Long-Lived Coherence on a µHz Scale Optical Magnetic Quadrupole Transition.

We report on the coherent excitation of the ultranarrow ^{1}S_{0}-^{3}P_{2} magnetic quadrupole transition in ^{88}Sr. By confining atoms in a state insensitive optical lattice, we achieve excitation fractions of 97(1)% and observe linewidths as narrow as 58(1) Hz. With Ramsey spectroscopy, we find coherence times of 14(1) ms, which can be extended to 266(36) ms using a spin-echo sequence. We determine the lifetime of the ^{3}P_{2} level for spontaneous emission of magnetic quadrupole radiation to be 110(31) min, confirming long-standing theoretical predictions. These results establish an additional clock transition in strontium and pave the way for applications of the metastable ^{3}P_{2} state in quantum computing and quantum simulations.

State-Dependent Optical Lattices for the Strontium Optical Qubit.

We demonstrate state-dependent optical lattices for the Sr optical qubit at the tune-out wavelength for its ground state. We tightly trap excited state atoms while suppressing the effect of the lattice on ground state atoms by more than 4 orders of magnitude. This highly independent control over the qubit states removes inelastic excited state collisions as the main obstacle for quantum simulation and computation schemes based on the Sr optical qubit. Our results also reveal large discrepancies in the atomic data used to calibrate the largest systematic effect of Sr optical lattice clocks.

A new approach in three dimensions to define pre- and intraoperative condyle-fossa relationships in orthognathic surgery - is there an effect of general anaesthesia on condylar position?

Incorrect registration of the condylar position in orthognathic surgery is supposed to cause postoperative relapse, condylar resorption and temporomandibular disorders. The aim of this prospective study was to evaluate the influence of general anaesthesia on centric relation (CR). Therefore, CR registered preoperatively in the awake patient and CR registered intraoperatively under general anaesthesia were recorded in 30 patients (14 men, 16 women) undergoing orthognathic surgery (skeletal class I: n=3, II: n=13, III: n=14; symmetric: n=20; asymmetric: n=10). CR records were digitized and, through superimposition on the preoperative cone beam computed tomography of the patient's skull, the superior, anterior and posterior joint space and the volumetric congruence of 120 condyles were analysed. The linear measurements of joint spaces did not demonstrate any clinically relevant discrepancy between the CR measured in the awake and anaesthetized patient. In contrast, volumetric analysis revealed statistically significant differences between both states, with an intraoperative condylar sag predominantly in the posterior-inferior direction. The patient's skeletal class or symmetry had no significant influence on the intraoperative condylar displacement. Thus, the risk of fixing the condyle in an unphysiological position supports the idea of using intraoperative condylar positioning devices to achieve predictable and stable outcomes.

Fast optimization and dose calculation in scanned ion beam therapy.

PURPOSE: Particle therapy (PT) has advantages over photon irradiation on static tumors. An increased biological effectiveness and active target conformal dose shaping are strong arguments for PT. However, the sensitivity to changes of internal geometry complicates the use of PT for moving organs. In case of interfractionally moving objects adaptive radiotherapy (ART) concepts known from intensity modulated radiotherapy (IMRT) can be adopted for PT treatments. One ART strategy is to optimize a new treatment plan based on daily image data directly before a radiation fraction is delivered [treatment replanning (TRP)]. Optimizing treatment plans for PT using a scanned beam is a time consuming problem especially for particles other than protons where the biological effective dose has to be calculated. For the purpose of TRP, fast optimization and fast dose calculation have been implemented into the GSI in-house treatment planning system (TPS) TRiP98. METHODS: This work reports about the outcome of a code analysis that resulted in optimization of the calculation processes as well as implementation of routines supporting parallel execution of the code. To benchmark the new features, the calculation time for therapy treatment planning has been studied. RESULTS: Compared to the original version of the TPS, calculation times for treatment planning (optimization and dose calculation) have been improved by a factor of 10 with code optimization. The parallelization of the TPS resulted in a speedup factor of 12 and 5.5 for the original version and the code optimized version, respectively. Hence the total speedup of the new implementation of the authors' TPS yielded speedup factors up to 55. CONCLUSIONS: The improved TPS is capable of completing treatment planning for ion beam therapy of a prostate irradiation considering organs at risk in this has been overseen in the review process. Also see below 6 min.

Upgrade and benchmarking of a 4D treatment planning system for scanned ion beam therapy.

PURPOSE: Upgrade and benchmarking of a research 4D treatment planning system (4DTPS) suitable for realistic patient treatment planning and treatment simulations taking into account specific requirements for scanned ion beam therapy, i.e., modeling of dose heterogeneities due to interplay effects and range changes caused by patient motion and dynamic beam delivery. METHODS: The 4DTPS integrates data interfaces to 4D computed tomography (4DCT), deformable image registration and clinically used motion monitoring devices. The authors implemented a novel data model for 4D image segmentation using Boolean mask volume datasets and developed an algorithm propagating a manually contoured reference contour dataset to all 4DCT phases. They further included detailed treatment simulation and dose reconstruction functionality, based on the irregular patient motion and the temporal structure of the beam delivery. The treatment simulation functionality was validated against experimental data from irradiation of moving radiographic films in air, 3D moving ionization chambers in a water phantom, and moving cells in a biological phantom with a scanned carbon ion beam. The performance of the program was compared to results obtained with predecessor programs. RESULTS: The measured optical density distributions of the radiographic films were reproduced by the simulations to (-2 ± 12)%. Compared to earlier versions of the 4DTPS, the mean agreement improved by 2%, standard deviations were reduced by 7%. The simulated dose to the moving ionization chambers in water showed an agreement with the measured dose of (-1 ± 4)% for the typical beam configuration. The mean deviation of the simulated from the measured biologically effective dose determined via cell survival was (617 ± 538) mGy relative biological effectiveness corresponding to (10 ± 9)%. CONCLUSIONS: The authors developed a research 4DTPS suitable for realistic treatment planning on patient data and capable of simulating dose delivery to a moving patient geometry for scanned ion beams. The accuracy and reliability of treatment simulations improved considerably with respect to earlier versions of the 4DTPS.

Myosin heavy chain composition of single muscle fibers in male distance runners.

The purpose of this study was to characterize the myosin heavy chain (MHC) composition of single muscle fibers from the gastrocnemius of male collegiate distance (DIST; n = 7), middle-distance (MID; n = 6), and recreational runners (REC; n = 6). Additionally, mATPase histochemistry was used to serve as a comparison to previous studies and the single fiber MHC technique. SDS-PAGE of single muscle fibers revealed a higher proportion of MHC I in DIST compared to MID and REC (74.9 +/- 4.3 vs 54.4 +/- 2.8 vs 56.2 +/- 2.9 %, respectively; p < 0.05), less MHC IIa/IIx in DIST compared to MID and REC (0.0 +/- 0.0 vs 6.0 +/- 2.4 vs 15.9 +/- 4.2 %, respectively; p < 0.05), and more total hybrids (I/IIa+IIa/IIx+I/IIa/IIx) in REC than both run groups, DIST and MID (23.0 +/- 3.3 vs 6.2 +/- 1.1 vs 13.2 +/- 2.6 %, respectively; p < 0.05). ATPase histochemistry (pH 4.54) revealed a higher percentage of type I fibers in DIST compared to MID and REC (71.1 +/- 3.1 vs 56.3 +/- 2.5 vs 59.8 +/- 2.3 %, respectively; p < 0.05), a higher percentage of type IIa in MID compared to DIST and REC (43.3 +/- 2.7 vs 28.5 +/- 3.1 vs. 30.2 +/- 3.1 %, p < 0.05), and a higher distribution of type IIb in REC than both run groups (10.0 +/- 2.7 vs 0.4 +/- 0.2 vs 0.4 +/- 0.2 %, p < 0.05). These results suggest that distance running leads to an increase in MHC I expression, training for mid-distance events leads to a prevalence of MHC IIa, and run training leads to a decrease in hybrid fibers.

[Comparison of optical methods for estimating the opening of the canopy and leaf area in leafy forests]. / Comparaison de méthodes optiques pour estimer l'ouverture de la canopée et l'indice foliaire en forêt feuillue.

Based on inversion of gap fraction data (Poisson model of foliage distribution), three optical methods using the Demon, the Plant Canopy Analyzer LAI-2000 (PCA) and hemispherical photographs, have been compared to estimate canopy openness (CO) and leaf area index (LAI) in a mature, neutrophil, oak-beech-hornbeam forest on mull in eastern France. Mean CO over the whole hemisphere was similar for PCA (7.9%) and hemispherical photographs (8.0%). The needle method, a vertical point quadrat method, applied to the litter after leaf fall has served as a reference to LAI (4.7). The Demon provided the estimate (4.9) closest to the reference value. The PCA and hemispherical photographs underestimate mean LAI by 30% (3.3) and 19% (3.8), respectively, if used without correction. Based on fish-eye sensors, LAI estimates can be improved if 3 annuli (4.2) or 2 annuli (4.5) are used in place of 5 with the PCA, or by means of logarithmic averaging of gap fractions over azimuth at an appropriate angular resolution (180 degrees: 4.6, or 120 degrees: 5.2) with hemispherical photographs. Not taking into account azimuthal variation in gap fraction distribution generates a more important error than the error induced by light scattering near horizon. In order to improve LAI estimates, an original iterative procedure is presented, which allows the simultaneous calculation of LAI over a broad range of angular azimuthal resolutions.

Discovery and evaluation of a series of 3-acylindole imidazopyridine platelet-activating factor antagonists.

Studies conducted with the goal of discovering a second-generation platelet-activating factor (PAF) antagonist have identified a novel class of potent and orally active antagonists which have high aqueous solubility and long duration of action in animal models. The compounds arose from the combination of the lipophilic indole portion of Abbott's first-generation PAF antagonist ABT-299 (2) with the methylimidazopyridine heterocycle moiety of British Biotechnology's BB-882 (1) and possess the positive attributes of both of these clinical candidates. Structure-activity relationship (SAR) studies indicated that modification of the indole and benzoyl spacer of lead compound 7b gave analogues that were more potent, longer-lived, and bioavailable and resulted in the identification of 1-(N, N-dimethylcarbamoyl)-4-ethynyl-3-[3-fluoro-4-[(1H-2-methylimidazo[4,5-c] pyrid-1-yl)methyl]benzoyl]indole hydrochloride (ABT-491, 22 m.HCl) which has been evaluated extensively and is currently in clinical development.

Visual prognosis in giant cell arteritis.

PURPOSE: The visual prognosis in giant cell arteritis (GCA) was evaluated over a 5-year period. METHODS: The authors reviewed the records of all patients with a diagnosis of GCA established at the Mayo Clinic over a 5-year period regarding visual status. Follow-up data for these patients were obtained 5 years later. RESULTS: Of the 245 patients studied, 34 (14%) permanently lost vision because of GCA. In 32 of these patients, the visual deficit developed before glucocorticoid therapy for GCA was begun; in the 2 other patients, the visual loss occurred after the diagnosis was made and therapy was started. Visual loss progressed in three patients after initiation of oral glucocorticoids, and in five other patients vision improved. After 5 years, the probability of loss of vision developing after initiating oral glucocorticoid treatment was determined to be 1% (Kaplan-Meier technique), and the probability of additional loss was 13% in patients with GCA who had a visual deficit at the time therapy was begun. CONCLUSION: The development or progression of visual loss was rare after the initiation of glucocorticoid therapy.

Detection of Epstein-Barr virus in lymphoid tissues of patients with infectious mononucleosis by in situ hybridization.

Although the immunological response during infectious mononucleosis (IMN) has been studied in detail, little is known about the spread of Epstein-Barr virus (EBV) in lymphoid organs or the topographical distribution of the infected cells. In this study, EBV was detected in 11 lymph nodes, 4 tonsils, and 1 spleen of 16 patients with IMN. The predominant cell type positive for the EBV genome was identified as small lymphocytes localized chiefly within typical T areas, preferentially in perifollicular and interfollicular regions of the lymph node. A few endothelia of epithelioid venules were also found to be positive. Furthermore, a small number of sinus lining cells of lymph nodes exhibited labelling. Altogether, only a small number of cells, not exceeding 1 per cent of all cells, were infected with EBV. Our results show that only a small number of lymphocytes carry the EBV and that besides B lymphocytes, other cell constituents of lymphatic tissues are infected by EBV during IMN.

Optic nerve sheath meningoceles. Clinical and radiographic features in 13 cases with a review of the literature.

Thirteen patients with dilated intraorbital optic nerve sheaths with an expanded, patulous cerebrospinal fluid (CSF) space were studied with high-resolution computed tomography (CT) or magnetic resonance imaging (MRI). Eleven patients had bilateral findings. Headache or visual complaints, or both, were present in all patients. Signs of optic nerve dysfunction were present in eight patients. Three patients had visual acuity worse than 20/200. Cerebrospinal fluid pressure was mildly elevated in two patients. Three patients underwent a surgical procedure; visual acuity improved in one. The authors propose the term meningocele for this condition and suggest MRI with fat-suppression techniques and off-axis sagittal views as the radiographic procedure of choice.

Late juvenile-onset Krabbe's disease.

Krabbe's disease is an autosomal recessive leukodystrophy characterized by a lack of galactocerebroside beta-galactosidase activity. In contrast to the classic early infantile-onset form of Krabbe's disease, less recognized, late-onset variants exist. The authors present a case of late juvenile-onset Krabbe's disease, including the associated magnetic resonance imaging (MRI) findings. Most patients with late-onset Krabbe's disease present with visual loss due to optic atrophy. Associated gait abnormalities and parental consanguinity should increase the clinician's suspicion that a child may have late-onset Krabbe's disease. Because of the prolonged survival in late-onset Krabbe's disease, the recent development of bone marrow transplantation for these patient makes diagnosis of this disorder particularly important.

Familial cavernous malformations of the central nervous system and retina.

We studied a family in which 4 persons from three generations had multiple cavernous malformations ("angiomas") of the central nervous system (CNS) and/or retina and found accounts in the literature of sixteen other families with this condition. In these families with familial cavernous malformation of the CNS and retina, 92% of pathologically documented vascular malformations were cavernous; 50% of those subjects affected had multiple CNS and/or retinal vascular malformations and 68% (excluding probands) were symptomatic. Cutaneous vascular lesions were an inconsistant manifestation. Autosomal dominant inheritance with high penetrance was confirmed.

Minimal oculomotor nerve paresis secondary to unruptured intracranial aneurysm.

In 12 patients with minimal oculomotor nerve deficits due to unruptured intracranial aneurysm, the nerve-related findings were incomplete and at least one element (ptosis, mydriasis, or extraocular muscle weakness) was spared in every patient. Although symptomatic, the affected cranial nerve III functions were only partially lost. Six patients had ptosis and mydriasis, three had ptosis and diplopia, two had mydriasis and diplopia, and one had mydriasis alone. Eleven patients had accompanying headaches that were remarkably variable and difficult to categorize. Cerebral angiography showed the aneurysms, but computed tomography missed one third of them. The symptomatic aneurysm arose from the internal carotid artery in six patients, and from the distal basilar artery in six. Fragments of a cranial nerve III palsy associated with recent onset and ipsilateral headache suggest an enlarging internal carotid or distal basilar artery aneurysm.

Risk factors for diabetic retinopathy: a population-based study in Rochester, Minnesota.

Retinopathy is an important sequela of diabetes mellitus, but clinical risk factors for this condition have rarely been assessed in a geographically defined population. In this population-based study, the 1135 Rochester, Minnesota, residents with diabetes mellitus initially diagnosed between 1945 and 1969 (incidence cohort) were followed through their complete medical records in the community to January 1, 1982. Because most of the cases of diabetic retinopathy in Rochester residents developed in patients with non-insulin-dependent diabetes mellitus (NIDDM), risk factors for diabetic retinopathy were examined in this group (N = 1031). A proportional hazards model identified the following risk factors for diabetic retinopathy in NIDDM: elevated initial fasting blood glucose level, marked obesity, and earlier age at onset of diabetes. Stratified analyses indicated that duration of diabetes was also significantly associated with an increased risk of retinopathy. Two secular trends, increasing detection of "mild" NIDDM and decreasing risk of diabetic retinopathy, had a major effect on retinopathy risk assessment. These data also suggest that insulin therapy is not an independent risk factor for diabetic retinopathy.

Magnetic resonance imaging for neurotoxicity in long-term survivors of carcinoma.

Neurotoxicity is a potential complication of combined chemotherapy and whole-brain radiotherapy in long-term survivors of carcinoma. Clinical features of this neurotoxicity are similar to those manifested in the leukoencephalopathy of pediatric patients with leukemia who have been treated prophylactically with whole-brain radiotherapy and chemotherapy. Magnetic resonance imaging, because of its ability to distinguish cortical gray matter and white matter and its utility for studying demyelinating diseases, was used in the assessment of five long-term survivors of carcinoma who had clinical evidence of neurotoxicity. On magnetic resonance examinations, all five patients had profound abnormalities in the periventricular white matter. These changes were considerably more pronounced than those seen on computed tomographic scanning. Thus, magnetic resonance imaging may serve as a useful procedure for early detection of neurotoxicity in patients with carcinoma who have received cerebral radiotherapy and chemotherapy.

Chronic idiopathic anhidrosis.

We describe the cases of eight patients with chronic idiopathic anhidrosis. These patients were heat intolerant and became hot, flushed, dizzy, dyspneic, and weak but did not sweat when the ambient temperature was high or when they exercised. Four patients had preganglionic sudomotor lesions and in the remaining 4 the lesion appeared to be postganglionic. The patients did not have orthostatic hypotension, other evidence of generalized autonomic failure, or symptomatic somatic neuropathy. One patient regained thermoregulatory sweat function and no patient's condition progressed to generalized autonomic failure. Chronic idiopathic anhidrosis appears to be distinctly different from other autonomic neuropathies that tend to carry much poorer prognoses.

Incidence of diabetic retinopathy and blindness: a population-based study in Rochester, Minnesota.

Among the 1135 Rochester residents discovered to have diabetes in the period 1945-69, the prevalence of retinopathy was 2.6% at the time of initial diagnosis. Among those free of retinopathy at diagnosis of diabetes, the subsequent incidence of any retinopathy was 17.4 per 1000 person-years and for proliferative retinopathy alone was 1.6 per 1000 person-years, based on 12,000 person-years of follow-up. The incidence rate of retinopathy was almost three times greater among residents with insulin-dependent (IDDM) than with non-insulin-dependent diabetes (NIDDM); however, the actual number of retinopathy cases was over four times greater among the more numerous residents with NIDDM. By 20 yr after diagnosis of diabetes, the cumulative incidence of retinopathy approached 70% among IDDM subjects and was 30% and 36%, respectively, among the obese and nonobese NIDDM residents. The epidemiologic patterns for proliferative retinopathy were qualitatively similar to those for nonproliferative retinopathy. The risk of blindness was greater among those with proliferative than with nonproliferative retinopathy but was substantial even for those without retinopathy. Most blindness was caused by factors other than isolated diabetic retinopathy.

Visual status after transsphenoidal surgery at the Mayo Clinic, 1971-1982.

In 1,003 patients who underwent transsphenoidal surgery for sellar and parasellar lesions, the surgical mortality was 0.7% (seven patients). Only 25 patients experienced visual complications. Pituitary adenomas were found in 851 patients, of whom 714 underwent visual acuity and visual field testing both before and after their transsphenoidal operations. Among this group, visual acuity had been reduced in 115; postoperatively it was restored to normal or improved in 53, remained the same in 60, and became worse in two. Visual fields, which had been abnormal preoperatively in 230 cases, were restored to normal or improved in 168, remained the same in 52, and became worse in ten. There were also five patients whose vision was normal preoperatively but not postoperatively; thus, the total of those whose sight became worse after transsphenoidal surgery was 17. Surgical mortality in the group with adenomas was 0.5% (four of 851 patients). Nine adenomas recurred during follow-up. Of 40 patients with craniopharyngiomas, 21 had abnormal vision preoperatively; postoperatively, nine were improved and two were worse. In 40 cases surgical exploration failed to disclose any abnormality. There were 12 patients with chordomas and 60 with miscellaneous sellar and parasellar tumors.

Acute panautonomic neuropathy.

Two patients with acute panautonomic neuropathy had severe impairment of sympathetic and parasympathetic function of acute onset. Autonomic tests suggesting a postganglionic lesion and direct evidence of loss of unmyelinated and small myelinated fibers on nerve biopsy were found in Patient 1. There was a selective loss of small myelinated and unmyelinated nerve fibers; C potential was absent in the in vitro compound action potential; dopamine-beta-hydroxylase activity was unmeasurable. No definite abnormalities were found on the nerve biopsy of Patient 2. The acute panautonomic neuropathies appear to comprise a spectrum of somatic and autonomic involvement.