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Babies in intensive care are at higher risk for meningitis and sensorineural hearing loss (SNHL). We reviewed the rate of SNHL among definite cases of bacterial/fungal meningitis in our neonatal intensive care unit over a 16-year period (2006–2021). We identified 16 confirmed meningitis cases among 16 070 admissions: 8 of 10 surviving infants with available diagnostic audiology had normal/satisfactory hearing while 2 of 10 had SNHL. Both infants with permanent hearing loss had been born extremely preterm and received potentially ototoxic antimicrobials. Larger studies are needed to clarify whether SNHL occurs mainly due to meningitis itself or to its antimicrobial drug treatment.

Influenza A virus (IAV) infections are a significant recurrent threat to public health and a significant burden on global economy, highlighting the need for developing more effective therapies. Natural killer (NK) cells play a pivotal role in the control of pulmonary IAV infection, however, little is known about the therapeutic potential of adoptively transferred NK cells for viral infections. Here, we investigated the antiviral activity of CYNK, human placental hematopoietic stem cell-derived NK cells, against IAV infection in vitro. Virus infection induced the expression of NK cell activating ligands on respiratory epithelial cells, resulting in enhanced recognition by CYNK cells. Upon co-culture with IAV-infected epithelial cells, CYNK exhibited elevated degranulation and increased production of IFN-γ, TNF-α and GM-CSF in a virus dose-dependent manner. Furthermore, CYNK showed virus dose-dependent cytotoxicity against IAV-infected cells. The antiviral activity of CYNK was mediated by NKp46 and NKG2D. Together, these data demonstrate that CYNK possesses potent antiviral function against IAV and warrant clinical investigations for adoptive NK cell therapies against viral infections.

Abstract It is well-established that the process of learning and capability building is core to economic development and structural transformation. Since knowledge is ‘sticky’, a key component of this process is learning-by-doing, which can be achieved via a variety of mechanisms including international research collaboration. Uncovering significant inter-country research ties using Scopus co-authorship data, we show that within-region collaboration has increased over the past five decades relative to international collaboration. Further supporting this insight, we find that while communities present in the global collaboration network before 2000 were often based on historical geopolitical or colonial lines, in more recent years they increasingly align with a simple partition of countries by regions. These findings are unexpected in light of a presumed continual increase in globalisation, and have significant implications for the design of programmes aimed at promoting international research collaboration and knowledge diffusion.

Objective Disagreement exists between rheumatology and primary care societies regarding gout management. This paper describes a formal process for gathering input from stakeholders in the planning of a trial to compare gout management strategies. Methods We recruited patients, nurses, physician assistants, primary care clinicians, and rheumatologists to participate in a modified Delphi panel (mDP) to provide input on design of a trial focused on optimal management for primary care patients with gout. The 16 panelists received a plain‐language briefing document that discussed the rationale for the trial, key clinical issues in gout, and aspects of trial design. The panelists also received information and considerations on nine voting questions (VQs), judged to be the key design questions. Cognitive interviews with panelists ensured that the VQs were understood by the range of panelists involved in the mDP. Panelists were asked to score all VQs from 1 (definitely no) to 9 (definitely yes). Two voting rounds were conducted—round 1 by email and round 2 by video conference. Results The VQs were modified through the cognitive interviews. The round 1 voting resulted in consensus on eight items, with consensus defined as median voting score in the same tercile (1‐3, 4‐6 or 7‐9). Re‐voting at the meeting (round 2) reached consensus on the remaining item. Conclusion An mDP with various stakeholders facilitated consensus on the design of a trial of different management strategies for chronic gout. This method may be useful for designing trials of clinical questions with substantial disagreement across stakeholders.

Objective The increase in cardiovascular events (CVEs) in systemic lupus erythematosus (SLE) is not fully explained by traditional risk factors. We previously identified four biomarkers (proinflammatory high‐density lipoprotein, leptin, soluble TNF‐like weak inducer of apoptosis (sTWEAK), and homocysteine) that we combined with age and diabetes to create the predictors of risk for elevated flares, damage progression, and increased cardiovascular diseasein patients with SLE (PREDICTS) risk profile. PREDICTS more accurately identified patients with SLE at risk for progression of subclinical atherosclerosis than any individual variable. We examined whether PREDICTS can also identify patients with SLE at risk for future CVEs. Methods A total of 342 patients with SLE and 155 matched control subjects participated in this longitudinal prospective study. A high PREDICTS score was defined as three or more predictors or diabetes + one or more predictor. The biomarkers were measured at baseline using published methods. All major adverse CVEs (MACEs) were confirmed by medical record review. Results During 116 months of follow‐up, 5% of patients with SLE died, 12% had a cerebrovascular event, and 5% had a cardiac event. Overall, 20% of patients with lupus experienced any new MACE compared with 5% of control subjects (P < 0.0001). More patients with SLE with a new MACE had high PREDICTS score at baseline (77%) versus patients with no new events (34%) (P < 0.0001). High baseline PREDICTS score also associated with cerebrovascular (P < 0.0001) and cardiac events (P < 0.0001) in SLE. Using Cox regression, a baseline high PREDICTS score associated with a 3.7‐fold increased hazard ratio (HR) for a new MACE (P < 0.0001) in SLE. Hypertension (HR = 2.1; P = 0.006) was also a risk. Conclusion A high PREDICTS score and hypertension confer increased risk for new MACEs in patients with SLE.

The accurate measurement of the cognitive load a learner encounters in a given task is critical to the understanding and application of Cognitive Load Theory (CLT). However, as a covert psychological construct, cognitive load represents a challenging measurement issue. To date, this challenge has been met mostly by subjective self-reports of cognitive load experienced in a learning situation. In this paper, we find that a valid and reliable index of cognitive load can be obtained through item response modeling of student performance. Specifically, estimates derived from item response modeling of relative difficulty (i.e., the difference between item difficulty and person ability locations) can function as a linear measure that combines the key components of cognitive load (i.e., mental load, mental effort, and performance). This index of cognitive load (relative difficulty) was tested for criterion (concurrent) validity in Year 2 learners (N = 91) performance on standardized educational numeracy and literacy assessments. Learners’ working memory (WM) capacity significantly predicted our proposed cognitive load (relative difficulty) index across both numeracy and literacy domains. That is, higher levels of WM were related to lower levels of cognitive load (relative difficulty), in line with fundamental predictions of CLT. These results illustrate the validity, utility and potential of this objective item response modeling approach to capturing individual differences in cognitive load across discrete learning tasks.

Purpose: Nintedanib is an approved treatment for idiopathic pulmonary fibrosis (IPF), which slows disease progression. Management of patients with IPF receiving nintedanib can be complicated by tolerability issues, comorbidities, and concomitant medications. We developed consensus recommendations on the management of dosing, adverse events and comorbidities in patients with IPF treated with nintedanib. Methods: A modified Delphi process using 3 questionnaires was used to survey 14 pulmonologists experienced in using nintedanib. Panelists rated their agreement with statements on a Likert scale from −5 (strongly disagree) to +5 (strongly agree). Consensus was predefined as a mean score of ⩽−2.5 or ⩾+2.5 with a standard deviation not crossing zero. Results: The panelists’ recommendations were largely aligned with clinical trial data, real-world evidence, and the prescribing information, and provided additional guidance regarding minimizing gastrointestinal effects, periodic monitoring for liver dysfunction, caution with respect to concomitant administration of cytochrome P450 3A4 and P-glycoprotein 1 inhibitors and inducers and anticoagulants, and management of comorbidities. The panelists unanimously agreed that adverse event management should be individualized, based on careful consideration of the risks and benefits of each possible intervention and discussion with the patient. Conclusions: These consensus recommendations provide additional guidance on the appropriate management of IPF with nintedanib, for use alongside evidence-based literature and the prescribing information.

It is well known that several types of cardiac arrhythmias can occur after a seizure, with ictal sinus tachycardia being the most common. However, post-ictal atrial fibrillation (PIAF) is a rare phenomenon with significant clinical implications.We describe the case of an epilepsy patient with prolonged PIAF. Our case is that of a 62-year-old female with seizure onset at 51 years of age. She had a left hemispheric meningioma that was resected with ongoing seizures. She described frequent episodes of chest fluttering lasting for several hours post-ictally. During video-EEG monitoring (VEEG), she had a typical seizure with staring and word finding difficulty. This was associated with the occurrence of atrial fibrillation with rapid ventricular rate that lasted 18 hours.We discuss the relation between seizures and prolonged PIAF as it relates to the need for anticoagulation, use of appropriate antiseizure medications, and the possible association with SUDEP.

A key challenge in System of Systems (SoS) engineering is the analysis and maintenance of global properties under SoS evolution, and the integration of new constituent elements. There is a need to model the constituent systems composing a SoS in order to allow the analysis of emergent behaviours at the SoS boundary. The Contract pattern allows the engineer to specify constrained behaviours to which constituent systems are required to conform in order to be a part of the SoS. However, the Contract pattern faces some limitations in terms of its accessibility and suitability for verifying contract compatibility. To address these deficiencies, we propose the enrichment of the Contract pattern, which hitherto has been defined using SysML and the COMPASS Modelling Language (CML), by utilising SysML and Object Constraint Language (OCL). In addition, we examine the potential of interface automata, a notation for improving loose coupling between interfaces of constituent systems defined according to the contract, as a means of enabling the verification of contract compatibility. The approach is demonstrated using a case study in audio/video content streaming.

Consumer spending on organic food products has grown rapidly. Some claim that organics have ecological, equity, and health advantages over conventional food and therefore should be subsidized. Here we explore the distributive impacts of an organic fruit subsidy that reduces the retail price of organic fruit in the US by 10 percent. We estimate the impact of the subsidy on organic fruit demand in a representative poor, middle income, and rich US household using three analytical methods; including two econometric and one machine learning. We do not find strong evidence of regressive redistribution due to our simulated organic fruit subsidy; the poor household's relative reaction to the subsidy is not much different than the reaction at the other two households. However, the infra-marginal savings from the subsidy tend to be larger in richer households.

[This corrects the article DOI: 10.1371/journal.pone.0211199.].