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We study Bayesian methods for large-scale linear inverse problems, focusing on the challenging task of hyperparameter estimation. Typical hierarchical Bayesian formulations that follow a Markov Chain Monte Carlo approach are possible for small problems but are not computationally feasible for problems with a very large number of unknown inverse parameters. In this work, we describe an empirical Bayes (EB) method to estimate hyperparameters that maximize the marginal posterior, i.e., the probability density of the hyperparameters conditioned on the data, and then we use the estimated hyperparameters to compute the posterior of the unknown inverse parameters. For problems where the computation of the square root and inverse of prior covariance matrices are not feasible, we describe an approach based on the generalized Golub-Kahan bidiagonalization to approximate the marginal posterior and seek hyperparameters that minimize the approximate marginal posterior. Numerical results from seismic and atmospheric tomography demonstrate the accuracy, robustness, and potential benefits of the proposed approach. [ABSTRACT FROM AUTHOR]

Although causal evidence synthesis is critical for the policy sciences—whether it be analysis for policy or analysis of policy—its repeatable, systematic, and transparent execution remains challenging due to the growing volume, variety, and velocity of policy-relevant evidence generation as well as the complex web of relationships within which policies are usually situated. To address these shortcomings, we develop a novel, semi-automated approach to synthesizing causal evidence from policy-relevant documents. Specifically, we propose the use of natural language processing (NLP) for the extraction of causal evidence and subsequent homogenization of the text; causal mapping for the collation, visualization, and summarization of complex interdependencies within the policy system; and graph analytics for further investigation of the structure and dynamics of the causal map. We illustrate this approach by applying it to a collection of 28 articles on the emissions trading scheme (ETS), a policy instrument of increasing importance for climate change mitigation. In all, we find 300 variables and 284 cause-effect pairs in our input dataset (consisting of 4524 sentences), which are reduced to 70 unique variables and 119 cause-effect pairs after homogenization. We create a causal map depicting these relationships and analyze it to demonstrate the perspectives and policy-relevant insights that can be obtained. We compare these with select manually conducted, previous meta-reviews of the policy instrument, and find them to be not only broadly consistent but also complementary. We conclude that, despite remaining limitations, this approach can help synthesize causal evidence for policy analysis, policy making, and policy research. [ABSTRACT FROM AUTHOR]

Antenatal inflammation in the form of chorioamnionitis (fetal membranes; HCA) and funisitis (umbilical vessels; FUN) is a major risk factor for preterm birth. Exposure to HCA + FUN affects infants by releasing mediators that may suppress respiratory drive. While the association between clinical chorioamnionitis (CCA) and (depressed) spontaneous breathing has been described, we have investigated the association between breathing and HCA + FUN. Infants born < 30 weeks' gestation with available placental pathology assessments were included. Infants were compared at multiple levels: infants with vs without HCA + FUN (comparison 1) and infants with subclinical HCA + FUN vs infants without any chorioamnionitis (comparison 2). The primary outcome was breathing effort, defined as minute volume (MV) of spontaneous breathing in the first 5 min after birth. We also assessed tidal volume (Vt), respiratory rate (RR), heart rate (HR), oxygen saturation (SpO2) and oxygen requirement (FiO2). Regression analyses were performed to control for confounding factors. One hundred eighty-six infants were included (n = 75 infants with HCA + FUN vs. n = 111 infants without HCA + FUN). Comparison 1: Infants with HCA + FUN had lower gestational ages 26+5 (25+0–28+1; median (IQR) and lower birthweights (mean ± SD; 943 ± 264) compared to infants without HCA + FUN (28+4 (27+0–29+1) weeks, p < 0.001 and 1023 ± 270 g, p = 0.049). Comparison 2: Subclinical HCA + FUN was diagnosed in 46/75 HCA + FUN infants. Infants with subclinical HCA + FUN had lower gestational ages (26+6 (25+1–28+3) vs. 28+4 (27+2–29+1) weeks, p < 0.001) without significant differences for birthweights (987 ± 248 vs. 1027 ± 267 g, p = 0.389) compared to infants without any chorioamnionitis (n = 102 infants). After adjustment, HCA + FUN was associated with lower MV (p = 0.025), but subclinical HCA + FUN was not (p = 0.226). HCA + FUN and subclinical HCA + FUN were associated with lower Vt (p = 0.003; p = 0.014), SpO2 at 5 min (p = 0.021; 0.036) and SpO2/FiO2 ratio (p = 0.028; p = 0.040). Conclusion: HCA + FUN and subclinical HCA + FUN are associated with reduced oxygenation and parameters that reflect breathing effort in premature infants at birth. What is Known: • Acute antenatal inflammation, in the form of chorioamnionitis (fetal membranes) and funisitis (umbilical vessels), affects a large proportion of premature infants. • Clinical chorioamnionitis is associated with reduced breathing effort and oxygenation in premature infants at birth. What is New: • Histological and subclinical chorioamnionitis and funisitis are associated with reduced breathing effort parameters and oxygenation in premature infants at birth. [ABSTRACT FROM AUTHOR]

Hantaan virus (HTNV) and Puumala virus (PUUV) are pathogenic zoonoses found in Asia and Europe, respectively. We conducted a randomized Phase 1 clinical trial of individual HTNV and PUUV DNA vaccines targeting the envelope glycoproteins (GnGc), as well as a combined HTNV/PUUV DNA vaccine delivered at varying doses using the PharmaJet Stratis® needle-free injection system (NCT02776761). Cohort 1 and 2 vaccines consisted of 2 mg/vaccination of HTNV or PUUV plasmid, respectively. Cohort 3 vaccine consisted of 2 mg/vaccination of 1:1 mixture of HTNV and PUUV vaccines. Vaccinations were administered on Days 0, 28, 56, and 168. The vaccines were safe and well tolerated. Neutralizing antibody responses were elicited in 7/7 (100%) subjects who received the HTNV DNA (Cohort 1) and 6/6 (100%) subjects who received the PUUV DNA (Cohort 2) vaccines alone. The combination vaccine resulted in 4/9 (44%) seroconversion against both viruses. After the first two vaccinations, the seroconversion rates for the HTNV and PUUV vaccines were >80%. [ABSTRACT FROM AUTHOR]

We develop a method for the extraction of the surface impedance tensor of a generic reflective metasurface using an analytic relation between the tensorial surface impedance and the four polarisation-dependent reflection coefficients. We apply this technique to experimental data obtained from a metasurface with a rhomboidal unit cell in the 16–26 GHz range, but note that it could be applied to reflective metasurfaces in any frequency regime. The extraction method can also be applied to model data to facilitate the design process of spatially graded tensorial metasurfaces that allow for full control of the form of the scattered field. [ABSTRACT FROM AUTHOR]

Erythroderma, an inflammatory skin condition characterized by widespread erythema with variable degrees of exfoliation, pustulation, or vesiculobullous formation, is associated with high morbidity and mortality. Determining the underlying cause of erythroderma frequently presents a diagnostic challenge, which may contribute to the condition's relatively poor prognosis. This review covers the clinical presentation, pathophysiology, diagnosis, and treatment of erythroderma. It discusses similarities and differences among the many underlying etiologies of the condition and differences between erythrodermic and non-erythrodermic presentations of the same dermatosis. Finally, this article explores current research that may provide future tools in the diagnosis and management of erythroderma. [ABSTRACT FROM AUTHOR]

Background: Neuroblastoma is the most common extracranial solid tumor in children and accounts for 15% of pediatric cancer related deaths. Targeting neuroblastoma with immunotherapies has proven challenging due to a paucity of immune cells in the tumor microenvironment and the release of immunosuppressive cytokines by neuroblastoma tumor cells. We hypothesized that combining an oncolytic Herpes Simplex Virus (oHSV) with natural killer (NK) cells might overcome these barriers and incite tumor cell death. Methods: We utilized MYCN amplified and non-amplified neuroblastoma cell lines, the IL-12 expressing oHSV, M002, and the human NK cell line, NK-92 MI. We assessed the cytotoxicity of NK cells against neuroblastoma with and without M002 infection, the effects of M002 on NK cell priming, and the impact of M002 and priming on the migratory capacity and CD107a expression of NK cells. To test clinical applicability, we then investigated the effects of M002 and NK cells on neuroblastoma in vivo. Results: NK cells were more attracted to neuroblastoma cells that were infected with M002. There was an increase in neuroblastoma cell death with the combination treatment of M002 and NK cells both in vitro and in vivo. Priming the NK cells enhanced their cytotoxicity, migratory capacity and CD107a expression. Conclusions: To the best of our knowledge, these investigations are the first to demonstrate the effects of an oncolytic virus combined with self-maintaining NK cells in neuroblastoma and the priming effect of neuroblastoma on NK cells. The current studies provide a deeper understanding of the relation between NK cells and neuroblastoma and these data suggest that oHSV increases NK cell cytotoxicity towards neuroblastoma. [ABSTRACT FROM AUTHOR]

Snark is a form of verbal aggression that uses humor to diminish a victim. The present study explored predictors of U.S. teachers' use of snark in the classroom. Kindergarten-12th grade teachers (N = 516) self-reported on their social and emotional competencies (i.e., perspective taking, forgiveness, mindfulness, expressive suppression, and decision-making skills), experiences of occupational health and personal well-being (i.e., burnout, job satisfaction, depression, and life satisfaction) and snark use. Stepwise multilevel models indicated that teachers' social and emotional competencies, and subsequently, their occupational health and well-being, explained significant portions of the variance in snark use. Specifically, teachers with greater perspective taking skills reported less frequent snark use, and those who used expressive suppression reported more frequent snark use. Burnout, job satisfaction, depression, and life satisfaction were all positively associated with greater snark use. Results are described in relation to research on adult social and emotional competencies, teachers' occupational health and well-being, and teachers' conflict management strategies. This study sets the stage for future research to investigate the effects of teachers' snark use on student outcomes. [ABSTRACT FROM AUTHOR]

Objective: To estimate the cost-effectiveness of online behavioral interventions (EczemaCareOnline.org.uk) designed to support eczema self-care management for parents/carers and young people from an NHS perspective. Methods: Two within-trial economic evaluations, using regression-based approaches, adjusting for baseline and pre-specified confounder variables, were undertaken alongside two independent, pragmatic, parallel group, unmasked randomized controlled trials, recruiting through primary care. Trial 1 recruited 340 parents/carers of children aged 0–12 years and Trial 2 337 young people aged 13–25 years with eczema scored ≥ 5 on Patient-Oriented Eczema Measure (POEM). Participants were randomized (1:1) to online intervention plus usual care or usual care alone. Resource use, collected via medical notes review, was valued using published unit costs in UK £Sterling 2021. Quality-of-life was elicited using proxy CHU-9D in Trial 1 and self-report EQ-5D-5L in Trial 2. Results: The intervention was dominant (cost saving and more effective) with a high probability of cost-effectiveness (> 68%) in most analyses. The exception was the complete case cost–utility analysis for Trial 1 (omitting participants with children aged < 2), with adjusted incremental cost savings of -£34.15 (95% CI – 104.54 to 36.24) and incremental QALYs of – 0.003 (95% CI – 0.021 to 0.015) producing an incremental cost per QALY of £12,466. In the secondary combined (Trials 1 and 2) cost-effectiveness analysis, the adjusted incremental cost was -£20.35 (95% CI – 55.41 to 14.70) with incremental success (≥ 2-point change on POEM) of 10.3% (95% CI 2.3–18.1%). Conclusion: The free at point of use online eczema self-management intervention was low cost to run and cost-effective. Trial registration: This trial was registered prospectively with the ISRCTN registry (ISRCTN79282252). URL www.EczemaCareOnline.org.uk. [ABSTRACT FROM AUTHOR]

This study investigated preservice teachers' experiences of helping peers with technical support. Considering college-aged students prefer to seek help from relative experts rather than instructors, the rationale for the study was to contribute to the literature on relative expertise by exploring how preservice teachers supported peers. A mixed methods approach was employed using (1) social network analysis to find and identify the preservice teachers who assisted the greatest number of peers and (2) phenomenological interviewing and thematic analysis to understand how they helped their peers with technical support. Findings show that prior to serving as a relative expert around technical support, a preservice teacher explores tools and becomes comfortable with offering support. Findings also show how relative experts are approached by peers, how they offer support, and what changes they exhibit in confidence and comfort as a result of offering support. The findings in this study could be leveraged by teacher education programs to increase outcomes related to technology use and relative expertise. Implications and future research directions are noted including the potential value of peer technical support to help preservice teachers more easily transition to inservice teaching. [ABSTRACT FROM AUTHOR]

Sexual harassment is an intractable problem that harms the students, community, culture, and success of institutes of higher education (IHEs). The alarming prevalence of sexual harassment at IHEs highlights the urgent need for effective prevention programs. However, there are few empirically supported preventive interventions that effectively target the factors that most impact the determinants, trajectory, and short- and intermediate-term effects of sexual harassment. In this paper, we overview the problem of sexual harassment and propose an organizing framework to help IHEs develop effective interventions to prevent sexual harassment. Guided by prevention science, we propose a framework—modified from SAMHSA's (2019) guidelines for prevention practitioners—that underscores the criticality of trauma- and equity-informed characteristics in prevention programs. We offer a discussion on how IHEs must consider and evaluate the empirical evidence of effectiveness, flexibility, cultural competency, and sustainability when developing and adapting prevention programs to reduce and—ultimately—ameliorate sexual harassment. We conclude with recommendations that can provide a roadmap for higher education stakeholders and researchers to prevent this urgent public health concern. [ABSTRACT FROM AUTHOR]

For children and young adults, living with chronic kidney disease (CKD) poses physical, mental, and social challenges. The mental health functioning of children and adolescents with CKD plays an important role in the medical, educational, vocational, and quality of life outcomes, yet receives little systematic attention in the busy pediatric nephrology clinic. This article will provide an overview of the prevalence of mental illness and symptoms in children and young adults with CKD, strategies to assess for dysfunction, and the long-term outcomes associated with impaired functioning. While there is a relative dearth of literature regarding evidence-based interventions in this population to improve mental health functioning, we provide "best practice" strategies based on the available literature to address emotional and/or behavioral challenges once they are identified. More research is needed to define appropriate interventions to alleviate mental health issues and social-emotional distress, and this review of the literature will serve to provide directions for future research. [ABSTRACT FROM AUTHOR]

Purpose: Telemedicine approaches to autism (ASD) assessment have become increasingly common, yet few validated tools exist for this purpose. This study presents results from a clinical trial investigating two approaches to tele-assessment for ASD in toddlers. Methods: 144 children (29% female) between 17 and 36 months of age (mean = 2.5 years, SD = 0.33 years) completed tele-assessment using either the TELE-ASD-PEDS (TAP) or an experimental remote administration of the Screening Tool for Autism in Toddlers (STAT). All children then completed traditional in-person assessment with a blinded clinician, using the Mullen Scales of Early Learning (MSEL), Vineland Adaptive Behavior Scales, 3rd Edition (VABS-3), and Autism Diagnostic Observation Schedule (ADOS-2). Both tele-assessment and in-person assessment included a clinical interview with caregivers. Results: Results indicated diagnostic agreement for 92% of participants. Children diagnosed with ASD following in-person assessment who were missed by tele-assessment (n = 8) had lower scores on tele- and in-person ASD assessment tools. Children inaccurately identified as having ASD by tele-assessment (n = 3) were younger than other children and had higher developmental and adaptive behavior scores than children accurately diagnosed with ASD by tele-assessment. Diagnostic certainty was highest for children correctly identified as having ASD via tele-assessment. Clinicians and caregivers reported satisfaction with tele-assessment procedures. Conclusion: This work provides additional support for the use of tele-assessment for identification of ASD in toddlers, with both clinicians and families reporting broad acceptability. Continued development and refinement of tele-assessment procedures is recommended to optimize this approach for the needs of varying clinicians, families, and circumstances. [ABSTRACT FROM AUTHOR]

Most very premature infants breathe at birth but require respiratory support in order to stimulate and support their breathing. A significant proportion of premature infants are affected by chorioamnionitis, defined as an umbrella term for antenatal inflammation of the foetal membranes and umbilical vessels. Chorioamnionitis produces inflammatory mediators that potentially depress the respiratory drive generated in the brainstem. Such respiratory depression could maintain itself by delaying lung aeration, hampering respiratory support at birth and putting infants at risk of hypoxic injury. This inflammatory-mediated respiratory depression may contribute to an association between chorioamnionitis and increased requirement of neonatal resuscitation in premature infants at birth. This narrative review summarises mechanisms on how respiratory drive and spontaneous breathing could be influenced by chorioamnionitis and provides possible interventions to stimulate spontaneous breathing. Conclusion: Chorioamnionitis could possibly depress respiratory drive and spontaneous breathing in premature infants at birth. Interventions to stimulate spontaneous breathing could therefore be valuable. What is Known: • A large proportion of premature infants are affected by chorioamnionitis, antenatal inflammation of the foetal membranes and umbilical vessels. What is New: • Premature infants affected by chorioamnionitis might be exposed to higher concentrations of respiratory drive inhibitors which could depress breathing at birth. • Premature infants affected by chorioamnionitis seem to be associated with a higher and more extensive requirement of resuscitation at birth. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease of 2019 (COVID-19) has disproportionately affected adults with kidney disease. Data regarding outcomes among children with kidney disease are limited. The North American Pediatric Renal Trials Collaborative Studies Registry (NAPRTCS) has followed children with chronic kidney disease (CKD) since 1987 at 87 participating centers. This study aimed to evaluate the impact of COVID-19 among participants enrolled in the three arms of the registry: CKD, dialysis, and transplant. Methods: This was a retrospective cohort study of COVID-19 among participants in the NAPRTCS CKD, dialysis, and transplant registries from 2020 to 2022. Where appropriate, t-tests, chi-square analyses, and univariate logistic regression were used to evaluate the data. Results: The cohort included 1505 NAPRTCS participants with recent data entry; 260 (17%) had documented COVID-19. Infections occurred in all three registry arms, namely, 10% (n = 29) in CKD, 11% (n = 67) in dialysis, and 26% (n = 164) in transplant. The majority of participants (75%) were symptomatic. Hospitalizations occurred in 17% (n = 5) of participants with CKD, 27% (n = 18) maintenance dialysis participants, and 26% (n = 43) of transplant participants. Fourteen percent (n = 4) of CKD participants and 10% (n = 17) of transplant participants developed acute kidney injury (AKI), and a total of eight participants (one CKD, seven transplant) required dialysis initiation. Among transplant participants with moderate to severe illness, 40–43% developed AKI and 29–40% required acute dialysis. There were no reported deaths. Conclusions: COVID-19 was documented in 17% of active NAPRTCS participants. While there was no documented mortality, the majority of participants were symptomatic, and a quarter required hospitalization. [ABSTRACT FROM AUTHOR]

CRISPR-Cas9 is a powerful tool for genome editing, but the strict requirement for an NGG protospacer-adjacent motif (PAM) sequence immediately next to the DNA target limits the number of editable genes. Recently developed Cas9 variants have been engineered with relaxed PAM requirements, including SpGCas9 (SpG) and the nearly PAM-less SpRY-Cas9 (SpRY). However, the molecular mechanisms of how SpRY recognizes all potential PAM sequences remains unclear. Here, we combine structural and biochemical approaches to determine how SpRY interrogates DNA and recognizes target sites. Divergent PAM sequences can be accommodated through conformational flexibility within the PAM-interacting region, which facilitates tight binding to off-target DNA sequences. Nuclease activation occurs ~1000-fold slower than for Streptococcus pyogenes Cas9, enabling us to directly visualize multiple on-pathway intermediate states. Experiments with SpG position it as an intermediate enzyme between Cas9 and SpRY. Our findings shed light on the molecular mechanisms of PAMless genome editing. [ABSTRACT FROM AUTHOR]

Background: 5-Fluorouracil (5-FU) remains a core component of systemic therapy for colorectal cancer (CRC). However, response rates remain low, and development of therapy resistance is a primary issue. Combinatorial strategies employing a second agent to augment the therapeutic effect of chemotherapy is predicted to reduce the incidence of treatment resistance and increase the durability of response to therapy. Methods: Here, we employed quantitative proteomics approaches to identify novel druggable proteins and molecular pathways that are deregulated in response to 5-FU, which might serve as targets to improve sensitivity to chemotherapy. Drug combinations were evaluated using 2D and 3D CRC cell line models and an ex vivo culture model of a patient-derived tumour. Results: Quantitative proteomics identified upregulation of the mitosis-associated protein Aurora B (AURKB), within a network of upregulated proteins, in response to a 24 h 5-FU treatment. In CRC cell lines, AURKB inhibition with the dihydrogen phosphate prodrug AZD1152, markedly improved the potency of 5-FU in 2D and 3D in vitro CRC models. Sequential treatment with 5-FU then AZD1152 also enhanced the response of a patient-derived CRC cells to 5-FU in ex vivo cultures. Conclusions: AURKB inhibition may be a rational approach to augment the effectiveness of 5-FU chemotherapy in CRC. [ABSTRACT FROM AUTHOR]

Having a walkable built environment is important to encourage active school transport. The aim of this study was to measure the walkability of all Perth, Western Australia (WA) schools and investigate whether differences in walkability exist by school type, socioeconomic status (SES) and/or subregion. Geographic Information Systems technology was used to measure walkability (i.e., traffic exposure and pedestrian connectivity) surrounding all Perth schools (n = 651) in 2021. Walkability scores and their individual components were compared using odds ratios and one-way ANOVAs with post-hoc comparisons by school type (primary, secondary and K-12; government and non-government), school SES and subregion. The majority of Perth schools (73.8%) were below the WA Planning Commission’s target for a walkable catchment area. Neighbourhoods surrounding high SES schools were significantly more walkable than neighbourhoods surrounding medium and low SES schools (mean walkability scores: 12.4, 10.5, 10.1, respectively, p <.001). Neighbourhoods surrounding schools located in the Central subregion (mean 12.3) were significantly more walkable than neighbourhoods surrounding schools located in the North-West (mean 11.0, p =.024), South Metropolitan (mean 10.0, p <.001) and North-East (mean 8.4, p <.001) subregions. No significant differences in walkability index scores were found for school type. This study found a large proportion of Perth schools were surrounded by disconnected street networks and that neighbourhoods surrounding high SES schools were, on average, more walkable than neighbourhoods surrounding medium and low SES schools. The results highlight the importance of modifying the built environment to increase opportunities for active school transport, particularly in low and medium socio-economic areas. [ABSTRACT FROM AUTHOR]

Cutaneous T-cell lymphomas (CTCL) are a rare group of T-cell neoplasms which infiltrate the skin and can result in substantial morbidity and mortality. Risk factors for CTCL are still poorly understood though recent studies suggest chemical exposures may play a role in its development. To further characterize patient-centered risk factors for CTCL, especially compared with matched controls, we performed one of the largest prospective cohort survey studies to date to examine patient-reported exposures and health-related quality of life (HRQoL) in association with concurrent clinical disease characteristics. Patient demographics, lifestyle factors, and chemical exposures were collected via clinical data and surveys. Descriptive statistics, ANOVA, Chi-square tests and t tests were utilized to compare patient-reported exposures and HRQoL in patients with CTCL versus matched healthy controls (HC). Statistically significant differences were identified between patients and HC in terms of race (non-white race 22.4% in CTCL patients vs. 18.8% in HC, P = 0.01), and education level (high school or less 41.6% in CTCL patients vs. 14.3% in HC, P = 0.001), but not with Fitzpatrick skin type (P = 0.11) or smoking status (P = 0.28). Notably, 36.0% of the CTCL patients reported exposures to chemicals, a near threefold increased percentage when compared to HC (12.9%). Among various chemical exposures, 27.0% of the CTCL patients specifically reported industrial chemical exposure, a more than two-fold increased percentage when compared to HC (12.9%). Itch and pain were significantly associated with skin disease severity (as evaluated by CTCL-specific mSWAT score) in advanced stage disease (stages IIB–IVB) (r = 0.48 and 0.57, P < 0.05). Itch and body mass index (BMI) were weakly associated with skin disease severity in early-stage disease (stages IA–IIA) (r = 0.27 and 0.20, P < 0.05). [ABSTRACT FROM AUTHOR]

The primary aims of the current study were to explore differences among adolescent parentification profiles and to determine the extent to which those profiles are linked to physical health and life satisfaction among adolescents. While parentification roles in adolescents have been found to be detrimental to mental health outcomes, minimal research has focused on its relation to other outcomes (e.g., physical health outcomes). Also, there is a dearth of empirically-supported knowledge on how family culture might shape those outcomes. A large sample of Polish-speaking adolescents (N = 41,162 adolescents aged 12–21 years old) participated in a survey research study focused on family structure and adolescent functioning. We used cluster analysis to identify patterns of parent caregiving and to explore associations between those patterns and health and life satisfaction. Cluster analysis techniques identified five parent caregiving profiles: (a) satisfied emotional parent caregiving, (b) dissatisfied youth with moderate levels of parent caregiving, (c) satisfied youth with low levels of parent caregiving, (d) dissatisfied youth with low levels of parent caregiving, and (e) conflicted parent caregiving. Mean levels of physical health and life satisfaction were found to be highest for adolescents in the following cluster profiles: "satisfied emotional parent caregiving" and "conflicted parent caregiving." The lowest means were found in the following cluster profiles: "dissatisfied youth with moderate levels of parent caregiving" and "satisfied youth with low levels of parent caregiving." The results of all analyses are discussed as well as implications for future research and family therapy. [ABSTRACT FROM AUTHOR]

Background: Familial partial lipodystrophy (FPLD) is an inherited disorder of white adipose tissue that causes premature cardiometabolic disease. There is no clear diagnostic criteria for FPLD, and this may explain the under-detection of this condition. Aim: This pilot study aimed to describe the clinical features of women with FPLD and to explore the value of adipose tissue measurements that could be useful in diagnosis. Methods: In 8 women with FPLD and 4 controls, skinfold measurements, DXA and whole-body MRI were undertaken. Results: Whole genome sequencing was negative for monogenic metabolic causes, but polygenic scores for partial lipodystrophy were elevated in keeping with FPLD type 1. The mean age of diagnosis of DM was 31 years in the FPLD group. Compared with controls, the FPLD group had increased HOMA-IR (10.3 vs 2.9, p = 0.028) and lower mean thigh skinfold thickness (19.5 mm vs 48.2 mm, p = 0.008). The FPLD group had lower percentage of leg fat and an increased ratio of trunk to leg fat percentage on DXA. By MRI, the FPLD group had decreased subcutaneous adipose tissue (SAT) volume in the femoral and calf regions (p < 0.01); abdominal SAT, visceral adipose tissue, and femoral and calf muscle volumes were not different from controls. Conclusion: Women with FPLD1 in Singapore have significant loss of adipose but not muscle tissue in lower limbs and have early onset of diabetes. Reduced thigh skinfold, and increased ratio of trunk to leg fat percentage on DXA are potentially clinically useful markers to identify FPLD1. [ABSTRACT FROM AUTHOR]

Introduction: Prophylactic treatment of hemophilia B with recombinant factor IX (rFIX) molecules with enhanced pharmacokinetics including rIX-FP (albutrepenonacog alfa; Idelvion©) and rFIXFc (eftrenonacog alfa; Alprolix©) have commonly been used in the clinic. In the absence of head-to-head comparative trials, the aim of this study was to estimate the efficacy of rIX-FP versus rFIXFc using matching-adjusted indirect comparisons (MAICs). Methods: MAIC analyses leveraged individual patient data from the PROLONG-9FP trial and published summary-level data from the B-LONG trial for subjects who received weekly prophylaxis regimens. Individual patient data were used to assign weights and balance subjects from PROLONG-9FP with subjects from B-LONG on baseline disease severity, age, prior FIX regimen, and body mass index (BMI). Six efficacy outcomes were analyzed including annualized bleeding rate (ABR), annualized spontaneous bleeding rate (AsBR), annualized joint bleeding rate (AjBR), and the proportion of subjects without bleeding events (for total, spontaneous, and joint bleeding events). Results: After adjustment for baseline disease severity, age, prior FIX regimen, and BMI, rIX-FP was associated with a statistically significant decrease in AsBR (rate ratio [RR] 0.42; 95% confidence interval [CI] 0.22, 0.82; P = 0.0107), and the proportion of patients without bleeding events (odds ratio [OR] 3.24; 95% CI 1.41, 7.45; P = 0.0057), spontaneous bleeding events (OR 3.47; 95% CI 1.56, 7.73; P = 0.0023), and joint bleeding events (OR 2.41; 95% CI 1.10, 5.26; P = 0.0274) compared with rFIXFc. Prophylactic treatment with rIX-FP was also associated with a numerically lower ABR (RR 0.75; 95% CI 0.32, 1.75; P = 0.5095) and AjBR (RR 0.82; 95% CI 0.37, 1.82; P = 0.6178). Conclusion: The MAICs demonstrated that weekly prophylaxis treatment of severe hemophilia B with rIX-FP resulted in favorable efficacy outcomes as compared to rFIXFc. These findings suggest rIX-FP may offer improved clinical benefits over rFIXFc. [ABSTRACT FROM AUTHOR]

Background: Few longitudinal studies have evaluated the impact of chronic kidney disease (CKD) duration on health-related quality of life (HRQOL). The study's aim was to determine how HRQOL changes over time in childhood CKD. Methods: Study participants were children in the chronic kidney disease in children (CKiD) cohort who completed the pediatric quality of life inventory (PedsQL) on three or more occasions over the course of two or more years. Generalized gamma (GG) mixed-effects models were applied to assess the effect of CKD duration on HRQOL while controlling for selected covariates. Results: A total of 692 children (median age = 11.2) with a median of 8.3 years duration of CKD were evaluated. All subjects had a GFR greater than 15 ml/min/1.73 m2. GG models with child self-report PedsQL data indicated that longer CKD duration was associated with improved total HRQOL and the 4 domains of HRQOL. GG models with parent-proxy PedsQL data indicated that longer duration was associated with better emotional but worse school HRQOL. Increasing trajectories of child self-report HRQOL were observed in the majority of subjects, while parents less frequently reported increasing trajectories of HRQOL. There was no significant relationship between total HRQOL and time-varying GFR. Conclusions: Longer duration of the disease is associated with improved HRQOL on child self-report scales; however, parent-proxy results were less likely to demonstrate any significant change over time. This divergence could be due to greater optimism and accommodation of CKD in children. Clinicians can use these data to better understand the needs of pediatric CKD patients. [ABSTRACT FROM AUTHOR]

The ability to perform sophisticated, high-throughput optogenetic experiments has been greatly enhanced by recent open-source illumination devices that allow independent programming of light patterns in single wells of microwell plates. However, there is currently a lack of instrumentation to monitor such experiments in real time, necessitating repeated transfers of the samples to stand-alone analytical instruments, thus limiting the types of experiments that could be performed. Here we address this gap with the development of the optoPlateReader (oPR), an open-source, solid-state, compact device that allows automated optogenetic stimulation and spectroscopy in each well of a 96-well plate. The oPR integrates an optoPlate illumination module with a module called the optoReader, an array of 96 photodiodes and LEDs that allows 96 parallel light measurements. The oPR was optimized for stimulation with blue light and for measurements of optical density and fluorescence. After calibration of all device components, we used the oPR to measure growth and to induce and measure fluorescent protein expression in E. coli. We further demonstrated how the optical read/write capabilities of the oPR permit computer-in-the-loop feedback control, where the current state of the sample can be used to adjust the optical stimulation parameters of the sample according to pre-defined feedback algorithms. The oPR will thus help realize an untapped potential for optogenetic experiments by enabling automated reading, writing, and feedback in microwell plates through open-source hardware that is accessible, customizable, and inexpensive.An open source, 96-well plate reader allows simultaneous optogenetic stimulation and absorbance/fluorescence measurements in each well. [ABSTRACT FROM AUTHOR]

Following two periods of dike intrusion in 2021 at Fagradalsfjall, Iceland, one of which led to an eruption, a third dike intrusion commenced on 30 July 2022. A sudden increase in seismicity occurred within the diking area, with approximately 1700 automatically detected earthquakes > M1 within 24 h. Strong earthquakes were felt over several days within a wider area (largest MW 5.3). The timeline and spatial distribution of seismicity suggested it resulted from diking, together with triggered seismicity in nearby areas releasing stored tectonic stress. Geodetic observations revealed displacements consistent with a dike intrusion, and geodetic modeling on 2 August revealed a best-fit model with a shallow top depth of the dike (~1 km), and high magma inflow rate (~49 m3/s). Also considering a decline in seismicity, a warning was issued that the likelihood of a new eruption in the coming days was high. An effusive eruption started the next day (3 August) on a ~375-m-long fissure, with an initial extrusion rate of 32 m3/s. The projected surface location of the dike (from the optimal model) was within 49–110 m of the eruptive fissure. We present a timeline of the activity and monitoring response in the days both preceding and following the eruption onset. We compare the details of the activity that occurred prior to this diking and eruption to the previous events at Fagradalsfjall to improve understanding of unrest preceding eruptions. [ABSTRACT FROM AUTHOR]

Intracranial metastases in prostate cancer are uncommon but clinically aggressive. A detailed molecular characterization of prostate cancer intracranial metastases would improve our understanding of their pathogenesis and the search for new treatment strategies. We evaluated the clinical and molecular characteristics of 36 patients with metastatic prostate cancer to either the dura or brain parenchyma. We performed whole genome sequencing (WGS) of 10 intracranial prostate cancer metastases, as well as WGS of primary prostate tumors from men who later developed metastatic disease (n = 6) and nonbrain prostate cancer metastases (n = 36). This first whole genome sequencing study of prostate intracranial metastases led to several new insights. First, there was a higher diversity of complex structural alterations in prostate cancer intracranial metastases compared to primary tumor tissues. Chromothripsis and chromoplexy events seemed to dominate, yet there were few enrichments of specific categories of structural variants compared with non-brain metastases. Second, aberrations involving the AR gene, including AR enhancer gain were observed in 7/10 (70%) of intracranial metastases, as well as recurrent loss of function aberrations involving TP53 in 8/10 (80%), RB1 in 2/10 (20%), BRCA2 in 2/10 (20%), and activation of the PI3K/AKT/PTEN pathway in 8/10 (80%). These alterations were frequently present in tumor tissues from other sites of disease obtained concurrently or sequentially from the same individuals. Third, clonality analysis points to genomic factors and evolutionary bottlenecks that contribute to metastatic spread in patients with prostate cancer. These results describe the aggressive molecular features underlying intracranial metastasis that may inform future diagnostic and treatment approaches. [ABSTRACT FROM AUTHOR]

Th17 cells that produce Interleukin IL-17 are pathogenic in many human diseases, including inflammatory bowel disease, but are, paradoxically, essential for maintaining the integrity of the intestinal barrier in a non-inflammatory state. However, the intracellular mechanisms that regulate distinct transcriptional profiles and functional diversity of Th17 cells remain unclear. Here we show Raftlin1, a lipid raft protein, specifically upregulates and forms a complex with RORγt in pathogenic Th17 cells. Disruption of the RORγt-Raftlin1 complex results in the reduction of pathogenic Th17 cells in response to Citrobacter rodentium; however, there is no effect on nonpathogenic Th17 cells in response to commensal segmented filamentous bacteria. Mechanistically, we show that Raftlin1 recruits distinct phospholipids to RORγt and promotes the pathogenicity of Th17 cells. Thus, we have identified a mechanism that drives the pathogenic function of Th17 cells, which could provide a platform for advanced therapeutic strategies to dampen Th17-mediated inflammatory diseases. IL-17 secreting Th17 cells have established roles in numerous immune-pathologies but paradoxically are required homeostatically in the maintenance of the intestinal barrier. Here the authors establish Raftlin-1 in the recruitment of phospholipids that are linked to the emergence of pathogenic Th17 cells in animal models of bowel inflammation. [ABSTRACT FROM AUTHOR]

Severe, protracted symptoms are associated with poor outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In a placebo-controlled study of casirivimab and imdevimab (CAS + IMD) in persons at high risk of severe coronavirus disease 2019 (COVID-19; n = 3816), evolution of individual symptoms was assessed for resolution patterns across risk factors, and baseline SARS-CoV-2-specific antibody responses against S1 and N domains. CAS + IMD versus placebo provided statistically significant resolution for 17/23 symptoms, with greater response linked to absence of endogenous anti–SARS-CoV-2 immunoglobulin (Ig)G, IgA, or specific neutralizing antibodies at baseline, or high baseline viral load. Resolution of five key symptoms (onset days 3–5)—dyspnea, cough, feeling feverish, fatigue, and loss of appetite—independently correlated with reduced hospitalization and death (hazard ratio range: 0.31–0.56; P < 0.001–0.043), and was more rapid in CAS + IMD-treated patients lacking robust early antibody responses. Those who seroconverted late still benefited from treatment. Thus, highly neutralizing COVID-19-specific antibodies provided by CAS + IMD treatment accelerated key symptom resolution associated with hospitalization and death in those at high risk for severe disease as well as in those lacking early, endogenous neutralizing antibody responses. [ABSTRACT FROM AUTHOR]

Pyridoxal 5'-phosphate (PLP)-dependent enzymes utilize a vitamin B6-derived cofactor to perform a myriad of chemical transformations on amino acids and other small molecules. Some PLP-dependent enzymes, such as serine hydroxymethyltransferase (SHMT), are promising drug targets for the design of small-molecule antimicrobials and anticancer therapeutics, while others have been used to synthesize pharmaceutical building blocks. Understanding PLP-dependent catalysis and the reaction specificity is crucial to advance structure-assisted drug design and enzyme engineering. Here we report the direct determination of the protonation states in the active site of Thermus thermophilus SHMT (TthSHMT) in the internal aldimine state using room-temperature joint X-ray/neutron crystallography. Conserved active site architecture of the model enzyme TthSHMT and of human mitochondrial SHMT (hSHMT2) were compared by obtaining a room-temperature X-ray structure of hSHMT2, suggesting identical protonation states in the human enzyme. The amino acid substrate serine pathway through the TthSHMT active site cavity was tracked, revealing the peripheral and cationic binding sites that correspond to the pre-Michaelis and pseudo-Michaelis complexes, respectively. At the peripheral binding site, the substrate is bound in the zwitterionic form. By analyzing the observed protonation states, Glu53, but not His residues, is proposed as the general base catalyst, orchestrating the retro-aldol transformation of L-serine into glycine. Serine hydroxymethyltransferase (SHMT) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme and a promising drug target, however, PLP-dependent catalysis remains underexplored. Here, the authors report joint X-ray/neutron structures of Thermus thermophilus SHMT in the internal aldimine state and in complex with L-serine substrate trapped at the peripheral binding site, revealing positions of hydrogen atoms, assigning the protonation states and electrical charges of residues, and proposing a catalytic mechanism. [ABSTRACT FROM AUTHOR]

Introduction: Implementation of the Drug Burden Index (DBI) as a risk assessment tool in clinical practice may facilitate deprescribing. Objective: The purpose of this study is to evaluate how a comprehensive intervention bundle using the DBI impacts (i) the proportion of older inpatients with at least one DBI-contributing medication stopped or dose reduced on discharge, compared with admission; and (ii) the changes in deprescribing of different DBI-contributing medication classes during hospitalisation. Methods: This before-and-after study was conducted in an Australian metropolitan tertiary referral hospital. Patients aged ≥ 75 years admitted to the acute aged care service for ≥ 48 h from December 2020 to October 2021 and prescribed DBI-contributing medication were included. During the control period, usual care was provided. During the intervention, access to the intervention bundle was added, including a clinician interface displaying DBI score in the electronic medical record. In a subsequent 'stewardship' period, a stewardship pharmacist used the bundle to provide clinicians with patient-specific recommendations on deprescribing of DBI-contributing medications. Results: Overall, 457 hospitalisations were included. The proportion of patients with at least one DBI-contributing medication stopped/reduced on discharge increased from 29.9% (control period) to 37.5% [intervention; adjusted risk difference (aRD) 6.5%, 95% confidence intervals (CI) −3.2 to 17.5%] and 43.1% (stewardship; aRD 12.1%, 95% CI 1.0–24.0%). The proportion of opioid prescriptions stopped/reduced rose from 17.9% during control to 45.7% during stewardship (p = 0.04). Conclusion: Integrating a comprehensive intervention bundle and accompanying stewardship program is a promising strategy to facilitate deprescribing of sedative and anticholinergic medications in older inpatients. [ABSTRACT FROM AUTHOR]

Starting from compound 5 (CCF0058981), a structure-based optimization of the P1 subsite was performed against the severe acute respiratory syndrome coronavirus (SARS-CoV-2) main protease (3CLpro). Inhibitor 5 and the compounds disclosed bind to 3CLpro using a non-covalent mode of action that utilize a His163 H-bond interaction in the S1 subpocket. In an effort to examine more structurally diverse P1 groups a number of azoles and heterocycles were designed. Several azole ring systems and replacements, including C-linked azoles, with similar or enhanced potency relative to 5 were discovered (28, 29, and 30) with demonstrated IC50 values <100 nM. In addition, pyridyl and isoquinoline P1 groups were successful as P1 replacements leading to 3-methyl pyridyl 36 (IC50 = 85 nM) and isoquinoline 27 (IC50 = 26 nM). High resolution X-ray crystal structures of these inhibitors were utilized to confirm binding orientation and guide optimization. These findings have implications toward antiviral development and preparedness to combat SARS-like zoonotic coronavirus outbreaks. [ABSTRACT FROM AUTHOR]

While new vaccines for SARS-CoV-2 are authorized based on neutralizing antibody (nAb) titer against emerging variants of concern, an analogous pathway does not exist for preventative monoclonal antibodies. In this work, nAb titers were assessed as correlates of protection against COVID-19 in the casirivimab + imdevimab monoclonal antibody (mAb) prevention trial (ClinicalTrials.gov #NCT4452318) and in the mRNA-1273 vaccine trial (ClinicalTrials.gov #NCT04470427). In the mAb trial, protective efficacy of 92% (95% confidence interval (CI): 84%, 98%) is associated with a nAb titer of 1000 IU50/ml, with lower efficacy at lower nAb titers. In the vaccine trial, protective efficacies of 93% [95% CI: 91%, 95%] and 97% (95% CI: 95%, 98%) are associated with nAb titers of 100 and 1000 IU50/ml, respectively. These data quantitate a nAb titer correlate of protection for mAbs benchmarked alongside vaccine induced nAb titers and support nAb titer as a surrogate endpoint for authorizing new mAbs. Here the authors assess neutralizing antibody (nAb) levels as correlate of protection in a monoclonal antibody prevention trial and a vaccine trial for COVID-19 and show that nAb titers correlate with clinical protection against COVID-19 supporting nAb titer as a surrogate endpoint for authorization of monoclonal antibodies. [ABSTRACT FROM AUTHOR]

The distribution of marine sponges in the tropical Southwest Pacific Ocean is largely unexplored despite the vital ecological role of sponges in coral reefs and their value as sources of metabolites for drug design. Several collection campaigns to the French Polynesian archipelagos (Society, Marquesas, Tuamotu, Gambier, and Austral) were conducted to assess the bio- and chemodiversity of the island groups. In the course of these scientific expeditions, more than 200 identified sponge specimens were acquired, for which we were able to assign 102 Molecular Operational Taxonomic Units (MOTUs). Based on these MOTUs, we assessed, in the largest analysis of its kind for this area to date, the sponge composition and faunistic overlaps of the marine province Southeast Polynesia with Marquesas and Central Polynesia. We also compared the sponge fauna of these Eastern Indo-Pacific provinces with marine provinces of the adjacent Central Indo-Pacific realm. Our findings corroborate that sponge faunal similarity within marine realms is higher than among realms, and follows the marine barriers to gene flow observed for other taxa. We detected high levels of provincial endemism for marine sponges, consistent with findings from other Indo-Pacific regions. At the level of province, geographical distance and ocean surface currents influence faunal similarity, and constitute the primary factors for the connectivity of sponge faunas between the disjunct and remote island groups in the tropical Southwest Pacific Ocean. [ABSTRACT FROM AUTHOR]

Biobanks containing formalin-fixed, paraffin-embedded (FFPE) tissues from animals and human atomic-bomb survivors exposed to radioactive particulates remain a vital resource for understanding the molecular effects of radiation exposure. These samples are often decades old and prepared using harsh fixation processes which limit sample imaging options. Optical imaging of hematoxylin and eosin (H&E) stained tissues may be the only feasible processing option, however, H&E images provide no information about radioactive microparticles or radioactive history. Synchrotron X-ray fluorescence microscopy (XFM) is a robust, non-destructive, semi-quantitative technique for elemental mapping and identifying candidate chemical element biomarkers in FFPE tissues. Still, XFM has never been used to uncover distribution of formerly radioactive micro-particulates in FFPE canine specimens collected more than 30 years ago. In this work, we demonstrate the first use of low-, medium-, and high-resolution XFM to generate 2D elemental maps of ~ 35-year-old, canine FFPE lung and lymph node specimens stored in the Northwestern University Radiobiology Archive documenting distribution of formerly radioactive micro-particulates. Additionally, we use XFM to identify individual microparticles and detect daughter products of radioactive decay. The results of this proof-of-principle study support the use of XFM to map chemical element composition in historic FFPE specimens and conduct radioactive micro-particulate forensics. [ABSTRACT FROM AUTHOR]

Research has yet to determine how relationships outside of the family system may buffer negative outcomes associated with hopelessness among racial minority youth. In a sample of Black American youth (N = 512; 49% females) and their parents or caregivers, this study used longitudinal growth models to explore whether youth relationships (attachment to peers and attachment to school) moderated the association between caregiver distress (depressive symptoms and traumatic stress), and youth hopelessness. Adolescents' gender was examined to determine if there were gender differences present in these associations. Four linear growth models showed a significant change in levels of hopelessness over time for youth and a significant positive relation between caregiver distress and youth level of hopelessness. Attachment to peers and attachment to school did not equally moderate the relation between caregiver psychological distress and youth hopelessness. The type of caregiver distress had a differential effect on youth hopelessness in the context of the moderation models and based on gender. The type of caregiver distress had a differential effect on youth hopelessness in the context of the moderation models and based on gender. Implications for the importance of non-familial attachments among Black American youth with distressed parents are discussed. [ABSTRACT FROM AUTHOR]

Introduction: Vitamin D has gained attention in the medical community due to its critical role in calcium homeostasis and overall bone health. No standard vitamin D dosing protocol in fracture care has been established for patients deficient in 25-hydroxyvitamin D. This prospective and randomized study aimed to find a dosing regimen that would safely achieve and maintain a therapeutic level of 25-hydroxyvitamin D in deficient patients over three months. Materials and methods: Between June 2016 and May 2017, 48 patients with baseline total 25-hydroxyvitamin D less than 30.0 ng/mL were randomly assigned to either group one (one dose of 100,000 international units (IU) of Vitamin D2) or group 2 (100,000 IU of Vitamin D2 once weekly for twelve weeks) or group 3 (50,000 IU of Vitamin D2 daily for ten days followed by 2,000 IU of Vitamin D3 daily for 74 days). Baseline serum levels were drawn followed by interval levels at week 2, 6 and 12. The primary outcome was to determine which protocol could achieve and maintain therapeutic levels of total 25-hydroxyvitamin D over the course of three months. Our secondary outcome was to monitor for negative side effects. Results: Group 1 did not show any statistically significant increase in serum levels and had no reported side effects. There was a statistically significant increase in serum total 25-hydroxyvitamin D in group 2 between all-time points except between weeks 6 and 12. Two (12.5%) participants in group 2 reported side effects. Group 3 had the greatest change in serum levels from weeks 0 to 2 but had a significant decrease between weeks 2 and 6. No change was seen between weeks 6 and 12. Three (17.5%) participants in group 3 reported side effects. Conclusions: Group 2 sustained and maintained a satisfactory level of total 25-hydroxyvitamin D over three months without any severe side effects. [ABSTRACT FROM AUTHOR]

Behavioral difficulties among African American youth are disproportionately detrimental to their future well-being compared to when demonstrated by White American youth. The majority of gene-environment studies of behavior have been conducted with European ancestry samples, limiting our knowledge of these processes among African Americans. This study examined the influence of positive and negative neighborhood conditions, in the context of genetic risk, on behavioral difficulties among low-income African American adolescents. Data were from the Genes, Environment, and Neighborhood Initiative study of African American youth in high-poverty neighborhoods, n = 524, M age = 15.89, SD = 1.42. DNA samples were collected using the Oragene Discovery 500 series, and polygenic risk scores for behavioral difficulties computed. Neighborhood informal social control, social cohesion, physical disorder, and social disorder were assessed. Adolescent alcohol use, hyperactivity/inattention and conduct problems were examined as outcomes. After controlling for polygenic risk, lower levels of neighborhood social disorder and higher levels of social cohesion were associated with fewer youth-reported hyperactivity/inattention and conduct problems. Less social disorder also was associated with fewer parent-reported behavioral difficulties. Neighborhood characteristics did not moderate associations between genetic risk and the outcomes. Higher levels of positive and lower levels of negative neighborhood characteristics can be associated with lower levels of behavioral difficulties among African American youth living in poverty, even after taking into account genetic risk. [ABSTRACT FROM AUTHOR]

In this work, a multi-resonant metasurface that can be tailored to absorb microwaves at one or more frequencies is explored. Surface shapes based on an 'anchor' motif, incorporating hexagonal, square and triangular-shaped resonant elements, are shown to be readily tailorable to provide a targeted range of microwave responses. A metasurface consisting of an etched copper layer, spaced above a ground plane by a thin (< 1/10th of a wavelength) low-loss dielectric is experimentally characterised. The fundamental resonances of each shaped element are exhibited at 4.1 GHz (triangular), 6.1 GHz (square) and 10.1 GHz (hexagonal), providing the potential for single- and multi-frequency absorption across a range that is of interest to the food industry. Reflectivity measurements of the metasurface demonstrate that the three fundamental absorption modes are largely independent of incident polarization as well as both azimuthal and elevation angles. [ABSTRACT FROM AUTHOR]