There is little literature about the mortality associated with bronchiectasis. The aim of the present study was to investigate factors affecting mortality in patients with bronchiectasis. In total, ...91 patients were examined for aetiology, pulmonary function tests, high-resolution computed tomography, sputum microbiology and quality of life scores and were then followed over 13 yrs. Overall, 29.7% of the patients died. On multivariate analysis, age, St George's Respiratory Questionnaire activity score, Pseudomonas aeruginosa infection, total lung capacity (TLC), residual volume/TLC and the transfer factor coefficient were all independently associated with mortality. In patients with moderate to severe bronchiectasis, mortality is associated with a degree of restrictive and obstructive disease, poor gas transfer and chronic pseudomonas infection. These features should guide future research into disease progression, and identify those patients needing intensive treatment.
Abstract Introduction In recognition of the advances and evidence based changes in clinical practice that have occurred in recent years and taking into account the knowledge and experience ...accumulated through the voluntary breast unit certification programme, Eusoma has produced this up-dated and revised guidelines on the requirements of a Specialist Breast Centre (BC). Methods The content of these guidelines is based on evidence from the recent relevant peer reviewed literature and the consensus of a multidisciplinary team of European experts. The guidelines define the requirements for each breast service and for the specialists who work in specialist Breast Centres. Results The guidelines identify the minimum requirements needed to set up a BC, these being an integrated Breast Centre, dealing with a sufficient number of cases to allow effective working and continuing expertise, dedicated specialists working with a multidisciplinary approach, providing all services throughout the patients pathway and data collection and audit. It is essential that the BC also guarantees the continuity of care for patients with advanced (metastatic) disease offering treatments according to multidisciplinary competencies and a high quality palliative care service. The BC must ensure that comprehensive support and expertise may be needed, not only through the core BC team, but also ensure that all other medical and paramedical expertise that may be necessary depending on the individual case are freely available, referring the patient to the specific care provider depending on the problem. Conclusions Applying minimum requirements and quality indicators is essential to improve organisation, performance and outcome in breast care. Efficacy and compliance have to be constantly monitored to evaluate the quality of patient care and to allow appropriate corrective actions leading to improvements in patient care.
Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. We surveyed the immune compartment of 16 tissues from 12 adult donors by ...single-cell RNA sequencing and VDJ sequencing generating a dataset of ~360,000 cells. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of finely phenotyped immune cell types, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. Our multitissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis, and antigen receptor sequencing.
ABSTRACT
ATLASGAL is an 870-µm dust survey of 420 deg2 the inner Galactic plane and has been used to identify ∼10 000 dense molecular clumps. Dedicated follow-up observations and complementary ...surveys are used to characterize the physical properties of these clumps, map their Galactic distribution, and investigate the evolutionary sequence for high-mass star formation. The analysis of the ATLASGAL data is ongoing: We present an up-to-date version of the catalogue. We have classified 5007 clumps into four evolutionary stages (quiescent, protostellar, young stellar objects and H ii regions) and find similar numbers of clumps in each stage, suggesting a similar lifetime. The luminosity-to-mass (Lbol/Mfwhm) ratio curve shows a smooth distribution with no significant kinks or discontinuities when compared to the mean values for evolutionary stages indicating that the star formation process is continuous and that the observational stages do not represent fundamentally different stages or changes in the physical mechanisms involved. We compare the evolutionary sample with other star formation tracers (methanol and water masers, extended green objects and molecular outflows) and find that the association rates with these increases as a function of evolutionary stage, confirming that our classification is reliable. This also reveals a high association rate between quiescent sources and molecular outflows, revealing that outflows are the earliest indication that star formation has begun and that star formation is already ongoing in many of the clumps that are dark even at 70 µm.
The majority of tumor-infiltrating T cells exhibit a terminally exhausted phenotype, marked by a loss of self-renewal capacity. How repetitive antigenic stimulation impairs T cell self-renewal ...remains poorly defined. Here, we show that persistent antigenic stimulation impaired ADP-coupled oxidative phosphorylation. The resultant bioenergetic compromise blocked proliferation by limiting nucleotide triphosphate synthesis. Inhibition of mitochondrial oxidative phosphorylation in activated T cells was sufficient to suppress proliferation and upregulate genes linked to T cell exhaustion. Conversely, prevention of mitochondrial oxidative stress during chronic T cell stimulation allowed sustained T cell proliferation and induced genes associated with stem-like progenitor T cells. As a result, antioxidant treatment enhanced the anti-tumor efficacy of chronically stimulated T cells. These data reveal that loss of ATP production through oxidative phosphorylation limits T cell proliferation and effector function during chronic antigenic stimulation. Furthermore, treatments that maintain redox balance promote T cell self-renewal and enhance anti-tumor immunity.
We describe SGC-GAK-1 (11), a potent, selective, and cell-active inhibitor of cyclin G-associated kinase (GAK), together with a structurally related negative control SGC-GAK-1N (14). 11 was highly ...selective in an in vitro kinome-wide screen, but cellular engagement assays defined RIPK2 as a collateral target. We identified 18 as a potent RIPK2 inhibitor lacking GAK activity. Together, this chemical probe set can be used to interrogate GAK cellular biology.
To establish the diagnostic accuracy of the Montreal Cognitive Assessment (MoCA) when screening externally validated cognition in Parkinson disease (PD), by comparison with a PD-focused test (Scales ...for Outcomes in Parkinson disease-Cognition SCOPA-COG) and the standardized Mini-Mental State Examination (S-MMSE) as benchmarks.
A convenience sample of 114 patients with idiopathic PD and 47 healthy controls was examined in a movement disorders center. The 21 patients with dementia (PD-D) were diagnosed using Movement Disorders Society criteria, externally validated by detailed independent functional and neuropsychological tests. The 21 patients with mild cognitive impairment (PD-MCI) scored 1.5 SD or more below normative data in at least 2 measures in 1 of 4 cognitive domains. Other patients had normal cognition (PD-N).
Primary outcomes using receiver operating characteristic (ROC) curve analyses showed that all 3 mental status tests produced excellent discrimination of PD-D from patients without dementia (area under the curve AUC, 87%-91%) and PD-MCI from PD-N patients (AUC, 78%-90%), but the MoCA was generally better suited across both assessments. The optimal MoCA screening cutoffs were <21/30 for PD-D (sensitivity 81%; specificity 95%; negative predictive value NPV 92%) and <26/30 for PD-MCI (sensitivity 90%; specificity 75%; NPV 95%). Further support that the MoCA is at least equivalent to the SCOPA-COG, and superior to the S-MMSE, came from the simultaneous classification of the 3 PD patient groups (volumes under a 3-dimensional ROC surface, chance = 17%: MoCA 79%, confidence interval CI 70%-89%; SCOPA-COG 74%, CI 62%-86%; MMSE-Sevens item 56%, CI 44%-68%; MMSE-World item 62%, CI 50%-73%).
The MoCA is a suitably accurate, brief test when screening all levels of cognition in PD.
The extragalactic background light (EBL), a diffuse photon field in the optical and infrared range, is a record of radiative processes over the universe's history. Spectral measurements of blazars at ...very high energies (>100 GeV) enable the reconstruction of the spectral energy distribution (SED) of the EBL, as the blazar spectra are modified by redshift- and energy-dependent interactions of the gamma-ray photons with the EBL. The spectra of 14 VERITAS-detected blazars are included in a new measurement of the EBL SED that is independent of EBL SED models. The resulting SED covers an EBL wavelength range of 0.56-56 m, and is in good agreement with lower limits obtained by assuming that the EBL is entirely due to radiation from cataloged galaxies.
Cardiac resynchronization therapy (CRT) with or without a defibrillator reduces morbidity and mortality in selected patients with heart failure (HF) but response can be variable. We sought to ...identify pre-implantation variables that predict the response to CRT in a meta-analysis using individual patient-data.
An individual patient meta-analysis of five randomized trials, funded by Medtronic, comparing CRT either with no active device or with a defibrillator was conducted, including the following baseline variables: age, sex, New York Heart Association class, aetiology, QRS morphology, QRS duration, left ventricular ejection fraction (LVEF), and systolic blood pressure. Outcomes were all-cause mortality and first hospitalization for HF or death. Of 3782 patients in sinus rhythm, median (inter-quartile range) age was 66 (58-73) years, QRS duration was 160 (146-176) ms, LVEF was 24 (20-28)%, and 78% had left bundle branch block. A multivariable model suggested that only QRS duration predicted the magnitude of the effect of CRT on outcomes. Further analysis produced estimated hazard ratios for the effect of CRT on all-cause mortality and on the composite of first hospitalization for HF or death that suggested increasing benefit with increasing QRS duration, the 95% confidence bounds excluding 1.0 at ∼140 ms for each endpoint, suggesting a high probability of substantial benefit from CRT when QRS duration exceeds this value.
QRS duration is a powerful predictor of the effects of CRT on morbidity and mortality in patients with symptomatic HF and left ventricular systolic dysfunction who are in sinus rhythm. QRS morphology did not provide additional information about clinical response.
NCT00170300, NCT00271154, NCT00251251.
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