Ultra-narrow linewidth quantum dot coherent comb lasers with self-injection feedback locking.

We have used an external cavity self-injection feedback locking (SIFL) system to simultaneously reduce the optical linewidth of over 39 individual wavelength channels of an InAs/InP quantum dot (QD) coherent comb laser (CCL). Linewidth reduction from a few MHz to less than 200 kHz is observed. Measured phase noise spectra clearly indicate a significant decrease in phase noise in the frequency range above 2 kHz. The RF beating signal between two adjacent channels also shows a substantial reduction in 3-dB linewidth from 10 kHz to 300 Hz with the SIFL system, and a corresponding drop in baseline level (-27 dB to -50 dB).

High performance InAs/InP quantum dot 34.462-GHz C-band coherent comb laser module.

We have developed an InAs/InP quantum dot (QD) C-band coherent comb laser (CCL) module with actively stabilized absolute wavelength and power, and channel spacing of 34.462 GHz with ± 100 ppm accuracy. The total output power is up to 46 mW. The integrated average relative intensity noise (RIN) values of the lasing spectrum and a filtered single channel at 1540.19 nm were -165.6 dB/Hz and -130.3 dB/Hz respectively in the frequency range from 10 MHz to 10 GHz. The optical linewidth of the 45 filtered individual channels between 1531.77 nm to 1543.77 nm ranged from 850 kHz to 2.16 MHz. We have also analyzed the noise behaviors of each individual channel.

Enhanced photonic crystal cavity-waveguide coupling using local slow-light engineering.

This Letter introduces an enhanced cavity-waveguide coupling architecture based upon slow-light engineering in a two-port photonic crystal system. After analyzing the system transmittance using coupled-mode theory, the system is probed experimentally and shown to have increased transmittance due to the enhanced cavity-waveguide coupling. Such a coupling architecture may facilitate next-generation planar lightwave circuitry such as onchip quantum information processing or high precision light-matter sensing applications.

Interplay between crystal phase purity and radial growth in InP nanowires.

The interplay between crystal phase purity and radial growth in InP nanowires is investigated. By modifying the growth rate and V/III ratio, regions of high or low stacking fault density can be controllably introduced into wurtzite nanowires. It is found that regions with high stacking fault density encourage radial growth. Through careful choice of growth conditions pure wurtzite InP nanowires are then grown which exhibit narrow 4.2 K photoluminescence linewidths of 3.7 meV at 1.490 meV, and no evidence of emission related to stacking faults or zincblende insertions.

Selective epitaxy of semiconductor nanopyramids for nanophotonics.

We present a detailed study of the parameters which affect the geometrical perfection of nanopyramids used for the site-selected nucleation of quantum dots. Through an understanding of crystal facet formation, we demonstrate that undesirable high index planes can be suppressed using carefully optimized lithography together with properly orientated source fluxes in the growth reactor. High quality InP nanopyramids are reported with individual InAs/InP quantum dots positioned with high precision. This represents an important milestone for the fabrication of complex quantum dot based nanophotonic devices.

An L-band monolithic InAs/InP quantum dot mode-locked laser with femtosecond pulses.

We have developed an InAs/InP quantum dot (QD) gain material using a double cap growth procedure and GaP sublayer to tune QDs into the L-band. By using it, a passive L-band mode-locked laser with pulse duration of 445 fs at the repetition rate of 46 GHz was demonstrated. The 3-dB linewidth of the RF spectrum is less than 100 KHz. The lasing threshold injection current is 24 mA with an external differential quantum efficiency of 22% and an average output power of 27 mW. The relationship between pulse duration and 3-dB spectral bandwidth as a function of injection current was investigated.

312-fs pulse generation from a passive C-band InAs/InP quantum dot mode-locked laser.

For the first time, we report femtosecond pulses from a passive single-section InAs/InP quantum-dot (QD) mode-locked laser (MLL) with the active length of 456 microm and ridge width of 2.5 microm at the C-band wavelength range. Without any external pulse compression, the transform-limited Gaussian-pulses are generated at the 92 GHz repetition rate with the 312 fs pulse duration, which is the shortest pulse from any directly electric-pumping semiconductor MLLs to our best knowledge. The lasing threshold injection current and external differential quantum efficiency are 17.2 mA and 38%, respectively. We have also investigated the working principles of the proposed QD MLLs.

Cautionary tales in the clinical interpretation of studies of diagnostic tests.

The use of investigational tests in making a diagnosis is a core activity of physicians and one that requires an understanding of the accuracy and usefulness of specific tests in discriminating between several diagnostic possibilities. Studies of diagnostic tests are frequently methodologically flawed and their results are often not well understood or applied in clinical practice. This article defines the performance characteristics of diagnostic tests, describes several commonly encountered deficiencies in study design which may invalidate reports of new diagnostic tests, and explains a Bayesian approach to interpreting test results in terms of disease probability.

Improving quality and safety of hospital care: a reappraisal and an agenda for clinically relevant reform.

Improving quality and safety of hospital care is now firmly on the health-care agenda. Various agencies within different levels of government are pursuing initiatives targeting hospitals and health professionals that aim to identify, quantify and lessen medical error and suboptimal care. Although not denying the value of such 'top-down' initiatives, more attention may be needed towards 'bottom-up' reform led by practising physicians. This article discusses factors integral to delivery of safe, high-quality care grouped under six themes: clinical workforce, teamwork, patient participation in care decisions, indications for health-care interventions, clinical governance and information systems. Following this discussion, a 20-point action plan is proposed as an agenda for future reform capable of being led by physicians, together with some cautionary notes about relying too heavily on information technology, use of non-clinical quality personnel and quantitative evaluative approaches as primary strategies in improving quality.

Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease.

BACKGROUND: Individuals with chronic bronchitis or chronic obstructive pulmonary disease (COPD) may suffer recurrent exacerbations with an increase in volume and/or purulence of sputum. Because of the personal and healthcare costs associated with exacerbations, any therapy that reduces the number of exacerbations is useful. There is a marked difference between countries in terms of prescribing of mucolytics depending on whether or not they are perceived to be effective. OBJECTIVES: To assess the effects of oral mucolytics in adults with stable chronic bronchitis or COPD. SEARCH STRATEGY: We have searched the Cochrane Airways Group Specialised Register and reference lists of articles on four separate occasions, the most recent being in June 2005. This is the third major update. SELECTION CRITERIA: Randomised trials that compared oral mucolytic therapy with placebo for at least two months in adults with chronic bronchitis or COPD. Studies of people with asthma and cystic fibrosis were excluded. DATA COLLECTION AND ANALYSIS: One reviewer extracted data. Study authors and drug companies were contacted for missing information. MAIN RESULTS: Twenty six trials were included (7335 participants). Compared with placebo, there was a significant reduction in the number of exacerbations per patient with oral mucolytics (weighted mean difference (WMD) -0.05 per month, 95% confidence interval -0.05, -0.04). Using the annualised rate of exacerbations in the control patients of 2.6 per year, this is a 20% reduction. The number of days of disability also fell (WMD -0.56, 95% confidence interval -0.77, -0.35). A recent study has shown that the benefit may apply only to those patients not already receiving inhaled corticosteroids. The number of patients who remained exacerbation-free was greater in the mucolytic group (OR 2.13 (95% CI 1.86 to 2.42)). There was no difference in lung function or in adverse effects reported between the treatments. AUTHORS' CONCLUSIONS: In subjects with chronic bronchitis or COPD, treatment with mucolytics was associated with a small reduction in acute exacerbations and a reduction in total number of days of disability. Benefit may be greater in individuals who have frequent or prolonged exacerbations, or those who are repeatedly admitted to hospital with exacerbations with COPD. They should be considered for use, through the winter months at least, in patients with moderate or severe COPD in whom inhaled corticosteroids (ICS) are not prescribed.

Influenza vaccine for patients with chronic obstructive pulmonary disease.

BACKGROUND: Influenza vaccinations are currently recommended in the care of people with COPD, but these recommendations are based largely on evidence from observational studies with very few randomised controlled trials (RCTs) reported. Influenza infection causes excess morbidity and mortality in COPD patients but there is also the potential for influenza vaccination to cause adverse effects or not to be cost effective. OBJECTIVES: To evaluate the evidence from RCTs for a treatment effect of influenza vaccination in COPD subjects. Outcomes of interest were exacerbation rates, hospitalisations, mortality, lung function and adverse effects. SEARCH STRATEGY: We searched the Cochrane Airways Group Specialised Register of trials, and reference lists of articles. References were also provided by a number of drug companies we contacted. SELECTION CRITERIA: RCTs that compared live or inactivated virus vaccines with placebo, either alone or with another vaccine in persons with COPD. Studies of people with asthma were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data. All entries were double checked. Study authors and drug companies were contacted for missing information. MAIN RESULTS: Eleven trials were included but only six of these were specifically performed in COPD patients. The others were conducted on elderly and high-risk individuals, some of whom had chronic lung disease. Inactivated vaccine in COPD patients resulted in a significant reduction in the total number of exacerbations per vaccinated subject compared with those who received placebo (weighted mean difference (WMD) -0.37, 95% confidence interval -0.64 to -0.11, P = 0.006). This was due to the reduction in "late" exacerbations occurring after three or four weeks (WMD -0.39, 95% CI -0.61 to -0.18, P = 0.0004). In Howells 1961, the number of patients experiencing late exacerbations was also significantly less (odds ratio 0.13, 95% CI 0.04 to 0.45, P = 0.002). Both Howells 1961 and Wongsurakiat 2004 found that inactivated influenza vaccination reduced influenza -related respiratory infections (WMD 0.19, 95% CI 0.07 to 0.48, P = 0.0005). In both COPD patient and in elderly patients (only a minority of whom had COPD), there was a significant increase in the occurrence of local adverse reactions in vaccinees, but the effects were generally mild and transient. There was no evidence of an effect of intranasal live attenuated virus when this was added to inactivated intramuscular vaccination. The studies are too small to have detected any effect on mortality. An updated search conducted in September 2001 did not yield any further studies. A search in 2003 yielded two further reports of the same eligible study Gorse 2003. A search in 2004 yielded two reports of the another eligible study Wongsurakiat 2004. The author informed us of another report of the same study Wongsurakiat 2004/2. AUTHORS' CONCLUSIONS: It appears, from the limited number of studies performed, that inactivated vaccine reduces exacerbations in COPD patients. The size of effect was similar to that seen in large observational studies, and was due to a reduction in exacerbations occurring three or more weeks after vaccination, and due to influenza. There is a mild increase in transient local adverse effects with vaccination, but no evidence of an increase in early exacerbations.

Injectable vaccines for preventing pneumococcal infection in patients with chronic obstructive pulmonary disease.

BACKGROUND: As chronic obstructive pulmonary disease (COPD) progresses, exacerbations can occur with increasing frequency. One goal of therapy in COPD is to try and prevent these exacerbations, thereby reducing disease morbidity and associated healthcare costs. Pneumococcal vaccinations are considered to be one strategy for reducing the risk of infective exacerbations. OBJECTIVES: To determine the safety and efficacy of pneumococcal vaccination in COPD. The primary outcome assessed was acute exacerbations. Secondary outcomes of interest included episodes of pneumonia, hospital admissions, adverse events related to treatment, disability, change in lung function, mortality, and cost effectiveness. SEARCH STRATEGY: We searched the Cochrane Airways Group COPD trials register using pre-specified terms. We also conducted additional handsearches of conference abstracts. The last round of searches were performed in April 2006. SELECTION CRITERIA: Only randomised controlled trials assessing the effects of injectable pneumococcal vaccine in people with COPD were included. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and three review authors independently assessed trial quality. MAIN RESULTS: Although 10 studies cited in 11 publications were identified that met the inclusion criteria for this review, only four of these provided data on participants with COPD. The studies which did provide data for this review consisted of two trials using a 14-valent vaccine, and two using a 23-valent injectable vaccine. Data for the primary outcome, acute exacerbation of COPD, was available from only one of the four studies. The odds ratio of 1.43 (95% confidence interval (CI) 0.31 to 6.69) between interventions was not statistically significant. Of the secondary outcomes for which data were available and could be extracted, none reached statistical significance. Three studies provided dichotomous data for persons who developed pneumonia (OR 0.89, 95% CI 0.58 to 1.37, n = 748). Rates of hospital admissions and emergency department visits came from a single study. There was no significant reduction in the odds of all-cause mortality 1 to 48 months post-vaccination (Peto odds ratio 0.94, 95% CI 0.67 to 1.33, n = 888), or for death from cardiorespiratory causes (OR 1.07, 95% CI 0.69 to 1.66). AUTHORS' CONCLUSIONS: There is no evidence from randomised controlled trials that injectable pneumococcal vaccination in persons with COPD has a significant impact on morbidity or mortality. Further large randomised controlled trials would be needed to ascertain if the small benefits suggested by individual studies are real.

Comparison of the effects of nebulised and inhaled salbutamol on breathlessness in severe COPD.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) often report greater relief of breathlessness with nebulised bronchodilators than with the same medicine administered from a metered dose inhaler (MDI). This suggests that the nebulised medicines may have an effect on breathlessness over and above changes in lung function resulting from bronchodilatation. METHODS: Twenty-four subjects with COPD and breathlessness at rest participated in this randomised, crossover trial. The mean age was 72 years and the mean FEV(1) was 26% of predicted. Subjects were studied on four separate days. On two days they were treated with nebulised salbutamol and on the other 2 days with salbutamol from an MDI and spacer. With each method of delivery, local anaesthetic cream was applied to the face on one day and to the back of the hand on the other. RESULTS: Five minutes after administration of salbutamol the subjects were significantly less breathless with nebulised salbutamol but by 45 min both treatments resulted in equivalent relief. There was no difference between the treatments in the change in FEV(1) or VC and application of local anaesthetic to the face did not influence the response. CONCLUSION: There was a small early benefit with nebulised salbutamol but this was not sustained and was not affected by topical anaesthesia. The benefit of nebulisation does not appear to be large enough to warrant the routine, widespread use of nebulised bronchodilators for the treatment of stable COPD.

The determination of the size and shape of buried InAs/InP quantum dots by transmission electron microscopy.

Bright-field, diffraction-contrast imaging in the transmission electron microscope has been applied to the determination of the diameter and height populations of a single layer of buried, pure, InAs/InP quantum dots (QDs). Plan-view diffraction contrast from the QDs was observed to increase significantly when the sample was tilted away from the [001] growth direction to near the [111] zone-axis orientation. This added contrast was a result of contributions to the displacement of atoms in a direction perpendicular to the electron beam arising from strain in the growth direction. Since the strain in the growth direction was about an order of magnitude larger than the strain perpendicular to the growth direction, as the sample is tilted away from the [001] zone-axis condition, the larger strain component increases the projected strain thereby increasing the QD contrast in the image. For the sample studied, both of the populations for the QD diameter and the image contrast were observed to be multimodal with the seven peaks in the contrast distribution correlating with seven distinct populations of QDs each differing in height by one monolayer (ML), from 3 to 9MLs. An analysis of the theoretically expected and experimentally observed standard deviations in the Gaussian fits to the QD diameter and height distributions provided an additional constraint in the selection of the optimal model for the multimodal distributions.

Cardioselective beta-blockers for chronic obstructive pulmonary disease: a meta-analysis.

Beta-blocker therapy has a mortality benefit in patients with hypertension, heart failure and coronary artery disease, as well as during the perioperative period. These drugs have traditionally been considered contraindicated in patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to assess the effect of cardioselective beta-blockers on respiratory function of patients with COPD. Comprehensive searches were performed of the EMBASE, MEDLINE and CINAHL databases from 1966 to May 2001, and identified articles and related reviews were scanned. Randomised, blinded, controlled trials that studied the effects of cardioselective beta-blockers on the forced expiratory volume in 1 s (FEV1) or symptoms in patients with COPD were included in the analysis. Interventions studied were the administration of beta-blocker, given either as a single dose or for longer duration, and the use of beta2-agonist given after the study drug. Outcomes measured were the change in FEV1 from baseline and the number of patients with respiratory symptoms. Eleven studies of single-dose treatment and 8 of continued treatment were included. Cardioselective beta-blockers produced no significant change in FEV1 or respiratory symptoms compared to placebo, given as a single dose (-2.05% [95% CI, -6.05% to 1.96%]) or for longer duration (-2.55% [CI, -5.94% to 0.84]), and did not significantly affect the FEV1 treatment response to beta2-agonists. Subgroup analyses revealed no significant change in results for those participants with severe chronic airways obstruction or for those with a reversible obstructive component. In conclusion, cardioselective beta-blockers given to patients with COPD do not produce a significant reduction in airway function or increase the incidence of COPD exacerbations. Given their demonstrated benefit in conditions such as heart failure, coronary artery disease and hypertension, cardioselective beta-blockers should be considered for patients with COPD.

Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease.

BACKGROUND: Individuals with chronic bronchitis or chronic obstructive pulmonary disease (COPD) may suffer recurrent exacerbations with an increase in volume and/or purulence of sputum and any therapy that reduced the number of exacerbations would be useful. There is a marked difference between countries in terms of the prescribing of mucolytics depending on whether or not they are perceived to be effective. OBJECTIVES: To assess the effects of oral mucolytics in adults with stable chronic bronchitis or COPD. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and reference lists of articles. SELECTION CRITERIA: Randomised trials that compared oral mucolytic therapy with placebo for at least two months in adults with chronic bronchitis or COPD. Studies of people with asthma and cystic fibrosis were excluded. DATA COLLECTION AND ANALYSIS: One reviewer extracted data. Study authors and drug companies were contacted for missing information. MAIN RESULTS: Twenty two trials were included. Compared with placebo, there was a significant reduction in the number of exacerbations per patient with oral mucolytics (weighted mean difference (WMD) -0.067 per month, 95% confidence interval -0.079, -0.055, p<0.001) which is a 29% reduction. The annualised rate of exacerbations in the control patients was 2.7 per year. The number of days of disability also fell on mucolytic therapy (WMD -0.56, 95% confidence interval -0.77, -0.35, p<0.001). The number of patients who remained exacerbation-free was greater in the mucolytic group thanin the placebo group (OR 2.22, 95% confidence interval 1.93, 2.54, p<0.001). There was no difference in lung function or in adverse effects reported between treatments. REVIEWER'S CONCLUSIONS: In subjects with chronic bronchitis or COPD, treatment with mucolytics was associated with a small reduction in acute exacerbations and a somewhat greater reduction in total number of days of disability.

Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease.

BACKGROUND: Individuals with chronic bronchitis or chronic obstructive pulmonary disease (COPD) may suffer recurrent exacerbations with an increase in volume and/or purulence of sputum and any therapy that reduced the number of exacerbations would be useful. There is a marked difference between countries in terms of prescribing of mucolytics depending on whether or not they are perceived to be effective. OBJECTIVES: To assess the effects of oral mucolytics in adults with stable chronic bronchitis or COPD. SEARCH STRATEGY: We have searched the Cochrane Airways Group trials register and reference lists of articles, on three separate occasions. SELECTION CRITERIA: Randomised trials that compared oral mucolytic therapy with placebo for at least two months in adults with chronic bronchitis or COPD. Studies of people with asthma and cystic fibrosis were excluded. DATA COLLECTION AND ANALYSIS: One reviewer extracted data. Study authors and drug companies were contacted for missing information. MAIN RESULTS: Twenty three trials were included. Compared with placebo, there was a significant reduction in the number of exacerbations per patient with oral mucolytics (weighted mean difference (WMD) -0.066 per month, 95% confidence interval -0.077, -0.054, p<0.001). Using the annualised rate of exacerbations in the control patients of 2.7 per year, this is a 29% reduction. The number of days of disability also fell (WMD -0.56, 95% confidence interval -0.77, -0.35, p<0.001). The number of patients who remained exacerbation-free was greater in the mucolytic group (OR 2.22, 95% confidence interval 1.93, 2.54, p<0.001). There was no difference in lung function or in adverse effects reported between treatments. REVIEWER'S CONCLUSIONS: In subjects with chronic bronchitis or COPD, treatment with mucolytics was associated with a small reduction in acute exacerbations and a somewhat greater reduction in total number of days of disability.

Influenza vaccine for patients with chronic obstructive pulmonary disease.

BACKGROUND: Influenza vaccinations are currently recommended in the care of people with COPD, but these recommendations are based largely on evidence from observational studies with very few randomised controlled trials (RCTs) reported. Influenza infection causes excess morbidity and mortality in COPD patients but there is also the potential for influenza vaccination to cause adverse effects or not to be cost effective. OBJECTIVES: To evaluate the evidence from RCTs for a treatment effect of influenza vaccination in COPD subjects. Outcomes of interest were exacerbation rates, hospitalisations, mortality, lung function and adverse effects. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and reference lists of articles. References were also provided by a number of drug companies we contacted. SELECTION CRITERIA: RCTs that compared live or inactivated virus vaccines with placebo, either alone or with another vaccine in persons with COPD. Studies of people with asthma were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data. All entries were double checked. Study authors and drug companies were contacted for missing information. MAIN RESULTS: Nine trials were included but only four of these were specifically performed in COPD patients. The others were conducted on elderly and high-risk individuals, some of whom had chronic lung disease. In one study of inactivated vaccine in COPD patients there was a significant reduction in the total number of exacerbations per vaccinated subject compared with those who received placebo (weighted mean difference (WMD) -0.45, 95% confidence interval -0.75 to -0.15, p = 0.004). This difference was mainly due to the reduction in exacerbations occurring after 3 weeks (WMD -0.44, (95% CI -0.68 to -0.20, p<0.001). The number of patients experiencing late exacerbations was also significantly less (OR= 0.13, 95%CI 0.04 to 0.45, p=0.002). There was no evidence of an effect of intranasal live attenuated virus when this was added to inactivated intramuscular vaccination. In studies in elderly patients (only a minority of whom had COPD), there was a significant increase in the occurrence of local adverse reactions in vaccinees, but the effects were generally mild and transient. REVIEWER'S CONCLUSIONS: It appears, from the limited number of studies performed, that inactivated vaccine may reduce exacerbations in COPD patients. The size of effect was similar to that seen in large observational studies, and was due to a reduction in exacerbations occurring three or more weeks after vaccination. In elderly, high risk patients there was an increase in adverse effects with vaccination, but these are seen early and are usually mild and transient.

Breathlessness in older people.

Breathlessness in the elderly is a common clinical problem but should not be considered an inevitable consequence of the aging process. Because of the diverse causes and the possibility of more than one underlying mechanism, the approach to the breathless patient needs to be comprehensive with investigations guided by specific clinical questions. Once the underlying reversible factors have been identified and treated as far as practicable, management of the chronically breathless patient is based on symptom relief, exercise conditioning, optimisation of breathing patterns and patient education. Interventions should be objectively evaluated using symptom scores or a measure of exercise tolerance rather than a physiological measure alone. As there is the potential for harm (including cost), treatments offering no benefit should be promptly withdrawn.

Characteristics of patients admitted to hospital with chronic obstructive pulmonary disease.

AIMS: To examine the characteristics of patients admitted to Auckland Hospital with chronic obstructive pulmonary disease (COPD) and to assess their management prior to hospitalisation. METHODS: Prospective survey of 99 patients admitted with COPD over an 8 week period. Of these, 80 patients were interviewed about their social circumstances, physical functioning, smoking habits and medical treatment. They also had their inhaler technique checked and FEV1 measured. RESULTS: Subjects had a mean age of 70.6 years with a mean FEV1 of 29% of predicted. 45% lived alone and a third still smoked. The mean value for their usual physical functioning was 15.4 (possible 10-30) on the SF-36 health status questionnaire. 84% of all subjects used a beta-agonist, 50% an anticholinergic bronchodilator, 69% inhaled steroids, 18% oral steroids, and 19% theophylline. 40% used nebulised medication and only 6% had domiciliary oxygen. 40% reported having an influenza vaccination in the preceding year and 27% had participated in some form of pulmonary rehabilitation. The mean length of stay was 7.5 days. CONCLUSIONS: Patients hospitalized for COPD report marked impairment in physical functioning, despite which many live alone. They frequently use inhaled and oral steroids, and nebulised medication, but only a minority had received an influenza vaccination or attended pulmonary rehabilitation.