Personality traits, especially neuroticism, strongly predict psychopathology. The domestic dog (Canis lupus familiaris Linnaeus, 1758) is used as a natural model for psychiatric disorders, but the similarity between dog and human personality and the association between dog personality and unwanted behavioral traits, such as fearfulness, aggressiveness, and impulsivity/inattention, remain unknown. This study utilized structural equation modeling (SEM) with survey data of 11,360 dogs to examine the associations and correlations between seven personality and ten unwanted behavioral traits. Personality traits included insecurity, energy, training focus, aggressiveness/dominance, human sociability, dog sociability, and perseverance. Unwanted behavioral traits included fearfulness, noise sensitivity, fear of surfaces/heights, separation anxiety, barking, stranger-directed aggression, owner-directed aggression, dog-directed aggression, hyperactivity/impulsivity, and inattention. We first fitted confirmatory factor models for the unwanted behavioral traits and the best model grouped unwanted behaviors into four latent traits: fear-related behavior, fear-aggression, aggression, and impulsivity/inattention and used this structure in the subsequent SEM model. Especially, insecurity, which resembles the human neuroticism trait, was strongly associated with unwanted behavior, paralleling the association between neuroticism and psychopathology. Similarly, training focus, resembling conscientiousness, was negatively related to impulsivity/inattention, and aggressiveness/dominance was associated with aggressive behaviors, resembling associations of conscientiousness and agreeableness with attention deficit hyperactivity disorder and aggression-related psychopathology, respectively. These results indicate that dog personality traits resemble human personality traits, suggesting that their neurological and genetic basis may also be similar and making the dog a suitable animal model for human behavior and psychiatric disorders.

The design of robots that interact autonomously with the environment and exhibit complex behaviours is an open challenge that can benefit from understanding what makes living beings fit to act in the world. Neuromorphic engineering studies neural computational principles to develop technologies that can provide a computing substrate for building compact and low-power processing systems. We discuss why endowing robots with neuromorphic technologies - from perception to motor control - represents a promising approach for the creation of robots which can seamlessly integrate in society. We present initial attempts in this direction, highlight open challenges, and propose actions required to overcome current limitations.

The optoelectronic properties of metal-halide perovskites (MHPs) are affected by lattice fluctuations. Using ultrafast pump-probe spectroscopy, we demonstrate that in state-of-the-art mixed-cation MHPs ultrafast photo-induced bandgap narrowing occurs with a linear to super-linear dependence on the excited carrier density ranging from 10¹⁷ cm^-3 to above 10¹⁸ cm^-3. Time-domain terahertz spectroscopy reveals carrier localization increases with carrier density. Both observations, the anomalous dependence of the bandgap narrowing and the increased carrier localization can be rationalized by photo-induced lattice fluctuations. The magnitude of the photo-induced lattice fluctuations depends on the intrinsic instability of the MHP lattice. Our findings provide insight into ultrafast processes in MHPs following photoexcitation and thus help to develop a concise picture of the ultrafast photophysics of this important class of emerging semiconductors.

Recent evidence shows that carbon emissions in China are likely to peak ahead of 2030. However, the social and economic impacts of such an early carbon peak have rarely been assessed. Here we focus on the economic costs and health benefits of different carbon mitigation pathways, considering both possible socio-economic futures and varying ambitions of climate policies. We find that an early peak before 2030 in line with the 1.5 °C target could avoid ~118,000 and ~614,000 PM_2.5 attributable deaths under the Shared Socioeconomic Pathway 1, in 2030 and 2050, respectively. Under the 2 °C target, carbon mitigation costs could be more than offset by health co-benefits in 2050, bringing a net benefit of $393-$3,017 billion (in 2017 USD value). This study not only provides insight into potential health benefits of an early peak in China, but also suggests that similar benefits may result from more ambitious climate targets in other countries.

Recent studies uncovered the emerging roles of SAPCD2 (suppressor anaphase-promoting complex domain containing 2) in several types of human cancer. However, the functions and underlying mechanisms of SAPCD2 in the progression of neuroblastoma (NB) remain elusive. Herein, through integrative analysis of public datasets and regulatory network of GSK-J4, a small-molecule drug with anti-NB activity, we identified SAPCD2 as an appealing target with a high connection to poor prognosis in NB. SAPCD2 promoted NB progression in vitro and in vivo. Mechanistically, SAPCD2 could directly bind to cytoplasmic E2F7 but not E2F1, alter the subcellular distribution of E2F7 and regulate E2F activity. Among the E2F family members, the roles of E2F7 in NB are poorly understood. We found that an increasing level of nuclear E2F7 was induced by SAPCD2 knockdown, thereby affecting the expression of genes involved in the cell cycle and chromosome instability. In addition, Selinexor (KTP-330), a clinically available inhibitor of exportin 1 (XPO1), could induce nuclear accumulation of E2F7 and suppress the growth of NB. Overall, our studies suggested a previously unrecognized role of SAPCD2 in the E2F signaling pathway and a potential therapeutic approach for NB, as well as clues for understanding the differences in subcellular distribution of E2F1 and E2F7 during their nucleocytoplasmic shuttling.

Purpose of review: Electronic nicotine delivery systems such as e-cigarettes are commonly felt to be harmless devices when compared to traditional cigarettes. However, an increasing number of studies support the biological plausibility for the potential detrimental effects of vaping on the respiratory mucosa. To date, few human studies have been carried out on adult vapers showing a reduction in lung function testing, especially in those with asthma, whereas the effects of vaping on children and adolescents have not been elucidated so far.

Recent findings: Several cross-sectional, national, population-based studies on large groups of adolescents have been carried out showing an association between vape exposure and self-reported asthma diagnosis and/or respiratory symptoms in this age group. The effects of second and third-hand exposure together with those of active and passive exposure in pregnancy, are almost completely unknown.

Summary: This review outlines recent data on the potential effects of vaping on asthma, focusing on vape composition, reported effects on the respiratory mucosa, available data in adolescents, and reasons behind the current vaping epidemic. The evidence so far available both in animals and humans suggests that vaping is not harmless, and its exposure should be limited in children and adolescents, especially when affected by asthma.

Purpose of review: The interplay of asthma and coronavirus disease 2019 (COVID-19) in children is yet unknown. The purpose of this review is to determine the interplay of asthma and asthma therapeutics and COVID-19.

Recent findings: There is no evidence to date that asthma is a risk factor for more severe COVID-19 outcomes, especially in children. There is actually some basis to suggest that children with atopic asthma may be at reduced risk of asthma exacerbations during COVID-19. The impact of asthma therapeutics on COVID-19 outcomes is unclear, but guidance is relatively uniform in recommending that those with asthma remain on current asthma medications. A focus on social determinants of health may be increasingly important during the pandemic and beyond.

Summary: Asthma in children appears to be more friend, than foe, during COVID-19.

Multiple lines of genetic and archaeological evidence suggest that there were major demographic changes in the terminal Late Pleistocene epoch and early Holocene epoch of sub-Saharan Africa^1-4. Inferences about this period are challenging to make because demographic shifts in the past 5,000 years have obscured the structures of more ancient populations^3,5. Here we present genome-wide ancient DNA data for six individuals from eastern and south-central Africa spanning the past approximately 18,000 years (doubling the time depth of sub-Saharan African ancient DNA), increase the data quality for 15 previously published ancient individuals and analyse these alongside data from 13 other published ancient individuals. The ancestry of the individuals in our study area can be modelled as a geographically structured mixture of three highly divergent source populations, probably reflecting Pleistocene interactions around 80-20 thousand years ago, including deeply diverged eastern and southern African lineages, plus a previously unappreciated ubiquitous distribution of ancestry that occurs in highest proportion today in central African rainforest hunter-gatherers. Once established, this structure remained highly stable, with limited long-range gene flow. These results provide a new line of genetic evidence in support of hypotheses that have emerged from archaeological analyses but remain contested, suggesting increasing regionalization at the end of the Pleistocene epoch.

The human brain is a highly plastic 'complex' network-it is highly resilient to damage and capable of self-reorganisation after a large perturbation. Clinically, neurological deficits secondary to iatrogenic injury have very few active treatments. New imaging and stimulation technologies, though, offer promising therapeutic avenues to accelerate post-operative recovery trajectories. In this study, we sought to establish the safety profile for 'interventional neurorehabilitation': connectome-based therapeutic brain stimulation to drive cortical reorganisation and promote functional recovery post-craniotomy. In n = 34 glioma patients who experienced post-operative motor or language deficits, we used connectomics to construct single-subject cortical networks. Based on their clinical and connectivity deficit, patients underwent network-specific transcranial magnetic stimulation (TMS) sessions daily over five consecutive days. Patients were then assessed for TMS-related side effects and improvements. 31/34 (91%) patients were successfully recruited and enrolled for TMS treatment within two weeks of glioma surgery. No seizures or serious complications occurred during TMS rehabilitation and 1-week post-stimulation. Transient headaches were reported in 4/31 patients but improved after a single session. No neurological worsening was observed while a clinically and statistically significant benefit was noted in 28/31 patients post-TMS. We present two clinical vignettes and a video demonstration of interventional neurorehabilitation. For the first time, we demonstrate the safety profile and ability to recruit, enroll, and complete TMS acutely post-craniotomy in a high seizure risk population. Given the lack of randomisation and controls in this study, prospective randomised sham-controlled stimulation trials are now warranted to establish the efficacy of interventional neurorehabilitation following craniotomy.

Objective: Differences in cardiovascular disease (CVD) incidence between men and women have been widely reported. Next to sex-related (biological) characteristics, gender-related (sociocultural) characteristics may partly explain how these differences arise. In this exploratory study, we examined the associations between selected gender-related characteristics and CVD incidence.

Methods: We linked baseline data of 18 058 participants without CVD from the population-based, multiethnic HEalthy LIfe in an Urban Setting study (Amsterdam, the Netherlands) to CVD incidence data, based on hospital admission and death records from Statistics Netherlands in 2013-2018. Using Cox regression analyses, we studied associations of time spent on household work, doing home repairs, primary earner status, type of employment, working in a male-dominated or female-dominated occupation and desire for emotional support with CVD incidence, stratified by sex. Analyses were adjusted for age, ethnicity and socioeconomic status.

Results: In men, gender-related characteristics were not associated with higher CVD incidence. In women, homemakers had a higher hazard for CVD compared with full-time workers (HR 2.34, 95% CI 1.35 to 4.04), whereas those spending a moderate amount of time on household work had a lower hazard for CVD than those spending little time (HR 0.56, 95% CI 0.34 to 0.95).

Conclusion: Although we found no evidence for associations between gender-related characteristics and CVD incidence in men, being the homemaker and moderate time spent on household work appeared to be associated with CVD incidence in women. Thus, attention to gender-related characteristics might in future help to identify subgroups that may benefit from additional prevention strategies.

Keywords: coronary artery disease; epidemiology; heart failure; risk factors; stroke.

Aminoglycosides (AGs) are commonly used antibiotics that cause deafness through the irreversible loss of cochlear sensory hair cells (HCs). How AGs enter the cochlea and then target HCs remains unresolved. Here, we performed time-lapse multicellular imaging of cochlea in live adult hearing mice via a chemo-mechanical cochleostomy. The in vivo tracking revealed that systemically administered Texas Red-labeled gentamicin (GTTR) enters the cochlea via the stria vascularis and then HCs selectively. GTTR uptake into HCs was completely abolished in transmembrane channel-like protein 1 (TMC1) knockout mice, indicating mechanotransducer channel-dependent AG uptake. Blockage of megalin, the candidate AG transporter in the stria vascularis, by binding competitor cilastatin prevented GTTR accumulation in HCs. Furthermore, cilastatin treatment markedly reduced AG-induced HC degeneration and hearing loss in vivo. Together, our in vivo real-time tracking of megalin-dependent AG transport across the blood-labyrinth barrier identifies new therapeutic targets for preventing AG-induced ototoxicity.

Keywords: aminoglycoside; drug tracking; in vivo cochlear imaging; megalin; ototoxicity.

Entropic outlier sparsification (EOS) is proposed as a cheap and robust computational strategy for learning in the presence of data anomalies and outliers. EOS dwells on the derived analytic solution of the (weighted) expected loss minimization problem subject to Shannon entropy regularization. An identified closed-form solution is proven to impose additional costs that depend linearly on statistics size and are independent of data dimension. Obtained analytic results also explain why the mixtures of spherically symmetric Gaussians-used heuristically in many popular data analysis algorithms-represent an optimal and least-biased choice for the nonparametric probability distributions when working with squared Euclidean distances. The performance of EOS is compared to a range of commonly used tools on synthetic problems and on partially mislabeled supervised classification problems from biomedicine. Applying EOS for coinference of data anomalies during learning is shown to allow reaching an accuracy of [Formula: see text] when predicting patient mortality after heart failure, statistically significantly outperforming predictive performance of common learning tools for the same data.

Keywords: entropy; mislabeling; outlier detection; regularization; sparsification.

Keywords: colorectal cancer; obesity.

This article advances two views on the role of evaluative judgment in clinical assessments of decision-making capacity. The first is that it is rationally impossible for such assessments to exclude judgments of the values a patient uses to motivate their decision-making. Predictably, and second, attempting to exclude such judgments sometimes yields outcomes that contain intractable dilemmas that harm patients. These arguments count against the prevailing model of assessment in common law countries-the four abilities model-which is often incorrectly advertised as being value-neutral in respect of patient decision-making both by its proponents and in statute. A straightforward evaluative model of capacity assessment which wears its values on its sleeves and is biased against what are called 'serious prudential mistakes' avoids these rational and practical problems.

Keywords: capacity; informed consent; personal autonomy.

Introduction: Multiparametric MRI (mpMRI) has become the standard imaging technique for the diagnosis of prostate cancer. However, mpMRI pathways are depending on experience, expertise, and information transfer from radiology to urology. Micro-ultrasound (Micro-US) is a new system, using high frequency (up to 29 MHz) and high resolution (down to 75 µm) ultrasound images. We evaluated the diagnostic performance of Micro-US in the detection of the prostate cancer index lesion and compared its performance to mpMRI using pathological whole mount sections as the reference.

Materials and methods: We retrospectively reviewed the data of 32 patients with diagnosis of prostate cancer and scheduled for radical prostatectomy and who underwent Micro-US before surgery. Still images and cineloops of Micro-US were recorded. Sixteen patients had also mpMRI images with acceptable quality and complete sequences available. For validation purposes each prostate was partitioned into 12 sectors for a total of 192 sectors evaluated. Micro-US and mpMRI images were both scored according to a validated system (PRI-MUS and Pi-RADS) where a score ≥3 was suspicious for both scores. Preoperative and postoperative results regarding the identification of the index lesion, the biggest lesion visible, were then compared and sensitivity, specificity, negative and positive predictive values, and accuracy were calculated.

Results: Median age was 67 years, median PSA was 6.2ng/ml, and median cancer volume of the index lesion was 3.1cc. The sensitivity of Micro-US in the index lesion detection was 76.5%, specificity 76.6%, negative predictive value 85.6%, positive predictive value 64.1% and 76.6% of accuracy. The sensitivity of mpMRI was 65.1%, specificity 93.4%, negative predictive value 83.2%, positive predictive value 84.3%, and 81.8% of accuracy (all p> .05).

Conclusion: Micro-US showed good reliability in identifying prostate cancer index lesions. Its performance is comparable to that of mpMRI.

Keywords: Diagnosis; Micro-ultrasound; Multiparametric magnetic resonance imaging; Prostate biopsy; Prostate cancer.

Background and objectives: Novel aptamer-based technologies can identify >7000 analytes per sample, offering a high-throughput alternative to traditional immunoassays in biomarker discovery. However, the specificity for distinct proteins has not been thoroughly studied in the context of CKD.

Design, setting, participants, & measurements: We assessed the use of SOMAscan, an aptamer-based technology, for the quantification of eight immune activation biomarkers and cystatin C among 498 African American Study of Kidney Disease and Hypertension (AASK) participants using immunoassays as the gold standard. We evaluated correlations of serum proteins as measured by SOMAscan versus immunoassays with each other and with iothalamate-measured GFR. We then compared associations between proteins measurement with risks of incident kidney failure and all-cause mortality.

Results: Six biomarkers (IL-8, soluble TNF receptor superfamily member 1B [TNFRSF1B], cystatin C, soluble TNF receptor superfamily member 1A [TNFRSF1A], IL-6, and soluble urokinase-type plasminogen activator receptor [suPAR]) had non-negligible correlations (r=0.94, 0.93, 0.89, 0.85, 0.46, and 0.23, respectively) between SOMAscan and immunoassay measurements, and three (IL-10, IFN-γ, and TNF-α) were uncorrelated (r=0.08, 0.07, and 0.02, respectively). Of the six biomarkers with non-negligible correlations, TNFRSF1B, cystatin C, TNFRSF1A, and suPAR were negatively correlated with measured GFR and associated with higher risk of kidney failure. IL-8, TNFRSF1B, cystatin C, TNFRSF1A, and suPAR were associated with a higher risk of mortality via both methods. On average, immunoassay measurements were more strongly associated with adverse outcomes than their SOMAscan counterparts.

Conclusions: SOMAscan is an efficient and relatively reliable technique for quantifying IL-8, TNFRSF1B, cystatin C, and TNFRSF1A in CKD and detecting their potential associations with clinical outcomes.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_02_23_CJN11700921.mp3.

Keywords: AASK (African American Study of Kidney Disease and Hypertension); antibodies; biological assay; chronic inflammation; chronic kidney disease; end-stage renal disease; mortality.

Objective: Intelectin-1 is an anti-inflammatory adipokine encoded by the Intelectin 1 (ITLN1) gene. Genetic variations in the ITLN1 gene affect the risk of coronary artery disease (CAD) and related CAD risk factors. In this study, we aimed to investigate whether the ITLN1 gene Val109Asp polymorphism has an effect on the severity of CAD and serum lipid levels in both men and women.

Methods: A total of 493 subjects who underwent coronary angiography (43.5% women, mean age 63.1±9.5 years) were grouped as individuals with critical CAD (≥70% stenosis, n=202), non-critical CAD (31%-69% stenosis, n=90), and non-CAD (control group) (1%-30% stenosis, n=201). Genotyping was performed using LightSNiP assay in Real-Time PCR.

Results: The frequency of the Val allele was significantly different among all the patients with critical CAD (n=41) and non-CAD control (n=51) groups in women (p=0.033) but not in men (n=77 and n=38). Women with the Val allele had a 1.69-fold increased risk for critical CAD (p=0.033). In addition, the presence of Val allele was associated with higher coronary stenosis after adjustment for several confounders only in women with critical CAD (p=0.025). Furthermore, carriers of the Val allele exhibited an increased low-density lipoprotein cholesterol (LDL-C) in men with critical CAD than in those with non-CAD (p<0.05).

Conclusion: These results suggest that the Val allele of the ITLN1 Val109Asp polymorphism is associated with critical CAD and high LDL-C levels in our study population. Further studies are required to elucidate the effect of Val109Asp polymorphism on CAD pathogenesis.

Introduction: Patients with lower limb injuries are commonly discharged from the ED with the affected area immobilised. Rigid casting of the lower limb is known to be a risk factor for the development of venous thromboembolism (VTE), making thromboprophylaxis in this population an important consideration for clinicians in the ED. The use of structured risk assessment methods (RAMs) to evaluate VTE risk and recommend thromboprophylaxis to those at higher risk is widespread in the UK. However, the evidence informing this practice is nearly exclusively based on studies of patients with rigid lower limb casts but many patients with knee injuries, including some with significant thrombotic risk factors, are managed in semi-rigid ('cricket') knee splints. These are both removable and allow free movement of the ankle, but the baseline risk of VTE and the performance of different RAMs in this population are not known.

Methods: Consecutive patients (≥14 years) discharged from the ED at Aberdeen Royal Infirmary, between 1 January 2010 and 31 December 2021, in a semi-rigid knee splint were identified retrospectively and followed up to 3 months after splint removal for the development of symptomatic VTE. Secondarily, data permitting the assessment of five different RAMs (NICE, GEMNet, an Aberdeen tool, the Plymouth score (V.2) and the L-TRiP(cast) score) were extracted systematically and compared.

Results: In 510 patients (mean age 32 (SD 16) years, 62% male) none received thromboprophylaxis and all completed follow-up. Two patients developed symptomatic VTE (0.4%, 95% CI 0.1% to 1.4%). The different RAMs varied considerably in the proportions identified for thromboprophylaxis from GEMNet (47%) to the L-TRiP(cast) score (2%), but no RAM was able to identify the two patients who progressed to VTE.

Conclusions: In our cohort of patients managed in semi-rigid removable knee splints, the risk of symptomatic VTE was low, about 1 in 250, and current methods of VTE risk assessment did not prove clinically useful.

Keywords: thromboembolic disease.

Objectives: COVID-19 is associated with significant morbidity and mortality. This study aims to synthesize evidence to assess the cost-effectiveness of remdesivir (RDV) for the treatment of hospitalized patients with COVID-19 in England and Wales.

Methods: A probabilistic cost-effectiveness analysis was conducted informed by 2 large trials and uses a partitioned survival approach to assess short- and long-term clinical consequences and costs associated with COVID-19 in a hypothetical cohort of hospitalized patients requiring supplemental oxygen at the start of treatment. Given that it is uncertain whether RDV reduces death, 2 analyses are presented, assuming RDV either reduces death or does not. Published sources were used for long-term clinical, quality of life, and cost parameters.

Results: Under the assumption that RDV reduces death, the incremental cost-effectiveness ratio for RDV is estimated at £11 881 per quality-adjusted life-year gained compared with standard of care (SoC) (probabilistic incremental cost-effectiveness ratio £12 400). The probability for RDV to be cost-effective is 74% at a willingness-to-pay threshold of £20 000 per quality-adjusted life-year gained. RDV was no longer cost-effective when the hazard ratio for overall survival compared with SoC was >0·915.

Conclusions: Results from this study suggest that using RDV for the treatment of hospitalized patients with COVID-19 is likely to represent a cost-effective use of National Health Service resources at current willingness-to-pay threshold in England and Wales, only if it prevents death. Results needs to be interpreted caution as vaccination was introduced and the SoC and evidence available have also evolved considerably since the analysis is conducted.

Keywords: COVID-19; United Kingdom; coronavirus; cost-effectiveness; economic evaluation; health technology assessment; remdesivir.

Objectives: The use of preventive medication in palliative oncology patients may be inappropriate due to limited life expectancy. Deprescribing tools are available but time-consuming and not always tailored to this specific population. Our primary goal was to identify potentially inappropriate medications (PIMs) in palliative oncology patients with a life expectancy of up to 2 years using an adapted deprescribing tool. Our secondary aim was to identify patient characteristics associated with the presence of PIMs.

Methods: Oncology patients with a life expectancy of up to 2 years were included cross-sectionally. An adapted deprescribing tool was developed to identify PIMs. Logistic regression was used to identify factors associated with having PIMs.

Results: A total of 218 patients were included in this study of which 56% had at least one PIM with a population mean of 1.1 PIM per patient. Most frequently defined PIMs were antihypertensive drugs and gastric acid inhibitors. Identification of PIMs by review took an estimated 5-10 min per patient. Polypharmacy, age >65 years and inpatient/outpatient status were found to be associated with having at least one PIM.

Conclusions: Deprescribing is possible in more than half of palliative oncology patients with a life expectancy of up to 2 years. The adapted deprescribing tool used is non-time consuming and suitable for palliative oncology patients, regardless of age.

Keywords: drug misuse; medical oncology; palliative care; pharmacy service, hospital; preventive medicine.