Investigating the effects of long-term dornase alfa use on lung function using registry data.

BACKGROUND: Dornase alfa (DNase) is one of the commonest cystic fibrosis (CF) treatments and is often used for many years. However, studies have not evaluated the effectiveness of its long-term use. We aimed to use UK CF Registry data to investigate the effects of one-, two-, three-, four- and five-years of DNase use on lung function to see if the benefits of short-term treatment use are sustained long term. METHODS: We analysed data from 4,198 people in the UK CF Registry from 2007 to 2015 using g-estimation. By controlling for time-dependent confounding we estimated the effects of long-term DNase use on percent predicted FEV1 (ppFEV1) and investigated whether the effect differed by ppFEV1 at treatment initiation or by age. RESULTS: Considering the population as a whole, there was no significant effect of one-year's use of DNase; change in ppFEV1 over one year was -0.1% in the treated compared to the untreated (p = 0.51) and this did not change with long-term use. However, treatment was estimated to be more beneficial in people with lower lung function (p  70%

A novel 3D volumetric method for directly quantifying porosity and pore space morphology in flocculated suspended sediments.

Flocculated suspended sediments (flocs) are found in a variety of environments globally, and their transport and behavior bear substantial importance to several industries including fisheries, aquaculture, and shipping. Additionally, the modelling of their behavior is important for estuarine and coastal flood prediction and defence, and the process of flocculation occurs in other unrelated industries such as paper and chemical production. Floc porosity is conventionally assessed using inferential indirect or proxy data approaches. These methods underestimate floc porosity % by c. 30% and cannot measure the micro-scale complexity of these pore spaces and networks, rendering inputs to models sub-optimal. This study introduces a novel 3D porosity and pore space quantification protocol, that produces directly quantified porosity % and pore space data.•3D floc data from micro-CT scanning is segmented volumetrically•This segmented volume is quantified to extract porosity and several pore space parameters from the floc structure

A structure-function based approach to floc hierarchy and evidence for the non-fractal nature of natural sediment flocs

Abstract Natural sediment flocs are fragile, highly irregular, loosely bound aggregates comprising minerogenic and organic material. They contribute a major component of suspended sediment load and are critical for the fate and flux of sediment, carbon and pollutants in aquatic environments. Understanding their behaviour is essential to the sustainable management of waterways, fisheries and marine industries. For several decades, modelling approaches have utilised fractal mathematics and observations of two dimensional (2D) floc size distributions to infer levels of aggregation and predict their behaviour. Whilst this is a computationally simple solution, it is highly unlikely to reflect the complexity of natural sediment flocs and current models predicting fine sediment hydrodynamics are not efficient. Here, we show how new observations of fragile floc structures in three dimensions (3D) demonstrate unequivocally that natural flocs are non-fractal. We propose that floc hierarchy is based on observations of 3D structure and function rather than 2D size distribution. In contrast to fractal theory, our data indicate that flocs possess characteristics of emergent systems including non-linearity and scale-dependent feedbacks. These concepts and new data to quantify floc structures offer the opportunity to explore new emergence-based floc frameworks which better represent natural floc behaviour and could advance our predictive capacity

Abnormal temporal lobe morphology in asymptomatic relatives of patients with hippocampal sclerosis: A replication study.

We investigated gray and white matter morphology in patients with mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE+HS) and first-degree asymptomatic relatives of patients with mTLE+HS. Using T1-weighted magnetic resonance imaging (MRI), we sought to replicate previously reported findings of structural surface abnormalities of the anterior temporal lobe in asymptomatic relatives of patients with mTLE+HS in an independent cohort. We performed whole-brain MRI in 19 patients with mTLE+HS, 14 first-degree asymptomatic relatives of mTLE+HS patients, and 32 healthy control participants. Structural alterations in patients and relatives compared to controls were assessed using automated hippocampal volumetry and cortical surface-based morphometry. We replicated previously reported cortical surface area contractions in the ipsilateral anterior temporal lobe in both patients and relatives compared to healthy controls, with asymptomatic relatives showing similar but less extensive changes than patients. These findings suggest morphologic abnormality in asymptomatic relatives of mTLE+HS patients, suggesting an inherited brain structure endophenotype

Pore, live root and necromass quantification in complex heterogeneous wetland soils using X-ray computed tomography

Subsurface structures and especially the interactions between pores, roots and other organic matter elements have a strong impact on ecosystem functioning. Yet despite recent progress in the application of X-ray Computed Microtomography (µCT) to soil structure in agricultural science, applications to the more complex and heterogeneous substrates found in natural soils, specifically wetland soils, remain sparse. We apply X-ray µCT to a complex heterogenous soil and develop a robust segmentation method to quantify the pores, live roots and necromass. This approach significantly improves the detection of the organic matter elements, and gives us unprecedented detail and resolution in the segmentation of pores, live roots and necromass at a high spatial resolution (62.5 µm in this study). We identify several situations where pores and organic matter interact in the soil, including the disconnected air spaces (aerenchyma) that run within the Spartina stem and roots, tubular-shaped pores left behind by decaying roots, and lateral roots deploying within structural fragilities in the sediment. The capacity of X-ray µCT to distinguish the connected live root system from the necromass opens possibilities for applications to determine key wetland soil functions such as soil cohesivity, soil nutrient exchanges and soil carbon dynamics

First-trimester or second-trimester screening, or both, for Down's syndrome

BACKGROUND: It is uncertain how best to screen pregnant women for the presence of fetal Down's syndrome: to perform first-trimester screening, to perform second-trimester screening, or to use strategies incorporating measurements in both trimesters.METHODS: Women with singleton pregnancies underwent first-trimester combined screening (measurement of nuchal translucency, pregnancy-associated plasma protein A [PAPP-A], and the free beta subunit of human chorionic gonadotropin at 10 weeks 3 days through 13 weeks 6 days of gestation) and second-trimester quadruple screening (measurement of alpha-fetoprotein, total human chorionic gonadotropin, unconjugated estriol, and inhibin A at 15 through 18 weeks of gestation). We compared the results of stepwise sequential screening (risk results provided after each test), fully integrated screening (single risk result provided), and serum integrated screening (identical to fully integrated screening, but without nuchal translucency).RESULTS: First-trimester screening was performed in 38,167 patients; 117 had a fetus with Down's syndrome. At a 5 percent false positive rate, the rates of detection of Down's syndrome were as follows: with first-trimester combined screening, 87 percent, 85 percent, and 82 percent for measurements performed at 11, 12, and 13 weeks, respectively; with second-trimester quadruple screening, 81 percent; with stepwise sequential screening, 95 percent; with serum integrated screening, 88 percent; and with fully integrated screening with first-trimester measurements performed at 11 weeks, 96 percent. Paired comparisons found significant differences between the tests, except for the comparison between serum integrated screening and combined screening.CONCLUSIONS: First-trimester combined screening at 11 weeks of gestation is better than second-trimester quadruple screening but at 13 weeks has results similar to second-trimester quadruple screening. Both stepwise sequential screening and fully integrated screening have high rates of detection of Down's syndrome, with low false positive rates

Basal topographic controls on rapid retreat of Humboldt Glacier, northern Greenland

This is the final version of the article. Available from CUP via the DOI in this record.Discharge from marine-terminating outlet glaciers accounts for up to half the recent mass loss from the Greenland ice sheet, yet the causal factors are not fully understood. Here we assess the factors controlling the behaviour of Humboldt Glacier (HG), allowing us to evaluate the influence of basal topography on outlet glacier response to external forcing since part of HG’s terminus occupies a large overdeepening. HG’s retreat accelerated dramatically after 1999, coinciding with summer atmospheric warming of up to 0.19°C a–1 and sea-ice decline. Retreat was an order of magnitude greater in the northern section of the terminus, underlain by a major basal trough, than in the southern section, where the bedrock is comparatively shallow. Velocity change following retreat was spatially non-uniform, potentially due to a pinning point near HG’s northern lateral margin. Consistent with observations, numerical modelling demonstrates an order-of-magnitude greater sensitivity to sea-ice buttressing and crevasse depth (used as a proxy for atmospheric warming) in the northern section. The trough extends up to 72 km inland, so it is likely to facilitate sustained retreat and ice loss from HG during the 21st century.Funding for this work was provided by a Durham Doctoral Studentship to J.R.C. Radio-echo sounding data were acquired and processed through UK Natural Environment Research Council (NERC) grant NE/H020667 to J.A.D. and P.C. and a G. Unger Vetlesen grant to the University of Texas Institute for Geophysics (UTIG). GrOGG laser altimetry was supported by NNXAD33G to D.D.B. This paper is UTIG contribution No. 2733. S.S.R.J. was supported by UK NERC fellowship NE/J018333/1

Complete Genome Sequence of a Novel Avian Paramyxovirus (APMV-13) Isolated from a Wild Bird in Kazakhstan.

A novel avian paramyxovirus was identified during annual viral surveillance of wild bird populations in Kazakhstan in 2013. The virus was isolated from a white fronted goose (Anser albifrons) in northern Kazakhstan. Here, we report the complete genome sequence of the isolate, which we suggest should constitute a novel serotype

The impact of pre-restoration land-use and disturbance on sediment structure, hydrology and the sediment geochemical environment in restored saltmarshes

Saltmarshes are being lost or degraded as a result of human activity resulting in loss of critical ecosystem services including the provision of wild species diversity, water quality regulation and flood regulation. To compensate, saltmarshes are being restored or re-created, usually driven by legislative requirements for increased habitat diversity, flood regulation and sustainable coastal defense. Yet, there is increasing evidence that restoration may not deliver anticipated ecosystem services; this is frequently attributed to poor drainage and sediment anoxia. However, physical sediment characteristics, hydrology and the sediment geochemical environment are rarely examined in restoration schemes, despite such factors being critical for plant succession. This study presents the novel integration of 3D-computed X-ray microtomography to quantify sediment structure and porosity, with water level and geochemical data to understand the impact of pre-restoration land use and disturbance on the structure and functioning of restored saltmarshes. The study combines a broad-scale investigation of physical sediment characteristics in nine de-embanked saltmarshes across SE England, with an intensive study at one site examining water levels, sediment structure and the sediment geochemical environment. De-embankment does not restore the hydrological regime, or the physical/chemical framework in the saltmarshes and evidence of disturbance includes a reduction in microporosity, pore connectivity and water storage capacity, a lack of connectivity between the sub-surface environment and overlying floodwaters, and impeded sub-surface water flow and drainage. This has significant consequences for the sediment geochemical environment. This disturbance is evident for at least two decades following restoration and is likely to be irreversible. It has important implications for plant establishment in particular, ecosystem services including flood regulation, nutrient cycling and wild species diversity and for future restoration design

A Personalized Self-Management Rehabilitation System for Stroke Survivors: A Quantitative Gait Analysis Using a Smart Insole.

Background: In the United Kingdom, stroke is the single largest cause of adult disability and results in a cost to the economy of £8.9 billion per annum. Service needs are currently not being met; therefore, initiatives that focus on patient-centered care that promote long-term self-management for chronic conditions should be at the forefront of service redesign. The use of innovative technologies and the ability to apply these effectively to promote behavior change are paramount in meeting the current challenges. Objective: Our objective was to gain a deeper insight into the impact of innovative technologies in support of home-based, self-managed rehabilitation for stroke survivors. An intervention of daily walks can assist with improving lower limb motor function, and this can be measured by using technology. This paper focuses on assessing the usage of self-management technologies on poststroke survivors while undergoing rehabilitation at home. Methods: A realist evaluation of a personalized self-management rehabilitation system was undertaken in the homes of stroke survivors (N=5) over a period of approximately two months. Context, mechanisms, and outcomes were developed and explored using theories relating to motor recovery. Participants were encouraged to self-manage their daily walking activity; this was achieved through goal setting and motivational feedback. Gait data were collected and analyzed to produce metrics such as speed, heel strikes, and symmetry. This was achieved using a “smart insole” to facilitate measurement of walking activities in a free-living, nonrestrictive environment. Results: Initial findings indicated that 4 out of 5 participants performed better during the second half of the evaluation. Performance increase was evident through improved heel strikes on participants’ affected limb. Additionally, increase in performance in relation to speed was also evident for all 5 participants. A common strategy emerged across all but one participant as symmetry performance was sacrificed in favor of improved heel strikes. This paper evaluates compliance and intensity of use. Conclusion: Our findings suggested that 4 out of the 5 participants improved their ability to heel strike on their affected limb. All participants showed improvements in their speed of gait measured in steps per minute with an average increase of 9.8% during the rehabilitation program. Performance in relation to symmetry showed an 8.5% average decline across participants, although 1 participant improved by 4%. Context, mechanism, and outcomes indicated that dual motor learning and compensatory strategies were deployed by the participants