Summary Background Encephalitis has many causes, but for most patients the cause is unknown. We aimed to establish the cause and identify the clinical differences between causes in patients with ...encephalitis in England. Methods Patients of all ages and with symptoms suggestive of encephalitis were actively recruited for 2 years (staged start between October, 2005, and November, 2006) from 24 hospitals by clinical staff. Systematic laboratory testing included PCR and antibody assays for all commonly recognised causes of infectious encephalitis, investigation for less commonly recognised causes in immunocompromised patients, and testing for travel-related causes if indicated. We also tested for non-infectious causes for acute encephalitis including autoimmunity. A multidisciplinary expert team reviewed clinical presentation and hospital tests and directed further investigations. Patients were followed up for 6 months after discharge from hospital. Findings We identified 203 patients with encephalitis. Median age was 30 years (range 0–87). 86 patients (42%, 95% CI 35–49) had infectious causes, including 38 (19%, 14–25) herpes simplex virus, ten (5%, 2–9) varicella zoster virus, and ten (5%, 2–9) Mycobacterium tuberculosis ; 75 (37%, 30–44) had unknown causes. 42 patients (21%, 15–27) had acute immune-mediated encephalitis. 24 patients (12%, 8–17) died, with higher case fatality for infections from M tuberculosis (three patients; 30%, 7–65) and varicella zoster virus (two patients; 20%, 2–56). The 16 patients with antibody-associated encephalitis had the worst outcome of all groups—nine (56%, 30–80) either died or had severe disabilities. Patients who died were more likely to be immunocompromised than were those who survived (OR=3·44). Interpretation Early diagnosis of encephalitis is crucial to ensure that the right treatment is given on time. Extensive testing substantially reduced the proportion with unknown cause, but the proportion of cases with unknown cause was higher than that for any specific identified cause. Funding The Policy Research Programme, Department of Health, UK.
Most stars become white dwarfs after they have exhausted their nuclear fuel (the Sun will be one such). Between one-quarter and one-half of white dwarfs have elements heavier than helium in their ...atmospheres, even though these elements ought to sink rapidly into the stellar interiors (unless they are occasionally replenished). The abundance ratios of heavy elements in the atmospheres of white dwarfs are similar to the ratios in rocky bodies in the Solar System. This fact, together with the existence of warm, dusty debris disks surrounding about four per cent of white dwarfs, suggests that rocky debris from the planetary systems of white-dwarf progenitors occasionally pollutes the atmospheres of the stars. The total accreted mass of this debris is sometimes comparable to the mass of large asteroids in the Solar System. However, rocky, disintegrating bodies around a white dwarf have not yet been observed. Here we report observations of a white dwarf--WD 1145+017--being transited by at least one, and probably several, disintegrating planetesimals, with periods ranging from 4.5 hours to 4.9 hours. The strongest transit signals occur every 4.5 hours and exhibit varying depths (blocking up to 40 per cent of the star's brightness) and asymmetric profiles, indicative of a small object with a cometary tail of dusty effluent material. The star has a dusty debris disk, and the star's spectrum shows prominent lines from heavy elements such as magnesium, aluminium, silicon, calcium, iron, and nickel. This system provides further evidence that the pollution of white dwarfs by heavy elements might originate from disrupted rocky bodies such as asteroids and minor planets.
The human transcriptome annotation is regarded as one of the most complete of any eukaryotic species. However, limitations in sequencing technologies have biased the annotation toward multi-exonic ...protein coding genes. Accurate high-throughput long read transcript sequencing can now provide additional evidence for rare transcripts and genes such as mono-exonic and non-coding genes that were previously either undetectable or impossible to differentiate from sequencing noise.
We developed the Transcriptome Annotation by Modular Algorithms (TAMA) software to leverage the power of long read transcript sequencing and address the issues with current data processing pipelines. TAMA achieved high sensitivity and precision for gene and transcript model predictions in both reference guided and unguided approaches in our benchmark tests using simulated Pacific Biosciences (PacBio) and Nanopore sequencing data and real PacBio datasets. By analyzing PacBio Sequel II Iso-Seq sequencing data of the Universal Human Reference RNA (UHRR) using TAMA and other commonly used tools, we found that the convention of using alignment identity to measure error correction performance does not reflect actual gain in accuracy of predicted transcript models. In addition, inter-read error correction can cause major changes to read mapping, resulting in potentially over 6 K erroneous gene model predictions in the Iso-Seq based human genome annotation. Using TAMA's genome assembly based error correction and gene feature evidence, we predicted 2566 putative novel non-coding genes and 1557 putative novel protein coding gene models.
Long read transcript sequencing data has the power to identify novel genes within the highly annotated human genome. The use of parameter tuning and extensive output information of the TAMA software package allows for in depth exploration of eukaryotic transcriptomes. We have found long read data based evidence for thousands of unannotated genes within the human genome. More development in sequencing library preparation and data processing are required for differentiating sequencing noise from real genes in long read RNA sequencing data.
Tackling human fungal infections Brown, Gordon D; Denning, David W; Levitz, Stuart M
Science,
2012-May-11, 2012-05-11, 20120511, Letnik:
336, Številka:
6082
Journal Article
Recenzirano
Odprti dostop
Fungi infect billions of people every year, yet their contribution to the global burden of disease is largely unrecognized. Most are "relatively" minor infections, but millions contract diseases that ...kill at least as many people as tuberculosis or malaria. Although true mortality rates are unknown because of a lack of good epidemiological data, the incidence of invasive fungal infections is rising as a result of modern medical interventions and immunosuppressive diseases, such as AIDS. Despite the high mortality rates of invasive fungal infections, they remain understudied and underdiagnosed as compared with other infectious diseases. What can be done to remedy this unfortunate situation?
Hidden killers: human fungal infections Brown, Gordon D; Denning, David W; Gow, Neil A R ...
Science translational medicine,
2012-Dec-19, Letnik:
4, Številka:
165
Journal Article
Recenzirano
Although fungal infections contribute substantially to human morbidity and mortality, the impact of these diseases on human health is not widely appreciated. Moreover, despite the urgent need for ...efficient diagnostic tests and safe and effective new drugs and vaccines, research into the pathophysiology of human fungal infections lags behind that of diseases caused by other pathogens. In this Review, we highlight the importance of fungi as human pathogens and discuss the challenges we face in combating the devastating invasive infections caused by these microorganisms, in particular in immunocompromised individuals.
The burden of Congenital Rubella Syndrome (CRS) is typically underestimated in routine surveillance. Updated estimates are needed following the recent WHO position paper on rubella and recent GAVI ...initiatives, funding rubella vaccination in eligible countries. Previous estimates considered the year 1996 and only 78 (developing) countries.
We reviewed the literature to identify rubella seroprevalence studies conducted before countries introduced rubella-containing vaccination (RCV). These data and the estimated vaccination coverage in the routine schedule and mass campaigns were incorporated in mathematical models to estimate the CRS incidence in 1996 and 2000-2010 for each country, region and globally.
The estimated CRS decreased in the three regions (Americas, Europe and Eastern Mediterranean) which had introduced widespread RCV by 2010, reaching <2 per 100,000 live births (the Americas and Europe) and 25 (95% CI 4-61) per 100,000 live births (the Eastern Mediterranean). The estimated incidence in 2010 ranged from 90 (95% CI: 46-195) in the Western Pacific, excluding China, to 116 (95% CI: 56-235) and 121 (95% CI: 31-238) per 100,000 live births in Africa and SE Asia respectively. Highest numbers of cases were predicted in Africa (39,000, 95% CI: 18,000-80,000) and SE Asia (49,000, 95% CI: 11,000-97,000). In 2010, 105,000 (95% CI: 54,000-158,000) CRS cases were estimated globally, compared to 119,000 (95% CI: 72,000-169,000) in 1996.
Whilst falling dramatically in the Americas, Europe and the Eastern Mediterranean after vaccination, the estimated CRS incidence remains high elsewhere. Well-conducted seroprevalence studies can help to improve the reliability of these estimates and monitor the impact of rubella vaccination.
We use administrative data from the Internal Revenue Service to examine long-term impacts of childhood Medicaid eligibility expansions on outcomes in adulthood at each age from 19 to 28. Greater ...Medicaid eligibility increases college enrolment and decreases fertility, especially through age 21. Starting at age 23, females have higher contemporaneous wage income, although male increases are imprecise. Together, both genders have lower mortality. These adults collect less from the earned income tax credit and pay more in taxes. Cumulatively from ages 19 to 28, at a 3% discount rate, the federal government recoups 58 cents of each dollar of its “investment” in childhood Medicaid.
BACKGROUND/OBJECTIVE
Cigarette smoking is a significant health problem within the US military. Data from the 2003–2007 Behavioral Risk Factor Surveillance System (BRFSS) were used to estimate and ...compare the prevalence of smoking among US veterans with that of adults who did not serve in the US armed forces.
METHODS
Data from the BRFSS, a state-based random-digit dialed telephone survey supported by the Centers for Disease Control and Prevention, were used to estimate the prevalence of current smoking among adults (aged ≥18 years) who reported ever serving on active duty in the United States Armed Forces. We compared, by birth cohort, age-adjusted smoking prevalence among veterans with that of adults who did not serve in the military.
RESULTS
A total of 224,169 US veterans participated during 2003–2007. The age-adjusted prevalence of smoking during the period was 27.0% (standard error, 0.36) among veterans and 21% (0.12) among non-veterans. For both groups, the prevalence decreased across years from 29% (0.79) in 2003 to 25% (0.82) in 2007 among veterans and from 23% (0.29) in 2003 to 20% (0.26) in 2007 among non-veterans. Among veterans, smoking prevalence was highest among men born between 1975–1984 (36%; 90%CI = 33.7–37.5) and those born between 1985–1989 (37%; 90%CI = 31.7–48.2) with lower prevalences among men born between 1945–1954 (26%; 90%CI = 25.1–26.3), 1955–1964 (33%; 90%CI = 32.3–34.3), and 1965–1974 (27%; 90%CI = 26.0–28.1). The prevalence of smoking was 43% (90%CI = 39.0–47.6) among veterans with self-reported coronary heart disease (CHD), greater than that for non-veterans with CHD (31%; 90%CI = 28.6–33.1).
CONCLUSIONS
Although the prevalence of smoking has declined among US adults, there are opportunities to further reduce smoking among US veterans, particularly young veterans for whom the prevalence of smoking is similar to that of the US adult population during the late 1960s/early 1970s. Continued work is necessary to target the high smoking prevalence among veterans with CHD, a group for which smoking cessation is especially important.
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