Muonic atom spectroscopy with microgram target material.

Muonic atom spectroscopy-the measurement of the x rays emitted during the formation process of a muonic atom-has a long standing history in probing the shape and size of nuclei. In fact, almost all stable elements have been subject to muonic atom spectroscopy measurements and the absolute charge radii extracted from these measurements typically offer the highest accuracy available. However, so far only targets of at least a few hundred milligram could be used as it required to stop a muon beam directly in the target to form the muonic atom. We have developed a new method relying on repeated transfer reactions taking place inside a 100 bar hydrogen gas cell with an admixture of 0.25% deuterium that allows us to drastically reduce the amount of target material needed while still offering an adequate efficiency. Detailed simulations of the transfer reactions match the measured data, suggesting good understanding of the processes taking place inside the gas mixture. As a proof of principle we demonstrate the method with a measurement of the 2p-1s muonic x rays from a 5  µ g gold target.

High-Precision Ramsey-Comb Spectroscopy Based on High-Harmonic Generation.

High-harmonic generation (HHG) is widely used for up-conversion of amplified (near) infrared ultrafast laser pulses to short wavelengths. We demonstrate that Ramsey-comb spectroscopy, based on two such pulses derived from a frequency-comb laser, enables us to observe phase effects in this process with a few mrad precision. As a result, we could perform the most accurate spectroscopic measurement based on light from HHG, illustrated with a determination of the 5p^{6}→5p^{5}8s^{2}[3/2]_{1} transition at 110 nm in ^{132}Xe. We improve its relative accuracy 10^{4} times to a value of 2.3×10^{-10}. This is 3.6 times better than shown before involving HHG, and promising to enable 1S-2S spectroscopy of He^{+} for fundamental tests.

High-power femtosecond mid-infrared optical parametric oscillator at 7 µm based on CdSiP(2).

We report a femtosecond optical parametric oscillator (OPO) for the mid-infrared (mid-IR), generating a record average power of 110 mW at 7 µm. The OPO, based on CdSiP(2) (CSP) as the nonlinear crystal, provides idler wavelength tuning across 6540-7186 nm with spectral bandwidths >400 nm at -10 dB level over the entire range, and a maximum bandwidth of 478 nm at 6.9 µm. To the best of our knowledge, this is the highest average power generated from a femtosecond OPO in the deep mid-IR. The OPO also provides near-IR signal wavelengths tunable across 1204-1212 nm with a usable power of 450 mW in 418-fs pulses at 1207 nm. The simultaneously measured signal and idler power exhibit a passive stability better than 1.6% rms and 3% rms, respectively. A mid-IR idler spectral stability with a standard deviation of the frequency fluctuations better than 40 MHz over 15 min, limited by the measurement resolution, is realized. Using the mid-IR idler from the CSP OPO, we perform Fourier-transform spectroscopy to detect liquid phase organic solvent, toluene (C(7)H(8)), in the molecular fingerprint region.

[Laparoscopic promontofixation: defining early morbidity using a standardized method]. / Promontofixation par cœlioscopie : évaluation de la morbidité précoce par une méthode standardisée.

OBJECTIVE: Adverse event reporting for laparoscopic promontofixation is highly variable and non-standardized in the literature. The aim of this study was to better characterize early postoperative complications of laparoscopic promontofixation for genital prolapse using a standardized reporting methodology. PATIENTS AND METHODS: A retrospective study was conducted on 174 women with genital prolapse undergoing laparoscopic promontofixation from January 2008 to January 2013. Complications arising during the first month after surgery were reviewed according to the Clavien and Dindo classification. RESULTS: At least one postoperative adverse event was reported in 57 out of 174 (33 %) women, grade 1 in 22 patients (13 %), grade 2 in 31 patients (18 %) and grade 3 in 4 patients (2 %). No patient experienced a grade 4 or 5 complication. Fifty-three out of 57 (93 %) complications were grade 1 or 2. The most frequently reported adverse event (n=24; 14 %) was constipation (grade 2). DISCUSSION AND CONCLUSION: Laparoscopic promontofixation is a safe procedure with almost exclusively benign (grade 1 or 2) early complications. The hypothesis of induction or increasing constipation by this type of genital prolapse surgery should be further evaluated.

Diffusion weighted imaging with background body signal suppression / T2 image fusion in magnetic resonance mammography for breast cancer diagnosis.

INTRODUCTION: Dynamic Contrast-Enhanced Magnetic Resonance Mammography (DCE-MRM) represents the most sensitive examination for breast cancer (BC) diagnosis. However literature data reports very inhomogeneous specificity. The aim of our study was to evaluate the clinical efficiency of a new MRM technique - diffusion weighted imaging with background body signal suppression T2 image fusion in BC diagnosis, compared to DCE-MRM. METHODS: We retrospectively analyzed 50 consecutive DCE-MRM examinations with DWIBS sequence from the archives of the Department of Radiology, Lyon Sud Hospital, (02.2010- 02.2011), summing up to 64 breast lesions. Fusions were created using the Osirix software from the DWIBS images (b=1000 s mm2) and their T2 correspondents. Interpretation was performed using an adapted BI-RADS system. The final histopathological examination or a minimum 6-months follow-up served as gold standard. RESULTS: Out of the 64 examined breast lesions, 35(54.7%) were classified as malignant by DCE-MRM and 24(37.5%) cases by DWIBS T2, respectively. Thus the DWIBS T2 fusion had a Sensitivity of 62.5%(95%CI:35.4-84.8) and a Specificity of 70.8%(95%CI:55.9-83.3) while DCE-MRM had a higher Sensitivity: 87.5%(95%CI:61.6-98.4) but a lower Specificity: 56.2%(95%CI:41.1-70.5). CONCLUSION: DWIBS T2 fusion is an innovative MRM technique, with a specificity superior to DCE-MRM, showing a large potential for improving the clinical efficiency of classical MRM.

[Adrenal vein thrombosis during pregnancy]. / Thrombose veineuse surrénalienne en cours de grossesse.

Pregnancy represents an inner transitional prothrombotic state; that is why other coagulation abnormalities may be revealed during this time. Factor V Leiden mutation is the most frequent inherited thrombophilia in the general population. We report the case of a patient by whom this mutation has been revealed during pregnancy by an adrenal vein thrombosis. Through this case, we will review the physiopathology of resistance to activated protein C and its consequences.

Clinical implications of axillary sentinel lymph node 'micrometastases' in breast cancer.

AIMS: The aim of this study was to determine, from a series of cases, the frequency and prognostic factors of invasion of non-sentinel lymph nodes when the axillary sentinel lymph node contains a metastasis < or =2 mm, and thereby select a population in which completion axillary dissection could be omitted. METHODS: Between July 1996 and July 2003, 62 patients, which axillary sentinel lymph node contained a metastasis < or =2 mm had an evaluation of the axillary non-sentinel lymph nodes. Eleven patients had also an evaluation of internal mammary lymph nodes. RESULTS: Eleven patients had axillary non-sentinel lymph node invasion: six by metastases < or =2 mm and five by macrometastases. When internal mammary lymph nodes were also concerned, nodal invasion apart from the axillary sentinel lymph node was seen in 14 patients. Vascular lymphatic invasion was the only factor, statistically significant, linked to non-sentinel lymph node invasion (p = 0.02). CONCLUSION: Whatever the size or method of histological detection (pN1mi or pN0(i+)), the presence of a metastasis < or =2 mm in the axillary sentinel lymph node leads us to carry out completion axillary dissection to optimize staging and loco-regional control of the disease.

Sub-urethral tape treatment of female urinary incontinence--morbidity assessment of the trans-obturator route and a new tape (I-STOP): a multi-centre experiment involving 604 cases.

PURPOSE: To make an assessment of the morbidity related to using the trans-obturator route (TOT); findings after one year for the 140 first cases and preliminary results of short term morbidity after 604 implants. PATIENTS AND METHOD: This retrospective, multi-centre study involves the 604 first procedures with a 1-3 month follow-up. The mean patient age was 57 years. 92% of the patients underwent an isolated urinary incontinence cure and 8% had associated surgery. 47.3% of the cases had pure stress urinary incontinence and 52.7% had mixed incontinence. A 12-month minimum follow-up period was applied to the first 140 cases operated between September 2002 and January 2003. Patient assessment was made by a clinical examination in the first three months and their satisfaction rate expressed after 1 year. RESULTS: Operative complications were very few: 0.5% vesical perforations, 0.3% vaginal perforations, no urethral wounds, 0.8% 200-300 ml haemorrhages, two perineal haematomas (0.33%). The post-operative period was marked by: 1.5% transient retentions, 2.3% transient pain, 2.5% urinary infections, 1.3% transient dysuria. The 1-3 month follow-up of 572 patients shows a 5.2% rate of de novo symptoms. Patient assessment of 131 subjects after one year revealed an encouraging satisfaction rate of 85.5% with a 1.5% rate of de novo dysuria and urgency. To date there have been no serious or specific complications attributable to the surgical route adopted. The morbidity is not affected by associated surgery. CONCLUSION: The trans-obturator route combines low morbidity with a low rate of de novo symptoms on a large series. These results will have to be corroborated by further studies.

[Reliability of basic geriatric assessment]. / Untersuchung zur Reliabilität des Geriatrischen Basisassessments.

This study investigates the Geriatric Basis Assessment (GBA) in terms of its reliability. Data from 1037 patients were collected. The reliability was estimated relating to the lambda 2 coefficient. It is necessary to define the items in different categories: the first variable means valuation 1 of each item and not 2, 3, 4; the second variable means valuation 1, 2 against 3, 4; the third variable means the valuation 1, 2, 3 and not 4. The table shows only little difference concerning the lambda 2 coefficients. In conclusion, 80% of the variability of the GBA items can be explained by differences in the patients themselves, while 20% is due to the inaccurate assessment system. For 343 patients, data for both Barthel index and GBA were available. As presumed, correlations between Barthel and connected GBA items were observed. However, the correlations were too weak to predict the Barthel scores from the corresponding GBA item accurately enough. The Barthel index appears to include similar, but not exactly the same aspects as the GBA. The reliability of the Barthel index (lambda 2 = 0.89 for the first variable) is slightly higher compared to the GBA but it is not suitable as a criterion of validity. Both the validity of the GBA and the Barthel index can not be determined lacking an external measure. As an example, a suitable criterion of validity could be the reintegration into the familiar surroundings preceding the hospital stay. When developing the GBA, it was not assumed that geriatric patients could be correctly diagnosed on the basis of an overall score alone or to allocate them to adequate care using that score as a sole indicator. Crucial for these purposes is the test profile as a whole, including the impairments, disabilities handicaps, and last but not least the diseases of the individual patient. Furthermore, the depiction of the GBA profile at admission and discharge allows one to identify those items, on which therapy has a significant influence and those which remain more or less stable. As presumed, items with minor initial deficits (e.g., motivation, eyesight, hearing, depression, capability of verbal expression, situative adaptability, understanding) showed only small differences between admission and discharge. On the other hand, items strongly influenced by geriatric treatment were, e.g., mobility (walking, transfer), functions of internal medicine, and domestic care. Prognostically significant are those items which are crucial for reintegration and describe a deficiency but cannot be altered reliably. Such items are the person, to whom the patient relates most closely, situative adaptability, motivation, orientation, capability of verbal expression, and possibly depression. All of these parameters are more difficult to influence than the activities of daily living assessed by the Barthel index. Further investigations should clarify whether the GBA can be a reliable tool for allocating a patient to adequate care. However, the requirement for such a criterion of validity is that this allocation is truly optimal for the patient.

Incidence and time course of cardiovascular side effects during spinal anesthesia after prophylactic administration of intravenous fluids or vasoconstrictors.

UNLABELLED: We studied the time course of arterial hypotension and/or bradycardia requiring treatment during spinal anesthesia and compared the efficacy of i.v. fluid or vasoconstrictor administration for the prevention of these side effects. Patients (n = 1066) were randomly allocated to either a volume group (lactated Ringer's solution 15 mL/kg within 15 min before spinal anesthesia), a dihydroergotamine group (10 microg/kg i.m. 15 min before anesthesia), or a placebo group. All patients breathed O2-enriched air during spinal anesthesia (4 mL of plain 0.5% bupivacaine). With the placebo, there were side effects (mean incidence 22.9%) for up to 45 min after the start of anesthesia. Dihydroergotamine reduced the incidence of side effects, preferentially the late ones, more (mean incidence 11.8%) than fluid administration (mean incidence 16.9%), which was effective only during the first 15 min of anesthesia. Both heart rate and arterial pressure decreased within 15 min before the manifestation of symptoms. In a subgroup of patients, the incidence of side effects (8%) was greatly reduced by the intraoperative application of both sedatives and opioids. We conclude that cardiovascular side effects may occur at any time during spinal anesthesia. Fluid administration reduced the incidence of early events, but dihydroergotamine the late events. IMPLICATIONS: Cardiovascular side effects requiring treatment occurred at any time during spinal anesthesia in our placebo-controlled study, regardless of the prophylactic regimen (fluid infusions versus dihydroergotamine).

Anxiolytic-like behavior after lesion of the tuberomammillary nucleus E2-region.

The tuberomammillary nucleus (TM), located in the posterior hypothalamic region, consists of five subgroups and is the only known source of brain histamine. In the present experiment, rats received bilateral ibotenic acid or sham lesions in the rostroventral part of the TM (E2-region). Three weeks later they were tested on the elevated plus-maze test of fear and anxiety. Lesions in the tuberomammillary E2-region elevated the time spent on the open arms, as well as excursions into the end of the open arms, increased scanning over the edge of an open arm, and decreased risk-assessment from an enclosed arm. Thus, partial destruction of TM intrinsic neurons can induce anxiolytic-like effects which are possibly related to a lesion-induced reduction of histaminergic activity.

Unilateral lesion of dorsal hippocampus enhances reinforcing lateral hypothalamic stimulation in the contralateral hemisphere.

Whereas convincing evidence exists for an important role of the hippocampus in mechanisms underlying memory and encoding of location in space, the contribution of the hippocampus to the system underlying central processes of reinforcement is less well established. Scattered data suggesting that hippocampal ablation increases the effectiveness of positive reinforcers have alternatively been interpretated in terms of general and unspecific behavioral disinhibition, which results in higher levels of activity and rates of responding. In the present experiment, 22 Wistar rats were either given a neurotoxic or a sham lesion in the CA1 region of the hippocampus, and the effect on lateral hypothalamic self-stimulation behavior was assessed. To control for nonspecific performance effects rates of lever pressing were assessed ipsi- and contralateral to the lesioned hemisphere as well as under condition of extinction (current set to zero). Following the neurotoxic lesion the animals displayed significant higher rates of self-stimulation at the electrode sites in the hypothalamus situated contralateral but not ipsilateral to the hemisphere with the lesion compared with controls. The increase in self-stimulation commenced on the third day postlesion and was maintained over the 8 days of testing. The lesion did not change the animals' behavior under extinction. Thus, the hippocampal lesion led to an amplification of rewarding lateral hypothalamic self-stimulation behavior, indicative of a lesion induced disinhibition of the brain's reinforcement system.

Single-subject experiments to determine individually differential effects of anxiolytics in generalized anxiety disorder.

In the pharmacotherapy of chronic generalized anxiety disorder (GAD) rationally grounded guidelines on the treatment to choose in individual cases are not evident in the literature. The present study was designed to address this question in 30 patients with chronic GAD. Within a period of 31 weeks amitriptyline 30 mg/day, flupentixole 1.5 mg/day, clotiazepam 15 mg/day and placebo were administered 4 times for 1 week, double-blind and at random to each patient. U tests showed that in 19 patients one agent was superior to the other substances (p < 0.05). There was no significant difference between the drugs in 11 patients. However, a meta-analysis across all single-subject experiments showed that in individual patients suffering from chronic GAD differential effects of anxiolytic agents can be found by means of single-subject experiments (p < 0.001). The findings lend further support to the hypothesis that, in an approach to optimize pharmacological treatment of patients suffering from chronic GAD, single-subject experiments may be useful.

Effects of chronic substance P treatment and intracranial fetal grafts on learning after hippocampal kainic acid lesions.

The purpose of this experiment was to investigate whether the neurokinin substance P (SP) can enhance adaptive graft effects on learning and memory functions in animals with lesions of the hippocampus. Adult male Wistar rats received a bilateral kainic acid (KA) lesion of the dorsal hippocampus. One week postlesion, bilateral grafts of fetal hippocampal tissue suspension were applied into the damaged region in half of the animals, whereas the other half received sham transplants (physiological saline). Animals of the control group received a bilateral sham lesion of the hippocampus and sham transplants. One week after transplantation surgery, the rats were tested in the place version of the Morris water maze over a period of 9 weeks. Then they were tested for SP-induced conditioned place preference and on a step-through inhibitory avoidance task. All animals received IP injections of either SP (5 or 50 micrograms/kg) or the SP vehicle (0.5 ml/kg). The treatment with SP or the vehicle was begun 1 week after transplantation and was performed 5 days a week over a period of 10 weeks. During behavioral tests in the water maze and avoidance task, application of the substances was performed 5 h after testing. For the conditioned place preference test, the conditioning trials were performed immediately after drug administration; the test trials were given 24 h later. Chronic administration of 50 micrograms/kg SP, but not 5 micrograms/ kg SP, was found to improve water maze performance in lesioned animals with and without grafts. Unexpectedly, the lesion group with the graft without additional SP treatment was not superior to the lesion group devoid of the graft in this task. The rats without lesions of the hippocampus still showed a conditioned place preference to 50 micrograms/kg SP after 9 weeks of repeated SP applications. In the inhibitory avoidance task, the grafts facilitated retention performance independent of whether SP treatment was given. The morphological analysis of the transplants revealed higher graft volumes and a higher diameter of large pyramidal neurons (> 10 microns) in rats chronically treated with 50 micrograms/kg SP.

Can a shuttlebox computer analog be used to condition human avoidance behavior?

Freedman (1990) introduced a computer analog of the shuttlebox paradigm and presented results to show that this analog could be used for studying human avoidance conditioning. In the present study, a first experimental phase was conducted to test how the fact that the tone was considered aversive in the instructions and the intensity of this tone affect avoidance behavior. In a transfer-of-control test phase, it was tested as to whether the warning stimulus presented as a cue to the aversive stimulus had acquired either aversive or informative quality. An effect of instructions was observed for both levels of the auditive stimulus, and a stimulus effect was found for those groups that were given the instructions that described the tone as aversive. In the case of subjects who in the first phase achieved a certain learning criterion, it was recorded how often they in the second phase selected a condition in which the warning signal of the first phase was not presented. No transfer of control was observed. Thus, no positive evidence was found indicating that Freedman's computer analog could be used for studying human avoidance conditioning.

Parametric analysis of sojourn times in conditioned place preference experiments.

In conditioned place preference experiments, groups of animals are typically compared by means of the total time spent in a treatment environment. The total times are often positively skewed, which prohibits the use of parametric procedures that require normal distributions. Common response time models for such total times are also inadequate because the fit of the models to the data is often poor. The present paper assumes that the sojourn times of a single animal are independent and that they all follow the same 1-parameter exponential model. The exponential parameter allows a number of simple interpretations. We propose point estimates, confidence intervals, a goodness-of-fit test, and a test for comparing 2 samples. The procedures are also applied to single animals, and a test is given for comparing the animals of a group. The kind of parametric analysis suggested enables better interpretation than does the simple distribution-free comparison of 2 groups based on the total time spent in the treatment environment.

Quantitative analysis of recovery curves.

It is assumed that recovery curves may be produced either by a dynamic process caused by a feedback mechanism or by a linear compensation process which is independent of previous compensation. Based on this assumption, 3 types of recovery functions are derived. Two behavior functions correspond to each of these types of recovery curves, one starting at a low level and the other at a high level. For each of the resulting 6 types of behavior curves, examples of real data have been reported in literature. Elementary parameter estimates are provided and substantial interpretations of the parameters are given. Behavior measures are derived for the data from an illustrative example, and 1 of the 6 behavior curves is fitted to this data. By additionally taking into account a physical repair function which is assumed to cause a certain delay in recovery, it is shown that an even better fit can be achieved.

Comments on the paper by Möller et al. (1989): problems in single-case evaluation.

Möller et al. (1989) investigated the effects of sleep deprivation on depressive patients using a single-case analysis based on Kleiter's 1986 approach. Here it is discussed why it is so difficult to perform single-case analyses and why Kleiter's approach in particular may lead to wrong interpretations of the data. It is indicated that any kind of single-case analysis is based on assumptions which possibly do not hold and that it is therefore always precarious to base substantial conclusions on this type of analysis.