What makes a rhythm complex? The influence of musical training and accent type on beat perception.

Perception of a regular beat in music is inferred from different types of accents. For example, increases in loudness cause intensity accents, and the grouping of time intervals in a rhythm creates temporal accents. Accents are expected to occur on the beat: when accents are "missing" on the beat, the beat is more difficult to find. However, it is unclear whether accents occurring off the beat alter beat perception similarly to missing accents on the beat. Moreover, no one has examined whether intensity accents influence beat perception more or less strongly than temporal accents, nor how musical expertise affects sensitivity to each type of accent. In two experiments, we obtained ratings of difficulty in finding the beat in rhythms with either temporal or intensity accents, and which varied in the number of accents on the beat as well as the number of accents off the beat. In both experiments, the occurrence of accents on the beat facilitated beat detection more in musical experts than in musical novices. In addition, the number of accents on the beat affected beat finding more in rhythms with temporal accents than in rhythms with intensity accents. The effect of accents off the beat was much weaker than the effect of accents on the beat and appeared to depend on musical expertise, as well as on the number of accents on the beat: when many accents on the beat are missing, beat perception is quite difficult, and adding accents off the beat may not reduce beat perception further. Overall, the different types of accents were processed qualitatively differently, depending on musical expertise. Therefore, these findings indicate the importance of designing ecologically valid stimuli when testing beat perception in musical novices, who may need different types of accent information than musical experts to be able to find a beat. Furthermore, our findings stress the importance of carefully designing rhythms for social and clinical applications of beat perception, as not all listeners treat all rhythms alike.

Outcomes of sequential tube shunts in complicated glaucoma.

OBJECTIVE: To evaluate intraocular pressure (IOP) control, change in visual acuity, and complications in eyes that have undergone a second glaucoma tube shunt procedure. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Twenty-two eyes of 22 patients that have undergone sequential tube implants for management of glaucoma. METHODS: Parameters analyzed included IOP, visual acuity, and number of hypotensive agent before each shunt procedure and at last follow-up visit. The overall IOP lowering effect attributable to each tube shunt was calculated. Any ocular complications after the second tube shunt were recorded. Success was defined as an IOP between 6 and 21 mm Hg and a 20% reduction in IOP from the second tube shunt procedure. Qualified successes met one of these two requirements at the last follow-up visit. Total failures did not meet any of the above criteria, required additional surgical intervention to lower IOP, or both. MAIN OUTCOME MEASURES: Intraocular pressure control, visual acuity preservation, and complications. RESULTS: At the last follow-up visit, the average percent reduction in IOP from both tube shunt procedures was 42+/-21%. The average percent IOP reduction from the second tube shunt was 33+/-17%. Eleven (50%) patients met the criteria for success, 8 (36.4%) patients were qualified successes, and 3 (13.6%) were failures. The median number of hypotensive agents decreased from two to one. Ten patients experienced new or worse pseudophakic bullous keratopathy after the second tube shunt, six of whom underwent penetrating keratoplasty. Thirteen (59%) patients maintained visual acuity within one line of their second tube shunt pre-operative Snellen visual acuity. Seven (32%) patients lost more than 2 lines, and one patient lost light perception. CONCLUSIONS: Although corneal morbidity is a common complication, a second tube shunt does not cause higher-than-expected rates of other complications associated with tube shunt surgery. Eyes that undergo a second tube shunt procedure can achieve pressure control, require fewer hypotensive agents, and may maintain stable visual acuity.

The effect of mitomycin C on Molteno implant surgery: a 1-year randomized, masked, prospective study.

PURPOSE: The authors assess whether adjunctive mitomycin C improves Molteno tube shunt surgery in terms of intraocular pressure (IOP), visual acuity, and complication rates. PATIENTS AND METHODS: Twenty-five eyes of twenty-five consecutive patients undergoing double-plate Molteno implant surgery were randomized to receive either mitomycin C (MMC) 0.4 mg/mL for 2 minutes or a control balanced salt solution in a masked, prospective study. Intraocular pressure, visual acuity, and complications were recorded 1 week and 1, 3, 6, and 12 months after surgery. A repeated measures analysis of variance (ANOVA) model was used to test the overall effect of the drug on IOP and percent change from preoperative IOP. RESULTS: Thirteen eyes received balanced salt solution and 12 eyes received MMC. There was no difference between the groups with respect to age, preoperative IOP, log mean angle of resolution (LogMar) visual acuity, or number of preoperative medications. Except for week 1, there were no differences between the groups at any of the clinic visits with respect to IOP and percent change from baseline IOP. Analysis of the visual acuity (LogMar) showed reduction in vision for both groups. Complications were similar in each group, as were number of postoperative hypotensive agents required. CONCLUSIONS: Adjunct MMC does not demonstrate a significant difference in outcomes compared with placebo in pressure-ridged Molteno implant surgery. Results of this study are limited by a small number of patients in each group and a fixed dose of MMC.

Conjoint IGF-I and insulin infusion shows diverse interactive effects in diabetic rats.

Studies in diabetic rodents and humans provide evidence that IGF-I may alleviate the diabetic state and insulin resistance to some degree. To assess the efficacy of IGFs as an adjunct treatment with insulin in diabetes, we infused IGF-I or des(1-3)IGF-I for 7 days at 0, 10.7, 26.7, and 66.8 nmol/day to streptozotocin-induced diabetic rats in conjunction with infusions of 0, 2.2, 5.6, or 14 nmol/day insulin. Both insulin and des(1-3)IGF-I increased body weight gain by 7 g/day compared with controls (1.2 g/day), but there was no additive effect. However, for nitrogen retention, the effects of des(1-3)IGF-I were additive with those of 2.2 nmol/day insulin. Des(1-3)IGF-I was two- to threefold more potent than IGF-I. At comparable rates of total nitrogen retention, carcass nitrogen retention was approximately 35% higher with insulin than with IGF treatment, indicating a differential tissue response. IGFs did not alter carcass fat content. Des(1-3)IGF-I increased liver glycogen additively with insulin but reduced glucosuria only when given with 5.6 nmol insulin per day, indicating the possibility of a facilitatory effect, perhaps via increased insulin sensitivity. Insulin was 10- to 25-fold more potent in these glucoregulatory actions. Differential effects of the hormones were also observed for kidney, liver, and thymus weights. We conclude that IGFs and especially the more potent des(1-3)IGF-I may have a role as an adjunct to insulin therapy in diabetic patients.

Acute Effect of Topical (beta-Adrenergic Antagonists on Normal Perimacular Hemodynamics.

PURPOSE: beta-adrenergic antagonists are the most commonly prescribed antiglaucoma medications. The nonselective beta blocker timolol has been shown to either increase or to not affect retinal blood flow, despite the suggestion that the drug may cause vasoconstriction due to its blockade of beta-2 receptors. Other beta blockers with unique pharmacologies may produce different effects on blood flow. We studied the effects of betaxolol (beta-1 selective antagonist), carteolol (nonselective beta-antagonist with intrinsic sympathomimetic activity), and levobunolol (nonselective beta antagonist with intrinsic sympathomimetic activity), and levobunolol (nonselective beta antagonist with active polar metabolite) on perimacular hemodynamics. METHOD: On four separate occasions separated by at least 10 days, 16 normal subjects performed measurements of heart rate, blood pressure, IOP, and blue field entoptic simulation assessment of leukocyte velocity and density before and 2 h after instillation of one of the three drugs or an artificial tears placebo. RESULTS: IOP was significantly reduced by all three drugs as compared to placebo (p < 0.05, Bonferroni-corrected two-tailed paired t-test). No significant differences were found in heart rate, blood pressure, and perimacular leukocyte velocity or density in any of the treatment conditions as compared to placebo. CONCLUSIONS: Betaxolol, carteolol, and levobunolol do not appear to significantly alter perimacular hemodynamics 2 h after administration. The absence of any acute change in hemodynamics despite the drop in IOP suggests normal autoregulation maintained constant blood flow.

Effects of insulin and insulin-like growth factors on protein and energy metabolism in tumour-bearing rats.

The effects of insulin-like growth factor-1 (IGF-I), and a more potent variant LR3-IGF-I, which binds poorly to IGF-binding proteins, were investigated in rats bearing a mammary adenocarcinoma. The effect of insulin, either alone or in combination with LR3-IGF-I, was also investigated. Peptides were infused via osmotic minipumps for 6-7 days after tumour size reached 5% of body weight. Infusion of IGFs alone at either 200 or 500 microgram/day significantly decreased food intakes as well as circulating levels of insulin and glucose, and consequently failed to promote muscle protein accretion in the host. Tumour growth was increased by the IGFs, especially by LR3-IGF-I, even though these peptides did not promote growth of the adenocarcinoma in cell culture. Infusion of LR3-IGF-I, and to a lesser extent IGF-I, led to decreased rates of muscle protein synthesis and increased muscle protein breakdown, but each of these measures was closely related to the final tumour burden (r2 = 0.454 and 0.810 respectively; P < 0.01) and possibly resulted from a decrease in substrate supply to the host tissues. Insulin infusion (100 micrograms/day) increased food consumption by more than 50% and significantly decreased tumour growth. Insulin and LR3-IGF-I had a synergistic effect on host weight, which increased by 19.1 +/- 1.9, -1.1 +/- 4.7 and 37.9 +/- 1.5 g for insulin, LR3-IGF-I and combined treatments respectively. Carcass protein was increased by more than 10% with insulin treatment, due to increased rates of synthesis and decreased rates of muscle protein breakdown, but LR3-IGF-I had no positive effect on carcass protein accretion, either alone or in combination with insulin. Similarly, the amount of carcass fat was increased almost 2-fold by insulin treatment, whereas it was decreased by 30% by LR3-IGF-I. These changes may have arisen either from direct hormone effects on metabolism or from the indirect effects of food intake, or both. Our results suggest that IGF administration may exacerbate an insulin insufficiency associated with the tumour-bearing state and further decrease metabolic substrate supply to the host. This can be overcome by co-infusion of insulin.

Surgical management of the paralyzed eyelid.

The most devastating sequelae of the facial nerve paralysis is the loss of eyelid function. The inability to blink, lubricate and protect the globe can lead to exposure keratitis, corneal abrasion and even the loss of vision. Eyelid closure is approximately 85% upper eyelid and 15% lower eyelid. In order to ensure adequate protection of the globe, deficiencies of both eyelids must be addressed. We report our experience with 20 patients with eyelid paralysis. Upper lid reanimation was performed by the placement of gold lid weights on the tarsal plate. Lower lid reanimation procedures included lateral canthopexy and horizontal lid shortening. A discussion of the above-mentioned procedures, the timing of the procedures and a critical analysis of results will be included. A comprehensive approach to the management of the paralyzed eye will be presented.

Clinicians into management: the experience in context.

This paper interprets the experience of a sample of 60 clinicians becoming involved in formal management, mainly at hospital unit level, in the historical context of changing health service organisation. This includes the introduction of managerialism and the evolution of the NHS into a structured network based around purchaser/provider relationships. The conclusion is that these clinicians are becoming involved in management, and making the personal and social adjustments necessary for this, but in a way that leaves medical culture, and their allegiance to it, at the present largely intact. This is achieved largely through the organisational mechanism of clinical directorates, which promise to function as professional groups from the clinical point of view and as business units from the managerial perspective. An argument is put forward, based on a theoretical view compatible with the data from the clinicians' experience, that this mode of medical involvement in management may operate without undue conflict in the longer term if: (a) clinicians accept the degree of local professional regulation that this model applies; and (b) the conflict between medical need and available resource can be dealt with elsewhere in the system without passing it back to hospitals and clinical directorates. On the other hand it is possible that conflict will increase if the consequences of management control systems and objectives percolate down through the management hierarchy and cross into the medical domain, via clinical directorates.

Muscle protein breakdown in premature human infants.

Muscle protein breakdown in premature human infants can be quantified from the urinary excretion ratio of 3-methylhistidine (3MH) to creatinine. Only single urine samples are needed and no prior treatment of the infant is required. Use of this procedure over the past 10 years has established that rates of muscle protein breakdown increase rapidly in response to stress, infection or inadequate nutrition and return to normal once successful treatment has been achieved. Higher rates are also observed in very early premature infants. No effects of sex, time of day or the route of nutrient intake, whether parenteral or enteral, are observed. A marked fall in 3MH excretion occurs following indomethacin treatment, consistent with responses to prostaglandin inhibitors established previously in isolated muscle.

Quality assurance.

The QA process is recommended to anyone seeking to upgrade patient care delivery. It clarifies theories and gives substance to progressive ideas being considered for adoption. Certainly it tends to prevent premature and ill-conceived presentations. When an action is instituted, QA provides the framework that can be used to facilitate the change. As an afterthought, but as a welcome benefit, QA can foster teamwork and camaraderie among staff who assist in problem solving or bringing an idea to fruition.

Sequential urinary N tau-methylhistidine to creatinine ratios in premature infants.

The present study was undertaken to establish normal values of the N tau-methylhistidine to creatinine excretion ratio in very premature infants, to observe changes with postnatal age, and to determine whether or not reliable data on this index of myofibrillar protein breakdown could be obtained from untimed urine samples without recourse to the 24-hour collections used previously. The normal range (95% confidence limits) of the molar excretion ratio for unstressed infants was established to be between 0.0248 and 0.0440. Narrower limits of variability occurred when nutrient intake was controlled at a satisfactory level or when comparisons were between sequential urine samples from single infants. No diurnal changes could be detected. We conclude that analyses of N tau-methylhistidine and creatinine on spot urine samples permit the calculation of an excretion ratio that is reproducible both within and between individual infants and that should be useful in assessing changes in myofibrillar protein breakdown caused by differences in clinical, pharmacologic, or nutritional status.

Growth hormone-induced changes in myofibrillar protein breakdown in hypopituitary children.

1. Creatinine and N tau-methylhistidine excretion rates have been measured in 13 hypopituitary children to calculate the body muscle contents and rates of myofibrillar protein breakdown. Analyses have been made during periods of growth hormone withdrawal and subsequent administration. 2. The creatinine excretion rate was lower in the hypopituitary children, indicating a lower muscle content per kg body weight. This difference persisted even in children who had received growth hormone for several years. 3. Excretion of N tau-methylhistidine was reduced by the administration of growth hormone. 4. The fractional breakdown rate of myofibrillar protein, as calculated from the N tau-methylhistidine to creatinine molar excretion ratio, averaged 1.76%/day in the four youngest children during growth hormone withdrawal. This was significantly higher than for control children of a similar age (P less than 0.02) and was reduced to the normal rate of 1.47%/day by growth hormone administration. 5. In older children the fractional rate of myofibrillar protein degradation remained in the normal range irrespective of growth hormone treatment. 6. These results are discussed in the context of the anabolic effects of growth hormone on muscle being partly explained by its action to decrease rates of protein breakdown.

Measurements of myofibrillar protein breakdown in newborn human infants.

1. Myofibrillar protein breakdown was calculated from the urinary excretion ratio of NT- methylhistidine (3-methylhistidine) to creatinine in newborn premature and full-term infants. Representative values were obtained from single voidings provided that the infant's metabolic status was stable. 2. NT- Methylhistidine in infant urine was measured by a rapid Auto Analyser method and shown to give similar values to those obtained by ion-exchange separation techniques. 3. The molar excretion ratio of NR- methylhistidine to creatinine averaged 0.0159 in urine samples obtained within 12 h after birth. A similar ratio was found in amniotic fluid collected at birth. It is argued that this ratio does not reflect a low rate of myofibrillar protein breakdown in the foetus, but rather a more effective transplacental passage of NT- methylhistidine than of creatinine. 4. The urinary ratio increased during the first 2 days after birth to a plateau at 0.0372. This represents a myofibrillar protein degradation rate of 3.40% day-1 in full-term infants. 5. The molar excretion ratio during the period 40-120 h after birth increased in premature infants and reflects a fractional degradation rate of 5.34% day-1 in those infants weighting less than 1 kg at birth. 6. Lower excretion ratios were found in some infants of diabetic mothers and in athyroid infants. 7. The urinary excretion ratio of NT-methylhistidine to creatinine is presented as a useful method for evaluating the breakdown rate of myofibrillar protein in neonates and can be applied to a number of abnormal nutritional or hormonal states.

Penetration of piperacillin into bronchial mucosa and sputum.

Bronchial mucosal biopsies were obtained during fibreoptic bronchoscopy in 12 patients receiving a new semisynthetic penicillin, piperacillin. The piperacillin levels estimated in bronchial mucosa exceeded those required to eradicate organisms associated with acute bronchitis, Haemophilus influenzae and Streptococcus pneumoniae, and compared favourably with those required for activity against a wide variety of anaerobic and Gram-negative organisms including Pseudomonas aeruginosa. Sputum and serum piperacillin levels were obtained from eight patients with bronchial disease receiving a five to seven day course (8 to 16 g/day). Sputum/serum level ratios were constant for the two dosages (10.7% for 8 g/day; 14.3% for 16 g/day) suggesting a diffusion transfer process, although the presence of pus in the sputum appeared to facilitate penetration. Seven patients achieved sputum levels exceeding those required for activity against Haemophilus influenzae and Streptococcus influenzae, and four for Pseudomonas aeruginosa. This study provides pharmacolinetic support of the use of piperacillin in bronchopulmonary infection.

Pharmacokinetics of piperacillin in renal failure.

Patients with chronic renal failure who received bolus doses of piperacillin maintained high serum levels for up to six hours. The percentage of the injected dose which was detectable in the urine in 24 hours was reduced proportionately to the severity of the renal failure.