Decomposing neural responses to melodic surprise in musicians and non-musicians: Evidence for a hierarchy of predictions in the auditory system.

Neural responses to auditory surprise are typically studied with highly unexpected, disruptive sounds. Consequently, little is known about auditory prediction in everyday contexts that are characterized by fine-grained, non-disruptive fluctuations of auditory surprise. To address this issue, we used IDyOM, a computational model of auditory expectation, to obtain continuous surprise estimates for a set of newly composed melodies. Our main goal was to assess whether the neural correlates of non-disruptive surprising sounds in a musical context are affected by musical expertise. Using magnetoencephalography (MEG), auditory responses were recorded from musicians and non-musicians while they listened to the melodies. Consistent with a previous study, the amplitude of the N1m component increased with higher levels of computationally estimated surprise. This effect, however, was not different between the two groups. Further analyses offered an explanation for this finding: Pitch interval size itself, rather than probabilistic prediction, was responsible for the modulation of the N1m, thus pointing to low-level sensory adaptation as the underlying mechanism. In turn, the formation of auditory regularities and proper probabilistic prediction were reflected in later components: The mismatch negativity (MMNm) and the P3am, respectively. Overall, our findings reveal a hierarchy of expectations in the auditory system and highlight the need to properly account for sensory adaptation in research addressing statistical learning.

Survival of localized NSCLC patients without active treatment or treated with SBRT.

BACKGROUND: Little information on the natural history of patients with localized NSCLC is available since many of the studies covering the subject lack information on pathological confirmation, staging procedures and comorbidity. No randomized studies have compared SBRT with no treatment for patients with localized NSCLC. The purpose of this study was to evaluate whether SBRT has influence on overall survival for patients with localized NSCLC and investigate the effect of baseline ventilatory lung function on overall survival. MATERIAL AND METHODS: From 2007 to 2013, 136 patients treated with SBRT at Odense University Hospital were prospectively recorded. The thoracic SBRT consisted of three fractions of 15-22 Gy delivered in 9 days. For comparison, a national group of 73 untreated patients in the same time period was extracted from the Danish Lung Cancer Registry. All patients had histologically/cytologically proven NSCLC T1-2N0M0 with a tumour diameter ≤5 cm. RESULTS: The 5-year relative survival was 44% versus 7% for the SBRT and untreated groups, respectively. In a propensity score matched comparison the median overall survival was 47 months versus 11 months for the SBRT and untreated groups, respectively (p < .05). On multivariate analysis, SBRT was significantly associated with improved prognosis while ECOG performance status 2+ and tumour diameter ≥3 cm significantly predicted poorer prognosis. Severe to very severe reduction of forced expiratory volume in one second (FEV1) did not predict poorer survival for the SBRT treated patients with localized NSCLC. CONCLUSIONS: SBRT offers more favourable survival than no treatment for patients with localized NSCLC. Performance status of 0-1, tumour diameter less than 3 cm and SBRT predicted improved survival. SBRT should not be withheld for patients with localized NSCLC based on poor ventilatory lung function.

Oxytocin improves synchronisation in leader-follower interaction.

The neuropeptide oxytocin has been shown to affect social interaction. Meanwhile, the underlying mechanism remains highly debated. Using an interpersonal finger-tapping paradigm, we investigated whether oxytocin affects the ability to synchronise with and adapt to the behaviour of others. Dyads received either oxytocin or a non-active placebo, intranasally. We show that in conditions where one dyad-member was tapping to another unresponsive dyad-member - i.e. one was following another who was leading/self-pacing - dyads given oxytocin were more synchronised than dyads given placebo. However, there was no effect when following a regular metronome or when both tappers were mutually adapting to each other. Furthermore, relative to their self-paced tapping partners, oxytocin followers were less variable than placebo followers. Our data suggests that oxytocin improves synchronisation to an unresponsive partner's behaviour through a reduction in tapping-variability. Hence, oxytocin may facilitate social interaction by enhancing sensorimotor predictions supporting interpersonal synchronisation. The study thus provides novel perspectives on how neurobiological processes relate to socio-psychological behaviour and contributes to the growing evidence that synchronisation and prediction are central to social cognition.

Impact of airway lability, atopy, and tobacco smoking on the development of asthma-like symptoms in asymptomatic teenagers.

AIM: To investigate the impact of airway lability, atopy, and tobacco smoking on the development of asthma-like symptoms in asymptomatic subjects. METHODS: In this prospective, community-based study, 271 asymptomatic adolescents with an average age at inclusion of 13.9 years were followed for 6.4 years. Airway lability was assessed at baseline by three tests, including exercise challenge, airway provocation with methacholine, and monitoring of peak expiratory flow. Atopy was defined by one or more positive reactions (> or = 3-mm weal) to 10 common aeroallergens by skin prick testing. The influence of airway lability, atopy, and smoking on the development of asthma-like symptoms was assessed by logistic regression. RESULTS: During the 6-year study period, 68 of the previously asymptomatic teenagers (25%) developed asthma-like symptoms. Among those, 50% reported cough only, 29% reported wheezing only, and 21% reported both wheezing and coughing. Hyperresponsiveness to methacholine (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.1 to 11.6), smoking (OR, 2.1; 95% CI, 1. 2 to 3.8), and atopy (OR, 3.5; 95% CI, 1.8 to 6.8) each contributed independently to explain symptom development (wheezing and cough together). Girls, but not boys, with airway lability were less likely to take up smoking, compared with subjects of that set with no airway lability (32% vs 51%; p < 0.05). No effect of airway lability on the likelihood of giving up smoking could be demonstrated, nor did the presence of atopy have any significant impact on smoking behavior. CONCLUSION: Hyperresponsiveness to methacholine, atopy, and smoking were independent risk factors for the development of asthma-like symptoms during adolescence. The presence of airway lability may prevent girls from taking up smoking.

Salbutamol powder inhaled from the Diskhaler compared to salbutamol as nebulizer solution in severe chronic airways obstruction.

The bronchodilatory effect of four doses of salbutamol powder (1.6 mg) from a multi-dose dry powder inhaler, the Diskhaler, was compared to the effect of 2.5 ml salbutamol nebulizer solution (1 mg ml-1) from a jet nebulizer, Pari Inhalierboy, in a randomized, double-blind, double-dummy, cross-over study performed on 2 consecutive days. Thirty-two patients with severe chronic obstructive pulmonary disease (COPD), a mean FEV1 = 29% of predicted value, and at least a 15% increase in FEV1 after inhaling 5 mg nebulized terbutaline were included. Twenty-eight patients were evaluated: 17 women and 11 men with a mean age of 67 years (range 53-82 years). The mean increases in FEV1 were greater after inhalation via the Diskhaler, although there was no difference in the patients' subjective assessment of the treatments. The powder inhaler was also effective in patients with the lowest baseline FEV1 and the lowest inspiratory peak flow through the inhaler. The study demonstrates that dry powder inhalation of salbutamol via a Diskhaler is at least as effective as inhalation of salbutamol via a jet nebulizer in providing bronchodilation in patients with severe COPD.

Terbutaline inhalations by the Turbuhaler as replacement for domiciliary nebulizer therapy in severe chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) are often treated with high dose inhalations of beta 2-agonists. We compared domiciliary therapy with terbutaline administered by the Turbuhaler and by a jet nebulizer. Forty nebulizer users with severe COPD were included in the randomized, double-blind, cross-over study. Terbutaline was inhaled t.i.d. for 2 weeks as dry powder (5 doses = 2.5 mg) by Turbuhaler or as solution (2 ml = 5 mg) by jet nebulizer (Pari Inhalierboy). The mean age of the 25 completing patients was 66 years (range: 54-81), the mean FEV1 was 0.73 l or 29% of predicted (range: 11-55%). The period where the Turbuhaler delivered the active drug was preferred by 16 patients, the nebulizer period by seven (P = 0.09). The median score concerning feeling of control over the disease--according to the Chronic Respiratory Disease Questionnaire--was better after the Turbuhaler period (P = 0.01). Other scores concerning disease related quality of life, the daily peak expiratory flow rates, the additional use of a metered dose inhaler were not significantly different for the two types of treatment. It is concluded that high dose domiciliary terbutaline treatment by Turbuhaler can replace nebulizer treatment in most patients with severe COPD.

N-acetylcysteine by metered dose inhaler in the treatment of chronic bronchitis: a multi-centre study.

Sixty-five patients with chronic bronchitis were studied at five different centres in a double-blind, randomized trial. Two parallel groups were treated with either N-acetylcysteine or placebo by metered dose inhalers for 16 weeks. Following a 1-week run-in period, each patient recorded subjective impressions of the drug action on their bronchitic symptoms in a diary once a week. In addition, exacerbations were registered. Lung function testing and adverse effects were evaluated by four visits to the chest clinics during the 16 weeks. We could not demonstrate that N-acetylcysteine by metered dose inhalers had any significant effect on patients' feeling of well-being, sensation of dyspnoea, intensity of coughing, mucus production, or expectoration or lung function. Its effect in reducing exacerbations could not be estimated because of a very low number of exacerbations reported. N-acetylcysteine inhalation was safe when used over a 16-week period.

Orally administered N-acetylcysteine may improve general well-being in patients with mild chronic bronchitis.

Oral N-acetylcysteine (NAC) exerts a beneficial action in chronic bronchitis by reducing the number of exacerbations. There have been few studies of the effect of NAC (or of any other drug) on general well-being in chronic bronchitis. We used an established psychiatric instrument (General Health Questionnaire; GHQ) and a visual analogue scale (VAS) to measure well-being in a 22-week, placebo-controlled, double-blind, parallel-group study of NAC administered as sustained release tablets 600 mg b.i.d., including during the winter months, to patients with mild chronic bronchitis. One hundred and fifty-three patients were accepted for randomized treatment, 129 finished the study (59 NAC, 70 placebo), and well-being was measured in 105 (46 NAC, 59 placebo). The number of observed exacerbations was unexpectedly low in both groups. The number was lowest in the NAC group, however, the difference did not reach statistical significance in the present study (P = 0.08). There were no statistically significant differences between NAC and placebo in subjective symptom scores, FEV1 or FVC. The distribution of GHQ score at baseline was uneven, but NAC was significantly superior to placebo in terms of a favourable effect on GHQ score. GHQ score correlated with the number of exacerbations, and VAS correlated with GHQ score. This study therefore demonstrates the validity of measuring general well-being in patients with mild chronic bronchitis. Future studies of the treatment of chronic bronchitis should use a battery of more specifically adapted instruments which are now becoming available to measure well-being.

Rate of fall-applied liquid swine manure: effects on runoff transport of sediment and phosphorus.

Reducing the delivery of phosphorus (P) from land-applied manure to surface water is a priority in many watersheds. Manure application rate can be controlled to manage the risk of water quality degradation. The objective of this study was to evaluate how application rate of liquid swine manure affects the transport of sediment and P in runoff. Liquid swine manure was land-applied and incorporated annually in the fall to runoff plots near Morris, Minnesota. Manure application rates were 0, 0.5, 1, and 2 times the rate recommended to supply P for a corn (Zea mays L.)-soybean [Glycine max (L.) Merr.] rotation. Runoff volume, sediment, and P transport from snowmelt and rainfall were monitored for 3 yr. When manure was applied at the highest rate, runoff volume and sediment loss were less than the control plots without manure. Reductions in runoff volume and soil loss were not observed for spring runoff when frozen soil conditions controlled infiltration rates. The reduced runoff and sediment loss from manure amended soils compensated for addition of P, resulting in similar runoff losses of total P among manure application rates. However, losses of dissolved P increased with increasing manure application rate for runoff during the spring thaw period. Evaluation of water quality risks from fall-applied manure should contrast the potential P losses in snowmelt runoff with the potential that incorporated manure may reduce runoff and soil loss during the summer.

Herbicide banding and tillage system interactions on runoff losses of alachlor and cyanazine.

Herbicides transported to surface waters by agricultural runoff are partitioned between solution and solid phases. Conservation tillage that reduces upland erosion will also reduce transport of herbicides associated with the solid phase. However, transport of many herbicides occurs predominantly in solution. Conservation tillage practices may or may not reduce transport of solution-phase herbicides, as this depends on the runoff volume. Reducing herbicide application rate is another approach to minimize off-site transport. Herbicide banding can reduce herbicide application rates and costs by one-half or more. Our objective was to compare herbicide losses in runoff from different tillage practices and with band- or broadcast-applied herbicides. The herbicides alachlor [2-chloro-2',6'-diethyl-N-(methoxymethyl)acetanilide] and cyanazine [2-[[4-chloro-6-(ethylamino)-1,3,5-triazin-2-yl]amino]-2-methylpropionitrile] were broadcast- or band-applied to plots managed in a moldboard plow, chisel plow, or ridge till system. Herbicide concentration in runoff was largest for the first runoff event occurring after application and then decreased in subsequent events proportional to the cumulative rain since the herbicide application. When herbicides were broadcast-applied, losses of alachlor and cyanazine in runoff followed the order: moldboard plow > chisel plow > ridge till. Conservation tillage systems reduced runoff loss of herbicides by reducing runoff volume and not the herbicide concentration in runoff. Herbicide banding reduced the concentration and loss of herbicides in runoff compared with the broadcast application. Herbicide losses in the water phase averaged 88 and 97% of the total loss for alachlor and cyanazine, respectively. Cyanazine was more persistent than alachlor in the soil.

Wrestling With 'Making Weight'.

Certifying growing young athletes to wrestle at below-normal weights may stunt their growth, lower their grades, and impede their social development. They probably won't wrestle well, either.

[Allergic alveolitis among pigeon breeders in the county of Funen]. / Allergisk alveolitis blandt fynske dueholdere.

Two hundred pigeon breeders from the county of Funen were invited to participate in the study. No definite cases of allergic alveolitis were found among the 68 participants. 40% had experienced airway and/or general symptoms in connection with pigeon exposure. However, most of these symptoms could be explained as irritation of the airway and chronic bronchitis. Precipitating antibodies to pigeon serum and to an aqueous pigeon bloom extract were determined. The antibody titers did not differ in pigeon breeders with or without symptoms. Smokers had lower antibody titers to pigeon antigens and a lower level of total serum IgG, but reported symptoms in connection with pigeon exposure as often as non smokers.

[Oxygen treatment and cigarette smoking. A potentially fatal combination]. / Iltbehandling og cigaretrygning. En potentielt letal kombination.

The case of a 60 year old male, who died while smoking in bed during oxygen therapy, is presented. The patient suffered from chronic airway obstruction and emphysema with respiratory insufficiency and he died from carbon monoxide poisoning, after the bed linen and the oxygen cylinder were ignited. Domiciliary oxygen therapy should not be prescribed to patients, who do not give up smoking.

[Occurrence of the yeast, Cryptococcus (Cr) neoformans, in pigeon droppings]. / Forekomst af gaersvampen Cryptococcus (Cr.) neoformans i duegødning.

Pigeon droppings were collected in Copenhagen and Odense. In samples from pigeon lofts, cryptococci were found in 33% from Copenhagen and in 16% from Odense. All of the species of cryptococci found were Cr. neoformans. These findings are compared with the previous Danish investigations. The frequent occurrence of cryptococci in AIDS patients is mentioned.

[Steroid response after long-term treatment with oral N-acetylcysteine in patients with chronic obstructive bronchitis]. / Steroidrespons efter langtidsbehandling med oral N-acetylcystein hos patienter med kronisk obstruktiv bronchitis.

The significance of long-term treatment with N-acetylcystein (NAC) for the steroid response on pulmonary function and general symptoms was investigated in patients with chronic bronchitis and moderate respiratory obstruction. All of the patients had received preliminary treatment with oral NAC in a dosage of 1,200 mg daily (Mucomyst Retard) or a placebo for 22 weeks in a double-blind design. After the conclusion of the long-term treatment but before the code was revealed, 37 non-allergic patients with irreversible respiratory obstruction participated in a follow-up investigation with 30 mg prednisone daily for 14 days. The peak flow was measured twice daily and the symptoms of bronchitis were registered by completion of 13 visual analogue scales. Pulmonary function was measured by means of spirometry on days 0, 7 and 14, respectively. In both of the treated groups, slight increase in the daily registered peak flow was found but no changes in the results of spirometry or the symptoms. Comparison between the groups revealed a significantly greater increase in the evening peak flow in the group which had received preliminary treatment with NAC. It is concluded that, in this investigation, no clinically relevant effect of long-term preliminary treatment with NAC on the results of a steroid test was observed in patients with chronic bronchitis and moderate respiratory obstruction.

Terbutaline as powder inhalation from Bricanyl Turbuhaler compared to terbutaline as nebulizer solution in severe chronic airways obstruction.

Twenty two adults with severe chronic airways obstruction--FEV1 from 14 to 57% of predicted--participated on two consecutive days in an open cross over comparison of inhalation of 2 mg terbutaline powder by Bricanyl Turbuhaler and 5 mg terbutaline by a conventional jet nebulizer (Pari Inhalierboy). All participants were domiciliary users of nebulized terbutaline previous to inclusion in this study. The mean (SD) maximal increase in FEV1 within the 60 minutes following inhalation by Turbuhaler and by Pari Inhalierboy was 27% (15%) and 28% (15%). The mean (SD) maximal increase in FVC was 30% (20%) and 29% (16%). The differences were not statistically significant. All participants were able to produce inspiratory flows high enough to use the Turbuhaler. The study suggests that it will be possible to replace the use of nebulizers with powder inhalations, as far as the bronchodilating effects are concerned.

Individual utilization of anti-asthma medication by young adults: a prescription database analysis.

OBJECTIVES: To analyse and evaluate current practice of asthma therapy by use of computerized prescription data. DESIGN: Descriptive, non-interventive. SETTING: A pharmacoepidemiological database on computerized refund claims from pharmacies in the Odense region in Denmark. SUBJECTS: Persons aged 20-44, presenting prescriptions for asthma drugs during the period 1 October 1990 to 30 September 1991. MAIN OUTCOME MEASURES: Prevalence of asthma drug use, the regimes chosen, relationship between beta-agonist and steroid use by the individual patient. RESULTS: In all, 3020 persons used anti-asthma drugs, corresponding to a crude 1-year prevalence of 3.6%. Sixty per cent were women. The subjects had an average anti-asthma drug consumption corresponding to 86% of the population's average. The four most common regimes were inhaled beta-agonist monotherapy, inhaled beta-agonist and corticosteroid, oral beta-agonist monotherapy and inhaled corticosteroid monotherapy, altogether accounting for 79% of users. The proportion of corticosteroid users increased with increasing individual use of beta-agonists. With an annual beta-agonist purchase of 100-200 defined daily doses, still less than half also used steroids. CONCLUSION: The majority of patients use a regime agreeing with current guidelines, except that more patients should be prescribed corticosteroids. The observed large increase in asthma drug use is likely to be explained by an intensified treatment of individual patients, rather than an increased prevalence.