Metagenomics versus total RNA sequencing: most accurate data-processing tools, microbial identification accuracy and perspectives for ecological assessments.

Metagenomics and total RNA sequencing (total RNA-Seq) have the potential to improve the taxonomic identification of diverse microbial communities, which could allow for the incorporation of microbes into routine ecological assessments. However, these target-PCR-free techniques require more testing and optimization. In this study, we processed metagenomics and total RNA-Seq data from a commercially available microbial mock community using 672 data-processing workflows, identified the most accurate data-processing tools, and compared their microbial identification accuracy at equal and increasing sequencing depths. The accuracy of data-processing tools substantially varied among replicates. Total RNA-Seq was more accurate than metagenomics at equal sequencing depths and even at sequencing depths almost one order of magnitude lower than those of metagenomics. We show that while data-processing tools require further exploration, total RNA-Seq might be a favorable alternative to metagenomics for target-PCR-free taxonomic identifications of microbial communities and might enable a substantial reduction in sequencing costs while maintaining accuracy. This could be particularly an advantage for routine ecological assessments, which require cost-effective yet accurate methods, and might allow for the incorporation of microbes into ecological assessments.

Blood Variation Implicates Respiratory Limits on Elevational Ranges of Andean Birds.

AbstractThe extent to which species ranges reflect intrinsic physiological tolerances is a major question in evolutionary ecology. To date, consensus has been hindered by the limited tractability of experimental approaches across most of the tree of life. Here, we apply a macrophysiological approach to understand how hematological traits related to oxygen transport shape elevational ranges in a tropical biodiversity hot spot. Along Andean elevational gradients, we measured traits that affect blood oxygen-carrying capacity-total and cellular hemoglobin concentration and hematocrit, the volume percentage of red blood cells-for 2,355 individuals of 136 bird species. We used these data to evaluate the influence of hematological traits on elevational ranges. First, we asked whether the sensitivity of hematological traits to changes in elevation is predictive of elevational range breadth. Second, we asked whether variance in hematological traits changed as a function of distance to the nearest elevational range limit. We found that birds showing greater hematological sensitivity had broader elevational ranges, consistent with the idea that a greater acclimatization capacity facilitates elevational range expansion. We further found reduced variation in hematological traits in birds sampled near their elevational range limits and at high absolute elevations, patterns consistent with intensified natural selection, reduced effective population size, or compensatory changes in other cardiorespiratory traits. Our findings suggest that constraints on hematological sensitivity and local genetic adaptation to oxygen availability promote the evolution of the narrow elevational ranges that underpin tropical montane biodiversity.

Epidemiology of early and late-onset neonatal sepsis in an Australian regional special care nursery with a high proportion of Aboriginal and Torres Strait Islander births.

AIM: To describe the incidence and aetiology of early and late-onset neonatal sepsis and compare rates in Aboriginal and Torres Strait Islander infants against non-Indigenous infants in the Top End of the Northern Territory. METHODS: This was a retrospective case series of infants with positive blood or cerebrospinal fluid cultures at Royal Darwin Hospital between 2012 and 2016. Cultures from infants during initial hospital admission up to 120 days of age were included for analysis. Demographic, clinical, laboratory and treatment data were collected from medical records. Published definitions of sepsis and criteria for organism pathogenicity and were used to determine cases of sepsis. RESULTS: There were 52 episodes of sepsis in 45 infants. There were eight cases of early onset sepsis, with an incidence of 0.51 per 1000 live births. The incidence was similar for Aboriginal and non-Indigenous infants. The case fatality rate was 25%. Late-onset sepsis occurred in 44 cases, comprising 1.3% of all infants admitted to the special care nursery. Coagulase-negative Staphylococcus was the most frequently cultured organism. Case fatality rate was 11%. Aboriginal and Torres Strait Islander infants had a five-time higher risk of late-onset sepsis compared with non-Indigenous infants; however, their increased risk was not independent of other sepsis risk factors of low rates and prematurity. CONCLUSIONS: The incidence of culture-confirmed early and late-onset sepsis was low, but case fatality was high. Bacteraemia is an important contributor to neonatal and infant mortality in our setting.

Loneliness, physical activity, and mental health during COVID-19: a longitudinal analysis of depression and anxiety in adults over the age of 50 between 2015 and 2020.

OBJECTIVE: Loneliness and physical activity are important targets for research into the impact of COVID-19 because they have established links with mental health, could be exacerbated by social distancing policies, and are potentially modifiable. In this study, we aimed to identify whether loneliness and physical activity were associated with worse mental health during a period of mandatory social distancing in the UK. DESIGN: Population-based observational cohort study. SETTING: Mental health data collected online during COVID-19 from an existing sample of adults aged 50 and over taking part in a longitudinal study of aging. All had comparable annual data collected between 2015 and 2019. PARTICIPANTS: Three-thousand two-hundred and eighty-one participants aged 50 and over. MEASUREMENTS: Trajectories of depression (measured by PHQ-9) and anxiety (measured by GAD-7) between 2015 and 2020 were analyzed with respect to loneliness, physical activity levels, and a number of socioeconomic and demographic characteristics using zero-inflated negative binomial regression. RESULTS: In 2020, PHQ-9 score for loneliness, adjusted for covariates, was 3.23 (95% CI: 3.01-3.44), an increase of around 1 point on all previous years in this group and 2 points higher than people not rated lonely, whose score did not change in 2020 (1.22, 95% CI: 1.12-1.32). PHQ-9 was 2.60 (95% CI: 2.43-2.78) in people with decreased physical activity, an increase of .5 on previous years. In contrast, PHQ-9 in 2020 for people whose physical activity had not decreased was 1.66, 95% CI: 1.56-1.75, similar to previous years. A similar relationship was observed for GAD-7 though the absolute burden of symptoms lower. CONCLUSION: After accounting for pre-COVID-19 trends, we show that experiencing loneliness and decreased physical activity are risk factors for worsening mental health during the pandemic. Our findings highlight the need to examine policies which target these potentially modifiable risk factors.

Use of the Sports Concussion Assessment Tool 3 in Emergency Department Patients With Psychiatric Disease.

OBJECTIVE: The Sports Concussion Assessment Tool 3 (SCAT3) Symptom Evaluation (SE) is used in the emergency department (ED). This study aimed to examine the effects of psychiatric history on the SCAT3 SE symptom severity score (SSS). SETTING: Three US EDs. PARTICIPANTS: A total of 272 ED patients with suspected concussion. DESIGN: Prospective, nonrandomized, nonblinded study. The SCAT3 SE SSS, demographic data, medical information, and self-reported psychiatric history were obtained from patients by clinical research staff when they presented to the ED seeking standard clinical care. Concussion diagnoses were determined following a comprehensive assessment by an ED physician trained in managing concussions and adjudicated by supervising physicians. MAIN MEASURES: The primary outcome measure was SSS. The association between SSS, self-reported psychiatric disease, and concussion diagnosis was analyzed using multivariable linear regression. RESULTS: 68.4% of subjects were diagnosed with a concussion. After controlling for age, sex, race, history of previous concussion, and interval from injury to ED presentation, self-reported psychiatric history (adjusted regression coefficient (ßa): 16.9; confidence interval [CI]: 10.1, 23.6), and concussion diagnosis (ßa: 21.7; CI: 14.2, 29.2) were both independently associated with a significant increase in SSS. Subjects with a history of concussion had a significantly higher SSS (ßa: 9.1; CI: 1.8, 16.5). Interval from injury to ED presentation was also associated with a significant increase in SSS (ßa: 1.6 per 6-hour increase; CI: 0.4, 2.8). CONCLUSION: Our findings demonstrate that a history of preexisting psychiatric disease, as self-reported by patients with a suspected concussion treated in the ED, is independently associated with significantly higher scores on the SCAT3 SE. This suggests that a history of psychiatric illness may need to be accounted for when the SCAT3 SE is used in the ED for the assessment of concussion.

Predictable evolution toward flightlessness in volant island birds.

Birds are prolific colonists of islands, where they readily evolve distinct forms. Identifying predictable, directional patterns of evolutionary change in island birds, however, has proved challenging. The "island rule" predicts that island species evolve toward intermediate sizes, but its general applicability to birds is questionable. However, convergent evolution has clearly occurred in the island bird lineages that have undergone transitions to secondary flightlessness, a process involving drastic reduction of the flight muscles and enlargement of the hindlimbs. Here, we investigated whether volant island bird populations tend to change shape in a way that converges subtly on the flightless form. We found that island bird species have evolved smaller flight muscles than their continental relatives. Furthermore, in 366 populations of Caribbean and Pacific birds, smaller flight muscles and longer legs evolved in response to increasing insularity and, strikingly, the scarcity of avian and mammalian predators. On smaller islands with fewer predators, birds exhibited shifts in investment from forelimbs to hindlimbs that were qualitatively similar to anatomical rearrangements observed in flightless birds. These findings suggest that island bird populations tend to evolve on a trajectory toward flightlessness, even if most remain volant. This pattern was consistent across nine families and four orders that vary in lifestyle, foraging behavior, flight style, and body size. These predictable shifts in avian morphology may reduce the physical capacity for escape via flight and diminish the potential for small-island taxa to diversify via dispersal.

Energetics, lifestyle, and reproduction in birds.

Theoretical and empirical studies of life history aim to account for resource allocation to the different components of fitness: survival, growth, and reproduction. The pioneering evolutionary ecologist David Lack [(1968) Ecological Adaptations for Breeding in Birds (Methuen and Co., London)] suggested that reproductive output in birds reflects adaptation to environmental factors such as availability of food and risk of predation, but subsequent studies have not always supported Lack's interpretation. Here using a dataset for 980 bird species (Dataset S1), a phylogeny, and an explicit measure of reproductive productivity, we test predictions for how mass-specific productivity varies with body size, phylogeny, and lifestyle traits. We find that productivity varies negatively with body size and energetic demands of parental care and positively with extrinsic mortality. Specifically: (i) altricial species are 50% less productive than precocial species; (ii) species with female-only care of offspring are about 20% less productive than species with other methods of parental care; (iii) nonmigrants are 14% less productive than migrants; (iv) frugivores and nectarivores are about 20% less productive than those eating other foods; and (v) pelagic foragers are 40% less productive than those feeding in other habitats. A strong signal of phylogeny suggests that syndromes of similar life-history traits tend to be conservative within clades but also to have evolved independently in different clades. Our results generally support both Lack's pioneering studies and subsequent research on avian life history.

Metabolic 'engines' of flight drive genome size reduction in birds.

The tendency for flying organisms to possess small genomes has been interpreted as evidence of natural selection acting on the physical size of the genome. Nonetheless, the flight-genome link and its mechanistic basis have yet to be well established by comparative studies within a volant clade. Is there a particular functional aspect of flight such as brisk metabolism, lift production or maneuverability that impinges on the physical genome? We measured genome sizes, wing dimensions and heart, flight muscle and body masses from a phylogenetically diverse set of bird species. In phylogenetically controlled analyses, we found that genome size was negatively correlated with relative flight muscle size and heart index (i.e. ratio of heart to body mass), but positively correlated with body mass and wing loading. The proportional masses of the flight muscles and heart were the most important parameters explaining variation in genome size in multivariate models. Hence, the metabolic intensity of powered flight appears to have driven genome size reduction in birds.

Investigation of COVID-19 transmission during the first community outbreak in a remote island population, Falkland Islands, April to June 2022.

After 2 years of no community outbreaks of COVID-19, the Falkland Islands (FI) reported their first community case in April 2022. Because of high vaccine coverage (88% of entire population), no specific control measures were instigated, and cases spread rapidly. We undertook a retrospective cohort study to determine the extent of transmission and the effectiveness of COVID-19 vaccine in a population with limited natural immunity. We extracted data on age, sex, and vulnerability for the FI registered population from a patient information system and linked to COVID-19 case line-list and vaccination datasets. Cases were individuals with positive SARS-CoV-2 PCRs or Lateral Flow Devices (LFDs), from 26 April to 30 June 2022. Univariable analyses compared case risk factors to non-cases. Relative vaccine effectiveness was calculated using Poisson regression with robust error variance, comparing against individuals with vaccination more than the 20 weeks prior to the outbreak. Models were adjusted for age, sex, extreme vulnerability, and previous infection. Of the 3,343 registered population, 44% (n = 1,467) were cases, with no COVID-19 hospitalisations or deaths. In univariable analysis, being female (RR 1.12, p = 0.004) and under 18 years (RR 1.70, p<0.001) were associated with increased COVID-19 risk. Relative vaccine effectiveness was 39.0% (95% CI, 1.03 to 62.5) and 33.0% (95% CI, 8.3 to 51.0) 1 to 9 weeks after receiving 2nd and 1st boosters respectively. We showed widespread transmission in a small island population with limited natural immunity, disproportionately affecting children and women, indicative of transmission in educational and household settings. Despite limited natural immunity, our findings suggested that vaccination was effective protecting against severe disease and booster doses provided additional short-term protection against infection. We would recommend optimizing coverage with boosters of vaccine in remote island populations such as FI. Follow-up would be needed to assess duration of protection after booster vaccination.

High-definition transcranial direct current stimulation desynchronizes refractory status epilepticus.

Recently, we showed that high-definition transcranial direct current stimulation (hd-tDCS) can acutely reduce epileptic spike rates during and after stimulation in refractory status epilepticus (RSE), with a greater likelihood of patient discharge from the intensive care unit compared to historical controls. We investigate whether electroencephalographic (EEG) desynchronization during hd-tDCS can help account for observed anti-epileptic effects. Defining desynchronization as greater power in higher frequencies such as above 30 â€‹Hz ("gamma") and lesser power in frequency bands lower than 30 â€‹Hz, we analyzed 27 EEG sessions from 10 RSE patients who had received 20-minute session(s) of 2-milliamperes of transcranial direct current custom-targeted at the epileptic focus as previously determined by a clinical EEGer monitoring the EEG in real-time. During hd-tDCS, median relative power change over the EEG electrode chains in which power changes were maximal was +4.84%, -5.25%, -1.88%, -1.94%, and +4.99% for respective delta, theta, alpha, beta, and gamma frequency bands in the bipolar longitudinal montage (p â€‹= â€‹0.0001); and +4.13%, -5.44%, -1.81%, -3.23%, and +5.41% in the referential Laplacian montage (p â€‹= â€‹0.0012). After hd-tDCS, median relative power changes reversed over the EEG electrode chains in which power changes were maximal: -2.74%, +4.20%, +1.74%, +1.75%, and -4.68% for the respective delta, theta, alpha, beta, and gamma frequency bands in the bipolar longitudinal montage (p â€‹= â€‹0.0001); and +1.59%, +5.07%, +1.74%, +2.40%, and -5.12% in the referential Laplacian montage (p â€‹= â€‹0.0004). These findings are consistent with EEG desynchronization through theta-alpha-beta-gamma bands during hd-tDCS, helping account for the efficacy of hd-tDCS as an emerging novel anti-epileptic therapy against RSE.

A Pilot Study of High-Definition Transcranial Direct Current Stimulation in Refractory Status Epilepticus: The SURESTEP Trial.

Refractory status epilepticus (RSE) is a life-threatening emergency with high mortality and poor functional outcomes in survivors. Treatment is typically limited to intravenous anesthetic infusions and multiple anti-seizure medications. While ongoing seizures can cause permanent neurological damage, medical therapies also pose severe and life-threatening side effects. We tested the feasibility of using high-definition transcranial direct current stimulation (hd-tDCS) in the treatment of RSE. We conducted 20-min hd-tDCS sessions at an outward field orientation, intensity of 2-mA, 4 + 1 channels, and customized for deployment over the electrographic maximum of epileptiform activity ("spikes") determined by real-time clinical EEG monitoring. There were no adverse events from 32 hd-tDCS sessions in 10 RSE patients. Over steady dosing states of infusions and medications in 29 included sessions, median spike rates/patient fell by 50% during hd-tDCS on both automated (p = 0.0069) and human (p = 0.0277) spike counting. Median spike rates for any given stimulation session also fell by 50% during hd-tDCS on automated spike counting (p = 0.0032). Immediately after hd-tDCS, median spike rates/patient remained down by 25% on human spike counting (p = 0.018). Compared to historical controls, hd-tDCS subjects were successfully discharged from the intensive care unit (ICU) 45.8% more often (p = 0.004). When controls were selected using propensity score matching, the discharge rate advantage improved to 55% (p = 0.002). Customized EEG electrode targeting of hd-tDCS is a safe and non-invasive method of hyperacutely reducing epileptiform activity in RSE. Compared to historical controls, there was evidence of a cumulative chronic clinical response with more hd-tDCS subjects discharged from ICU.

Novel Analysis Identifying Functional Connectivity Patterns Associated with Posttraumatic Stress Disorder.

Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder that can result from experiencing traumatic events. Accurate diagnosis and optimal treatment strategies can be difficult to achieve, due to the heterogeneous etiology and symptomology of PTSD, and overlap with other psychiatric disorders. Advancing our understanding of PTSD pathophysiology is therefore critical. While functional connectivity alterations have shown promise for elucidating the neurobiological mechanisms of PTSD, previous findings have been inconsistent. Eleven patients with PTSD in our first cohort (PTSD-A) and 11 trauma-exposed controls (TEC) underwent functional magnetic resonance imaging. First, we investigated the intrinsic connectivity within known resting state networks (eg, default mode, salience, and central executive networks) previously implicated in functional abnormalities with PTSD symptoms. Second, the overall topology of network structure was compared between PTSD-A and TEC using graph theory. Finally, we used a novel combination of graph theory analysis and scaled subprofile modeling (SSM) to identify a disease-related, covarying pattern of brain network organization. No significant group differences were found in intrinsic connectivity of known resting state networks and graph theory metrics (clustering coefficients, characteristic path length, smallworldness, global and local efficiencies, and degree centrality). The graph theory/SSM analysis revealed a topographical pattern of altered degree centrality differentiating PTSD-A from TEC. This PTSD-related network pattern expression was additionally investigated in a separate cohort of 33 subjects who were scanned with a different MRI scanner (22 patients with PTSD or PTSD-B, and 11 healthy trauma-naïve controls or TNC). Across all participant groups, pattern expression scores were significantly lower in the TEC group, while PTSD-A, PTSD-B, and TNC subject profiles did not differ from each other. Expression level of the pattern was correlated with symptom severity in the PTSD-B group. This method offers potential in developing objective biomarkers associated with PTSD. Possible interpretations and clinical implications will be discussed.

Increased Pass Rates in Introductory Biology: Benefits and Potential Costs of Implementing a Mathematics Prerequisite in a Community College Setting.

We explored the impacts of a mathematics prerequisite on student success in Introductory Biology, focusing on students historically underserved in science, technology, engineering, and mathematics (STEM). Specifically, we studied Introductory Biology student outcomes 5 years before and 6 years after adding the prerequisite. Students who had not previously passed Intermediate Algebra had a 54.91% chance of passing Introductory Biology, compared with a ​​69.25% chance for students who had passed this math course. Furthermore, we found a disproportionate benefit of passing the math course for Pell Grant recipients. When considering pre- versus post-prerequisite terms of Introductory Biology, we found pass rates were significantly higher after the mathematics prerequisite was required, but grades were not. After the mathematics prerequisite, enrollments in Introductory Biology temporarily decreased in comparison to a similar chemistry course and the college's overall enrollments, a potential cost to students. Pell Grant recipients and women took Introductory Biology at the same rate as before, and contrary to our hypothesis, we saw the proportion of persons excluded due to ethnicity or race (PEER) students enrolled in Introductory Biology was higher after the implementation. This study provides a model for assessing prerequisites in a local context and contributes evidence that mathematical prerequisites can benefit students.

Histologic and Genotypic Characterization of Lung Cancer in the Inuit Population of the Eastern Canadian Arctic.

Inuit are the Indigenous Arctic peoples and residents of the Canadian territory of Nunavut who have the highest global rate of lung cancer. Given lung cancer's mortality, histological and genomic characterization was undertaken to better understand the disease biology. We retrospectively studied all Inuit cases from Nunavut's Qikiqtani (Baffin) region, referred to the Ottawa Hospital Cancer Center between 2001 and 2011. Demographics were compiled from medical records and tumor samples underwent pathologic/histologic confirmation. Tumors were analyzed by next generation sequencing (NGS) with a cancer hotspot mutation panel. Of 98 patients, the median age was 66 years and 61% were male. Tobacco use was reported in 87%, and 69% had a history of lung disease (tuberculosis or other). Histological types were: non-small cell lung carcinoma (NSCLC), 81%; small cell lung carcinoma, 16%. Squamous cell carcinoma (SCC) represented 65% of NSCLC. NGS on 55 samples demonstrated mutation rates similar to public lung cancer datasets. In SCC, the STK11 F354L mutation was observed at higher frequency than previously reported. This is the first study to characterize the histologic/genomic profiles of lung cancer in this population. A high incidence of SCC, and an elevated rate of STK11 mutations distinguishes this group from the North American population.

Healthcare utilisation and physical activities for older adults with comorbidities in the UK during COVID-19.

A major concern with COVID-19 was the impact it would have on individual health, the routine use of healthcare services, and physical activities, especially for older adults with comorbidities. To address this, we studied the association between these variables for older adults during the pandemic. To explore what policy instruments might be effective in mitigating the negative impacts, we investigated the effects of a shielding notice for those identified as vulnerable by the government and social media given it has been an important source for disseminating information of COVID-19. We employed a UK sample with 3,807 participants aged ≥50 from an online survey administered during May and June 2020. Based on numbers of comorbidities, we separated the sample into a higher comorbidity group with those in the upper quartile of the sample (n = 829) and a lower comorbidity group with the remainder (n = 2,978). Statistical methods include chi-squared analyses and cross-sectional regressions. We found that individuals with higher comorbidities were more likely to have poorer self-reported health and mental health and to receive a shielding notice from the government compared to those without (p < 0.05). Decreases in physical activities were associated with poorer self-reported health and the increases were associated with better self-reported health; on the other hand, the decreases were associated with poorer mental health, but the increases did not link to better mental health. Examination of the effects of policy instruments shows that a shielding notice was positively associated with primary care use. The notice generated greater reliance on telephone/video consultations compared to in-person consultations, but the impacts were less strong for people with higher comorbidities. Frequent use of social media raised the probability of increasing physical activities and reduced that of decreasing physical activities, implying social media being an effective tool in promoting physical activities during the lockdown and subsequent restrictions.

Healthcare utilisation, physical activity and mental health during COVID-19 lockdown: an interrupted time-series analysis of older adults in England.

COVID-19 measures which reduce interpersonal contact may be effective in containing the transmission, but their impacts on peoples' well-being and daily lives overtime remain unclear. Older adults are more vulnerable to both the virus and social isolation. It is therefore imperative to understand how they were affected during this period. Major concerns arising from the pandemic cover the aspects of mental health, healthcare utilisation and individual behavioural changes. Complementing the existing before-and-after analyses, we explore the impacts of easing and re-introducing COVID-19 measures by using a time-series data in England. The data was collected between May and November 2020 from the monthly surveys of the Platform for Research Online to Investigate Genetics and Cognition in Aging (PROTECT). Chi-squared analysis and interrupted time-series analysis were conducted to examine impacts of easing and re-introducing COVID-19 measures. Overall, mental health improves overtime but at a decreasing rate. The use of telephone/video consultations with a doctor or health professional presented a decreasing trend during the pandemic, whilst that of in-person consultation was increasing overtime. We observed significant variations in the time trends of mental health measures, healthcare utilisation and physical activity following the ease but not the re-introduction of COVID-19 measures. Future research is required to understand if these asymmetric impacts were driven by adaption of the people or stringency of the measures. Supplementary Information: The online version contains supplementary material available at 10.1007/s10433-022-00741-y.

Fixed drug eruption associated with intravenous contrast media: report in a woman receiving iohexol.

Fixed drug eruption, a medication-associated mucocutaneous reaction, rarely presents as a delayed adverse reaction to intravenous non-ionic contrast media. We describe a 57-year-old woman with a history of metastatic renal cell carcinoma who repeatedly developed a sharply demarcated, erythematous patch on her left breast after receiving the iodinated non-ionic contrast media iohexol for staging computed tomography scans. Recurrent fixed drug eruption may be avoided by using another contrast medium. Prophylactic treatment with systemic corticosteroids may prevent repeated fixed drug eruption if an alternative contrast agent cannot be used.