Triple Therapy for Cystic Fibrosis Phe508del-Gating and -Residual Function Genotypes.

BACKGROUND: Elexacaftor-tezacaftor-ivacaftor is a small-molecule cystic fibrosis transmembrane conductance regulator (CFTR) modulator regimen shown to be efficacious in patients with at least one Phe508del allele, which indicates that this combination can modulate a single Phe508del allele. In patients whose other CFTR allele contains a gating or residual function mutation that is already effectively treated with previous CFTR modulators (ivacaftor or tezacaftor-ivacaftor), the potential for additional benefit from restoring Phe508del CFTR protein function is unclear. METHODS: We conducted a phase 3, double-blind, randomized, active-controlled trial involving patients 12 years of age or older with cystic fibrosis and Phe508del-gating or Phe508del-residual function genotypes. After a 4-week run-in period with ivacaftor or tezacaftor-ivacaftor, patients were randomly assigned to receive elexacaftor-tezacaftor-ivacaftor or active control for 8 weeks. The primary end point was the absolute change in the percentage of predicted forced expiratory volume in 1 second (FEV1) from baseline through week 8 in the elexacaftor-tezacaftor-ivacaftor group. RESULTS: After the run-in period, 132 patients received elexacaftor-tezacaftor-ivacaftor and 126 received active control. Elexacaftor-tezacaftor-ivacaftor resulted in a percentage of predicted FEV1 that was higher by 3.7 percentage points (95% confidence interval [CI], 2.8 to 4.6) relative to baseline and higher by 3.5 percentage points (95% CI, 2.2 to 4.7) relative to active control and a sweat chloride concentration that was lower by 22.3 mmol per liter (95% CI, 20.2 to 24.5) relative to baseline and lower by 23.1 mmol per liter (95% CI, 20.1 to 26.1) relative to active control (P<0.001 for all comparisons). The change from baseline in the Cystic Fibrosis Questionnaire-Revised respiratory domain score (range, 0 to 100, with higher scores indicating better quality of life) with elexacaftor-tezacaftor-ivacaftor was 10.3 points (95% CI, 8.0 to 12.7) and with active control was 1.6 points (95% CI, -0.8 to 4.1). The incidence of adverse events was similar in the two groups; adverse events led to treatment discontinuation in one patient (elevated aminotransferase level) in the elexacaftor-tezacaftor-ivacaftor group and in two patients (anxiety or depression and pulmonary exacerbation) in the active control group. CONCLUSIONS: Elexacaftor-tezacaftor-ivacaftor was efficacious and safe in patients with Phe508del-gating or Phe508del-residual function genotypes and conferred additional benefit relative to previous CFTR modulators. (Funded by Vertex Pharmaceuticals; VX18-445-104 ClinicalTrials.gov number, NCT04058353.).

Lung Transplantation in Controlled Donation after Circulatory-Determination-of-Death Using Normothermic Abdominal Perfusion.

The main limitation to increased rates of lung transplantation (LT) continues to be the availability of suitable donors. At present, the largest source of lung allografts is still donation after the neurologic determination of death (brain-death donors, DBD). However, only 20% of these donors provide acceptable lung allografts for transplantation. One of the proposed strategies to increase the lung donor pool is the use of donors after circulatory-determination-of-death (DCD), which has the potential to significantly alleviate the shortage of transplantable lungs. According to the Maastricht classification, there are five types of DCD donors. The first two categories are uncontrolled DCD donors (uDCD); the other three are controlled DCD donors (cDCD). Clinical experience with uncontrolled DCD donors is scarce and remains limited to small case series. Controlled DCD donation, meanwhile, is the most accepted type of DCD donation for lungs. Although the DCD donor pool has significantly increased, it is still underutilized worldwide. To achieve a high retrieval rate, experience with DCD donation, adequate management of the potential DCD donor at the intensive care unit (ICU), and expertise in combined organ procurement are critical. This review presents a concise update of lung donation after circulatory-determination-of-death and includes a step-by-step protocol of lung procurement using abdominal normothermic regional perfusion.

Novel program for automatic calculation of EPG variables.

The electrical penetration graph (EPG) technique is the most powerful tool for studying the feeding behavior of pierce-sucking insects. However, calculating EPG variables is often very time-consuming, and consequently, several software programs have been developed for the automatic calculation of EPG variables. Here we present a new user-friendly Excel Workbook that uses a standardized list of EPG variables and follows expert guidelines for calculating them. The program developed in Visual Basic for Applications (VBA) is a step up from the existing software and allows easy data analysis and interpretation. It also includes a novel option for dealing with the common problem of "truncated"-waveforms artificially terminated by the end of recording. The only requirement to run the program is Microsoft Excel software running under a PC environment. The Workbook was validated by calculating variables from EPG recordings of aphids and psyllids and the results obtained were compared with those of existing software such as the Sarria Workbook. Our EPG Workbook provides researchers with a reliable and standardized tool for the automatic calculation of up to 127 EPG variables from phloem-sap-sucking insects.

Lung allograft transbronchial cryobiopsy for critical ventilated patients: a randomised trial.

BACKGROUND: Transbronchial lung cryobiopsy is an emerging technique for diagnosing pulmonary rejection. However, no prospective studies of this procedure for critically ill lung transplant recipients who require mechanical ventilation in the intensive care unit (ICU) have been performed. METHODS: From March 2017 to January 2020, we performed a prospective, randomised, comparative study to assess the diagnostic yield, histological quality and safety of transbronchial lung biopsy using biopsy forceps, a 1.9-mm cryoprobe or a 2.4-mm cryoprobe. RESULTS: 89 out of 129 consecutive transbronchial biopsy procedures (forceps group, 28 procedures; 1.9-mm cryoprobe group, 31 procedures; 2.4-mm cryoprobe group, 30 procedures) were randomised. Compared with lung samples from the forceps and 1.9-mm cryoprobe groups, lung samples from the 2.4-mm cryoprobe group allowed the most definitive diagnoses (p<0.01 and p=0.02, respectively), the most diagnoses of acute lung rejection (p<0.01 and p=0.01, respectively) and the most diagnoses of rejection severity (p<0.01 and p<0.01, respectively). These samples were larger (p<0.01 and p=0.04, respectively), had the most adequate alveolar tissue (p<0.01 and p=0.02, respectively), had more vessels per procedure (p<0.01 and p=0.01, respectively) and had no significant crush artefacts. Moderate bleeding was observed in 23% of cases (p=0.01 and p=0.08, respectively). No severe bleeding was observed. CONCLUSIONS: Transbronchial lung biopsy using a 2.4-mm cryoprobe allows the safe collection of lung tissue samples from critically ill lung transplant recipients who require mechanical ventilation in the ICU and has good diagnostic performance.

Granulomatous tattoo reaction treated with topical allopurinol.

Granulomatous reactions to tattoo ink have been frequently associated with exogenous pigment, although sometimes they are the manifestation of a cutaneous or an underlying systemic sarcoidosis. We report a case of a patient with a granulomatous reaction to a black tattoo pigment treated with 3% topical allopurinol for 3 months. We observed complete resolution without any side-effects. Examination and follow-up ruled out sarcoidosis. Oral allopurinol has been proven to be effective for the management of granulomatous reactions to tattoos. Based on the significant improvement we have described in our patient, we recommend new studies to reveal all the potential benefits of the topical use of allopurinol for the treatment of granulomatous reactions to tattoo ink.

Correction of Lacrimal Gland Ptosis in Blepharoplasty: A Systematic Review.

PURPOSE: Lacrimal gland ptosis has a prevalence of 10% to 15% in Caucasian patients, reaching up to 60% in older age. Its involuntary resection during blepharoplasty carries the potential risk of compromising corneal lubrication. The purpose of this systematic review is to check whether there is a consensus in the literature regarding the surgical procedure of choice and which outcomes and complications have been observed. METHODS: A systematic review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A search was carried out in the Medline, Scopus, and Cochrane databases in March 2022. RESULTS: A total of 16 studies involving 483 patients with lacrimal gland ptosis have been included. In 90.06% of patients, resuspension or direct refixation of the gland to the lacrimal fossa with suture to the orbital periosteum was performed. Follow up has been inconsistent, with an average of 18 months. Regarding complications, 5 recurrences and only 2 patients with persistent dry eye were observed. CONCLUSIONS: In general, the evidence is sparse. Nevertheless, repair of lacrimal gland ptosis is a relatively simple, reproducible, and safe surgical technique, with a low likelihood of recurrence, severe, or persistent complications. A classification is proposed for both the grading of ptosis and its treatment.

Burkitt's lymphoma in the adult as an unusual cause of large bowel obstruction.

Bowel obstruction is an uncommon clinical presentation in Burkitt´s lymphoma, specially in adults. This type of lymphoma is classified within B-cell non-Hodgkin´s lymphomas, which is characterized by its aggressiveness and quickly tumoral growth. The clinical presentation related to the gastrointestinal tract is unusual, but it can be presented as intussusception, obstruction or ischemic perforation. Here we describe a case of Burkitt´s lymphoma with bowel obstruction as a clinical debut.

Pelvic actinomycosis secondary to intrauterine device.

Actinomycosis is a rare bacterial infection causing lesions and abscesses, often mimicking tumors. It commonly affects the cervicofacial, abdominal, and thoracic regions. We present a case of a woman with an intrauterine device (IUD) who developed an abscess and abdominal symptoms. Initial studies suggested a tumor, but biopsy revealed inflammation. Subsequently, she was diagnosed with Actinomyces Israelii infection, her IUDwas removed, and she was treated with penicillin, resulting in improvement. Pelvic actinomycosis is uncommon and often diagnosed late, often post-surgery, requiring combined surgical and medical treatment.

Enhancing Image Quality via Robust Noise Filtering Using Redescending M-Estimators.

In the field of image processing, noise represents an unwanted component that can occur during signal acquisition, transmission, and storage. In this paper, we introduce an efficient method that incorporates redescending M-estimators within the framework of Wiener estimation. The proposed approach effectively suppresses impulsive, additive, and multiplicative noise across varied densities. Our proposed filter operates on both grayscale and color images; it uses local information obtained from the Wiener filter and robust outlier rejection based on Insha and Hampel's tripartite redescending influence functions. The effectiveness of the proposed method is verified through qualitative and quantitative results, using metrics such as PSNR, MAE, and SSIM.

Factors associated with mechanical ventilation in SARS-CoV-2 patients treated with high-flow nasal cannula oxygen and outcomes.

Five percent of patients infected with SARS-CoV-2 require advanced respiratory support. The high-flow nasal cannula oxygenotherapy (HFNCO) appears to be effective and safe to reduce the need for mechanical ventilation. However, the factors associated with HFNCO failure as well as the outcomes of patients receiving this noninvasive respiratory strategy remain unclear. Thus, we performed this study to determine factors leading to intubation of SARS-CoV-2 patients treated with HFNCO and patients' outcomes. We retrospectively analyzed the medical charts of patients admitted in our ICU center for acute respiratory failure due to SARS-CoV-2 infection and who initially benefited from HFNCO, between September 1, 2020, and March 1, 2021. We included all adults patients who received HFNCO and compared two groups: those treated with HFNCO alone and those who failed HFNCO. Patients treated with HFNCO and secondarily limited to the use of mechanical ventilation were excluded from the analysis. Sixty-nine patients were included, 33 were treated with HFNCO alone and 36 failed HFNCO. We found more patients with shock in the HFNCO failure group (p = 0.001). The mean IGSII score was higher in the HFNCO failure group (p < 0.001). The minimum PaO2 /FiO2 was lower in the HFNCO failure group (p = 0.024). The length of stay in ICU was higher in the HFNCO failure group (p < 0.001). The mean duration of HFNCO before intubation was 1.77 days. Six-week mortality was higher in the HFNCO failure group (p = 0.034). Ten patients had a complication during intubation. The HFNCO leads to reduce the intubation rate, the length of stay in ICU, and the mortality. Determining the factors associated with HFNCO failure is important to avoid complications following late intubation.

Survival After Lung Transplantation for Chronic Hypersensitivity Pneumonitis: Results From a Large International Cohort Study.

Repeated exposure to antigens via inhalation is the primary cause of hypersensitivity pneumonitis, a form of interstitial pneumonia. The chronic form of hypersensitivity pneumonitis leads to progressive loss of respiratory function; lung transplantation is the only therapeutic option for chronically ill patients. The ESTS Lung Transplantation Working Group conducted a retrospective multicentred cohort study to increase the body of knowledge available on this rare indication for lung transplantation. Data were collected for every patient who underwent lung transplant for hypersensitivity pneumonitis in participating centres between December 1996 and October 2019. Primary outcome was overall survival; secondary outcome was freedom from chronic lung allograft dysfunction. A total of 114 patients were enrolled from 9 centres. Almost 90% of patients were diagnosed with hypersensitivity pneumonitis before transplantation, yet the antigen responsible for the infection was identified in only 25% of cases. Eighty per cent of the recipients received induction therapy. Survival at 1, 3, and 5 years was 85%, 75%, and 70%, respectively. 85% of the patients who survived 90 days after transplantation were free from chronic lung allograft dysfunction after 3 years. The given study presents a large cohort of HP patients who underwent lung transplants. Overall survival rate is higher in transplanted hypersensitivity pneumonitis patients than in those suffering from any other interstitial lung diseases. Hypersensitivity pneumonitis patients are good candidates for lung transplantation.

Hospitalization, death, and probable reinfection in Peruvian healthcare workers infected with SARS-CoV-2: a national retrospective cohort study.

BACKGROUND: Peru has some of the worst outcomes worldwide as a result of the SARS-CoV-2 pandemic; it is presumed that this has also affected healthcare workers. This study aimed to establish whether occupation and other non-occupational variables were risk factors for possible reinfection, hospitalization, and mortality from COVID-19 in cohorts of Peruvian healthcare workers infected with SARS-CoV-2. METHODS: Retrospective cohort study. Healthcare workers who presented SARS-CoV-2 infection between March 1, 2020, and August 6, 2021, were included. Occupational cohorts were reconstructed from the following sources of information: National Epidemiological Surveillance System, molecular tests (NETLAB), results of serology and antigen tests (SICOVID-19), National Registry of Health Personnel (INFORHUS), and National Information System of Deaths (SINADEF). The incidence of probable reinfection, hospitalization, and death from COVID-19 was obtained in the cohorts of technicians and health assistants, nursing staff, midwives, dentists, doctors, and other healthcare workers. We evaluated whether the occupation and other non-occupational variables were risk factors for probable reinfection, hospitalization, and death from COVID-19 using log-binomial and probit binomial models, obtaining the adjusted relative risk (RRAJ). RESULTS: 90,398 healthcare workers were included in the study. Most cases were seen in technicians and health assistants (38.6%), and nursing staff (25.6%). 8.1% required hospitalization, 1.7% died from COVID-19, and 1.8% had probable reinfection. A similar incidence of probable reinfection was found in the six cohorts (1.7-1.9%). Doctors had a higher incidence of hospitalization (13.2%) and death (2.6%); however, they were also those who presented greater susceptibility linked to non-occupational variables (age and comorbidities). The multivariate analysis found that doctors (RRAJ = 1.720; CI 95: 1.569-1.886) had a higher risk of hospitalization and that the occupation of technician and health assistant was the only one that constituted a risk factor for mortality from COVID-19 (RRAJ = 1.256; 95% CI: 1.043-1.512). CONCLUSIONS: Peruvian technicians and health assistants would have a higher risk of death from COVID-19 than other healthcare workers, while doctors have a higher incidence of death probably linked to the high frequency of non-occupational risk factors. Doctors present a higher risk of hospitalization independent of comorbidities and age; likewise, all occupations show a similar risk of probable reinfection.

Hepatitis E virus infection and waste pickers: A case-control seroprevalence study.

Whether waste pickers are a risk group for hepatitis E virus (HEV) infection is largely unknown. This study aimed to determine the association between HEV exposure and the occupation of waste pickers and the work characteristics of waste pickers. An age-and gender-matched case-control seroprevalence study of 86 waste pickers and 86 control subjects of the general population was performed. We determined anti-HEV IgG antibodies in sera of cases and controls using a commercially available enzyme-linked immunoassay. The McNemar's test was used to assess the association between HEV seropositivity and the occupation of waste picker. The association between HEV seropositivity and work characteristics of waste pickers was assessed by bivariate and logistic regression analyses. Anti-HEV IgG antibodies were detected in 14 (16.3%) of the 86 waste pickers and in 8 (9.3%) of the 86 control subjects (McNemar's pair test: odds ratio (OR) = 13.0; 95% confidence interval (CI): 0.73-230.77; p = .02). Bivariate analysis showed that HEV exposure was associated with an ill status (p = .01) and reflexes impairment (p = .009). Logistic regression analysis showed that HEV seropositivity was associated with increasing age (OR = 6.52; 95% CI: 1.95-21.78; p = .002) and raising pigs (OR = 12.01; 95% CI: 1.48-97.26; p = .02). This is the first age- and gender-matched case-control study on the association between HEV infection and the occupation of waste picker. Waste pickers represent a risk group for HEV infection. Factors associated with HEV seropositivity found in this study may help in the design of optimal planning to avoid HEV infection.

Validation of a Spanish version of the Leicester Cough Questionnaire in cystic fibrosis.

Cough is a main symptom in cystic fibrosis (CF). We aim to validate a Spanish version of the Leicester Cough Questionnaire (LCQ-Sp) to measure the impact of cough in CF bronchiectasis. A prospective longitudinal multicentre study was performed. Internal consistency and score changes over a 15-day period in stable state were assessed to analyse reliability. Concurrent validity was analysed by correlation with Saint George's Respiratory Questionnaire (SGRQ) and convergent validity by assessing the association with clinical variables. Changes in scores between stable state and the first exacerbation were assessed to analyse responsiveness. 132 patients (29.73 ± 10.52 years) were enrolled in four hospitals. Internal consistency was high for the total score and good for the three domains (Cronbach's α 0.81-0.93). The test-retest reliability showed an intraclass correlation coefficient of 0.86 for the total score. The correlation between LCQ-Sp and SGRQ scores was -0.74. The LCQ-Sp score negatively correlated with sputum volume, and the mean score decreased at the beginning of exacerbations (16.04±3.81 vs 13.91±4.29) with a large effect size. The LCQ-Sp is a reliable, repeatable and responsive instrument to assess the impact of cough in CF bronchiectasis and is responsive to change in the event of exacerbations.

Low prevalence of anti-hepatitis E virus IgG antibodies in Tepehuanos in Mexico.

INTRODUCTION AND OBJECTIVE: The epidemiology of infection with hepatitis E virus (HEV) in Tepehuanos (a Mexican ethnic group living in rural areas) is largely unknown. This study aimed to determine the seroprevalence of and risk factors associated with HEV infection in Tepehuanos in Durango, Mexico, and to compare this seroprevalence with that in non-Tepehuanos. MATERIALS AND METHODS: Through a case-control seroprevalence study, we studied 146 Tepehuanos and 146 age- and gender-matched control subjects of the general population from rural settings. The frequency of anti-HEV IgG antibodies was determined using an enzyme-linked immunoassay. Bivariate and multivariate analyses were used to assess the association between seropositivity and socio-demographic, clinical and behavioral characteristics of the Tepehuanos. RESULTS: IgG antibodies against HEV were found in 5 (3.4%; 95% CI: 1.1-7.8) of 146 Tepehuanos and in 46 (31.5%; 95% CI: 24.1-39.7) of 146 control subjects (OR=0.01; 95% CI: 0.0007-0.20; P<0.000001). Bivariate analysis showed that HEV seropositivity was associated with age, consumption of meat from goat, sheep, boar, turkey and pigeon, and concrete flooring at home. However, these variables were no longer significant when analyzed by logistic regression. CONCLUSIONS: This is first study on the epidemiology of HEV exposure in Tepehuanos. We demonstrated serological evidence of HEV infection in this ethnic group. The seroprevalence of HEV exposure in Tepehuanos is low as compared with that found in non-Tepehuano people living in rural Durango. Further studies to determine the risk factors associated with HEV exposure in Tepehuanos are needed.

Postmortem Analysis Using Different Sensors and Technologies on Aramid Composites Samples after Ballistic Impact.

This work focuses on the combination of two complementary non-destructive techniques to analyse the final deformation and internal damage induced in aramid composite plates subjected to ballistic impact. The first analysis device, a 3D scanner, allows digitalising the surface of the tested specimen. Comparing with the initial geometry, the permanent residual deformation (PBFD) can be obtained according to the impact characteristics. This is a significant parameter in armours and shielding design. The second inspection technique is based on computed tomography (CT). It allows analysing the internal state of the impacted sample, being able to detect possible delamination and fibre failure through the specimen thickness. The proposed methodology has been validated with two projectile geometries at different impact velocities, being the reaction force history on the specimen determined with piezoelectric sensors. Different loading states and induced damages were observed according to the projectile type and impact velocity. In order to validate the use of the 3D scanner, a correlation between impact velocity and damage induced in terms of permanent back face deformation has been realised for both projectiles studied. In addition, a comparison of the results obtained through this measurement method and those obtained in similar works, has been performed in the same range of impact energy. The results showed that CT is needed to analyse the internal damage of the aramid sample; however, this is a highly expensive and time-consuming method. The use of 3D scanner and piezoelectric sensors is perfectly complementary with CT and could be relevant to develop numerical models or design armours.

Tox_(R)CNN: Deep learning-based nuclei profiling tool for drug toxicity screening.

Toxicity is an important factor in failed drug development, and its efficient identification and prediction is a major challenge in drug discovery. We have explored the potential of microscopy images of fluorescently labeled nuclei for the prediction of toxicity based on nucleus pattern recognition. Deep learning algorithms obtain abstract representations of images through an automated process, allowing them to efficiently classify complex patterns, and have become the state-of-the art in machine learning for computer vision. Here, deep convolutional neural networks (CNN) were trained to predict toxicity from images of DAPI-stained cells pre-treated with a set of drugs with differing toxicity mechanisms. Different cropping strategies were used for training CNN models, the nuclei-cropping-based Tox_CNN model outperformed other models classifying cells according to health status. Tox_CNN allowed automated extraction of feature maps that clustered compounds according to mechanism of action. Moreover, fully automated region-based CNNs (RCNN) were implemented to detect and classify nuclei, providing per-cell toxicity prediction from raw screening images. We validated both Tox_(R)CNN models for detection of pre-lethal toxicity from nuclei images, which proved to be more sensitive and have broader specificity than established toxicity readouts. These models predicted toxicity of drugs with mechanisms of action other than those they had been trained for and were successfully transferred to other cell assays. The Tox_(R)CNN models thus provide robust, sensitive, and cost-effective tools for in vitro screening of drug-induced toxicity. These models can be adopted for compound prioritization in drug screening campaigns, and could thereby increase the efficiency of drug discovery.

Association between Toxoplasma gondii infection and thyroid dysfunction: a case-control seroprevalence study.

BACKGROUND: The association between Toxoplasma gondii infection and thyroid disease has been poorly studied. Therefore, we sought to determine the association between T. gondii seropositivity and thyroid dysfunction. METHODS: We performed an age- and gender-matched case-control study of 176 patients suffering from hypothyroidism (n = 161) or hyperthyroidism (n = 15) and 528 control subjects without these diseases in a public hospital in Durango City, Mexico. Anti-Toxoplasma IgG antibodies were determined in sera from cases and controls using a commercially available enzyme-linked immunoassay. RESULTS: Anti-T. gondii IgG antibodies were found in 11 (6.3%) of 176 patients suffering from thyroid dysfunction and in 48 (9.1%) of 528 control subjects (OR = 0.66; 95% CI: 0.33-1.31; P = 0.23). Stratification by two groups of age (50 years and younger, and 51 year and older) showed that the youngest group of patients with thyroid dysfunction had a significantly lower seroprevalence of T. gondii infection than its age- and gender-matched control group (1/83: 1.2% vs 23/257: 8.6%; OR = 0.12; 95% CI: 0.01-0.93; P = 0.01). This stratification also showed that the youngest group of patients with hypothyroidism had a significantly lower seroprevalence of T. gondii infection than its age- and gender matched control group (0/75: 0% vs 21/233: 9.0%; P = 0.003). CONCLUSIONS: Our results suggest that thyroid dysfunction is not associated with seropositivity to T. gondii in general; however, in young (50 years or less) patients, a negative association between infection and thyroid dysfunction and hypothyroidism was found. Further research to confirm this negative association is needed.

Metaheuristic Optimisation Algorithms for Tuning a Bioinspired Retinal Model.

A significant challenge in neuroscience is understanding how visual information is encoded in the retina. Such knowledge is extremely important for the purpose of designing bioinspired sensors and artificial retinal systems that will, in so far as may be possible, be capable of mimicking vertebrate retinal behaviour. In this study, we report the tuning of a reliable computational bioinspired retinal model with various algorithms to improve the mimicry of the model. Its main contribution is two-fold. First, given the multi-objective nature of the problem, an automatic multi-objective optimisation strategy is proposed through the use of four biological-based metrics, which are used to adjust the retinal model for accurate prediction of retinal ganglion cell responses. Second, a subset of population-based search heuristics-genetic algorithms (SPEA2, NSGA-II and NSGA-III), particle swarm optimisation (PSO) and differential evolution (DE)-are explored to identify the best algorithm for fine-tuning the retinal model, by comparing performance across a hypervolume metric. Nonparametric statistical tests are used to perform a rigorous comparison between all the metaheuristics. The best results were achieved with the PSO algorithm on the basis of the largest hypervolume that was achieved, well-distributed elements and high numbers on the Pareto front.

Long-term benefits of airway clearance in bronchiectasis: a randomised placebo-controlled trial.

Keeping airways clear of mucus by airway clearance techniques seems essential in bronchiectasis treatment, although no placebo-controlled trials or any studies lasting longer than 3 months have been conducted. We evaluate the efficacy of the ELTGOL (slow expiration with the glottis opened in the lateral posture) technique over a 1-year period in bronchiectasis patients with chronic expectoration in a randomised placebo-controlled trial.Patients were randomised to perform the ELTGOL technique (n=22) or placebo exercises (n=22) twice-daily (ClinicalTrials.gov, NCT01578681). The primary outcome was sputum volume during the first intervention and 24 h later. Secondary outcomes included sputum volume during the intervention and 24 h later at month 12, exacerbations, quality of life, sputum analyses, pulmonary function, exercise capacity, systemic inflammation, treatment adherence, and side effects.Sputum volume during intervention and 24 h later was higher in the ELTGOL group than in the placebo group both at the beginning and end of the study. Patients in the ELTGOL group had fewer exacerbations (p=0.042) and a clinically significant improvement in the St George's Respiratory Questionnaire score (p<0.001) and the Leicester Cough Questionnaire score compared with the placebo group (p<0.001).Twice-daily ELTGOL technique over 1 year in bronchiectasis patients facilitated secretion removal and was associated with fewer exacerbations, improved quality of life, and reduced cough impact.