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Small pulmonary nodules (≤1.5 cm) are frequently detected on routine chest imaging and lung cancer screening studies. Our goal was to determine the clinical value of CT-guided core needle biopsy (CNB) in the evaluation of such nodules. In this single-center study, we retrospectively analyzed patient data (n = 44) for CNBs on lung nodules (≤1.5 cm) performed at our biopsy center between May 2017 and March 2020. We analyzed for the rate of pathology diagnosis, molecular/biomarker analysis, complications, and change in clinical management and outcome over a period ranging up to 60 months after biopsy. A pathology diagnosis of malignancy or benign lesion was obtained in 97.9% of biopsies in this cohort. The rate of complications was low with only 6.8% of patients requiring the insertion of a temporary small profile interventional radiology (IR) pigtail chest tube for pneumothorax. Out of the subset of biopsy specimens that were sent for tissue molecular analysis, 90% had enough tissue preserved after initial pathological analysis to obtain at least one molecular marker. Our data show that CT-guided CNB is safe and reliable, and should be considered for the evaluation of small, suspicious lung nodules found on routine screenings for the early detection and evaluation of malignant lesions.

To address the need for simple, safe, sensitive, and scalable SARS-CoV-2 tests, we validated and implemented a PCR test that uses a saliva collection kit use at home. Individuals self-collected 300 μl saliva in vials containing Darnell Rockefeller University Laboratory (DRUL) buffer and extracted RNA was assayed by RT-PCR (the DRUL saliva assay). The limit of detection was confirmed to be 1 viral copy/μl in 20 of 20 replicate extractions. Viral RNA was stable in DRUL buffer at room temperature up to seven days after sample collection, and safety studies demonstrated that DRUL buffer immediately inactivated virus at concentrations up to 2.75x106 PFU/ml. Results from SARS-CoV-2 positive nasopharyngeal (NP) swab samples collected in viral transport media and assayed with a standard FDA Emergency Use Authorization (EUA) test were highly correlated with samples placed in DRUL buffer. Direct comparison of results from 162 individuals tested by FDA EUA oropharyngeal (OP) or NP swabs with co-collected saliva samples identified four otherwise unidentified positive cases in DRUL buffer. Over six months, we collected 3,724 samples from individuals ranging from 3 months to 92 years of age. This included collecting weekly samples over 10 weeks from teachers, children, and parents from a pre-school program, which allowed its safe reopening while at-risk pods were quarantined. In sum, we validated a simple, sensitive, stable, and safe PCR-based test using a self-collected saliva sample as a valuable tool for clinical diagnosis and screening at workplaces and schools.

Access to books and a rich language environment at home are important for children's language development. In this study we explored self-reported reading practices in families in Norway (N = 1001) to gain insight into the reading habits parents have with their young children, and the factors that best explain book reading in Norwegian homes. By investigating relationships between how many books parents reported reading with their child last week, demographic factors, and orientational variables, we found that book reading is better explained by orientational factors -- such as children's interest in books and having reading routines in the home -- than by demographic factors (such as parents' educational level). The proportion of parents reporting reading no books, or only one book with their child in the last week was unexpectedly large (33%). The implication of these findings for the culture of reading in Norwegian homes is discussed.

This article explains how and why the learning activity "out and about in the eighteenth century" fosters students' understanding of historical and cultural issues related to gender and class in eighteenth-century novels.

Successful autologous skeletal myoblast transplantation into infarcted myocardium in a variety of animal models has demonstrated improvement in cardiac function. We evaluated the safety and feasibility of transplanting autologous myoblasts into infarcted myocardium of patients undergoing concurrent coronary artery bypass grafting (CABG) or left ventricular assist device implantation (LVAD). In addition, we sought to gain preliminary information on graft survival and any potential improvement of cardiac function. Eighteen patients with a history of ischemic cardiomyopathy participated in a phase I, nonrandomized, multicenter pilot study of autologous skeletal myoblast transplantation concurrent with CABG or LVAD implantation. Twelve patients with a history of previous myocardial infarction (MI) and a left ventricular ejection of less than 30% were enrolled in the CABG arm. In a second arm, six patients underwent LVAD implantation as a bridge to heart transplantation and were required to donate their heart for testing at the time of heart transplant. Myoblasts were successfully transplanted in all patients without any acute injection-related complications or significant long-term unexpected adverse events. Follow-up PET scans showed new areas of viability within the infarct scar in CABG patients. Echocardiography measured an average improvement in left ventricular ejection fraction (LVEF) from 25% to 34%. Histological evaluation in four out of five patients who underwent heart transplantation documented survival and engraftment of the skeletal myoblasts within the infarcted myocardium. These interim results demonstrate survival, feasibility, and safety of autologous myoblast transplantation and suggest that this modality may offer a potential therapeutic treatment for end-stage heart disease.

The International Committee on Systematics of Prokaryotes (ICSP) discussed and rejected in 2020 a proposal to modify the International Code of Nomenclature of Prokaryotes to allow the use of gene sequences as type for naming prokaryotes. An alternative nomenclatural code, the Code of Nomenclature of Prokaryotes Described from Sequence Data (SeqCode), which considers genome sequences as type material for naming species, was published in 2022. Members of the ICSP subcommittee for the taxonomy of the phylum Chlamydiae (Chlamydiota) consider that the use of gene sequences as type would benefit the taxonomy of microorganisms that are difficult to culture such as the chlamydiae and other strictly intracellular bacteria. We recommend the registration of new names of uncultured prokaryotes in the SeqCode registry.

Abstract New generation plasmid DNA vaccines may be a safe, fast and simple emergency vaccine platform for preparedness against emerging viral pathogens. Applying platform optimization strategies, we tested the pre-clinical immunogenicity and protective effect of a candidate DNA plasmid vaccine specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The DNA vaccine induced spike-specific binding IgG and neutralizing antibodies in mice, rabbits, and rhesus macaques together with robust Th1 dominant cellular responses in small animals. Intradermal and intramuscular needle-free administration of the DNA vaccine yielded comparable immune responses. In a vaccination-challenge study of rhesus macaques, the vaccine demonstrated protection from viral replication in the lungs following intranasal and intratracheal inoculation with SARS-CoV-2. In conclusion, the candidate plasmid DNA vaccine encoding the SARS-CoV-2 spike protein is immunogenic in different models and confers protection against lung infection in nonhuman primates. Further evaluation of this DNA vaccine candidate in clinical trials is warranted.

Background: The situation in the world today, encompassing multiple armed conflicts, notably in Ukraine, the Coronavirus pandemic and the effects of climate change, increases the likelihood of childhood exposure to physical injury and pain. Other effects of these worldwide hardships include poverty, malnutrition and starvation, also bringing with them other forms of trauma, including emotional harm, neglect and deliberate maltreatment. Objective: To review the neurobiology of the systems in the developing brain that are most affected by physical and emotional trauma and neglect. Method: The review begins with those that mature first, such as the somatosensory system, progressing to structures that have a more protracted development, including those involved in cognition and emotional regulation. Explored next are developing stress response systems, especially the hypothalamic–pituitary–adrenal axis and its central regulator, corticotropin-releasing hormone. Also examined are reward and anti-reward systems and genetic versus environmental influences. The behavioural consequences of interpersonal childhood trauma, focusing on self-harm and suicide, are also surveyed briefly. Finally, pointers to effective treatment are proffered. Results: The low-threshold nature of circuitry in the developing brain and lack of inhibitory connections therein result in heightened excitability, making the consequences of both physical and emotional trauma more intense. Sensitive and critical periods in the development of structures such as the amygdala render the nervous system more vulnerable to insults occurring at those points, increasing the likelihood of psychiatric disorders, culminating in self-harm and even suicide. Conclusion: In view of the greater excitability of the developing nervous system, and its vulnerability to physical and psychological injuries, the review ends with an exhortation to consider the long-term consequences of childhood trauma, often underestimated or missed altogether when faced with adults suffering mental health problems.

Two nutrient–phytoplankton–zooplankton (NZP) models for a closed ecosystem that incorporates a delay in nutrient recycling, obtained using the gamma distribution function with one or two degrees of freedom, are analysed. The models are described by systems of ordinary differential equations of four and five dimensions. The purpose of this study is to investigate how the mean delay of the distribution and the total nutrients affect the stability of the equilibrium solutions. Local stability theory and bifurcation theory are used to determine the long-time dynamics of the models. It is found that both models exhibit comparable qualitative dynamics. There are a maximum of three equilibrium points in each of the two models, and at most one of them is locally asymptotically stable. The change of stability from one equilibrium to another takes place through a transcritical bifurcation. In some hypotheses on the functional response, the nutrient–phytoplankton–zooplankton equilibrium loses stability via a supercritical Hopf bifurcation, causing the apparition of a stable limit cycle. The way in which the results are consistent with prior research and how they extend them is discussed. Finally, various application-related consequences of the results of the theoretical study are deduced.

The origins of this report, and of the Mental Health and Policing Working Group, can be traced to the unique situation Canadians have faced as a result of the COVID-19 pandemic. The unique circumstances of this global outbreak, which have for many Canadians resulted in serious illness and death, intensified economic uncertainties, altered family and lifestyle dynamics, and generated or exacerbated feelings of loneliness and social dislocation, rightly led the Royal Society of Canada’s COVID-19 Taskforce to consider the strains and other negative impacts on individual, group, and community mental health. With the central role that police too often play in the lives of individuals in mental and (or) emotional crisis, we were tasked with exploring what can be reasonably said about the state of our current knowledge of police responses to persons with mental illness.

We study a model for a network of synaptically coupled, excitable neurons to identify the role of coupling delays in generating different network behaviors. The network consists of two distinct populations, each of which contains one excitatory-inhibitory neuron pair. The two pairs are coupled via delayed synaptic coupling between the excitatory neurons, while each inhibitory neuron is connected only to the corresponding excitatory neuron in the same population. We show that multiple equilibria can exist depending on the strength of the excitatory coupling between the populations. We conduct linear stability analysis of the equilibria and derive necessary conditions for delay-induced Hopf bifurcation. We show that these can induce two qualitatively different phase-locked behaviors, with the type of behavior determined by the sizes of the coupling delays. Numerical bifurcation analysis and simulations supplement and confirm our analytical results. Our work shows that the resting equilibrium point is unaffected by the coupling, thus the network exhibits bistability between a rest state and an oscillatory state. This may help understand how rhythms spontaneously arise in neuronal networks.

The human brain constitutes one of the most advanced networks produced by nature, consisting of billions of neurons communicating with each other. However, this communication is not in real-time, with different communication or time-delays occurring between neurons in different brain areas. Here, we investigate the impacts of these delays by modeling large interacting neural circuits as neural-field systems which model the bulk activity of populations of neurons. By using a Master Stability Function analysis combined with numerical simulations, we find that delays (1) may actually stabilize brain dynamics by temporarily preventing the onset to oscillatory and pathologically synchronized dynamics and (2) may enhance or diminish synchronization depending on the underlying eigenvalue spectrum of the connectivity matrix. Real eigenvalues with large magnitudes result in increased synchronizability while complex eigenvalues with large magnitudes and positive real parts yield a decrease in synchronizability in the delay vs. instantaneously coupled case. This result applies to networks with fixed, constant delays, and was robust to networks with heterogeneous delays. In the case of real brain networks, where the eigenvalues are predominantly real, owing to the nearly symmetric nature of these weight matrices, biologically plausible, small delays, are likely to increase synchronization, rather than decreasing it.

Effective SARS-CoV-2 vaccines are urgently needed. Although most vaccine strategies have focused on systemic immunization, here we compared the protective efficacy of 2 adjuvanted subunit vaccines with spike protein S1: an intramuscularly primed/boosted vaccine and an intramuscularly primed/intranasally boosted mucosal vaccine in rhesus macaques. The intramuscular-alum–only vaccine induced robust binding and neutralizing antibody and persistent cellular immunity systemically and mucosally, whereas intranasal boosting with nanoparticles, including IL-15 and TLR agonists, elicited weaker T cell and Ab responses but higher dimeric IgA and IFN-α. Nevertheless, following SARS-CoV-2 challenge, neither group showed detectable subgenomic RNA in upper or lower respiratory tracts versus naive controls, indicating full protection against viral replication. Although mucosal and systemic protective mechanisms may differ, results demonstrate both vaccines can protect against respiratory SARS-CoV-2 exposure. In summary, we have demonstrated that the mucosal vaccine was safe after multiple doses and cleared the input virus more efficiently in the nasal cavity and thus may act as a potent complementary reinforcing boost for conventional systemic vaccines to provide overall better protection.

Despite research demonstrating the validity of the Ontario Domestic Assault Risk Assessment (ODARA) for appraising risk of subsequent intimate partner violence, gaps remain with regard to its actual use by police officers in the field. The primary goals of the current study were to assess the rate at which the ODARA was used by police officers for intimate partner violence (IPV) in the Canadian context and to identify factors associated with its use. The current study used 142 randomly selected police files meeting criteria for IPV from three police agencies in an Atlantic Canadian province, following province-wide training on domestic violence and the ODARA. The ODARA was used by police in 60.3% of cases, though more commonly when physical Violence was present at index (70%). Significant ODARA use variation was noted across the three police gencies. ODARAs were more likely administered when the suspect was using drugs/alcohol (76.4%), the incident was between parties in a current intimate relationship (67.0%), when physical violence occurred in the index event (70.6%), and when a weapon was used (84.2%). Decisions to arrest and recommend charges to the prosecutor were predicted by higher ODARA total scores, above and beyond the influence of the police organization, suspect/victim characteristics, and incident context variables. Results are discussed in the context of police discretion/decision-making and the need for stronger implementation and policy use guidelines for risk appraisal by police officers, which includes a better understanding of IPV and the ODARA.