Current estimates of global flood exposure are made using datasets that distribute population counts homogenously across large lowland floodplain areas. When intersected with simulated water depths, ...this results in a significant mis-estimation. Here, we use new highly resolved population information to show that, in reality, humans make more rational decisions about flood risk than current demographic data suggest. In the new data, populations are correctly represented as risk-averse, largely avoiding obvious flood zones. The results also show that existing demographic datasets struggle to represent concentrations of exposure, with the total exposed population being spread over larger areas. In this analysis we use flood hazard data from a ~90 m resolution hydrodynamic inundation model to demonstrate the impact of different population distributions on flood exposure calculations for 18 developing countries spread across Africa, Asia and Latin America. The results suggest that many published large-scale flood exposure estimates may require significant revision.
The term SWEDD (scans without evidence for dopaminergic deficit) refers to the absence, rather than the presence, of an imaging abnormality in patients clinically presumed to have Parkinson's disease ...(PD). However, such a term has since been widely used in the medical literature, even as a diagnostic label. While many authors have suggested that different disorders of PD lookalikes may account for a proportion of SWEDD cases, others have claimed that some of them may have a benign subtype of PD. Thus, there has been ensuing controversy and confusion and the use of this term continues without clarity of what it represents. We have systematically reviewed all the studies involving patients with SWEDD with the aim of shedding light on what these patients actually have. It becomes clear from this systematic review that while most 'SWEDD' cases are due to a clinical misdiagnosis of PD, there exists a small proportion of patients with SWEDD who may have PD on the basis of a positive levodopa response, clinical progression, imaging and/or genetic evidence. The latter challenge the seemingly incontrovertible relationship between dopaminergic tracer binding and the diagnosis of nigrostriatal parkinsonism, particularly PD. Patients with SWEDD are unlikely to reflect a single clinical entity and we suggest that the term SWEDD should be abandoned.
Clinical diagnosis of multiple system atrophy is challenging and many patients with Lewy body disease (i.e. Parkinson's disease or dementia with Lewy bodies) or progressive supranuclear palsy are ...misdiagnosed as having multiple system atrophy in life. The clinical records of 203 patients with a clinical diagnosis of multiple system atrophy were reviewed to identify diagnostic pitfalls. We also examined 12 features supporting a diagnosis of multiple system atrophy (red flag features: orofacial dystonia, disproportionate antecollis, camptocormia and/or Pisa syndrome, contractures of hands or feet, inspiratory sighs, severe dysphonia, severe dysarthria, snoring, cold hands and feet, pathological laughter and crying, jerky myoclonic postural/action tremor and polyminimyoclonus) and seven disability milestones (frequent falls, use of urinary catheters, wheelchair dependent, unintelligible speech, cognitive impairment, severe dysphagia, residential care). Of 203 cases, 160 (78.8%) were correctly diagnosed in life and had pathologically confirmed multiple system atrophy. The remaining 21.2% (43/203) had alternative pathological diagnoses including Lewy body disease (12.8%; n = 26), progressive supranuclear palsy (6.4%; n = 13), cerebrovascular diseases (1%; n = 2), amyotrophic lateral sclerosis (0.5%; n = 1) and cerebellar degeneration (0.5%; n = 1). More patients with multiple system atrophy developed ataxia, stridor, dysphagia and falls than patients with Lewy body disease; resting tremor, pill-rolling tremor and hallucinations were more frequent in Lewy body disease. Although patients with multiple system atrophy and progressive supranuclear palsy shared several symptoms and signs, ataxia and stridor were more common in multiple system atrophy. Multiple logistic regression analysis revealed increased likelihood of multiple system atrophy versus Lewy body disease and progressive supranuclear palsy if a patient developed orthostatic hypotension or urinary incontinence with the requirement for urinary catheters multiple system atrophy versus Lewy body disease: odds ratio (OR): 2.0, 95% confidence interval (CI): 1.1-3.7, P = 0.021; multiple system atrophy versus progressive supranuclear palsy: OR: 11.2, 95% CI: 3.2-39.2, P < 0.01. Furthermore, autonomic dysfunction within the first 3 years from onset can differentiate multiple system atrophy from progressive supranuclear palsy (multiple system atrophy versus progressive supranuclear palsy: OR: 3.4, 95% CI: 1.2-9.7, P = 0.023). Multiple system atrophy patients with predominant parkinsonian signs had a higher number of red flag features than patients with Lewy body disease (OR: 8.8, 95% CI: 3.2-24.2, P < 0.01) and progressive supranuclear palsy (OR: 4.8, 95% CI: 1.7-13.6, P < 0.01). The number of red flag features in multiple system atrophy with predominant cerebellar signs was also higher than in Lewy body disease (OR: 7.0, 95% CI: 2.5-19.5, P < 0.01) and progressive supranuclear palsy (OR: 3.1, 95% CI: 1.1-8.9, P = 0.032). Patients with multiple system atrophy had shorter latency to reach use of urinary catheter and longer latency to residential care than progressive supranuclear palsy patients, whereas patients with Lewy body disease took longer to reach multiple milestones than patients with multiple system atrophy. The present study has highlighted features which should improve the ante-mortem diagnostic accuracy of multiple system atrophy.
In this paper we seek to understand the nature of flood spatial dependence over the conterminous United States. We extend an existing conditional multivariate statistical model to enable its ...application to this large and heterogenous region and apply it to a 40‐year data set of ~2,400 U.S. Geological Survey gauge series records to simulate 1,000 years of U.S. flooding comprising more than 63,000 individual events with realistic spatial dependence. A continental‐scale hydrodynamic model at 30 m resolution is then used to calculate the economic loss arising from each of these events. From this we are able to compute the probability that different values of U.S. annual total economic loss due to flooding are exceeded (i.e., a loss‐exceedance curve). Comparing these data to an observed flood loss‐exceedance curve for the period 1988–2017 shows a reasonable match for annual losses with probability below 10% (e.g., >1 in 10‐year return period). This analysis suggests that there is a 1% chance of U.S. annual fluvial flood losses exceeding $78Bn in any given year, and a 0.1% chance of them exceeding $136Bn. Analysis of the set of stochastic events and losses yields new insights into the nature of flooding and flood risk in the United States. In particular, we confirm the strong relationship between flood affected area and event peak magnitude, but show considerable variability in this relationship between adjacent U.S. regions. The analysis provides a significant advance over previous national flood risk analyses as it gives the full loss‐exceedance curve instead of simply the average annual loss.
Plain Language Summary
Traditional flood risk analyses make the assumption that flow probability (the chance that a given river discharge is exceeded) does not vary within river catchments within an event. Real floods, however, do not look like this: In some places flooding is more severe than in others. Over a few tens of kilometers of river assuming the same event return period everywhere is perfectly fine, but over larger areas it breaks down. At national scales traditional risk analyses can only estimate the average annual loss. To estimate the total annual losses that might occur in more extreme flooding years the risk analysis needs to be based on more realistic spatial patterns of flooding. In this paper we use a sophisticated statistical model, based on U.S. Geological Survey river flow data, to simulate 1,000 years of spatially realistic U.S. flooding comprising more than 63,000 individual events. By calculating the damage for each event as a dollar value, we are able to estimate the probability of the United States experiencing particular levels of annual flood losses. We show that there is a 1% chance of U.S. annual fluvial flood losses exceeding $78Bn in any given year, and a 0.1% chance of them exceeding $136Bn.
Key Points
1,000 years of realistic U.S. flood patterns, comprising >63,000 individual events, are simulated using a statistical model
Monetary losses for each event are calculated using a continental hydrodynamic model at 30 m resolution
The analysis suggests that there is a 1% chance of U.S. annual fluvial flood losses exceeding $78Bn in any given year
Troublesome involuntary movements in the absence of dopaminergic medication, so-called off-medication dyskinesias, are a serious adverse effect of fetal neural grafts that hinders the development of ...cell-based therapies for Parkinson's disease. The mechanisms underlying these dyskinesias are not well understood, and it is not known whether they are the same as in the dyskinesias induced by l-dopa treatment. Using in vivo brain imaging, we show excessive serotonergic innervation in the grafted striatum of two patients with Parkinson's disease, who had exhibited major motor recovery after transplantation with dopamine-rich fetal mesencephalic tissue but had later developed off-medication dyskinesias. The dyskinesias were markedly attenuated by systemic administration of a serotonin 5-hydroxytryptamine (5-HT) receptor (5-HT(1A)) agonist, which dampens transmitter release from serotonergic neurons, indicating that the dyskinesias were caused by the serotonergic hyperinnervation. Our observations suggest strategies for avoiding and treating graft-induced dyskinesias that result from cell therapies for Parkinson's disease with fetal tissue or stem cells.
Summary Background Surgical intervention for advanced Parkinson's disease is an option if medical therapy fails to control symptoms adequately. We aimed to assess whether surgery and best medical ...therapy improved self-reported quality of life more than best medical therapy alone in patients with advanced Parkinson's disease. Methods The PD SURG trial is an ongoing randomised, open-label trial . At 13 neurosurgical centres in the UK, between November, 2000, and December, 2006, patients with Parkinson's disease that was not adequately controlled by medical therapy were randomly assigned by use of a computerised minimisation procedure to immediate surgery (lesioning or deep brain stimulation at the discretion of the local clinician) and best medical therapy or to best medical therapy alone. Patients were analysed in the treatment group to which they were randomised, irrespective of whether they received their allocated treatment. The primary endpoint was patient self-reported quality of life on the 39-item Parkinson's disease questionnaire (PDQ-39). Changes between baseline and 1 year were compared by use of t tests. This trial is registered with Current Controlled Trials , number ISRCTN34111222. Findings 366 patients were randomly assigned to receive immediate surgery and best medical therapy (183) or best medical therapy alone (183). All patients who had surgery had deep brain stimulation. At 1 year, the mean improvement in PDQ-39 summary index score compared with baseline was 5·0 points in the surgery group and 0·3 points in the medical therapy group (difference −4·7, 95% CI −7·6 to −1·8; p=0·001); the difference in mean change in PDQ-39 score in the mobility domain between the surgery group and the best medical therapy group was −8·9 (95% CI −13·8 to −4·0; p=0·0004), in the activities of daily living domain was −12·4 (−17·3 to −7·5; p<0·0001), and in the bodily discomfort domain was −7·5 (−12·6 to −2·4; p=0·004). Differences between groups in all other domains of the PDQ-39 were not significant. 36 (19%) patients had serious surgery-related adverse events; there were no suicides but there was one procedure-related death. 20 patients in the surgery group and 13 in the best medical therapy group had serious adverse events related to Parkinson's disease and drug treatment. Interpretation At 1 year, surgery and best medical therapy improved patient self-reported quality of life more than best medical therapy alone in patients with advanced Parkinson's disease. These differences are clinically meaningful, but surgery is not without risk and targeting of patients most likely to benefit might be warranted. Funding UK Medical Research Council, Parkinson's UK, and UK Department of Health.
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