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Surface enhanced resonance Raman (SERS) is a powerful optical technique, which can help enhance the sensitivity of Raman spectroscopy aided by noble metal nanoparticles (NPs). However, current SERS‐NPs are often suboptimal, which can aggregate under physiological conditions with much reduced SERS enhancement. Herein, a robust one‐pot method has been developed to synthesize SERS‐NPs with more uniform core diameters of 50 nm, which is applicable to both non‐resonant and resonant Raman dyes. The resulting SERS‐NPs are colloidally stable and bright, enabling NP detection with low‐femtomolar sensitivity. An algorithm has been established, which can accurately unmix multiple types of SERS‐NPs enabling potential multiplex detection. Furthermore, a new liposome‐based approach has been developed to install a targeting carbohydrate ligand, i.e., hyaluronan, onto the SERS‐NPs bestowing significantly enhanced binding affinity to its biological receptor CD44 overexpressed on tumor cell surface. The liposomal hyaluronan (HA)‐SERS‐NPs enabled visualization of spontaneously developed breast cancer in mice in real time guiding complete surgical removal of the tumor, highlighting the translational potential of these new glyco‐SERS‐NPs.

Abstract Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism resulting from a deficiency of phenylalanine hydroxylase (PAH). If untreated by dietary restriction of phenylalanine intake, impaired postnatal cognitive development results from the neurotoxic effects of excessive phenylalanine (Phe). Signs and symptoms include severe intellectual disability and behavior problems with a high frequency of seizures and variable microcephaly. Maternal PKU syndrome refers to fetal damage resulting in congenital abnormalities when the mother has untreated PKU during pregnancy. Here, we report an intellectually normal 32‐year‐old female who presented with recurrent pregnancy loss and two neonatal deaths with congenital heart disease, microcephaly, intrauterine growth restriction, and respiratory distress. She was diagnosed with PKU through exome sequencing performed for carrier testing with a homozygous pathogenic variant in the PAH gene, c.169_171del, p.(Glu57del) that is associated with classical PKU. Consistent with the genetic finding, she had a markedly increased plasma phenylalanine concentration of 1642 μmol/L (normal

Abstract Small voids in the absorber layer of thin‐film solar cells are generally suspected to impair photovoltaic performance. They have been studied on Cu(In,Ga)Se2 cells with conventional laboratory techniques, albeit limited to surface characterization and often affected by sample‐preparation artifacts. Here, synchrotron imaging is performed on a fully operational as‐deposited solar cell containing a few tens of voids. By measuring operando current and X‐ray excited optical luminescence, the local electrical and optical performance in the proximity of the voids are estimated, and via ptychographic tomography, the depth in the absorber of the voids is quantified. Besides, the complex network of material‐deficit structures between the absorber and the top electrode is highlighted. Despite certain local impairments, the massive presence of voids in the absorber suggests they only have a limited detrimental impact on performance.

Background and aims: Cancer and atherosclerosis share common risk factors and inflammatory pathways that promote their proliferation via vascular endothelial growth factor (VEGF). Because CCs cause mechanical injury and inflammation in atherosclerosis, we investigated their presence in solid cancers and their activation of IL-1β, VEGF, CD44, and Ubiquityl-Histone H2B (Ub-H2B), that promote cancer growth. Methods: Tumor specimens from eleven different types of human cancers and atherosclerotic plaques were assessed for CCs, free cholesterol content and IL1-β by microscopy, immunohistochemistry, and biochemical analysis. Breast and colon cancer cell lines were cultured with and without CCs to select for expression of VEGF, CD44, and Ub-H2B. Western blot and immunofluorescence were performed on cells to assess the effect of CCs on signaling pathways. Results: Cancers displayed higher CC content (+2.29 ± 0.74 vs +1.46 ± 0.84, p

Using national data from Project Implicit, the authors examine state-level variations in implicit and explicit bias against Asian Americans held by non–Asian Americans ( n = 196,678) from 2018 to 2022. The authors also explore state-level sociodemographic correlates of both types of bias. The findings reveal considerable heterogeneity in implicit and explicit bias across states. Moreover, Republican and swing states had higher levels of implicit bias against Asian Americans, and states with older median ages and greater percentages of Asian populations were associated with less explicit bias. This study underscores the importance of state-level variation in and structural factors of biases against Asian Americans as contexts for examining attitudes toward Asian Americans.

We look to the past as prologue for guidance in predicting and circumventing potential psychosocial–ethical challenges, including those that may influence the attachment process for some parents. We consider the evolution of bioethics and developmental psychology as they intersect with newborn screening while exploring potential implications of positive findings, be they false positives, true positives, or secondary as well as incidental findings. We reflect on navigating the complex landscape that may be significantly impacted by variable phenotypes, the age of onset, and uncertain prognoses, mindful of the diagnostic odyssey continuum. We explore select facets of ethical and psychological challenges encountered with positive newborn screening findings by highlighting enduring debates to improve the policy process in public health and medicine. We believe substantive empirical research is needed, including long-term follow-up, routine prenatal assessment of tolerance for uncertainties, and especially innovative methodologies to better evaluate potential psychological distress that may be present in some at-risk individuals during the perinatal period preceding and following reports of positive findings. Mitigation strategies building on lessons learned from NBS and clinical follow-up should be implemented and studied. We conclude by pondering why we remain far afield from providing these services. Research directed towards understanding the implications of positive NBS findings will further reduce the burdens on families and care providers alike and should lead to improved communication.

Levels of family functioning are an important consideration in determining appropriate clinical and educational intervention approaches for families and older adults. Theoretical and applied approaches are reviewed with the emphasis on specific interventions that support different levels of family functioning and caregiving. Additionally, different dynamics within the family and their relations with aging family members are examined. This paper updates and expands discussions on levels of family functioning considerations by Sterns et al. using Blocher’s theory of level of human effectiveness. Further levels of family functioning include the theories developed by Bowen’s family systems theory. A present-day consideration is important for counseling, case management, caregiving, and treatment planning to assist families and their aging family member.

A public university's computing outreach program focused on four key strategies for increasing the depth and breadth of science, technology, engineering, and mathematics (STEM) education. This paper describes the development and implementation of a project management hands-on learning laboratory activity within the context of the university's outreach strategies. The first two strategies, establishing relationships with the primary and secondary (K-12) level partner schools and implementing whole-grade participation, have led to repeat visits by students over several years. The third strategy, hands-on learning laboratory activities, has successfully engaged K-12 students, as indicated by the assessment results that provide evidence of successful student learning. The fourth strategy, producer-consumer collaborations, has facilitated the efficient matching of faculty expertise with K-12 teacher needs. The results include the evidence that outreach strategies can have a positive influence on student engagement in STEM education at multiple points in the K-12 education experience.

We analyze the effect of growth on non-(100) surfaces resulting from incomplete planarization of spalled GaAs wafers on the defect structure of GaAs solar cell layers grown by hydride vapor phase epitaxy (HVPE). Controlled spalling of (100)-oriented GaAs has the potential to reduce substrate costs for III-V epitaxy; however, it creates regularly faceted surfaces that may complicate the growth of high-quality III-V optoelectronic devices. We leverage the anisotropic growth rate of HVPE to planarize these faceted GaAs substrates, reducing the surface roughness and degree of faceting. We observe degraded solar cell performance and material quality in sample areas where facets are not completely removed. We used dark lock-in thermography and photoluminescence to identify recombination in areas that were not fully planarized. We used cathodoluminescence to identify the presence of extended defects in these regions, which are correlated with bandgap fluctuations in the material. We hypothesize that these defects were created by strain from compositional fluctuations in ternary alloys grown on the faceted surfaces. This work elucidates the potential issues of solar cells grown on faceted surfaces and builds understanding toward realizing high performance III-V photovoltaics with the cost-reduction potential of controlled spalling.

Abstract T cells are important for controlling ovarian cancer (OC). We previously demonstrated that combinatorial use of a personalized whole-tumor lysate-pulsed dendritic cell vaccine (OCDC), bevacizumab (Bev), and cyclophosphamide (Cy) elicited neoantigen-specific T cells and prolonged OC survival. Here, we hypothesize that adding acetylsalicylic acid (ASA) and low-dose interleukin (IL)-2 would increase the vaccine efficacy in a recurrent advanced OC phase I trial (NCT01132014). By adding ASA and low-dose IL-2 to the OCDC-Bev-Cy combinatorial regimen, we elicited vaccine-specific T-cell responses that positively correlated with patients’ prolonged time-to-progression and overall survival. In the ID8 ovarian model, animals receiving the same regimen showed prolonged survival, increased tumor-infiltrating perforin-producing T cells, increased neoantigen-specific CD8+ T cells, and reduced endothelial Fas ligand expression and tumor-infiltrating T-regulatory cells. This combinatorial strategy was efficacious and also highlighted the predictive value of the ID8 model for future ovarian trial development.

Abstract Background Repeated inflammation of the pancreas can cause pancreatitis or diabetes. It is well recognized that the organic acidemias may be complicated by pancreatitis but less recognized are other metabolic disorders in which pancreatitis can occur. This study shows that long-term follow-up of patients with various metabolic disorders in Korea revealed several with episodes of isolated pancreatitis or diabetes concomitantly with pancreatitis. Results and discussion In this study, two patients with methylmalonic aciduria (MMA), two with propionic acidemia (PPA), one with fatty acid oxidation disorder (FAOD), and one with hyperornithinemia, gyrate atrophy, and juvenile onset diabetes mellitus (DM) were clinically followed for up to 10 – 21 years. Two Korean siblings with MMA showed recurrent pancreatitis from the age of 15 and 19, respectively. The frequency of admission due to pancreatitis was up to 11 times. One patient with MMA developed diabetes mellitus at the age of 20. The other patient with MMA developed recurrent pancreatitis at 4 years and diabetes at 8 years of age. One of the patients with PPA presented with diabetic ketoacidosis. The other PPA patient died of cardiac arrest at age 10. The patient with FAOD presented with pancreatitis at 10 years and died at the age of 15 years due to cardiac arrest. A 35-year-old woman with hyperornithinemia/gyrate atrophy was diagnosed with juvenile onset diabetes at the age of 7 years. No pancreatitis occurred during the follow-up period. Conclusions We conclude that various metabolic disorders can trigger acute or chronic pancreatitis. Proper and prompt multidisciplinary management of metabolic derangement is crucial for preventing pancreatic damage. Further clinical and investigational studies are required to elucidate the pathogenesis of pancreatitis and diabetes mellitus in patients with inborn errors in metabolism.

Surface enhanced resonance Raman (SERS) is a powerful optical technique, which can help enhance the sensitivity of Raman spectroscopy aided by noble metal nanoparticles (NPs). However, current SERS‐NPs are often suboptimal, which can aggregate under physiological conditions with much reduced SERS enhancement. Herein, a robust one‐pot method has been developed to synthesize SERS‐NPs with more uniform core diameters of 50 nm, which is applicable to both non‐resonant and resonant Raman dyes. The resulting SERS‐NPs are colloidally stable and bright, enabling NP detection with low‐femtomolar sensitivity. An algorithm has been established, which can accurately unmix multiple types of SERS‐NPs enabling potential multiplex detection. Furthermore, a new liposome‐based approach has been developed to install a targeting carbohydrate ligand, i.e., hyaluronan, onto the SERS‐NPs bestowing significantly enhanced binding affinity to its biological receptor CD44 overexpressed on tumor cell surface. The liposomal hyaluronan (HA)‐SERS‐NPs enabled visualization of spontaneously developed breast cancer in mice in real time guiding complete surgical removal of the tumor, highlighting the translational potential of these new glyco‐SERS‐NPs. [ABSTRACT FROM AUTHOR]

Naceur Rekaya,1 Alexandra Pickersgill,1 Louisa Harvey2 1Pfizer R&D Ltd, Device Centre of Excellence, Cambridge, UK; 2Harvey Medical Consulting Ltd, Cambridge, UKCorrespondence: Naceur RekayaPfizer R&D Ltd, Device Centre of Excellence, Granta Park, Great Abington, Cambridge CB21 6GP, UKTel +44 1304 616 161Email naceur.rekaya@pfizer.comPurpose: A novel device (sleeve) has been developed that attaches to compatible autoinjectors and is designed to improve the patient experience, particularly for those with limited manual dexterity. This study was designed to explore whether user experience is improved when using the Enbrel® MyClic® autoinjector in conjunction with the sleeve. The Enbrel MyClic autoinjector contains etanercept (Enbrel®), a biologic drug that patients self-administer subcutaneously for the treatment of rheumatoid arthritis (RA).Patients and methods: Twenty-four adult patients (16 female) with RA and varying degrees of manual dexterity impairment took part in this user study. Written informed consent was supplied by each patient prior to performing the study. They each performed two simulated injections into skin pads, one with the Enbrel MyClic alone and the other with the Enbrel MyClic + sleeve. Following the simulated injections, participants answered questions about their experience of using the sleeve and rated the following on a scale of 1 (poor experience) to 7 (optimal experience): overall use; ease of preparation; ease of administration; ease of learning to use; look, feel and size of the device; overall experience.Results: Participants rated the Enbrel MyClic + sleeve more highly than the Enbrel MyClic alone for overall use, ease of administration, feel, size and overall experience. Participants with severe dexterity impairment (n = 12) were more likely to rate these features as better with the sleeve in place than those with mild dexterity impairment (n = 10). Three-quarters of participants said they would request the sleeve if it became available and all said that they would recommend it to others. The main benefits cited by participants were better grip and a better feeling of control.Conclusion: Addition of the sleeve improved patients’ experience of using the Enbrel MyClic. The benefits of the sleeve outweighed any inconvenience associated with the additional steps needed to prepare the device.Keywords: human factors, usability, user study

Urocanic aciduria is caused by a deficiency in the enzyme urocanase (E.C. 4.2.1.49) encoded by the gene UROC1. In the past, deficiency of urocanase has been associated with intellectual disability in a few case studies with some suggestion that the enzyme deficiency was the causative etiology. Here, we describe two phenotypically normal siblings with compound heterozygous pathogenic variants in UROC1 and characteristic biochemical evidence of urocanase deficiency collected utilizing untargeted metabolomic analysis. These findings suggest that urocanic aciduria may represent an otherwise benign biochemical phenotype and that those individuals with concurrent developmental delay should continue to be evaluated for other underlying causes for their symptoms. Keywords: UROC1, Urocanic aciduria, Untargeted metabolomics, Cis-urocanate, Trans-urocanate, Imidazole propionate

Abstract Background The greatest opportunity for lifelong impact of genomic sequencing is during the newborn period. The “BabySeq Project” is a randomized trial that explores the medical, behavioral, and economic impacts of integrating genomic sequencing into the care of healthy and sick newborns. Methods Families of newborns are enrolled from Boston Children’s Hospital and Brigham and Women’s Hospital nurseries, and half are randomized to receive genomic sequencing and a report that includes monogenic disease variants, recessive carrier variants for childhood onset or actionable disorders, and pharmacogenomic variants. All families participate in a disclosure session, which includes the return of results for those in the sequencing arm. Outcomes are collected through review of medical records and surveys of parents and health care providers and include the rationale for choice of genes and variants to report; what genomic data adds to the medical management of sick and healthy babies; and the medical, behavioral, and economic impacts of integrating genomic sequencing into the care of healthy and sick newborns. Discussion The BabySeq Project will provide empirical data about the risks, benefits and costs of newborn genomic sequencing and will inform policy decisions related to universal genomic screening of newborns. Trial registration The study is registered in ClinicalTrials.gov Identifier: NCT02422511. Registration date: 10 April 2015.

Caitlin Richardson-Royer,1 Imran Naqvi,1 Christopher Riffel,1 Lawrence Harvey,1 Domonique Smith,1 Dagmawe Ayalew,1 Nasim Motayar,1 Yaw Amoateng-Adjepong,1,2 Constantine A Manthous3 1The Jewish Hospital of Cincinnati, Cincinnati, OH, USA; 2Yale University School of Medicine, New Haven, CT, USA; 3Lawrence & Memorial Hospital, New London, CT, USA Background: Previous studies have demonstrated that video of and scripted information about cardiopulmonary resuscitation (CPR) can be deployed during clinician–patient end-of-life discussions. Few studies, however, examine whether video adds to verbal information-sharing. We hypothesized that video augments script-only decision-making. Methods: Patients aged >65 years admitted to hospital wards were randomized to receive evidence-based information (“script”) vs. script plus video of simulated CPR and intubation. Patients’ decisions registered in the hospital record, by hospital discharge were compared for the two groups. Results: Fifty script-only intervention patients averaging 77.7 years were compared to 50 script+video patients with a mean age of 74.7 years. Eleven of 50 (22%) in each group declined CPR; and an additional three (script) vs. four (script+video) refused intubation for respiratory failure. There were no differences in sex, self-reported health trajectory, functional limitations, length of stay, or mortality associated with decisions. Conclusion: The rate at which verbally informed hospitalized elders opted out of resuscitation was not impacted by adding a video depiction of CPR. Keywords: end of life, cardiopulmonary resuscitation, CPR, intubation, mechanical ventilation, autonomy

Inverted metamorphic Ga0.3In0.7As photovoltaic converters with sub‐0.60 eV bandgaps grown on InP and GaAs are presented. Threading dislocation densities are 1.3 ± 0.6 × 106 and 8.9 ± 1.7 × 106 cm−2 on InP and GaAs, respectively. The devices generate open‐circuit voltages of 0.386 and 0.383 V, respectively, under irradiance producing a short‐circuit current density of ≈10 A cm−2, yielding bandgap‐voltage offsets of 0.20 and 0.21 V. Power and broadband reflectance measurements are used to estimate thermophotovoltaic (TPV) efficiency. The InP‐based cell is estimated to yield 1.09 W cm−2 at 1100 °C versus 0.92 W cm−2 for the GaAs‐based cell, with efficiencies of 16.8 versus 9.2%. The efficiencies of both devices are limited by sub‐bandgap absorption, with power weighted sub‐bandgap reflectances of 81% and 58%, respectively, the majority of which is assumed to occur in the graded buffers. The 1100 °C TPV efficiencies are estimated to increase to 24.0% and 20.7% in structures with the graded buffer removed, if previously demonstrated reflectance is achieved. These devices also have application to laser power conversion in the 2.0–2.3 µm atmospheric window. Peak laser power converter efficiencies of 36.8% and 32.5% are estimated under 2.0 µm irradiances of 1.86 and 2.81 W cm−2, respectively. [ABSTRACT FROM AUTHOR]

Small voids in the absorber layer of thin‐film solar cells are generally suspected to impair photovoltaic performance. They have been studied on Cu(In,Ga)Se2 cells with conventional laboratory techniques, albeit limited to surface characterization and often affected by sample‐preparation artifacts. Here, synchrotron imaging is performed on a fully operational as‐deposited solar cell containing a few tens of voids. By measuring operando current and X‐ray excited optical luminescence, the local electrical and optical performance in the proximity of the voids are estimated, and via ptychographic tomography, the depth in the absorber of the voids is quantified. Besides, the complex network of material‐deficit structures between the absorber and the top electrode is highlighted. Despite certain local impairments, the massive presence of voids in the absorber suggests they only have a limited detrimental impact on performance. [ABSTRACT FROM AUTHOR]

Classic homocystinuria (HCU) was added to newborn screening (NBS) by Robert Guthrie a few years after the disorder was first described. The justification for NBS was similar to that for PKU, that presymptomatic identification and early dietary treatment would prevent the clinical consequences, which, for HCU, are mental deficiency, ectopia lentis, skeletal abnormalities, and thromboembolism. It was assumed that identifying increased methionine in the screening blood specimen would identify all affected neonates. However, it is now clear that many with HCU are missed by NBS, mainly because the methionine level in the first days of life is normal or below the cutoff level in the NBS program. This includes virtually all of those with B6-responsive HCU. Thus, a more effective method of NBS for HCU should be considered. Included among the possibilities are decreasing the methionine cutoff level, requiring an increase in the Met/Phe ratio if the methionine level is not at or greater than the cutoff level, using methionine as the primary screen with homocysteine as a second-tier test, or replacing methionine with homocysteine as the primary screen. Homocysteine is the primary metabolite that increases in HCU, while the methionine increase is secondary, so homocysteine is usually increased before the increase in methionine, almost always during the first few days of life. Finally, targeted gene screening might be considered. All of these possibilities would impose added expense and labor to NBS, so meeting these challenges would likely require a regional or national effort.