcium were significantly increased in myocytes after exposure to oxidized glutathione and reversed by glutaredoxin. The increase in current correlated with an increase in open probability of the channel assessed as changes in single-channel activity after exposing the human long N-terminal Ca(v)1.2 to H(2)O(2) or oxidized glutathione. We also demonstrate that the Ca(v)1.2 channel is significantly glutathionylated in ischemic human heart. We conclude that oxidative stress is associated with an increase in glutathionylation of the Ca(v)1.2 channel protein. We suggest that the associated constitutive activity contributes to the development of pathology in ischemic heart disease.

Cytoskeletal proteins stabilize cell structure but also regulate subcellular distribution of mitochondria and cardiac L-type Ca2+ channel (LTCC) activity. We have previously demonstrated that mitochondrial function can be regulated by alterations in LTCC activity. This effect was attenuated when the cytoskeleton was disrupted with latrunculin A. To further explore this, we determined whether regulation of mitochondrial function by the LTCC is altered in a murine model of Duchenne Muscular Dystrophy(mdx). Mitochondrial membrane potential (Ψm) and metabolic activity was assessed after activation of the LTCC in cardiac myocytes isolated from C57BL/10ScSn-Dmdmdx/Arc (mdx) and C57BL/10ScSnArc (control) mice. Exposure of control myocytes to 10μM BayK(-) (LTCC agonist) caused a 11.4±1.7% increase in Ψm assessed as alterations in JC-1 compared to myocytes exposed to inactive BayK(+) (n=8, p

In most yeast species, the mitochondrial DNA (mtDNA) has been reported to be a circular molecule. However, two cases of linear mtDNA with specific termini have previously been described. We examined the frequency of occurrence of linear forms of mtDNA among yeasts by pulsed-field gel electrophoresis. Among the 58 species from the genera Pichia and Williopsis that we examined, linear mtDNA was found with unexpectedly high frequency. Thirteen species contained a linear mtDNA, as confirmed by restriction mapping, and labeling, and electron microscopy. The mtDNAs from Pichia pijperi, Williopsis mrakii, and P. jadinii were studied in detail. In each case, the left and right terminal fragments shared homologous sequences. Between the terminal repeats, the order of mitochondrial genes was the same in all of the linear mtDNAs examined, despite a large variation of the genome size. This constancy of gene order is in contrast with the great variation of gene arrangement in circular mitochondrial genomes of yeasts. The coding sequences determined on several genes were highly homologous to those of the circular mtDNAs, suggesting that these two forms of mtDNA are not of distant origins.

Provocation tests (PTs) with the suspected compounds are considered the 'gold standard' for establishing or excluding a diagnosis of hypersensitivity to non-steroidal anti-inflammatory drugs (NSAIDs). However, only a few studies have evaluated the potential determinants of positive responses to PTs.The aims of this study are to assess the reliability of clinical histories as indicators of NSAID hypersensitivity, as well as the risk factors for a positive PT.Two hundred and seventy-five subjects with an unequivocal history of NSAID hypersensitivity reactions underwent PTs with the suspected drugs. To establish the potential determinants of positive PTs, we examined the following variables: gender, age at the time of reaction (40 or ≥40 years), family and personal histories of atopy, patients who had reacted to one or more NSAIDs, time interval between drug intake and symptom onset (immediate or non-immediate reactions), time interval between the last drug reaction and the allergologic examination (≤12 or12 months), and inclusion in a category of the Stevenson et al. classification.Two hundred and fourteen (77.8%) subjects tolerated the suspected drugs and 61 (22.2%) reacted. Age40 years, male gender, immediate reactions, and time interval ≤12 months were significant risk factors for a positive PT.Our study confirms that clinical histories are not reliable tools for diagnosing NSAID hypersensitivity. Therefore, we recommend that suspected cases should undergo drug PTs. However, further studies on large samples of NSAID-sensitive patients are necessary to establish the risk factors that allow the number of candidates for PTs to be reduced.

Extreme hypoglycorrhachia is usually caused by bacterial meningitis; however, suspicion should be raised if a patient with persistent extreme hypoglycorrhachia, pleocytosis and negative microbiological studies remains refractory to antimicrobial therapy. Viola describes the case of a 55-year-old man with chronic leptomeningitis and persistent hypoglycorrhachia, who was found to have Currarino syndrome. This syndrome is a complex genetic disorder that includes the following triad: sacral bony defect, presacral mass, and an anorectal malformation. Leptomeningitis in this patient was attributed to cholesterol crystals contained in a large presacral cyst with a communicating fistula to the CNS. Background. A 55-year-old man presented with 4 months of chronic meningitis, neutrophilic pleocytosis and extreme hypoglycorrhachia—an abnormally low concentration of glucose in the cerebrospinal fluid (CSF). A previous neurological work-up had revealed no noteworthy abnormalities. Despite the brief improvements that were seen after numerous trials of antibiotics and corticosteroids, the symptoms relapsed soon after corticosteroids were discontinued. Lumbar puncture revealed cholesterol crystals in the CSF and imaging studies revealed a sickle-shaped sacrum, partial rectal stenosis, and a communicating presacral meningocele with an epidermoid–dermoid mass. Extreme hypoglycorrhachia seems almost always to be bacterial in origin, but its differential diagnosis is, nevertheless, extensive. The definition, physiology, pathophysiology and differential diagnosis of hypoglycorrhachia are reviewed here. Investigations. Physical examination, laboratory testing, multiple imaging studies including CT and MRI of the brain and spinal cord, as well as myelography and CSF analysis. Diagnosis. Cholesterol-induced leptomeningitis in a patient with Currarino syndrome, a triad that consists of sacral bone defects, congenital hindgut anomaly, and a presacral tumor. Management. The patient was initially treated with multiple antimicrobials and steroids. However, once the cholesterol crystals and communicating presacral cyst were identified, the condition was successfully managed with surgically resection of the cyst.

Limitations to current long range weather radars include reduced coverage of the lower atmosphere, coarse cross range resolution and coarse temporal resolution due to the mechanical scanning. A proposed network of low cost, short range digital radars for monitoring hydrometeor phenomena is described and its potential benefit in providing lower atmospheric coverage is discussed. The benefits of replacing the scanning antenna at each node of the network with a phased array are also discussed.

There exist no standardized methods for culturing cardiac rhythm management devices. To identify the most optimal culturing method, we compared various techniques that comprise vortex, sonication, and incubation or combinations thereof. Incubation alone yielded bacterial colony counts similar to those of other culturing combinations and is the least labor-intensive.

Summary 1. Calcium is necessary for myocardial function, including contraction and maintenance of cardiac output. Calcium is also necessary for myocardial energetics and production of ATP by mitochondria, but the mechanisms for calcium regulation by mitochondria are still not fully resolved. 2. The cytoskeleton plays an important role in maintaining a cell’s integrity. It is now recognized that cytoskeletal proteins can also assist in the transmission of signals from the plasma membrane to intracellular organelles. Cytoskeletal proteins can regulate the function of the L-type Ca2+ channel and alter intracellular calcium homeostasis. 3. Recent evidence suggests that calcium influx through the L-type Ca2+ channel is sufficient to alter a number of mitochondrial functional parameters, including superoxide production, NADH production and metabolic activity, assessed as the formation of formazan from tetrazolium salt. This occurs in a calcium-dependent manner. 4. Activation of the L-type Ca2+ channel also alters mitochondrial membrane potential in a calcium-independent manner and this is assisted by movement of the auxiliary β2-subunit through F-actin filaments. 5. Because the L-type Ca2+ channel is the initiator of contraction, a functional coupling between the channels and mitochondria may assist in meeting myocardial energy demand on a beat-to-beat basis.

The Liquid Lithium Divertor (LLD) on NSTX will be the first test of a fully-toroidal liquid lithium divertor in a high-power magnetic confinement device. It will replace part of the lower outboard divertor between a specified inside and outside radius, and ultimately provide a lithium surface exposed to the plasma with enough depth to absorb a significant particle flux.

Photogrammetry, a state-of-the-art technique of metrology employing digital photographs as the vehicle for measurement, has been investigated in the fusion environment. Benefits of this high tolerance methodology include relatively easy deployment for multiple point measurements and deformation/distortion studies. Depending on the equipment used, photogrammetric systems can reach tolerances of 25 microns (0.001 in) to 100 microns (0.004 in) on a 3-meter object. During the fabrication and assembly of the National Compact Stellarator Experiment (NCSX) the primary measurement systems deployed were CAD coordinate-based computer metrology equipment and supporting algorithms such as both interferometer-aided (IFM) and absolute distance measurementbased (ADM) laser trackers, as well as portable Coordinate Measurement Machine (CMM) arms. Photogrammetry was employed at NCSX as a quick and easy tool to monitor coil distortions incurred during welding operations of the machine assembly process and as a way to reduce assembly downtime for metrology processes. This paper will explore the use of photogrammetry on NCSX during field period assembly (FPA) and the results it achieved. It will also explore other applications of this method and discuss future plans for use.

The fastening of the National Compact Stellarator Experiment's (NCSX) modular coils presented a number of engineering and manufacturing challenges due to the high magnetic forces, need to control induced currents, tight tolerances and restrictive space envelope. A fastening method using high strength studs, jack nuts, insulating spacers, bushings and alumina coated shims was developed which met the requirements. A test program was conducted to verify the design. The tests included measurements of flatness of the spacers, determination of contact area, torque vs. tension of the studs and jack nuts, friction coefficient tests on the alumina and G-10 insulators, electrical tests, and tension relaxation tests due to temperature excursions from room temperature to liquid nitrogen temperatures. This paper will describe the design and the results of the test program.

The National Compact Stellarator Experiment (NCSX) required precise positioning of the field coils in order to generate suitable magnetic fields. A set of three modular field coils were assembled to form the Half Field-Period Assemblies (HPA). Final assembly of the HPA required a welded shear plate to join individual coils in the nose region due to the geometric limitations and the strength constraints. Each of the modular coil windings was wound on a stainless steel alloy (Stellalloy) casting. The alloy is similar to austenitic 316 stainless steel. During the initial welding trials, severe distortion, of approximately 1/16″, was observed in the joint caused by weld shrinkage. The distortion was well outside the requirements of the design. Solutions were attempted through several simultaneous routes. The joint design was modified, welding processes were changed, and specialized heat reduction techniques were utilized. A final joint design was selected to reduce the amount of weld material needed to be deposited, while maintaining adequate penetration and strength. Several welding processes and techniques using Miller Axcess equipment were utilized that significantly reduced heat input. The final assembly of the HPA was successful. Distortion was controlled to 0.012″, well within the acceptable design tolerance range of 0.020″ over a 3.5 foot length.

The L-type Ca(2+) channel plays a critical role in cardiac function as the main route for entry of calcium into cardiac myocytes. It is essential to excitability as it shapes the long plateau phase of the cardiac action potential that is unique to cardiac ventricular myocytes. It is necessary for contraction as it triggers the release of calcium from sarcoplasmic reticulum stores for actin-myosin interaction. The L-type Ca(2+) channel also regulates cytoplasmic calcium levels. It is well recognised that an increase in intracellular calcium is involved in the activation of growth-promoting signal pathways. Recently reactive oxygen species have been implicated in the activation of signal pathways and the development of pathological hypertrophy. There is now evidence that implicates activation of the L-type Ca(2+) channel with persistent alterations in calcium homeostasis and cellular reactive oxygen species production as a possible trigger of cardiac hypertrophy. A number of different approaches have been used to modify channel function with the view to preventing ischemia-reperfusion injury, cardiac hypertrophy or cardiac failure providing good evidence that the L-type Ca(2+) channel may be an efficacious target in the prevention of cardiac pathology.

In this paper we report the molecular cloning of the gene encoding the bovine brain ribonuclease. The nucleotide sequence determined in this work shows a high degree of identity to the homologous gene encoding the bovine pancreatic ribonuclease. Processing of the primary transcripts of these genes also follows a similar pathway, splicing of the unique intron in the 5' untranslated region occurs at corresponding positions. Expression of the bovine brain ribonuclease gene can be detected both at the transcriptional and translational levels in all the regions of the brain examined.

The L-type Ca(2+) channel is responsible for initiating contraction in the heart. Mitochondria are responsible for meeting the cellular energy demands and calcium is required for the activity of metabolic intermediates. We examined whether activation of the L-type Ca(2+) channel alone is sufficient to alter mitochondrial function. The channel was activated directly with the dihydropyridine agonist BayK(-) or voltage-clamp of the plasma membrane and indirectly by depolarization of the membrane with high KCl. Activation of the channel increased superoxide production (assessed as changes in dihydroethidium fluorescence), NADH production and metabolic activity (assessed as formation of formazan from tetrazolium) in a calcium-dependent manner. Activation of the channel also increased mitochondrial membrane potential assessed as changes in JC-1 fluorescence. The response was reversible upon inactivation of the channel during voltage-clamp of the plasma membrane and did not appear to require calcium. We examined whether the response may be mediated through movement of cytoskeletal proteins. Depolymerization of actin or exposing cells to a peptide directed against the alpha-interacting domain of the alpha(1C)-subunit of the channel (thereby preventing movement of the beta-subunit) attenuated the increase in mitochondrial membrane potential. We conclude that activation of the L-type Ca(2+) channel can regulate mitochondrial function and the response appears to be modulated by movement through the cytoskeleton.

Administration of meropenem to penicillin-allergic patients who might benefit from this treatment is usually avoided because of a 47.4% rate of cross-reactivity to imipenem, the prototype of the carbapenem class of beta-lactam antibiotics, demonstrated in a single study on the basis of positive responses to skin tests with imipenem reagents. However, recent studies of ours have demonstrated a very low rate of cross-reactivity between penicillins and both meropenem and imipenem in adults.To assess cross-reactivity and tolerability of meropenem in children with documented penicillin allergy.One hundred and eight consecutive children who had suffered a total of 129 immediate reactions (120 urticarial and/or angioedematous manifestations and 9 anaphylactic shocks) to penicillins and had positive results to skin tests for at least one of the penicillin reagents tested underwent skin tests with meropenem and negative subjects were challenged with it.One subject (0.9%) displayed a positive intradermal test to meropenem. The remaining 107 subjects with negative skin tests to meropenem tolerated challenges. Challenges were not followed by full therapeutic courses.Our results demonstrate a low rate of cross-reactivity between penicillins and meropenem. Therefore, the practice of avoiding meropenem in children with immunoglobulin E-mediated hypersensitivity could be abandoned; in those who especially require meropenem treatment, prophylactic skin tests are advisable, because negative results indicate tolerability.

Corrigendum: Structural characterization of human heparanase reveals insights into substrate recognition

Postnatal exposure (from the second day after birth to 30 days) of rat pups to low levels of lead acetate (50 mg/kg body weight/day), administered by gastric intubation, yielded a maximum blood level of 76.1 micrograms/100 ml, at day 15 of age. Cerebellar and hippocampal lead contents were 8.67 micrograms/100 mg and 11.7 micrograms/100 mg, respectively, at day 30 of age. This lead exposure has been shown to elicit little change in some biochemical parameters in cerebellum and hippocampus. At the three ages investigated (5, 15, and 30 days after birth) there were no alterations of body weight; brain, cerebellum, and hippocampus wet weight; and DNA, RNA, protein and phospholipid content, either in total tissue or in mitochondria. A similar invariance following lead exposure was observed in mitochondrial succinate dehydrogenase and cytochrome oxidase activities. After intraperitoneal administration, the incorporation of [methyl-14C]thymidine into DNA and [5,6-3H]uridine into RNA of cerebellum and hippocampus showed a significant decrease only at day 5, reaching the control value at 15 and 30 days of age. After intraperitoneal injection, [2-3H]glycerol incorporation into total lipids and phospholipids of cerebellum and hippocampus also showed no significant changes in Pb-treated pups compared to controls at all three postnatal ages. We concluded that subclinical lead administration exerts its effect by slowing cell proliferation in the very early growth phase of the brain. It is likely that a metabolic compensative response to subtoxic effect of lead acetate may be brought about in cerebellum and hippocampus during critical phases of nervous system development between days 15 and 30.

The National Compact Stellarator Experiment (NCSX) is being constructed at the Princeton Plasma Physics Laboratory (PPPL) in partnership with the Oak Ridge National Laboratory (ORNL). Its mission is to develop the physics understanding of the compact stellarator and evaluate its potential for future fusion energy systems. Compact stellarators use 3D plasma shaping to produce a magnetic configuration that can be steady state without current drive or feedback control of instabilities. The NCSX has major radius 1.4 m, aspect ratio 4.4, 3 field periods, and a quasi-axisymmetric magnetic field. It is predicted to be stable and have good magnetic surfaces at beta > 4% and to have tokamak-like confinement properties. The device will provide the plasma configuration flexibility and the heating and diagnostic access needed to test physics predictions. Component production has advanced substantially since the first contracts were placed in 2004. Manufacture of the vacuum vessel was completed in 2006. All eighteen modular coil winding forms have been delivered, and twelve modular coils have been wound and epoxy impregnated. A contract for the (planar) toroidal field coils was placed in 2006 and manufacture is in progress. Assembly activities have begun and will be the project's main focus in the next few years. The engineering challenge of NCSX is to meet the requirements for complex geometries and tight tolerances within the cost and schedule constraints of a construction project. This paper will focus on how the engineering challenges of component production have been resolved, and how the assembly challenges are being met.

The national compact stellarator experiment (NCSX) will have an extensive set of external magnetic diagnostics. These include flux loops on the exterior surface of the vacuum vessel. Data from these sensors will be integrated with other magnetic sensors and used for plasma control and to constrain magnetic equilibrium reconstructions. NCSX is currently under construction at the Princeton Plasma Physics Laboratory (PPPL). The ex-vessel flux loops must be installed during machine construction since they will ultimately be trapped in the space between the vacuum vessel and the modular coil support shell. Detailed designs have been completed, locator templates have been fabricated and approximately one third of the 225 total loops have been installed as of mid February 2007. Modeling was performed by PPPL to determine the optimum size, placement and number of turns. Engineering of the flux loops was challenging as they must be accurately positioned, optimized geometry maintained and they must be robust and reliable in a bake and cryogenic environment for the lifetime of NCSX. Designs for the ex-vessel flux loops that meet these requirements are presented.

The National Compact Stellarator Experiment (NCSX) is being constructed at the Princeton Plasma Physics Laboratory (PPPL) in partnership with the Oak Ridge National Laboratory (ORNL). The stellarator core is designed to produce a compact 3-D plasma that combines stellarator and tokamak physics advantages. The complex geometry and tight fabrication tolerances of NCSX create some unique engineering and assembly challenges. This paper will describe a few of the challenges of the machine's Modular Coils and vacuum vessel field period assembly and how they are being solved. Coil assembly began in November 2005 and to date 3 Modular Coils have been completed. One vacuum vessel 120deg section has been delivered and field period assembly work began in May 2006. Machine sector sub-assembly, machine assembly, and testing will follow, leading to First Plasma in 2011.