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The Soča Valley is the fastest-growing destination in Slovenia, with an international reputation that has been rising over the last 10 years. This is largely due to a growing demand Europe-wide for active outdoor tourism, but also to quality product development at the local level, backed by well-coordinated marketing and distribution. © World Bank 2021 Information Dr Roger Carter and Gaëlle Connolly, adapted from case study prepared for a Handbook on Destination Management for the World Bank (publication due in 2021) © World Bank, used with permission, with additional material provided by Janko Humar, Roger Carter, Gaëlle Connolly and David Ward-Perkins, used with permission.

Two driving factors underlie this tourism initiative: the decision to create a Louvre satellite museum in the ex-industrial town of Lens and the candidature for UNESCO World Heritage status for the mining area in the Pas-de-Calais region of France. The challenge is how best to develop tourism in an area which has no previous experience or reputation as a tourist destination. ‘Mission Louvre-Lens Tourisme’ was launched in 2010. This case describes the journey in the last decade of developing and implementing the strategy. Information Dr Roger Carter and Gaëlle Connolly, adapted from a case study prepared for the OECD manual Operationalisation of Destinations Management Organisations in Romania (March 2020) © CAB International 2021

The recent successful launch of the Orbital Micro Systems GEMS-1 IOD (Global Environmental Monitoring System In-orbit Demonstrator) satellite carrying the University of Colorado’s MiniRad 118-GHz imager/sounder instrument provides the basis for a new means of observing atmospheric precipitation, temperature, and related state variables. GEMS-1 supports an 8-channel passive microwave radiometer operating at the 118.7503 GHz oxygen resonance with cross-track scanning imaging system providing cross- and along track Nyquist sampling at 17 km 3dB spatial resolution. It is precisely calibrated using cold space views along with and an on board reference, yielding the first low-cost commercial weather satellite imagery. GEMS is the first of a constellation of approximately 50 such satellites of progressively improving resolution and spectral coverage that will collectively provide Nyquist time-sampling of precipitation and related weather variables on a global basis, and using microwave frequencies will provide such information probing through most cloud cover. Presented will be first light imagery and on-orbit performance data from the GEMS-1 mission, including validation data on the satellite brightness temperatures. Products will include calibrated multispectral imagery, temperature profiles, retrieved rain rate, and precipitation cell top altitude. The expansion of the GEMS-1 mission to the full GEMS constellation will be outlined.

Objectives: Intraductal Papillary Mucinous Neoplasms (IPMNs) are associated with risk of pancreatic ductal adenocarcinoma (PDAC). It is unclear if an IPMN in individuals at high risk of PDAC should be considered as a positive screening result or as an incidental finding. Stratified Familial Pancreatic Cancer (FPC) populations were used to determine if IPMN risk is linked to familial risk of PDAC.Methods: This is a cohort study of 321 individuals from 258 kindreds suspected of being FPC and undergoing secondary screening for PDAC through the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC). Computerised tomography, endoscopic ultrasound of the pancreas and magnetic resonance imaging were used. The risk of being a carrier of a dominant mutation predisposing to pancreatic cancer was stratified into three even categories (low, medium and high) based on: Mendelian probability, the number of PDAC cases and the number of people at risk in a kindred.Results: There was a median (interquartile range, IQR) follow-up of 2 (0-5) years and a median (IQR) number of investigations per participant of 4 (2-6). One PDAC, two low-grade neuroendocrine tumours and 41 cystic lesions were identified, including 23 IPMN (22 branch-duct, BD). The PDAC case occurred in the top 10% of risk, the BD-IPMN cases were evenly distributed amongst risk categories: low (6/107), medium (10/107) and high (6/107) (P=0.63).Conclusions: The risk of finding BD-IPMN was independent of genetic predisposition and so they should be managed according to guidelines for incidental finding of IPMN

Background: Dihydropyrimidine dehydrogenase (DPD) tumour expression may provide added value to human equilibrative nucleoside transporter-1 (hENT1) tumour expression in predicting survival following pyrimidine-based adjuvant chemotherapy. Methods: DPD and hENT1 immunohistochemistry and scoring was completed on tumour cores from 238 patients with pancreatic cancer in the ESPAC-3(v2) trial, randomised to either postoperative gemcitabine or 5-fluorouracil/folinic acid (5FU/FA). Results: DPD tumour expression was associated with reduced overall survival (hazard ratio, HR = 1.73 [95% confidence interval, CI = 1.21-2.49], p = 0.003). This was significant in the 5FU/FA arm (HR = 2.07 [95% CI = 1.22-3.53], p = 0.007), but not in the gemcitabine arm (HR = 1.47 [0.91-3.37], p = 0.119). High hENT1 tumour expression was associated with increased survival in gemcitabine treated (HR = 0.56 [0.38-0.82], p = 0.003) but not in 5FU/FA treated patients (HR = 1.19 [0.80-1.78], p = 0.390). In patients with low hENT1 tumour expression, high DPD tumour expression was associated with a worse median [95% CI] survival in the 5FU/FA arm (9.7 [5.3-30.4] vs 29.2 [19.5-41.9] months, p = 0.002) but not in the gemcitabine arm (14.0 [9.1-15.7] vs. 18.0 [7.6-15.3] months, p = 1.000). The interaction of treatment arm and DPD expression was not significant (p = 0.303), but the interaction of treatment arm and hENT1 expression was (p = 0.009). Conclusion: DPD tumour expression was a negative prognostic biomarker. Together with tumour expression of hENT1, DPD tumour expression defined patient subgroups that might benefit from either postoperative 5FU/FA or gemcitabine.

BackgroundSurgery followed by chemotherapy is the primary modality of cure for patients with resectable pancreatic cancer but is associated with significant morbidity. The aim of the present study was to evaluate the role of cardiopulmonary exercise testing (CPET) in predicting post-operative adverse events and fitness for chemotherapy after major pancreatic surgery.MethodsPatients who underwent a pancreaticoduodenectomy or total pancreatectomy for pancreatic head lesions and had undergone pre-operative CPET were included in this retrospective study. Data on patient demographics, comorbidity and results of pre-operative evaluation were collected. Post-operative adverse events, hospital stay and receipt of adjuvant therapy were outcome measures.ResultsOne hundred patients were included. Patients with an anaerobic threshold less than 10ml/kg/min had a significantly greater incidence of a post-operative pancreatic fistula [International Study Group for Pancreatic Surgery (ISGPS) Grades A–C, 35.4% versus 16%, P = 0.028] and major intra-abdominal abscesses [Clavien–Dindo (CD) Grades III–V, 22.4% versus 7.8%, P = 0.042] and were less likely to receive adjuvant therapy [hazard ratio (HR) 6.30, 95% confidence interval (CI) 1.25–31.75, P = 0.026]. A low anaerobic threshold was also associated with a prolonged hospital stay (median 20 versus 14 days, P = 0.005) but not with other adverse events.DiscussionCPET predicts a post-operative pancreatic fistula, major intra-abdominal abscesses as well as length of hospital stay after major pancreatic surgery. Patients with a low anaerobic threshold are less likely to receive adjuvant therapy.

Pre-oxygenation in the seated (sitting) position has been associated with better oxygenation. This randomised, cross over study compared oxygenation in the supine position with that in the 45° seated position in 40 young, healthy volunteers. Oxygen was administered through a circle system and tight fitting facemask. Transcutaneous P(O)₂ levels were recorded at 10-s intervals from two measurement points during 4 min of oxygenation in the two positions. The mean (SD) values of 12 measurements taken between the third and fourth minute were recorded. There was no difference in the increase in tissue oxygenation when comparing the supine and seated positions (32.7 (7.3) vs 32.6 (6.7) kPa, respectively). We conclude that there is no evidence that pre-oxygenation in the 45° seated position improves tissue oxygenation in young healthy volunteers compared with the supine position.

Aims Heart failure (HF) and chronic obstructive pulmonary disease (COPD) frequently coexist. No study has prospectively examined the effects of beta-blockade in those with both conditions. Methods and results We randomized 27 patients with HF and coexistent moderate or severe COPD to receive bisoprolol or placebo, titrated to maximum tolerated dose over 4 months. The primary outcome was forced expiratory volume in 1 s (FEV1). The study is registered with ClinicalTrials.gov, number: NCT00702156. Patients were elderly and predominantly male. Cardiovascular comorbidity, smoking history, and pulmonary function were similar in each group (mean FEV1 1.37 vs. 1.26 L, P = 0.52). A reduction in FEV1 occurred after 4 months following treatment with bisoprolol compared with placebo (−70 vs. +120 mL, P = 0.01). Reversibility following inhaled β2-agonist and static lung volumes were not impaired by bisoprolol. All measures of health status exhibited a consistent non-significant improvement, including the Short Form 36 physical and mental component scores (2.6 vs. 0.5 and 0.8 vs. −0.3, respectively), Minnesota Living with Heart Failure Questionnaire (−2.5 vs. 3.5) and Chronic Respiratory Questionnaire (0.07 vs. −0.24). The mean number of COPD exacerbations was similar in the bisoprolol and placebo groups (0.50 and 0.31, respectively, P = 0.44). Conclusion Initiation of bisoprolol in patients with HF and concomitant moderate or severe COPD resulted in a reduction in FEV1. However, symptoms and quality of life were not impaired.

Aims:To characterise the spectrum of nasal symptomatology and nasendoscopic abnormalities seen in patients attending an asthma clinic, and to relate these symptoms to the likelihood of finding nasendoscopic abnormalities which merit treatment.Methods:Forty-three patients attending a problem asthma clinic were enrolled in an observational study. Cardinal nasal symptoms – obstruction, congestion, hyposmia, rhinorrhoea, sneezing, epistaxis or other symptoms – were graded as none (zero), mild (one), moderate (two) or severe (three), giving a maximum nasal symptom score of 21. Asthma symptoms and lung function were measured. Nasendoscopy was then performed.Results:Obstruction was the most common cardinal nasal symptom (seen in 15 patients), the median nasal symptom score was 5.3 (range zero to 14) and only three patients had no nasal symptoms. There was no correlation between nasal symptom score and severity of asthma symptoms or forced expiratory volume in one second. Twenty-two patients had a normal appearance on ENT examination (median nasal symptom score four). The nasendoscopic abnormalities seen comprised polyps (n = 8; median nasal symptom score five), deviated nasal septum (n = 7; median nasal symptom score four), oedematous mucosa (n = 4; median nasal symptom score seven) and other abnormalities (n = 2). Individual nasal symptoms were poor predictors of individual nasal pathologies, with hyposmia the best individual predictor of any abnormality (positive predictive value 80 per cent). The presence of a combination of symptoms increased the likelihood of any nasendoscopic abnormality, with obstruction, rhinorrhoea and hyposmia together having a positive predictive value of 100 per cent.Conclusions:Nasal symptoms are much more frequent than structural abnormalities in patients attending a problem asthma clinic. The threshold for ENT referral should be lower when the patient complains of a symptom complex including hyposmia. Furthermore, concurrent hyposmia, obstruction and rhinorrhoea should be seen as an indication for ENT referral.

Background: Within-breath reactance from forced oscillometry estimates resistance via its inspiratory component (X rs,insp ) and flow limitation via its expiratory component (X rs,exp ). Aim: To assess whether reactance can detect recovery from an exacerbation of chronic obstructive pulmonary disease (COPD). Method: 39 subjects with a COPD exacerbation were assessed on three occasions over 6 weeks using post-bronchodilator forced oscillometry, arterial blood gases, spirometry including inspiratory capacity, symptoms and health-related quality of life (HRQOL). Results: Significant improvements were seen in all spirometric variables except the ratio of forced expiratory volume in 1 s (FEV 1 ) to vital capacity, ranging in mean (SEM) size from 11.0 (2.2)% predicted for peak expiratory flow to 12.1 (2.3)% predicted for vital capacity at 6 weeks. There was an associated increase in arterial partial pressure of oxygen (PaO 2 ). There were significant mean (SEM) increases in both X rs,insp and X rs,exp (27.4 (6.7)% and 37.1 (10.0)%, respectively) but no change in oscillometry resistance (R rs ) values. Symptom scales and HRQOL scores improved. For most variables, the largest improvement occurred within the first week with spirometry having the best signal-to-noise ratio. Changes in symptoms and HRQOL correlated best with changes in FEV 1 , PaO 2 and X rs,insp . Conclusions: The physiological changes seen following an exacerbation of COPD comprised both an improvement in operating lung volumes and a reduction in airway resistance. Given the ease with which forced oscillometry can be performed in these subjects, measurements of X rs,insp and X rs,exp could be useful for tracking recovery.

Background Semiquantitative EUS-elastography has been introduced to distinguish between malignant and benign pancreatic lesions. This study investigated whether semiquantitative EUS-guided transient real time elastography increases the diagnostic accuracy for solid pancreatic lesions compared to EUS-FNA. Patients and methods This single centre prospective cohort study included all patients with solitary pancreatic lesions on EUS during one year. Patients underwent EUS-FNA and semiquantitative EUS-elastography during the same session. EUS and elastography results were compared with final diagnosis which was made on the basis of tissue samples and long-term outcome. Results 91 patients were recruited of which 68 had pancreatic malignancy, 17 showed benign disease and 6 had cystic lesions and were excluded from further analysis. Strain ratios from malignant lesions were significantly higher (24.00; 8.01–43.94 95% CI vs 44.00; 32.42–55.00 95% CI) and ROC analysis indicated optimal cut-off of 24.82 with resulting sensitivity, specificity and accuracy of 77%, 65% and 73% respectively. B-mode EUS and EUS-FNA had an accuracy for the correct diagnosis of malignant lesions of 87% and 85%. When lowering the cut-off strain ratio for elastography to 10 the sensitivity rose to 96% with specificity of 43% and accuracy of 84%, resulting in the least accurate EUS-based method. This was confirmed by pairwise comparison. Conclusion Semiquantitative EUS-elastography does not add substantial value to the EUS-based assessment of solid pancreatic lesions when compared to B-mode imaging.

Heart transplantation is an established treatment for end stage heart failure. In addition to increased life expectancy, heart transplant recipients report a remarkable improvement in symptoms and functional capacity. Exercise performance following heart transplantation, however, remains impaired even in the absence of exertional symptoms. We have assessed the response to exercise in 47 patients with cardiac failure prior to and then at yearly intervals to five years post transplantation. All patients performed incremental symptom limited exercise tests during which minute ventilation (V'E), oxygen consumption (V'O2) and carbon dioxide production (V'CO2) and heart rate (HR) were measured. Ventilatory response (V'E/V'CO2), anaerobic threshold (V'O2 AT %predicted) and heart rate response (HR/VO2) were calculated. The dead space to tidal volume ratio (VD/VT) and alveolar-arterial oxygen gradient (A-aO2) were computed from transcutaneous monitoring. Despite substantial improvement in subjective functional capacity, heart transplant recipients continue to have limited exercise performance [Maximal V'O2% predicted pre-transplant 41.3 (2.2); 1 year 48.6 (1.7), p 2 AT% 31.5 (1.1); 1 year 35.6 (1.0); respectively p2 response [24.0(1.8) vs 79.6(4.2)] were significantly reduced compared to pre-transplant values. The heart rate response remained lower compared to predicted at 5 years post-transplant although there was a significant increase compared to one year post-transplant (32.9 vs 24.0mls/bt). There was a weak but significant relationship between maximal VO2 and peak HR (0.39, pE/V'CO2 45.6 (2.5)] and decreased significantly following transplantation [1 yr 34.1 (1.3), respectively pD/VT after transplantation, it remained higher than normal [Pre VD/VT at maximum exercise 0.35 (0.02); 1 yr 0.31 (0.02); pE/VCO2 and VD/VT at two years post-transplantation with no further change at up to 5 years post transplantation [VE/VCO2 32.0 (1.0); VD/VT 0.29 (0.01)]. Although cardiac output is markedly improved after transplantation, due to chronotropic incompetence associated with denervation, its response remains subnormal and this may explain the residual abnormalities of ventilatory and gas exchange responses to exercise following transplantation.

OBJECTIVE Whole-body plethysmography is a common method of measuring pulmonary function. Although this technique provides a sensitive measure of pulmonary function, it can be problematic and unsuitable in some patients. The development of more accessible techniques would be beneficial. METHODS A prospective study was performed to validate diaphragm ultrasonography as an alternative to whole-body plethysmography in patients referred for pulmonary function testing. Diaphragm movement and position were assessed by ultrasonography after standard pulmonary function testing using whole-body plethysmography. RESULTS A wide range of lung function was observed. Standard lung volumes were as follows: total lung capacity, 5.57 +/- 1.31 L, residual volume, 2.27 +/- 0.56 L; and vital capacity, 3.30 +/- 0.98 L (mean +/- SD). The ratio of forced expiratory volume in 1 second to forced vital capacity was calculated as 0.69 +/- 0.08. Ultrasonography showed that mean diaphragm excursion values were 11.1 +/- 3.8 mm (2-dimensional), 14.7 +/- 4.1 mm during quiet breathing (M-mode), and 14.8 +/- 3.9 mm during a maximal sniff (M-mode). The velocity of diaphragm movement rose sharply during the sniff maneuver from 15.2 +/- 5.8 mm/s during quiet breathing to 104.0 +/- 33.4 mm/s. Static 2-dimensional measures of diaphragm position at the end of quiet inspiration or expiration correlated with standard measures of lung volume on plethysmography (eg, a correlation coefficient of 0.83 was obtained with end inspiration and vital capacity). All measures of diaphragm movement (whether by 2-dimensional or M-mode techniques) were poorly correlated with any lung volumes measured. CONCLUSIONS These data suggest that dynamic measurements using diaphragm ultrasonography provide a relatively poor measure of pulmonary function in relation to whole-body plethysmography.

Background/Aims: The influence of type of surgery and occurrence of post-operative complications on survival following adjuvant therapy for pancreatic cancer are uncertain. Methods: Cox proportional hazard modelling was used to investigate the influence of type of surgery and the presence of complications on survival in conjunction with clinico-pathological variables in the 550 patients of the ESPAC-1 adjuvant randomized controlled trial. Results: Standard Kausch-Whipple (KW) was performed in 282 (54%) patients, 186 (35%) had a pylorus-preserving (PP) KW, 39 (7%) had a distal pancreatectomy and 21 (4%) had a total pancreatectomy. Post-operative complications were reported in 140 (27%) patients. PP-KW patients survived longer with a median (95% CI) survival of 19.9 (17.3, 23.1) months compared to 14.8 (13.0, 16.7) for KW patients (χ2LR = 15.1, p < 0.001). KW patients were more likely however to have R1 margins (67 (24%) vs. 29 (16%), χ2 = 4.59, p = 0.032), poorly differentiated tumours (70 (26%) vs. 19 (10%), χ2 = 18.65, p < 0.001) and positive lymph nodes (165 (60%) vs. 81 (44%), χ2 = 11.32, p < 0.001). Post-operative complications did not significantly affect survival. Independent prognostic factors were tumour grade, nodal status and tumour size but not type of surgery or post-operative complications. There was a survival benefit for chemotherapy irrespective of the type of surgery or post-operative complications. Conclusions: The KW and PP-KW procedures did not significantly influence the hazard of death in the presence of tumour staging, demonstrating that ESPAC-1 surgeons showed good judgement in their choice of operation. Post-operative complications did not adversely affect the survival benefit from adjuvant chemotherapy.

Organisations and members of the public are becoming accustomed to the increasing velocity, frequency and variety of cyber-attacks that they have been facing over the last few years. In response to this challenge, it is important to explore what can be done to offer commercial and private users a reliable and functioning environment. This paper discusses how cyber threats might evolve in the future and seeks to explore these threats more fully. Attention is paid to the changing nature of cyber-attackers and their motivations and what this means for organisations. Finally, useful and actionable steps are provided, which practitioners can use to understand how they can start to address the future challenges of cyber security.

Study objectives: Although impairment of the diffusingcapacity of the lung for carbon monoxide (D lco ) in hearttransplant recipients is well-documented, there are limited data on itsimpact on exercise capacity in these patients. The aim of this studywas to determine the effect of D lco reduction on exercisecapacity in heart transplant recipients. Design: Descriptive cohort study. Setting: A regionalcardiopulmonary transplant center. Participants: Twenty-six heart transplant recipients who were studied before andafter transplantation compared with 26 healthy volunteers. Measurements: Spirometry and static lung volumeswere measured using body plethysmography, D lco was measured using the single-breath technique, and progressivecardiopulmonary exercise was performed using a bicycle ergometer, continuous transcutaneous blood gas monitoring, and on-line analysis ofminute ventilation, oxygen uptake (V o 2 ),and carbon dioxide production. Results: Beforetransplantation, the mean percent predicted for hemoglobin-correctedD lco was reduced in patients (73.2%) compared to healthycontrol subjects (98.8%; p o 2 (V o 2 max) increased after transplantation(increase, 41.3 to 48.6% of predicted; p lco and, V o 2 max after transplantation( r = 0.61; p = 0.001), but not beforetransplantation ( r = 0.09; p = 0.66).D lco was also inversely correlated with other respiratoryresponses to exercise, including the following: the ventilatoryresponse to exercise ( r = −0.44; p r = −43; p r = −0.45;p lco before transplantation. Conclusion: D lco reduction after hearttransplantation appears to represent persistent gas exchange impairmentand contributes to exercise limitation in heart transplantrecipients.

The slow response characteristics of the combined transcutaneous electrode have been viewed as a major disadvantage when compared with other types of non-invasive assessment of gas exchange during exercise testing. We have previously shown that by using the highest recommended temperature of 45 degrees C to reduce response times, and combining this with an exercise protocol of gradual work load increments, that this allows changes in arterial blood gases to be closely followed by transcutaneous values. In the present study we have validated the use of a transcutaneous electrode for estimation of alveolar-arterial oxygen gradient (AaO2) and dead space to tidal volume ratio (V(D)/V(T)) during exercise, against values calculated from direct arterial blood gas analysis. One hundred measurements were made in 20 patients with various cardiopulmonary disorders who underwent exercise testing. Exercise testing was performed by bicycle ergometry with a specific protocol involving gradual work load increments at 2 min intervals. Transcutaneous gas tensions were measured by a heated combined O2 and CO2 electrode. Arterial blood was sampled at the midpoint of each stage of exercise and transcutaneous tensions noted at the end of each stage. The mean difference of the AaO2 gradient calculated from blood gas tensions obtained by the two methods was 0.14 kPa. The limits of agreement were -0.26 and 0.63 kPa. The same values for V(D)/V(T) calculated from gas tensions measured by the two methods were: mean difference 0001; limits of agreement -0.0242 and 0.0252. For both these parameters there was an even scatter around the mean value on Bland and Altman analysis. The findings of this study suggest that estimation of parameters of gas exchange using transcutaneous values during exercise testing is reliable, provided the electrode is heated to a slightly higher temperature than usual and the work load increments are gradual, allowing for the latency in the response time of the system. This system allows the assessment of the contribution of ventilation/perfusion inequality to breathlessness on exertion in patients, provided an initial arterial or ear lobe capillary sample is obtained for calibration purposes. This technique is particularly valuable in patients undergoing repeat exercise tests as it circumvents the need for arterial cannulation.

OBJECTIVES—To determine the mechanism of impairment of pulmonary transfer factor for carbon monoxide (TLCO) in heart transplant candidates, as this is the most common lung function abnormality. SETTING—Regional cardiopulmonary transplant centre. METHODS—TLCO and its components (the diffusing capacity of the alveolar-capillary membrane (DM) and the pulmonary capillary blood volume (VC)) were measured using the Roughton and Forster method and the single breath technique in 38 patients with severe chronic heart failure awaiting heart transplantation (mean age 51 years, range 19 to 61; mean left ventricular ejection fraction 12.8%). Results were compared with data from 26 normal subjects (mean age 47 years, range 27 to 62). RESULTS—Mean per cent predicted TLCO, DM, and VC were significantly reduced in patients (69.9%, 81.4%, and 80.2% of predicted, respectively) compared with controls (97.7%, 100.1%, and 102.3% of predicted, respectively, p

Oxygen is the commonest drug prescribed in hospitals. The inhaled concentration is altered by the administered oxygen flow rate, the characteristics of the delivery device and the patient's respiratory pattern. Using healthy volunteers we measured the inspired oxygen concentration achieved with different devices both at rest and when the breathing pattern of respiratory failure was simulated by binding the subjects' chests until the forced expiratory volume in 1 s was reduced by > 50% and the respiratory rate was > 25 breaths.min(-1). With this respiratory pattern, there was a statistically significant fall in F(I)o(2) while administering oxygen via a Hudson mask at 4 l.min(-1) (23.8% (95% CI 17.4-30.3%) reduction), 12 l.min(-1), humidified (17.8% (95% CI 8.8-26.7%) reduction) and 24 l.min(-1), humidified (12.2% (95% CI 5.0-19.3%) reduction). There was no statistically significant change with a nonrebreathing (reservoir) mask at 15 and 110 l.min(-1) or with a Vapotherm 2000i at 40 l.min(-1), humidified, via nasal prongs. We conclude that the F(I)o(2) delivered by high flow devices is unaffected when the breathing pattern of respiratory failure is simulated. The F(I)o(2) achieved at rest by a nonrebreathing mask (0.68) is less than that often quoted in the literature.

In contrast to the standard single-breath transfer factor for carbon monoxide ( T lCO), there are no specific guidelines or recommendations for the measurement of its components, the pulmonary capillary blood volume ( V C ) and membrane component ( D M ), by the Roughton and Forster method. Ten randomly selected heart transplant patients (three life-long non-smokers, seven ex-smokers > 1 yr, age range 24–55 years) were assessed on two occasions using either the standard or high-oxygen mixture as the first inspired gas in random order. Ten normal subjects (all non-smokers, age range 23–54 years) were assessed on two occasions using either a long protocol (30 min waiting time between repeat measurements in an individual set) or a short protocol (5 min waiting time). Two technically acceptable results of T lCO were used to derive a mean value for D M and V C for each set of measurements (Transflow, P. K. Morgan, Kent, U.K.). The different sequences of gas mixtures produced no significant differences between the values obtained in ten heart transplant patients for mean T lCO (mmol min −1 kPa −1 ) (standard first 5·13 ± 1·15, high-oxygen first 5·14 ± 1·12; limits of agreement −0·57 to 0·59 for D M or for V C . The long or short protocol produced no significant differences between the means of T lCO (mmol min −1 kPa −1 ) (long 8·0 ± 1·9, short 8·0 ± 1·9; limits agreement −0·5 to 0·5), D M or V C . This allows the development of a standard test protocol of short duration (about 40 min) making it practical for clinical use without compromising the precision or reproducibility of the results obtained.

Nineteen percent of women are habitual snorers, yet most snoring studies report only on male snorers. The aim of this study was to identify the factors responsible for habitual snoring in women. Twenty-four snorers and 16 controls were studied prospectively in a special snoring clinic. Snorers were shorter (p =.005) and heavier (p =.001), and with greater body mass index (BMI; p

The aim of the present study was to examine the relationship between the clinicopathological status, the pre- and postoperative systemic inflammatory response and survival in patients undergoing potentially curative resection for ductal adenocarcinoma of the head of the pancreas. Patients (n = 65) who underwent resection of ductal adenocarcinoma of the head of pancreas between 1993 and 2001, and had pre- and postoperative measurements of C-reactive protein, were included in the study. The majority of patients had stage III disease (International Union Against Cancer Criteria, IUCC), positive circumferential margin involvement (R1), tumour size greater than 25 mm with perineural and lymph node invasion and died within the follow-up period. On multivariate analysis, tumour size (hazard ratio (HR) 2.10, 95% confidence interval (CI) 1.20-3.68, P = 0.009), vascular invasion (HR 2.58, 95% CI 1.48-4.50, P0.001) and postoperative C-reactive protein (HR 2.00, 95% CI 1.14-3.52, P = 0.015) retained independent significance. Those patients with a postoperative C-reactive proteinor = 10 mg l(-1) had a median survival of 21.5 months compared with 8.4 months in those patients with a C-reactive protein10 mg l(-1) (P0.001). The results of the present study indicate that, in patients who have undergone potentially curative resection for ductal adenocarcinoma of the head of pancreas, the presence of a systemic inflammatory response predicts poor outcome.

The mechanism of breathlessness on exertion in patients with chronic heart failure are still not fully understood. We therefore investigated the effects of ventilatory and gas exchange abnormalities on exercise capacity in chronic heart failure. Exercise testing was performed in 30 patients with exertional breathlessness due to chronic heart failure and in 30 controls, using continuous transcutaneous blood gas monitoring. Maximal symptom-limited oxygen consumption as (V'O2) as a percentage predicted was reduced in patients (45 +/- 10%; mean +/- SD) compared to controls (87 +/- 7). The ventilatory response (minute ventilation/carbon dioxide production (V'E/V'CO2)) was significantly increased in patients compared to controls (39.9 +/- 7.7 and 25.9 +/- 3.6, respectively). The dead space to tidal volume ratio (VD/VT) was raised in patients compared to controls at rest (0.45 +/- 0.04 vs 0.35 +/- 0.02, respectively) and this persisted on exertion (0.40 +/- 0.05 in patients and 0.20 +/- 0.05 in controls). At maximal symptom-limited exercise, V'E/V'CO2 was inversely related to the % predicted V'O2 in patients, but not in controls (r = -0.62 and r = -0.24, respectively). In patients, V'E/V'CO2 was significantly correlated with VD/VT at maximum exercise (r = 0.82). Patients with chronic heart failure have a significant degree of "wasted ventilation" on exertion, which is associated with increased ventilatory response. The increased ventilatory response on exertion appears to contribute to exercise limitation in these patients.

Dysfunctional breathing (DB) is recognized as an associated problem in patients with asthma and may be identified by the Nijmegen questionnaire. We conducted an observational study to determine if breathing control therapy (BCT) improved Nijmegen scores or asthma-related quality of life in patients attending a problem asthma clinic.Nijmegen and Mini Asthma Quality of Life (Mini-AQLQ) questionnaires were completed. Patients with a positive Nijmegen (or = 23, DB) were referred for BCT and progressive exercise testing (PET) to seek confirmation of dysfunctional breathing. Follow-up questionnaire data were collected at 6 months.A total of 102 patients were studied. The total mean Nijmegen score was 26.4 (range 1-61). Those with a scoreor = 23 (DB group, n = 65, 64%) had significantly lower Mini-AQLQ (mean 2.83) than the non-DB group (n = 37, mean 4.12, 95% CI for difference 0.87, 1.87, p0.0001). There was a strong relationship between Nijmegen score and Mini-AQLQ (r = -0.63, p0.001) at baseline; 10 of 17 DB patients who completed PET showed inappropriate hyperventilation. Follow-up data, available for Nijmegen and Mini-AQLQ in 44 and 46 patients respectively, showed no significant change in either of these parameters.The strong relationship between Mini-AQLQ and Nijmegen scores and poor relationship between Nijmegen scores and PET-identified inappropriate hyperventilation suggest that a positive Nijmegen score overestimates the presence of dysfunctional breathing in patients with moderate to severe asthma. We found no evidence that a moderate intensity breathing control intervention had any impact on Nijmegen scores or asthma-related quality of life in this patient group.

Lie algebras have many varied applications, both in mathematics and mathematical physics. This book provides a thorough but relaxed mathematical treatment of the subject, including both the Cartan-Killing-Weyl theory of finite dimensional simple algebras and the more modern theory of Kac-Moody algebras. Proofs are given in detail and the only prerequisite is a sound knowledge of linear algebra. The first half of the book deals with classification of the finite dimensional simple Lie algebras and of their finite dimensional irreducible representations. The second half introduces the theory of Kac-Moody algebras, concentrating particularly on those of affine type. A brief account of Borcherds algebras is also included. An Appendix gives a summary of the basic properties of each Lie algebra of finite and affine type.