PacBio high fidelity (HiFi) sequencing reads are both long (15-20 kb) and highly accurate (> Q20). Because of these properties, they have revolutionised genome assembly leading to more accurate and ...contiguous genomes. In eukaryotes the mitochondrial genome is sequenced alongside the nuclear genome often at very high coverage. A dedicated tool for mitochondrial genome assembly using HiFi reads is still missing.
MitoHiFi was developed within the Darwin Tree of Life Project to assemble mitochondrial genomes from the HiFi reads generated for target species. The input for MitoHiFi is either the raw reads or the assembled contigs, and the tool outputs a mitochondrial genome sequence fasta file along with annotation of protein and RNA genes. Variants arising from heteroplasmy are assembled independently, and nuclear insertions of mitochondrial sequences are identified and not used in organellar genome assembly. MitoHiFi has been used to assemble 374 mitochondrial genomes (368 Metazoa and 6 Fungi species) for the Darwin Tree of Life Project, the Vertebrate Genomes Project and the Aquatic Symbiosis Genome Project. Inspection of 60 mitochondrial genomes assembled with MitoHiFi for species that already have reference sequences in public databases showed the widespread presence of previously unreported repeats.
MitoHiFi is able to assemble mitochondrial genomes from a wide phylogenetic range of taxa from Pacbio HiFi data. MitoHiFi is written in python and is freely available on GitHub ( https://github.com/marcelauliano/MitoHiFi ). MitoHiFi is available with its dependencies as a Docker container on GitHub (ghcr.io/marcelauliano/mitohifi:master).
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The availability of direct‐acting antiviral agents for the treatment of hepatitis C virus (HCV) infection has resulted in a profound shift in the approach to the management of this infection. These ...changes have affected the practice of solid organ transplantation by altering the framework by which patients with end‐stage organ disease are managed and receive organ transplants. The high level of safety and efficacy of these medications in patients with chronic HCV infection provides the opportunity to explore their use in the setting of transplanting organs from HCV‐viremic patients into non–HCV‐viremic recipients. Because these organs are frequently discarded and typically come from younger donors, this approach has the potential to save lives on the solid organ transplant waitlist. Therefore, an urgent need exists for prospective research protocols that study the risk versus benefit of using organs for hepatitis C–infected donors. In response to this rapidly changing practice and the need for scientific study and consensus, the American Society of Transplantation convened a meeting of experts to review current data and develop the framework for the study of using HCV viremic organs in solid organ transplantation.
This article summarizes key points from a recent multidisciplinary meeting addressing the expansion of transplanting hepatitis C virus–infected donor organs in solid organ recipients. Fishman and Forns respond in an editorial on page 2755, and the conversation continues in the Letters to the Editor section (pages 2986, 2988, 2989).
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The prevalence of type 2 diabetes mellitus (T2DM) has been increasing, owing to increases in overweight and obesity, decreasing physical activity and the changing demographic structure of the ...population. People can develop T2DM without symptoms and up to 20% may be undiagnosed. They may have diabetic complications, such as retinopathy, by the time they are diagnosed, or may suffer a heart attack, without warning. Undiagnosed diabetes can be detected by raised blood glucose levels.
The aim of this review was to provide an update for the UK National Screening Committee (NSC) on screening for T2DM.
As this review was undertaken to update a previous Health Technology Assessment review published in 2007, and a more recent Scottish Public Health Network review, searches for evidence were restricted from 2009 to end of January 2012, with selected later studies added. The databases searched were MEDLINE, EMBASE, MEDLINE-in-Process & Other Non-Indexed Citations, Science Citation Index and Conference Proceedings Citation Index. The case for screening was considered against the criteria used by the NSC to assess proposed population screening programmes.
Population screening for T2DM does not meet all of the NSC criteria. Criterion 12, on optimisation of existing management, has not been met. A report by the National Audit Office (NAO) gives details of shortcomings. Criterion 13 requires evidence from high-quality randomised controlled trials that screening is beneficial. This has not been met. The Ely trial of screening showed no benefit. The ADDITION trial was not a trial of screening, but showed no benefit in cardiovascular outcomes from intensive management in people with screen-detected T2DM. Criterion 18 on staffing and facilities does not appear to have been met, according to the NAO report. Criterion 19 requires that all other options, including prevention, should have been considered. A large proportion of cases of T2DM could be prevented if people avoided becoming overweight or obese. The first stage of selection would use risk factors, using data held on general practitioner computer systems, using the QDiabetes Risk Score, or by sending out questionnaires, using the Finnish Diabetes Risk Score (FINDRISC). Those at high risk would have a measure of blood glucose. There is no perfect screening test. Glycated haemoglobin (HbA1c) testing has advantages in not requiring a fasting sample, and because it is a predictor of vascular disease across a wider range than just the diabetic one. However, it lacks sensitivity and would miss some people with diabetes. Absolute values of HbA1c may be more useful as part of overall risk assessment than a dichotomous 'diabetes or not diabetes' diagnosis. The oral glucose tolerance test is more sensitive, but inconvenient, more costly, has imperfect reproducibility and is less popular, meaning that uptake would be lower.
When considered against the NSC criteria, the case for screening is less strong than it was in the 2007 review. The main reason is the absence of cardiovascular benefit in the two trials published since the previous review. There is a case for selective screening as part of overall vascular risk assessment. Population screening for T2DM does not meet all of the NSC criteria.
The National Institute for Health Research Health Technology Assessment programme.
Summary Background Approaches to removal of sedation and mechanical ventilation for critically ill patients vary widely. Our aim was to assess a protocol that paired spontaneous awakening trials ...(SATs)—ie, daily interruption of sedatives—with spontaneous breathing trials (SBTs). Methods In four tertiary-care hospitals, we randomly assigned 336 mechanically ventilated patients in intensive care to management with a daily SAT followed by an SBT (intervention group; n=168) or with sedation per usual care plus a daily SBT (control group; n=168). The primary endpoint was time breathing without assistance. Data were analysed by intention to treat. This study is registered with ClinicalTrials.gov , number NCT00097630. Findings One patient in the intervention group did not begin their assigned treatment protocol because of withdrawal of consent and thus was excluded from analyses and lost to follow-up. Seven patients in the control group discontinued their assigned protocol, and two of these patients were lost to follow-up. Patients in the intervention group spent more days breathing without assistance during the 28-day study period than did those in the control group (14·7 days vs 11·6 days; mean difference 3·1 days, 95% CI 0·7 to 5·6; p=0·02) and were discharged from intensive care (median time in intensive care 9·1 days vs 12·9 days; p=0·01) and the hospital earlier (median time in the hospital 14·9 days vs 19·2 days; p=0·04). More patients in the intervention group self-extubated than in the control group (16 patients vs six patients; 6·0% difference, 95% CI 0·6% to 11·8%; p=0·03), but the number of patients who required reintubation after self-extubation was similar (five patients vs three patients; 1·2% difference, 95% CI −5·2% to 2·5%; p=0·47), as were total reintubation rates (13·8% vs 12·5%; 1·3% difference, 95% CI −8·6% to 6·1%; p=0·73). At any instant during the year after enrolment, patients in the intervention group were less likely to die than were patients in the control group (HR 0·68, 95% CI 0·50 to 0·92; p=0·01). For every seven patients treated with the intervention, one life was saved (number needed to treat was 7·4, 95% CI 4·2 to 35·5). Interpretation Our results suggest that a wake up and breathe protocol that pairs daily spontaneous awakening trials (ie, interruption of sedatives) with daily spontaneous breathing trials results in better outcomes for mechanically ventilated patients in intensive care than current standard approaches and should become routine practice.
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Introduction This study determined the effectiveness of the Tobacco Tactics intervention. Design/setting/participants This was a pragmatic, quasi-experimental study conducted from 2010 to 2013 and ...analyzed from 2014 to 2015 in five Michigan community hospitals; three received the Tobacco Tactics intervention, and two received usual care. Smokers (N=1,528) were identified during hospitalization, and sent surveys and cotinine tests after 6 months. Changes in pre- to post-intervention quit rates in the intervention sites were compared with usual care control sites. Intervention The toolkit for nurses included: (1) 1 continuing education unit contact hour for training; (2) a PowerPoint presentation on behavioral and pharmaceutical interventions; (3) a pocket card entitled “Helping Smokers Quit: A Guide for Clinicians”; (4) behavioral and pharmaceutical protocols; and (5) a computerized template for documentation. The toolkit for patients included: (1) a brochure; (2) a cessation DVD; (3) the Tobacco Tactics manual; (4) a 1-800-QUIT-NOW card; (5) nurse behavioral counseling and pharmaceuticals; (6) physician reminders to offer brief advice to quit coupled with medication sign-off; and (7) follow-up phone calls by trained hospital volunteers. Main outcome measures The effectiveness of the intervention was measured by 6-month 30-day point prevalence; self-reported quit rates with NicAlert® urinary biochemical verification (48-hour detection period); and the use of electronic medical record data among non-responders. Results There were significant improvements in pre- to post-intervention self-reported quit rates (5.7% vs 16.5%, p <0.001) and cotinine-verified quit rates (4.3% vs 8.0%, p <0.05) in the intervention sites compared with no change in the control sites. Propensity-adjusted multivariable analyses showed a significant improvement in self-reported 6-month quit rates from the pre- to post-intervention time periods in the intervention sites compared to the control sites ( p =0.044) and a non–statistically significant improvement in the cotinine-verified 6-month quit rate. Conclusions The Tobacco Tactics intervention, which meets the Joint Commission standards for inpatient smoking, has the potential to significantly decrease smoking among inpatient smokers. Trial Registration This study is registered at www.clinicaltrial.gov NCT01309217.
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Highlights • Implementing electronic hand hygiene monitoring systems is challenging. • Well-planned implementation strategies and sharing of best practices is key. • Meaningful use of data empowers ...staff and supports patient safety goals. • Strategies must also include plans for ongoing support and maintenance.
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We report the first detection of hepatitis E virus in rabbits in Australia. While conducting metatranscriptomic sequencing of liver samples collected from domestic rabbits that had died, we detected ...hepatitis E virus in three samples. Two viral genome sequences were obtained, which shared 96% nucleotide identity and clustered with hepatitis E strains isolated from rabbits and humans in Europe. This raises a potential public health risk in Australia, as the abundance of wild rabbits and the increasing popularity of domestic rabbits as pets represent a substantial human/rabbit interface to allow for potential zoonotic infections to occur.
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Nucleic acid amplification is enormously useful to the biotechnology and clinical diagnostic communities; however, to date point-of-use PCR has been hindered by thermal cycling architectures and ...protocols that do not allow for near-instantaneous results. In this work we demonstrate PCR amplification of synthetic SARS respiratory pathogenic targets and bacterial genomic DNA in less than three minutes in a hardware configuration utilizing convenient sample loading and disposal. Instead of sample miniaturization techniques, near-instantaneous heating and cooling of 5 μL reaction volumes is enabled by convective heat transfer of a thermal fluid through porous media combined with an integrated electrical heater. This method of rapid heat transfer has enabled 30 cycles of PCR amplification to be completed in as little as two minutes and eighteen seconds. Surprisingly, multiple enzymes have been shown to work at these breakthrough speeds on our system. A tool for measuring enzyme kinetics now exists and can allow polymerase optimization through directed evolution studies. Pairing this instrument technology with modified polymerases should result in a new paradigm for high-throughput, ultra-fast PCR and will hopefully improve our ability to quickly respond to the next viral pandemic.
Oxidative stress with dysregulated inflammation are hallmarks of sepsis. Zinc and selenium have important antioxidant functions, such that they could be important in patients with sepsis. We used an ...in vitro approach to assess the effect of zinc and selenium on oxidative stress, mitochondrial function, and inflammatory responses in conditions mimicking sepsis and related the findings to plasma concentrations and biomarkers in patients with and without sepsis.
Human endothelial cells were exposed to a range of zinc and selenium concentrations in conditions mimicking sepsis. Zinc, selenium, and a series of biomarkers of oxidative stress and inflammation were measured in plasma from critically ill patients with and without sepsis.
Culturing cells with different concentrations of zinc caused altered zinc transporter protein expression and cellular zinc content, and selenium affected glutathione peroxidase 3 activity. Although zinc or selenium at physiological concentrations had no effect on interleukin-6 release in vitro, higher concentrations of the trace elements were associated with improved mitochondrial function. Plasma zinc and selenium concentrations were low in patients zinc: median (range) 4.6 (2.1–6.5) μM in control patients without sepsis and 3.1 (1.5–5.4) μM in patients with sepsis, P=0.002; and selenium: 0.78 (0.19–1.32) μM in control patients and 0.42 (0.22–0.91) μM in sepsis patients, P=0.0009. Plasma concentrations of interleukin-6, other biomarkers of inflammation, and markers of oxidative damage to proteins and lipids were elevated, particularly in patients with sepsis, and were inversely related to plasma zinc and selenium concentrations.
Zinc and selenium concentrations were reduced in critically ill patients, with increased oxidative stress and inflammatory biomarkers, particularly in patients with sepsis. Oxidative stress as a result of suboptimal selenium and zinc concentrations might contribute to damage of key proteins.
ClinicalTrials.gov: registration number NCT01328509.
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The first gamma-ray burst (GRB) confirmed to be bright enough to be seen with the naked eye, GRB 080319B at redshift z = 0.937, allowed for exquisite follow-up observations across the electromagnetic ...spectrum. We present our detailed optical and infrared (IR) observations of the afterglow, consisting of over 5000 images starting 51 s after the GRB trigger, in concert with our own analysis of the Swift UVOT, Burst Alert Telescope (BAT), and XRT data. The event is extreme not only in observed properties but also intrinsically: it was the most luminous event ever recorded at optical and IR wavelengths and had an exceedingly high isotropic-equivalent energy release in gamma -rays. At early times, the afterglow evolution is broadly consistent with being reverse-shock dominated, but then is subsumed by a forward shock at around 1000 s. The overall spectral energy distribution, spanning from ultraviolet through near-IR wavelengths, shows no evidence for a significant amount of dust extinction in the host frame. The afterglow evolution, however, is highly chromatic: starting at about 1000 s the index shifts blueward before shifting back to the red at late times. In our deepest late-time observations, we find tentative evidence for an optical jet break and a luminous supernova. Finally, we examine the detectability of such events with current and future facilities and find that such an event could be detected in gamma rays by BAT out to z = 10.7 (8 sigma ), while the nominal EXIST sensitivity would allow detection to z 32. At the K band, this source would have been easily detected with meter-class telescopes to z 17.
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