Neural Network Based Methods for the Survival Analysis of Idiopathic Pulmonary Fibrosis Patients from a Baseline CT Acquisition

Idiopathic pulmonary fibrosis is an interstitial lung disease that causes scarring of the lungs, leading to a decline in lung function and eventually death. Because this disease has a heterogeneous disease progression, predictive models could guide clinicians in making decisions about disease management. Some survival analysis methods, such as Cox, seek to rank participants based on their predicted survivability. However, Cox cannot directly output a survival time. DeepHit is a neural network based survival analysis method which predicts the most likely histogram bin of survival time. A disadvantage of DeepHit is that, when training, an error of one year is equivalent to an error of one hundred years. A common problem encountered is that training data is often censored, where the exact time of death is unknown except that it is past a censoring time. Here, a comparison of neural network approaches utilising five different losses is presented. Compared are; ranking based approaches (such as Cox or Cox with a memory bank of previous predictions) and death distribution based approaches (such as DeepHit and likelihood with a uniform or Gaussian distribution to sample censoring times). The input to each model is a single computed tomography volume (plus optionally clinical features) and the output is a survival time. Improvements over previous work includes; a larger model with a learned downsampling, a parameterised activation (which starts linear and becomes non-linear), a softplus output, orthogonal initialisation, an optimiser integrating weight decay, gradient accumulation, and an annealed learning rate. Evaluations used include; mean and relative absolute error, the concordance index, the Brier score, and a visual analysis of Grad-CAM results. Overall, the likelihood models performed the best, with DeepHit a close second and both Cox models a distant last. The uniform likelihood model performed marginally better than the alternative

CenTime: Event-conditional modelling of censoring in survival analysis

Survival analysis is a valuable tool for estimating the time until specific events, such as death or cancer recurrence, based on baseline observations. This is particularly useful in healthcare to prognostically predict clinically important events based on patient data. However, existing approaches often have limitations; some focus only on ranking patients by survivability, neglecting to estimate the actual event time, while others treat the problem as a classification task, ignoring the inherent time-ordered structure of the events. Additionally, the effective utilisation of censored samples−data points where the event time is unknown− is essential for enhancing the model's predictive accuracy. In this paper, we introduce CenTime, a novel approach to survival analysis that directly estimates the time to event. Our method features an innovative event-conditional censoring mechanism that performs robustly even when uncensored data is scarce. We demonstrate that our approach forms a consistent estimator for the event model parameters, even in the absence of uncensored data. Furthermore, CenTime is easily integrated with deep learning models with no restrictions on batch size or the number of uncensored samples. We compare our approach to standard survival analysis methods, including the Cox proportional-hazard model and DeepHit. Our results indicate that CenTime offers state-of-the-art performance in predicting time-to-death while maintaining comparable ranking performance. Our implementation is publicly available at https://github.com/ahmedhshahin/CenTime

Protection and mechanism of action of a novel human respiratory syncytial virus vaccine candidate based on the extracellular domain of small hydrophobic protein

Infections with human respiratory syncytial virus (HRSV) occur globally in all age groups and can have devastating consequences in young infants. We demonstrate that a vaccine based on the extracellular domain (SHe) of the small hydrophobic (SH) protein of HRSV, reduced viral replication in challenged laboratory mice and in cotton rats. We show that this suppression of viral replication can be transferred by serum and depends on a functional IgG receptor compartment with a major contribution of FcRI and FcRIII. Using a conditional cell depletion method, we provide evidence that alveolar macrophages are involved in the protection by SHe-specific antibodies. HRSV-infected cells abundantly express SH on the cell surface and are likely the prime target of the humoral immune response elicited by SHe-based vaccination. Finally, natural infection of humans and experimental infection of mice or cotton rats does not induce a strong immune response against HRSV SHe. Using SHe as a vaccine antigen induces immune protection against HRSV by a mechanism that differs from the natural immune response and from other HRSV vaccination strategies explored to date. Hence, HRSV vaccine candidates that aim at inducing protective neutralizing antibodies or T-cell responses could be complemented with a SHe-based antigen to further improve immune protection

Effect of four plant species on soil 15N-access and herbage yield in temporary agricultural grasslands

Positive plant diversity-productivity relationships have been reported for experimental semi-natural grasslands (Cardinale et al. 2006; Hector et al. 1999; Tilman et al. 1996) as well as temporary agricultural grasslands (Frankow-Lindberg et al. 2009; Kirwan et al. 2007; Nyfeler et al. 2009; Picasso et al. 2008). Generally, these relationships are explained, on the one hand, by niche differentiation and facilitation (Hector et al. 2002; Tilman et al. 2002) and, on the other hand, by greater probability of including a highly productive plant species in high diversity plots (Huston 1997). Both explanations accept that diversity is significant because species differ in characteristics, such as root architecture, nutrient acquisition and water use efficiency, to name a few, resulting in composition and diversity being important for improved productivity and resource use (Naeem et al. 1994; Tilman et al. 2002). Plant diversity is generally low in temporary agricultural grasslands grown for ruminant fodder production. Grass in pure stands is common, but requires high nitrogen (N) inputs. In terms of N input, two-species grass-legume mixtures are more sustainable than grass in pure stands and consequently dominate low N input grasslands (Crews and Peoples 2004; Nyfeler et al. 2009; Nyfeler et al. 2011). In temperate grasslands, N is often the limiting factor for productivity (Whitehead 1995). Plant available soil N is generally concentrated in the upper soil layers, but may leach to deeper layers, especially in grasslands that include legumes (Scherer-Lorenzen et al. 2003) and under conditions with surplus precipitation (Thorup-Kristensen 2006). To improve soil N use efficiency in temporary grasslands, we propose the addition of deep-rooting plant species to a mixture of perennial ryegrass and white clover, which are the most widespread forage plant species in temporary grasslands in a temperate climate (Moore 2003). Perennial ryegrass and white clover possess relatively shallow root systems (Kutschera and Lichtenegger 1982; Kutschera and Lichtenegger 1992) with effective rooting depths of <0.7 m on a silt loamy site (Pollock and Mead 2008). Grassland species, such as lucerne and chicory, grow their tap-roots into deep soil layers and exploit soil nutrients and water in soil layers that the commonly grown shallow-rooting grassland species cannot reach (Braun et al. 2010; Skinner 2008). Chicory grown as a catch crop after barley reduced the inorganic soil N down to 2.5 m depth during the growing season, while perennial ryegrass affected the inorganic soil N only down to 1 m depth (Thorup-Kristensen 2006). Further, on a Wakanui silt loam in New Zealand chicory extracted water down to 1.9 m and lucerne down to 2.3 m soil depth, which resulted in greater herbage yields compared with a perennial ryegrass-white clover mixture, especially for dryland plots (Brown et al. 2005). There is little information on both the ability of deep- and shallow-rooting grassland species to access soil N from different vertical soil layers and the relation of soil N-access and herbage yield in temporary agricultural grasslands. Therefore, the objective of the present work was to test the hypotheses 1) that a mixture comprising both shallow- and deep-rooting plant species has greater herbage yields than a shallow-rooting binary mixture and pure stands, 2) that deep-rooting plant species (chicory and lucerne) are superior in accessing soil N from 1.2 m soil depth compared with shallow-rooting plant species, 3) that shallow-rooting plant species (perennial ryegrass and white clover) are superior in accessing soil N from 0.4 m soil depth compared with deep-rooting plant species, 4) that a mixture of deep- and shallow-rooting plant species has greater access to soil N from three soil layers compared with a shallow-rooting two-species mixture and that 5) the leguminous grassland plants, lucerne and white clover, have a strong impact on grassland N acquisition, because of their ability to derive N from the soil and the atmosphere

Pre-Fibrillar α-Synuclein Mutants Cause Parkinson's Disease-Like Non-Motor Symptoms in Drosophila

Parkinson's disease (PD) is linked to the formation of insoluble fibrillar aggregates of the presynaptic protein α-Synuclein (αS) in neurons. The appearance of such aggregates coincides with severe motor deficits in human patients. These deficits are often preceded by non-motor symptoms such as sleep-related problems in the patients. PD-like motor deficits can be recapitulated in model organisms such as Drosophila melanogaster when αS is pan-neurally expressed. Interestingly, both these deficits are more severe when αS mutants with reduced aggregation properties are expressed in flies. This indicates that that αS aggregation is not the primary cause of the PD-like motor symptoms. Here we describe a model for PD in Drosophila which utilizes the targeted expression of αS mutants in a subset of dopadecarboxylase expressing serotonergic and dopaminergic (DA) neurons. Our results show that targeted expression of pre-fibrillar αS mutants not only recapitulates PD-like motor symptoms but also the preceding non-motor symptoms such as an abnormal sleep-like behavior, altered locomotor activity and abnormal circadian periodicity. Further, the results suggest that the observed non-motor symptoms in flies are caused by an early impairment of neuronal functions rather than by the loss of neurons due to cell death

Suboptimal management of severe menopausal symptoms by Nigerian Gynaecologists: a call for mandatory continuing medical education for physicians

<p>Abstract</p> <p>Background</p> <p>Effective management of menopause is an important way to improve the quality of life of the increasing number of older women. The study sought to find out if Nigerian Gynaecologists offer effective treatment for severe menopausal symptoms.</p> <p>Methods</p> <p>126 Nigerian Gynaecologists representing the six health zones of Nigeria were interviewed to determine the menopausal symptoms they had ever encountered in their practices, frequency of the symptoms, treatments ever offered for severe symptoms including their attitude to, and practice of hormone replacement therapy.</p> <p>Results</p> <p>A Nigerian Gynaecologist encountered an average of one patient with menopausal symptoms every three months (range: 0-3 patients per month). The commoner symptoms they encountered were hot flushes (88%), insomnia (75.4%), depression (58.0%), irritability (56.3%), night sweats (55.6%) and muscle pains (54.8%) while urinary symptoms (16.7%) and fracture (1.6%) were less common. Treatments ever offered for severe symptoms were reassurance (90.5%), anxiolytics (68.3%), analgesics (14.3), HRT (7.9%), Vitamins (4%), Beta-blockers (3.2%) and Danazol (2.4%). These treatments were offered as a matter of institutional traditions rather than being based on any evidence of their efficacy.</p> <p>Conclusion</p> <p>The result revealed that most Nigerian Gynaecologists prefer reassurance and anxiolytics for managing severe menopausal symptoms instead of evidence-based effective therapies. A policy of mandatory continuing medical education for Nigerian physicians is recommended to ensure evidence-based management of gynaecological problems, including menopause.</p

Mechanical versus manual chest compressions in the treatment of in-hospital cardiac arrest patients in a non-shockable rhythm : a randomised controlled feasibility trial (COMPRESS-RCT)

Background Mechanical chest compression devices consistently deliver high-quality chest compressions. Small very low-quality studies suggest mechanical devices may be effective as an alternative to manual chest compressions in the treatment of adult in-hospital cardiac arrest patients. The aim of this feasibility trial is to assess the feasibility of conducting an effectiveness trial in this patient population. Methods COMPRESS-RCT is a multi-centre parallel group feasibility randomised controlled trial, designed to assess the feasibility of undertaking an effectiveness to compare the effect of mechanical chest compressions with manual chest compressions on 30-day survival following in-hospital cardiac arrest. Over approximately two years, 330 adult patients who sustain an in-hospital cardiac arrest and are in a non-shockable rhythm will be randomised in a 3:1 ratio to receive ongoing treatment with a mechanical chest compression device (LUCAS 2/3, Jolife AB/Stryker, Lund, Sweden) or continued manual chest compressions. It is intended that recruitment will occur on a 24/7 basis by the clinical cardiac arrest team. The primary study outcome is the proportion of eligible participants randomised in the study during site operational recruitment hours. Participants will be enrolled using a model of deferred consent, with consent for follow-up sought from patients or their consultee in those that survive the cardiac arrest event. The trial will have an embedded qualitative study, in which we will conduct semi-structured interviews with hospital staff to explore facilitators and barriers to study recruitment. Discussion The findings of COMPRESS-RCT will provide important information about the deliverability of an effectiveness trial to evaluate the effect on 30-day mortality of routine use of mechanical chest compression devices in adult in-hospital cardiac arrest patients

Is it reliable to assess visual attention of drivers affected by Parkinson's disease from the backseat?—a simulator study

BACKGROUND: Current methods of determining licence retainment or cancellation is through on-road driving tests. Previous research has shown that occupational therapists frequently assess drivers' visual attention while sitting in the back seat on the opposite side of the driver. Since the eyes of the driver are not always visible, assessment by eye contact becomes problematic. Such procedural drawbacks may challenge validity and reliability of the visual attention assessments. In terms of correctly classified attention, the aim of the study was to establish the accuracy and the inter-rater reliability of driving assessments of visual attention from the back seat. Furthermore, by establishing eye contact between the assessor and the driver through an additional mirror on the wind screen, the present study aimed to establish how much such an intervention would enhance the accuracy of the visual attention assessment. METHODS: Two drivers with Parkinson's disease (PD) and six control drivers drove a fixed route in a driving simulator while wearing a head mounted eye tracker. The eye tracker data showed where the foveal visual attention actually was directed. These data were time stamped and compared with the simultaneous manual scoring of the visual attention of the drivers. In four of the drivers, one with Parkinson's disease, a mirror on the windscreen was set up to arrange for eye contact between the driver and the assessor. Inter-rater reliability was performed with one of the Parkinson drivers driving, but without the mirror. RESULTS: Without mirror, the overall accuracy was 56% when assessing the three control drivers and with mirror 83%. However, for the PD driver without mirror the accuracy was 94%, whereas for the PD driver with a mirror the accuracy was 90%. With respect to the inter-rater reliability, a 73% agreement was found. CONCLUSION: If the final outcome of a driving assessment is dependent on the subcategory of a protocol assessing visual attention, we suggest the use of an additional mirror to establish eye contact between the assessor and the driver. The clinicians' observations on-road should not be a standalone assessment in driving assessments. Instead, eye trackers should be employed for further analyses and correlation in cases where there is doubt about a driver's attention

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Spatial and Seasonal Distribution of American Whaling and Whales in the Age of Sail

American whalemen sailed out of ports on the east coast of the United States and in California from the 18th to early 20th centuries, searching for whales throughout the world’s oceans. From an initial focus on sperm whales (Physeter macrocephalus) and right whales (Eubalaena spp.), the array of targeted whales expanded to include bowhead whales (Balaena mysticetus), humpback whales (Megaptera novaeangliae), and gray whales (Eschrichtius robustus). Extensive records of American whaling in the form of daily entries in whaling voyage logbooks contain a great deal of information about where and when the whalemen found whales. We plotted daily locations where the several species of whales were observed, both those caught and those sighted but not caught, on world maps to illustrate the spatial and temporal distribution of both American whaling activity and the whales. The patterns shown on the maps provide the basis for various inferences concerning the historical distribution of the target whales prior to and during this episode of global whaling