Performance of the Los Alamos National Laboratory spallation-driven solid-deuterium ultra-cold neutron source.

In this paper, we describe the performance of the Los Alamos spallation-driven solid-deuterium ultra-cold neutron (UCN) source. Measurements of the cold neutron flux, the very low energy neutron production rate, and the UCN rates and density at the exit from the biological shield are presented and compared to Monte Carlo predictions. The cold neutron rates compare well with predictions from the Monte Carlo code MCNPX and the UCN rates agree with our custom UCN Monte Carlo code. The source is shown to perform as modeled. The maximum delivered UCN density at the exit from the biological shield is 52(9) UCN/cc with a solid deuterium volume of ~1500 cm(3).

Improved constraints on an axion-mediated force.

Low mass pseudoscalars, such as the axion, can mediate macroscopic parity and time-reversal symmetry-violating forces. We searched for such a force between polarized electrons and unpolarized atoms using a novel, magnetically unshielded torsion pendulum. We improved the laboratory bounds on this force by more than 10 orders of magnitude for pseudoscalars heavier than 1 meV and have constrained this force over a broad range of astrophysically interesting masses (10 µeV to 10 meV).

Reliability of the noninvasive sequence methods to estimate baroreflex function using the paradigm of brain death.

BACKGROUND: Various techniques have been developed to estimate spontaneous baroreflex sensitivity noninvasively. However, in the EuroBaVar study it has been shown that they yield differing results. AIM OF THE STUDY: To investigate the reliability of these methods further we compared the results of the most common sequence techniques. We used the paradigm of brain death with the absence of any baroreflex function. METHODS: In a prospective study we recorded breathing pattern, ECG and continuous blood pressure in 10 consecutive brain dead subjects of a neurointensive care unit. EuroBaVar sequence techniques 12-18 (ST12-ST18) were applied to the data sets and the number of sequences compared. RESULTS: Techniques which are based on thresholds in terms of blood pressure or R-R interval changes yielded the least false positive results: technique ST12, ST13, and ST14 detected very few sequences, while ST18 detected no sequence at all. Techniques using a correlation threshold (ST15-ST17) found a high number. CONCLUSION: This study demonstrates clearly that many of the sequence techniques used to estimate baroreflex sensitivity render false positive results in the unique paradigm of brain death. Thus, the method should be selected with regard to the biological signal and the pathophysiological background.

First measurement of the neutron beta asymmetry with ultracold neutrons.

We report the first measurement of an angular correlation parameter in neutron beta decay using polarized ultracold neutrons (UCN). We utilize UCN with energies below about 200 neV, which we guide and store for approximately 30 s in a Cu decay volume. The interaction of the neutron magnetic dipole moment with a static 7 T field external to the decay volume provides a 420 neV potential energy barrier to the spin state parallel to the field, polarizing the UCN before they pass through an adiabatic fast passage spin flipper and enter a decay volume, situated within a 1 T field in a 2x2pi solenoidal spectrometer. We determine a value for the beta-asymmetry parameter A_{0}=-0.1138+/-0.0046+/-0.0021.

Particle-physics implications of a recent test of the gravitational inverse-square law.

We use data from our recent search for violations of the gravitational inverse-square law to constrain dilaton, radion, and chameleon exchange forces as well as arbitrary vector or scalar Yukawa interactions. We test the interpretation of the PVLAS Collaboration effect and a conjectured "fat-graviton" scenario and constrain the gamma_{5} couplings of pseuodscalar bosons and arbitrary power-law interactions.

Measurements of ultracold-neutron lifetimes in solid deuterium.

We present the first measurements of the survival time of ultracold neutrons (UCNs) in solid deuterium (SD2). This critical parameter provides a fundamental limitation to the effectiveness of superthermal UCN sources that utilize solid ortho-deuterium as the source material. These measurements are performed utilizing a SD2 source coupled to a spallation source of neutrons, providing a demonstration of UCN production in this geometry and permitting systematic studies of the influence of thermal up-scatter and contamination with para-deuterium on the UCN survival time.

Detection of Borrelia burgdorferi-specific DNA in urine specimens from patients with erythema migrans before and after antibiotic therapy.

A nested PCR was developed for the detection of Borrelia burgdorferi-specific DNA in the urine of patients with erythema migrans. The target for the nested PCR was a specific region of the flagellin gene; the detection limit was less than five organisms of B. burgdorferi including all three species B. burgdorferi sensu stricto, B. afzelii, and B. garinii. A prospective, controlled, blinded study was performed with 26 patients with erythema migrans to evaluate the nested PCR method with clinical samples. B. burgdorferi-specific DNA could be detected in urine specimens from 22 of 24 patients with erythema migrans (sensitivity, 91.61%). Immediately after therapy, 11 of 19 patients still yielded positive results (58%). Eight weeks after therapy, 2 of 16 patients (13%) were positive by PCR of urine, and 20 weeks after treatment none of seven investigated urine samples was reactive. Essential for the sensitivity that was obtained was the development of a simple DNA extraction procedure. The results of the study indicate that the described method is highly sensitive and allows for the effective control of the efficacy of antibiotic therapy in patients with early Lyme borreliosis.

Polymerase chain reaction control of antibiotic treatment in dermatoborreliosis.

Assessment of the efficacy of an antibiotic drug used in patients with various manifestations of dermatoborreliosis is crucial. Clinical judgement alone (resolution of the present dermatologic lesion, prevention of later major or minor sequelae) is not sufficient in erythema migrans and acrodermatitis chronica atrophicans. Thus, laboratory tests are desirable to prove the benefit of an antimicrobial agent. It was intended to establish a constant parameter--besides the clinical picture--for assessing the efficacy of antibiotic treatment in patients with dermatoborreliosis in terms of eradication of Borrelia burgdorferi from the site of infection. Polymerase chain reaction (PCR) was therefore performed from pretreatment biopsy specimens from lesional skin of 36 erythema migrans patients (m:f = 15:21, mean age 49 years) and seven acrodermatitis chronica atrophicans patients (m:f = 0:7, mean age 59 years), respectively. After antibiotic therapy with minocycline (100 mg, orally twice daily, 14 days) for erythema migrans, and ceftriaxone (2 g, intravenously once daily, 14 days) for acrodermatitis chronica atrophicans another punch biopsy was obtained and analysed by PCR. In pretreatment specimens, B. burgdorferi-specific DNA was amplified by PCR in 23/36 erythema migrans patients (69%), and in 5/7 acrodermatitis chronica atrophicans patients (71%). After antibiotic therapy, PCR yielded negative results in all of these cases. Clinically, all patients showed complete recovery or at least marked improvement of lesions at this time. PCR appears to be a reliable parameter for the assessment of the efficacy of antibiotic treatment in dermatoborreliosis.

No detection of Borrelia burgdorferi-specific DNA in erythema migrans lesions after minocycline treatment.

BACKGROUND AND DESIGN: Early treatment of erythema migrans is important to prevent late complications. Minocycline possesses several attributes, making it potentially useful in the treatment of borrelial infections. In our study, minocycline was administered to 14 patients with erythema migrans. Punch biopsy specimens were obtained from the (affected) skin of all patients before and after therapy. The formalin-fixed, paraffin-embedded specimens were analyzed by polymerase chain reaction for the presence of Borrelia burgdorferi-specific DNA. RESULTS: Polymerase chain reaction assay succeeded in amplifying B burgdorferi-specific DNA from the first biopsy specimen, obtained from the border of erythema migrans before initiating treatment, in eight (57%) of 14 patients. At the end of minocycline therapy, however, polymerase chain reaction analysis disclosed no B burgdorferi-specific DNA in any of the 14 patients. The good clinical response of our patients with erythema migrans substantiates our molecular findings. CONCLUSIONS: The presented polymerase chain reaction data, together with the clinical outcome, indicate that minocycline may be useful for treatment of early Lyme borreliosis.

Granulomatous panniculitis caused by Candida albicans: a case presenting with multiple leg ulcers.

A 61-year-old woman had rapidly enlarging ulcers on both legs and three draining subcutaneous nodules on the left thigh. Findings of skin biopsy specimens revealed granulomatous panniculitis with a large number of blastospores and pseudohyphae. Candida albicans was cultured from the ulcers, the nodules, the mouth, the esophagus and gastric juice, feces, and urine. The ulcers healed after 5 months of therapy with itraconazole. Predisposing factors were diabetes mellitus, dysfunction of the hypothalamic-pituitary system, hypochromic anemia, and prior treatment with a broad-spectrum antibiotic. In contrast to three other reported cases of Candida panniculitis, our patient had not undergone immunosuppressive therapy.

Nodular focal fatty infiltration of the liver in acquired porphyria cutanea tarda.

A case is reported of acquired porphyria cutanea tarda (PCT) due to administered valproate acid in an epileptic patient. Sonography (US) and computed tomography (CT) showed multiple nodular, well-defined lesions of the liver. Biopsy confirmed the diagnosis of focal fatty infiltration and revealed additionally the signs of hepatic involvement in PCT. Focal fatty infiltration should be considered in patients with multiple liver lesions if there is a predisposing condition. PCT can be a further cause of this type of infiltration.

[Diagnosis of pigmented skin lesions using surface microscopy]. / Diagnosi delle lesioni cutanee pigmentate per mezzo della microscopia di superficie.

The clinical diagnosis of cutaneous pigmented tumors is often difficult. Surface microscopy represents an interesting approach to this problem. For this in vivo investigation, a stereomicroscope, a glass slide and immersion oil are used. In order to improve the clinicopathological correlation of pigmented skin lesions, morphological criteria discerned by surface microscopy--such as pigment network or black dots--were compared with the corresponding histological features. Surface microscopy opens a new dimension for the diagnosis and differential diagnosis of malignant melanomas, dysplastic nevi, or non-melanocytic pigmented tumors, and allows a better pre-operative assessment of these lesions.

Quantitative evaluation of melanoma cell invasion in three-dimensional confrontation cultures in vitro using automated image analysis.

Tumor invasion is a crucial feature of tumor growth in vivo. Confrontation cultures of multicellular melanoma spheroids and embryonic chick heart fragments provide a model for invasive growth in vitro. We have developed an image analysis method, which facilitates the objective measurement of tumor cell invasion in this model. Cryostat sections of confrontation cultures were immunohistochemically stained with an antiserum directed against the stromal component for automated recognition of the stroma tissue. The slides were automatically processed by a grey level based computerized image analysis system. On Spearman's rank correlation test, 25 out of 39 parameters correlated with the reference value of invasion, which was derived from the subjective evaluation of five independent observers. Two parameters combining the stroma margin and the total amount of stroma tissue completely reproduced the judgement of the morphologists in our test set. The quantitative evaluation of tumor invasion in vitro by automated image analysis may be helpful in pharmacologic and pathogenetic studies of tumor growth.

Karyometry of melanocytic lesions: quantitative assessment of the 'maturation to the depth'.

40 cases each of malignant melanoma. Spitz's nevus and benign intradermal nevus were examined using an interactive image analysis system. 60 consecutive nuclei were evaluated in the upper and lower portion of the melanocytic lesions. Besides basic karyometric data, a 'maturation parameter' (MP) expressing the previously described 'maturation to the depth' was assessed in each individual case, by calculating the ratio of the nuclear area in the deep portion and in the superficial portion. When the three parameters (superficial nuclear area, deep nuclear area and maturation parameter) were evaluated separately (k-nearest neighbour method), the efficiency of the superficial nuclear area was only 19%, compared with 72% for the deep nuclear area and 94% for the maturation parameter. Combination of the maturation parameter and the deep nuclear area provided an efficiency of 98% with a sensitivity of 98% and a specificity of 97%. The results indicate that the maturation parameter is superior to conventional karyometric data in the differentiation between benign and malignant melanocytic lesions.

Morphometrical analysis of mycosis fungoides on paraffin-embedded sections.

Morphometry was carried out on H&E stained paraffin sections of 29 cases of contact dermatitis (CD) and 35 cases of mycosis fungoides (MF) (patch stage 12; plaque stage 11; tumor stage 12); 9 nuclear parameters, mean thickness of the infiltrate and 5 stereological parameters were assessed for each slide. Application of a non-parametric discriminant analysis (k-nearest neighbour method) which is based on median of nuclear areas, mean maximal nuclear diameter, volume density and numerical density of nuclei provided discrimination between CD and patch stage MF at an efficiency of 82.9% (specifity 86.7%, sensitivity 61.5%). Efficiency of discrimination between CD and plaque stage was 92.5% (specifity 89.7%, sensitivity 91.7%) and between CD and tumor stage 100% when discriminant analysis was based on the mean thickness of the infiltrate. Although unequivocal discrimination between CD and MF cannot be achieved in each individual case, morphometry on routine paraffin material obviously provides additional objective criteria for the diagnosis of early MF.

Nuclear parameters in the superficial and deep portion of melanocytic lesions--a morphometrical investigation.

Morphometric techniques in diagnostic pathology of pigmented skin lesions are not yet well established. The so-called maturation of melanocytes (nevus cells) with progressive descent into the dermis is one important criterion to differentiate benign from malignant melanocytic lesions in conventional histology. We therefore examined morphometrically the nuclear parameters of melanocytes (nevus cells) in the superficial and deep portion of 120 pigmented skin tumors (40 cases each of malignant melanoma. Spitz's nevus and benign dermal nevus) with special emphasis on the "maturation to the depth". A "maturation parameter" (MP) was assessed in each individual case, calculating the ratio of the nuclear area in the deep portion and in the superficial portion. The mean values of MP were 0.720 +/- 0.11 for dermal nevi, 0.725 +/- 0.10 for Spitz's nevi and 1.125 +/- 0.11 for malignant melanoma. The difference between malignant melanoma and both groups of benign nevi was statistically significant (p less than or equal to 0.01). The efficiency of the maturation parameter was 0.95 for the distinction of dermal nevi and malignant melanomas, and 0.97 for the distinction of Spitz's nevi and malignant melanoma. Measurements of the superficial portion only revealed comparatively low efficiency values (0.70 and 0.56, respectively). Our results indicate that morphometric evaluations of the nuclear area of melanocytes (nevus cells) in the deep portion of the infiltrate are more discriminative than those in the superficial portions. The establishment of the MP allows a better differentiation between benign and malignant melanocytic lesions and therefore morphometric methods may obviously be a helpful tool in the diagnosis of melanocytic skin tumors.