A repeating fast radio burst source in a globular cluster.

Fast radio bursts (FRBs) are flashes of unknown physical origin1. The majority of FRBs have been seen only once, although some are known to generate multiple flashes2,3. Many models invoke magnetically powered neutron stars (magnetars) as the source of the emission4,5. Recently, the discovery6 of another repeater (FRB 20200120E) was announced, in the direction of the nearby galaxy M81, with four potential counterparts at other wavelengths6. Here we report observations that localized the FRB to a globular cluster associated with M81, where it is 2 parsecs away from the optical centre of the cluster. Globular clusters host old stellar populations, challenging FRB models that invoke young magnetars formed in a core-collapse supernova. We propose instead that FRB 20200120E originates from a highly magnetized neutron star formed either through the accretion-induced collapse of a white dwarf, or the merger of compact stars in a binary system7. Compact binaries are efficiently formed inside globular clusters, so a model invoking them could also be responsible for the observed bursts.

A repeating fast radio burst source localized to a nearby spiral galaxy.

Fast radio bursts (FRBs) are brief, bright, extragalactic radio flashes1,2. Their physical origin remains unknown, but dozens of possible models have been postulated3. Some FRB sources exhibit repeat bursts4-7. Although over a hundred FRB sources have been discovered8, only four have been localized and associated with a host galaxy9-12, and just one of these four is known to emit repeating FRBs9. The properties of the host galaxies, and the local environments of FRBs, could provide important clues about their physical origins. The first known repeating FRB, however, was localized to a low-metallicity, irregular dwarf galaxy, and the apparently non-repeating sources were localized to higher-metallicity, massive elliptical or star-forming galaxies, suggesting that perhaps the repeating and apparently non-repeating sources could have distinct physical origins. Here we report the precise localization of a second repeating FRB source6, FRB 180916.J0158+65, to a star-forming region in a nearby (redshift 0.0337 ± 0.0002) massive spiral galaxy, whose properties and proximity distinguish it from all known hosts. The lack of both a comparably luminous persistent radio counterpart and a high Faraday rotation measure6 further distinguish the local environment of FRB 180916.J0158+65 from that of the single previously localized repeating FRB source, FRB 121102. This suggests that repeating FRBs may have a wide range of luminosities, and originate from diverse host galaxies and local environments.

A direct localization of a fast radio burst and its host.

Fast radio bursts are astronomical radio flashes of unknown physical nature with durations of milliseconds. Their dispersive arrival times suggest an extragalactic origin and imply radio luminosities that are orders of magnitude larger than those of all known short-duration radio transients. So far all fast radio bursts have been detected with large single-dish telescopes with arcminute localizations, and attempts to identify their counterparts (source or host galaxy) have relied on the contemporaneous variability of field sources or the presence of peculiar field stars or galaxies. These attempts have not resulted in an unambiguous association with a host or multi-wavelength counterpart. Here we report the subarcsecond localization of the fast radio burst FRB 121102, the only known repeating burst source, using high-time-resolution radio interferometric observations that directly image the bursts. Our precise localization reveals that FRB 121102 originates within 100 milliarcseconds of a faint 180-microJansky persistent radio source with a continuum spectrum that is consistent with non-thermal emission, and a faint (twenty-fifth magnitude) optical counterpart. The flux density of the persistent radio source varies by around ten per cent on day timescales, and very long baseline radio interferometry yields an angular size of less than 1.7 milliarcseconds. Our observations are inconsistent with the fast radio burst having a Galactic origin or its source being located within a prominent star-forming galaxy. Instead, the source appears to be co-located with a low-luminosity active galactic nucleus or a previously unknown type of extragalactic source. Localization and identification of a host or counterpart has been essential to understanding the origins and physics of other kinds of transient events, including gamma-ray bursts and tidal disruption events. However, if other fast radio bursts have similarly faint radio and optical counterparts, our findings imply that direct subarcsecond localizations may be the only way to provide reliable associations.

Pulmonary function of patients with spontaneous pneumothorax in relation to the extent of emphysema-like changes.

The aim of the present study was to analyse pulmonary function parameters of patients with spontaneous pneumothorax (SP) in relation to the extent of emphysema-like changes (ELCs). Pulmonary function tests were performed in 85 patients with unilateral SP, 6 weeks after video-assisted thoracoscopy (VAT). In 63 patients, thoracic computer tomography (CT) was obtained. An ELCs score, based on findings of CT and VAT, was used to quantify ELCs, ranging from 0 (expressing no ELCs) to 3 (expressing extensive ELCs). Emphysema-like changes were detected during VAT in 74% of patients, of which 70% were considered larger than 2 cm. An ELCs score > or = 2 was found in 27 patients. Clinical characteristics of the patients grouped according to thoracoscopical findings and ELCs score did not differ, except for age. Patients with large ELCs were significantly older than patients without ELCs or small ELCs (P = 0.0009). In patients with large ELCs and ELCs score > or = 2, increased mean percentages of predicted total lung capacity and decreased diffusing capacity (KCO) were found. None of the patients exhibited all pulmonary function criteria of emphysema, in contrast to 43% of the patients with an ELCs score > or = 2. KCO was the only pulmonary function parameter which was decreased in smokers, especially in patients with large ELCs or ELCs score > or = 2. Static lung compliance (Cstat) was the only pulmonary function parameter which was increased in patients with recurrent SP. The authors concluded that KCO is related to smoking behaviour and ELCs in patients with SP. Cstat is the only parameter which is increased in patients with recurrent SP. The discrepancy between pulmonary function and macroscopical parenchymal changes could be explained by the fact that not all patients with SP are old enough at presentation to show all signs of emphysema with pulmonary function testing. On the other hand, it might be possible that ELCs in SP cause different pulmonary function abnormalities than in centriacinar or panacinar emphysema.

Prediction of peak oxygen uptake in men using pulmonary and hemodynamic variables during exercise.

PURPOSE: Many attempts have been made to predict peak VO2 from data obtained at rest or submaximal exercise. Predictive submaximal tests using the heart rate (HR) response have limited accuracy. Some tests incorporate submaximal gas exchange data, but a predictive test without gas exchange measurements would be of benefit. Addition of stroke volume and pulmonary function (PF) measurements might increase the predictability of a submaximal exercise test. METHODS: In this study, an incremental exercise test (10 W x min(-1)) was performed in 30 healthy men of various habitual activity levels. Step-wise multiple regression analysis was used to isolate the most important predictor variables of peak VO2 from a set of measurements of PF: lung volumes, diffusion capacity, airway resistance, and maximum inspiratory and expiratory pressures; gas exchange; minute ventilation (V(E)), tidal volume (V(T)), respiratory exchange ratio (RER = carbon dioxide output divided by VO2); and hemodynamics (HR, stroke index (SI) = stroke volume/body surface area, and mean arterial pressure). These measurements were made at rest and during submaximal exercise. RESULTS: Using the set of PF variables (expressed as percentages of predicted), FEV1 explained 30% of the variance of peak VO2. No other PF variables were predictive. After addition of resting hemodynamic data, SI was included in the prediction equation, raising the predictability to 40%. At the 60-W exercise level, 48% of the variance in peak VO2 could be explained by SI and FEV1. At 150 W, the prediction increased to 81%. At this level VCO2/O2 (RER) also entered the prediction equation of peak VO2: 6.44 x FEV1(%) + 13.0 x SI - 1921 x RER + 2380 (SE = 142 mL x min(-1) x m(-2), P < 0.0001). Leaving out the gas exchange variable RER, maximally 64% of the variance in peak VO2 could be explained. CONCLUSION: In conclusion, inclusion of pulmonary function and hemodynamic measurements could improve the prediction accuracy of a submaximal exercise test. The submaximal exercise test should be performed until a level of 150 W is reached. Noninvasive stroke volume measurements by means of EIC have additional value to measurement of HR alone. Finally, measurement of gas exchange significantly improves the predictability of peak VO2.

Employment and disability for work in patients with COPD: a cross-sectional study among Dutch patients.

OBJECTIVES: The aim was to gain insight into work experiences and problems of subjects with chronic obstructive pulmonary disease (COPD) to develop more effective guidelines for preventing work disability and work loss. METHODS: A total of 617 patients aged 45-60, recruited from pulmonary outpatient clinics and general practices, completed a questionnaire on (respiratory) health and work history. RESULTS: Of the patients 43% were female, 52% were employed and more than half were less educated. Comorbidity was present in 52% of the study group. Of those who stopped working (N=260), 36% stopped before the onset of COPD, 39% stopped because of COPD and 25%, although having COPD, had other reasons to stop. Of the patients with a work history 39% had an invalidity benefit: 21% of the working and 60% of the non-working patients. For one-third of these patients COPD was not the reason for having an invalidity benefit. For 56% of those who had a benefit because of COPD, comorbidity contributed to work disability. No difference in current smoking habit was seen between working patients and non-working patients. Yet, non-working patients were more often smokers at the moment they stopped working. Furthermore, former smokers who still worked stopped smoking at a younger age than former smokers who stopped working. Compared with workers and independent of smoking habit, former workers were more exposed to dust/irritants, had their work(place) less frequently modified and had more unfavourable (social) work experiences. CONCLUSION: For employees with COPD, work loss is often multi-factorial. Comorbidity is often present and an important cause for work loss. Therefore occupational health guidance has to take other interfering (health) factors than COPD into consideration as well. In preventing work disability, work(place) adjustment merits more attention.

A continuous method for the estimation of adenosine deaminase catalytic concentration in pleural effusions with a Hitachi 705 discrete analyser.

An assay of adenosine deaminase activity in pleural effusions is described. For the continuous determination of adenosine deaminase, the liberated ammonia is estimated by coupling the liberated NH3 with 2-oxoglutarate. The reaction is followed by the decrease of NADH absorbance at 340 nm. The assay was optimized for a Hitachi 705 analyser, with respect to pH, adenosine concentration and glutamate dehydrogenase activity. The assay is linear to an adenosine deaminase catalytic concentration of 110 U/l. Elevated adenosine deaminase activities are found in pleural effusions of patients with tuberculosis, empyema and mesothelioma. Although elevated adenosine deaminase activity in pleural effusion is not pathognomonic for tuberculosis, it may be valuable as a first screening parameter.

Adenosine deaminase activity, not diagnostic for tuberculous pleurisy.

We have measured adenosine deaminase (ADA) in pleural effusions of 95 patients, using a method optimalised for rapid determination on a Hitachi 705 analyzer. High ADA activity was found in four of the five patients with tuberculous pleurisy, in four of the seven with empyema and in three of the seven patients with mesothelioma. One patient with very high serum ADA activity due to liver disease also had a high activity in the pleural effusion. Low activity was found in all patients with other neoplastic pleural effusions, parapneumonic pleural effusions, transudates, and in pleural effusions due to some other diseases. We conclude that in a country with a low tuberculosis incidence a high ADA activity in pleural effusion in neither sensitive nor specific enough to rely on the diagnosis of tuberculous pleurisy. Routine determination of ADA is not recommended; in selected cases, however, it may be useful.

Subjective sleep quality and mental fitness in asthmatic patients.

Asthmatic patients from our outpatient pulmonary clinic were asked to fill out a questionnaire about their sleep and daytime fitness. Seventy-eight responded. Sixty-five healthy persons served as a control group. Patients reported decreased sleep quality, decreased daytime mental fitness, and increased daytime somnolence. There was no relation between these features and lung function, bronchial hyperreactivity, or nocturnal asthma. We conclude that these asthmatic patients reported more sleep disturbances and daytime somnolence than healthy control persons.

The effects of a community-based pulmonary rehabilitation programme on exercise tolerance and quality of life: a randomized controlled trial.

The present multicentre study evaluates the differences in efficacy between a 3 month rehabilitation programme including drug treatment, and a 3 month control period of drug treatment only, for asthmatic patients and patients with chronic obstructive pulmonary disease (COPD). The programme was run by physiotherapists in eight local practices, and included exercise training, patient education, breathing retraining, evacuation of mucus, relaxation techniques, and recreational activities. In a randomized controlled trial with a cross-over design, the effects of rehabilitation were evaluated 3 and 6 months after baseline measurements in terms of exercise tolerance and quality of life (QOL). Exercise tolerance was assessed using submaximal cycle ergometer tests and 6 min walking tests. QOL was evaluated by means of the Chronic Respiratory Disease Questionnaire (CRDQ). After 3 months, the patients who started with rehabilitation showed significant improvements in endurance time (421 s) and cardiac frequency (6 beats.min-1) during cycling, walking distance (39 m), and total CRDQ score (17 points) compared to the control group. These improvements were still significant after 6 months. Additional analysis indicated that the asthmatic patients and the patients with COPD responded to rehabilitation in a similar way, with the exception that there was a greater improvement in walking distance for asthmatics. Improvements in exercise tolerance were not significantly correlated with improvements in QOL. Rehabilitation of patients with asthma or chronic obstructive pulmonary disease in local physiotherapy practices improves exercise tolerance and quality of life.

Nocturnal waking and morning dip of peak expiratory flow in clinically stable asthma patients during treatment. Occurrence and patient characteristics.

The occurrence of nocturnal waking due to asthma and morning dip of the peak expiratory flow (PEF), and the associated patient characteristics were investigated in 103 clinically stable asthmatic patients from a pulmonary outpatient clinic. Analysis of a 1 week diary showed a mean week morning PEF dip (i.e. morning/daytime highest PEF) of 12%. A mean dip of > or = 20% was found in 20% of the patients. Three groups were distinguished: 10% were 'nocturnal-waking patients' (waking up > or = 2 nights a week with a PEF dip of > or = 20%); 19% 'morning-dipping patients' (patients with > or = 3 dips a week of > or = 20% but with waking up on < 2 nights a week) leaving 71% 'remaining patients'. 28% of all patients showed morning PEF dips. In a questionnaire, waking every night was reported by 9%, at least once a week by 42% and once a month by 72%. In 'nocturnal-waking patients' FEV1 and morning and evening PEFs were lower than in 'remaining patients'; complaints during the night and on rising were more severe. The morning PEF dip was the same in 'nocturnal-waking patients' and 'morning-dipping patients'. The occurrence of waking was the same in 'morning-dipping patients' and in the 'remaining patients'. There were no differences in other clinical parameters among the three groups. We conclude that a subset of clinically stable asthma patients presents morning dips and nocturnal waking. They do not differ substantially from the remaining patients in other clinical characteristics.

Treatment of nocturnal asthma by addition of oral slow-release albuterol to standard treatment in stable asthma patients.

Nocturnal and early-morning complaints in asthma patients are sometimes difficult to treat. We investigated the efficacy of an oral osmotically controlled release (OR) formulation of albuterol 8 mg in 35 patients with stable asthma and nocturnal complaints and/or morning dipping of the peak expiratory flow (PEF). The mean age was 45 years (range 22-70), the FEV(1) was 61 +/- 20% of predicted, and inhaled steroids were used by 32 patients. Albuterol OR was added to their usual treatment. The use of theophyllines and oral adrenergics was not allowed. Twice-daily (b.i.d.) dosing was compared to one dose at night and to placebo. The three-period crossover study was double-blind placebo-controlled with treatment periods of 2 weeks. Responses have been analyzed by means of multiple regression analysis at a significance level of 5%. There was no significant difference of the FEV(1) or the weekly means of PEFs between the periods. During the b.i.d. treatment, the daytime and nocturnal symptom scores, used rescue medication, subjective sleep quality, and nocturnal waking tended to be better. Mental fitness was improved, but significantly only in the morning. We concluded that additional treatment with albuterol 8 mg OR once or twice daily did not lead to an overall clinical improvement in this group of patients with nocturnal asthma during standard treatment. In view of the tendency to improvement, it may be worth trying this treatment in individual patients.

The long-term effects of pulmonary rehabilitation in patients with asthma and chronic obstructive pulmonary disease: a research synthesis.

OBJECTIVE: To present a critical review and meta-analysis of studies evaluating the long-term effects of pulmonary rehabilitation in patients with asthma and chronic obstructive pulmonary disease (COPD). DATA SOURCES: A database of articles published over the last 45 years, compiled by using medical subject heading key words pulmonary, obstructive, rehabilitation, and exercise. Articles not written in English, Dutch, or German and abstracts were excluded. STUDY SELECTION: Selected studies (1) evaluated the effects of pulmonary rehabilitation, (2) included patients with asthma or COPD older than 18 years, (3) evaluated outcome measures of exercise capacity or health related quality of life (HRQL), and (4) included a control condition lacking exercise training. DATA EXTRACTION: Independent extraction by two reviewers. DATA SYNTHESIS: For each outcome, summary effects were computed by pooling standardized mean differences as well as raw mean differences. Significant improvements were found for all outcomes (p < .001). Sensitivity analyses for methodological quality of the selected studies did not change summary effect sizes. Effect sizes were significantly heterogeneous for the outcome endurance time (p < .0001). Pooling raw mean differences revealed overall effects in 6-minute walking distance (49+/-26 m) and all 4 dimensions of the chronic respiratory questionnaire (range, 0.5+/-0.3 to 0.8+/-0.3 points), indicating substantial improvements in these outcomes. Significant summary effect sizes were found up to 9 months after finishing rehabilitation for maximal exercise capacity (p < .003) and 6-minute walking distance (p < .005). CONCLUSIONS: Patients with asthma and COPD benefit from pulmonary rehabilitation.

Comparison of the respiratory and hemodynamic responses of healthy subjects to exercise in three different protocols.

Although the importance of exercise testing has been well established, standardization of protocols is lacking. In the current study three protocols were compared with respect to respiratory and hemodynamic variables at submaximal and peak exercise. Fifteen healthy young men underwent three maximal exercise tests using the following protocols: (I) an increase of 30 Watt, every three minutes; (II) an increase of 10 Watt, every minute; (III) a continuous load increase of 10 Watt/min. Respiratory measurements were made of oxygen uptake (VO2), carbon dioxide output (VCO2), minute ventilation (VE) and tidal volume (VT). Hemodynamic measurements were made of ECG, heart rate (HR), blood pressure and stroke volume (SV). The latter variable was measured by means of electrical impedence cardiography (EIC). There were no differences in mean maximum load or peak-VO2 between protocols I, II and III. The course of SV was similar in all protocols, i.e. an increase of about 30% until 100 Watt, with a subsequent stabilization until maximum load. All other hemodynamic measurements were similar in both protocols, too. Significant differences were found in submaximal values of VO2 and VCO2. There were no differences in other gas-exchange variables at any moment during exercise. With respect to the VO2max or the hemodynamic response to exercise, any protocol can be used. For the evaluation of submaximal exercise, the protocol that has been used has to be taken into account. Differences at these levels are not related to differences in hemodynamic responses.