Using bacterial biomarkers to identify early indicators of cystic fibrosis pulmonary exacerbation onset

Acute periods of pulmonary exacerbation are the single most important cause of morbidity in cystic fibrosis patients, and may be associated with a loss of lung function. Intervening prior to the onset of a substantially increased inflammatory response may limit the associated damage to the airways. While a number of biomarker assays based on inflammatory markers have been developed, providing useful and important measures of disease during these periods, such factors are typically only elevated once the process of exacerbation has been initiated. Identifying biomarkers that can predict the onset of pulmonary exacerbation at an early stage would provide an opportunity to intervene before the establishment of a substantial immune response, with major implications for the advancement of cystic fibrosis care. The precise triggers of pulmonary exacerbation remain to be determined; however, the majority of models relate to the activity of microbes present in the patient's lower airways of cystic fibrosis. Advances in diagnostic microbiology now allow for the examination of these complex systems at a level likely to identify factors on which biomarker assays can be based. In this article, we discuss key considerations in the design and testing of assays that could predict pulmonary exacerbations

Monitoring of Collapsed Built-Up Areas with High Resolution SAR Images

A 16-year-old male with cystic fibrosis (CF) was admitted to hospital with a severe infective exacerbation. Despite standard management, including conventionally selected intravenous antibiotics for Pseudomonas aeruginosa chest physiotherapy, and institution of noninvasive ventilation (NIV) for progressive hypercapneic respiratory failure, he continued to deteriorate. Direct sputum sensitivity testing (DSST) revealed a novel combination of antibiotics that resulted in a rapid and remarkable clinical improvement. DSST is a form of "whole" sputum sensitivity testing that provides information on antibiotic synergy, and may more accurately reflect in vivo antibiotic sensitivity patterns in cystic fibrosis.</p

Kori Bustards (\u3ci\u3eArdeotis kori\u3c/i\u3e) respond to vegetation density and elevation in the Northern Tuli Game Reserve, Botswana L\u27abondance de l\u27Outarde kori (\u3ci\u3eArdeotis kori\u3c/i\u3e) varie selon la végétation et l\u27élévation dans la réserve de chasse de Northern Tuli, Botswana

Conservation planning and decision making for species of concern requires precise information on abundance and habitat associations. We conducted transect surveys throughout the Northern Tuli Game Reserve, Botswana during June–July 2014 and May– July 2015 to estimate the occupancy and abundance of Kori Bustards (Ardeotis kori). The probability of occupancy of Kori Bustards was greater in areas with tree canopy cover ≤ 50% (ψ2014 = 0.37, SE ± 0.09; ψ2015 = 0.39, SE ± 0.06) when compared with areas with tree canopy cover \u3e 50% (ψ2014 = 0.00, SE ± 0.00; ψ2015 = 0.00, SE ± 0.00). Densities of Kori Bustards ranged from 0.03–5.02 individuals/km² at our study sites. They showed annual variation, and densities were highest in areas where vegetation was classified as sparse or bare soil. Areas at low (≤ 540 m above sea level) and high (≥ 540 m above sea level) elevations at our study sites also exhibited differences in density of Kori Bustards but elevational differences varied among years. Areas categorized as both sparse vegetation and higher elevation had the highest estimated densities in 2014 with 5.02 individuals/km². Areas categorized as sparse vegetation and lower elevation had the highest densities in 2015 with 2.20 individuals/km². Our study demonstrates that areas of sparse vegetation and open canopy areas are important to Kori Bustards. However, open canopy areas outside of reserves may be at risk of conversion to row crop and other forms of agriculture as human populations and demands for food increase. Habitat-specific information will be useful for future studies to identify risks during landscape conservation planning within the range of the Kori Bustard. La planification de la conservation et la prise de décisions pour les espèces préoccupantes requièrent des données précises sur leur abondance et leurs associations avec l\u27habitat. Nous avons effectué des relevés par transects dans la réserve de chasse de Northern Tuli, au Botswana, en juin-juillet 2014 et mai-juillet 2015, afin de déterminer l\u27occurrence et la densité d\u27Outardes kori (Ardeotis kori). La probabilité d\u27occurrence des outardes était supérieure dans les endroits où la voûte forestière couvrait ≤ 50 % (ψ2014 = 0,37, écarttype ± 0,09; ψ2015 = 0,39, écart-type ± 0,06) comparativement aux endroits où la voûte couvrait \u3e 50 % (ψ2014 = 0,00, écart-type ± 0,00; ψ2015 = 0,00, écart-type ± 0,00). Les densités de cette outarde s\u27élevaient de 0,03 à 5,02 individus/km² dans nos sites d\u27étude. Les densités montraient des variations annuelles et étaient plus élevées dans les endroits où la végétation était classée comme « éparse » ou « sol nu ». Les densités ont aussi différé selon les endroits de basse (≤ 540 m au-dessus du niveau de la mer) ou de haute (≥ 540 m ASL) élévation dans nos sites d\u27étude, et ces différences ont varié entre les années. Les endroits classés à la fois comme de végétation éparse et de haute élévation ont hébergé les densités les plus élevées en 2014, soit 5,02 individus/km². Les endroits classés à la fois comme de végétation éparse et de basse élévation ont hébergé les densités les plus élevées en 2015, soit 2,20 individus/km². Notre étude indique que les endroits de végétation éparse et ceux où la voûte est ouverte sont importants pour les Outardes kori. Toutefois, les endroits où la voûte forestière est ouverte à l\u27extérieur des réserves risquent peut-être d\u27être affectés à la culture en rangs ou à d\u27autres formes d\u27agriculture considérant que la population humaine et la demande alimentaire augmentent. Les données relatives à l\u27habitat seront utiles pour les éventuelles recherches visant à identifier les risques au moment de la planification de la conservation du paysage dans l\u27aire de répartition de l\u27Outarde kori

Novel approaches to diagnosis and management of hereditary transthyretin amyloidosis

© Author(s) (or their employer(s)) 2022. Open access This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0Hereditary transthyretin amyloidosis (ATTRv) is a severe, adult-onset autosomal dominant inherited systemic disease predominantly affecting the peripheral and autonomic nervous system, heart, kidney and the eyes. ATTRv is caused by mutations of the transthyretin (TTR) gene, leading to extracellular deposition of amyloid fibrils in multiple organs including the peripheral nervous system. Typically, the neuropathy associated with ATTRv is characterised by a rapidly progressive and disabling sensorimotor axonal neuropathy with early small-fibre involvement. Carpal tunnel syndrome and cardiac dysfunction frequently coexist as part of the ATTRv phenotype. Although awareness of ATTRv polyneuropathy among neurologists has increased, the rate of misdiagnosis remains high, resulting in significant diagnostic delays and accrued disability. A timely and definitive diagnosis is important, given the emergence of effective therapies which have revolutionised the management of transthyretin amyloidosis. TTR protein stabilisers diflunisal and tafamidis can delay the progression of the disease, if treated early in the course. Additionally, TTR gene silencing medications, patisiran and inotersen, have resulted in up to 80% reduction in TTR production, leading to stabilisation or slight improvement of peripheral neuropathy and cardiac dysfunction, as well as improvement in quality of life and functional outcomes. The considerable therapeutic advances have raised additional challenges, including optimisation of diagnostic techniques and management approaches in ATTRv neuropathy. This review highlights the key advances in the diagnostic techniques, current and emerging management strategies, and biomarker development for disease progression in ATTRv.SV gratefully acknowledges funding support from the National Health and Medical Research Council (NHMRC) of Australia (project grant numbers 510233, 1024915 and 1055778; program grant number 1132524; dementia research team grant number 1095127; and Partnership Project number 1153439) and the Motor Neuron Disease Research Institute of Australia. MCK was supported by a NHMRC Practitioner Fellowship (number 1156093).info:eu-repo/semantics/publishedVersio

Group problem-solving skills training for self-harm: randomised controlled trial

Background: Rates of self-harm are high and have recently increased. This trend and the repetitive nature of self-harm pose a significant challenge to mental health services. Aims: To determine the efficacy of a structured group problem-solving skills training (PST) programme as an intervention approach for self-harm in addition to treatment as usual (TAU) as offered by mental health services. Method: A total of 433 participants (aged 18-64 years) were randomly assigned to TAU plus PST or TAU alone. Assessments were carried out at baseline and at 6-week and 6-month follow-up and repeated hospital-treated self-harm was ascertained at 12-month follow-up. Results: The treatment groups did not differ in rates of repeated self-harm at 6-week, 6-month and 12-month follow-up. Both treatment groups showed significant improvements in psychological and social functioning at follow-up. Only one measure (needing and receiving practical help from those closest to them) showed a positive treatment effect at 6-week (P = 0.004) and 6-month (P = 0.01) follow-up. Repetition was not associated with waiting time in the PST group. Conclusions: This brief intervention for self-harm is no more effective than treatment as usual. Further work is required to establish whether a modified, more intensive programme delivered sooner after the index episode would be effective

A quality-of-life measure for adults with primary ciliary dyskinesia: QOL-PCD

Primary ciliary dyskinesia (PCD) is characterised by chronic suppurative lung disease, rhino-sinusitis, hearing impairment and sub-fertility. We have developed the first multidimensional measure to assess health-related quality of life (HRQoL) in adults with PCD (QOL-PCD). Following a literature review and expert panel meeting, open-ended interviews with patients investigated the impact of PCD on HRQoL in the UK and North America (n=21). Transcripts were content analysed to derive saturation matrices. Items were rated for relevance by patients (n=49). Saturation matrices, relevance scores, literature review, evaluation of existing measures, and expert opinion contributed to development of a preliminary questionnaire. The questionnaire was refined following cognitive interviews (n=18). Open-ended interviews identified a spectrum of issues unique to adults with PCD. Saturation matrices confirmed comprehensive coverage of content. QOL-PCD includes 48 items covering the following seven domains: Physical Functioning, Emotional Functioning, Treatment Burden, Respiratory and Sinus Symptoms, Ears and Hearing, Social Functioning, and Vitality and Health Perceptions. Cognitive testing confirmed that content was comprehensive and the items were well-understood by respondents. Content validity and cognitive testing supported the items and structure. QOL-PCD has been translated into other languages and is awaiting psychometric testing

Tai Chi for Osteopenic Women: Design and Rationale of a Pragmatic Randomized Controlled Trial

Background: Post-menopausal osteopenic women are at increased risk for skeletal fractures. Current osteopenia treatment guidelines include exercise, however, optimal exercise regimens for attenuating bone mineral density (BMD) loss, or for addressing other fracture-related risk factors (e.g. poor balance, decreased muscle strength) are not well-defined. Tai Chi is an increasingly popular weight bearing mind-body exercise that has been reported to positively impact BMD dynamics and improve postural control, however, current evidence is inconclusive. This study will determine the effectiveness of Tai Chi in reducing rates of bone turnover in post-menopausal osteopenic women, compared with standard care, and will preliminarily explore biomechanical processes that might inform how Tai Chi impacts BMD and associated fracture risks. Methods/Design: A total of 86 post-menopausal women, aged 45-70y, T-score of the hip and/or spine -1.0 and -2.5, have been recruited from primary care clinics of a large healthcare system based in Boston. They have been randomized to a group-based 9-month Tai Chi program plus standard care or to standard care only. A unique aspect of this trial is its pragmatic design, which allows participants randomized to Tai Chi to choose from a pre-screened list of community-based Tai Chi programs. Interviewers masked to participants' treatment group assess outcomes at baseline and 3 and 9 months after randomization. Primary outcomes are serum markers of bone resorption (C-terminal cross linking telopeptide of type I collagen), bone formation (osteocalcin), and BMD of the lumbar spine and proximal femur (dual-energy X-ray absorptiometry). Secondary outcomes include health-related quality-of-life, exercise behavior, and psychological well-being. In addition, kinetic and kinematic characterization of gait, standing, and rising from a chair are assessed in subset of participants (n = 16) to explore the feasibility of modeling skeletal mechanical loads and postural control as mediators of fracture risk. Discussion: Results of this study will provide preliminary evidence regarding the value of Tai Chi as an intervention for decreasing fracture risk in osteopenic women. They will also inform the feasibility, value and potential limitations related to the use of pragmatic designs for the study of Tai Chi and related mind-body exercise. If the results are positive, this will help focus future, more in-depth, research on the most promising potential mechanisms of action identified by this study. Trial registration: This trial is registered in Clinical Trials.gov, with the ID number of NCT01039012

Reliability of capturing foot parameters using digital scanning and the neutral suspension casting technique

<p>Abstract</p> <p>Background</p> <p>A clinical study was conducted to determine the intra and inter-rater reliability of digital scanning and the neutral suspension casting technique to measure six foot parameters. The neutral suspension casting technique is a commonly utilised method for obtaining a negative impression of the foot prior to orthotic fabrication. Digital scanning offers an alternative to the traditional plaster of Paris techniques.</p> <p>Methods</p> <p>Twenty one healthy participants volunteered to take part in the study. Six casts and six digital scans were obtained from each participant by two raters of differing clinical experience. The foot parameters chosen for investigation were cast length (mm), forefoot width (mm), rearfoot width (mm), medial arch height (mm), lateral arch height (mm) and forefoot to rearfoot alignment (degrees). Intraclass correlation coefficients (ICC) with 95% confidence intervals (CI) were calculated to determine the intra and inter-rater reliability. Measurement error was assessed through the calculation of the standard error of the measurement (SEM) and smallest real difference (SRD).</p> <p>Results</p> <p>ICC values for all foot parameters using digital scanning ranged between 0.81-0.99 for both intra and inter-rater reliability. For neutral suspension casting technique inter-rater reliability values ranged from 0.57-0.99 and intra-rater reliability values ranging from 0.36-0.99 for rater 1 and 0.49-0.99 for rater 2.</p> <p>Conclusions</p> <p>The findings of this study indicate that digital scanning is a reliable technique, irrespective of clinical experience, with reduced measurement variability in all foot parameters investigated when compared to neutral suspension casting.</p

Penerapan Metode Scoring System untuk Penilaian Latihan Pemahaman Materi Ibadah Sholat Fardhu dan Sunnah

Ibadah Sholat merupakan kewajiban yang harus senantiasa dikerjakan oleh umat muslim. Tidak hanya mengutamakan ibadah sholat fardhu, melainkan Allah juga menganjurkan untuk menyempurnakan dengan melakukan ibadah sholat sunnah. Dalam pelaksanaannya, umat muslim masih membutuhkan panduan mengenai tuntunan sholat tersebut secara praktis dan bersifat mobile, sementara mobilitas manusia semakin tinggi. Oleh karena itu, pada penelitian ini telah membangun aplikasi tuntunan sholat baik fardhu dan sunnah berbasis android yang dilengkapi dengan latihan kemampuan pemahaman materi mengenai sholat fardhu dan sunnah. Tujuannya adalah mampu meningkatkan kualitas setiap orang yang ingin belajar sholat dengan melakukan latihan kemampuan pemahaman materi tersebut. Sistem penilaiannya menggunakan metode pengukuran, yaitu metode scoring system. Metode scoring system adalah metode yang memberikan evaluasi terhadap kelayakan subyek tes dalam bentuk nilai. Dari hasil pengujian menunjukkan bahwasannya aplikasi penilaian latihan ini mampu menilai tingkat pemahaman materi berdasarkan hasil tes yang diperoleh menggunakan metode scoring system