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Single particle analysis has become a key structural biology technique. Experimental images are extremely noisy, and during iterative refinement it is possible to stably incorporate noise into the reconstruction. Such "over-fitting" can lead to misinterpretation of the structure and flawed biological results. Several strategies are routinely used to prevent over-fitting, the most common being independent refinement of two sides of a split dataset. In this study, we show that over-fitting remains an issue within regions of low local signal-to-noise, despite independent refinement of half datasets. We propose a modification of the refinement process through the application of a local signal-to-noise filter SIDESPLITTER. We show that our approach can reduce over-fitting for both idealised and experimental data while maintaining independence between the two sides of a split refinement. SIDESPLITTER refinement leads to improved density, and can also lead to improvement of the final resolution in extreme cases where datasets are prone to severe over-fitting, such as small membrane proteins.Objectives A major open question, affecting the decisions of policy makers, is the estimation of the true number of Covid-19 infections. Most of them are undetected, because of a large number of asymptomatic cases. We provide an efficient, easy to compute and robust lower bound estimator for the number of undetected cases. Methods A modified version of the Chao estimator is proposed, based on the cumulative time-series distributions of cases and deaths. Heterogeneity has been addressed by assuming a geometrical distribution underlying the data generation process. An (approximated) analytical variance of the estimator has been derived to compute reliable confidence intervals at 95% level. Results A motivating application to the Austrian situation is provided and compared with an independent and representative study on prevalence of Covid-19 infection. Our estimates match well with the results from the independent prevalence study, but the capture-recapture estimate has less uncertainty involved as it is based on a larger sample size. Results from other European countries are mentioned in the discussion. The estimated ratio of the total estimated cases to the observed cases is around the value of 2.3 for all the analyzed countries. Conclusions The proposed method answers to a fundamental open question "How many undetected cases are going around?". CR methods provide a straightforward solution to shed light on undetected cases, incorporating heterogeneity that may arise in the probability of being detected.Objectives To report atypical pathogen clinical trial data comparing delafloxacin to moxifloxacin in treatment of adults with community-acquired bacterial pneumonia (CABP). Methods Multiple diagnostic methods were employed to diagnose atypical infections including culture, serology, and urinary antigen. Results The microbiological intent-to-treat (MITT) population included 520 patients; 30% had an atypical bacterial pathogen identified (156/520). Overall, 13.1% (68/520) had monomicrobial atypical infection and 2.3% (12/520) had polymicrobial all-atypical infections. Among patients with polymicrobial infections,Streptococcus pneumoniae was the most frequently occurring co-infecting organism and Chlamydia pneumoniae was the most frequently occurring co-infecting atypical organism. For Mycoplasma pneumoniae and Legionella pneumophila, serology yielded the highest number of diagnoses. Delafloxacin and moxifloxacin had similar in-vitro activity against M. pneumoniae and delafloxacin had greater activity against L. pneumophila. Two macrolide resistant M. pneumoniae isolates were recovered. No fluoroquinolone resistant M. pneumoniae were isolated. The rates of microbiological success (documented or presumed eradication) at test-of-cure were similar between the delafloxacin and moxifloxacin groups. There was no evidence of a correlation between MIC and outcome; a high proportion of favorable outcomes were observed across all delafloxacin baseline MICs. Conclusions Delafloxacin may be considered a treatment option as monotherapy for CABP in adults, where broad spectrum coverage including atypical activity is desirable. ClinicalTrials.gov Identifier NCT03534622.Background Despite effective antibiotics and vaccines, bacterial meningitis (BM) remains one of the leading causes of morbidity and mortality in young infants worldwide. Data from Africa on the aetiology and antibiotic susceptibility are scarce. Objective To describe the aetiology of BM in Angolan infants less then 90 days of age. Methods A prospective, observational, single-site study was conducted from February 2016 to October 2017 in the Paediatric Hospital of Luanda. All cerebrospinal fluid samples (CSF) from infants aged less then 90 days with suspected BM or neonatal sepsis were assessed. The local laboratory performed microscopy, chemistry, culture, and susceptibility testing. PCR for vaccine-preventable pathogens was performed in Johannesburg, South Africa. Results Of the 1287 infants, 299 (23%) had confirmed or probable BM. Of the 212 (16%) identified bacterial isolates from CSF, the most common were Klebsiella spp (30 cases), Streptococcus pneumoniae (29 cases), Streptococcus agalactiae (20 cases), Escherichia coli (17 cases), and Staphylococcus aureus (11 cases). A fifth of pneumococci (3/14; 21%) showed decreased susceptibility to penicillin, whereas methicillin-resistant S. aureus (MRSA) was encountered in 4/11 cases (36%). Of the gram-negative isolates, 6/45 (13%) were resistant to gentamicin and 20/58 (34%) were resistant to third-generation cephalosporins. Twenty-four percent (33/135) of the BM cases were fatal, but this is likely an underestimation. selleck inhibitor Conclusions BM was common among infants less then 90 days of age in Luanda. Gram-negative bacteria were predominant and were often resistant to commonly used antibiotics. Continued surveillance of the antibiogram is pivotal to detect potential changes without delay.Recent studies have reported that surfaces and objects in the rooms of infected patients that are frequently touched by both medical staff and patients could be contaminated with SARS-CoV-2. In December 2019, Wuhan China suffered the earliest from this COVID-19 pandemic, and we took that opportunity to investigate whether the SARS-CoV-2 RNA exists in the ward environment after a long time from exposure. We found that on the 28th day following the discharge of COVID-19 patients, SARS-CoV-2 RNA could still be detected on the surfaces of pagers and in drawers in the isolation wards. Thorough disinfection of the ward environment was subsequently performed, after which these surfaces in the isolation wards tested negative for the presence of SARS-CoV-2 RNA. The findings remind us that the contaminated environment in the wards may become potential infectious resources and that despite a long time from exposure, the thorough disinfection in the COVID-10 units after is still necessary.

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