The impact of a nationwide hands-on workshop on the diagnostic rates and management of obstetrical anal sphincter Injuries in Israel.

AIM: The aim was to evaluate the influence of a half day, hands-on, workshop on the detection and repair of obstetric anal sphincter injuries (OASIs). METHOD: Starting in February 2011, hands-on workshops for the diagnosis and repair of OASIs were delivered by trained urogynaecologists in departments of tertiary medical centres in Israel. The structure of the hands-on workshop resembles the workshop organized at the International Urogynecological Association annual conferences. Participants included medical staff, midwives and surgical residents from each medical centre. We collected data regarding the rate of OASIs, 1 year before and 1 year following the workshop, in 11 medical centres. The study population was composed of parturients with the following inclusion criteria: singleton pregnancy, vertex presentation and vaginal delivery. Pre-viable preterm gestations (< 24 weeks), birth weight < 500 g, stillborn, and those with major congenital anomalies, multifoetal pregnancies, breech presentations and caesarean deliveries were excluded from the analysis. RESULTS: In the reviewed centres, 70 663 (49.3%) women delivered prior to the workshop (pre-workshop group) and 72 616 (50.7%) women delivered following the workshop (post-workshop group). Third- or fourth-degree perineal tears occurred in 248 women (0.35%) before the workshop, and in 328 (0.45%) following the workshop, a significant increase of 28.7% (P = 0.002). The increase in diagnosis was significant also in women with third-degree tears alone, 226 women (0.32%) before the workshop and 298 (0.41%) following the workshop, an increase of 28.3% (P = 0.005). CONCLUSION: The detection rate of OASIs has significantly increased following the hands-on workshop. The implementation of such programmes is crucial for increasing awareness and detection rates of OASI following vaginal deliveries.

Quantum Interference between Photons from an Atomic Ensemble and a Remote Atomic Ion.

Many remote-entanglement protocols rely on the generation and interference of photons produced by nodes within a quantum network. Quantum networks based on heterogeneous nodes provide a versatile platform by utilizing the complementary strengths of the differing systems. Implementation of such networks is challenging, due to the disparate spectral and temporal characteristics of the photons generated by the different quantum systems. Here, we report on the observation of quantum interference between photons generated from a single ion and an atomic ensemble. The photons are produced on demand by each source located in separate buildings, in a manner suitable for quantum networking. Given these results, we analyze the feasibility of hybrid ion-ensemble remote entanglement generation.

Retinal vascular diameters in relation to physical activity in Danish children - The CHAMPS Eye Study.

Our objective was to determine associations between retinal vascular caliber and physical activity (PA) in a school-based child cohort. In a prospective study, we created a childhood cumulative average PA-index using objectively measured PA (accelerometry) assessed at four periods between 2009 and 2015. Cumulative exposure to PA intensities was estimated. Cross-sectional examinations on biomarkers, anthropometry, and ophthalmological data including retinal fundus photographs were performed in 2015. Semi-automated measurements of retinal vascular diameters were performed and summarized into central retinal arteriolar and venular equivalents (CRAE, CRVE). We included 307 participants. Mean age in 2015 was 15.4 years (0.7). The mean CRAE and CRVE were 156.5 µm (2.8) and 217.6 µm (7.7), respectively. After adjusting for age, gender, and axial length, more time in PA was independently related to thinner retinal venules (ß-coefficient = -1.25 µm/%, 95% confidence interval = -2.20, -0.30, P < .01). Sedentary time was associated with wider venules (P < .01). Furthermore, birthweight (ß-coefficient = 0.56 µm/%, 95% confidence interval = 0.18, 0.95, P < .01) was associated with CRVE. Blood pressure was associated with thinner retinal arterioles (ß-coefficient = -0.19 µm/mmHg, 95% confidence interval = -0.36, -0.01, P = .04). We concluded that children with higher PA in childhood had thinner retinal venular caliber. Our results suggest that PA during childhood positively impacts the retinal microcirculation and that retinal vascular analysis may be a possible assessment to detect microvascular impairments in children with an increased risk of future cardiovascular disease.

Anomalous Broadening in Driven Dissipative Rydberg Systems.

We observe interaction-induced broadening of the two-photon 5s-18s transition in ^{87}Rb atoms trapped in a 3D optical lattice. The measured linewidth increases by nearly 2 orders of magnitude with increasing atomic density and excitation strength, with corresponding suppression of resonant scattering and enhancement of off-resonant scattering. We attribute the increased linewidth to resonant dipole-dipole interactions of 18s atoms with blackbody induced population in nearby np states. Over a range of initial atomic densities and excitation strengths, the transition width is described by a single function of the steady-state density of Rydberg atoms, and the observed resonant excitation rate corresponds to that of a two-level system with the measured, rather than natural, linewidth. The broadening mechanism observed here is likely to have negative implications for many proposals with coherently interacting Rydberg atoms.

Storage and retrieval of collective excitations on a long-lived spin transition in a rare-earth ion-doped crystal.

Robust, long-lived optical quantum memories are important components of many quantum information and communication protocols. We demonstrate coherent generation, storage, and retrieval of excitations on a long-lived spin transition via spontaneous Raman scattering in a rare-earth ion-doped crystal. We further study the time dynamics of the optical correlations in this system. This is the first demonstration of its kind in a solid and an enabling step toward realizing a solid-state quantum repeater.

Sellar hemangioblastoma mimicking a macroadenoma.

PURPOSE: Hemangioblastomas (HGB) are slow growing benign vascular tumors that arise almost always from the cerebellum and the spinal cord. Supratentorial location is extremely rare with approximately 130 cases published to date. We present a case of a sellar hemangioblastoma. CASE REPORT: An eleven year-old girl presented with a sellar and suprasellar tumor that seemed to be a macroadenoma. A transsphenoidal approach was attempted but excessive intraoperative bleeding made the resection not feasible. A second transcranial approach was successful in partially removing the lesion and decompressing the optic chiasm and the pituitary stalk. Pathological review revealed a seller hemangioblastoma. screening for Von Hippel Lindeau Syndrome was negative. CONCLUSION: The preoperative diagnosis of HGB is extremely difficult in this case but would have been essential in order to choose the right surgical approach.

Enhancing image contrast using coherent states and photon number resolving detectors.

We experimentally map the transverse profile of diffractionlimited beams using photon-number-resolving detectors.We observe strong compression of diffracted beam profiles for high detected photon number. This effect leads to higher contrast than a conventional irradiance profile between two Airy disk-beams separated by the Rayleigh criterion.

Electromagnetically induced transparency in inhomogeneously broadened solid media.

We study, theoretically and experimentally, electromagnetically induced transparency (EIT) in two different solid-state systems. Unlike many implementations in homogeneously broadened media, these systems exhibit inhomogeneous broadening of their optical and spin transitions typical of solid-state materials. We observe EIT lineshapes typical of atomic gases, including a crossover into the regime of Autler-Townes splitting, but with the substitution of the inhomogeneous widths for the homogeneous values. We obtain quantitative agreement between experiment and theory for the width of the transparency feature over a range of optical powers and inhomogeneous linewidths. We discuss regimes over which analytical and numerical treatments capture the behavior. As solid-state systems become increasingly important for scalable and integratable quantum optical and photonic devices, it is vital to understand the effects of the inhomogeneous broadening that is ubiquitous in these systems. The treatment presented here can be applied to a variety of systems, as exemplified by the common scaling of experimental results from two different systems.

Spontaneous avalanche dephasing in large Rydberg ensembles.

Strong dipole-exchange interactions due to spontaneously produced contaminant states can trigger rapid dephasing in many-body Rydberg ensembles [E. Goldschmidt et al., PRL 116, 113001 (2016)]. Such broadening has serious implications for many proposals to coherently use Rydberg interactions, particularly Rydberg dressing proposals. The dephasing arises as a runaway process where the production of the first contaminant atoms facilitates the creation of more contaminant atoms. Here we study the time dependence of this process with stroboscopic approaches. Using a pump-probe technique, we create an excess "pump" Rydberg population and probe its effect with a different "probe" Rydberg transition. We observe a reduced resonant pumping rate and an enhancement of the excitation on both sides of the transition as atoms are added to the pump state. We also observe a timescale for population growth significantly shorter than predicted by homogeneous mean-field models, as expected from a clustered growth mechanism where high-order correlations dominate the dynamics. These results support earlier works and confirm that the time scale for the onset of dephasing is reduced by a factor which scales as the inverse of the atom number. In addition, we discuss several approaches to minimize these effects of spontaneous broadening, including stroboscopic techniques and operating at cryogenic temperatures. It is challenging to avoid the unwanted broadening effects, but under some conditions they can be mitigated.

Fluorouracil combined with the pure (6S)-stereoisomer of folinic acid in high doses for treatment of patients with advanced colorectal carcinoma: a phase I-II study.

BACKGROUND: Potentiation of the antitumor activity of fluorouracil (5-FU) by folinic acid has been demonstrated in patients with colorectal adenocarcinoma. Modulation is due to the interaction of thymidylate synthase, fluorodeoxyuridine monophosphate, and methylene tetrahydrofolate, which leads to the formation of a stable ternary complex with concomitant enzyme inactivation. Folinic acid consists of a mixture of equal parts of two stereoisomers differing in chirality at the C-6 carbon of the pteridine ring. Only the levorotatory (6S)-stereoisomer of folinic acid is transformed into active folate cofactors. However, the (6R)-stereoisomer of folinic acid is not inert; it was shown to interfere with the (6S) form at the cellular level. PURPOSE: The possibility of a deleterious effect of the unnatural stereoisomer on the modulation of 5-FU led us to carry out a phase I-II study of 5-FU combined with the (6S)-stereoisomer of folinic acid given in high doses for treatment of patients with advanced colorectal carcinoma. We also determined the plasma pharmacokinetics of folates after intravenous (IV) injection of (6S)-folinic acid at the dose used in this study. METHODS: Treatment consisted of 5-FU (350-550 mg/m2 per day by IV infusion for 2 hours) and (6S)-folinic acid (100 mg/m2 per day by IV bolus injection) given for 5 consecutive days; the treatment was repeated every 21 days. Twenty-five patients with advanced colorectal carcinoma, who had had no prior chemotherapy, were evaluated for antitumor activity. The quantity of folates in plasma was measured using a microbiological assay. RESULTS: The median follow-up time was 9 months (range, 3.5-15.2 months). The response rate was 52% (complete response, 12%; partial response, 40%). The median time to disease progression for responding patients was 9.2 months (range, 5.9-15+ months). The estimated probability of survival at 12 months was 73%. Palliative improvement in quality of life was achieved in most patients who had symptoms due to the tumor before the start of treatment. The dose-limiting toxic effects were grade 3 diarrhea, dermatitis, and oral mucositis. Grade 4 toxicity did not occur. Myeloid toxicity was minor. After IV injection, (6S)-folinic acid was rapidly cleared from plasma (mean half-lives: alpha = 7.2 minutes and beta = 126 minutes). The mean concentration of the unchanged compound 2 hours after injection was 5.8 mumol/L. CONCLUSION: The (6S)-form of folinic acid potentiates the antitumor effect of 5-FU given concomitantly. IMPLICATION: Our results justify a more complete exploration of the pure active stereoisomer as a modulator of the fluoropyrimidines.

Treatment of advanced colorectal and gastric adenocarcinomas with 5-fluorouracil and high-dose folinic acid.

We report the results of an expanded trial of 5-fluorouracil (5-FU) combined with high-dose folinic acid for treatment of patients with advanced colorectal or advanced gastric adenocarcinoma. In each treatment course, the patients received both 5-FU (340 to 400 mg/m2/d by intravenous (IV) infusion for a period of 15 minutes) and folinic acid (200 mg/m2/d by IV bolus) for 5 consecutive days, with a 21-day interval between courses. Eighty-six patients with colorectal carcinoma were evaluated. The combined complete and partial response rates were 39% for 54 patients who did not receive prior chemotherapy and 22% for 32 patients who had previously received chemotherapy. Four patients who were previously resistant to 5-FU attained objective responses. The median time to disease progression for the 28 responders was 10 months. The median survival time of responders was 19.5 months, and the probability of their being alive at 2 years was 40%. Of 27 patients with gastric adenocarcinoma, 13 (48%) responded to therapy. Their median time to disease progression was 5.5 months. The median survival time of responders was 11 months, and their probability of being alive at 15 months was 30%. Toxicity was within acceptable limits. Toxic effects included stomatitis, diarrhea, conjunctivitis, skin rash, and mild myeloid hypoplasia. In a separate study, plasma concentrations of L-folates greater than 10(-5) mol/L were achieved after a rapid single IV injection of 200 mg/m2 of folinic acid. Comparisons of our results with those reported in previous studies on 5-FU administered as a single agent suggest that, in advanced colorectal and gastric adenocarcinoma, folinic acid administered in high doses enhances the effectiveness of 5-FU administered concomitantly. Furthermore, some colorectal tumors that were previously resistant to 5-FU become sensitive to this drug. The survival of the patients who responded to therapy was markedly improved over that observed in reported series of untreated patients with advanced colorectal and gastric adenocarcinomas.

Quantum simulation. Two-dimensional superexchange-mediated magnetization dynamics in an optical lattice.

The interplay of magnetic exchange interactions and tunneling underlies many complex quantum phenomena observed in real materials. We study nonequilibrium magnetization dynamics in an extended two-dimensional (2D) system by loading effective spin-1/2 bosons into a spin-dependent optical lattice and use the lattice to separately control the resonance conditions for tunneling and superexchange. After preparing a nonequilibrium antiferromagnetically ordered state, we observe relaxation dynamics governed by two well-separated rates, which scale with the parameters associated with superexchange and tunneling. With tunneling off-resonantly suppressed, we observe superexchange-dominated dynamics over two orders of magnitude in magnetic coupling strength. Our experiment will serve as a benchmark for future theoretical work as the detailed dynamics of this 2D, strongly correlated, and far-from-equilibrium quantum system remain out of reach of current computational techniques.

Vapreotide, a somatostatin analogue, in cryptosporidiosis and other AIDS-related diarrhoeal diseases.

OBJECTIVE: To evaluate the efficacy and tolerance of vapreotide, a new somatostatin analogue, in the treatment of refractory AIDS-related diarrhoea. DESIGN: An open, non-comparative pilot trial. SETTING: The trial was conducted in 10 medical centres in France. PATIENTS, PARTICIPANTS: Thirty-four AIDS patients with chronic diarrhoea unresponsive to conventional antidiarrhoeal therapy were enrolled. Cryptosporidiosis was diagnosed in 21 out of 30 evaluable patients. Mean number of stools prior to therapy was 10.1 +/- 4.9 per day (range, 3-20 stools per day). INTERVENTION: After initial baseline studies, patients received subcutaneous vapreotide at escalating doses of 400 (23 patients) or 500 micrograms (seven patients), between two and six times daily. MAIN OUTCOME MEASURES: Efficacy was assessed after 14 days of therapy, when it was found to be effective. Responders were offered the opportunity to continue receiving therapy. RESULTS: Four patients demonstrated a complete response and 12 a partial response with greater than 50% reduction in daily stool emission. Fourteen patients did not respond to doses up to 2400 micrograms/day. Patients with conditions other than cryptosporidiosis had a significantly higher probability of response (P = 0.013), as did those with milder diarrhoea (less than 10 stools per day). Median duration of response was 1.5 months (range, 0.5-5 months); relapse occurred in five out of eight responders despite maintenance therapy. Toxicity was minimal. CONCLUSIONS: We conclude that AIDS patients with diarrhoea not caused by Cryptosporidium may benefit from vapreotide therapy.

Fate of aclacinomycin-A and its metabolites effect on cell growth and macromolecular synthesis.

The relationship between the structure and activity of aclacinomycin-A (ACM) metabolites was investigated in vitro in Friend leukaemia cells (FLC). The cytotoxic effect was related to the ease with which ACM and its metabolites accumulate in the nucleus. Cellular uptake and nuclear incorporation are influenced by the hexopyranoses linked to aklavinone (AKV) and by the two methyls linked to the L-rhodosamine amino groups. The effect of ACM and its metabolites on macromolecular synthesis depended on the drug concentrations and the exposure time. ACM was the most active in the inhibition of nucleic acid synthesis whereas it had no direct effect on protein synthesis even at high drug concentrations. When cells were treated for a short time with low drug concentrations (1 microM), RNA synthesis was inhibited to a greater extent than DNA synthesis. But when incubated for longer periods, inhibition of DNA synthesis increased further. RNA and DNA syntheses were both inhibited to about the same extent only when cells were exposed to the higher drug concentrations (10 microM). We conclude therefore that at low drug concentrations the effect on DNA synthesis is probably a consequence of RNA synthesis inhibition. The early DNA synthesis inhibition which occurs at higher drug concentrations may result from the direct action on the cellular genome.

Cytotoxic synergism of methioninase in combination with 5-fluorouracil and folinic acid.

Potentiation of the cytotoxic activity of 5-fluorouracil (FUra) by folinic acid (5-HCO-H4folate) is due to elevation of the methylene tetrahydrofolate (CH2-H4folate) level, which increases the stability of the ternary complex of thymidylate synthase (TS), fluorodeoxyuridine monophosphate, and CH2-H4folate that inactivates the TS. Methionine deprivation results in the production of tetrahydrofolate (H4folate) and, subsequently, CH2-H4folate from methyl tetrahydrofolate, as a consequence of the induction of methionine synthesis. We hypothesized that the efficacy of FUra could be augmented by the combination of high-concentration 5-HCO-H4folate and recombinant methioninase (rMETase), a methionine-cleaving enzyme. Studies in vitro were performed with the cell line CCRF-CEM. Cytotoxic synergism of FUra + rMETase and FUra + 5-HCO-H4folate + rMETase was demonstrated with the combination index throughout a broad concentration range of FUra and rMETase. A subcytotoxic concentration of rMETase reduced the IC50 of FUra by a factor of 3.6, and by a factor of 7.5, in the absence and in the presence of 5-HCO-H4folate, respectively. 5-HCO-H4folate increased the intracellular concentrations of CH2-H4folate and H4folate from their baseline levels. Concentrations of folates were not changed by exposure to rMETase. Levels of free TS in cells treated with FUra + 5-HCO-H4folate and with FUra + rMETase were lower than those in cells exposed to FUra alone. The decrease of TS was still more pronounced in cells treated with FUra + 5-HCO-H4folate + rMETase. The synergism described in this study will be a basis for further exploration of combinations of fluoropyrimidines, folates, and rMETase.

Retinal detachment after cataract extraction in myopic eyes.

PURPOSE: To determine the incidence of retinal detachment (RD) after cataract extraction in people 40 years of age or older with axial myopia (i.e., axial length > or = 25.5 mm). SETTING: Fifteen Danish eye clinics. METHODS: Two hundred forty-five eyes had cataract extraction performed at 15 eye clinics; 237 eyes had extracapsular cataract extraction (ECCE) and 8 eyes, intracapsular cataract extraction (ICCE). Postoperative data were reported by the practicing ophthalmologists. Mean follow-up was 27 months (range 14 to 32 months). RESULTS: Five RDs occurred in the 245 eyes (2.0%). Excluding the ICCE cases and the two cases of combined cornea transplantation and ECCE, RD occurred in 4 of the 235 eyes that had ECCE (1.7%). The incidence after ECCE with posterior chamber lens implantation was 1.4%. Complete postoperative status was reported on 158 eyes. Forty-eight eyes (30.4%) had a neodymium:YAG capsulotomy and 3 (6.0%) developed an RD 1, 3.5, and 21 months after the capsulotomy. CONCLUSION: The RD incidence after ECCE with posterior chamber lens implantation was low but higher than that in unselected populations. The incidence increased after laser capsulotomy.

[A case of septicemia by a Corynebacterium of the J. K. group]. / A propos d'un cas de septicémie a Corynebacterium du groupe J. K.

We have reported a case of septicaemia caused by "Corynebacterium of group J. K." in a patient with acute myeloblastic leukaemia. Recent studies by Riley (1978) have shown that the corynebacteria, saprophytes of the skin and mucosa have a resistance to common antibiotics. Corynebacteria that are only sensitive to virginiamycin and vancomycin are a potential danger for immunosuppressed patients and patients with artificial heart valves, the appropriate choice of antibiotic can be difficult in these patients.

Phase I-II study of aclacinomycin for a treatment of acute myeloid leukemia.

Aclacinomycin A (ACM) was administered for induction treatment to 40 previously treated acute myeloid leukemia (AML) patients. 38 patients aged 2 to 80 years (mean +/- SE, 35.0 +/- 3.2 years) with overt AML were evaluated; of these, seventeen patients were given ACM after an unsuccessful attempt to obtain a complete remission (CR) with various regimens comprising adriamycin (ADM) or daunorubicin (DNR) and were considered resistant to these drugs. Thirteen patients received ACM at a daily dose of 10 to 30 mg/m2 IV bolus until the maximum total dose of 300 mg/m2 per course was reached or until unacceptable toxicity appeared; of these patients, 2 (15%) attained a CR. Twenty-five patients were given 10-day courses of ACM at the daily dose of 15 mg/m2 IV bolus with 10-day intervals between courses; with this regimen 11 patients (44%) attained a CR. The overall CR rate was 34%. Total doses necessary to attain a CR ranged from 150 to 600 mg/m2. CR was attained by 6 patients (35%) of the 17 who were previously resistant to ADM or DNR. The incidence and severity of the toxic effects such as mucositis, diarrhea, vomiting and infection were related to the dose of ACM administered during each course of therapy. However, in patients who received 150 mg/m2 per course the toxicity was within acceptable limits. Alopecia was not observed. Transient T-wave inversion was observed in 3 patients and atrial flutter developed in one patient. Therefore, we conclude that ACM is a new major drug in the treatment of AML.