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Objective: To determine the efficacy of screening mammography by age, number of mammographic views per screen, screening interval, and duration of follow-up.Design: Literature review and meta-analysis. DATA IDENTIFICATION AND ANALYSIS: Literature search of English-language studies reported from January 1966 to October 31, 1993, using MEDLINE, manual literature review, and consultation with experts. A total of 13 studies were selected, and their results were combined using meta-analytic techniques based on the assumption of fixed effects.Main Results: The overall summary relative risk (RR) estimate for breast cancer mortality for women aged 50 to 74 years undergoing screening mammography compared with those who did not was 0.74 (95% confidence interval [CI], 0.66 to 0.83). The magnitude of the benefit in this age group was similar regardless of number of mammographic views per screen, screening interval, or duration of follow-up. In contrast, none of the summary RR estimates for women aged 40 to 49 years was significantly less than 1.0, irrespective of screening intervention or duration of follow-up. The overall summary RR estimate in women aged 40 to 49 years was 0.93 (95% CI, 0.76 to 1.13); the summary RR estimate for those studies that used two-view mammography was 0.87 (95% CI, 0.68 to 1.12) compared with 1.02 (95% CI, 0.73 to 1.44) for those studies that used one-view mammography, and for those studies with 7 to 9 years of follow-up, the summary RR estimate was 1.02 (95% CI, 0.82 to 1.27) compared with 0.83 (95% CI, 0.65 to 1.06) for those studies with 10 to 12 years of follow-up.Conclusion: Screening mammography significantly reduces breast cancer mortality in women aged 50 to 74 years after 7 to 9 years of follow-up, regardless of screening interval or number of mammographic views per screen. There is no reduction in breast cancer mortality in women aged 40 to 49 years after 7 to 9 years of follow-up. Screening mammography may be effective in reducing breast cancer mortality in women aged 40 to 49 years after 10 to 12 years of follow-up, but the same benefit could probably be achieved by beginning screening at menopause or 50 years of age. [ABSTRACT FROM AUTHOR]

Purpose: To provide recommendations and standard operating procedures for intensive care units and hospital preparedness for an influenza pandemic.Methods: Based on a literature review and expert opinion, a Delphi process was used to define the essential topics.Results: Key recommendations include: Hospitals should increase their ICU beds to the maximal extent by expanding ICU capacity and expanding ICUs into other areas. Hospitals should have appropriate beds and monitors for these expansion areas. Establish a management system with control groups at facility, local, regional and/or national levels to exercise authority over resources. Establish a system of communication, coordination and collaboration between the ICU and key interface departments. A plan to access, coordinate and increase labor resources is required with a central inventory of all clinical and non-clinical staff. Delegate duties not within the usual scope of workers' practice. Ensure that adequate essential medical equipment, pharmaceuticals and supplies are available. Protect patients and staff with infection control practices and supporting occupational health policies. Maintain staff confidence with reassurance plans for legal protection and assistance. Have objective, ethical, transparent triage criteria that are applied equitably and publically disclosed. ICU triage of patients should be based on the likelihood for patients to benefit most or a 'first come, first served' basis. Develop protocols for safe performance of high-risk procedures. Train and educate staff.Conclusions: Mortality, although inevitable during a severe influenza outbreak or disaster, can be reduced by adequate preparation. [ABSTRACT FROM AUTHOR]

Study Objectives: To our knowledge, the predictors of respiratory failure (RF) and long-term mechanical ventilation have not previously been examined in patients with wound botulism associated with black tar heroin use.Design: Retrospective case series.Setting: A large university hospital.Patients: Twenty consecutive patients from 1991 to 1998 with a diagnosis of wound botulism associated with drug use as identified through chart records from a single institution.Results: The predominant mode of drug use was subcutaneous (75%). Fifteen of 20 patients (75%) developed RF. The clinical presentation was similar in groups with RF and without RF. Of those patients who received antitoxin within 12 h of presentation, 57% required mechanical ventilation compared to 85% of patients receiving the antitoxin after 12 h. The median durations of mechanical ventilation were 11 days for those who received antitoxin within 12 h, and 54 days for those who did not receive antitoxin within 12 h. The duration of mechanical ventilation for patients receiving antibiotics within 12 h was 35 days vs 54 days for patients receiving antibiotics after 12 h. Early tracheostomy (< 10 days after initial intubation) was associated with a shorter duration of mechanical ventilation (median, 45 days vs 60 days, respectively).Conclusion: Early antitoxin administration may decrease the need for and duration of mechanical ventilation among patients with wound botulism. Early tracheostomy may be beneficial for patients with RF. [ABSTRACT FROM AUTHOR]

To assess risk for human exposure to avian influenza viruses (AIV), we sampled California wild birds and marine mammals during October 2005-August 2007 and estimated human-wildlife contact. Waterfowl hunters were 8 times more likely to have contact with AIV-infected wildlife than were persons with casual or occupational exposures (p<0.0001). [ABSTRACT FROM AUTHOR]

Abstract Background The Lysiphlebus fabarum group is a taxonomically poorly resolved complex of aphid parasitoids, presently split into three described species that comprise sexual (arrhenotokous) and asexual (thelytokous) lineages of unknown relationship. Specifically, it is unclear how asexuals evolved from sexuals in this system, to what extent reproductive modes are still connected by genetic exchange, how much the complex is structured by geography or by host-associated differentiation, and whether species designations are valid. Using a combination of population genetic and phylogenetic approaches, we addressed these issues in a comprehensive sample of parasitoid wasps from across Europe. Results Asexual reproduction predominated in parasitoids of the L. fabarum group, with asexual populations exhibiting high genotypic diversity. Sexual populations were only common in southern France; elsewhere sexual reproduction was restricted to specific aphid hosts. Although reproductive modes were aggregated on the mitochondrial genealogy and significantly differentiated at nuclear microsatellite loci, there was clear evidence for genetic exchange, especially on hosts attacked by sexual and asexual parasitoids. The microsatellite data further revealed that parasitoids collected from certain host aphids were significantly differentiated, yet the mitochondrial sequence variation across the entire L. fabarum group did not exceed 1.32% and exhibited a very shallow topology. Morphological characters used for delineation of described species were found to be phylogenetically non-conservative. Conclusions Our results suggest that the sexual-asexual L. fabarum group represents a young complex of lineages with incomplete isolation between reproductive modes. We propose three mechanisms of genetic exchange that may jointly explain the high genotypic diversity observed in asexual parasitoids: (i) the formation of new asexual lineages via 'contagious parthenogenesis', (ii) introgression from sexual lineages through matings between sexual males and thelytokous females, and (iii) 'cryptic sex' within asexuals, mediated by rare males that thelytokous lines are known to produce spontaneously. The partially strong differentiation among wasps collected from different aphids suggests that host specialization can evolve readily in these parasitoids. Finally, we conclude that in the light of our data, the current taxonomic division of the L. fabarum group into three species cannot be upheld.

Purpose: To provide recommendations and standard operating procedures (SOPs) for intensive care unit (ICU) and hospital preparations for an influenza pandemic or mass disaster with a specific focus on enhancing coordination and collaboration between the ICU and other key stakeholders.Methods: Based on a literature review and expert opinion, a Delphi process was used to define the essential topics including coordination and collaboration.Results: Key recommendations include: (1) establish an Incident Management System with Emergency Executive Control Groups at facility, local, regional/state or national levels to exercise authority and direction over resource use and communications; (2) develop a system of communication, coordination and collaboration between the ICU and key interface departments within the hospital; (3) identify key functions or processes requiring coordination and collaboration, the most important of these being manpower and resources utilization (surge capacity) and re-allocation of personnel, equipment and physical space; (4) develop processes to allow smooth inter-departmental patient transfers; (5) creating systems and guidelines is not sufficient, it is important to: (a) identify the roles and responsibilities of key individuals necessary for the implementation of the guidelines; (b) ensure that these individuals are adequately trained and prepared to perform their roles; (c) ensure adequate equipment to allow key coordination and collaboration activities; (d) ensure an adequate physical environment to allow staff to properly implement guidelines; (6) trigger events for determining a crisis should be defined.Conclusions: Judicious planning and adoption of protocols for coordination and collaboration with interface units are necessary to optimize outcomes during a pandemic. [ABSTRACT FROM AUTHOR]

Objectives: Lefamulin, a pleuromutilin antibiotic approved for community-acquired bacterial pneumonia (CABP), was evaluated for microbiological efficacy in a prespecified pooled analysis of LEAP 1 and 2 phase 3 clinical trial data in patients with CABP., Methods: In LEAP 1, adults (PORT risk class III‒V) received intravenous (IV) lefamulin 150 mg every 12 h (q12h) for 5‒7 days or moxifloxacin 400 mg every 24 h (q24h) for 7 days, with optional IV-to-oral switch. In LEAP 2, adults (PORT II‒IV) received oral lefamulin 600 mg q12h for 5 days or moxifloxacin 400 mg q24h for 7 days. Primary outcomes were early clinical response (ECR) at 96 ± 24 h after treatment start and investigator assessment of clinical response (IACR) 5‒10 days after the last dose. Secondary outcomes included ECR and IACR in patients with a baseline CABP pathogen (detected via culture, urinary antigen testing, serology and/or real-time PCR)., Results: Baseline CABP pathogens were detected in 709/1289 patients (55.0%; microbiological intention-to-treat population). The most frequently identified pathogens were Streptococcus pneumoniae (61.9% of patients) and Haemophilus influenzae (29.9%); 25.1% had atypical pathogens and 33.1% had polymicrobial infections. Pathogens were identified most frequently by PCR from sputum, followed by culture from respiratory specimens. In patients with baseline CABP pathogens, ECR rates were 89.3% (lefamulin) and 93.0% (moxifloxacin); IACR success rates were 83.2% and 86.7%, respectively. Results were consistent across CABP pathogens, including drug-resistant isolates and polymicrobial infections., Conclusion: Lefamulin is a valuable IV and oral monotherapy option for empirical and directed CABP treatment in adults., Competing Interests: Declaration of Competing Interests SP and SPG are employees of/stockholders in Nabriva Therapeutics plc; LG, EA and JS were employees of/stockholders in Nabriva Therapeutics plc at the time of the analysis; AFD has served as a consultant for ContraFect, IterumTx, MicuRx, Nabriva Therapeutics, Paratek, Shionogi, Tetraphase, Union Therapeutics and UTILITY; SH and PP are employees of Accelerō® Bioanalytics GmbH and Covance Central Laboratory Services, respectively, which were contracted by Nabriva Therapeutics to assist in the performance of confirmatory and specialised testing for the LEAP 1 and LEAP 2 trials; GJM has received grants from ContraFect and Nabriva Therapeutics; CS has served as a consultant for Allergan and Nabriva Therapeutics, has received grants from the National Institutes of Health and the Health Resources & Services Administration, and has received non-financial support from the State of California; TMF has served as a consultant for bioMérieux, Curetis, Melinta, Merck, Motif BioSciences, Nabriva Therapeutics, Paratek, Pfizer and Shionogi Inc. and has received grants from Nabriva Therapeutics; JEV has received grants or research contracts from the Bill and Melinda Gates Foundation, Melinta Therapeutics, Nabriva Therapeutics, the National Institutes of Health and Pfizer; KBW has received research grants and/or contracts from Akonni Biosystems, Covance, Inc., Everest Pharmaceuticals, mFluiDx, Roche Molecular Systems, SpeeDx, Ltd., US Centers for Disease Control and Prevention (CDC), National Institutes of Health and Wockhardt Ltd., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Few interventions are known to reduce the incidence of respiratory failure that occurs following elective surgery (postoperative respiratory failure; PRF). We previously reported risk factors associated with PRF that occurs within the first 5 days after elective surgery (early PRF; E-PRF); however, PRF that occurs six or more days after elective surgery (late PRF; L-PRF) likely represents a different entity. We hypothesized that L-PRF would be associated with worse outcomes and different risk factors than E-PRF., Methods: This was a retrospective matched case-control study of 59,073 consecutive adult patients admitted for elective non-cardiac and non-pulmonary surgical procedures at one of five University of California academic medical centers between October 2012 and September 2015. We identified patients with L-PRF, confirmed by surgeon and intensivist subject matter expert review, and matched them 1:1 to patients who did not develop PRF (No-PRF) based on hospital, age, and surgical procedure. We then analyzed risk factors and outcomes associated with L-PRF compared to E-PRF and No-PRF., Results: Among 95 patients with L-PRF, 50.5% were female, 71.6% white, 27.4% Hispanic, and 53.7% Medicare recipients; the median age was 63 years (IQR 56, 70). Compared to 95 matched patients with No-PRF and 319 patients who developed E-PRF, L-PRF was associated with higher morbidity and mortality, longer hospital and intensive care unit length of stay, and increased costs. Compared to No-PRF, factors associated with L-PRF included: preexisiting neurologic disease (OR 4.36, 95% CI 1.81-10.46), anesthesia duration per hour (OR 1.22, 95% CI 1.04-1.44), and maximum intraoperative peak inspiratory pressure per cm H 2 0 (OR 1.14, 95% CI 1.06-1.22)., Conclusions: We identified that pre-existing neurologic disease, longer duration of anesthesia, and greater maximum intraoperative peak inspiratory pressures were associated with respiratory failure that developed six or more days after elective surgery in adult patients (L-PRF). Interventions targeting these factors may be worthy of future evaluation., (© 2022. The Author(s).)

Further advancing black soldier fly (BSF) farming for waste valorisation and more sustainable global protein supplies critically depends on targeted exploitation of genotype-phenotype associations in this insect, comparable to conventional livestock. This study used a fully crossed factorial design of rearing larvae of four genetically distinct BSF strains ( F ST : 0.11-0.35) on three nutritionally different diets (poultry feed, food waste, poultry manure) to investigate genotype-by-environment interactions. Phenotypic responses included larval growth dynamics over time, weight at harvest, mortality, biomass production with respective contents of ash, fat, and protein, including amino acid profiles, as well as bioconversion and nitrogen efficiency, reduction of dry matter and relevant fibre fractions, and dry matter loss (emissions). Virtually all larval performance and body composition traits were substantially influenced by diet but also characterised by ample BSF genetic variation and, most importantly, by pronounced interaction effects between the two. Across evaluated phenotypes, variable diet-dependent rankings and the lack of generally superior BSF strains indicate the involvement of trade-offs between traits, as their relationships may even change signs. Conflicting resource allocation in light of overall BSF fitness suggests anticipated breeding programs will require complex and differential selection strategies to account for pinpointed trait maximisation versus multi-purpose resilience.

What Is This Summary About?: Bacterial pneumonia is an infection of the lung caused by bacteria that is potentially deadly, costly, and affects millions of people worldwide every year. Treatment is becoming more challenging-many current treatments no longer work well because some strains of bacteria that cause pneumonia have become resistant to current antibiotics. Many of the antibiotics that do still work have undesirable side effects. Therefore, new antibiotics that work differently are needed to treat bacterial pneumonia. Lefamulin (brand name, Xenleta ® ) is an antibiotic that was approved to treat bacterial pneumonia caught outside a hospital (also called community-acquired bacterial pneumonia, or CABP) based on results of two clinical studies. In both studies, participants started treatment with lefamulin before the type of bacteria causing the infection was known. Lefamulin was well tolerated and worked well in 5 to 7 days to kill the bacteria causing the infection and to improve symptoms in almost all participants with CABP., What Were the Results?: After the studies were completed, the researchers looked back at what kinds of bacteria were identified from the study participants. Lefamulin worked well to kill bacteria and to improve CABP symptoms for most kinds of infecting bacteria, including bacteria resistant to many current antibiotics., What Do the Results Mean?: These results suggest that lefamulin, by itself, provides a much-needed treatment option for CABP that covers most of the key bacteria causing this infection.

Lefamulin was the first systemic pleuromutilin antibiotic approved for intravenous and oral use in adults with community-acquired bacterial pneumonia based on two phase 3 trials (Lefamulin Evaluation Against Pneumonia [LEAP]-1 and LEAP-2). This pooled analysis evaluated lefamulin efficacy and safety in adults with community-acquired bacterial pneumonia caused by atypical pathogens ( Mycoplasma pneumoniae , Legionella pneumophila , and Chlamydia pneumoniae ). In LEAP-1, participants received intravenous lefamulin 150 mg every 12 h for 5-7 days or moxifloxacin 400 mg every 24 h for 7 days, with optional intravenous-to-oral switch. In LEAP-2, participants received oral lefamulin 600 mg every 12 h for 5 days or moxifloxacin 400 mg every 24 h for 7 days. Primary outcomes were early clinical response at 96 ± 24 h after first dose and investigator assessment of clinical response at test of cure (5-10 days after last dose). Atypical pathogens were identified in 25.0% (91/364) of lefamulin-treated patients and 25.2% (87/345) of moxifloxacin-treated patients; most were identified by ≥1 standard diagnostic modality ( M. pneumoniae 71.2% [52/73]; L. &nbsp; pneumophila 96.9% [63/65]; C. pneumoniae 79.3% [46/58]); the most common standard diagnostic modality was serology. In terms of disease severity, more than 90% of patients had CURB-65 (confusion of new onset, blood urea nitrogen > 19 mg/dL, respiratory rate ≥ 30 breaths/min, blood pressure <90 mm Hg systolic or ≤60 mm Hg diastolic, and age ≥ 65 years) scores of 0-2; approximately 50% of patients had PORT (Pneumonia Outcomes Research Team) risk class of III, and the remaining patients were more likely to have PORT risk class of II or IV versus V. In patients with atypical pathogens, early clinical response (lefamulin 84.4-96.6%; moxifloxacin 90.3-96.8%) and investigator assessment of clinical response at test of cure (lefamulin 74.1-89.7%; moxifloxacin 74.2-97.1%) were high and similar between arms. Treatment-emergent adverse event rates were similar in the lefamulin (34.1% [31/91]) and moxifloxacin (32.2% [28/87]) groups. Limitations to this analysis include its post hoc nature, the small numbers of patients infected with atypical pathogens, the possibility of PCR-based diagnostic methods to identify non-etiologically relevant pathogens, and the possibility that these findings may not be generalizable to all patients. Lefamulin as short-course empiric monotherapy, including 5-day oral therapy, was well tolerated in adults with community-acquired bacterial pneumonia and demonstrated high clinical response rates against atypical pathogens.

Osteal macrophages (osteomacs) support osteoblast function and promote bone anabolism, but their contribution to osteoporosis has not been explored. Although mouse ovariectomy (OVX) models have been repeatedly used, variation in strain, experimental design and assessment modalities have contributed to no single model being confirmed as comprehensively replicating the full gamut of osteoporosis pathological manifestations. We validated an OVX model in adult C3H/HeJ mice and demonstrated that it presents with human postmenopausal osteoporosis features with reduced bone volume in axial and appendicular bone and bone loss in both trabecular and cortical bone including increased cortical porosity. Bone loss was associated with increased osteoclasts on trabecular and endocortical bone and decreased osteoblasts on trabecular bone. Importantly, this OVX model was characterized by delayed fracture healing. Using this validated model, we demonstrated that osteomacs are increased post-OVX on both trabecular and endocortical bone. Dual F4/80 (pan-macrophage marker) and tartrate-resistant acid phosphatase (TRAP) staining revealed osteomacs frequently located near TRAP + osteoclasts and contained TRAP + intracellular vesicles. Using an in vivo inducible macrophage depletion model that does not simultaneously deplete osteoclasts, we observed that osteomac loss was associated with elevated extracellular TRAP in bone marrow interstitium and increased serum TRAP. Using in vitro high-resolution confocal imaging of mixed osteoclast-macrophage cultures on bone substrate, we observed macrophages juxtaposed to osteoclast basolateral functional secretory domains scavenging degraded bone byproducts. These data demonstrate a role for osteomacs in supporting osteoclastic bone resorption through phagocytosis and sequestration of resorption byproducts. Overall, our data expose a novel role for osteomacs in supporting osteoclast function and provide the first evidence of their involvement in osteoporosis pathogenesis. © 2021 American Society for Bone and Mineral Research (ASBMR)., (© 2021 American Society for Bone and Mineral Research (ASBMR).)

Objective: To describe the pattern of transmission of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) during 2 nosocomial outbreaks of coronavirus disease 2019 (COVID-19) with regard to the possibility of airborne transmission., Design: Contact investigations with active case finding were used to assess the pattern of spread from 2 COVID-19 index patients., Setting: A community hospital and university medical center in the United States, in February and March, 2020, early in the COVID-19 pandemic., Patients: Two index patients and 421 exposed healthcare workers., Methods: Exposed healthcare workers (HCWs) were identified by analyzing the electronic medical record (EMR) and conducting active case finding in combination with structured interviews. Healthcare coworkers (HCWs) were tested for COVID-19 by obtaining oropharyngeal/nasopharyngeal specimens, and RT-PCR testing was used to detect SARS-CoV-2., Results: Two separate index patients were admitted in February and March 2020, without initial suspicion for COVID-19 and without contact or droplet precautions in place; both patients underwent several aerosol-generating procedures in this context. In total, 421 HCWs were exposed in total, and the results of the case contact investigations identified 8 secondary infections in HCWs. In all 8 cases, the HCWs had close contact with the index patients without sufficient personal protective equipment. Importantly, despite multiple aerosol-generating procedures, there was no evidence of airborne transmission., Conclusion: These observations suggest that, at least in a healthcare setting, most SARS-CoV-2 transmission is likely to take place during close contact with infected patients through respiratory droplets, rather than by long-distance airborne transmission.

Macrophage-targeted therapies, including macrophage colony-stimulating factor 1 (CSF1), have been shown to have pro-repair impacts post-fracture. Preclinical/clinical applications of CSF1 have been expedited by development of chimeric CSF1-Fc which has extended circulating half-life. Here, we used mouse models to investigate the bone regenerative potential of CSF1-Fc in healthy and osteoporotic fracture. We also explored whether combination of CSF1-Fc with interleukin (IL)-4 provided additional fracture healing benefit in osteopenic bone. Micro-computed tomography, in situ histomorphometry, and bone mechanical parameters were used to assess systemic impacts of CSF1-Fc therapy in naive mice (male and female young, adult and geriatric). An intermittent CSF1-Fc regimen was optimized to mitigate undesirable impacts on bone resorption and hepatosplenomegaly, irrespective of age or gender. The intermittent CSF1-Fc regimen was tested in a mid-diaphyseal femoral fracture model in healthy bones with treatment initiated 1-day post-fracture. Weekly CSF1-Fc did not impact osteoclasts but increased osteal macrophages and improved fracture strength. Importantly, this treatment regimen also improved fracture union and strength in an ovariectomy-model of delayed fracture repair. Combining CSF1-Fc with IL-4 initiated 1-week post-fracture reduced the efficacy of CSF1-Fc. This study describes a novel strategy to specifically achieve bone regenerative actions of CSF1-Fc that has the potential to alleviate fragility fracture morbidity and mortality., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Implementing insects, such as the black soldier fly larvae (BSFL), as animal feed commonly includes the previous removal of substantial amounts of fat. This fat may represent an as yet underutilized energy source for livestock. However, transfer of lauric and myristic acid, prevalent in BSFL fat and undesired in human nutrition, into animal-source foods like eggs may limit its implementation. To quantify this, a laying hen experiment was performed comprising five different diets (10 hens/diet). These were a control diet with soybean oil and meal and a second diet with soybean oil but with partially defatted BSFL meal as protein source. The other three diets were based on different combinations of partially defatted BSFL meal and fat obtained by two different production methods. Lauric acid made up half of the BSFL fat from both origins. Both BSFL fats also contained substantial amounts of myristic and palmitic acid. However, in the insect-based diets, the net transfer from diet to egg yolk was less than 1% for lauric acid, whereas the net transfer for myristic and palmitic acid was about 30% and 100%, respectively. The net transfer did not vary between BSFL originating from production on different larval feeding substrates. The results illustrate that hens are able to metabolize or elongate very large proportions of ingested lauric acid and myristic acid, which are predominant in the BSFL lipids (together accounting for as much as 37 mol%), such that they collectively account for less than 3.5 mol% of egg yolk fatty acids., (© 2021 AOCS.)

Rationale: There is little doubt that aerosols play a major role in the transmission of SARS-CoV-2. The significance of the presence and infectivity of this virus on environmental surfaces, especially in a hospital setting, remains less clear., Objectives: We aimed to analyze surface swabs for SARS-CoV-2 RNA and infectivity, and to determine their suitability for sequence analysis., Methods: Samples were collected during two waves of COVID-19 at the University of California, Davis Medical Center, in COVID-19 patient serving and staff congregation areas. qRT-PCR positive samples were investigated in Vero cell cultures for cytopathic effects and phylogenetically assessed by whole genome sequencing., Measurements and Main Results: Improved cleaning and patient management practices between April and August 2020 were associated with a substantial reduction of SARS-CoV-2 qRT-PCR positivity (from 11% to 2%) in hospital surface samples. Even though we recovered near-complete genome sequences in some, none of the positive samples (11 of 224 total) caused cytopathic effects in cultured cells suggesting this nucleic acid was either not associated with intact virions, or they were present in insufficient numbers for infectivity. Phylogenetic analysis suggested that the SARS-CoV-2 genomes of the positive samples were derived from hospitalized patients. Genomic sequences isolated from qRT-PCR negative samples indicate a superior sensitivity of viral detection by sequencing., Conclusions: This study confirms the low likelihood that SARS-CoV-2 contamination on hospital surfaces contains infectious virus, disputing the importance of fomites in COVID-19 transmission. Ours is the first report on recovering near-complete SARS-CoV-2 genome sequences directly from environmental surface swabs., Competing Interests: The authors have declared that no competing interests exist.

Background: Safe and effective oral antibiotics are needed for outpatient management of moderate to severe community-acquired bacterial pneumonia (CABP)., Objective: We describe a post-hoc analysis of adults with CABP managed as outpatients from the Lefamulin Evaluation Against Pneumonia (LEAP) 2 double-blind, noninferiority, phase 3 clinical trial., Methods: LEAP 2 compared the efficacy and safety of oral lefamulin 600 mg every 12 h (5 days) vs. oral moxifloxacin 400 mg every 24 h (7 days) in adults (inpatients and outpatients) with Pneumonia Outcomes Research Team (PORT) risk classes II‒IV., Results: Overall, 41% (151 of 368) of patients receiving lefamulin and 43% (159 of 368) of patients receiving moxifloxacin started treatment as outpatients-44% and 40%, respectively, were PORT risk class III/IV, and 21% in both groups had CURB-65 scores of 2‒3. Early clinical response (at 96 ± 24 h) and investigator assessment of clinical response success rates at test of cure (5‒10 days after last study drug dose) were high and similar in both groups among all (lefamulin, 91% vs. moxifloxacin, 89‒90%), PORT risk class III/IV (89‒91% vs. 88‒91%), and CURB-65 score 2‒3 (87‒90% vs. 82‒88%) outpatients. Few outpatients (lefamulin, 2.6%; moxifloxacin, 2.5%) discontinued the study drug because of treatment-emergent adverse events (TEAEs). No outpatient in the lefamulin group was hospitalized for a TEAE, compared with 5 patients (3%), including two deaths, in the moxifloxacin group., Conclusions: These data suggest that 5 days of oral lefamulin can be given in lieu of fluoroquinolones for outpatient treatment of adults with CABP and PORT risk class III/IV or CURB-65 scores of 2‒3., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Lefamulin, a first-in-class pleuromutilin antibiotic approved for intravenous and oral use in adults with community-acquired bacterial pneumonia (CABP), was noninferior to moxifloxacin in the Lefamulin Evaluation Against Pneumonia (LEAP) 1 intravenous-to-oral switch study and the LEAP 2 oral-only study. Using pooled LEAP 1/2 data, we examined lefamulin efficacy/safety overall and within subgroups of patients presenting with comorbidities typical in CABP management., Methods: In LEAP 1, adults with CABP were randomized to receive intravenous lefamulin (150 mg every 12 h) for 5‒7 days or moxifloxacin (400 mg every 24 h) for 7 days, with optional intravenous-to-oral switch if predefined improvement criteria were met. In LEAP 2, adults with CABP were randomized to receive oral lefamulin (600 mg every 12 h) for 5 days or moxifloxacin (400 mg every 24 h) for 7 days. Both studies assessed early clinical response (ECR) at 96 ± 24 h after first study drug dose and investigator assessment of clinical response (IACR) at test-of-cure (5‒10 days after last dose). Pooled analyses of the overall population used a 10% noninferiority margin., Results: Lefamulin (n = 646) was noninferior to moxifloxacin (n = 643) for ECR (89.3% vs 90.5%, respectively; difference  - 1.1%; 95% CI  - 4.4 to 2.2); IACR success rates at test-of-cure were similarly high (≥ 85.0%). High efficacy with both lefamulin and moxifloxacin was also demonstrated across all well-represented patient subgroups, including those with advanced age, diabetes mellitus, a history of cardiovascular diseases (e.g., hypertension, congestive heart failure, or arrhythmia) or chronic lung diseases (e.g., asthma or chronic obstructive pulmonary disease), elevated liver enzymes, or mild-to-moderate renal dysfunction. No new safety signals were identified., Conclusions: Lefamulin may provide a valuable intravenous/oral monotherapy alternative to fluoroquinolones or macrolides for empiric treatment of patients with CABP, including cases of patients at risk for poor outcomes due to age or various comorbidities., Trial Registration: ClinicalTrials.gov LEAP 1 (NCT02559310; Registration Date: 24/09/2015) and LEAP 2 (NCT02813694; Registration Date: 27/06/2016).

Background: The black soldier fly (Hermetia illucens) is the most promising insect candidate for nutrient-recycling through bioconversion of organic waste into biomass, thereby improving sustainability of protein supplies for animal feed and facilitating transition to a circular economy. Contrary to conventional livestock, genetic resources of farmed insects remain poorly characterised. We present the first comprehensive population genetic characterisation of H. illucens. Based on 15 novel microsatellite markers, we genotyped and analysed 2862 individuals from 150 wild and captive populations originating from 57 countries on seven subcontinents., Results: We identified 16 well-distinguished genetic clusters indicating substantial global population structure. The data revealed genetic hotspots in central South America and successive northwards range expansions within the indigenous ranges of the Americas. Colonisations and naturalisations of largely unique genetic profiles occurred on all non-native continents, either preceded by demographically independent founder events from various single sources or involving admixture scenarios. A decisive primarily admixed Polynesian bridgehead population serially colonised the entire Australasian region and its secondarily admixed descendants successively mediated invasions into Africa and Europe. Conversely, captive populations from several continents traced back to a single North American origin and exhibit considerably reduced genetic diversity, although some farmed strains carry distinct genetic signatures. We highlight genetic footprints characteristic of progressing domestication due to increasing socio-economic importance of H. illucens, and ongoing introgression between domesticated strains globally traded for large-scale farming and wild populations in some regions., Conclusions: We document the dynamic population genetic history of a cosmopolitan dipteran of South American origin shaped by striking geographic patterns. These reflect both ancient dispersal routes, and stochastic and heterogeneous anthropogenic introductions during the last century leading to pronounced diversification of worldwide structure of H. illucens. Upon the recent advent of its agronomic commercialisation, however, current human-mediated translocations of the black soldier fly largely involve genetically highly uniform domesticated strains, which meanwhile threaten the genetic integrity of differentiated unique local resources through introgression. Our in-depth reconstruction of the contemporary and historical demographic trajectories of H. illucens emphasises benchmarking potential for applied future research on this emerging model of the prospering insect-livestock sector.

International travel goes hand in hand with medical delivery to underserved communities. The global health care worker can be exposed to a wide range of infectious diseases during their global experiences. A pretravel risk assessment visit and all appropriate vaccinations and education must be performed. Universal practices of water safety, food safety, and insect avoidance will prevent most travel-related infections and complications. Region-specific vaccinations will further reduce illness risk. An understanding of common travel-related illness signs and symptoms is helpful. Emerging pathogens that can cause a pandemic should be understood to avoid health care worker infection and spread., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The black soldier fly (Diptera: Stratiomyidae, Hermetia illucens) is renowned for its bioconversion ability of organic matter, and is the worldwide most widely used source of insect protein. Despite varying extensively in morphology, it is widely assumed that all black soldier flies belong to the same species, Hermetia illucens. We here screened about 600 field-collected and cultured flies from 39 countries and six biogeographic regions to test this assumption based on data for three genes (mitochondrial COI, nuclear ITS2 & 28S rDNA) and in order to gain insights into the phylogeography of the species., Results: Our study reveals a surprisingly high level of intraspecific genetic diversity for the mitochondrial barcoding gene COI (divergences up to 4.9%). This level of variability is often associated with the presence of multiple species, but tested nuclear markers (ITS2 and 28S rDNA) were invariant and fly strain hybridization experiments under laboratory conditions revealed reproductive compatibility. COI haplotype diversity is not only very high in all biogeographic regions (56 distinct haplotypes in total), but also in breeding facilities and research centers from six continents (10 haplotypes: divergences up to 4.3%). The high genetic diversity in fly-breeding facilities is mostly likely due to many independent acquisitions of cultures via sharing and/or establishing new colonies from field-collected flies. However, explaining some of the observed diversity in several biogeographic regions is difficult given that the origin of the species is considered to be New World (32 distinct haplotypes) and one would expect severely reduced genetic diversity in the putatively non-native populations in the remaining biogeographic regions. However, distinct, private haplotypes are known from the Australasian (N = 1), Oriental (N = 4), and the Eastern Palearctic (N = 4) populations. We reviewed museum specimen records and conclude that the evidence for introductions is strong for the Western Palearctic and Afrotropical regions which lack distinct, private haplotypes., Conclusions: Based on the results of this paper, we urge the black soldier fly community to apply molecular characterization (genotyping) of the fly strains used in artificial fly-breeding and share these data in research publications as well as when sharing cultures. In addition, fast-evolving nuclear markers should be used to reconstruct the recent invasion history of the species.

Importance: New antibacterials are needed to treat community-acquired bacterial pneumonia (CABP) because of growing antibacterial resistance and safety concerns with standard care., Objective: To evaluate the efficacy and adverse events of a 5-day oral lefamulin regimen in patients with CABP., Design, Setting, and Participants: A phase 3, noninferiority randomized clinical trial conducted at 99 sites in 19 countries that included adults aged 18 years or older with a Pneumonia Outcomes Research Team (PORT) risk class of II, III, or IV; radiographically documented pneumonia; acute illness; 3 or more CABP symptoms; and 2 or more vital sign abnormalities. The first patient visit was on August 30, 2016, and patients were followed up for 30 days; the final follow-up visit was on January 2, 2018., Interventions: Patients were randomized 1:1 to receive oral lefamulin (600 mg every 12 hours for 5 days; n = 370) or moxifloxacin (400 mg every 24 hours for 7 days; n = 368)., Main Outcomes and Measures: The US Food and Drug Administration (FDA) primary end point was early clinical response at 96 hours (within a 24-hour window) after the first dose of either study drug in the intent-to-treat (ITT) population (all randomized patients). Responders were defined as alive, showing improvement in 2 or more of the 4 CABP symptoms, having no worsening of any CABP symptoms, and not receiving any nonstudy antibacterial drug for current CABP episode. The European Medicines Agency coprimary end points (FDA secondary end points) were investigator assessment of clinical response at test of cure (5-10 days after last dose) in the modified ITT population and in the clinically evaluable population. The noninferiority margin was 10% for early clinical response and investigator assessment of clinical response., Results: Among 738 randomized patients (mean age, 57.5 years; 351 women [47.6%]; 360 had a PORT risk class of III or IV [48.8%]), 707 (95.8%) completed the trial. Early clinical response rates were 90.8% with lefamulin and 90.8% with moxifloxacin (difference, 0.1% [1-sided 97.5% CI, -4.4% to ∞]). Rates of investigator assessment of clinical response success were 87.5% with lefamulin and 89.1% with moxifloxacin in the modified ITT population (difference, -1.6% [1-sided 97.5% CI, -6.3% to ∞]) and 89.7% and 93.6%, respectively, in the clinically evaluable population (difference, -3.9% [1-sided 97.5% CI, -8.2% to ∞]) at test of cure. The most frequently reported treatment-emergent adverse events were gastrointestinal (diarrhea: 45/368 [12.2%] in lefamulin group and 4/368 [1.1%] in moxifloxacin group; nausea: 19/368 [5.2%] in lefamulin group and 7/368 [1.9%] in moxifloxacin group)., Conclusions and Relevance: Among patients with CABP, 5-day oral lefamulin was noninferior to 7-day oral moxifloxacin with respect to early clinical response at 96 hours after first dose., Trial Registrations: ClinicalTrials.gov Identifier: NCT02813694; European Clinical Trials Identifier: 2015-004782-92.

The Plain community is the fastest-growing religious minority in Wisconsin. This community has a high incidence of genetic disorders, many of which are identifiable through newborn screening. We describe efforts by the Wisconsin Newborn Screening Program (WNSP) to improve health care in the Plain community by targeting early identification of, and intervention for, patients with inherited metabolic disorders. WNSP formed partnerships with families and health care providers to increase awareness of screening procedures and the intended benefits of screening, modify testing algorithms to enhance detection, and establish medical homes for patients with confirmed disorders. The estimated number of Plain newborns screened increased by 25.5% during the study period, from 547 in 2011 to 736 in 2017; 122 persons underwent carrier testing, and 143 newborns received second-tier testing. From 2014 to 2017, affected patients received 71 metabolic evaluations in their community medical home without travel to major health centers. This article demonstrates how a comprehensive public health program can help increase screening rates, enhance detection, and establish follow-up care in a hard-to-reach religious community. A key lesson learned was the importance of communication among all stakeholders to develop an effective public health program.

Pneumonia is one of the leading causes of mortality and hospitalization among US adults. The decision to admit patients from the emergency department is a major one because of its impact on patients and the hospital. The diagnosis of pneumonia is often clinical and based on symptoms and signs combined with radiographic findings. There are multiple severity assessments available that can guide treatment, prognosis, and disposition. Viruses are an important cause of pneumonia and require early recognition and treatment. The recommended treatment for community-acquired pneumonia includes a beta lactam plus a macrolide or a respiratory fluoroquinolone., (© 2017 Elsevier Inc. All rights reserved.)

It is as yet unknown if behavioral and neural correlates of performance monitoring in socially anxious individuals are affected by whether feedback is provided by a person or a computer. This fMRI study investigated modulation of feedback processing by feedback source (person vs. computer) in participants with high (HSA) (N=16) and low social anxiety (LSA) (N=16). Subjects performed a choice task in which they were informed that they would receive positive or negative feedback from a person or the computer. Subjective ratings indicated increased arousal and anxiety in HSA versus LSA, most pronounced for social and negative feedback. FMRI analyses yielded hyperactivation in ventral medial prefrontal cortex (vmPFC)/anterior cingulate cortex (ACC) and insula for social relative to computer feedback, and in mPFC/ventral ACC for positive relative to negative feedback in HSA as compared to LSA. These activation patterns are consistent with increased interoception and self-referential processing in social anxiety, especially during processing of positive feedback. Increased ACC activation in HSA to positive feedback may link to unexpectedness of (social) praise as posited in social anxiety disorder (SAD) psychopathology. Activation in rostral ACC showed a reversed pattern, with decreased activation to positive feedback in HSA, possibly indicating altered action values depending on feedback source and valence. The present findings corroborate a crucial role of mPFC for performance monitoring in social anxiety., (Copyright © 2016 Elsevier Inc. All rights reserved.)

"Downhill" varices are a rare cause of acute upper gastrointestinal bleeding and are generally due to obstruction of the superior vena cava (SVC). Often these cases of "downhill" varices are missed diagnoses as portal hypertension but fail to improve with medical treatment to reduce portal pressure. We report a similar case where recurrent variceal bleeding was initially diagnosed as portal hypertension but later found to have SVC thrombosis presenting with recurrent hematemesis. A 39-year-old female with history of end-stage renal disease presented with recurrent hematemesis. Esophagogastroduodenoscopy (EGD) revealed multiple varices. Banding and sclerotherapy were performed. Extensive evaluation did not show overt portal hypertension or cirrhosis. Due to ongoing bleeding requiring resuscitation, she underwent internal jugular (IJ) and SVC venogram in preparation for transjugular intrahepatic portosystemic shunt (TIPS), which demonstrated complete IJ and SVC occlusion. She underwent balloon angioplasty with stent placement across SVC occlusion with complete resolution of her varices and resolved hematemesis. "Downhill" varices are extremely rare, though previously well described. Frequently, patients are misdiagnosed with underlying liver disease. High index of suspicion and investigation of alternative causes of varices is prudent in those without underlying liver diseases. Prompt diagnosis and appropriate intervention can significantly improve morbidity and mortality.

Background: Honeybees provide economically and ecologically vital pollination services to crops and wild plants. During the last decade elevated colony losses have been documented in Europe and North America. Despite growing consensus on the involvement of multiple causal factors, the underlying interactions impacting on honeybee health and colony failure are not fully resolved. Parasites and pathogens are among the main candidates, but sublethal exposure to widespread agricultural pesticides may also affect bees., Methodology/principal Findings: To investigate effects of sublethal dietary neonicotinoid exposure on honeybee colony performance, a fully crossed experimental design was implemented using 24 colonies, including sister-queens from two different strains, and experimental in-hive pollen feeding with or without environmentally relevant concentrations of thiamethoxam and clothianidin. Honeybee colonies chronically exposed to both neonicotinoids over two brood cycles exhibited decreased performance in the short-term resulting in declining numbers of adult bees (-28%) and brood (-13%), as well as a reduction in honey production (-29%) and pollen collections (-19%), but colonies recovered in the medium-term and overwintered successfully. However, significantly decelerated growth of neonicotinoid-exposed colonies during the following spring was associated with queen failure, revealing previously undocumented long-term impacts of neonicotinoids: queen supersedure was observed for 60% of the neonicotinoid-exposed colonies within a one year period, but not for control colonies. Linked to this, neonicotinoid exposure was significantly associated with a reduced propensity to swarm during the next spring. Both short-term and long-term effects of neonicotinoids on colony performance were significantly influenced by the honeybees' genetic background., Conclusions/significance: Sublethal neonicotinoid exposure did not provoke increased winter losses. Yet, significant detrimental short and long-term impacts on colony performance and queen fate suggest that neonicotinoids may contribute to colony weakening in a complex manner. Further, we highlight the importance of the genetic basis of neonicotinoid susceptibility in honeybees which can vary substantially.

Infectious bronchitis virus (IBV) was detected in 185 samples originating from chicken flocks of various commodity groups in Canada. Flocks with clinical signs such as respiratory challenge, sudden death, egg production problems, or nephropathogenic conditions, and randomly selected flocks sampled at slaughter as part of an Ontario broiler surveillance project, were included. Most samples were from Ontario and Québec; however, a small number from British Columbia, Nova Scotia, and Newfoundland and Labrador were also analysed. The nucleotide sequence of the spike (S) protein gene was compared with sequences available in GenBank. Based on their S gene sequence similarities, Canadian IBVs could be divided into nine genotypes belonging to four groups: Canadian variant virus, strain Qu&#95;mv; the classic, vaccine-like viruses, Connecticut and Massachusetts; US variant-like virus strains, California 1734/04, California 99, CU&#95;82792, Pennsylvania 1220/98 and Pennsylvania Wolg/98; and non-Canadian, non-US virus, strain 4/91. Based on the field situation, the effectiveness of current vaccination practices mostly based on Massachusetts and Connecticut-type vaccines appeared generally satisfactory for minimizing the damage due to infection with Canadian variant and US variant-like viruses. However, the recent outbreaks of severe respiratory disease and production problems in Ontario chicken flocks related to the incursion of IBV strain 4/91 were not prevented by standard vaccination protocols. It appears that IBV strain 4/91 has now become endemic in Ontario and the need for 4/91-type vaccines must be evaluated.