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PurposeThis paper explores how entrepreneurial culture (EC) and organizational learning (OL) determine the entrepreneurial orientation (EO) of new technology-based firms (NTBFs). These NTBFs are located in Isfahan Science and Technology Town (ISTT), Iran. These entities face substantial challenges in a highly-sanctioned economy, which makes adopting, acquiring or transferring new technologies daunting.Design/methodology/approachThis paper analyzes a sample of 200 NTBFs. The participants were trained chief executive officers and observed by applying pre-test and post-test designs. As a final step, empirical data were collected using questionnaires and analyzed accordingly. The structural equation modeling (SEM) with the partial least squares (PLS) approach was used by the SmartPLS2 software.Findings OL was found to mediate the relationship between EC and EO in the studied NTBFs. Additionally, the indirect effect of EC on EO and the direct impact of OL on EO were significant (=1.96). Therefore, this study focuses on selected NTBFs within Iran's particular and distinctive context.Research limitations/implicationsThis study has several limitations. These were the time consuming nature, the lack of cooperation by managers and the COVID-19 pandemic-related challenges. Nonetheless, the findings offer several important implications for practitioners, scholars and policymakers.Originality/valueThe paper sought to explore how EC and OL determine EO in Iranian NTBFs. It, thus, investigates the case of a highly-sanctioned context during the coronavirus pandemic, which imposed several basic and technological limitations on their practices.

PurposeAs the youngest generation – Generation Z (Gen Z) – enters the workplace, there is a growing interest in this cohort's career needs and expectations. This paper explores the under-researched topic of Gen Z project management (Gen Z PM) professionals. In addition to shedding light on the factors that positively affect Gen Z PM professionals' early career-development phase, this research aims to identify specific organization-led practices that can foster sustainable early PM careers and so achieve greater workforce sustainability.Design/methodology/approachThrough the lens of the resource-based view (RBV), Gen Z PM professionals are considered critical resources that can help ensure workforce sustainability in project-based organizations (PBOs). Semi-structured in-depth interviews were conducted with 25 Gen Z PM professionals in Australia to explore the professionals' early career experiences and the organizational-support initiatives that facilitate positive experiences. The results were analyzed using thematic analysis.FindingsThe results revealed that most Gen Z PMs experienced many challenges and a lack of support during their early career phase: Gen Z value (1) mentoring, (2) time for training and development, (3) showing support and guidance, (4) understand skill-gaps and (5) reasonable workloads. Through catering to these needs, PBOs can ensure better career sustainability for their young Gen Z talent and, therefore, greater workforce sustainability for the project profession.Originality/valueAccording to the career sustainability lens, PBOs play a significant role in ensuring that their valuable young PM talent are supported and retained in the profession. This research sheds light on what Gen Z PM professionals value in their early careers, which guided recommendations to better support this new generation of project professionals.

The use of 1 Enoch in the letter of Jude extends to more than a single explicit citation in vv. 14–15. Jude also contains a series of allusions to 1 Enoch, including several important ones that have previously gone unnoticed. The purpose of this essay is to explore why the author of Jude chose to emphasize Enoch and the Enochic tradition in such a prominent way in his letter. Our thesis is that the author of Jude emphasized Enoch not only because, for him and his community, the Enochic tradition was absolutely foundational to their understanding of both the Lord Jesus Christ and eschatological salvation, but also because the same Enochic tradition was under strong attack by the false teachers whom Jude denounces in the letter. The essay aims to show that 1 Enoch is much more foundational to the interpretation of Jude than previously suspected.

Prudential regulators seek to ensure that the institutions (banks, insurers, pension schemes) making financial promises to their customers are capable of meeting those promises. Over time that has caused them to take an increasingly holistic view of the risks faced by those entities. It should be no surprise, therefore, that risks caused by climate change have emerged over the past decade as requiring concerted attention, both from the institutions and the prudential regulators who supervise them. Institutions and prudential regulators urgently need to design frameworks and processes that capture and assess the risks from climate change in a way that is tractable, rigorous and capable of integration into their existing frameworks and processes. This paper maps briefly how the practice of prudential regulation has evolved in recent years across a number of major jurisdictions (the United Kingdom, the European Union, Australia, South Africa and Singapore) to engage with the risks from climate change. This has value in its own right. Climate change is the most urgent existential risk currently facing mankind. However, the analysis in this article also provides a case study of how prudential regulation itself needs to be conceived, and in particular the need for prudential regulators to be ready continually to address nascent types of risk, the precise dimensions and nature of which emerge only over time.

The National Institutes of Health Toolbox Cognition Battery (NIHTB-CB) has both English- and Spanish-language versions producing crystallized and fluid cognition composite scores. This study examined measurement invariance between languages of administration. If established, measurement invariance would indicate that the composite scores measure the same construct across languages and provide scores that can be meaningfully compared and harmonized in future analyses.Participants from the NIHTB-CB normative sample included adults tested in English (For age-adjusted and demographic-adjusted scores, the two-factor model fit adequately well, and each factor had adequate reliability among English- and Spanish-speaking participants. Strict invariance was established across languages of administration for both age-adjusted and demographic-adjusted scores.These findings support the harmonization of the English- and Spanish-language NIHTB-CB crystallized and fluid composite scores, indicating that the composite scores measure the same constructs on the same scale. The results support future studies merging data from participants evaluated in both languages. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Epilepsy is increasingly considered a disorder of brain networks. Studying these networks with functional connectivity can help identify hubs that facilitate the spread of epileptiform activity. Surgical resection of these hubs may lead patients who suffer from drug-resistant epilepsy to seizure freedom. Here, we aim to map non-invasively epileptogenic networks, through the virtual implantation of sensors estimated with electric and magnetic source imaging, in patients with drug-resistant epilepsy. We hypothesize that highly connected hubs identified non-invasively with source imaging can predict the epileptogenic zone and the surgical outcome better than spikes localized with conventional source localization methods (dipoles). We retrospectively analysed simultaneous high-density electroencephalography (EEG) and magnetoencephalography data recorded from 37 children and young adults with drug-resistant epilepsy who underwent neurosurgery. Using source imaging, we estimated virtual sensors at locations where intracranial EEG contacts were placed. On data with and without spikes, we computed undirected functional connectivity between sensors/contacts using amplitude envelope correlation and phase locking value for physiologically relevant frequency bands. From each functional connectivity matrix, we generated an undirected network containing the strongest connections within sensors/contacts using the minimum spanning tree. For each sensor/contact, we computed graph centrality measures. We compared functional connectivity and their derived graph centrality of sensors/contacts inside resection for good (n = 22, ILAE I) and poor (n = 15, ILAE II–VI) outcome patients, tested their ability to predict the epileptogenic zone in good-outcome patients, examined the association between highly connected hubs removal and surgical outcome and performed leave-one-out cross-validation to support their prognostic value. We also compared the predictive values of functional connectivity with those of dipoles. Finally, we tested the reliability of virtual sensor measures via Spearman’s correlation with intracranial EEG at population- and patient-level. We observed higher functional connectivity inside than outside resection (P < 0.05, Wilcoxon signed-rank test) for good-outcome patients, on data with and without spikes across different bands for intracranial EEG and electric/magnetic source imaging and few differences for poor-outcome patients. These functional connectivity measures were predictive of both the epileptogenic zone and outcome (positive and negative predictive values ≥55%, validated using leave-one-out cross-validation) outperforming dipoles on spikes. Significant correlations were found between source imaging and intracranial EEG measures (0.4 ≤ rho ≤ 0.9, P < 0.05). Our findings suggest that virtual implantation of sensors through source imaging can non-invasively identify highly connected hubs in patients with drug-resistant epilepsy, even in the absence of frank epileptiform activity. Surgical resection of these hubs predicts outcome better than dipoles.

Birds transport ticks into Canada during northward spring migration, and some of these ticks are infected with tick-borne zoonotic pathogens. Some Amblyomma species harbour pathogens that cause debilitating diseases that can be fatal to humans, and domestic and wildlife animals. At least 65 Amblyomma spp. are indigenous in the Western Hemisphere, and approximately half bite humans. Amblyomma longirostre carries Rickettsia amblyommatis which causes spotted fever group rickettsiosis, a febrile disease in humans. Additionally, Amblyomma maculatum harbors and transmits Rickettsia parkeri, a spotted fever group rickettsiosis, and this tick bites humans. In the present study, we use two technologies to identify ticks. To confirm identification, we took microphotographs followed by DNA barcoding of the cytochrome c oxidase I gene. Based on molecular analysis, we confirmed that the two Amblyomma spp. were Amblyomma longirostre, a neotropical tick and Amblyomma maculatum, the Gulf Coast tick. Based on our tick-bird findings, we confirm that migratory songbirds transport Amblyomma ticks into Canada, and have the potential, either directly or indirectly, to transmit tick-borne zoonotic pathogens to humans.

Intraindividual variability (IIV) in cognitive performance has been associated with cognitive decline and reductions in white matter integrity, but the predictive utility of IIV-between versus IIV-within domains is unknown. The present study aimed to determine if IIV-within a "frontal-subcortical" domain may be a more robust predictor of changes in general cognitive status and functional independence over time than IIV-between cognitive domains.Mixed linear modeling was used to analyze the relationship between cognitive IIV and cognitive and functional status in 651 controls, 211 people with mild cognitive impairment, and 218 people with Alzheimer's disease over a 5-year period.Both IIV-between and IIV-within a frontal-subcortical domain improved prediction of cognitive and functional declines beyond demographic characteristics, genetic risk, and vascular integrity. IIV-between showed the greatest effect over time and was driven primarily by increases in IIV-within.Cognitive IIV, especially between cognitive domains, may be useful for identifying individuals at risk for cognitive and functional decline. Findings may facilitate investigations into mechanisms underlying declines in global cerebral integrity and aid clinical trials aimed at early detection and treatment. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A fluorine-18 labelled probe was developed to target bromodomain and extraterminal (BET) proteins for molecular imaging of cancer with positron emission tomography.

The stability of polymer nanoparticle dispersions is strongly impacted by the glass transition temperature of constituent polymers.

In this study, we use laser ablation MC-ICP-MS as a rapid sampling tool to characterize the isotopic composition of uranium in μm-sized uranium oxide particles.

Myeloid dendritic cells (DCs) and macrophages are mononuclear phagocytes with key roles in the immune system. As antigen-presenting cells, they link innate detection of microbes with programming adaptive immune responses. Myeloid DCs and macrophages also play critical roles in development, promote tissue homeostasis, and direct repair in response to injury and inflammation. As cellular migration and organelle dynamics are intimately connected with these processes, it is necessary to develop tools to track myeloid cell behavior and function. Here, we build on previously established protocols to isolate primary human myeloid cells from peripheral blood and report an optimized method for their genetic modification with lentiviral vectors to study processes related to cell migration, activation, and organelle dynamics. Specifically, we provide a protocol for delivering genetically encoded fluorescent markers into primary monocyte-derived DCs (MDDCs) and monocyte-derived macrophages (MDMs) to label mitochondria, peroxisomes, and whole cells. We describe the isolation of primary CD14+ monocytes from peripheral blood using positive selection with magnetic beads and, alternatively, isolation based on plastic adherence. Isolated CD14+ cells can be transduced with lentiviral vectors and subsequently cultured in the presence of cytokines to derive MDDCs or MDMs. This protocol is highly adaptable for cotransduction with vectors to knock down or overexpress genes of interest. These tools enable mechanistic studies of genetically modified myeloid cells through flow cytometry, fluorescence microscopy, and other downstream assays. © 2022 Wiley Periodicals LLC. Basic Protocol: Transduction of MDDCs and MDMs with lentiviral vectors encoding fluorescent markers Alternate Protocol 1: Isolation of monocytes by plastic adhesion Alternate Protocol 2: Transduction of MDDCs and MDMs with lentiviral vectors to knock down or overexpress genes of interest Support Protocol 1: Production and purification of lentiviral vectors for transduction into primary human myeloid cells Support Protocol 2: Flow cytometry of MDDCs and MDMs Support Protocol 3: Fixed and live-cell imaging of fluorescent markers in MDMs and MDDCs.

Polymeric colloids have shown potential as "building blocks" in applications ranging from formulations of Pickering emulsions and drug delivery systems to advanced materials, including colloidal crystals and composites. However, for applications requiring tunable properties of charged colloids, obstacles in fabrication can arise through limitations in process scalability and chemical versatility. In this work, the capabilities of flash nanoprecipitation (FNP), a scalable nanoparticle (NP) fabrication technology, are expanded to produce charged polystyrene colloids using sulfonated polystyrene ionomers as a new class of NP stabilizers. Through experimental exploration of formulation parameters, increases in the ionomer content are shown to reduce the particle size, mitigating a significant trade-off between the final particle size and inlet concentration; thus, expanding the processable material throughput of FNP. Further, the degree of sulfonation is found to impact stabilization with optimal performance achieved by selecting ionomers with intermediate (2.45-5.2 mol %) sulfonation. Simulations of single ionomer chains and their arrangement in multicomponent NPs provide molecular insights into the assembly and structure of NPs wherein the partitioning of ionomers to the particle surface depends on the polymer molecular weight and degree of sulfonation. By combining the insights from simulations with diffusion-limited growth kinetics and parametric fits to experimental data, a simple design formulation relation is proposed and validated. This work highlights the potential of ionomer-based stabilizers for controllably producing charged NP dispersions in a scalable manner.

Health literacy is the ability to understand and interpret health information and navigate the health-care system. Low health literacy is associated with poorer health knowledge and disease management, increased chronic illness, underutilisation of preventative health services and increased hospitalisations. The aim of the study is to review the available literature on the relationship between parental health literacy and health outcomes for children with chronic disease in high-income countries (HIC) and low- and middle-income countries (LMIC).We systematically searched Medline, EMBASE and Web of Science, and assessed study quality using the Newcastle Ottawa Scale. We reviewed all relevant studies, and identified themes using thematic analysis.Of 1167 studies assessed, 49 were included in the review. All studies were of adequate quality. Twenty-two were from LMIC and 27 from HIC. Six themes were identified: Parental health literacy, parental education, socio-economic conditions, identity and culture, family factors, and health behaviours. In both HIC and LMIC, lower parental health literacy was associated with poorer child health outcomes. Disease-specific knowledge was found in a number of papers to directly impact parent health behaviour and child health outcomes, and may mitigate the effects of low parental health literacy.There is a clear link between parental health literacy, health behaviour and health outcomes for children with chronic disease. Disease-specific knowledge as a target for health-care interventions holds promise for application in low-resourced settings with parents (particularly mothers) who have lower health literacy, where disease-specific education may improve child health outcomes, although more research is required to determine how we can best facilitate these programmes.

The trilobite Needmorella new genus, with type species N. simoni new genus new species from the late Emsian to mid-Eifelian Needmore Shale of West Virginia, is a distinctive member of the subfamily Synphoriinae. It also occurs in the same formation in Pennsylvania and Virginia. It is not very similar to other Devonian representatives of the subfamily and is considered to have its origins in a morphologically less-derived ancestor because it shares certain similarities with Silurian genera, including the very short anterior cephalic border unmodified by crenulations or spines, S2 that is not largely reduced to a deep pit adaxially, the relatively low inflation of L3, and the well-defined interpleural furrows on the pygidium. Other particularly distinctive characters of the genus include the very long genal spines and the abaxially inflated and expanded posterior pleural bands on the thorax and pygidium that project slightly distally. The conventional concept of the Devonian synphoriine Anchiopsis Delo, 1935 appears to be incompatible with the holotype of the type species, judging from the early illustrations of the specimen, and the genus could be a synonym of Synphoria Clarke, 1894.UUID: http://zoobank.org/4a820e27-54ec-4f7b-a408-675e62b75154

Objective:Pediatric patients who undergo general anesthesia (GA) for dentistry may be treated in different venues. This retrospective study compared patients treated in an ambulatory surgery center (ASC) to those treated in a hospital operating room (H-OR). The 2-venue model was also compared with a historical hospital-only model.Methods:Twelve months of data were collected via records review: patient demographics, American Society of Anesthesiology (ASA) classification, and medical comorbidities. Data from patients treated at the H-OR 10 years prior were referenced for comparison.Results:Between July 2017 and June 2018, 1148 patients were treated: 635 at the ASC and 513 at the H-OR. The most common age range for both venues was 3 to 8 years. Of all the ASC patients, 78% were ASA I, while 48% of H-OR patients were ASA III (P < .001). The number of patients treated with the 2-venue model represented a 240% annual increase compared with those treated historically using the hospital-only model.Conclusion:Because of differences in patient medical comorbidities, both the ASC and H-OR are needed to adequately address the needs of pediatric dental patients who require GA. Treating healthy patients in an ASC also creates increased capacity in the H-OR to better accommodate those with higher medical acuity.

Next-generation membranes for purification and reuse of highly contaminated water require materials with precisely tuned functionality to address key challenges, including the removal of small, charge-neutral solutes. Bioinspired multifunctional membrane surfaces enhance transport properties, but the combinatorically large chemical space is difficult to navigate through trial and error. Here, we demonstrate a computational inverse design approach to efficiently identify promising materials and elucidate design rules. We develop a combined evolutionary optimization, machine learning, and molecular simulation workflow to spatially design chemical functional group patterning in a model nanopore that enhances transport of water relative to solutes. The genetic optimization discovers nonintuitive functionalization strategies that hinder the transport of solutes through the pore, simply by patterning hydrophobic methyl and hydrophilic hydroxyl functional groups. Examining these patterns, we demonstrate that they exploit an unexpected diffusive solute hopping mechanism. This inverse design procedure and the identification of novel molecular mechanisms for pore chemical heterogeneity to impact solute selectivity demonstrate new routes to the design of membrane materials with novel functionalities. More broadly, this work illustrates how chemical design is a powerful strategy to modulate water-mediated surface-solute interactions in complex, soft material systems that are relevant to diverse technologies.

ObjectiveExamine the relationship between the National Institutes of Health Toolbox Emotion Battery (Emotion Toolbox) and traditional measures in Parkinson’s disease (PD).MethodPersons with PD (n = 30) and cognitively healthy older adults (OA; n = 40) completed the Emotion Toolbox consisting of Well-Being, Negative Affect, and Social Satisfaction scores along with traditional measures of depression (Beck Depression Inventory-II [BDI-II]), anxiety (State–Trait Anxiety Inventory [STAI]), and apathy (Apathy Scale [AS]); total raw scores).ResultsSeparate bootstrapped analyses of covariance indicated that the PD group scored higher on BDI-II and STAI-State compared to OA (ps ConclusionsThe Emotion Toolbox showed moderate-strong correlations with traditional measures in persons with PD. Even so, it did not capture the group differences between PD and OA and had a somewhat lower classification accuracy rate for persons with PD who had a formal psychiatric diagnosis than traditional measures. Together, findings question the utility of the Emotion Toolbox as a stand-alone emotion screener in PD.

Persons with drug-resistant epilepsy may benefit from epilepsy surgery and should undergo presurgical testing to determine potential candidacy and appropriate intervention. Institutional expertise can influence use and availability of evaluations and epilepsy surgery candidacy. This census survey study aims to examine the influence of geographic region and other center characteristics on presurgical testing for medically intractable epilepsy.We analyzed annual report and supplemental survey data reported in 2020 from 206 adult epilepsy center directors and 136 pediatric epilepsy center directors in the United States. Test utilization data were compiled with annual center volumes, available resources, and US Census regional data. We used Wilcoxon rank-sum, Kruskal-Wallis, and chi-squared tests for univariate analysis of procedure utilization. Multivariable modeling was also performed to assign odds ratios (ORs) of significant variables.The response rate was 100% with individual element missingness 11% across 342 observations undergoing univariate analysis. A total of 278 complete observations were included in the multivariable models, and significant regional differences were present. For instance, compared to centers in the South, those in the Midwest used neuropsychological testing (OR = 2.87, 95% confidence interval [CI] = 1.2-6.86; p = .018) and fluorodeoxyglucose-positron emission tomography (OR = 2.74, 95% CI = = 1.14-6.61; p = .025) more commonly. For centers in the Northeast (OR = .46, 95% CI = .23-.93; p = .031) and West (OR = .41, 95% CI = .19-.87; p = .022), odds of performing single-photon emission computerized tomography were lower by nearly 50% compared to those in the South. Center accreditation level, demographics, volume, and resources were also associated with varying individual testing rates.Presurgical testing for drug-resistant epilepsy is influenced by US geographic region and other center characteristics. These findings have potential implications for comparing outcomes between US epilepsy centers and may inject disparities in access to surgical treatment.

The island sanctuary of Barrow Island on the edge of the inner North-West continental shelf of Australia holds significant environmental as well as Indigenous and colonial cultural value. Insights on past occupation dynamics, particularly in response to Post-Glacial sea-level rise, continue to emerge from analysis of archaeological assemblages. However, there is limited temporal and landscape information from the wider island with which to better contextualise the physical site formation history of these cultural records. We present a new, modelled Post-Glacial sea-level curve for the region and new geochronological and sedimentological data (including rare earth element and quartz microtextural data) from non-archaeological site contexts to help infer changes in the coastal environment. This new data provides new insights on the island's paleogeography and evolution since approximately 80 ka BP in the context of inherited Last Interglacial features and highly dynamic oceanographic processes. Ongoing physical weathering processes have influenced dune building and reworking, such that neither colour nor numeric age are reliable indicators of sediment compositional and textural maturity. The results continue to emphasise how the continued integration of the island's geological, sedimentological and archaeological records help to understand aspects of cultural site formation, as well as expose some of the limiting factors in our understanding of past and present island physical dynamics. Ministry of Education (MOE) National Research Foundation (NRF) Submitted/Accepted version This study was made possible through a Research Collaboration Award from the University of Western Australia, with additional funding provided from an Australian Research Council Discovery Early Career Award to IW (DE180100601). Archaeological data was collected by the Barrow Island Archaeological Project funded by an ARC Discovery Grant (DP130100802) 2013–2015 awarded to PV and team. Department of Biodiversity Conservation and Attractions, Chevron Australia and WA Oil are thanked for their logistical and personnel support in the field, as also are Mick O’Leary and Peter Kendrick. We acknowledge the support of Buurabalayji Thalanyji Aboriginal Corporation. We thank Dick Peltier for providing the ICE-7G_NA ice model and Kurt Lambeck and Anthony Purcell for providing the ANU-ICE ice model. The global ANU-ICE combination model used in this study was kindly provided by Holger Steffen. Tanghua Li is supported by the Singapore Ministry of Education Academic Research Fund MOE2019- T3-1-004 and MOE2018-T2-1-003, the National Research Foundation Singapore, and the Singapore Ministry of Education, under the Research Centers of Excellence initiative. The GIA modelling is conducted in part using the research computing facilities and/or advisory services offered by Information Technology Services, the University of Hong Kong. This work comprises Earth Observatory of Singapore contribution no. 424. The authors also acknowledge the facilities, and the scientific and technical assistance of Microscopy Australia at the Centre for Micro- scopy, Characterisation & Analysis, the University of Western Australia, a facility funded by the University, State and Commonwealth Govern- ments. Acknowledgement is given to Mark Basgall David Zeanah and David Glover of Sacramento University for use of artefact distribution maps; and to Mick O’Leary for the DEM image of the Chair (Loop Beach).

Alterations in tissue microstructure in normal-appearing white matter (NAWM), specifically measured by diffusion tensor imaging (DTI) fractional anisotropy (FA), have been associated with cognitive outcomes following stroke. The purpose of this study was to comprehensively compare conventional DTI measures of tissue microstructure in NAWM to diverse vascular brain lesions in people with cerebrovascular disease (CVD) and to examine associations between FA in NAWM and cerebrovascular risk factors. DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured in cerebral tissues and cerebrovascular anomalies from 152 people with CVD participating in the Ontario Neurodegenerative Disease Research Initiative (ONDRI). Ten cerebral tissue types were segmented including NAWM, and vascular lesions including stroke, periventricular and deep white matter hyperintensities, periventricular and deep lacunar infarcts, and perivascular spaces (PVS) using T1-weighted, proton density-weighted, T2-weighted, and fluid attenuated inversion recovery MRI scans. Mean DTI metrics were measured in each tissue region using a previously developed DTI processing pipeline and compared between tissues using multivariate analysis of covariance. Associations between FA in NAWM and several CVD risk factors were also examined. DTI metrics in vascular lesions differed significantly from healthy tissue. Specifically, all tissue types had significantly different MD values, while FA was also found to be different in most tissue types. FA in NAWM was inversely related to hypertension and modified Rankin scale (mRS). This study demonstrated the differences between conventional DTI metrics, FA, MD, AD, and RD, in cerebral vascular lesions and healthy tissue types. Therefore, incorporating DTI to characterize the integrity of the tissue microstructure could help to define the extent and severity of various brain vascular anomalies. The association between FA within NAWM and clinical evaluation of hypertension and disability provides further evidence that white matter microstructural integrity is impacted by cerebrovascular function.

Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) affects up to 4% of individuals. Common symptoms include nasal congestion/obstruction, nasal discharge, facial pain, and reduced sense of smell. This study describes patient- and physician-reported CRSwNP symptom burden and health-related quality of life (HRQOL) in a real-world clinical setting. Methods: This multinational, geographically diverse, point-in-time survey invited physicians to evaluate 5 consecutive adults with confirmed bilateral moderate to severe CRSwNP (consecutive sampling) plus the next 2 patients with recurrent nasal polyps and ≥1 surgery for polyp removal (oversampling). Patients’ and physicians’ surveys were assessed in the entire consecutive sample and by categories of physician-determined CRSwNP severity, and by categories of asthma comorbidity (total sample). Patients’ and physicians’ responses were compared in a matched sample. Results: The total sample of 1,782 patients comprised 1,296 (72.7%) from consecutive sampling and 486 (27.3%) from oversampling. Among the consecutive sample (mean age, 46.9 years), 1,122 (86.6%) had moderate and 174 (13.4%) had severe CRSwNP. Of 1,697 patients from total sampling with known asthma status, 708 (41.7%) had asthma and 989 (58.3%) did not. Patients’ self-reported symptom frequency, severity, and burden on HRQOL worsened with increasing CRSwNP severity and comorbid asthma. Physicians underreported prevalence, severity, and impact of symptoms on daily activities compared with patients (matched sample). Conclusion: Patients and physicians from real-world settings both described a considerable burden of CRSwNP, but physicians consistently reported fewer and less severe symptoms than patients. This suggests a more patient-centric view is needed when assessing CRSwNP symptom burden and HRQOL.

Putting on hearing aids (HAs) is a regular and crucial task for every hearing aid wearer. A sub-optimal insertion can impact user adoption and audiological benefit. Ability to visually evaluate the insertion can be helpful to achieve a proper physical fit of hearing aids or similar devices, but this is currently a challenging task. In this work we present CheckMyFit, a smartphone-based, automated solution enabling users to quickly take a photo of their hearing aid placement, and compare it with a reference ideal insertion. To evaluate the tool's usability and potential benefit we conducted two user studies: a) a pilot lab study with 7 participants, and b) a field study with 17 participants. In the two-week field study, older participants with no prior hearing aid experiences were instructed on hearing aid insertion remotely and performed daily insertions independently at home. We found that CheckMyFit is easy and quick to use for almost all participants. Ear-photo-aided insertions tend to have higher quality than insertions without the tool. This correlation was significant and persisted throughout the 2 weeks of the study, and is retained after a short break. This suggests that CheckMyFit tool can provide real-world benefit to new users learning to insert their hearing aids. We also used CheckMyFit to remotely facilitate the field study, demonstrating its potential usefulness in tele-medicine.

We report detailed functional analyses and genotype-phenotype correlations in 392 individuals carrying disease-causing variants in SCN8A, encoding the voltage-gated Na+ channel Nav1.6, with the aim of describing clinical phenotypes related to functional effects. Six different clinical subgroups were identified: Group 1, benign familial infantile epilepsy (n = 15, normal cognition, treatable seizures); Group 2, intermediate epilepsy (n = 33, mild intellectual disability, partially pharmaco-responsive); Group 3, developmental and epileptic encephalopathy (n = 177, severe intellectual disability, majority pharmaco-resistant); Group 4, generalized epilepsy (n = 20, mild to moderate intellectual disability, frequently with absence seizures); Group 5, unclassifiable epilepsy (n = 127); and Group 6, neurodevelopmental disorder without epilepsy (n = 20, mild to moderate intellectual disability). Those in Groups 1–3 presented with focal or multifocal seizures (median age of onset: 4 months) and focal epileptiform discharges, whereas the onset of seizures in patients with generalized epilepsy was later (median: 42 months) with generalized epileptiform discharges. We performed functional studies expressing missense variants in ND7/23 neuroblastoma cells and primary neuronal cultures using recombinant tetrodotoxin-insensitive human Nav1.6 channels and whole-cell patch-clamping. Two variants causing developmental and epileptic encephalopathy showed a strong gain-of-function (hyperpolarizing shift of steady-state activation, strongly increased neuronal firing rate) and one variant causing benign familial infantile epilepsy or intermediate epilepsy showed a mild gain-of-function (defective fast inactivation, less increased firing). In contrast, all three variants causing generalized epilepsy induced a loss-of-function (reduced current amplitudes, depolarizing shift of steady-state activation, reduced neuronal firing). Functional effects were known for 170 individuals. All 136 individuals carrying a functionally tested gain-of-function variant had either focal (n = 97, Groups 1–3) or unclassifiable (n = 39) epilepsy, whereas 34 individuals with a loss-of-function variant had either generalized (n = 14), no (n = 11) or unclassifiable (n = 6) epilepsy; only three had developmental and epileptic encephalopathy. Computational modelling in the gain-of-function group revealed a significant correlation between the severity of the electrophysiological and clinical phenotypes. Gain-of-function variant carriers responded significantly better to sodium channel blockers than to other anti-seizure medications, and the same applied for all individuals in Groups 1–3. In conclusion, our data reveal clear genotype-phenotype correlations between age at seizure onset, type of epilepsy and gain- or loss-of-function effects of SCN8A variants. Generalized epilepsy with absence seizures is the main epilepsy phenotype of loss-of-function variant carriers and the extent of the electrophysiological dysfunction of the gain-of-function variants is a main determinant of the severity of the clinical phenotype in focal epilepsies. Our pharmacological data indicate that sodium channel blockers present a treatment option in SCN8A-related focal epilepsy with onset in the first year of life.

Background: Multivitamin (MVI) use is a common health behavior but there is conflicting evidence from prospective studies about whether this behavior increases or decreases prostate cancer risk. Methods: Associations of MVI use and prostate cancer risk were evaluated using data from the Selenium and Vitamin E Cancer Prevention Trial (SELECT). Cox proportional hazards models estimated associations of MVI use with risk of total, low-, and high-grade prostate cancer. Longitudinal data were used to evaluate screening and biopsy patterns. To account for differential biopsy patterns, the probability of prostate cancer was estimated for men with a positive screening value but no biopsy. Incidence density ratios were used to approximate HRs, and associations of MVI use with predicted prostate cancer risk were compared with observed. Results: Analyses of data from observed biopsies suggest a respective 19% (95% confidence interval, 10%–28%) and 21% (12%–31%) higher risk of high-grade prostate cancer for current and long-term MVI use, compared with no use. Current and long-term MVI use was associated with a shorter time to first on-study biopsy, indicating the potential for detection bias. After accounting for differential acceptance of biopsy, associations of MVI use with prostate cancer were attenuated and not statistically significant. Conclusions: In SELECT, biopsy acceptance patterns differed by MVI use. Estimates of associations of MVI use with prostate cancer risk based on observed biopsy data may be biased by differential acceptance of biopsy. Impact: Differential biopsy ascertainment may impact associations of risk factors and prostate cancer. Detailed screening and biopsy data can be used to analytically minimize such bias.

A new mineral species, hydroxymcglassonite-(K), ideally KSr4Si8O20(OH)·8H2O, has been found in the Wessels mine, Kalahari Manganese Field, Northern Cape Province, South Africa. It is granular ( E. Hydroxymcglassonite-(K) is insoluble in water or hydrochloric acid. An electron microprobe analysis yielded an empirical formula (based on 13 non-H cations pfu) K1.01(Sr2.99Ca1.03)Σ4.02Si7.99O20(OH)·8H2O, which can be simplified to K(Sr,Ca)4Si8O20(OH)·8H2O. Hydroxymcglassonite-(K) is tetragonal with space group P4/mnc and unit-cell parameters a = 9.0792(2), c = 16.1551(9) Å, V = 1331.70(9) Å3, and Z = 2. It is isostructural with hydroxyapophyllite-(K), KCa4Si8O20(OH)·8H2O, with Sr substituting for Ca. The crystal structure of hydroxy-mcglassonite-(K) is characterized by SiO4 tetrahedra sharing corners to form (Si8O20)8– sheets parallel to (001), which are connected by the K and B (= Sr + Ca) cations, as well as hydrogen bonding. The K cation is coordinated by eight H2O groups, and the average K–O distance of 2.941(3) Å is shorter than that of 2.950(3)–2.975(3) Å in hydroxyapophyllite-(K) or fluorapophyllite-(K). The B cation is sevenfold-coordinated (4O + 2H2O + OH), and the average B-O distance of 2.522(3) Å is noticeably longer than that of 2.422–2.435 Å in hydroxyapophyllite-(K) or fluorapophyllite-(K). The Raman spectra of hydroxymcglassonite-(K) and hydroxyapophyllite-(K) are very comparable, especially in the O-H stretching region. The discovery of hydroxymcglassonite-(K), the first Sr-bearing mineral of the apophyllite group, implies that more Sr-bearing members of the group may be found in nature or synthesized in laboratories, but the possibility for an incomplete solid solution between hydroxyapophyllite-(K) and hydroxymcglassonite-(K), due to the size difference between Sr2+ and Ca2+, cannot be ruled out.

Background and ObjectiveSocial desirability bias, the tendency to underreport undesirable behaviors, may be one reason patients with Parkinson disease (PD) underreport symptoms of impulse control disorders (ICDs).MethodsWe compared rates of ICD endorsement on questionnaires administered face-to-face and online in 60 patients with mild-to-moderate idiopathic PD. Participants also completed a self-report measure of social desirability.ResultsWe found a significantly higher prevalence of any ICD based on online (56.7%) vs in-person (33.3%) administration. Significantly higher endorsement of items related to hypersexuality in men and compulsive eating and buying in women were found with online administration. Social desirability bias was positively correlated with ICD symptom endorsement across all items and subscales.DiscussionThe results highlight the importance of social context/setting and the need for sensitivity and discretion when screening for ICD symptoms. Although a higher level of symptom endorsement does not necessarily imply a greater level of accuracy, more work is needed to determine which method of administration is most accurate for clinical and research practice.

Bisphosphonates limit resorption by inhibiting osteoclast formation and activation. They are removed during preparation of demineralized bone matrix (DBM) particles, but it is not known if osteogenesis and incorporation of mineralized bone allografts from patients treated with oral bisphosphonates are affected in vivo.Human block allografts from 3 bisphosphonate-treated donors and 3 age and sex-matched control donors who had not received bisphosphonates were obtained (Musculoskeletal Transplant Foundation); one-half from each donor was demineralized. In the first study, 3 × 2-mm mineralized and demineralized cylindrical grafts were implanted bilaterally in the femoral metaphysis of 56 rats. In the second study, samples from each group were pooled, prepared as particles, and implanted bilaterally in the femoral marrow canal of 24 rats. Osseointegration, defined as native bone in contact with allograft, was assessed at 10 weeks by micro-computed tomography (CT) and histomorphometry.Micro-CT showed greater bone volume in sites treated with demineralized samples compared with the control mineralized and bisphosphonate-exposed mineralized samples. More new bone was generated along the cortical-endosteal interface compared with mineralized samples. Histology showed significantly less new bone in contact with the mineralized bisphosphonate-exposed allograft (10.4%) compared with mineralized samples that did not receive bisphosphonates (22.8%) and demineralized samples (31.7% and 42.8%). A gap was observed between native bone and allograft in the bisphosphonate-exposed mineralized samples (0.50 mm 2 ). The gap area was significantly greater compared with mineralized samples that did not receive bisphosphonates (0.16 mm 2 ) and demineralized samples (0.10 and 0.03 mm 2 ).Mineralized allografts were osseointegrated, but not remodeled or replaced by living bone, preventing full regeneration of the bone defect. Prior treatment of the donor with bisphosphonates affected osteogenesis, preventing osteointegration and remodeling of the allograft into the regenerating bone.Clinical use of mineralized allografts from patients who had received bisphosphonate therapy needs to be evaluated; in this animal model, such grafts were not integrated into the host bone or remodeled, and full regeneration of the bone defects was prevented.

Purpose: This clinical focus article describes a literacy intervention protocol developed for mid-elementary students struggling with reading and writing. This clinical focus article begins with a discussion of the clinical questions and reasoning behind the choice of two major targets that include (a) improved reading fluency and (b) improved writing (spelling and composition) when integrated with reading. Extant research and expert opinion supporting each target are summarized. The protocol was implemented by a speech-language pathologist (SLP) with three third-grade students in a series of seven procedural steps described in detail. Clinician and teacher observations of student behaviors during protocol implementation and potential explanations are discussed. Conclusions: Although SLPs are encouraged to take on literacy intervention and the literature is robust with applicable research, there is less discussion of exactly how to approach intervention with older struggling readers who have both reading and writing needs. This clinical focus article illustrates how the marriage of clinical reasoning/experience and research can shape the choice of targets and step-by-step procedures to reduce this practice gap. SLPs are encouraged to consider whether the protocol holds promise for addressing literacy needs of students on their caseloads.

Life expectancy for people with Down syndrome (DS) has increased to 60 years, although poor oral health affects their quality of life. Panoramic radiographs (PRs) are usually well-tolerated by people with DS and can provide valuable diagnostic data for treatment planning and research. Methods A scoping review of peer-reviewed articles published between 1971and 2021 was conducted in accordance with the PRISMA extension for scoping reviews to determine the scope of use of PRs for people with DS.937 papers were screened, and 52 papers were included and charted into seven categories in this review. A high prevalence of tooth agenesis (TA) and other anomalies were reported in 45% of papers. Severe periodontal disease was considered characteristic of DS in the 1970s-80s and the benefit of time-consuming treatment was questioned. Since 2000 case reports illustrate that improved oral care, orthodontic treatment, and dental implants under local or general anaesthetic can improve the quality of life for people with DS.PRs play an important role in the diagnosis of anomalies, periodontal disease, and implant planning for patients with DS. This review highlights the gaps in research of caries, pathology, TMJ, systemic disease indicators, and guidelines for dentists. Systematic PR viewing, with a knowledge of characteristic features of DS, will assist diagnosis of pathology and improve comprehensive dental care treatment planning for children and adults with DS.