Demonstration of improved laser preheat with a cryogenically cooled magnetized liner inertial fusion platform.

We report on progress implementing and testing cryogenically cooled platforms for Magnetized Liner Inertial Fusion (MagLIF) experiments. Two cryogenically cooled experimental platforms were developed: an integrated platform fielded on the Z pulsed power generator that combines magnetization, laser preheat, and pulsed-power-driven fuel compression and a laser-only platform in a separate chamber that enables measurements of the laser preheat energy using shadowgraphy measurements. The laser-only experiments suggest that ∼89% ± 10% of the incident energy is coupled to the fuel in cooled targets across the energy range tested, significantly higher than previous warm experiments that achieved at most 67% coupling and in line with simulation predictions. The laser preheat configuration was applied to a cryogenically cooled integrated experiment that used a novel cryostat configuration that cooled the MagLIF liner from both ends. The integrated experiment, z3576, coupled 2.32 ± 0.25 kJ preheat energy to the fuel, the highest to-date, demonstrated excellent temperature control and nominal current delivery, and produced one of the highest pressure stagnations as determined by a Bayesian analysis of the data.

[Metabolic acidosis : Diagnosis and treatment]. / Metabolische Azidose : Diagnostik und Therapie.

Acid-base disorders and in particular metabolic acidosis are very common in critically ill patients and contribute significantly to morbidity and mortality. We shed light on the most common causes, the pathophysiology and treatments. Particular attention will be paid to the common practice of substituting sodium bicarbonate in the light of recent study results.

Polycapillary x-ray lenses for single-shot, laser-driven powder diffraction.

X-ray diffraction measurements to characterize phase transitions of dynamically compressed high-Z matter at Mbar pressures require both sufficient photon energy and fluence to create data with high fidelity in a single shot. Large-scale laser systems can be used to generate x-ray sources above 10 keV utilizing line radiation of mid-Z elements. However, the laser-to-x-ray energy conversion efficiency at these energies is low, and thermal x-rays or hot electrons result in unwanted background. We employ polycapillary x-ray lenses in powder x-ray diffraction measurements using solid target x-ray emission from either the Z-Beamlet long-pulse or the Z-Petawatt (ZPW) short-pulse laser systems at Sandia National Laboratories. Polycapillary lenses allow for a 100-fold fluence increase compared to a conventional pinhole aperture while simultaneously reducing the background significantly. This enables diffraction measurements up to 16 keV at the few-photon signal level as well as diffraction experiments with ZPW at full intensity.

Renal complications of cancer therapies.

Cancer patients often exhibit preexisting renal impairment and are simultaneously at risk for developing further kidney injury due to direct or indirect complications of oncological therapies. The nature of kidney injury is highly dependent on the therapy regimen used, and the spectrum of possible kidney stressors has widened as a result of the development of new therapeutic modalities such as molecular therapy or immunotherapy. Indirect renal complications are often due to volume depletion or other therapy-related side effects. Direct toxicity from "classic" chemotherapy treatments such as cisplatin usually leads to acute tubular necrosis, whereas treatment with protein kinase inhibitors is more likely to cause disorders such as thrombotic microangiopathy. Immunotherapy often affects kidneys through the development of acute interstitial nephritis. Because of the high risk of nephrological complications in oncological patients, close monitoring of renal function and the early involvement of a nephrologist are strongly recommended.

Self-generated surface magnetic fields inhibit laser-driven sheath acceleration of high-energy protons.

High-intensity lasers interacting with solid foils produce copious numbers of relativistic electrons, which in turn create strong sheath electric fields around the target. The proton beams accelerated in such fields have remarkable properties, enabling ultrafast radiography of plasma phenomena or isochoric heating of dense materials. In view of longer-term multidisciplinary purposes (e.g., spallation neutron sources or cancer therapy), the current challenge is to achieve proton energies well in excess of 100 MeV, which is commonly thought to be possible by raising the on-target laser intensity. Here we present experimental and numerical results demonstrating that magnetostatic fields self-generated on the target surface may pose a fundamental limit to sheath-driven ion acceleration for high enough laser intensities. Those fields can be strong enough (~105 T at laser intensities ~1021 W cm-2) to magnetize the sheath electrons and deflect protons off the accelerating region, hence degrading the maximum energy the latter can acquire.

The role of interventions in the cancer evolution-an evolutionary games approach.

We propose to endow evolutionary gamemodels with changes of the phenotypes adjustment during the transient generations performed by the parameters in the payoff matrix which determine the fitness resulting from different interactions between players. These changes represent an alteration of access to external resources which, in turn, may reflect anticancer treatment. In the case of spatial games, these functions are represented by an additional lattice where another and parallel game based on cellular automata is performed. The main assumption of the spatial games is that each cell on the lattice is represented by a player following only one strategy. We propose to consider cells on the spatial lattice as heterogeneous (instead of homogeneous), so that each particular player may contain mixed phenotypes. Spatial games of the type, proposed by us, are called multidimensional spatial evolutionary games (MSEG). It may happen that within the population, all of the players have diverse phenotypes (which probably better describes biological phenomena). The additional lattice representing the evolution of resources increases only the dimension of the lattice in the MSEG.

Risk prediction of acute kidney injury by [TIMP-2]•[IGFBP7].

Acute kidney injury (AKI) is a common syndrome with increased mortality, a heavy burden of illness and high cost. The Kidney Disease Improving Global Outcomes (KDIGO) criteria for staging of AKI have been validated in large patient cohorts and classify AKI into three stages. In order to achieve prevention or early therapy, the focus of scientific interest is early detection and risk prediction of AKI. The combination of the two cell cycle arrest markers [TIMP-2]·[IGFBP7] in the urine shows good results in the risk prediction of AKI in different clinical settings (intensive care medicine, sepsis, cardiac surgery, emergency department). Clinical use is currently being tested in different randomized intervention studies.

A high-speed two-frame, 1-2 ns gated X-ray CMOS imager used as a hohlraum diagnostic on the National Ignition Facility (invited).

A novel x-ray imager, which takes time-resolved gated images along a single line-of-sight, has been successfully implemented at the National Ignition Facility (NIF). This Gated Laser Entrance Hole diagnostic, G-LEH, incorporates a high-speed multi-frame CMOS x-ray imager developed by Sandia National Laboratories to upgrade the existing Static X-ray Imager diagnostic at NIF. The new diagnostic is capable of capturing two laser-entrance-hole images per shot on its 1024 × 448 pixels photo-detector array, with integration times as short as 1.6 ns per frame. Since its implementation on NIF, the G-LEH diagnostic has successfully acquired images from various experimental campaigns, providing critical new information for understanding the hohlraum performance in inertial confinement fusion (ICF) experiments, such as the size of the laser entrance hole vs. time, the growth of the laser-heated gold plasma bubble, the change in brightness of inner beam spots due to time-varying cross beam energy transfer, and plasma instability growth near the hohlraum wall.

Obstetric and gynecologic problems associated with eating disorders.

OBJECTIVE: This article summarizes the literature on obstetric and gynecologic complications associated with eating disorders. METHOD: We performed a comprehensive search of the current literature on obstetric and gynecologic complications associated with eating disorders using PubMed. More recent randomized-controlled trials and larger data sets received priority. We also chose those that we felt would be the most relevant to providers. RESULTS: Common obstetric and gynecologic complications for women with eating disorders include infertility, unplanned pregnancy, miscarriage, poor nutrition during pregnancy, having a baby with small head circumference, postpartum depression and anxiety, sexual dysfunction and complications in the treatment for gynecologic cancers. There are also unique associations by eating disorder diagnosis, such as earlier cessation of breastfeeding in anorexia nervosa; increased polycystic ovarian syndrome in bulimia nervosa; and complications of obesity as a result of binge eating disorder. DISCUSSION: We focus on possible biological and psychosocial factors underpinning risk for poor obstetric and gynecological outcomes in eating disorders. Understanding these factors may improve both our understanding of the reproductive needs of women with eating disorders and their medical outcomes. We also highlight the importance of building multidisciplinary teams to provide comprehensive care to women with eating disorders during the reproductive years.

A typical Wegeners granulomatosis -- but not pauci-immune!

We present a the case of 58-year old man who was admitted to hospital with typical clinical features (bloody nasal discharge, arthralgia, acute kidney injury with a nephritic syndrome) consisting with Wegeners granulomatosis (WG). CT-scan showed pulmonary nodules and antineutrophil cytoplasmatic antibodies (ANCA) were elevated. A kidney biopsy showed a crescentic glomerulonephritis, but not pauci-immune-immune with a histopathological staining of a mesangioproliferative IgA-glomerulonephritis. The patient was put on prednisolone and i.v. cyclophosphamid (CYCLOPS-protocol (1). The anti-proteinase-3 antibody titer decreased and the CT-scan showed decreased activity of Wegener's granulomatosis (BVAS 26 dropped to 2) and the patient`s serum creatinine level was stable. The exact nosological relation of mesangial IgA-nephropathy to WG is still unclear. This case underlines that knowledge of renal histology is essential in the management of patients with renal disease, especially in patients with hematuria and/or proeinuria with positive ANCA.

[Hypertension due to aortic coarctation--a missed clinical diagnosis]. / Hypertonie bei Aortenisthmusstenose--eine übersehene klinische Diagnose.

HISTORY AND FINDINGS: A 30-year-old woman presented to our emergency department with severe headaches, dizziness and uncontrolled hypertension. She had arterial hypertension and a known heart murmur since adolescence. Previous medical work up did not reveal any cause for secondary hypertension. Recently her blood pressure had been difficult to control. A systolic murmur as well as absent inguinal and feet pulses were notable at the physical examination. INVESTIGATIONS: When performing doppler ultrasound the closing pressures of the dorsalis pedis arteries were only 70 mm Hg compared to a blood pressure reading of 160 mm Hg on the upper arms. Thoracic magnetic resonance imaging showed subtotal aortic coarctation causing the differences in blood pressures. Echocardiography and cardiac catheterization additionally revealed a moderately stenosed bicuspid aortic valve, the pressure gradient across the coarctation was 30 mm Hg. THERAPY AND COURSE: Despite the severity of the coarctation an interventional approach was favoured instead of a classical operative therapy. Balloon dilatation with stent implantation was performed without complications. Since the intervention blood pressure have remained normotensive, the coarctation gradient being markedly reduced. CONCLUSIONS: In young patients with arterial hypertension, as well as in cases of severe and refractory hypertension, causes of secondary hypertension must be looked for and excluded. Especially when hypertension occurs in adolescence, aortic coarctation should be taken into account, in addition to renal or endocrine causes. A thorough physical examination with cardiac auscultation and checking of all peripheral pulses is the crucial step to the diagnosis.

[Salt appetite, cramps and palpitations in a 21-year old medical secretary]. / Salzhunger, Krämpfe und Palpitationen bei einer 21-jährigen Arzthelferin.

Hypokalemia is a common finding. The clinical presentation can be paralyses and cardiac arrhythmias. We present a normotensive young woman with salt appetite, cramps and palpitations. In our case report the patient shows a positive family history for hypopotassemia, a metabolic alkalosis with hypotension, and hypocalciuria with an increased urinary potassium loss. The levels of renin and aldosterone were elevated. After a negative testing for metabolites of diuretics, we obtained a positive result of the suspected SLC12A3 genetic test. This mutation leads to a failure of the thiazide-sensitive sodium-2-chloride-cotransporter, the so called Gitelman syndrome, which presents similar to a chronic thiazide therapy. The Gitelman syndrome is a rare disease with renal potassium loss and hypotension. Especially in young patients around the age of twenty or in patients with chronic intractable hypopotassemia a Gitelman syndrome should be considered.

[A 65-year-old man with history of claudication, palpable purpura and livedo reticularis]. / Claudicatio intermittens, palpable Purpura und Livedo reticularis bei einem 65-jährigen Patienten.

HISTORY AND ADMISSION FINDINGS: A 65-year-old man was admitted with history of claudication symptoms and painful skin lesions of the lower legs. Physical examination showed palpable purpura of the lower legs and livedo reticularis, most marked at the forefoot and toes. INVESTIGATIONS: Computed tomography (CT) showed an aortic mass 2 cm above the bifurcation. This was treated after angiography with a covered stent. Biopsy of the skin lesions showed no sign of vasculitis and no cholesterol crystals. TREATMENT AND COURSE: The patient was discharged and remained symptom-free for 9 months. He was readmitted at that time with recurrent complaints. CT revealed a subtotal stenosis of the aortic stent. A skin biopsy showed CD31-positive tumor cells in small arteries. Biopsy of a new osteolytic lesion in the ileum confirmed the diagnosis of angiosarcoma of the aorta. The patient decided in favor of palliative care and was discharged from the hospital. CONCLUSION: Primary tumors of the aorta, although they are rare, should be considered in the presence of an intravascular mass with stenosis to blood flow. A skin biopsy is easy to conduct and often leads to the final diagnosis.

A controlled clinical trial to evaluate the effect of GanedenBC(30) on immunological markers.

GanedenBC(30), a probiotic, has been shown to significantly increase T-cell production of TNF-alpha after ex vivo exposure to a strain of adenovirus (AdenoVI) or influenza A (H3N2 Texas strain [FluTex]). The current controlled study was designed to further evaluate the effect of GanedenBC(30) on immunological marker levels following viral exposure. Ten healthy subjects' baseline immunological marker levels were analyzed. Subjects consumed 1 capsule/day of GanedenBC(30) for 28 days and returned for post-treatment immunological marker evaluation. Subjects' baseline measurements served as their own control. All subjects completed the study with no adverse events; however, one subject was excluded from the final analysis based on a reasonable consideration as an outlier. CD3+CD69+ cells, IL-6, IL-8, interferon-gamma (IFN-gamma) and TNF-alpha levels were increased after exposure to AdenoVI and FluTex. IL-1beta levels also increased after exposure to AdenoVI but were decreased after ex vivo exposure to FluTex. CD3+CD69+ cells increased significantly (P = 0.023) after exposure to both viral strains. Differences in IL-8 levels after FluTex exposure achieved statistical significance (P = 0.039) as did IFN-gamma levels after AdenoVI exposure (P = 0.039). A regimen of one capsule per day containing 500 million CFU of GanedenBC30 may be a safe and effective option for enhancing the immunological response to common viral respiratory tract infections.

Fibrogenic growth factors in encapsulating peritoneal sclerosis.

BACKGROUND: Increased local levels of fibrogenic growth hormones contribute substantially to the process of encapsulating peritoneal sclerosis (EPS) in animal models. METHODS: We analyzed probes from patients with normal kidney function (n = 10), with normal kidney function and inflammation (n = 10), on PD without (n = 10) and with EPS (n = 9). We investigated the degree of fibrosis and the number of vessels and vasculopathy. Additionally, we investigated the expression of NFkappaB, TGFbeta1, TGFbeta1 receptor, TGFbeta2, TGFbeta2 receptor, FGF-BP, CTGF and VEGF by immunohistochemistry. RESULTS: In EPS, we found an exclusive upregulation of VEGF (normal 0, appendicitis 1.0 +/- 1.2, PD 1.7 +/- 1.8 and EPS 5.7 +/- 4.4; p < 0.0001), whereas in PD, CTGF was significantly increased (normal 6.0 +/- 2.8, appendicitis 7.3 +/- 2.5, PD 10.0 +/- 1.8 and EPS 7.3 +/- 2.1; p = 0.0059). The results for the TGFbeta system and NFkappaB were not uniform, in EPS no increases were demonstrable. Vasculopathy was significantly more pronounced in EPS (normal 0.4 +/- 0.5, appendicitis 0.2 +/- 0.3, PD 1.0 +/- 0.7 and EPS 1.6 +/- 1.2; p < 0.0001) than in PD or inflammation (normal 30 +/- 16, appendicitis 82 +/- 48, PD 1,936 +/- 952 and EPS 2,613 +/- 1,209; p < 0.0001), whereas the density of vessels were decreased (normal 125 +/- 114, appendicitis 817 +/- 347, PD 81 +/- 57 and EPS 36 +/- 33; p < 0.0001). CONCLUSIONS: The process of EPS was associated with increased VEGF in the peritoneum. The reduced density of vessels compared with marked fibrosis could point to hypoxia as an inducer.

Controlled transport and focusing of laser-accelerated protons with miniature magnetic devices.

This Letter demonstrates the transporting and focusing of laser-accelerated 14 MeV protons by permanent magnet miniature quadrupole lenses providing field gradients of up to 500 T/m. The approach is highly reproducible and predictable, leading to a focal spot of (286 x 173) microm full width at half maximum 50 cm behind the source. It decouples the relativistic laser-proton acceleration from the beam transport, paving the way to optimize both separately. The collimation and the subsequent energy selection obtained are perfectly applicable for upcoming high-energy, high-repetition rate laser systems.

Pacemaker infection with propionibacterium and a nephritic sediment.

Like any other implanted foreign body, the different parts of pacemakers (pulse generator pocket, epicardial or transvenous leads) can become infected. Staphylococcus aureus and coagulase-negative staphylococci are the causative organisms in most of the cases (65 â 75%), propionibacterium is described to be involved in only 1% of cases. This report describes a case of nephritic sediment in a young female patient with a pacemaker implantation 9 years ago because of a third degree atrioventricular block, in which a battery exchange was necessary 2.5 years ago. This young patient was referred from a nephrologist for renal biopsy because of a nephritic sediment and diffuse complaints including low-grade fever with a suspected underlying autoimmune disease. The laboratory examinations were all negative with the exception of a diminished C3 complement level. Blood cultures were positive for propionibacterium, but the microbiologists were considering it as a contamination. 11 more blood cultures collected thereafter were all positive and a transesophageal ultrasound revealed a small vegetation at 1 of the transvenous electrodes of the pacemaker. Because of a penicillin allergy she was treated with clindamycin, and the blood cultures were negative after a few days. After a full course (7 weeks) of antibiotic treatment the C3 complement level normalized and a series of 10 blood cultures remained negative 10 â 15 days after discontinuation of antibiotic therapy. Discussing all the differential diagnoses of a nephritic sediment combined with hypocomplementemia, positive blood cultures and a vegetation on a pacemaker electrode in the transesophageal ultrasound, the diagnosis of an immune complex glomerulonephritis due to a propionibacterium pacemaker infection needs no confirmation by renal biopsy.

Robust association of the APOE epsilon4 allele with premature myocardial infarction especially in patients without hypercholesterolaemia: the Aachen study.

BACKGROUND: Genetic influence on the manifestation of coronary artery disease (CAD) and myocardial infarction (MI) has been shown previously. From many candidate genes the APOE (apolipoprotein E) with the major alleles epsilon2/epsilon3/epsilon4 is in the focus of interest. MATERIALS AND METHODS: In 1817 patients admitted for their first left heart catheterization at a premature age (males < 55 and females < 65) the association of APOE alleles with MI was analysed. Genotyping was done by 5' exonuclease assay (TaqMan). RESULTS APOE was significantly associated with hypercholesterolaemia (epsilon4 72% vs. epsilon3 66% vs. epsilon2 51%; P < 0.0001), and premature MI (epsilon4 57% vs. epsilon3 50% vs. epsilon2 41%; P < 0.0001; hazard ratio 1.41, 95%CI 1.14-1.75). In patients without hypercholesterolaemia, the APOE allele epsilon4 was highly predictive for the presence of premature MI (epsilon4 55% vs. epsilon3 45% vs. epsilon2 28%; P < 0.0001; hazard ratio 1.75, 95%CI 1.19-2.57). CONCLUSION: The APOEepsilon4 allele shows a robust association with premature MI independent of hypercholesterolaemia.