CRISPR-based rapid molecular diagnostic tests for fusion-driven leukemias.

Fusion oncogenes can be cancer-defining molecular alterations that are essential for diagnosis and therapy selection.1,2 Rapid and accessible molecular diagnostics for fusion-driven leukemias such as acute promyelocytic leukemia (APL), Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), and chronic myeloid leukemia (CML) are unavailable, creating a barrier to timely diagnosis and effective targeted therapy in many healthcare settings, including community hospitals and low-resource environments. We developed CRISPR-based RNA-fusion transcript detection assays using SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) for the diagnosis of fusion-driven leukemias. We validated these assays using diagnostic APL and CML patient samples from academic centers and dried blood spots from low-resource environments, demonstrating 100% sensitivity and specificity. We identified assay optimizations to enable the use of these tests outside of tertiary cancer centers and clinical laboratories, enhancing the potential impact of this technology. Rapid point-of-care diagnostics can improve outcomes in cancer patients by expanding access to therapies for highly treatable diseases that would otherwise lead to serious adverse outcomes due to delayed or missed diagnoses.

Evaluation of the Transfemoral Bone-Implant Interface Properties Using Vibration Analysis.

Evaluating the bone-implant interface (BII) properties of osseointegrated transfemoral (TFA) implants is important for early failure detection and prescribing loads during rehabilitation. The objective of this work is to derive and validate a 1D finite element (FE) model of the Osseointegrated Prosthetic Limb (OPL) TFA system that can: (1) model its dynamic behaviour and (2) extract the BII properties. The model was validated by: (1) comparing the 1D FE formulation to the analytical and 3D FE solutions for a simplified cylinder, (2) comparing the vibration modes of the actual TFA geometry using 1D and 3D FE models, and (3) evaluating the BII properties for three extreme conditions (LOW, INTERMEDIATE, and HIGH) generated using 3D FE and experimental (where the implant was embedded, using different adhesives, in synthetic femurs) signals for additional validation. The modes predicted by the 1D FE model converged to the analytical and the 3D FE solutions for the cylinder. The 1D model also matched the 3D FE solution with a maximum frequency difference of 2.02% for the TFA geometry. Finally, the 1D model extracted the BII stiffness and the system's damping properties for the three conditions generated using the 3D FE simulations and the experimental INTERMEDIATE and HIGH signals. The agreement between the 1D FE and the 3D FE solutions for the TFA geometry indicates that the 1D model captures the system's dynamic behaviour. Distinguishing between the different BII conditions demonstrates the 1D model's potential use for the non-invasive clinical evaluation of the TFA BII properties.

The 10-Item Physical Function Scale as a Sarcopenia Screening Tool for Patients on Hemodialysis.

OBJECTIVE: We investigated the accuracy of the 10-item Physical Function (PF-10) questions of the SF-36 quality of life questionnaire as a sarcopenia screening tool among patients on hemodialysis. METHODS: A cross-sectional, multicenter study that included adult patients on hemodialysis. The revised European Working Group on Sarcopenia in Older People was used to diagnose sarcopenia. The 10 questions about daily activities from the SF-36 quality of life questionnaire were used to appoint the PF-10, where the final score could range from 10 to 30, and the lower the worse the physical function. The PF-10 accuracy to identify confirmed sarcopenia (low muscle strength + low muscle mass) was assessed through a receiver operating characteristic curve and the cutoff was calculated using the Youden index. RESULTS: One hundred eighty-five patients were included (median 59 years; 45% female). Prevalence of confirmed sarcopenia was 31.4%. The median PF-10 score was 23 (interquartile range: 17-27) and a significant association with all sarcopenia measurements was found (all P < .05). The best cutoff calculated from the receiver operating characteristic curve was ≤26 points (area under the curve = 0.69, 95% confidence interval 0.61-0.77) with sensitivity and specificity of 96.6% and 71.0%, respectively. Moreover, patients with ≤26 points (n = 133, 72%) had a higher prevalence of low muscle strength by handgrip (53 vs. 19%; P < .001) and 5-time sit-to-stand (41 vs. 10%; P < .001), low gait speed (44 vs. 19%; P = .002), confirmed sarcopenia (39 vs. 11%; P < .001), and severe sarcopenia (26 vs. 4%; P = .001), but not low muscle mass (49 vs. 35%; P = .08), in comparison with those >26 points (n = 52, 28%). CONCLUSION: The PF-10 may be a useful physical dysfunction and sarcopenia screening tool in patients on hemodialysis. A PF-10 threshold of around 26 points appeared to display the fairest accuracy for diagnosing sarcopenia.

Genetic Architecture and Clinical Outcomes of Combined Lipid Disturbances.

BACKGROUND: Dyslipoproteinemia often involves simultaneous derangements of multiple lipid traits. We aimed to evaluate the phenotypic and genetic characteristics of combined lipid disturbances in a general population-based cohort. METHODS: Among UK Biobank participants without prevalent coronary artery disease, we used blood lipid and apolipoprotein B concentrations to ascribe individuals into 1 of 6 reproducible and mutually exclusive dyslipoproteinemia subtypes. Incident coronary artery disease risk was estimated for each subtype using Cox proportional hazards models. Phenome-wide analyses and genome-wide association studies were performed for each subtype, followed by in silico causal gene prioritization and heritability analyses. Additionally, the prevalence of disruptive variants in causal genes for Mendelian lipid disorders was assessed using whole-exome sequence data. RESULTS: Among 450 636 UK Biobank participants: 63 (0.01%) had chylomicronemia; 40 005 (8.9%) had hypercholesterolemia; 94 785 (21.0%) had combined hyperlipidemia; 13 998 (3.1%) had remnant hypercholesterolemia; 110 389 (24.5%) had hypertriglyceridemia; and 49 (0.01%) had mixed hypertriglyceridemia and hypercholesterolemia. Over a median (interquartile range) follow-up of 11.1 (10.4-11.8) years, incident coronary artery disease risk varied across subtypes, with combined hyperlipidemia exhibiting the largest hazard (hazard ratio, 1.92 [95% CI, 1.84-2.01]; P=2×10-16), even when accounting for non-HDL-C (hazard ratio, 1.45 [95% CI, 1.30-1.60]; P=2.6×10-12). Genome-wide association studies revealed 250 loci significantly associated with dyslipoproteinemia subtypes, of which 72 (28.8%) were not detected in prior single lipid trait genome-wide association studies. Mendelian lipid variant carriers were rare (2.0%) among individuals with dyslipoproteinemia, but polygenic heritability was high, ranging from 23% for remnant hypercholesterolemia to 54% for combined hyperlipidemia. CONCLUSIONS: Simultaneous assessment of multiple lipid derangements revealed nuanced differences in coronary artery disease risk and genetic architectures across dyslipoproteinemia subtypes. These findings highlight the importance of looking beyond single lipid traits to better understand combined lipid and lipoprotein phenotypes and implications for disease risk.

Cerebrovascular Effects of Sildenafil in Small Vessel Disease: The OxHARP Trial.

BACKGROUND: Vascular cognitive impairment due to cerebral small vessel disease is associated with cerebral pulsatility, white matter hypoperfusion, and reduced cerebrovascular reactivity (CVR), and is potentially improved by endothelium-targeted drugs such as cilostazol. Whether sildenafil, a phosphodiesterase-5 inhibitor, improves cerebrovascular dysfunction is unknown. METHODS: OxHARP trial (Oxford Haemodynamic Adaptation to Reduce Pulsatility) was a double-blind, randomized, placebo-controlled, 3-way crossover trial after nonembolic cerebrovascular events with mild-moderate white matter hyperintensities (WMH), the most prevalent manifestation of cerebral small vessel disease. The primary outcome assessed the superiority of 3 weeks of sildenafil 50 mg thrice daily versus placebo (mixed-effect linear models) on middle cerebral artery pulsatility, derived from peak systolic and end-diastolic velocities (transcranial ultrasound), with noninferiority to cilostazol 100 mg twice daily. Secondary end points included the following: cerebrovascular reactivity during inhalation of air, 4% and 6% CO2 on transcranial ultrasound (transcranial ultrasound-CVR); blood oxygen-level dependent-magnetic resonance imaging within WMH (CVR-WMH) and normal-appearing white matter (CVR-normal-appearing white matter); cerebral perfusion by arterial spin labeling (magnetic resonance imaging pseudocontinuous arterial spin labeling); and resistance by cerebrovascular conductance. Adverse effects were compared by Cochran Q. RESULTS: In 65/75 (87%) patients (median, 70 years;79% male) with valid primary outcome data, cerebral pulsatility was unchanged on sildenafil versus placebo (0.02, -0.01 to 0.05; P=0.18), or versus cilostazol (-0.01, -0.04 to 0.02; P=0.36), despite increased blood flow (∆ peak systolic velocity, 6.3 cm/s, 3.5-9.07; P<0.001; ∆ end-diastolic velocity, 1.98, 0.66-3.29; P=0.004). Secondary outcomes improved on sildenafil versus placebo for CVR-transcranial ultrasound (0.83 cm/s per mm Hg, 0.23-1.42; P=0.007), CVR-WMH (0.07, 0-0.14; P=0.043), CVR-normal-appearing white matter (0.06, 0.00-0.12; P=0.048), perfusion (WMH: 1.82 mL/100 g per minute, 0.5-3.15; P=0.008; and normal-appearing white matter, 2.12, 0.66-3.6; P=0.006) and cerebrovascular resistance (sildenafil-placebo: 0.08, 0.05-0.10; P=4.9×10-8; cilostazol-placebo, 0.06, 0.03-0.09; P=5.1×10-5). Both drugs increased headaches (P=1.1×10-4), while cilostazol increased moderate-severe diarrhea (P=0.013). CONCLUSIONS: Sildenafil did not reduce pulsatility but increased cerebrovascular reactivity and perfusion. Sildenafil merits further study to determine whether it prevents the clinical sequelae of small vessel disease. REGISTRATION: URL: https://www.clinicaltrials.gov/study/NCT03855332; Unique identifier: NCT03855332.

Patient-Reported Outcomes in Phase 3 Clinical Trials for Blood Cancers: A Systematic Review.

Importance: Published research suggests that patient-reported outcomes (PROs) are neither commonly collected nor reported in randomized clinical trials (RCTs) for solid tumors. Little is known about these practices in RCTs for hematological malignant neoplasms. Objective: To evaluate the prevalence of PROs as prespecified end points in RCTs of hematological malignant neoplasms, and to assess reporting of PROs in associated trial publications. Evidence Review: All issues of 8 journals known for publishing high-impact RCTs (NEJM, Lancet, Lancet Hematology, Lancet Oncology, Journal of Clinical Oncology, Blood, JAMA, and JAMA Oncology) between January 1, 2018, and December 13, 2022, were searched for primary publications of therapeutic phase 3 trials for adults with hematological malignant neoplasms. Studies that evaluated pretransplant conditioning regimens, graft-vs-host disease treatment, or radiotherapy as experimental treatment were excluded. Data regarding trial characteristics and PROs were extracted from manuscripts and trial protocols. Univariable analyses assessed associations between trial characteristics and PRO collection or reporting. Findings: Ninety RCTs were eligible for analysis. PROs were an end point in 66 (73%) trials: in 1 trial (1%) as a primary end point, in 50 (56%) as a secondary end point, and in 15 (17%) as an exploratory end point. PRO data were reported in 26 of 66 primary publications (39%): outcomes were unchanged in 18 and improved in 8, with none reporting worse PROs with experimental treatment. Trials sponsored by for-profit entities were more likely to include PROs as an end point (49 of 55 [89%] vs 17 of 35 [49%]; P < .001) but were not significantly more likely to report PRO data (20 of 49 [41%] vs 6 of 17 [35%]; P = .69). Compared with trials involving lymphoma (18 of 29 [62%]) or leukemia or myelodysplastic syndrome (18 of 28 [64%]), those involving plasma cell disorders or multiple myeloma (27 of 30 [90%]) or myeloproliferative neoplasms (3 of 3 [100%]) were more likely to include PROs as an end point (P = .03). Similarly, compared with trials involving lymphoma (3 of 18 [17%]) or leukemia or myelodysplastic syndrome (5 of 18 [28%]), those involving plasma cell disorders or multiple myeloma (16 of 27 [59%]) or myeloproliferative neoplasms (2 of 3 [67%]) were more likely to report PROs in the primary publication (P = .01). Conclusions and Relevance: In this systematic review, almost 3 of every 4 therapeutic RCTs for blood cancers collected PRO data; however, only 1 RCT included PROs as a primary end point. Moreover, most did not report resulting PRO data in the primary publication and when reported, PROs were either better or unchanged, raising concern for publication bias. This analysis suggests a critical gap in dissemination of data on the lived experiences of patients enrolled in RCTs for hematological malignant neoplasms.

Corrigendum: Lithium-ion battery second life: pathways, challenges and outlook.

[This corrects the article DOI: 10.3389/fchem.2024.1358417.].

Stopping at C2 Versus C3/4 in Elective Posterior Cervical Decompression and Fusion: A 5-Year Follow-up Study.

STUDY DESIGN: This is a retrospective cohort study. OBJECTIVE: In patients undergoing elective posterior cervical laminectomy and fusion (PCLF) with a minimum of 5-year follow-up, we sought to compare reoperation rates between patients with an upper instrumented vertebra (UIV) of C2 versus C3/4. SUMMARY OF BACKGROUND DATA: The long-term outcomes of choosing between C2 versus C3/4 as the UIV in PCLF remain unclear. METHODS: A single-institution, retrospective cohort study from a prospective registry was conducted of patients undergoing elective, degenerative PCLF from December 2010 to June 2018. The primary exposure was UIV of C2 versus C3/4. The primary outcome was reoperation. Multivariable logistic regression controlled for age, smoking, diabetes, and fusion to the thoracic spine. RESULTS: Of the 68 patients who underwent PCLF with 5-year follow-up, 27(39.7%) had a UIV of C2, and 41(60.3%) had a UIV of either C3/4. Groups had similar duration of symptoms (P=0.743), comorbidities (P>0.999), and rates of instrumentation to the thoracic spine (70.4% vs. 53.7%, P=0.210). The C2 group had significantly longer operative time (231.8±65.9 vs. 181.6±44.1 mins, P<0.001) and more fused segments (5.9±1.8 vs. 4.2±0.9, P<0.001). Reoperation rate was lower in the C2 group compared with C3/4 (7.4% vs. 19.5%), though this did not reach statistical significance (P=0.294). Multivariable logistic regression showed increased odds of reoperation for the C3/4 group compared with the C2 group (OR=3.29, 95%CI=0.59-18.11, P=0.170), though statistical significance was not reached. Similarly, the C2 group had a lower rate of instrumentation failure (7.4% vs. 12.2%, P=0.694) and adjacent segment disease/disk herniation (0% vs. 7.3%, P=0.271), though neither trend attained statistical significance. CONCLUSIONS: Patients with a UIV of C2 had less than half the number of reoperations and less adjacent segment disease, though neither trend was statistically significant. Despite a lack of statistical significance, whether a clinically meaningful difference exists between UIV of C2 versus C3/4 should be validated in larger samples with long-term follow-up. LEVEL OF EVIDENCE: Level-3.

Wrist Motion Assessment in Tennis Players using Three-Dimensional Motion Capture and Dynamic Electromyography.

Background Tennis players often present with ulnar-sided wrist pain, which may reflect repetitive stress and/or faulty mechanics. There is a role for investigating the biomechanics of tennis strokes and how they may relate to wrist pathology. The purpose of this study was to investigate whether three-dimensional motion capture technology and dynamic electromyography (EMG), when used to study groundstrokes in elite junior tennis players, reveals patterns of upper extremity motion that may correlate with the development of clinically relevant pathology. Case Description Three-dimensional kinematic and EMG data were collected from two United States Tennis Association-ranked adolescent tennis players during groundstrokes. There were several observed differences in the two players' degree and timing of pronation/supination, ulnar/radial deviation, and flexion/extension during their strokes. Clinical Significance Advanced motion capture technology facilitates a nuanced understanding of complex movements involved in groundstroke production. This methodology may be useful for identifying athletes who are at risk for injury and guiding rehabilitation for players experiencing pain. Level of Evidence IV.

A multifaceted suite of metrics for comparative myoelectric prosthesis controller research.

Upper limb robotic (myoelectric) prostheses are technologically advanced, but challenging to use. In response, substantial research is being done to develop person-specific prosthesis controllers that can predict a user's intended movements. Most studies that test and compare new controllers rely on simple assessment measures such as task scores (e.g., number of objects moved across a barrier) or duration-based measures (e.g., overall task completion time). These assessment measures, however, fail to capture valuable details about: the quality of device arm movements; whether these movements match users' intentions; the timing of specific wrist and hand control functions; and users' opinions regarding overall device reliability and controller training requirements. In this work, we present a comprehensive and novel suite of myoelectric prosthesis control evaluation metrics that better facilitates analysis of device movement details-spanning measures of task performance, control characteristics, and user experience. As a case example of their use and research viability, we applied these metrics in real-time control experimentation. Here, eight participants without upper limb impairment compared device control offered by a deep learning-based controller (recurrent convolutional neural network-based classification with transfer learning, or RCNN-TL) to that of a commonly used controller (linear discriminant analysis, or LDA). The participants wore a simulated prosthesis and performed complex functional tasks across multiple limb positions. Analysis resulting from our suite of metrics identified 16 instances of a user-facing problem known as the "limb position effect". We determined that RCNN-TL performed the same as or significantly better than LDA in four such problem instances. We also confirmed that transfer learning can minimize user training burden. Overall, this study contributes a multifaceted new suite of control evaluation metrics, along with a guide to their application, for use in research and testing of myoelectric controllers today, and potentially for use in broader rehabilitation technologies of the future.

Improving Human Diets and Welfare through Using Herbivore-Based Foods: 2. Environmental Consequences and Mitigations.

Animal-sourced foods are important for human nutrition and health, but they can have a negative impact on the environment. These impacts can result in land use tensions associated with population growth and the loss of native forests and wetlands during agricultural expansion. Increased greenhouse gas emissions, and high water use but poor water quality outcomes can also be associated. Life cycle analysis from cradle-to-distribution has shown that novel plant-based meat alternatives can have an environmental footprint lower than that of beef finished in feedlots, but higher than for beef raised on well-managed grazed pastures. However, several technologies and practices can be used to mitigate impacts. These include ensuring that grazing occurs when feed quality is high, the use of dietary additives, breeding of animals with higher growth rates and increased fecundity, rumen microbial manipulations through the use of vaccines, soil management to reduce nitrous oxide emission, management systems to improve carbon sequestration, improved nutrient use efficacy throughout the food chain, incorporating maize silage along with grasslands, use of cover crops, low-emission composting barns, covered manure storages, and direct injection of animal slurry into soil. The technologies and systems that help mitigate or actually provide solutions to the environmental impact are under constant refinement to enable ever-more efficient production systems to allow for the provision of animal-sourced foods to an ever-increasing population.

Early and rapid development of bronchiolitis obliterans syndrome after allogeneic hematopoietic cell transplantation.

Bronchiolitis obliterans (BO) is a form of graft-versus-host disease (GVHD) in the lung and manifests as moderate to severe airflow obstruction after hematopoietic stem cell transplantation (HCT). New-onset airflow obstruction on spirometry is considered diagnostic of bronchiolitis obliterans syndrome (BOS). BOS affects about 5% of all HCT recipients. In general, BO is thought of as a late complication of HCT, usually occurring after day 100 post-transplantation. However, the onset of airflow obstruction can be rapid and is most often irreversible even with treatment. We describe a patient who rapidly developed severe airflow obstruction less than one month after transplantation following the development of upper airway symptoms. Despite aggressive immunosuppression, the patient had no improvement in airflow obstruction. We hypothesize that early screening and treatment may help prevent BOS after HCT.

Treatment approach and outcomes of patients with accelerated/blast-phase myeloproliferative neoplasms in the current era.

ABSTRACT: Progression of myeloproliferative neoplasms (MPNs) to accelerated or blast phase is associated with poor survival outcomes. Since 2017 there have been several therapies approved for use in acute myeloid leukemia (AML); these therapies have been incorporated into the management of accelerated/blast-phase MPNs (MPN-AP/BP). We performed a multicenter analysis to investigate outcomes of patients diagnosed with MPN-AP/BP in 2017 or later. In total, 202 patients were identified; median overall survival (OS) was 0.86 years. We also analyzed patients based on first-line treatment; the 3 most common approaches were intensive chemotherapy (n = 65), DNA methyltransferase inhibitor (DNMTi)-based regimens (n = 65), and DNMTi + venetoclax-based regimens (n = 54). Median OS was not significantly different by treatment type. In addition, we evaluated response by 2017 European LeukemiaNet AML criteria and 2012 MPN-BP criteria in an effort to understand the association of response with survival outcomes. We also analyzed outcomes in 65 patients that received allogeneic hematopoietic stem cell transplant (allo-HSCT); median OS was 2.30 years from time of allo-HSCT. Our study demonstrates that survival among patients with MPN-AP/BP is limited in the absence of allo-HSCT even in the current era of therapeutics and underscores the urgent need for new agents and approaches.

Innovations in conditioning and post-transplant maintenance in AML: genomically informed revelations on the graft-versus-leukemia effect.

Acute Myeloid Leukemia (AML) is the prototype of cancer genomics as it was the first published cancer genome. Large-scale next generation/massively parallel sequencing efforts have identified recurrent alterations that inform prognosis and have guided the development of targeted therapies. Despite changes in the frontline and relapsed standard of care stemming from the success of small molecules targeting FLT3, IDH1/2, and apoptotic pathways, allogeneic stem cell transplantation (alloHSCT) and the resulting graft-versus-leukemia (GVL) effect remains the only curative path for most patients. Advances in conditioning regimens, graft-vs-host disease prophylaxis, anti-infective agents, and supportive care have made this modality feasible, reducing transplant related mortality even among patients with advanced age or medical comorbidities. As such, relapse has emerged now as the most common cause of transplant failure. Relapse may occur after alloHSCT because residual disease clones persist after transplant, and develop immune escape from GVL, or such clones may proliferate rapidly early after alloHSCT, and outpace donor immune reconstitution, leading to relapse before any GVL effect could set in. To address this issue, genomically informed therapies are increasingly being incorporated into pre-transplant conditioning, or as post-transplant maintenance or pre-emptive therapy in the setting of mixed/falling donor chimerism or persistent detectable measurable residual disease (MRD). There is an urgent need to better understand how these emerging therapies modulate the two sides of the GVHD vs. GVL coin: 1) how molecularly or immunologically targeted therapies affect engraftment, GVHD potential, and function of the donor graft and 2) how these therapies affect the immunogenicity and sensitivity of leukemic clones to the GVL effect. By maximizing the synergistic action of molecularly targeted agents, immunomodulating agents, conventional chemotherapy, and the GVL effect, there is hope for improving outcomes for patients with this often-devastating disease.

Advancements and Challenges in the Treatment of AML.

The therapeutic arsenal for the management of AML has expanded significantly in recent years. Before 2017, newly diagnosed AML was treated with either standard cytarabine- and anthracycline-based induction chemotherapy (for all fit patients) or a single-agent hypomethylating agent (in unfit patients or those 75 years and older). While assessing patient fitness remains important, characterizing the disease biology has become critical to select the optimal initial therapy for each patient with more options available. FLT3 inhibitors, gemtuzumab ozogamicin, and CPX-351 have been shown to improve outcomes for specific subsets of patients. Venetoclax (VEN) with a hypomethylating agent (HMA) is the standard-of-care frontline regimen for most older patients, except perhaps for those with an IDH1 mutation where ivosidenib with azacitidine may also be considered. On the basis of the success seen with HMA/VEN in older patients, there is now increasing interest in incorporating VEN into frontline regimens in younger patients, with promising data from multiple early phase studies. This article focuses on recent updates and ongoing challenges in the management of AML, with a particular focus on the ongoing challenge of secondary AML and considerations regarding the selection of initial therapy in younger patients. An overview of common side effects and toxicities associated with targeted therapies is also presented here, along with recommended strategies to mitigate these risks.

Gender, race, and space: A qualitative exploration of young Black women's perceptions of urban neighborhoods.

How people think and feel about their neighborhood impacts the way they think of themselves and their futures. These linkages are especially important to understand in the case of urban-residing young Black women. Researchers know very little about what contributes to young Black adults' urban neighborhood perceptions and often rely on "expert" definitions of markers of neighborhood quality. These definitions and subsequent explorations of residents' neighborhood assessment have not adequately considered intersecting oppressive systems that structure urban spaces both physically and socially. Further, within-group diversity of young Black adults based on other social identities, such as gender and class, has gone underexplored in research on residents' neighborhood assessment. We used theory from Black feminist geography and sociology to guide our thematic analysis of interviews with young Black women (N = 9) regarding their urban neighborhood quality. We sought to explore the aspects or features of the neighborhood that young Black women discussed and how social identities may play a role in young Black women's descriptions of their urban neighborhoods. We argue three themes tell an overarching story of young Black women's urban spatial critical analysis: (1) outsiders' perceptions versus our realities, (2) gendered safety, and (3) visibility of young Black women. Young Black women's narratives highlighted communal aspects of neighborhood evaluation and attention to dominant narratives regarding marginalized groups and urban spaces.

Lithium-ion battery second life: pathways, challenges and outlook.

Net zero targets have resulted in a drive to decarbonise the transport sector worldwide through electrification. This has, in turn, led to an exponentially growing battery market and, conversely, increasing attention on how we can reduce the environmental impact of batteries and promote a more efficient circular economy to achieve real net zero. As these batteries reach the end of their first life, challenges arise as to how to collect and process them, in order to maximise their economical use before finally being recycled. Despite the growing body of work around this topic, the decision-making process on which pathways batteries could take is not yet well understood, and clear policies and standards to support implementation of processes and infrastructure are still lacking. Requirements and challenges behind recycling and second life applications are complex and continue being defined in industry and academia. Both pathways rely on cell collection, selection and processing, and are confronted with the complexities of pack disassembly, as well as a diversity of cell chemistries, state-of-health, size, and form factor. There are several opportunities to address these barriers, such as standardisation of battery design and reviewing the criteria for a battery's end-of-life. These revisions could potentially improve the overall sustainability of batteries, but may require policies to drive such transformation across the industry. The influence of policies in triggering a pattern of behaviour that favours one pathway over another are examined and suggestions are made for policy amendments that could support a second life pipeline, while encouraging the development of an efficient recycling industry. This review explains the different pathways that end-of-life EV batteries could follow, either immediate recycling or service in one of a variety of second life applications, before eventual recycling. The challenges and barriers to each pathway are discussed, taking into account their relative environmental and economic feasibility and competing advantages and disadvantages of each. The review identifies key areas where processes need to be simplified and decision criteria clearly defined, so that optimal pathways can be rapidly determined for each end-of-life battery.

Improving Human Diets and Welfare through Using Herbivore-Based Foods: 1. Human and Animal Perspectives.

Human health and diet are closely linked. The diversity of diets consumed by humans is remarkable, and most often incorporates both animal and plant-based foods. However, there has been a recent call for a reduced intake of animal-based foods due to concerns associated with human health in developed countries and perceived impacts on the environment. Yet, evidence for the superior nutritional quality of animal-sourced food such as meat, milk, and eggs, compared with plant-based foods, indicates that consumption of animal-sourced food should and will continue. This being the case, the aim here is to examine issues associated with animal-sourced foods in terms of both the quantification and mitigation of unintended consequences associated with environment, animal health, and herd management. Therefore, we examined the role of animal proteins in human societies with reference to the UN-FAO issues associated with animal-sourced foods. The emphasis is on dominant grazed pastoral-based systems, as used in New Zealand and Ireland, both with temperate moist climates and a similar reliance on global markets for generating net wealth from pastoral agricultural products. In conclusion, animal-sourced foods are shown to be an important part of the human diet. Production systems can result in unintended consequences associated with environment, animal health, and herd management, and there are technologies and systems to provide solutions to these that are available or under refinement.

The role of vascularized bone grafting for scaphoid nonunions in adolescents.

A total of 26 adolescent patients were treated for scaphoid nonunion with a vascularized bone graft from either the medial femoral condyle or dorsal distal radius. There was an 85% union incidence, improved carpal alignment and a low incidence of complications.