Forced vital capacity trajectories in patients with idiopathic pulmonary fibrosis: a secondary analysis of a multicentre, prospective, observational cohort

BACKGROUND: Idiopathic pulmonary fibrosis is a progressive fibrotic lung disease with a variable clinical trajectory. Decline in forced vital capacity (FVC) is the main indicator of progression; however, missingness prevents long-term analysis of patterns in lung function. We aimed to identify distinct clusters of lung function trajectory among patients with idiopathic pulmonary fibrosis using machine learning techniques. METHODS: We did a secondary analysis of longitudinal data on FVC collected from a cohort of patients with idiopathic pulmonary fibrosis from the PROFILE study; a multicentre, prospective, observational cohort study. We evaluated the imputation performance of conventional and machine learning techniques to impute missing data and then analysed the fully imputed dataset by unsupervised clustering using self-organising maps. We compared anthropometric features, genomic associations, serum biomarkers, and clinical outcomes between clusters. We also performed a replication of the analysis on data from a cohort of patients with idiopathic pulmonary fibrosis from an independent dataset, obtained from the Chicago Consortium. FINDINGS: 415 (71%) of 581 participants recruited into the PROFILE study were eligible for further analysis. An unsupervised machine learning algorithm had the lowest imputation error among tested methods, and self-organising maps identified four distinct clusters (1-4), which was confirmed by sensitivity analysis. Cluster 1 comprised 140 (34%) participants and was associated with a disease trajectory showing a linear decline in FVC over 3 years. Cluster 2 comprised 100 (24%) participants and was associated with a trajectory showing an initial improvement in FVC before subsequently decreasing. Cluster 3 comprised 113 (27%) participants and was associated with a trajectory showing an initial decline in FVC before subsequent stabilisation. Cluster 4 comprised 62 (15%) participants and was associated with a trajectory showing stable lung function. Median survival was shortest in cluster 1 (2·87 years [IQR 2·29-3·40]) and cluster 3 (2·23 years [1·75-3·84]), followed by cluster 2 (4·74 years [3·96-5·73]), and was longest in cluster 4 (5·56 years [5·18-6·62]). Baseline FEV1 to FVC ratio and concentrations of the biomarker SP-D were significantly higher in clusters 1 and 3. Similar lung function clusters with some shared anthropometric features were identified in the replication cohort. INTERPRETATION: Using a data-driven unsupervised approach, we identified four clusters of lung function trajectory with distinct clinical and biochemical features. Enriching or stratifying longitudinal spirometric data into clusters might optimise evaluation of intervention efficacy during clinical trials and patient management. FUNDING: National Institute for Health and Care Research, Medical Research Council, and GlaxoSmithKline

Age-Related Attenuation of Dominant Hand Superiority

The decline of motor performance of the human hand-arm system with age is well-documented. While dominant hand performance is superior to that of the non-dominant hand in young individuals, little is known of possible age-related changes in hand dominance. We investigated age-related alterations of hand dominance in 20 to 90 year old subjects. All subjects were unambiguously right-handed according to the Edinburgh Handedness Inventory. In Experiment 1, motor performance for aiming, postural tremor, precision of arm-hand movement, speed of arm-hand movement, and wrist-finger speed tasks were tested. In Experiment 2, accelerometer-sensors were used to obtain objective records of hand use in everyday activities

CITES, wild plants, and opportunities for crime

The illegal trade in endangered plants damages both the environment and local communities by threatening and destroying numerous species and important natural resources. There is very little research which systematically addresses this issue by identifying specific opportunities for crime. This article presents the results of an interdisciplinary study which brings together criminological and conservation science expertise to identify criminal opportunities in the illegal wild plant trade and suggest strategies in order to prevent and mitigate the problem. Methodologically, the study adapts a crime proofing of legislation approach to the UN Convention on the International Trade in Endangered Species of Wild Fauna and Flora and is based on documentary and interview data. Situational crime prevention is used as a framework to provide points for effective intervention

Cutaneous lesions of the external ear

Skin diseases on the external aspect of the ear are seen in a variety of medical disciplines. Dermatologists, othorhinolaryngologists, general practitioners, general and plastic surgeons are regularly consulted regarding cutaneous lesions on the ear

Mitoxantrone Induces Natural Killer Cell Maturation in Patients with Secondary Progressive Multiple Sclerosis

Mitoxantrone is one of the few drugs approved for the treatment of progressive multiple sclerosis (MS). However, the prolonged use of this potent immunosuppressive agent is limited by the appearance of severe side effects. Apart from its general cytotoxic effect, the mode of action of mitoxantrone on the immune system is poorly understood. Thus, to develop safe therapeutic approaches for patients with progressive MS, it is essential to elucidate how mitoxantrone exerts it benefits. Accordingly, we initiated a prospective single-arm open-label study with 19 secondary progressive MS patients. We investigated long-term effects of mitoxantrone on patient peripheral immune subsets using flow cytometry. While we corroborate that mitoxantrone persistently suppresses B cells in vivo, we show for the first time that treatment led to an enrichment of neutrophils and immunomodulatory CD8low T cells. Moreover, sustained mitoxantrone applications promoted not only persistent NK cell enrichment but also NK cell maturation. Importantly, this mitoxantrone-induced NK cell maturation was seen only in patients that showed a clinical response to treatment. Our data emphasize the complex immunomodulatory role of mitoxantrone, which may account for its benefit in MS. In particular, these results highlight the contribution of NK cells to mitoxantrone efficacy in progressive MS

Macular thickness measurements in healthy Norwegian volunteers: an optical coherence tomography study

<p>Abstract</p> <p>Background</p> <p>Ethnic, intersubject, interoperator and intermachine differences in measured macular thickness seem to exist. Our purpose was to collect normative macular thickness data in Norwegians and to evaluate the association between macular thickness and age, gender, parity, and contraception status.</p> <p>Methods</p> <p>Retinal thickness was measured by Stratus Optical Coherence Tomography in healthy subjects. Mean macular thickness (MMT) was analyzed by repeated measures ANOVA with three dependent regional MMT-variables for interaction with age, gender, parity and oral contraception use. Exploratory correlation with age by the Pearson correlation test, both before and after stratification by gender was performed. Differences in MMT between older and younger subjects, between oral contraception users and non-users, as well as parous and nulliparous women were studied by post-hoc Student's t-tests.</p> <p>Results</p> <p>Central MMT in Norwegians was similar to values earlier reported in whites. MMT in central areas of 1 and 2.25 mm in diameter were higher in males than in females. In younger subjects (≤43 years) differences in MMT between genders were larger than in the mixed age group, whereas in older subjects (>43 years) the small differences did not reach the set significance level. No differences were found in minimal foveolar thickness (MMFT) between the genders in any age group.</p> <p>Mean foveal thickness (1 mm in diameter) was positively associated with age in females (r = 0.28, p = 0.03). MMFT was positively associated with age in all groups and reached significance both in females and in mixed gender group (r = 0.20, p = 0.041 and r = 0.26, p = 0.044 respectively).</p> <p>Mean foveal thickness and MMFT were significantly higher in parous than in nulliparous women, and age-adjusted ANOVA for MMFT revealed a borderline effect of parity.</p> <p>Conclusions</p> <p>Age and gender should be taken into consideration when establishing normal ranges for MMT in younger subjects. The gender difference in retinal thickness in young, but not older adults suggests a gonadal hormonal influence. The possible association between parity and retinal structure and its clinical relevance, should be studied further.</p

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta