The time of arrival of people in Australia is an unresolved question. It is relevant to debates about when modern humans first dispersed out of Africa and when their descendants incorporated genetic ...material from Neanderthals, Denisovans and possibly other hominins. Humans have also been implicated in the extinction of Australia's megafauna. Here we report the results of new excavations conducted at Madjedbebe, a rock shelter in northern Australia. Artefacts in primary depositional context are concentrated in three dense bands, with the stratigraphic integrity of the deposit demonstrated by artefact refits and by optical dating and other analyses of the sediments. Human occupation began around 65,000 years ago, with a distinctive stone tool assemblage including grinding stones, ground ochres, reflective additives and ground-edge hatchet heads. This evidence sets a new minimum age for the arrival of humans in Australia, the dispersal of modern humans out of Africa, and the subsequent interactions of modern humans with Neanderthals and Denisovans.
Complicated vascular anomalies have limited therapeutic options and cause significant morbidity and mortality. This Phase II trial enrolled patients with complicated vascular anomalies to determine ...the efficacy and safety of treatment with sirolimus for 12 courses; each course was defined as 28 days.
Treatment consisted of a continuous dosing schedule of oral sirolimus starting at 0.8 mg/m(2) per dose twice daily, with pharmacokinetic-guided target serum trough levels of 10 to 15 ng/mL. The primary outcomes were responsiveness to sirolimus by the end of course 6 (evaluated according to functional impairment score, quality of life, and radiologic assessment) and the incidence of toxicities and/or infection-related deaths.
Sixty-one patients were enrolled; 57 patients were evaluable for efficacy at the end of course 6, and 53 were evaluable at the end of course 12. No patient had a complete response at the end of course 6 or 12 as anticipated. At the end of course 6, a total of 47 patients had a partial response, 3 patients had stable disease, and 7 patients had progressive disease. Two patients were taken off of study medicine secondary to persistent adverse effects. Grade 3 and higher toxicities attributable to sirolimus included blood/bone marrow toxicity in 27% of patients, gastrointestinal toxicity in 3%, and metabolic/laboratory toxicity in 3%. No toxicity-related deaths occurred.
Sirolimus was efficacious and well tolerated in these study patients with complicated vascular anomalies. Clinical activity was reported in the majority of the disorders.
Children with cancer are frequently immunocompromised. While children are generally thought to be at less risk of severe SARS-CoV-2 infection than adults, comprehensive population-based evidence for ...the risk in children with cancer is unavailable. We aimed to produce evidence of the incidence and outcomes from SARS-CoV-2 in children with cancer attending all hospitals treating this population across the UK.
Retrospective and prospective observational study of all children in the UK under 16 diagnosed with cancer through data collection from all hospitals providing cancer care to this population. Eligible patients tested positive for SARS-CoV-2 on reverse transcription polymerase chain reaction (RT-PCR). The primary end-point was death, discharge or end of active care for COVID-19 for those remaining in hospital.
Between 12 March 2020 and 31 July 2020, 54 cases were identified: 15 (28%) were asymptomatic, 34 (63%) had mild infections and 5 (10%) moderate, severe or critical infections. No patients died and only three patients required intensive care support due to COVID-19. Estimated incidence of hospital identified SARS-CoV-2 infection in children with cancer under 16 was 3%.
Children with cancer with SARS-CoV-2 infection do not appear at increased risk of severe infection compared to the general paediatric population. This is reassuring and supports the continued delivery of standard treatment.
A paucity of studies have assessed the epidemiology of community-acquired pneumonia (CAP) that require ICU admission. We conducted a study on this group of patients with the primary objective of ...defining the incidence, epidemiology, and mortality rate of CAP in the ICUs in Louisville, Kentucky. The secondary objective was to estimate the number of patients who were hospitalized and the number of deaths that were associated with CAP in ICU in the United States.
What is epidemiology of CAP in the ICU in Louisville, Kentucky, and the projected incidence in the United States?
This was a secondary analysis of a prospective population-based cohort study. The setting was all nine adult hospitals in Louisville, Kentucky. The annual incidence of CAP in the ICU per 100,000 adults was calculated for the whole adult population of Louisville. The number of patients who were hospitalized because of CAP in ICU in the United States was estimated by multiplying the Louisville incidence rate of CAP in ICU by the 2014 US adult population.
From a total of 7,449 unique patients who were hospitalized with CAP, 1,707 patients (23%) were admitted to the ICU. The incidence of CAP in the ICU was 145 cases per 100,000 population of adults. Cases of CAP in the ICU were clustered in patients from areas of the city with high poverty. The mortality rate of patients with CAP in ICU was 27% at 30 days and 47% at one year. In the United States, the estimated number of patients who were hospitalized with CAP requiring the ICU was 356,326 per year, and the estimated number of deaths at 30 days and one year were 96,206 and 167,474, respectively.
Almost one in five patients who are hospitalized with CAP requires intensive care. Poverty is associated with CAP in the ICU. Nearly one-half of patients with CAP in the ICU will die within one year. Because of its significant burden, CAP in the ICU should be a high priority in research agenda and health policy.
Incidence estimates of hospitalizations for community-acquired pneumonia among children in the United States that are based on prospective data collection are limited. Updated estimates of pneumonia ...that has been confirmed radiographically and with the use of current laboratory diagnostic tests are needed.
We conducted active population-based surveillance for community-acquired pneumonia requiring hospitalization among children younger than 18 years of age in three hospitals in Memphis, Nashville, and Salt Lake City. We excluded children with recent hospitalization or severe immunosuppression. Blood and respiratory specimens were systematically collected for pathogen detection with the use of multiple methods. Chest radiographs were reviewed independently by study radiologists.
From January 2010 through June 2012, we enrolled 2638 of 3803 eligible children (69%), 2358 of whom (89%) had radiographic evidence of pneumonia. The median age of the children was 2 years (interquartile range, 1 to 6); 497 of 2358 children (21%) required intensive care, and 3 (<1%) died. Among 2222 children with radiographic evidence of pneumonia and with specimens available for bacterial and viral testing, a viral or bacterial pathogen was detected in 1802 (81%), one or more viruses in 1472 (66%), bacteria in 175 (8%), and both bacterial and viral pathogens in 155 (7%). The annual incidence of pneumonia was 15.7 cases per 10,000 children (95% confidence interval CI, 14.9 to 16.5), with the highest rate among children younger than 2 years of age (62.2 cases per 10,000 children; 95% CI, 57.6 to 67.1). Respiratory syncytial virus was more common among children younger than 5 years of age than among older children (37% vs. 8%), as were adenovirus (15% vs. 3%) and human metapneumovirus (15% vs. 8%). Mycoplasma pneumoniae was more common among children 5 years of age or older than among younger children (19% vs. 3%).
The burden of hospitalization for children with community-acquired pneumonia was highest among the very young, with respiratory viruses the most commonly detected causes of pneumonia. (Funded by the Influenza Division of the National Center for Immunization and Respiratory Diseases.).
Previous studies examining bacteremia in hospitalized children with pneumonia are limited by incomplete culture data. We sought to determine characteristics of children with bacteremic pneumonia ...using data from a large prospective study with systematic blood culturing.
Children <18 years hospitalized with pneumonia and enrolled in the multicenter Etiology of Pneumonia in the Community study between January 2010 and June 2012 were eligible. Bivariate comparisons were used to identify factors associated with bacteremia. Associations between bacteremia and clinical outcomes were assessed by using Cox proportional hazards regression for length of stay and logistic regression for ICU admission and invasive mechanical ventilation or shock.
Blood cultures were obtained in 2143 (91%) of 2358 children; 46 (2.2%) had bacteremia. The most common pathogens were
(
= 23, 50%),
(
= 6, 13%), and
(
= 4, 9%). Characteristics associated with bacteremia included male sex, parapneumonic effusion, lack of chest indrawing or wheezing, and no previous receipt of antibiotics. Children with bacteremia had longer lengths of stay (median: 5.8 vs 2.8 days; adjusted hazard ratio: 0.79 0.73-0.86) and increased odds of ICU admission (43% vs 21%; adjusted odds ratio: 5.21 3.82-6.84) and invasive mechanical ventilation or shock (30% vs 8%; adjusted odds ratio: 5.28 2.41-11.57).
Bacteremia was uncommonly detected in this large multicenter cohort of children hospitalized with community-acquired pneumonia but was associated with severe disease.
was detected most often. Blood culture was of low yield in general but may have greater use in those with parapneumonic effusion and ICU admission.
Discriminating between competing explanatory models as to which is more likely responsible for the growth of a network is a problem of fundamental importance for network science. The rules governing ...this growth are attributed to mechanisms such as preferential attachment and triangle closure, with a wealth of explanatory models based on these. These models are deliberately simple, commonly with the network growing according to a constant mechanism for its lifetime, to allow for analytical results. We use a likelihood-based framework on artificial data where the network model changes at a known point in time and demonstrate that we can recover the change point from analysis of the network. We then use real datasets and demonstrate how our framework can show the changing importance of network growth mechanisms over time.
Causes of late Quaternary extinctions of large mammals ("megafauna") continue to be debated, especially for continental losses, because spatial and temporal patterns of extinction are poorly known. ...Accurate latest appearance dates (LADs) for such taxa are critical for interpreting the process of extinction. The extinction of woolly mammoth and horse in northwestern North America is currently placed at 15,000-13,000 calendar years before present (yr BP), based on LADs from dating surveys of macrofossils (bones and teeth). Advantages of using macrofossils to estimate when a species became extinct are offset, however, by the improbability of finding and dating the remains of the last-surviving members of populations that were restricted in numbers or confined to refugia. Here we report an alternative approach to detect 'ghost ranges' of dwindling populations, based on recovery of ancient DNA from perennially frozen and securely dated sediments (sedaDNA). In such contexts, sedaDNA can reveal the molecular presence of species that appear absent in the macrofossil record. We show that woolly mammoth and horse persisted in interior Alaska until at least 10,500 yr BP, several thousands of years later than indicated from macrofossil surveys. These results contradict claims that Holocene survival of mammoths in Beringia was restricted to ecologically isolated high-latitude islands. More importantly, our finding that mammoth and horse overlapped with humans for several millennia in the region where people initially entered the Americas challenges theories that megafaunal extinction occurred within centuries of human arrival or were due to an extraterrestrial impact in the late Pleistocene.
In a large study of children hospitalized with community-acquired pneumonia, virus-bacterium coinfections resulted in worse outcomes than virus-only infections. Patterns of coinfections varied with ...the pathogen.
Abstract
Background
Recognition that coinfections are common in children with community-acquired pneumonia (CAP) is increasing, but gaps remain in our understanding of their frequency and importance.
Methods
We analyzed data from 2219 children hospitalized with CAP and compared demographic and clinical characteristics and outcomes between groups with viruses alone, bacteria alone, or coinfections. We also assessed the frequency of selected pairings of codetected pathogens and their clinical characteristics.
Results
A total of 576 children (26%) had a coinfection. Children with only virus detected were younger, more likely to be black, and more likely to have comorbidities such as asthma, compared with children infected with typical bacteria alone. Children with virus-bacterium coinfections had a higher frequency of leukocytosis, consolidation on chest radiography, parapneumonic effusions, intensive care unit admission, and need for mechanical ventilation and an increased length of stay, compared with children infected with viruses alone. Virus-virus coinfections were generally comparable to single-virus infections, with the exception of the need for oxygen supplementation, which was higher during the first 24 hours of hospitalization in some virus-virus pairings.
Conclusions
Coinfections occurred in 26% of children hospitalized for CAP. Children with typical bacterial infections, alone or complicated by a viral infection, have worse outcomes than children infected with a virus alone.
Abstract
Background
Parainfluenza virus (PIV) is a leading cause of lower respiratory tract infections. Although there are several distinct PIV serotypes, few studies have compared the clinical ...characteristics and severity of infection among the individual PIV serotypes and between PIV and other pathogens in patients with community-acquired pneumonia.
Methods
We conducted active population-based surveillance for radiographically confirmed community-acquired pneumonia hospitalizations among children and adults in 8 US hospitals with systematic collection of clinical data and respiratory, blood, and serological specimens for pathogen detection. We compared clinical features of PIV-associated pneumonia among individual serotypes 1, 2, and 3 and among all PIV infections with other viral, atypical, and bacterial pneumonias. We also compared in-hospital disease severity among groups employing an ordinal scale (mild, moderate, severe) using multivariable proportional odds regression.
Results
PIV was more commonly detected in children (155/2354; 6.6%) than in adults (66/2297; 2.9%) (P < .001). Other pathogens were commonly co-detected among PIV cases (110/221; 50%). Clinical features of PIV-1, PIV-2, and PIV-3 infections were similar to one another in both children and adults with pneumonia. In multivariable analysis, children with PIV-associated pneumonia exhibited similar severity to children with other nonbacterial pneumonia, whereas children with bacterial pneumonia exhibited increased severity (odds ratio, 8.42; 95% confidence interval, 1.88–37.80). In adults, PIV-associated pneumonia exhibited similar severity to other pneumonia pathogens.
Conclusions
Clinical features did not distinguish among infection with individual PIV serotypes in patients hospitalized with community-acquired pneumonia. However, in children, PIV pneumonia was less severe than bacterial pneumonia.
Clinical features did not reliably distinguish pneumonia with different parainfluenza virus (PIV) serotypes. Among children, PIV pneumonia was less severe than bacterial pneumonia, but in adults the severity of PIV pneumonia did not significantly differ from other pathogens.
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