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The harsh and hostile internal environment of semi-autogenous (SAG) mills renders real-time monitoring of some critical variables practically unmeasured. Typically, feed size fractions are known to cause mill fluctuations and impede the consistent processing behaviour of ores. There is, therefore, the need for continuous monitoring of mill parameters for optimal operation. In this paper, an acoustic-based sensing method is employed to estimate, in real time, a snapshot of the different feed size fractions presented to a laboratory-scale SAG mill. Employing the MATLAB 2020b programme, the mill acoustic signal is processed using various transform techniques such as power spectral density estimate (PSDE) by Welch’s method, discrete wavelet transform (DWT), wavelet packet transform (WPT), empirical mode decomposition (EMD), and variational mode decomposition (VMD). Different fractional bandpowers are obtained from the PSDE spectrum, while the statistical root mean square values are further extracted from DWT, WPT, EMD, and VMD as feature vectors. The features are used as input features in different machine-learning classification algorithms for different mill feed size fractions predictions. The various transform techniques and feed size fraction predictions are evaluated using the various performance indicators obtained from the confusion matrix such as accuracy, precision, sensitivity and F1 score. The study showed that the acoustic signal feature extraction techniques used in conjunction with the Support Vector Machine (SVM), linear discriminant analysis (LDA), and ensemble with subclass discriminant machine learning algorithms demonstrated improved performance for predicting feed size variations. Refereed/Peer-reviewed

This study examined gender-specific longitudinal pathways from harsh parenting through rumination to anxiety and depression symptoms among early adolescents from three countries and six subgroups. Participants were 567 mothers, 428 fathers, and 566 children (T1: Mage = 10.89; 50% girls) from Medellín, Colombia (n = 100); Naples, Italy (n = 95); Rome, Italy (n = 99); Durham, North Carolina, United States (Black n = 92, Latinx n = 80, and White n = 100). Parent reported maternal and paternal harsh parenting were measured at T1. Adolescent reported rumination was measured at T2 (Mage = 12.58) and anxiety and depression symptoms were measured at T1 and T3 (Mage = 13.71). Rumination mediated the pathway from maternal harsh discipline to girls’ anxiety and depression symptoms, controlling for baseline anxiety and depression symptoms. The more harsh discipline mothers used, the more their daughters ruminated, which in turn was associated with increased anxiety and depression symptoms. Exploratory moderated mediation analyses indicated that the strength of the mediational pathway from maternal harsh discipline through girls’ rumination to anxiety and depression symptoms decreased as the normativeness of harsh parenting increased. Mediational pathways for boys and for paternal harsh discipline were not significant. Our findings expand knowledge on specific contexts in which rumination is a mechanism for understanding pathways to anxiety and depression symptoms.

PURPOSE The long-term toxicities of chemotherapy and radiotherapy can represent a significant burden to testicular cancer survivors. Retroperitoneal lymph node dissection (RPLND) is an established treatment for testicular germ cell tumors with minimal late morbidity although little data exist on its efficacy in early metastatic seminoma. Surgery in early metastatic seminoma is a prospective phase II single-arm, multi-institutional trial of RPLND as first-line treatment for testicular seminoma with clinically low-volume retroperitoneal lymphadenopathy. PATIENTS AND METHODS Twelve sites in the United States and Canada prospectively enrolled adult patients with testicular seminoma and isolated retroperitoneal lymphadenopathy (1-3 cm). Open RPLND was performed by certified surgeons with a primary end point of 2-year recurrence-free survival (RFS). Complication rates, pathologic up/downstaging, recurrence patterns, adjuvant therapies, and treatment-free survival were assessed. RESULTS A total of 55 patients were enrolled, with a median (IQR) largest clinical lymph node size of 1.6 cm (1.3-1.9). RPLND pathology demonstrated a median (IQR) largest lymph node size of 2.3 cm (0.9-3.5); nine patients (16%) were pN0, 12 (22%) pN1, 31 (56%) pN2, and 3 (5%) pN3. One patient received adjuvant chemotherapy. With a median (IQR) follow-up of 33 months (12.0-61.6), 12 patients experienced recurrence, with a 2-year RFS of 81% and a recurrence rate of 22%. Of the patients who experienced recurrence, 10 were treated with chemotherapy and two underwent additional surgery. At last follow-up, all patients who experienced a recurrence were disease-free and the 2-year overall survival was 100%. Four patients (7%) experienced short-term complications, and four patients experienced long-term complications including incisional hernia (1) and anejaculation (3). CONCLUSION RPLND is a treatment option for testicular seminoma with clinically low-volume retroperitoneal lymphadenopathy and is associated with low long-term morbidity.

Increasing prevalence of native lowlanders sojourning to high altitudes (>2,500 m) for recreational, occupational, military, and competitive reasons has generated increased interest in physiological responses to multistressor environments. Exposure to hypoxia poses recognized physiological challenges that are amplified during exercise and further complicated by environments that might include combinations of heat, cold, and high altitude. There is a sparsity of data examining integrated responses in varied combinations of environmental conditions, with even less known about potential sex differences. How this translates into performance, occupational, and health outcomes requires further investigation. Acute hypoxic exposure decreases arterial oxygen saturation, resulting in a reflex hypoxic ventilatory response and sympathoexcitation causing an increase in heart rate, myocardial contractility, and arterial blood pressure, to compensate for the decreased arterial oxygen saturation. Acute altitude exposure impairs exercise performance, for example, reduced time to exhaustion and slower time trials, largely owing to impairments in pulmonary gas exchange and peripheral delivery resulting in reduced V̇o2max. This exacerbates with increasing altitude, as does the risk of developing acute mountain sickness and more serious altitude-related illnesses, but modulation of those risks with additional stressors is unclear. This review aims to summarize and evaluate current literature regarding cardiovascular, autonomic, and thermoregulatory responses to acute hypoxia, and how these may be affected by simultaneous thermal environmental challenges. There is minimal available information regarding sex as a biological variable in integrative responses to hypoxia or multistressor environments; we highlight these areas as current knowledge gaps and the need for future research.

Despite the remarkable success of autologous chimeric antigen receptor (CAR) T cells, some patients relapse due to tumor antigen escape and low or uneven antigen expression, among other mechanisms. Therapeutic options after relapse are limited, emphasizing the need to optimize current approaches. In addition, there is a need to develop allogeneic “off-the-shelf” therapies from healthy donors that are readily available at the time of treatment decision and can overcome limitations of current autologous approaches. To address both challenges simultaneously, we generated a CD20xCD22 dual allogeneic CAR T cell. Herein, we demonstrate that allogeneic CD20x22 CAR T cells display robust, sustained and dose-dependent activity in vitro and in vivo, while efficiently targeting primary B-cell non–Hodgkin lymphoma (B-NHL) samples with heterogeneous levels of CD22 and CD20. Altogether, we provide preclinical proof-of-concept data for an allogeneic dual CAR T cell to overcome current mechanisms of resistance to CAR T-cell therapies in B-NHL, while providing a potential alternative to CD19 targeting.

A series of Ruddlesden-Popper phase materials – La3PrNi3O10- δ, La2Pr2Ni3O10-δ and LaPr3Ni3O10- δ – were synthesised and investigated by neutron powder diffraction to understand the oxygen defect structure. The thermal expansion coefficient was calculated for all compositions and was found to be in the range of 13.0 - 13.4 × 10-6 ˚C-1, which is compatible with the commonly used electrolyte materials for solid oxide fuel cells. A weak preference for Pr occupying the M(2) site in the rocksalt layer was also observed. The majority of the oxygen vacancies were confined to the perovskite layers with a particular preference for O(1) and O(5) sites at high temperatures observed by neutron diffraction measurements. Further, a preference for a curved oxygen transport pathway around the NiO6 octahedra was observed which agrees with the published literature for these materials.

Computational simulation, based on Density Functional Theory (DFT), was carried out to develop a more powerful cathode material, La0.35Bi0.15Sr0.5FeO3-δ (LBSF), based on a first-generation cathode material, La0.5Sr0.5FeO3-δ (LSF) for use in proton-conducting solid oxide fuel cells (H-SOFCs). The calculation results show that the Bi substitution causes an oxygen p band center shift, which accelerates the oxygen reduction reaction (ORR). To prove this prediction, LBSF and LSF was synthesized successfully, and each surface was also characterized with X-ray photoelectron spectroscopy (XPS) and low energy ion scattering (LEIS), observing a surface Sr segregation and change after Bi substitution. The change proves an effective modification of surface segregation component. Subsequently, LBSF, applied into H-SOFCs, shows excellent performance with a peak power density of 1630 mW cm-2 at 700 ℃ when this material was employed as a cathode in a full H-SOFC.

Nanostructured La0.6Sr0.4CoO3- δ (LSC) thin film electrodes exhibit exceptionally high oxygen surface exchange properties, surpassing those of conventional microscale electrode structures, which are desirable for application in solid oxide cells (SOCs). Here, towards the goal of improving the long-term stability of electrochemical performance of nanostructured LSC thin films, a systematic investigation of the effect of processing temperatures on long-term stability was carried out. By varying the deposition temperature (from 500 °C to room temperature), the as-grown characteristic nanostructures of LSC thin films prepared using pulsed laser deposition can be tuned from highly dense nanocolumnar grains to nanofibrous structures with high porosity. From the comparison of the properties of the as-grown films and those annealed at 700 °C for 300 h, it was revealed that LSC thin films prepared at lower deposition temperatures are less prone to the grain sintering effect and cation interdiffusion and exhibit better interfacial stability and improved long-term performance.

The Australian Leishmania (Mundinia) macropodum parasite causes cutaneous leishmaniasis (CL) among marsupial species. While CL is a major public health burden globally, it is not clear if humans are naturally exposed to the unique L. macropodum. To assess whether humans have an IgG response to L. macropodum, we examined anti-Leishmania antibodies among humans residing in a region of marsupial Leishmania endemicity in Australia.Employing a serological enzyme-linked immunosorbent assay, we characterized Leishmania-specific IgG and IgG subclass responses to soluble Leishmania antigen (SLA) from L. macropodum and other Leishmania species (L. donovani, L. major and L. mexicana) in 282 blood donor samples.We found 20.57% of individuals demonstrated a positive total IgG response to L. macropodum. For individuals with antibodies to SLA from one Leishmania species, there was no increased likelihood of recognition to other Leishmania species. For samples with detectable L. macropodum IgG, IgG1 and IgG2 were the prevalent subclasses detected.It is not yet clear whether the IgG antibody detection in this study reflects exposure to Leishmania parasites or a cross-reactive immune response that was induced against an unrelated immunogen. Future studies should investigate whether L. macropodum can result in a viable infection in humans.

Purpose: This study aimed to use deep learning-based dose prediction to assess head and neck (HN) plan quality and identify suboptimal plans. Methods: A total of 245 VMAT HN plans were created using RapidPlan knowledge-based planning (KBP). A subset of 112 high-quality plans was selected under the supervision of an HN radiation oncologist. We trained a 3D Dense Dilated U-Net architecture to predict 3-dimensional dose distributions using 3-fold cross-validation on 90 plans. Model inputs included CT images, target prescriptions, and contours for targets and organs at risk (OARs). The model's performance was assessed on the remaining 22 test plans. We then tested the application of the dose prediction model for automated review of plan quality. Dose distributions were predicted on 14 clinical plans. The predicted versus clinical OAR dose metrics were compared to flag OARs with suboptimal normal tissue sparing using a 2 Gy dose difference or 3% dose-volume threshold. OAR flags were compared to manual flags by 3 HN radiation oncologists. Results: The predicted dose distributions were of comparable quality to the KBP plans. The differences between the predicted and KBP-planned D1%, D95%, and D99% across the targets were within -2.53%(SD=1.34%), -0.42%(SD=1.27%), and -0.12%(SD=1.97%), respectively, and the OAR mean and maximum doses were within -0.33Gy(SD=1.40Gy) and -0.96Gy(SD=2.08Gy). For the plan quality assessment study, radiation oncologists flagged 47 OARs for possible plan improvement. There was high interphysician variability; 83% of physician-flagged OARs were flagged by only one of 3 physicians. The comparative dose prediction model flagged 63 OARs, including 30 of 47 physician-flagged OARs. Conclusion: Deep learning can predict high-quality dose distributions, which can be used as comparative dose distributions for automated, individualized assessment of HN plan quality., Comment: updated to reflect the published peer-reviewed article

Deep Neural Networks (DNN) have significantly improved the capabilities for analysis and classification of data, including that of biomedical signals (eg. ElectroencephalogramEEG). Optimal classification of EEG signals from seizure onset zones has been challenging especially given the complexity of signals arising from multiple locations. Also, underlying electrophysiological abnormalities which signify epileptogenic zones have not been clearly defined. Previous studies have demonstrated, automatic feature generation based on deep learning as a useful tool for interictal epileptiform discharge (IEDs) detection. Also signals with transformations have been used in convolutional neural network (CNN) based models in the past for classifying EEG data. We explored the use of deep learning for identification of the seizure onset zones using regular dense neural network and CNN based models. After the training the model using sample data the results were validated with a smaller percentage (10%) of the data. The models were noted to be accurate in predicting the seizure onset zones with significant degree of accuracy (87–99%) with a much shorter duration of signal recorded, compared to previous studies. We further investigated model’s decision-making process with heatmapping (gradient-weighted class activation map: Grad-CAM) approach, combining with signal processing using Hilbert transform. To identify the visible features in the signal, which maximally contribute to the seizure onset zone prediction, correlation of heatmap and analytical signal of the EEG, was calculated. A high correlation between heatmap and analytical signal was noted, suggesting that the model may be utilizing the higher power regions of the data in decision making process. This study demonstrates the potential use of DNN based strategies in identifying the epileptogenic zones in the intracranial EEG. It also shows the heatmapping strategies can help in establishing how specific signal patterns may be contributing to the decision making of DNN.

Purpose Exercise interventions can increase physical activity and wellbeing of people living with/beyond cancer. However, little is known about maintenance of physical activity in this population ≥ 6 months post-exercise intervention, when theoretical evidence suggests behaviour maintenance occurs. Study aims are to (i) systematically review maintenance of physical activity ≥ 6-month post-exercise intervention, and (ii) investigate the influence of behaviour change techniques (BCTs) on physical activity maintenance in people living with/beyond cancer. Methods CINAHL, CENTRAL, EMBASE and PubMed databases were searched for randomised controlled trials up to August 2021. Trials including adults diagnosed with cancer that assessed physical activity ≥ 6 months post-exercise intervention were included. Results Of 142 articles assessed, 21 reporting on 18 trials involving 3538 participants were eligible. Five (21%) reported significantly higher physical activity ≥ 6 months post-exercise intervention versus a control/comparison group. Total number of BCTs (M = 8, range 2–13) did not influence intervention effectiveness. The BCTs Social support, Goal setting (behaviour), and Action planning, alongside supervised exercise, were important, but not sufficient, components for long-term physical activity maintenance. Conclusions Evidence for long-term physical activity maintenance post-exercise intervention for people living with/beyond cancer is limited and inconclusive. Further research is required to ensure the physical activity and health benefits of exercise interventions do not quickly become obsolete. Implications for Cancer Survivors Implementation of the BCTs Social support, Goal setting (behaviour), and Action planning, alongside supervised exercise, may enhance physical activity maintenance and subsequent health outcomes in people living with/beyond cancer.

Type 2 diabetes (T2D) is a large disease burden worldwide and represents an increasing and complex challenge for all societies. For the individual, T2D is a complex, multi-dimensional, and long-term challenge to manage, and it is challenging to establish and maintain good communication between the patient and healthcare professionals. This article presents DiaFocus, which is a mobile health sensing application for long-term ambulatory management of T2D. DiaFocus supports an adaptive collection of physiological, behavioral, and contextual data in combination with ecological assessments of psycho-social factors. This data is used for improving patient-clinician communication during consultations. DiaFocus is built using a generic data collection framework for mobile and wearable sensing and is highly extensible and customizable. We deployed DiaFocus in a 6-week feasibility study involving 12 patients with T2D. The patients found the DiaFocus approach and system useful and usable for diabetes management. Most patients would use such a system, if available as part of their treatment. Analysis of the collected data shows that mobile sensing is feasible for longitudinal ambulatory assessment of T2D, and helped identify the most appropriate target users being early diagnosed and technically literate T2D patients.

San forager populations in nineteenth-century southern Africa were forced to adapt to greatly destructive aspects of the colonial project. Forging new societies from heterogeneous sources, they engaged in prolonged armed insurgency, recording their exploits, presence and beliefs in the rock-art archive of the Maloti-Drakensberg. These images reference conflict and trauma, conventionally interpreted as visions of spiritual warfare. However, viewed through the lens of post-traumatic stress disorder (PTSD), deeper dimensions emerge. PTSD is the culturally subjective experience of generalizable neuropathologies which develop following a traumatic event. Diagnosable in diverse communities worldwide, it nonetheless requires insider idioms to understand its local expressions. We explore how PTSD manifested in this historic and cultural context; how its symptomatic social dysfunctions would have been understood in forager aetiology, and how its intrusive flashbacks would have intruded on altered-state experiences induced to heal the consequences of violence. We find that the artists were not passive victims of trauma, but rather used art symbolically to reconsolidate individual and collective understandings of traumatic events.

Purpose: The audiology literature is rich with work in the area of clinical masking, yet there is a perception that learning how to mask is difficult. The purpose of this study was to explore the experiences of audiology doctoral students and recent graduates in learning clinical masking. Method: This exploratory study used a cross-sectional survey design, sampling doctor of audiology (AuD) students and recent graduates to probe the perceived effort required and challenges experienced in learning clinical masking. A total of 424 survey responses were included in the analysis. Results: A large majority of respondents rated learning clinical masking as being challenging and effortful. Responses suggested that it took more than 6 months for confidence to develop. Qualitative analysis of the open-ended question uncovered four themes: “negative experience in the classroom”; “lack of consensus or variation in teaching”; “focus on content/rules”; and “positives, internal and external.” Conclusions: Survey responses shed light on the perception that clinical masking is difficult to learn and highlight teaching and learning strategies that affect the development of this skill. Students reported a negative experience when significant emphasis was placed on formulas and theories and when encountering multiple masking methods in the clinic. On the other hand, students found clinic, simulations, lab-based classes, and some classroom instruction beneficial to learning. Students reported that their learning process included use of cheat sheets, practicing independently, and conceptualizing the process of masking to support their learning.

Background: Nursing programs continue to use more adjunct faculty members to keep up with the demanding needs of the nursing workforce. Although various nursing programs use adjunct faculty, they differ in the available support and resources offered. A midwestern university offering postlicensure online nursing programs developed an adjunct teaching model to aid teaching requirements. Method: The authors proposed innovative strategies the nursing programs could use to enhance adjunct support and retention. Results: The integration of onboarding, orientation, and mentorship processes enhanced adjunct faculty support and overall retention within the programs. Conclusion: The need for nursing adjunct faculty is expected to continue, and programs must be prepared to use innovative strategies to support them. The use of the outlined onboarding, orientation, and mentorship processes are vital in supporting adjunct job satisfaction and retention. [ J Nurs Educ . 2023;62(X):XXX–XXX.]

Objectives. To assess changes in minor consent laws for sexually transmitted infection (STI) and HIV testing, treatment, and prevention services in all 50 US states and the District of Columbia from 1900 to 2021. Methods. We coded laws into minor consent for (1) health care generally; (2) STI testing, treatment, and prevention; (3) HIV testing, treatment, and prevention; and (4) pre- or postexposure prophylaxis for HIV prevention. We also coded confidentiality protections and required conditions (e.g., threshold clinician judgments). Results. The largest increase in states allowing minors to consent to STI services occurred during the 1960s and 1970s. By 2021, minors could consent independently to STI and HIV testing and treatment in all 50 states plus DC, STI prevention services in 32 jurisdictions, and HIV prevention services in 33 jurisdictions. Confidentiality protections for minors are rare. Prerequisites are common. Conclusions. Although the number of states allowing minors to consent independently to STI and HIV services has increased considerably, these laws have substantial limitations, including high complexity, prerequisites requiring clinician judgments, and neglect of confidentiality concerns. (Am J Public Health. 2023;113(4):397–407. https://doi.org/10.2105/AJPH.2022.307199 )

The purpose of this study is to compare the injury incidence of the 2018-2019 and 2020 National Football League (NFL) seasons with the 2021 season.Publicly released NFL weekly injury reports were queried to identify players listed as "out" or placed on injured reserve (IR) for at least one game in the 2018-2021 seasons. Injuries were then categorized into upper extremity, lower extremity, spine/core, and head. Incidence per 1,000 athlete exposures were calculated for each season and proportions of injuries by position were calculated separately for the 2018-2019, 2020, and 2021 cohorts. Incidence rate ratios (IRR) were used to compare injury rates.Overall injury incidence in the 2021 NFL season increased compared to the pre-COVID-19 seasons (2018-2019) in all anatomical zones except for the upper extremity. [28.70 vs. 23.09 per 1,000 exposures, IRR 1.24 (95% CI: 1.14-1.36); p0.001]. The injury rate remained elevated and further increased in 2021 compared to the 2020 season for all anatomical zones other than the spine/core [28.70 vs. 21.64 per 1,000 exposures, IRR 1.33 (1.19-1.47); p0.001]. No significant difference existed during the early season (weeks 1-4); however, injury rates after week 4 increased in 2021 compared to both the 2018-2019 and 2020 seasons.The injury incidence in the 2021 season remained elevated and increased further compared to both the 2018-2019 and 2020 seasons. Traumatic injuries resulting in missed games increased despite return to a more traditional season since the beginning of the COVID-19 pandemic. The injury rates significantly increased in mid- to late season.III, cross-sectional study.

Ants are found everywhere from garden to mountaintop. They are at their most diverse in the tropics, but that does not make the 61 species of our part of the world any less fascinating or significant. As social insects, ants have fascinating life histories. Ecologically, they are highly important and influential. From tiny guest ants living in the nests of bigger species to gigantic wood ant mounds with hundreds of thousands of workers, there is a lifetime of possibility for study. This edition of Ants covers the general biology and ecology of species occurring in Britain and Ireland, including the Channel Islands. The book presents photographs and descriptions of workers for all 61 species on the regional list, together with distribution maps. There is also an account of some of the exotic species that may turn up in heated buildings. The extensively illustrated keys deal with workers, queens and males of all the species. These have been specially written and are the first comprehensive keys since those of the first edition 30 years ago. There are also quick-check keys to workers and nests, as well as a detailed list of kit suppliers and an extensive reference list. Ants are among the most familiar of insects and can form a crucial part of their ecosystem, having an impact far greater than their small individual size would lead us to expect. This book is for anyone wanting to learn more about these endlessly interesting insects, by reading and by applying some of the methods discussed to make new discoveries.

Introduction: We sought to understand the relation between positive parenting and adolescent diet, whether adolescents' internalizing and externalizing behaviors mediate relations between positive parenting and adolescent diet, and whether the same associations hold for both boys and girls and across cultural groups. Methods: Adolescents (N = 1334) in 12 cultural groups in nine countries were followed longitudinally from age 12 to 15. We estimated two sets of multiple group structural equation models, one by gender and one by cultural group. Results: Modeling by gender, our findings suggest a direct effect of positive parenting at age 12 on a higher quality diet at age 15 for males (β =.140; 95% CI: 0.057, 0.229), but an indirect effect of positive parenting at age 12 on a higher quality diet at age 15 by decreasing externalizing behaviors at age 14 for females (β =.011; 95% CI: 0.002, 0.029). Modeling by cultural group, we found no significant direct effect of positive parenting at age 12 on the quality of adolescent diet at age 15. There was a significant negative effect of positive parenting at age 12 on internalizing (β = −.065; 95% CI: −0.119, −0.009) and externalizing at age 14 (β = −.033; 95% CI: −0.086, −0.018). Conclusions: We founder gender differences in the relations among positive parenting, adolescents' externalizing and internalizing behaviors, and adolescent diet. Our findings indicate that quality of parenting is important not only in promoting adolescent mental health but potentially also in promoting the quality of adolescents' diet.

Refereed/Peer-reviewed Lethal short-limb skeletal dysplasia Al-Gazali type (OMIM %601356), also called dysplastic cortical hyperostosis, Al-Gazali type, is an ultra-rare disorder previously reported in only three unrelated individuals. The genetic etiology for Al-Gazali skeletal dysplasia has up until now been unknown. Through international collaborative efforts involving seven clinical centers worldwide, a cohort of nine patients with clinical and radiographic features consistent with short-limb skeletal dysplasia Al-Gazali type was collected. The affected individuals presented with moderate intrauterine growth restriction, relative macrocephaly, hypertrichosis, large anterior fontanelle, short neck, short and stiff limbs with small hands and feet, severe brachydactyly, and generalized bone sclerosis with mild platyspondyly. Biallelic disease-causing variants in ADAMTSL2 were detected using massively parallel sequencing (MPS) and Sanger sequencing techniques. Six individuals were compound heterozygous and one individual was homozygous for pathogenic variants in ADAMTSL2. In one of the families, pathogenic variants were detected in parental samples only. Overall, this study sheds light on the genetic cause of Al-Gazali skeletal dysplasia and identifies it as a semi-lethal part of the spectrum of ADAMTSL2-related disorders. Furthermore, we highlight the importance of meticulous analysis of the pseudogene region of ADAMTSL2 where disease-causing variants might be located.

Public health communication about diet in Inuit communities must balance the benefits and risks associated with both country and store-bought food choices and processes to support Inuit well-being. An understanding of how dietary messages—public health communication addressing the health and safety of country and store-bought food—are developed and disseminated in the Arctic is currently lacking. As part of the Country Foods for Good Health study, this participatory research sought to characterize dietary messaging in the Inuvialuit Settlement Region (ISR), Northwest Territories (NWT), from the perspective of territorial, regional and local dietary message disseminators to further improve message communication in the region. We conducted an in-person interview (n=1) (February 2020), telephone interviews (n=13) (May-June 2020), and follow-up telephone interviews (n=5) (June 2021) with key informants about their involvement in developing and/or disseminating dietary messages about the health benefits and risks of country foods and/or store-bought foods in/for the ISR. Key informants interviewed included health professionals (n=5), government employees (n=6) and community nutrition or food program coordinators (n=3) located in Inuvik, Tuktoyaktuk, Paulatuk and Yellowknife, NWT. We conducted a thematic analysis on the 19 interviews. Our findings indicate that publicly disseminated dietary messages in the ISR are developed at all scales and communicated through a variety of methods. Dietary messages focus predominantly on encouraging healthy store-bought food choices and conveying nutritional advice about store-bought and country foods. As federal and territorial messaging is seldom tailored to the ISR, representation of the Inuvialuit food system and consideration of local food realities is generally lacking. There is a need to evaluate dietary messages and improve collaborations among Inuvialuit country food knowledge holders, researchers, and public health dietary message disseminators at all scales to develop more locally tailored and culturally relevant messaging in the ISR. We recommend utilizing a participatory, collaborative, culture-centered approach to dietary message development and dissemination in northern Indigenous contexts.

Sarah Fielding’s The Countess of Dellwyn tells Charlotte Lucum’s story. Seventeen, beautiful, raised in rural seclusion, her father manipulates her into marrying sixty-five year old Lord Dellwyn, a decrepit, gout-ridden and wealthy peer whose political influence Mr. Lucum hopes to secure in order to revive his own career. Eschewing the potential for the sentimental approach more obvious in some of Fielding’s other work and in near-contemporary novels such as Frances Sheridan’s Memoirs of Miss Sidney Bidulph (1761) and others, the narrative voice of The Countess of Dellwyn maintains a distinctly critical distance from its heroine, remorselessly identifying her manifold errors in choices and conduct and resisting casting her as a victim, despite the parts played in her story by both her father and Lord Dellwyn himself. Key to the Countess’s downfall is her seduction by fashionable society, a seduction whose effects become most evident when the recently-married couple retire to Lord Dellwyn’s country seat at the London season’s end. In discussing the use to which the narrative puts Lord Dellwyn’s “noble ancient Castle,” swiftly and fashionably redecorated by the young Countess, this article considers how the novel employs houses as a counterpoint to the prevailing critique of its young heroine.

The protective effect of physical activity on breast cancer incidence may partially be mediated by inflammation. Systematic searches of Medline, EMBASE, and SPORTDiscus were performed to identify intervention studies, Mendelian randomization studies, and prospective cohort studies that examined the effects of physical activity on circulating inflammatory biomarkers in adult women. Meta-analyses were performed to generate effect estimates. Risk of bias was assessed, and the Grading of Recommendations Assessment, Development, and Evaluation system was used to determine the overall quality of the evidence. Thirty-five intervention studies and one observational study met the criteria for inclusion. Meta-analyses of randomized controlled trials (RCT) indicated that, compared with control groups, exercise interventions reduced levels of C-reactive protein (CRP) [standardized mean difference (SMD) = −0.27, 95% confidence interval (CI) = −0.62 to 0.08), tumor necrosis factor alpha (TNFα, SMD = −0.63, 95% CI = −1.04 to −0.22), interleukin-6 (IL6, SMD = −0.55, 95% CI = −0.97 to −0.13) and leptin (SMD = −0.50, 95% CI = −1.10 to 0.09). Owing to heterogeneity in effect estimates and imprecision, evidence strength was graded as low (CRP, leptin) or moderate (TNFα and IL6). High-quality evidence indicated that exercise did not change adiponectin levels (SMD = 0.01, 95% CI = −0.14 to 0.17). These findings provide support for the biological plausibility of the first part of the physical activity—inflammation—breast cancer pathway.

This review synthesized and appraised the evidence for an effect of inflammation on breast cancer risk. Systematic searches identified prospective cohort and Mendelian randomization studies relevant to this review. Meta-analysis of 13 biomarkers of inflammation were conducted to appraise the evidence for an effect breast cancer risk; we examined the dose–response of these associations. Risk of bias was evaluated using the ROBINS-E tool and the quality of evidence was appraised with Grading of Recommendations Assessment, Development, and Evaluation. Thirty-four observational studies and three Mendelian randomization studies were included. Meta-analysis suggested that women with the highest levels of C-reactive protein (CRP) had a higher risk of developing breast cancer [risk ratio (RR) = 1.13; 95% confidence interval (CI), 1.01–1.26] compared with women with the lowest levels. Women with highest levels of adipokines, particularly adiponectin (RR = 0.76; 95% CI, 0.61–0.91) had a reduced breast cancer risk, although this finding was not supported by Mendelian randomization analysis. There was little evidence of an effect of cytokines, including TNFα and IL6, on breast cancer risk. The quality of evidence for each biomarker ranged from very low to moderate. Beyond CRP, the published data do not clearly support the role of inflammation in the development of breast cancer.

This paper presents an experimental study of the effect of wall cooling on the boundary-layer structures of a sharp-nosed, 5° half-angle cone in Mach 6 flow. An experimental methodology was developed that allowed quantitative measurements of second-mode disturbance growth over a range of wall-temperature ratios from [Formula: see text] without modifying the freestream disturbance environment. The cooling system comprised probe cooling, liquid nitrogen injection, and thermal insulation. The model temperature was monitored before each run, with thermocouples mounted at the base and nosetip piece agreeing within 3.3 K. Calibrated schlieren provided global and time-resolved measurements of the boundary-layer features at a freestream unit Reynolds number of [Formula: see text]. An increase in wall-cooling level was associated with a shrinking of the boundary layer and a lowering of wavepacket structure angle at the wall. Despite some outlying results, an overall trend of increasing disturbance frequency with decreasing surface temperature was observed; additionally, cooling increased the spectral amplitude and growth rate of second-mode disturbances, pushing the point of saturation upstream.

Data assimilation techniques for state and parameter estimation are frequently applied in the context of computational neuroscience. In this work, we show how an adaptive variant of the unscented Kalman filter (UKF) performs on the tracking of a conductance-based neuron model. Unlike standard recursive filter implementations, the robust adaptive unscented Kalman filter (RAUKF) jointly estimates the states and parameters of the neuronal model while adjusting noise covariance matrices online based on innovation and residual information. We benchmark the adaptive filter's performance against existing nonlinear Kalman filters and explore the sensitivity of the filter parameters to the system being modelled. To evaluate the robustness of the proposed solution, we simulate practical settings that challenge tracking performance, such as a model mismatch and measurement faults. Compared to standard variants of the Kalman filter the adaptive variant implemented here is more accurate and robust to faults.