Human Prion Diseases in the United States

BACKGROUND: Prion diseases are a family of rare, progressive, neurodegenerative disorders that affect humans and animals. The most common form of human prion disease, Creutzfeldt-Jakob disease (CJD), occurs worldwide. Variant CJD (vCJD), a recently emerged human prion disease, is a zoonotic foodborne disorder that occurs almost exclusively in countries with outbreaks of bovine spongiform encephalopathy. This study describes the occurrence and epidemiology of CJD and vCJD in the United States. METHODOLOGY/PRINCIPAL FINDINGS: Analysis of CJD and vCJD deaths using death certificates of US residents for 1979-2006, and those identified through other surveillance mechanisms during 1996-2008. Since CJD is invariably fatal and illness duration is usually less than one year, the CJD incidence is estimated as the death rate. During 1979 through 2006, an estimated 6,917 deaths with CJD as a cause of death were reported in the United States, an annual average of approximately 247 deaths (range 172-304 deaths). The average annual age-adjusted incidence for CJD was 0.97 per 1,000,000 persons. Most (61.8%) of the CJD deaths occurred among persons >or=65 years of age for an average annual incidence of 4.8 per 1,000,000 persons in this population. Most deaths were among whites (94.6%); the age-adjusted incidence for whites was 2.7 times higher than that for blacks (1.04 and 0.40, respectively). Three patients who died since 2004 were reported with vCJD; epidemiologic evidence indicated that their infection was acquired outside of the United States. CONCLUSION/SIGNIFICANCE: Surveillance continues to show an annual CJD incidence rate of about 1 case per 1,000,000 persons and marked differences in CJD rates by age and race in the United States. Ongoing surveillance remains important for monitoring the stability of the CJD incidence rates, and detecting occurrences of vCJD and possibly other novel prion diseases in the United States

Genetic adaptation to high altitude in the Ethiopian highlands

Background: Genomic analysis of high-altitude populations residing in the Andes and Tibet has revealed several candidate loci for involvement in high-altitude adaptation, a subset of which have also been shown to be associated with hemoglobin levels, including EPAS1, EGLN1, and PPARA, which play a role in the HIF-1 pathway. Here, we have extended this work to high- and low-altitude populations living in Ethiopia, for which we have measured hemoglobin levels. We genotyped the Illumina 1M SNP array and employed several genome wide scans for selection and targeted association with hemoglobin levels to identify genes that play a role in adaptation to high altitude. Results: We have identified a set of candidate genes for positive selection in our high-altitude population sample, demonstrated significantly different hemoglobin levels between high- and low-altitude Ethiopians and have identified a subset of candidate genes for selection, several of which also show suggestive associations with hemoglobin levels. Conclusions: We highlight several candidate genes for involvement in high-altitude adaptation in Ethiopia, including CBARA1, VAV3, ARNT2 and THRB. Although most of these genes have not been identified in previous studies of high-altitude Tibetan or Andean population samples, two of these genes (THRB and ARNT2) play a role in the HIF-1 pathway, a pathway implicated in previous work reported in Tibetan and Andean studies. These combined results suggest that adaptation to high altitude arose independently due to convergent evolution in high-altitude Amhara populations in Ethiopia

Chronic Wasting Disease and Potential Transmission to Humans

Chronic wasting disease (CWD) of deer and elk is endemic in a tri-corner area of Colorado, Wyoming, and Nebraska, and new foci of CWD have been detected in other parts of the United States. Although detection in some areas may be related to increased surveillance, introduction of CWD due to translocation or natural migration of animals may account for some new foci of infection. Increasing spread of CWD has raised concerns about the potential for increasing human exposure to the CWD agent. The foodborne transmission of bovine spongiform encephalopathy to humans indicates that the species barrier may not completely protect humans from animal prion diseases. Conversion of human prion protein by CWD-associated prions has been demonstrated in an in vitro cell-free experiment, but limited investigations have not identified strong evidence for CWD transmission to humans. More epidemiologic and laboratory studies are needed to monitor the possibility of such transmissions

The State of Addis Ababa 2021: Towards a Healthier City

The 'State of Addis Vol. II: Toward a healthier city' was written by an international multidisciplinary team, as the pandemic was unfolding. The report assesses the relationship between urban form and function and the spread of the COVID-19 pandemic, in Addis Ababa. It explores what is meant by a healthy city, and why planning for and investing in a healthy city, matters to Addis Ababa. It goes on to investigate the state of health, urban infrastructure and social services in the city. The socio-economic and health impacts of the pandemic are also explored further, together with the institutional response to the public health emergency. The findings provide insights on the role of urban form and infrastructure to urban health and urban resilience. Finally, the authors highlight a post-pandemic agenda for a healthier, more resilient city

Towards optimization-safe systems: analyzing the impact of undefined behavior

This paper studies an emerging class of software bugs called optimization-unstable code: code that is unexpectedly discarded by compiler optimizations due to undefined behavior in the program. Unstable code is present in many systems, including the Linux kernel and the Postgres database. The consequences of unstable code range from incorrect functionality to missing security checks. To reason about unstable code, this paper proposes a novel model, which views unstable code in terms of optimizations that leverage undefined behavior. Using this model, we introduce a new static checker called Stack that precisely identifies unstable code. Applying Stack to widely used systems has uncovered 160 new bugs that have been confirmed and fixed by developers.United States. Defense Advanced Research Projects Agency (DARPA Clean-slate design of Resilient, Adaptive, Secure Hosts (CRASH) program under contract #N66001-10-2-4089)National Science Foundation (U.S.) (NSF award CNS-1053143

Energy Proportionality and Workload Consolidation for Latency-Critical Applications

Energy proportionality and workload consolidation are important objectives towards increasing efficiency in large-scale datacenters. Our work focuses on achieving these goals in the presence of applications with microsecond-scale tail latency requirements. Such applications represent a growing subset of datacenter workloads and are typically deployed on dedicated servers, which is the simplest way to ensure low tail latency across all loads. Unfortunately, it also leads to low energy efficiency and low resource utilization during the frequent periods of medium or low load. We present the OS mechanisms and dynamic control needed to adjust core allocation and voltage/frequency settings based on the measured delays for latency-critical workloads. This allows for energy proportionality and frees the maximum amount of resources per server for other background applications, while respecting service-level objectives. The two key mechanism allow us to detect increases in queuing latencies and to re-assign flow groups between the threads of a latency-critical application in milliseconds without dropping or reordering packets. We compare the efficiency of our solution to the Pareto-optimal frontier of 224 distinct static configurations. Dynamic resource control saves 44%–54% of processor energy, which corresponds to 85%–93% of the Pareto-optimal upper bound. Dynamic resource control also allows background jobs to run at 32%–46% of their standalone throughput, which corresponds to 82%–92% of the Pareto bound

Mapping of Mycobacterium tuberculosis Complex Genetic Diversity Profiles in Tanzania and Other African Countries

The aim of this study was to assess and characterize Mycobacterium tuberculosis complex (MTBC) genotypic diversity in Tanzania, as well as in neighbouring East and other several African countries. We used spoligotyping to identify a total of 293 M. tuberculosis clinical isolates (one isolate per patient) collected in the Bunda, Dar es Salaam, Ngorongoro and Serengeti areas in Tanzania. The results were compared with results in the SITVIT2 international database of the Pasteur Institute of Guadeloupe. Genotyping and phylogeographical analyses highlighted the predominance of the CAS, T, EAI, and LAM MTBC lineages in Tanzania. The three most frequent Spoligotype International Types (SITs) were: SIT21/CAS1-Kili (n = 76; 25.94%), SIT59/LAM11-ZWE (n = 22; 7.51%), and SIT126/EAI5 tentatively reclassified as EAI3-TZA (n = 18; 6.14%). Furthermore, three SITs were newly created in this study (SIT4056/EAI5 n = 2, SIT4057/T1 n = 1, and SIT4058/EAI5 n = 1). We noted that the East-African-Indian (EAI) lineage was more predominant in Bunda, the Manu lineage was more common among strains isolated in Ngorongoro, and the Central-Asian (CAS) lineage was more predominant in Dar es Salaam (p-value<0.0001). No statistically significant differences were noted when comparing HIV status of patients vs. major lineages (p-value = 0.103). However, when grouping lineages as Principal Genetic Groups (PGG), we noticed that PGG2/3 group (Haarlem, LAM, S, T, and X) was more associated with HIV-positive patients as compared to PGG1 group (Beijing, CAS, EAI, and Manu) (p-value = 0.03). This study provided mapping of MTBC genetic diversity in Tanzania (containing information on isolates from different cities) and neighbouring East African and other several African countries highlighting differences as regards to MTBC genotypic distribution between Tanzania and other African countries. This work also allowed underlining of spoligotyping patterns tentatively grouped within the newly designated EAI3-TZA lineage (remarkable by absence of spacers 2 and 3, and represented by SIT126) which seems to be specific to Tanzania. However, further genotyping information would be needed to confirm this specificity