Performance comparison of Yb:YAG ceramics and crystal gain material in a large-area, high-energy, high average-power diode-pumped laser.

We compare for the first time the influence of different Yb:YAG gain media on the performance of a large-area, high average-power laser system with an output energy of up to 6 J. Monocrystalline slabs grown by a new technique without central growth defect are compared with ceramics. Small signal gain, maximum output energy and thermal lensing are compared for ceramic slabs with co-sintered amplified spontaneous emission (ASE) absorber cladding, monocrystalline slab with and without optically bonded ASE absorber cladding, and surface structured monocrystalline slabs. We show that these large monocrystals with optically bonded absorber cladding have similar performance to cladded ceramics, so far the only material for high-energy Yb:YAG lasers.

Effects of feeding strategy on milk production, reproduction, pasture utilization, and economics of autumn-calving dairy cows in eastern North Carolina.

A balance among stocking rate (SR), pasture management, and supplementary feeding is required to optimize overall farm performance and profitability in pasture-based dairying. Beginning in September 2003, a seasonal, autumn-calving, pasture-based farming system was established to address the effects of feeding strategy (FS; i.e., a unique combination of stocking and supplementation rate) on productive, reproductive, and economic performance of lactating herds over 3 yr. Eighty lactating cows (1/3 Holsteins, 1/3 Jerseys, and 1/3 crosses of those breeds) were randomly assigned to either a lesser stocking, lesser supplementation group [LSR; 2.2 cows/ha, 6.3 kg of dry matter (DM) of a corn-based concentrate consumed daily, n=40] or a greater stocking, greater supplementation group (HSR; 3.3 cows/ha, 9.2 kg of DM of a corn-based concentrate consumed daily, n=40). Pasture/forage crop rotations included annual ryegrass and sorghum-Sudan (50%), annual ryegrass and bermudagrass (20%), and a tall fescue-white clover pasture (30%). Pre- and postgrazing herbage mass values and grazing intervals (3,347±255.8 kg of DM/ha, 1,861±160.6 kg of DM/ha, 23.6±1.9 d) did not differ between FS. The nutritive value of fresh and conserved forages was similar between feeding strategies, except for acid detergent fiber in freshly grazed bermudagrass (29.6 vs. 26.3% of DM for LSR and HSR, respectively). Cows on HSR tended to spend more time on an adjacent feeding area where conserved forages were offered (85 vs. 61 d/yr) as opposed to grazing paddocks (204 vs. 228 d/yr). Lactation performance was greater for HSR; cows on HSR produced 10.8% more milk fat and 6.3% more milk protein than cows on LSR. Holstein cows produced the greatest amounts of mature-equivalent milk, but did not differ from crossbred cows in terms of energy-corrected milk, and mature-equivalent fat and protein yields. Reproductive efficiency did not differ among feeding strategy, but breed differences were observed; conception rates at first and all services, as well as pregnancy rates, were greater for Jersey and crossbred cows compared with Holsteins. The greater stocking rate required additional supplemental concentrate and time away from grazing paddocks, but reproductive efficiency was similar and overall lactation performance was greater. The greater stocking rate resulted in increased productivity and greater income over feed costs per unit of land.

Continuous-wave, multiple-order rotational Raman generation in molecular deuterium.

We demonstrate the generation of ≈10 rotational sidebands using continuous-wave stimulated Raman scattering in molecular deuterium. The generation occurs inside a high-finesse cavity at molecular gas pressures of ≈0.1 atm.

Continuous-wave high-power rotational Raman generation in molecular deuterium.

We report the generation of more than 300 mW of rotational Stokes output power in a CW Raman laser. The generation is achieved in low-pressure molecular deuterium inside a high-finesse cavity.

Does endoscopy diagnose early gastrointestinal cancer in patients with uncomplicated dyspepsia?

BACKGROUND: Recent guidelines from NICE have proposed that open access gastroscopy is largely limited to patients with "alarm" symptoms. AIMS AND METHODS: This study reviewed the outcome of all our patients with verified oesophageal or gastric carcinoma who presented with uncomplicated dyspepsia to see if endoscopic investigation is warranted in this group. All patients with histologically verified upper gastrointestinal (GI) cancers who presented over a period from 1998 to 2002 were identified. Their presenting symptoms, treatment, and outcome were analysed. RESULTS: 228 upper GI cancers (119 oesophageal, 109 gastric; mean age 72 years (29-99 years); 130 male, 82 female) were identified in 11 145 endoscopies performed. Only 14 patients (6.2%) presented without alarm symptoms; three patients were under 55 years of age and all had gastric carcinoma-one of these had chronic diarrhoea only. Eleven had dyspepsia or reflux symptoms only, and two were under surveillance for Barrett's oesophagus. Only five patients had a curative surgical resection and are still alive two-six years from diagnosis. A sixth patient had a curative operation but died of a cerebrovascular accident one year later. The remaining eight patients unfortunately had either metastatic disease or comorbidity, which precluded surgery. All of these died within two years of diagnosis, mean survival 10 months. CONCLUSION: Only five patients with dyspepsia and no alarm symptoms had resectable upper GI malignancies over a four year period. Limiting open access gastroscopy to those with alarm features only would "miss" a small number of patients who have curable upper GI malignancy.

Pharmacokinetics of nicotine carbomer enemas: a new treatment modality for ulcerative colitis.

BACKGROUND: Ulcerative colitis is largely a disease of nonsmokers, and transdermal nicotine is of therapeutic value in the active disease. Because side effects are common, we developed a topical enema formulation of nicotine. OBJECTIVE: To study the pharmacokinetics of nicotine complexed with a polyacrylic carbomer and administered by enema to eight healthy volunteers and to eight patients with active ulcerative colitis, verified sigmoidoscopically. PATIENTS AND METHODS: All 16 subjects were nonsmokers. The mean age for normal subjects was 33 years; the mean for patients with ulcerative colitis was 60 years. Median stool frequency for patients with ulcerative colitis was four daily. Patients were taking 5-amino salicylic acid compounds and five were taking oral prednisolone (median dose, 12 mg daily). Nicotine, 6 mg, complexed with carbomer 974P, 400 mg, was administered in a 100 ml enema after an overnight fast, with serial blood measurements taken over 8 hours. Serum nicotine and cotinine were measured by gas liquid chromatography. Area under the concentration-time curves were calculated by the trapezoidal method, and the terminal elimination half-life was derived by extrapolation of the log-linear terminal phase. RESULTS: With the exception of nicotine time to reach peak concentration, which was longer in patients (median of 60 minutes compared with 45 minutes; p < 0.005), other comparisons between normal subjects and patients showed no statistically significant difference, although there was considerable inter-subject variation. Maximum concentration of nicotine, 8.1 +/- 3.5 ng/ml, in the 16 subjects occurred after a median of 60 minutes (range, 30 to 180 minutes); maximum cotinine concentrations of 60.4 +/- 11.5 ng/ml occurred after 4 hours. Side effects in five subjects were mild (four subjects) or moderate (one subject) and included lightheadedness, nausea, and headache; these five subjects were female lifelong nonsmokers of low body weight. CONCLUSION: Because most of the active ingredient of nicotine is converted to continine on the first pass through the liver, substantial concentrations can be achieved at the site of disease with only modest rises in serum nicotine, which are responsible for side effects; cotinine has low pharmacologic activity. Topical administration of nicotine may be useful treatment for distal ulcerative colitis.

Eyeblink classical conditioning: hippocampal formation is for neutral stimulus associations as cerebellum is for association-response.

Extensive evidence has been amassed that the cerebellum, hippocampus, and associated circuitry are activated during classical conditioning of the nictitating membrane/eyeblink response. In this article, the authors argue that the cerebellum is essential to all eyeblink classical conditioning paradigms. In addition, the septohippocampal system plays a critical role when the classical conditioning paradigm requires the formation of associations in addition to the simple association between the conditioned and unconditioned stimuli. When only a simple conditioned stimulus--unconditioned stimulus association is needed, the septohippocampal system has a more limited, modulatory role. The neutral stimulus association versus simple association-response distinction is one of the ways in which declarative or relational memory can be separated from nondeclarative or nonrelational memory in classical conditioning paradigms.

Nitric oxide mediates a therapeutic effect of nicotine in ulcerative colitis.

BACKGROUND: Ulcerative colitis is a condition of nonsmokers in which nicotine is of therapeutic benefit. AIMS: To examine the in vitro effect of nicotine on colonic smooth muscle activity and the role of nitric oxide (NO) as a mediator. METHODS: Nicotine, 1-10 microM, was administered to strips of circular muscle from the distal sigmoid colon of 9 patients with active ulcerative colitis and 18 with colorectal cancer. The effect of electrical field stimulation (EFS) was examined before nicotine was added. Finally L-NAME, a NO synthetase inhibitor, was added before nicotine was administered again. RESULTS: Muscle strips developed similar spontaneous resting tone. In response to EFS, ulcerative colitis tissue developed lower tensions than the controls. Nicotine significantly reduced the resting tone and peak tension after EFS, with a greater effect in controls. With L-NAME, peak tensions were increased more in ulcerative colitis than controls, and nicotine produced a much smaller reduction. CONCLUSIONS: Nicotine reduces circular muscle activity, predominantly through the release of nitric oxide-this appears to be 'up-regulated' in active ulcerative colitis. These findings may explain some of the therapeutic benefit from nicotine (and smoking) in ulcerative colitis and may account for the colonic motor dysfunction in active disease.

Nicotine enemas for active ulcerative colitis--a pilot study.

BACKGROUND: Since transdermal nicotine is of value in the treatment of active ulcerative colitis but is often associated with side-effects, an alternative in the form of topical therapy with nicotine enemas has been developed. METHODS: In an open study, 22 patients with active colitis, all non-smokers, were asked to take a 100 mL enema containing 6 mg of nicotine every night for 4 weeks. Pre-trial treatment using mesalazine (n = 16), oral prednisolone (8), cyclosporin (1) and azathioprine (1) was kept constant for the month prior to assessment and during the study period. Symptoms, with stool frequency, were recorded on a diary card and an endoscopy was performed with rectal biopsy at the beginning of the study and after 4 weeks. RESULTS: Seventeen of the 22 patients completed 1 month of treatment. Mean duration of relapse was 29 weeks, range 3-94. Sixteen of 17 improved their St Mark's score. Urgency and stool frequency improved in 12 patients, sigmoidoscopic and histological scores in 10. Three patients had a full remission of symptoms with normal sigmoidoscopy. Six of 10 with a partial response continued with the enemas for a second month and five showed further improvement with full remission in two. The enema appeared effective when added to conventional treatment and produced few side-effects. CONCLUSION: Topical nicotine therapy for ulcerative colitis may have a place in future management, but controlled studies are needed.

Enteric-release glyceryl trinitrate in active Crohn's disease: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Mucosal ischaemia may contribute to the pathogenesis of Crohn's disease. Microvascular abnormalities have been found in colonic resection specimens, and mucosal levels of constitutive nitric oxide synthase are reduced. AIM: To assess the efficacy of a novel, enteric-release formulation of the nitric oxide donor, glyceryl trinitrate, aimed at increasing the mucosal circulation and relaxing smooth muscle in the affected bowel. METHODS: The trial was randomized, double-blind and placebo-controlled. Baseline disease activity was assessed by a structured symptom diary, with blood tests and a quality of life assessment. Patients with a Crohn's disease activity index of > or = 150 and < 450 were randomized to receive 12 weeks of either glyceryl trinitrate (initially 6 mg twice daily, increasing to 9 mg twice daily after 6 weeks) or an identical placebo. Assessments were repeated at 6 and 12 weeks. RESULTS: Seventy patients (22 male) entered the study; 34 were given glyceryl trinitrate and 36 placebo. At 12 weeks, there were no differences between the treatment groups in terms of Crohn's disease activity index, pain, stool frequency, inflammatory markers or quality of life scores. CONCLUSIONS: Enteric-release glyceryl trinitrate did not benefit patients with mild to moderately active Crohn's disease. Whilst ischaemia may contribute to the pathogenesis of Crohn's disease, our results fail to provide supportive evidence for this hypothesis.

Effect of smoking and transdermal nicotine on colonic nicotinic acetylcholine receptors in ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a disease largely of non-smokers, in which nicotine is of therapeutic value. The mode of action is unknown, but may involve nicotinic acetylcholine receptors (nAChRs) in the bowel wall. AIM: To investigate the presence of nAChRs in rectal mucosa, and the effect of smoking and nicotine on their expression. DESIGN: Prospective case-control study. METHODS: In situ hybridization (ISH) and immunocytochemistry (ICC) were used to show alpha3 nAChRs in colonic mucosa. Rectal mucosa was examined from controls (n=55) and patients with inactive UC (n=62), both smokers and non-smokers, by ICC, using two antibodies to show the density and distribution of receptors in the mucosa. Non-smokers with UC (n=43) were given transdermal nicotine or placebo patches for 6 months, and rectal biopsies, taken before and after treatment, were examined by ICC to show nAChRs. RESULTS: In normal colon, ISH and ICC showed alpha3 subunit in a wide variety of cells, including mucosal epithelium. In rectal biopsies, neither smoking nor nicotine influenced the expression of alpha3 immunoreactivity in epithelium, either in controls or UC. However, controls had a significantly greater density of immunodetectable mucosal epithelium alpha3 subunit, compared with UC patients. DISCUSSION: The presence of nAChRs in colonic epithelium may be pertinent to the beneficial effect of nicotine in UC, but since neither smoking nor nicotine treatment is associated with any change in the expression of epithelial alpha3 nAChRs, the effect may be due to functional changes in the receptor. The decreased number of alpha3 nAChRs in UC compared with controls may be related to an increased cell turnover in UC.

Anesthetic block of the dorsal penile nerve inhibits vibratory-induced ejaculation in men with spinal cord injuries.

OBJECTIVES: [corrected] We investigated which nerve pathways are necessary to achieve ejaculation using penile vibratory stimulation (PVS) in men with spinal cord injury (SCI). METHODS: Eight men with SCI were selected based on the presence of a bulbocavernosus reflex (BCR) and consistent antegrade ejaculation with PVS. Level of injury was cervical (4), upper thoracic (4), and lower thoracic (1). Mean age was 30.4 years (range 22 to 38). Usual responses to PVS included autonomic dysreflexia (4), erection (4), and consistent somatic responses such as abdominal contractions (8). Local anesthesia of the dorsal penile nerves (penile block) was achieved using 1% plain lidocaine injection. Effective penile block was confirmed by loss of the BCR. Two PVS ejaculation trials were performed: one trial during the penile block and one trial when the penile block had worn off. In 4 subjects, the bladder contents were analyzed for retrograde ejaculation. RESULTS: With the penile block, ejaculation was inhibited in 100% of the subjects. None of the bladder washings demonstrated sperm, indicating absence of retrograde ejaculation. None of the subjects exhibited their usual erectile response, somatic responses, or signs of autonomic dysreflexia. After the penile block wore off, PVS induced ejaculation in all subjects. If subjects usually had erection, somatic responses, or signs of autonomic dysreflexia, these also returned. CONCLUSIONS: Our data suggest that ejaculatory response to PVS in SCI men requires the presence of intact dorsal penile nerves.

Evaluation of behavioral disinhibition in P/NP and HAD1/LAD1 rats.

1. Two lines of rats specifically bred for alcohol preference were exposed to two different behavioral tasks that required behavioral inhibition to successfully solve. 2. Learning and performance of a step-down passive avoidance task and a differential reinforcement of low-rate responding task were studied in P/NP and HAD1/LAD1 rats. 3. While the P rats had difficulty in learning both tasks, HAD1, LAD1 and NP rats performed at control levels. 4. These data suggest that P rats, but not HAD1 rats, may have problems learning tasks that require inhibition of ongoing or previously learned behaviors.

Concurrent eyeblink classical conditioning and rotary pursuit performance: implications for independent nondeclarative memory systems.

The authors examined whether 2 nondeclarative tasks, simple eyeblink classical conditioning (EBCC) and rotary pursuit (RP), would interfere with each other when performed simultaneously. In Experiment 1,100 participants were assigned to 1 of 5 groups: paired EBCC/RP, unpaired EBCC/RP, paired EBCC as a single task, unpaired EBCC as a single task, and RP as a single task. Participants in the paired EBCC/RP group showed significantly greater acquisition of conditioned responses than did participants in the unpaired EBCC/RP group, and the unconditioned eyeblink response was similar in both groups. Comparisons of the paired EBCC/RP and paired EBCC-as-a-single-task groups indicated no differences in trials to criterion, but on some measures the single-task group conditioned better. Controls introduced in Experiment 2 did not change this pattern. Results provide some evidence for the lack of interference between EBCC and RP.

Intra-luminal nicotine reduces smooth muscle tone and contractile activity in the distal large bowel.

BACKGROUND: Nicotine may be of therapeutic value in ulcerative colitis (UC), although its mechanism of action has not been established. OBJECTIVE: To examine the effect of a solution of nicotine on sustained resting pressure (tone) and contractile activity in the human colon. METHODS: Ten healthy volunteers, and seven with UC in symptomatic remission took part; all were non-smokers. All 17 subjects were given nicotine or placebo solution on two separate occasions in a randomized sequence. A water-perfused manometry catheter, with openings at 5, 10 and 15 cm from the tip, was placed by rigid sigmoidoscopy in the recto-sigmoid region. Baseline tone and activity were measured for 15 min prior to instillation of 20 ml of saline alone or with nicotine, 1.2 mg, at pH 4.5. Observations were made over the subsequent 15-20 min. RESULTS: Baseline spontaneous activity in all subjects showed both high- and low-frequency components; in three patients with UC, the low-frequency activity was of high amplitude. The nicotine reduced both tone and activity in all subjects, with reduction or abolition of the large contractions in UC. Tone in all 17 subjects was reduced significantly at 3 min after nicotine (P = 0.000015, sign test); the rate of recovery varied in individuals. Results from normals and UC did not differ significantly from each other. No significant change in tone or activity was observed with the saline solution. CONCLUSION: Intra-luminal nicotine significantly reduces both smooth muscle tone and contractile activity in the recto-sigmoid colon in both normal subjects and patients with UC.

Using numerosity judgments to determine what is learned during automatization.

An important question in learning is the nature of the information required to support skilled, or automatic, performance. In 2 experiments, participants counted patterns of 8-10 objects displayed on a computer screen for 4 sessions of 240 trials each before being transferred to a different set of patterns for a final session of 240 trials. The patterns in the final session differed from those seen in the 4 training sessions in either overall configuration (Experiment 1) or identity of constituents (Experiment 2). Results indicated that both types of information are important in learning and automatization of a counting task and support the idea that what is attended to during training will be necessary to support subsequent automatic performance.

Disseminated aspergillosis in the acquired immunodeficiency syndrome.

The relationship of disseminated aspergillosis with human immunodeficiency virus (HIV) infection is unclear. In the initial case definition of acquired immunodeficiency syndrome (AIDS) developed by the Centres for Disease Control (CDC), Atlanta, aspergillosis was included as an AIDS-defining opportunistic infection. In view of the primary relationship of aspergillosis with neutropenia rather than with lymphocyte depletion, as well as the lack of aspergillar infections among reported AIDS cases, aspergillosis was later deleted from the CDC case definition of AIDS. We describe a case of disseminated aspergillosis in a patient with AIDS, with an extensive literature review of the subject.

Spatial and time distribution of dairy cattle excreta in an intensive pasture system.

This study determined distribution of feces and urine from 36 lactating dairy cattle (Bos taurus) managed in a rotationally grazed 0.74-ha endophyte-free tall fescue (Festuca arundinacea Schreb.)-white clover (Trifolium repens L.) pasture. Cows were observed for 24 h five times from July 1997 to April 1998, and for 13.5 h in September 1997. During each 24-h observation period, the first grazing period (12 h) used 54% of the paddock and the second grazing period (8 h) used the entire paddock. Times and locations of all defecations and urinations from a subgroup of eight cows, observed while in the pasture, feed area, milking parlor, or in transit were recorded during the observation periods listed above and another time in May 1997. On pasture, all defecations and urinations were surveyed and mapped for all 36 cows. Feces and urine from six observation periods covered an estimated 10% of the paddock area in one year. Within 30 m of the water tank, concentrations of feces and urine from three warm-season observations were significantly greater than concentrations during three cool-season observations. Percentages of defecations and urinations on the pasture, feeding, and milking areas were highly correlated (r > 0.90) with time spent in those areas. Pasture-based systems could reduce manure handling and storage requirements proportional to the time cattle are on pastures. Manure on the pasture was evenly distributed, except around the water tank during warm-weather grazings. Results indicate that pasture-based dairy systems may require smaller, less-expensive manure management systems compared with confinement dairy farms.

Classical eyeblink conditioning: clinical models and applications.

In this paper, we argue that the main reason that classical eyeblink conditioning has proven so useful when applied to clinical situations, is that a great deal of information is known about the behavioral and neural correlates of this form of associative learning. Presented here is a summary of three lines of research that have used classical eyeblink conditioning to study three different clinical conditions; autism, fetal alcohol syndrome, and obsessive-compulsive disorder. While seemingly very different clinical conditions, classical eyeblink conditioning has proven very useful for advancing our understanding of these clinical pathologies and the neural conditions that may underlie them.