Communication networks beyond the capacity crunch.

This issue of Philosophical Transactions of the Royal Society, Part A represents a summary of the recent discussion meeting 'Communication networks beyond the capacity crunch'. The purpose of the meeting was to establish the nature of the capacity crunch, estimate the time scales associated with it and to begin to find solutions to enable continued growth in a post-crunch era. The meeting confirmed that, in addition to a capacity shortage within a single optical fibre, many other 'crunches' are foreseen in the field of communications, both societal and technical. Technical crunches identified included the nonlinear Shannon limit, wireless spectrum, distribution of 5G signals (front haul and back haul), while societal influences included net neutrality, creative content generation and distribution and latency, and finally energy and cost. The meeting concluded with the observation that these many crunches are genuine and may influence our future use of technology, but encouragingly noted that research and business practice are already moving to alleviate many of the negative consequences.

Broadband wavelength and angle-resolved scattering characterization for nanophotonics investigations.

The characterization of scattered light is complex and relatively nonstandardized despite being of great importance to many optical technologies. While total scatter can be efficiently measured using integrating-sphere-based techniques, a detailed determination of the full bidirectional scattering distribution function is far more challenging, often requiring complicated and expensive equipment as well as substantial measurement time. Due to this, many research groups rely on simpler, angle-resolved scattering (ARS) measurements, yet these are typically carried out using a single wavelength source, therefore providing limited information. Here, we demonstrate a custom-built broadband angle-resolved optical spectrometer, which utilizes a supercontinuum white light laser source combined with a custom automated goniometer and a Si CCD array spectrometer in order to carry out broad spectral measurements of ARS. The use of a collimated supercontinuum allows for small area measurements that are often crucial for investigation of nanophotonic samples created using expensive fabrication techniques. The system has been tested and calibrated, and accuracy and reproducibility have been verified by integrating wavelength and ARS data over the angular range and comparing to calibrated integrating sphere measurements.

Prolonged school non-attendance in adolescence: a practical approach.

Prolonged school non-attendance in adolescence poses a significant public health concern. Adverse outcomes for adolescents who have missed out on the social and academic benefits of high school include mental health disorders and economic, social and relationship difficulties that may persist into adulthood. Healthcare professionals are often consulted in cases of prolonged school non-attendance. Diagnosis and management of specific physical and mental health problems must be the health professional's initial priority, with the subsequent development of a management plan to assist with school reintegration. Using a specific framework, an understanding of the factors contributing to a young person's school non-attendance can be developed. Intervention leading to a successful return to school has the potential to lower the risk of associated long-term adverse health outcomes.

Erbium-doped multi-element fiber amplifiers for space-division multiplexing operations.

Erbium-doped multi-element fiber (MEF) amplifiers have been fabricated to simultaneously amplify multiple transmission channels. MEF devices comprise of multiple single-core fibers (elements) combined in a common coating, with each element working as a single fiber in isolation. MEFs containing 3-elements and 7-elements have been fabricated and characterized. Each element of the fabricated MEFs provides nearly 32 dB of gain with a noise figure of <5 dB for an input signal level of -23 dBm at 1530 nm. Different permutations of element pairs within the MEFs were checked for crosstalk and none was detected, confirming the simultaneous multi-channel amplification capabilities of MEFs.

Corticosteroid responsiveness and clinical characteristics in childhood difficult asthma.

This study describes the clinical characteristics and corticosteroid responsiveness of children with difficult asthma (DA). We hypothesised that complete corticosteroid responsiveness (defined as improved symptoms, normal spirometry, normal exhaled nitric oxide fraction (F(eNO)) and no bronchodilator responsiveness (BDR <12%)) is uncommon in paediatric DA. We report on 102 children, mean+/-sd age 11.6+/-2.8 yrs, with DA in a cross-sectional study. 89 children underwent spirometry, BDR and F(eNO) before and after 2 weeks of systemic corticosteroids (corticosteroid response study). Bronchoscopy was performed after the corticosteroid trial. Of the 102 patients in the cross-sectional study, 88 (86%) were atopic, 60 (59%) were male and 52 (51%) had additional or alternative diagnoses. Out of the 81 patients in the corticosteroid response study, nine (11%) were complete responders. Of the 75 patients with symptom data available, 37 (49%) responded symptomatically, which was less likely if there were smokers in the home (OR 0.31, 95% CI 0.02-0.82). Of the 75 patients with available spirometry data, 35 (46%) had normal spirometry, with associations being BAL eosinophilia (OR 5.43, 95% CI 1.13-26.07) and high baseline forced expiratory volume in 1 s (FEV(1)) (OR 1.08, 95% CI 1.02-1.12). Of these 75 patients, BDR data were available in 64, of whom 36 (56%) had <12% BDR. F(eNO) data was available in 70 patients, of whom 53 (75%) had normal F(eNO). Airflow limitation data was available in 75 patients, of whom 17 (26%) had persistent airflow limitation, which was associated with low baseline FEV(1) (OR 0.93, 95% CI 0.90-0.97). Only 11% of DA children exhibited complete corticosteroid responsiveness. The rarity of complete corticosteroid responsiveness suggests alternative therapies are needed for children with DA.

Monocusp - novel common femoral vein monocusp surgery uncorrectable chronic venous insufficiency with aplastic/dysplastic valves.

OBJECTIVE: Previous reparative valvular surgical options directed at reconstructing damaged common femoral vein (CFV) valves associated with pathological chronic venous insufficiency (CVI) have not succeeded in reliably managing CVI. In consequence, venous valvuloplasty is rare and most patients are managed conservatively. As a result, monocusp surgery was identified as an optional surgical solution for this large underserved patient group. METHODS: Ulcer patients appear at wound clinics and often experience disappointing results. Monocusp valves were constructed utilizing viable vein wall in 14 operations on 11 patients. These patients were observed for four years to see if such an autogenous vein wall valve might control aggressive symptomatic CVI when faced with unusable valves. RESULTS: Long-term follow-up showed that the monocusp valves remained competent at four years. Symptomatic failures have not appeared at this time. Pain, swelling, ulcers and leg congestion were reliably reversed. VEnous INsufficiency Epidemiologic and Economic Study (VEINES) classification (see Abenhaim L, Krux X, VIENES Study collaborators. Angiology 1997;48:59 and Kurz X, Kahn SR, Abenhaim L, et al. Int Angiol 1999;18:83-102) improved over four years from 2.7 +/- 0.9 to 0 (P < 0.001); CEAP classifications (see Kistner RL, Eklof B, Masuda EM. Mayo Clin Proc 1996;71:338-45) improved from grade 4-6 to 0-1 (CEAP is not generally a postoperative grading system, but it can be used to develop some form of qualitative analyses as to intervention effectiveness, i.e. what existed preoperatively no longer exists postoperatively. Its postsurgery use is limited by (C5) classification - history of ulcer, which by definition cannot go below that with a history of ulcer even if the ulcer has been cured). Mean venous reflux scores decreased from 3.8 +/- 0.4 to 0.3 +/- 0.5 (P < 0.001). CONCLUSION: Monocusp implantation reliably resolved patient symptoms when unusable CFV valves were encountered. Postoperative CFV reflux is usually undetectable. The monocusp valve exhibits minimal thrombogenicity related to its viability with attendant antithrombotic hormone production capacity and has markedly improved the patient's quality of life. Full thickness monocusp surgery could become widespread with the difficult dysplastic/aplastic CVI patient subset because of its simplicity, repeatability, durability, low complication rate, effectiveness, persistent availability and viability providing nitric oxide synthase and thymomodulin hormone production capacity. The full thickness of vein wall has distinct advantages over other partial thickness valve creation methods because of its long-term vitality. Postoperative coumadin is recommended for six months to minimize risks of deep vein thrombosis and/or pulmonary embolism.

Efficient white light generation in secondary cores of holey fibers.

We report the generation of white light from a picosecond pump by efficient four-wave mixing processes. A 530 nm green source based on a frequency-doubled Yb-doped fiber laser generates strong red and blue sidebands in the secondary cores of a holey fiber with large air-filling factor. Phase matching is attributed to birefringence within the submicrometer-sized secondary cores induced by non-symmetric deformation during the fiber drawing.

Ultrastructure of the reticular basement membrane in asthmatic adults, children and infants.

Reticular basement membrane (RBM) thickening in asthma is considered to be the result of subepithelial fibrosis. Thus, the RBM in asthma should contain an excess of fibrils identified as interstitial collagen and the ratio of fibril to matrix should be increased above normal levels. Electron micrographs of the RBM were compared with those of interstitial collagen deeper in the bronchial wall using endobronchial biopsy specimens from adult asthmatics (aged 18-41 yrs (n = 10)), children with difficult asthma (aged 6-16 yrs (n = 10)), wheezy infants with reversible airflow limitation (aged 0.3-2 yrs (n = 10)) and age-matched nonasthmatic controls: 10 adults, nine children and nine symptomatic infants with normal lung function. Fibrils in the RBM were significantly thinner (median (range) width 39 (30-52) nm versus 59 (48-73) nm), and fewer fibrils were banded than in the interstitial collagen (ratio of banded to non-banded fibrils 0.08 (0-0.17) versus 0.22 (0-1.3)). The ratio of fibrils to matrix in the thickened RBM of asthmatics did not differ from that of their respective controls (1.34 (0.63-2.49) versus 1.18 (0.31-2.6)). The ratio of fibril to matrix in the thickened reticular basement membrane of asthmatics is normal, and, contrary to what is expected in fibrosis, the fibrils do not resemble those of interstitial collagen.

Can HRCT be used as a marker of airway remodelling in children with difficult asthma?

BACKGROUND: Whole airway wall thickening on high resolution computed tomography (HRCT) is reported to parallel thickening of the bronchial epithelial reticular basement membrane (RBM) in adult asthmatics. A similar relationship in children with difficult asthma (DA), in whom RBM thickening is a known feature, may allow the use of HRCT as a non-invasive marker of airway remodelling. We evaluated this relationship in children with DA. METHODS: 27 children (median age 10.5 [range 4.1-16.7] years) with DA, underwent endobronchial biopsy from the right lower lobe and HRCT less than 4 months apart. HRCTs were assessed for bronchial wall thickening (BWT) of the right lower lobe using semi-quantitative and quantitative scoring techniques. The semi-quantitative score (grade 0-4) was an overall assessment of BWT of all clearly identifiable airways in HRCT scans. The quantitative score (BWT %; defined as [airway outer diameter - airway lumen diameter]/airway outer diameter x100) was the average score of all airways visible and calculated using electronic endpoint callipers. RBM thickness in endobronchial biopsies was measured using image analysis. 23/27 subjects performed spirometry and the relationships between RBM thickness and BWT with airflow obstruction evaluated. RESULTS: Median RBM thickness in endobronchial biopsies was 6.7(range 4.6-10.0) microm. Median qualitative score for BWT of the right lower lobe was 1(range 0-1.5) and quantitative score was 54.3 (range 48.2-65.6)%. There was no relationship between RBM thickness and BWT in the right lower lobe using either scoring technique. No relationship was found between FEV1 and BWT or RBM thickness. CONCLUSION: Although a relationship between RBM thickness and BWT on HRCT has been found in adults with asthma, this relationship does not appear to hold true in children with DA.

Investigation of young children with severe recurrent wheeze: any clinical benefit?

The management of young children with severe recurrent wheeze is difficult because symptoms are often refractory to conventional asthma therapy and other diagnoses must be excluded. The present authors aimed to evaluate the outcome of detailed, invasive investigations in such patients. Children aged between 3 months and 5 yrs with severe recurrent wheezing, who had been referred to a tertiary centre, underwent a protocol of investigations including a chest computed tomography scan, blood tests, nasal ciliary brushings, fibreoptic bronchoscopy, bronchoalveolar lavage (BAL), endobronchial biopsy and passage of an oesophageal pH probe. A total of 47 children (25 males) with a median age of 26 (range 5-58) months underwent investigation. Of these, 39% were atopic, two-thirds had evidence of gastro-oesophageal reflux and 37 out of 47 had an abnormal bronchoscopy. Findings included structural abnormalities (13 out of 37), excessive mucus (20 out of 37) and macroscopic inflammation (10 out of 37). BAL revealed bacterial growth in 12 out of 44 (27%) patients. Good quality endobronchial biopsies were obtained from 36 out of 46 (78%) patients; of these, 44% had tissue eosinophilia and 28% had a thickened reticular basement membrane. Additional investigations (including bronchoscopy) in young children with severe wheeze may help to identify positive diagnoses and provide information to support a clinical diagnosis of asthma. This hypothesis-generating work should form the basis of future interventional studies.

Single-mode plane-polarized ytterbium-doped large-core fiber laser with 633-W continuous-wave output power.

We demonstrate a cladding-pumped single-mode plane-polarized ytterbium-doped fiber laser generating 633 W of continuous-wave output power at 1.1 microm with 67% slope efficiency and a polarization extinction ratio better than 16 dB. The laser is end pumped through both fiber ends and shows no evidence of roll-over, even at the highest output power, which is limited only by the available pump power.

A video questionnaire identifies upper airway abnormalities in preschool children with reported wheeze.

BACKGROUND: Accurate characterisation of subjects is essential to interpret data from studies investigating preschool wheezing. AIM: To assess whether a video questionnaire (VQ) identifies upper airway abnormalities in preschool children with reported wheeze. METHODS: Forty three children (median age 17 months, range 3-58) undergoing fibreoptic bronchoscopy for clinical investigation of troublesome noisy breathing at a tertiary centre were studied. Parents were shown a VQ with four clips (wheeze, stridor, and two other upper respiratory noises) and chose the clip(s) resembling their child's main symptom. Doctor observed symptoms, parental reported symptoms, and symptoms identified on VQ were related to bronchoscopy. RESULTS: Thirty subjects had wheeze as the main symptom: 19 had doctor observed wheeze (DOW) and 11 had parental reported wheeze (RW). Parents of two of the subjects with RW identified wheeze alone on VQ and both had normal bronchoscopic findings. Five of the remaining nine subjects with RW had upper airway abnormalities at bronchoscopy. Parents of six subjects with RW identified a noise other than wheeze on VQ; four of these had upper airway abnormalities. Parents of two subjects with RW did not identify a noise on VQ; one had upper airway abnormalities. Of the 19 with DOW, nine parents identified wheeze alone on VQ, and all had a normal upper airway. Parents of nine subjects with DOW identified a noise other than wheeze as an equal or only symptom, (no noise identified in one), and five had upper airway abnormalities. CONCLUSION: A VQ helps to identify upper airway abnormalities in preschool children with a history of wheezing.

Single-frequency, single-mode, plane-polarized ytterbium-doped fiber master oscillator power amplifier source with 264 W of output power.

We present a single-frequency, single-mode, plane-polarized ytterbium-doped all-fiber master oscillator power amplifier source at 1060 nm generating 264 W of continuous-wave output power. The final-stage amplifier operated with a high gain of 19 dB and a high conversion efficiency of 68%. There was no evidence of rollover from stimulated Brillouin scattering even at the highest output power, and the maximum output was limited only by the available pump power.

Airway inflammation in children with difficult asthma: relationships with airflow limitation and persistent symptoms.

BACKGROUND: The effective management and development of new treatments for children with difficult asthma requires investigation of the underlying airway pathology and its relationships with persistent symptoms and airflow limitation. METHODS: The density of immunologically distinct inflammatory cells and cells expressing interleukin (IL)-4, IL-5, and RANTES was determined in paraffin-embedded endobronchial biopsy specimens from 27 children with difficult asthma (6-16 years) following treatment with systemic corticosteroids. Eleven non-asthmatic children (7-16 years) acted as controls. Reticular basement membrane (RBM) thickness was also recorded and forced expiratory volume in 1 second (FEV(1)) and exhaled nitric oxide (FE(NO)) measured, the latter in asthmatic children only. RESULTS: RBM thickness was greater in the asthmatic than the control group (median (range) 7.4 (3.1-11.1) v 5.1 (3.5-7.5) microm, p = 0.02). No other significant tissue difference was seen, nor was there a difference between asthmatic subjects with daily symptoms after systemic corticosteroids and those who became asymptomatic. CD4+ T lymphocyte density was higher in asthmatic subjects with persistent airflow limitation (post-bronchodilator FEV(1)<80% predicted) than in those without (9.1 (5.5-13.6) v 3.5 (0.6-34.9)%, p = 0.027). Analysing all asthmatic subjects together, there were negative correlations between CD4+ T lymphocytes and both pre-bronchodilator FEV(1) (r = -0.57 (95% CI -0.79 to -0.23), p = 0.002) and post-bronchodilator FEV(1) (r = -0.61 (95% CI -0.81 to -0.29), p<0.001). There were no significant correlations between FE(NO) and inflammatory cells of any type. CONCLUSION: In children with difficult asthma treated with systemic corticosteroids, persistent airflow limitation is associated with a greater density of CD4+ T lymphocytes in endobronchial biopsy specimens.

The safety and quality of endobronchial biopsy in children under five years old.

BACKGROUND: Little is known about the airway pathology of wheezing disorders in infants and preschool children, partly owing to the difficulty of undertaking invasive studies in this age group. The safety of endobronchial biopsy and the quality of biopsies obtained were reviewed in infants and preschool children. METHODS: Case notes of children under five years of age who underwent bronchoscopy and endobronchial biopsy were reviewed. The safety of the procedure was compared in a control group matched for weight and age, undergoing bronchoscopy without endobronchial biopsy. A consultant histopathologist assessed biopsy quality. RESULTS: 33 patients (mean age 31 months, range 4 to 59) underwent bronchoscopy and endobronchial biopsy, and were matched with 33 controls (mean age 28 months, range 3 to 52). There was no significant difference between groups in the number, type, or severity of complications occurring during or after the procedure. Biopsies from 30 of the 33 subjects could be assessed. Reticular basement membrane was identified in all 30; inflammation could be assessed in 26; areas of smooth muscle were present in 23. CONCLUSIONS: In a group of preschool children undergoing bronchoscopy under general anaesthetic, performance of endobronchial biopsy carried no extra risk. The quality of biopsies obtained was usually sufficient to allow an assessment of remodelling and inflammation.

Relationship between exhaled nitric oxide and mucosal eosinophilic inflammation in children with difficult asthma, after treatment with oral prednisolone.

Exhaled nitric oxide (FE(NO)) has been proposed as a noninvasive marker of airway inflammation in asthma, and may reflect airway eosinophilia. We examined the relationship between FE(NO) and eosinophilic inflammation in endobronchial biopsies from 31 children with difficult asthma (mean age [range] 11.9 [6-17] yr), following 2 wk of prednisolone (40 mg/d). Endobronchial biopsy was also performed in seven children without asthma. Biopsy eosinophils were detected using antibody to major basic protein, and point-counting used to derive an "eosinophil score." FE(NO) readings and suitable biopsies for analysis were both obtained in 21 of 31 children with asthma. Adherence to prednisolone was demonstrated in 17 of these 21. Within this group, there was a correlation between FE(NO) and eosinophil score (r = 0.54, p = 0.03). The relationship was strongest in patients with persistent symptoms after prednisolone, in whom FE(NO) > 7 ppb was associated with a raised eosinophil score. For all patients, FE(NO) < 7 ppb was associated with an eosinophil score within the nonasthmatic range, regardless of symptoms. We propose that FE(NO) is associated with eosinophilic inflammation in children with difficult asthma, following prednisolone, and may help in identifying patients in whom persistent symptoms are associated with airway eosinophilia.

Asthma severity and inflammation markers in children.

UNLABELLED: The relationship of airway inflammation with asthma severity remains unclear. Our aim was to correlate the results of recommended methods of assessment of inflammation with measures of asthma control, in children with a wide range of asthma severity. The study was a cross-sectional investigation of 58 children receiving a wide range of treatment, including 10 treated without regular maintenance therapy and 29 treated with high-dose inhaled corticosteroids (CS). Exhaled nitric oxide (NO), serum eosinophil cationic protein (ECP), and induced sputum (processed for eosinophil count and ECP level) were related to recent symptoms, lung function, and bronchial responsiveness. There was no significant correlation between the results of any METHOD: Neither did any marker of airway inflammation relate to recent symptoms, unlike PC20, which did. There was a significant, inverse correlation between the forced expiratory volume in 1 s (FEV1) and both NO and sputum ECP (r=-0.46, p=<0.001; r=-0.48, p=0.004, respectively). Sputum eosinophils were inversely related to the dose of methacholine that corresponded to a 20% fall in FEV1 (PC20) (r=-0.57, p=0.02). Serum ECP did not relate to any measure of asthma control. There was no association of any recommended inflammation markers with current symptoms and only a weak relationship between them and physiological measures. The place of these markers remains unclear and their use in clinical practice needs further investigation by long-term longitudinal studies.

Children with difficult asthma: a practical approach.

Many open studies investigating the effects of innovative treatments for steroid-dependent asthma demonstrate some benefit. This is also true of the majority of placebo arms in placebo-controlled trials. This suggests that children with difficult asthma benefit from the high level of input that is typically provided in clinical trials, with or without additional medication. Such intensive management of patients, with the emphasis on establishing the diagnosis, improving adherence, and identifying provoking factors, is the key to optimizing asthma control for these children. For patients with genuinely severe asthma, despite high doses of conventional treatment, a greater understanding of the pathological basis of persistent symptoms is needed. Identification of different pathological subtypes of severe asthma should allow for more rational prescribing of asthma therapy, as well as the design of further trials of potential steroid-sparing treatments.

Evidence for different subgroups of difficult asthma in children.

BACKGROUND: Children with difficult asthma experience frequent symptoms despite treatment with high dose inhaled steroids. Persistent symptoms may result from persistent airway inflammation which can be monitored by measuring exhaled nitric oxide (NO). This study aimed to assess the role of airway inflammation, using NO as a surrogate, in children with difficult asthma and to investigate the response to oral prednisolone. METHODS: NO was measured in 23 children (mean age 11.7 years) with difficult asthma, before and after 2 weeks of treatment with oral prednisolone. The clinical response was assessed by spirometric tests, peak flow, bronchodilator use, and symptoms. Adherence to treatment was assessed by measuring serum prednisolone and cortisol concentrations. NO was measured in 55 healthy children to establish a normal range. RESULTS: NO concentrations were higher in asthmatic patients than in controls (geometric mean 11.2 v 5.3 ppb, p<0.01). Using grouped data, the concentration of NO fell following prednisolone (11.2 v 7.5 ppb, p<0.01) accompanied by an improvement in morning peak flow (p<0.05). The baseline NO concentration was raised (>12.5 ppb) in nine asthmatic patients and remained high after prednisolone in five. Thirteen had normal levels of NO (<12.5 ppb) before and after prednisolone. Thirteen asthmatic patients remained symptomatic following prednisolone; NO levels were raised on both occasions in five of these and were normal in seven. CONCLUSIONS: As a group, the asthmatic subjects demonstrated evidence of airway inflammation which responded to prednisolone. At least two subgroups of patients were identified: one with persistently raised NO levels despite treatment with oral prednisolone indicating ongoing steroid insensitive inflammation, and another with normal levels of NO. Both subgroups included patients with persistent symptoms, which suggests that different patterns of difficult asthma in children exist.

Difficult asthma: defining the problems.

A retrospective survey was undertaken of children with difficult asthma, attending a respiratory clinic. The clinical and laboratory profiles of asthmatic children who were poorly controlled on > or = 800 microg of inhaled corticosteroids (ICS) were studied and compared to children well-controlled on > or = 800 microg ICS. Assessments were made of atopy, growth, lung function, treatment adherence, home environment, and responsiveness to corticosteroids (CS). Fiftyseven "difficult" and 23 well-controlled children were studied. Significant differences in the home environment were identified. Smoking was significantly more common in the difficult-to-control group. Nine children had alternative diagnoses. Poor CS responsiveness was present in 10 children. Adverse home environments, poor treatment supervision, alternative diagnoses, and unresponsiveness to CS were the most important factors in difficult asthma. A full assessment, including bronchoscopy, is indicated to avoid unnecessary increases in CS to doses that could cause side-effects.