Search

Abstract Over the past few decades, the use of camera‐traps has revolutionized our ability to monitor populations of wild terrestrial mammals. While methods to estimate abundance from individually‐identifiable animals are well‐established, they are mostly restricted to species with clear natural markings or else necessitate invasive and often costly animal tagging campaigns. Estimating abundance or density from unmarked animals remains challenging. Several models recently developed to deal with this issue are promising, but are not widely used by field ecologists. Here, we developed a framework for applying the Space‐To‐Event (STE) model—originally designed to be used with time‐lapse images—on motion‐triggered camera‐trap data. Our approach involves performing bootstrap resampling on the photographic dataset to generate multiple datasets that are then used as input to the STE model. We tested our approach on 29 datasets, including 17 ungulate species from eight sites, in six different countries and various ecosystems. Then, we conducted a regression analysis to evaluate how variations in ecological and sampling conditions across studies affected the bias and precision of our STE density estimates. Our study shows that with a bootstrap resampling approach and information on animal activity and effective detection distances to animals, the STE model can be used to analyze motion‐trigger datasets and provide population density estimates that are similar to those from other methods. We found that measuring the camera viewshed was critical to prevent major negative biases in density estimates. Moreover, using a 1‐s sampling window was important to avoid the positive bias that results from violating the instantaneous‐sampling assumption. We found that precision increased with greater sampling effort and higher density populations. Based on these results, we highlight several issues from past studies that have applied the original timelapse‐based STE to motion‐trigger datasets, issues that our bootstrap resampling approach addresses. We caution that the STE model, whether applied to timelapse or motion‐triggered datasets, relies on strict assumptions. Any violations of these assumptions, such as non‐instantaneous sampling or the application of angle and distance of detection provided by the camera manufacturer, can cause biases in multiple directions that may be difficult to differentiate.

Abstract Land trusts have historically selected many project sites opportunistically, awaiting communication from willing sellers or donors interested in conserving their land. However, in light of the multiple ecological crises faced by land trusts, including climate change, biodiversity loss, and habitat destruction, there is a growing awareness of the need to practice land conservation with an increased pace, scale, and efficacy. In answer to that challenge, we provide one example of how a land trust can adopt methodology for the strategic selection of land protection project sites. Strategic land conservation, as demonstrated in this paper, involves thoughtful prioritization of the attributes of future conservation project sites. Following prioritization, spatial analysis of the region is conducted to identify sites that meet the prioritized attributes, in this case, resilience to climate change. The case study explored in this paper is the 2020 Strategic Land Conservation Plan created by Southwest Michigan Land Conservancy and its partners.

Objective Cognitive impairment (CI) in systemic lupus erythematosus (SLE) negatively impacts health‐related quality of life leading to activity limitations. This qualitative study aimed to (1) explore the effect of SLE‐related CI on activities of daily living and life role participation and (2) describe factors influencing activity restriction and life role participation. Methods Semistructured, in‐depth interviews of lived experience of CI in SLE were conducted with 24 participants with SLE. Sociodemographic and clinical data, and objective and subjective cognitive function, were collected to characterize participants. A qualitative thematic content analysis was undertaken guided by a framework analytical approach. Results Participants reported problems in multiple cognitive domains, with multiple perceived causes. CI was felt to impact work, social, domestic, and family life, health, and independence. Five overarching themes were represented in the data: (1) characterization of SLE‐reported CI, (2) perceived cause of CI, (3) perceived impact of CI on activities of daily living and life role participation, (4) adaptations for managing CI, and (5) influence of CI adaptations on activities of daily living and life role participation. Conclusion This study provides a better understanding of the patient experience of CI in SLE, how it impacts their lives, and what coping strategies they employ. It highlights the long‐term challenges those with CI in SLE undergo and provides evidence for the urgent need to implement multidisciplinary treatment options. When managing CI, it may be beneficial to evaluate and understand available psychosocial support resources to help identify and reinforce relevant adaptations to improve health‐related quality of life.

Abstract Introduction Head and neck cancer (HNC) is the eighth most common cancer in the United Kingdom. Survival rates improve when the cancer is diagnosed at an early stage, highlighting a key need to identify at‐risk patients. This study aimed to explore opportunistic HNC identification and referral by community pharmacists (CPs) using a symptom‐based risk assessment calculator, from the perspective of patients with a diagnosis of HNC. Methods Purposive sampling was used to recruit patients from the HNC pathway in three large teaching hospitals in Northern England. Qualitative methodology was used to collect data through an iterative series of semistructured telephone interviews. Framework analysis was utilised to identify key themes. Results Four main themes were constructed through the analytic process: (1) HNC presentation and seeking help; (2) the role of the CP; (3) public perception of HNC and (4) the role of a symptom‐based risk calculator. Participants agreed that CPs could play a role in the identification and referral of suspected HNCs, but there were concerns about access as patients frequently only encounter the medicine counter assistant when they visit the pharmacy. HNC symptoms are frequently attributed to common or minor conditions initially and therefore considered not urgent, leading to delays in seeking help. While there is public promotion for some cancers, there is little known about HNC. Early presentation of HNC can be quite variable, therefore raising awareness would help. The use of a symptom‐based risk calculator was considered beneficial if it enabled earlier referral and diagnosis. Participants suggested that it would also be useful if the public were made aware of it and could self‐assess their symptoms. Conclusion In principle, CPs could play a role in the identification and referral of HNC, but there was uncertainty as to how the intervention would work. Future research is needed to develop an intervention that would facilitate earlier identification and referral of HNC while not disrupting CP work and that would promote HNC and the risk calculator more widely. Patient or Public Contribution Patient and public involvement and engagement (PPIE) was integrated throughout the project. Initially, the proposal was discussed during a Cancer Head and Neck Group Experience (CHANGE) PPIE meeting. CHANGE was set up to support HNC research in 2018. The group is composed of seven members (four female, three male) with an age range of 50–71 years, who were diagnosed at Sunderland Royal Hospital. A patient representative from the University of Sunderland PPIE group and a trustee of the Northern HNC Charity were recruited as co‐applicants. They attended project management group meetings and reviewed patient‐facing documentation.

Abstract Introduction Undertaking physical activity, pre‐ and post‐operatively, can benefit recovery time and improve post‐surgical outcomes. One cohort of patients that have reported these benefits are those undergoing surgery for breast cancer. Yet, what remains unclear is the level to which physical activity interventions are implemented into standard surgical care for patients with breast cancer. Aims This systematic review aimed to examine existing qualitative evidence focusing on pre‐ and post‐operative physical activity interventions to better understand the benefits and shortcomings of physical activity within the surgical journey. Methods A systematic literature search was undertaken in November 2022, across five databases: MEDLINE, PsycINFO, Embase, CINAHL, and Scopus. Qualitative studies involving people with breast cancer who had undertaken a physical activity intervention, either pre‐ and/or post‐operatively, were included for analysis. The review was registered on PROSPERO: CRD42022372466 and performed according to PRISMA guidelines. The Critical Appraisal Skills Programme qualitative study checklist was used to assess study quality. Results Fourteen studies were included, comprising the perspectives of 418 people receiving surgery for breast cancer. One study implemented preoperative physical activity interventions; the remaining studies focused on post‐operative interventions. A narrative systematic review was undertaken due to heterogeneity in reported results. Four themes were developed by thematic analysis, centring on: (1) factors promoting engagement with physical activity interventions; (2) factors preventing engagement with physical activity interventions; (3) the impact of pre‐ and post‐operative interventions on physical and psychological health; and (4) participant recommendations for pre‐ and post‐operative interventions. Conclusion Pre‐ and post‐operative physical activity interventions were well‐accepted. Patients recognised factors which promoted or prevented engagement with interventions, as well as pre‐ and post‐operative physical and psychological benefits that arose as a result. Evidence based co‐design studies may further inform successful implementation of prescribed physical activity into standard care for surgical breast cancer patients.

Abstract Fish hatcheries are widely used to enhance fisheries and supplement declining wild populations. However, substantial evidence suggests that hatchery fish are subject to differential selection pressures compared to their wild counterparts. Domestication selection, or adaptation to the hatchery environment, poses a risk to wild populations if traits specific to success in the hatchery environment have a genetic component and there is subsequent introgression between hatchery and wild fish. Few studies have investigated domestication selection in hatcheries on a genomic level, and even fewer have done so in parallel across multiple hatchery–wild population pairs. In this study, we used low‐coverage whole‐genome sequencing to investigate signals of domestication selection in three separate hatchery populations of Chinook salmon, Oncorhynchus tshawytscha, after approximately seven generations of divergence from their corresponding wild progenitor populations. We sequenced 192 individuals from populations across Southeast Alaska and estimated genotype likelihoods at over six million loci. We discovered a total of 14 outlier peaks displaying high genetic differentiation (FST) between hatchery–wild pairs, although no peaks were shared across the three comparisons. Peaks were small (53 kb on average) and often displayed elevated absolute genetic divergence (Dxy) and linkage disequilibrium, suggesting some level of domestication selection has occurred. Our study provides evidence that domestication selection can lead to genetic differences between hatchery and wild populations in only a few generations. Additionally, our data suggest that population‐specific adaptation to hatchery environments likely occurs through different genetic pathways, even for populations with similar standing genetic variation. These results highlight the need to collect paired genotype–phenotype data to understand how domestication may be affecting fitness and to identify potential management practices that may mitigate genetic risks despite multiple pathways of domestication.

Toll-like receptors (TLRs) have a critical role in recognizing pathogenic patterns and initiating immune responses against TB and HIV. Previously, studies described the gene expression of TLRs in patients with TB and HIV. Here, we demonstrated TLRs protein expressions and their association with clinical status and plasma markers in TB, HIV, and TB/HIV coinfection. The phenotyping of TLR2, TLR4, and TLR9 on CD14+ monocytes and their subsets were determined by multicolor flow cytometry. Host plasma biomarkers and microbial indices were measured using Luminex Multiplex assay and standard of care tools, respectively. TLR2 expression significantly enhanced in TB, slightly increased in HIV but slightly reduced in TB/HIV coinfection compared to apparently health controls (HC). On the other hand, TLR4 expression was significantly increased in TB, HIV, and TB/HIV compared to HC. Expression of TLR4 was equally enhanced on classical and intermediate monocytes while higher TLR2 expression on intermediate than classical monocytes. TLR4 had a positive correlation pattern with plasma biomarkers while TLR2 had an inverse correlation pattern. TLR4 is associated with disease severity while TLR2 is with the immune-competent status of patients. Our findings demonstrated that the pattern of TLR expression is disease as well as monocyte subset specific and distinct factors drive these differences.

Background. Prevalence surveys in Ethiopia indicate smear negative pulmonary tuberculosis (SNPTB) taking the major share of the overall TB burden. It has also been a diagnostic dilemma worldwide leading to diagnostic delays and difficulty in monitoring treatment outcomes. This study determines and compares the clinical and imaging findings in SNPTB and smear positive PTB (SPPTB). Methodology. A case-control study was conducted on 313 PTB (173 SNPTB) patients. Data and sputum samples were collected from consented patients. Smear microscopy, GeneXpert, and culture analyses were performed on sputum samples. Data were analyzed using Stata version 17; a P value < 0.05 was considered statistically significant. Results. Of the 173 SNPTB patients, 42% were culture positive with discordances between test results reported by health facilities and Armauer Hansen Research Institute laboratory using concentrated smear microscopy. A previous history of TB and fewer cavitary lesions were significantly associated with SNPTB. Conclusions. Though overall clinical presentations of SNPTB patients resemble those seen in SPPTB patients, a prior history of TB was strongly associated with SNPTB. Subject to further investigations, the relatively higher discrepancies seen in TB diagnoses reflect the posed diagnostic challenges in SNPTB patients, as a higher proportion of these patients are also seen in Ethiopia.

Background. Primary hyperparathyroidism (PHPT) and familial hypocalciuric hypercalcaemia (FHH) are common causes of hypercalcaemia. Patients are mostly asymptomatic in the case of FHH and often so in the case of PHPT. In addition, biochemical parameters show considerable overlap, making differential diagnosis difficult. Genetic screening for inactivating variants in the calcium-sensing receptor (CASR) gene that are causative of FHH assists with the diagnosis since such variants are not generally associated with PHPT. However, novel CASR variants must undergo functional assessment before they can be definitively assigned a causative role in FHH. Case Presentations. We describe a 73-year-old female (patient A) who presented with mild parathyroid hormone (PTH)-dependent hypercalcaemia and a history of osteoporosis. Family history revealed that her sister (patient B) had presented a decade earlier with symptoms of PHPT including a history of mild hypercalcaemia and multiple renal calculi, prompting parathyroid surgery. However, a subtotal parathyroidectomy did not resolve her hypercalcaemia long term. On this basis, genetic screening was performed on patient A. This identified a heterozygous variant in the CASR, NM_000388.4:c.T101C: p.Leu34Pro (L34P). Functional analysis showed that the L34P variant was unable to produce mature, dimerized receptor and did not respond to Ca++ ions. Adopting American College of Medical Genetics-based guidelines, the variant was classified as 'Pathogenic (II)'. Patient B was subsequently found to carry the L34P variant heterozygously, confirming a diagnosis of FHH, not PHPT. Conclusion. This study shows the importance of examining patient’s family history in providing clues to the diagnosis in isolated cases of hypercalcaemia. In this case, history of a sister’s unsuccessful parathyroidectomy prompted genetic screening in a patient who might otherwise have undergone inappropriate parathyroid surgery. Screening detected an inactivating CASR variant, firming up a diagnosis of FHH. These studies reaffirm the requirement for functionally assessing novel CASR variants prior to assigning causality to FHH.

Abstract Objective Therapeutic strategies for patients with febrile infection‐related epilepsy syndrome (FIRES) are limited, ad hoc, and frequently ineffective. Based on evidence that inflammation drives pathogenesis in FIRES, we used ex vivo stimulation of peripheral blood mononuclear cells (PBMCs) to characterize the monocytic response profile before and after therapy in a child successfully treated with dexamethasone delivered intrathecally six times between hospital Day 23 and 40 at 0.25 mg/kg/dose. Methods PBMCs were isolated from serial blood draws acquired during refractory status epilepticus (RSE) and following resolution associated with intrathecal dexamethasone therapy in a previously healthy 9‐year‐old male that presented with seizures following Streptococcal pharyngitis. Cells were stimulated with bacterial or viral ligands and cytokine release was measured and compared to responses in age‐matched healthy control PBMCs. Levels of inflammatory factors in the blood and CSF were also measured and compared to pediatric healthy control ranges. Results During RSE, serum levels of IL6, CXCL8, HMGB1, S100A8/A9, and CRP were significantly elevated. IL6 was elevated in CSF. Ex vivo stimulation of PBMCs collected during RSE revealed hyperinflammatory release of IL6 and CXCL8 in response to bacterial stimulation. Following intrathecal dexamethasone, RSE resolved, inflammatory levels normalized in serum and CSF, and the PBMC hyperinflammatory response renormalized. Significance FIRES may be associated with a hyperinflammatory monocytic response to normally banal bacterial pathogens. This hyperinflammatory response may induce a profound neutrophil burden and the consequent release of factors that further exacerbate inflammation and drive neuroinflammation. Intrathecal dexamethasone may resolve RSE by resetting this inflammatory feedback loop.

Abstract Reliable estimates of population density are fundamental for managing and conserving wildlife. Spatially explicit capture–recapture (SECR) models in combination with information‐theoretic model selection criteria are frequently used to estimate population density. Variation in density and detectability is inevitable and, when unmodeled, can lead to erroneous estimates. Despite this knowledge, the performance of SECR models and information‐theoretic criteria remain relatively untested for populations with realistic levels of variation in density and detectability. We addressed this issue using simulations of American black bear (Ursus americanus) populations with variable density and detectability between sexes and across study areas. We first assessed the reliability of Akaike information criterion adjusted for small sample sizes (AICc) to correctly identify the true data generating model or a good approximating model. We then assessed the bias, accuracy, and precision of density estimates when such a model was selected or not. We demonstrated that unmodeled heterogeneity in detection and, more importantly, density can lead to pronounced bias. However, when a good approximating model is included in the candidate set, models with lower AICc included important forms of variation and yielded accurate estimates. We encourage researchers and practitioners to consider the impact of unmodeled variation in SECR models when making inferences and to strive to include covariates likely to be the most influential based on the species biology and ecology in candidate model sets. Doing so can improve the robustness of wildlife density estimation methods that can be leveraged to make more sound conservation and management decisions.

Abstract Among other approaches, camera trap distance sampling (CTDS) is used to estimate animal abundance from unmarked populations. It was formulated for videos and observation distances are measured at predetermined ‘snapshot moments’. Surveys recording still images with passive infrared motion sensors suffer from frequent periods where animals are not photographed, either because of technical delays before the camera can be triggered again (i.e. ‘camera recovery time’) or because they remain stationary and do not immediately retrigger the camera following camera recovery time (i.e. ‘retrigger delays’). These effects need to be considered when calculating temporal survey effort to avoid downwardly biased abundance estimates. Here, we extend the CTDS model for passive infrared motion sensor recording of single images or short photo series. We propose estimating ‘mean time intervals between triggers’ as combined mean camera recovery time and mean retrigger delays from the time interval distribution of pairs of consecutive pictures, using a Gamma and Exponential function, respectively. We apply the approach to survey data on red deer, roe deer and wild boar. Mean time intervals between triggers were very similar when estimated empirically and when derived from the model‐based approach. Depending on truncation times (i.e. the time interval between consecutive pictures beyond which data are discarded) and species, we estimated mean time intervals between retriggers between 8.28 and 15.05 s. Using a predefined snapshot interval, not accounting for these intervals, would lead to underestimated density by up to 96% due to overestimated temporal survey effort. The proposed approach is applicable to any taxa surveyed with camera traps. As programming of cameras to record still images is often preferred over video recording due to reduced consumption of energy and memory, we expect this approach to find broad application, also for other camera trap methods than CTDS.

Background Nonalcoholic fatty liver disease (NAFLD) and heart failure with preserved ejection fraction (HFpEF) share common risk factors, including obesity and diabetes. They are also thought to be mechanistically linked. The aim of this study was to define serum metabolites associated with HFpEF in a cohort of patients with biopsy‐proven NAFLD to identify common mechanisms. Methods and Results We performed a retrospective, single‐center study of 89 adult patients with biopsy‐proven NAFLD who had transthoracic echocardiography performed for any indication. Metabolomic analysis was performed on serum using ultrahigh performance liquid and gas chromatography/tandem mass spectrometry. HFpEF was defined as ejection fraction >50% plus at least 1 echocardiographic feature of HFpEF (diastolic dysfunction, abnormal left atrial size) and at least 1 heart failure sign or symptom. We performed generalized linear models to evaluate associations between individual metabolites, NAFLD, and HFpEF. Thirty‐seven out of 89 (41.6%) patients met criteria for HFpEF. A total of 1151 metabolites were detected; 656 were analyzed after exclusion of unnamed metabolites and those with >30% missing values. Fifty‐three metabolites were associated with the presence of HFpEF with unadjusted P value

Abstract We preview two processes that facilitate using formic acid (HCOOH) as a liquid hydrogen carrier to store renewably‐generated electrical energy and then release it to generate electrical power cleanly for backup or emergency applications. First, we show that simultaneously oxidizing an organic solute (typically a waste stream) can assist the electrochemical synthesis of formic acid by lowering the cell potential. The electrolyser comprises a hybrid 3‐chamber PEM stack that reduces CO₂ via a gas‐diffusion cathode boosted by the oxidation of aqueous methanol. However, the extent of the boosting needs to be optimized across the whole operation of the cell. Next, we present results from an intensified reactor for decomposing formic acid back into H₂ and CO₂ at elevated pressure so that the H₂ can be used in a fuel cell. The reactor combines three operations: Vaporization of the formic acid, its decomposition, and separation of the product stream. Their close coupling affords energy savings and a compact design that could be mounted on a mobile skid. We briefly discuss the electrode catalyst that facilitates the first process and two thermally activated catalysts (Ir supported on covalent triazine framework and Pd supported on carbon) that enable the second process.

Objective The purpose of this study was to evaluate a novel scoring system, the Encounter Appropriateness Score for You (EASY), to assess provider perceptions of telehealth appropriateness in rheumatology encounters. Methods The EASY scoring system prompts providers to rate their own encounters as follows: in‐person or telehealth acceptable, EASY = 1; in‐person preferred, EASY = 2; or telehealth preferred, EASY = 3. Assessment of the EASY scoring system occurred at a single academic institution from January 1, 2021, to August 31, 2021. Data were collected in three rounds: 1) initial survey (31 providers) assessing EASY responsiveness to five hypothetical scenarios, 2) follow‐up survey (34 providers) exploring EASY responsiveness to 11 scenario modifications, and 3) assessment of EASYs documented in clinic care. Results The initial and follow‐up surveys demonstrated responsiveness of EASYs to different clinical and nonclinical factors. For instance, less than 20% of providers accepted telehealth when starting a biologic for active rheumatoid arthritis, although more than 35% accepted telehealth in the same scenario if the patient lived far away or was well known to the provider. Regarding EASY documentation, 27 providers provided EASYs for 12,381 encounters. According to these scores, telehealth was acceptable or preferred for 29.7% of all encounters, including 21.4% of in‐person encounters. Conversely, 24.4% of telehealth encounters were scored as in‐person preferred. Conclusion EASY is simple, understandable, and responsive to changes in the clinical scenario. We have successfully accumulated 12,381 EASYs that can be studied in future work to better understand telehealth utility and optimize telehealth triage.

Abstract Species often exhibit regionally specific habitat associations, so habitat association models developed in one region might not be accurate or even appropriate for other regions. Three programs to survey wetland‐breeding birds covering (respectively) Great Lakes coastal wetlands, inland Great Lakes wetlands, and the Prairie Pothole Region offer an opportunity to test whether regionally specific models of habitat use by wetland‐obligate breeding birds are transferrable across regions. We first developed independent, regional population density models for four species of wetland‐obligate birds: Pied‐billed Grebe (Podilymbus podiceps), Virginia Rail (Rallus limicola), Sora (Porzana carolina), and American Bittern (Botaurus lentiginosus). We then used adjusted pseudo‐R2 values to compare the amount of variation explained by each model when applied to data collected in each of the three regions. Although certain habitat characteristics, such as emergent vegetation and wetland area, were consistently important across regions, models for each species differed by region—both in variables selected for inclusion and often in the directionality of relationships for common variables—indicating that habitat associations for these species are regionally specific. When we applied a model developed in one region to data collected in another region, we found that explanatory power was reduced in most (71%) models. Therefore, we suggest that ecological analyses should emphasize regionally specific habitat association models whenever possible. Nonetheless, models created from inland Great Lakes wetland data had higher median explanatory power when applied to other regions, and the amount of explanatory power lost by other transferred models was relatively small. Thus, while regionally specific habitat association models are preferable, in the absence of reliable regional data, habitat association models developed in one region may be applied to another region, but the results need to be cautiously interpreted. Additionally, we found that median explanatory power was higher when local‐scale habitat characteristics were included in the models, indicating that regionally specific models should ideally be based on a combination of local‐ and landscape‐scale habitat characteristics. Conservation practitioners can leverage such regionally specific models and associated monitoring data to help prioritize areas for management activities that contribute to regional conservation efforts.

Abstract Inclusive, comprehensive Stakeholder Identification and Mapping processes are vital for successful environmental management. This is relevant as multi‐disciplinary collaboration becomes increasingly popular, and the diversity of people influenced by, or involved in, the management of most projects is greater than ever before. Understanding how relevant parties are analysed in environmental management programmes is required to enable robust and considered methodologies as well as successful, just and equitable outcomes. The aim of this study was to improve the attribute mapping process, increasing transparency and ensuring representation is both comprehensive and equitable. A rapid scoping review of Scopus and Web of Science was undertaken to collate and analyse peer‐reviewed, published evidence on stakeholder analysis, with a focus on the mapping processes involved in identifying stakeholders and their attributes. Of the Initial 359 identified papers, 61 were included after three stages of screening. Our results indicate that there is little consistency among practitioners to ensure that Identifying and Mapping Stakeholders is representative:

Abstract Background Preventing parental intimate partner violence (IPV) or mitigating its negative effects early in the lifecourse is likely to improve population mental health. However, prevention of IPV is highly challenging and we know very little about how the mental health of children exposed to IPV can be improved. This study assessed the extent to which positive experiences were associated with depressive symptoms among children with and without experience of IPV. Method This study used data from the Avon Longitudinal Study of Parents and Children, a population‐based birth cohort. After excluding those without information on depressive symptoms at age 18, the final sample comprised 4490 participants. Parental intimate partner violence (physical or emotional cruelty reported by mother or partner) when the cohort child was aged 2–9 years. Depressive symptoms were measured with the Short Mood and Feelings Questionnaire (SMFQ) at age 18 years. Results Each additional report of parental intimate partner violence (over six reports) was associated with 0.047 (95% CI 0.027–0.066), or 4.7%, higher SMFQ score. Conversely, each additional positive experience (over 11 domains) was linked with −0.042 (95% CI −0.060 to −0.025) or 4.1%, lower SMFQ score. Among those with parental intimate partner violence (19.6% of participants), relationship with peers (effect size = 3.5%), school enjoyment (effect size = 1.2%), neighbourhood safety and cohesion (effect size = 1.8%) were associated with lower levels of depressive symptoms. Conclusions Most positive experiences were linked with lower levels of depressive symptoms regardless of parental intimate partner violence exposure. However, among those with parental IPV, this association was found only for relationships with peers, school enjoyment, neighbourhood safety and cohesion on depressive symptoms. If our findings are assumed to be causal, nurturing these factors may mitigate the harmful effects of parental intimate partner violence on depressive symptoms in adolescence.

Abstract Introduction Various techniques for whole breast radiation therapy (WBRT) have been reported to increase dose to contralateral tissues. Heart dose is of critical importance as there is no apparent dose threshold below which there is no risk. The aim of this study was to compare planning techniques for WBRT that achieves the best target dosimetry and lowest organ at risk (OAR) dose. Methods Thirty early‐stage whole breast patient datasets, 15 each left‐ and right‐sided cases, were retrospectively selected. Five techniques were generated for each data set: three‐dimensional conformal radiation therapy (3DCRT), hybrid intensity modulated radiation therapy (HYI), hybrid volumetric modulated arc therapy (VMAT) – (HYV), reduced arc VMAT – bowtie (BT), and BT flattening filter free (FFF) – (BTFFF). Plan goals and OARs were evaluated and compared between techniques. Results BT had the highest median conformity index (CI) values (0.82, IQR: 0.80–0.85 left and 0.83, IQR 0.80–0.86 right). BT recorded lower mean heart doses (median value 1.19Gy, IQR: 0.90–1.55), and BTFFF recorded lower heart V2.5 Gy, V5 Gy; median 3.96% (IQR: 2.90–6.80) and 0.90% (IQR: 0.50–1.50) respectively for left‐sided patients. There was a statistically significant difference in all ipsilateral lung measures, (p

Abstract Knowledge of the genetic basis of colorectal cancer has evolved over the past decades, allowing for the pre‐symptomatic identification of affected patients in those with familial syndromes and to the understanding of the multi‐step progression to carcinogenesis in tumors. Knowledge of the genes and pathways involved in colorectal cancer has allowed for targeted therapies in patients in addition to standard chemotherapy for those with metastases. Next‐generation sequencing technologies have now also allowed for the sensitive detection of circulating mutations derived from tumors, which can give insight into the presence of residual disease and has implications for changing the standard paradigms for treatment. This article will specifically review advances in targeted therapy in metastatic colon cancer and the progress being made in using circulating tumor DNA in patient management.

Abstract The winter fallow period common in annual cropping systems leaves soils vulnerable to erosion and nutrient loss, especially to nitrogen (N) leaching. This vulnerability can be mitigated with perennial crops that have living roots in the ground year‐round. The mechanisms, magnitude, and consistency with which perennial crops retain N are not clear. We used an experiment to test whether a perennial crop, miscanthus (Miscanthus × giganteus Greef et Deu.), would leach less N than continuous maize (Zea mays L.) and how soil net N mineralization (Nmin) may explain observed leaching under varied environment and management conditions. The experiment included three crossed factors: (1) cropping system (maize, juvenile miscanthus = 1–2 years old, mature miscanthus = 3–4 years old); (2) N fertilization (0 and 224 kg N ha−1); and (3) environment (four site‐years at two locations in Iowa, USA, that differed in climate and soil fertility). We measured N cycling dynamics, including: inorganic soil N (ammonium + nitrate), in situ Nmin, N leaching, crop N uptake, and calculated system N use efficiency. There were many complex interactions among factors. On average, cumulative Nmin under juvenile miscanthus was 111% greater than maize, but as miscanthus matured, there was no difference in Nmin between the perennial crop and maize. There was no difference in N leaching between juvenile miscanthus and maize, but mature miscanthus decreased N leaching by 42% and 88% compared to maize (with and without N fertilization, respectively). Across all treatments, there was no relationship between Nmin and N leaching, suggesting other mechanisms are regulating N leaching. Overall, mature miscanthus shows promise as a tool to reduce N losses in areas dominated by annual row‐crops.

ABSTRACT Atypical femur fractures (AFFs) are rare complications of anti‐resorptive therapy. Devastating to the affected individual, they pose a public health concern because of reduced uptake of an effective treatment for osteoporosis due to patient concern. The risk of AFF is increased sixfold to sevenfold in patients of Asian ethnicity compared with Europeans. Genetic factors may underlie the AFF phenotype. Given the rarity of AFFs, studying familial AFF cases is valuable in providing insights into any genetic predisposition. We present two Singaporean families, one comprising a mother (1‐a) and a daughter (1‐b), and the other comprising two sisters (2‐a and 2‐b). All four cases presented with bisphosphonate‐associated AFF. Whole‐exome sequencing (WES) was performed on 1‐b, 2‐a, and 2‐b. DNA for 1‐a was not available. Variants were examined using a candidate gene approach comprising a list of genes previously associated with AFF in the literature, as well as using unbiased filtering based on dominant and/or recessive inheritance patterns. Using a candidate gene approach, rare variants shared between all three cases were not identified. A rare variant in TMEM25, shared by the two sisters (2‐a and 2‐b), was identified. A rare heterozygous PLOD2 variant was present in the daughter case with AFF (1‐b), but not in the sisters. A list of potential genetic variants for AFF was identified after variant filtering and annotation analysis of the two sisters (2‐a and 2‐b), including a Gly35Arg variant in TRAF4, a gene required for normal skeletal development. Although the findings from this genetic analysis are inconclusive, a familial aggregation of AFFs is suggestive of a genetic component in AFF pathogenesis. We provide a comprehensive list of rare variants identified in these AFF familial cases to aid future genetic studies. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Abstract Extracellular vesicles (EVs) have shown promise as potential therapeutics for the treatment of various diseases. However, their rapid clearance after administration could be a limitation in certain therapeutic settings. To solve this, an engineering strategy is employed to decorate albumin onto the surface of the EVs through surface display of albumin binding domains (ABDs). ABDs were either included in the extracellular loops of select EV‐enriched tetraspanins (CD63, CD9 and CD81) or directly fused to the extracellular terminal of single transmembrane EV‐sorting domains, such as Lamp2B. These engineered EVs exert robust binding capacity to human serum albumins (HSA) in vitro and mouse serum albumins (MSA) after injection in mice. By binding to MSA, circulating time of EVs dramatically increases after different routes of injection in different strains of mice. Moreover, these engineered EVs show considerable lymph node (LN) and solid tumour accumulation, which can be utilized when using EVs for immunomodulation, cancer‐ and/or immunotherapy. The increased circulation time of EVs may also be important when combined with tissue‐specific targeting ligands and could provide significant benefit for their therapeutic use in a variety of disease indications.

Abstract Partial and/or heterogeneous irradiation of established (i.e., large, vascularized) tumors by α‐particles that exhibit only a 4–5 cell‐diameter range in tissue, limits the therapeutic effect, since regions not being hit by the high energy α‐particles are likely not to be killed. This study aims to mechanistically understand a delivery strategy to uniformly distribute α‐particles within established solid tumors by simultaneously delivering the same α‐particle emitter by two diverse carriers, each killing a different region of the tumor: (1) the cancer‐agnostic, but also tumor‐responsive, liposomes engineered to best irradiate tumor regions far from the vasculature, and (2) a separately administered, antibody, targeting any cancer‐cell's surface marker, to best irradiate the tumor perivascular regions. We demonstrate that on a prostate specific membrane antigen (PSMA)‐expressing prostate cancer xenograft mouse model, for the same total injected radioactivity of the α‐particle emitter Actinium‐225, any radioactivity split ratio between the two carriers resulted in better tumor growth inhibition compared to the tumor inhibition when the total radioactivity was delivered by any of the two carriers alone. This finding was due to more uniform tumor irradiation for the same total injected radioactivity. The killing efficacy was improved even though the tumor‐absorbed dose delivered by the combined carriers was lower than the tumor‐absorbed dose delivered by the antibody alone. Studies on spheroids with different receptor‐expression, used as surrogates of the tumors' avascular regions, demonstrated that our delivery strategy is valid even for as low as 1+ (ImmunoHistoChemistry score) PSMA‐levels. The findings presented herein may hold clinical promise for those established tumors not being effectively eradicated by current α‐particle radiotherapies.

Abstract The Seedlot Selection Tool and Climate‐Smart Restoration Tool are web‐based tools designed to match seedlots with planting sites assuming that seedlots are adapted to the past climates in which they evolved, primarily with respect to temperature and aridity. The tools map the climatic match of seedlots with the past or projected climates of planting sites. The challenge is that future climates are a moving target, which means that seedlots must be adapted to the near‐term climates as well as the climates of the mid‐ to late‐21st century. Because climate projections are uncertain, the prudent approach is to aim for the warmest climate that may be expected while ensuring that seedlots moved from warmer to colder locales are not moved so far that they risk cold damage. Uncertainty in climate projections may be mitigated by ensuring genetic diversity through mixing seed sources and having collections from many parents per seed source. Three examples illustrate how to effectively use the web tools: (1) choosing seedlots targeting different future climates for a mid‐elevation Douglas‐fir site in the Washington Cascades, (2) finding current and future seed sources for restoration of big sagebrush after fires in the Great Basin and Snake River Plain, and (3) planning to ensure that a Douglas‐fir seed inventory includes seedlots suitable for future climates in western Oregon and Washington.

Abstract Stepping‐stone restoration plantings can reconcile conservation goals and local land‐use needs in highly fragmented ecosystems. We explored how initial planting composition influences recruiting plant species density, diversity, abundance, and forest structure in a 13‐year‐old restoration experiment in Los Tuxtlas, Veracruz, Mexico. Treatments included eight fenced plantings with animal‐dispersed species, eight plantings with wind‐dispersed species, eight unplanted plots to favor natural succession, and eight plots in the primary forest as reference sites. We predicted that by attracting more seed dispersers, animal‐dispersed plantings would most closely resemble the primary forest. A census of trees taller than 2 m showed that while wind‐dispersed plantings had more recruits, the animal‐dispersed plantings most closely resembled the primary forest in pioneer abundance, species density and abundance of biotically dispersed and abiotically dispersed plants, individual tree basal area (in square meters per hectare), and vertical structure. The wind‐dispersed plantings more closely approximated the forest in non‐pioneer abundance and community composition. However, restoration treatments were more similar to each other than to the primary forest and did not differ in plant diversity. Animal‐dispersed and wind‐dispersed plantings did not differ in non‐pioneer species density and matched the primary forest in total plot basal area. Higher abundance of trees in wind‐plantings is explained by lower establishment limitations, seed legacy effects, and rapid reproduction of a few planted species. As the experiment continues, we expect treatment effects on seed dispersers will more strongly influence the recruiting plant community, leading the animal‐dispersed plantings to more closely resemble the primary forest in diversity and forest structure.

In this case study, we present a novel approach to care within a Home Treatment Team, using a behavioural contract. This is a signed, written agreement that targets specific behaviours for change. The concept draws on social learning theory in that it requires social interaction and a relationship to work. In psychiatric settings, the behavioural contract often finds use in Democratic Therapeutic Communities but rarely in crisis or acute services. In this case study, we attempted to use a behavioural contract within our Home Treatment Team to help a patient address his alcohol dependence and its subsequent effect on his daily living activities. The behavioural contract provided an alternative way to manage a crisis episode. We hope that other crisis service staff reading this case study may use a behavioural contract in their work to a similar beneficial effect.