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This paper examines capacity building and professional development in Western Australia's contemporary popular music sector. It reports on a mixed-methods qualitative-quantitative study into the lived experiences and needs of musicians and industry practitioners alike. It examines learning which is undertaken outside of formal education settings, and includes conferencing, one-on-one mentorship and other workshop based modes of delivery. As is reported, participants are overall positive about their experiences when engaging in such activities however several barriers exist as they relate to the required investments of time and money, modes of delivery and the focus of specific opportunities. A range of recommendations are made in order to address these barriers and support a diversification within the capacity building and professional development space.

Although the 2022 European LeukemiaNet (ELN) acute myeloid leukemia (AML) risk classification reliably predicts outcomes in younger patients treated with intensive chemotherapy, it is unclear whether it applies to adults ≥60 years treated with lower-intensity treatment (LIT). We aimed to test the prognostic impact of ELN risk in patients with newly diagnosed (ND) AML aged ≥60 years given LIT and to further refine risk stratification for these patients. A total of 595 patients were included: 11% had favorable-, 11% intermediate-, and 78% had adverse-risk AML. ELN risk was prognostic for overall survival (OS) (P < .001) but did not stratify favorable- from intermediate-risk (P = .71). Within adverse-risk AML, the impact of additional molecular abnormalities was further evaluated. Multivariable analysis was performed on a training set (n = 316) and identified IDH2 mutation as an independent favorable prognostic factor, and KRAS, MLL2, and TP53 mutations as unfavorable (P < .05). A mutation score was calculated for each combination of these mutations, assigning adverse-risk patients to 2 risk groups: -1 to 0 points (Beat-AML intermediate) vs 1+ points (Beat-AML adverse). In the final refined risk classification, ELN favorable- and intermediate-risk were combined into a newly defined Beat-AML favorable-risk group, in addition to mutation scoring within the ELN adverse-risk group. This approach redefines risk for older patients with ND AML and proposes refined Beat-AML risk groups with improved discrimination for OS (2-year OS, 48% vs 33% vs 11%, respectively; P < .001), providing patients and providers additional information for treatment decision-making.

Clonal cytopenia of undetermined significance (CCUS) represents a distinct disease entity characterized by myeloid-related somatic mutations with a variant allele fraction of ≥2% in individuals with unexplained cytopenia(s) but without a myeloid neoplasm (MN). Notably, CCUS carries a risk of progressing to MN, particularly in cases featuring high-risk mutations. Understanding CCUS requires dedicated studies to elucidate its risk factors and natural history. Our analysis of 357 CCUS patients investigated the interplay between clonality, cytopenia, and prognosis. Multivariate analysis identified 3 key adverse prognostic factors: the presence of splicing mutation(s) (score = 2 points), platelet count

Enasidenib (ENA) is an inhibitor of isocitrate dehydrogenase 2 (IDH2) approved for the treatment of patients with IDH2-mutant relapsed/refractory acute myeloid leukemia (AML). In this phase 2/1b Beat AML substudy, we applied a risk-adapted approach to assess the efficacy of ENA monotherapy for patients aged ≥60 years with newly diagnosed IDH2-mutant AML in whom genomic profiling demonstrated that mutant IDH2 was in the dominant leukemic clone. Patients for whom ENA monotherapy did not induce a complete remission (CR) or CR with incomplete blood count recovery (CRi) enrolled in a phase 1b cohort with the addition of azacitidine. The phase 2 portion assessing the overall response to ENA alone demonstrated efficacy, with a composite complete response (cCR) rate (CR/CRi) of 46% in 60 evaluable patients. Seventeen patients subsequently transitioned to phase 1b combination therapy, with a cCR rate of 41% and 1 dose-limiting toxicity. Correlative studies highlight mechanisms of clonal elimination with differentiation therapy as well as therapeutic resistance. This study demonstrates both efficacy of ENA monotherapy in the upfront setting and feasibility and applicability of a risk-adapted approach to the upfront treatment of IDH2-mutant AML. This trial is registered at www.clinicaltrials.gov as #NCT03013998.

In the perinatal period, reward and cognitive systems begin trajectories, influencing later psychiatric risk. The basal ganglia is important for reward and cognitive processing but early development has not been fully characterized. To assess age-related development, we used a measure of basal ganglia physiology, specifically brain tissue iron, obtained from nT2* signal in resting-state functional magnetic resonance imaging (rsfMRI), associated with dopaminergic processing. We used data from the Developing Human Connectome Project (n = 464) to assess how moving from the prenatal to the postnatal environment affects rsfMRI nT2*, modeling gestational and postnatal age separately for basal ganglia subregions in linear models. We did not find associations with tissue iron and gestational age [range: 24.29-42.29] but found positive associations with postnatal age [range:0-17.14] in the pallidum and putamen, but not the caudate. We tested if there was an interaction between preterm birth and postnatal age, finding early preterm infants (GA

Next-generation sequencing (NGS) to identify pathogenic mutations is an integral part of acute myeloid leukemia (AML) therapeutic decision-making. The concordance in identifying pathogenic mutations among different NGS platforms at different diagnostic laboratories has been studied in solid tumors but not in myeloid malignancies to date. To determine this interlaboratory concordance, we collected a total of 194 AML bone marrow or peripheral blood samples from newly diagnosed patients with AML enrolled in the Beat AML Master Trial (BAMT) at 2 academic institutions. We analyzed the diagnostic samples from patients with AML for the detection of pathogenic myeloid mutations in 8 genes (DNMT3A, FLT3, IDH1, IDH2, NPM1, TET2, TP53, and WT1) locally using the Hematologic Neoplasm Mutation Panel (50-gene myeloid indication filter) (site 1) or the GeneTrails Comprehensive Heme Panel (site 2) at the 2 institutions and compared them with the central results from the diagnostic laboratory for the BAMT, Foundation Medicine, Inc. The overall percent agreement was over 95% each in all 8 genes, with almost perfect agreement (κ > 0.906) in all but WT1, which had substantial agreement (κ = 0.848) when controlling for site. The minimal discrepancies were due to reporting variants of unknown significance (VUS) for the WT1 and TP53 genes. These results indicate that the various NGS methods used to analyze samples from patients with AML enrolled in the BAMT show high concordance, a reassuring finding given the wide use of NGS for therapeutic decision-making in AML.

Myelodysplastic neoplasms (MDS) are a collection of hematopoietic disorders with widely variable prognoses and treatment options. Accurate pathologic diagnoses present challenges because of interobserver variability in interpreting morphology and quantifying dysplasia. We compared local clinical site diagnoses with central, adjudicated review from 918 participants enrolled in the ongoing National Heart, Lung, and Blood Institute National MDS Natural History Study, a prospective observational cohort study of participants with suspected MDS or MDS/myeloproliferative neoplasms (MPNs). Locally, 264 (29%) were diagnosed as having MDS, 15 (2%) MDS/MPN overlap, 62 (7%) idiopathic cytopenia of undetermined significance (ICUS), 0 (0%) acute myeloid leukemia (AML) with

Abstract The Notch receptor is a pleiotropic signaling protein that translates intercellular ligand interactions into changes in gene expression via the nuclear localization of the Notch intracellular Domain (NICD). Using a combination of immunohistochemistry, RNA in situ, Optogenetics and super-resolution live imaging of transcription in human cells, we show that the N1ICD can form condensates that positively facilitate Notch target gene expression. We determined that N1ICD undergoes Phase Separation Coupled Percolation (PSCP) into transcriptional condensates, which recruit, enrich, and encapsulate a broad set of core transcriptional proteins. We show that the capacity for condensation is due to the intrinsically disordered transcriptional activation domain of the N1ICD. In addition, the formation of such transcriptional condensates acts to promote Notch-mediated super enhancer-looping and concomitant activation of the MYC protooncogene expression. Overall, we introduce a novel mechanism of Notch1 activity in which discrete changes in nuclear N1ICD abundance are translated into the assembly of transcriptional condensates that facilitate gene expression by enriching essential transcriptional machineries at target genomic loci.

Abstract Background Clinicians and researchers should consider the expected benefits and potential harms of an intervention. Parenting programmes are a widely used evidence-based intervention for child behaviour problems. However, few data are available on potential negative effects. The aims of this paper were to increase systematic knowledge of adverse event (AE) assessment in parenting programmes and to provide an AE assessment tool. Methods As part of the RISE project (prevention of child mental health problems in South-eastern Europe—adapt, optimise, test and extend parenting for lifelong health), we developed and tested an AE assessment procedure in three sequential studies for parents of children with child behaviour problems aged 2 to 9 years in North Macedonia, Republic of Moldova, and Romania. This paper reports on the development of the assessment tool in phase 1 (N = 140), phase 2 (N = 835), and the final experiences with using the optimised procedures in phase 3 (multisite randomised controlled trial, N = 823) in which AEs were assessed before, three times during intervention delivery, and at 1 year follow-up. At each time point, the participants completed a 12-item AE checklist. If moderate-to-severe problems of parent or child were reported, a structured follow-up interview was conducted. Results The response rate on the AE assessment tool increased from 6% (phase 1) to 100% (phase 3) indicating improvement in collecting these data based on the experiences of each phase. Results of the RCT (phase 3) showed generally low (S)AE frequencies with the finally optimised procedure: During the intervention, no serious adverse events (SAE) were registered; at least one AE was reported by 10% (after the first session), 7% (after the third session), and 4% (after the last fifth session) of participants. None of the identified (S)AEs was causally related to the study or intervention. Cost–benefit considerations are needed to determine the best way to ensure participant safety in parenting programmes. Conclusion The applied active AE assessment procedure provides a comprehensive AE assessment tool that can be used by others—with adaptations for the specific context, if needed. Based on our experiences, we outline recommendations for future studies. Trial registration ClinicalTrials.gov, registration number phase 1: NCT03552250; phase 2: NCT03865485, phase 3: NCT04721730 . Registered on 13 January 2021.

Abstract Spontaneous polarization and crystallographic orientations within ferroelectric domains are investigated using an epitaxially grown BiFeO3 thin film under bi-axial tensile strain. Four dimensional-scanning transmission electron microscopy (4D-STEM) and atomic resolution STEM techniques revealed that the tensile strain applied is not enough to cause breakdown of equilibrium BiFeO3 symmetry (rhombohedral with space group: R3c). 4D-STEM data exhibit two types of BiFeO3 ferroelectric domains: one with projected polarization vector possessing out-of-plane component only, and the other with that consisting of both in-plane and out-of-plane components. For domains with only out-of-plane polarization, convergent beam electron diffraction (CBED) patterns exhibit “extra” Bragg’s reflections (compared to CBED of cubic-perovskite) that indicate rhombohedral symmetry. In addition, beam damage effects on ferroelectric property measurements were investigated by systematically changing electron energy from 60 to 300 keV.

BackgroundPatients with acute myeloid leukemia (AML) who have tumor protein p53 (TP53) mutations or a complex karyotype have a poor prognosis, and hypomethylating agents are often used. The authors evaluated the efficacy of entospletinib, an oral inhibitor of spleen tyrosine kinase, combined with decitabine in this patient population.MethodsThis was a multicenter, open-label, phase 2 substudy of the Beat AML Master Trial (ClinicalTrials.gov identifier NCT03013998) using a Simon two-stage design. Eligible patients aged 60 years or older who had newly diagnosed AML with mutations in TP53 with or without a complex karyotype (cohort A; n = 45) or had a complex karyotype without TP53 mutation (cohort B; n = 13) received entospletinib 400 mg twice daily with decitabine 20 mg/m2 on days 1-10 every 28 days for up to three induction cycles, followed by up to 11 consolidation cycles, in which decitabine was reduced to days 1-5. Entospletinib maintenance was given for up to 2 years. The primary end point was complete remission (CR) and CR with hematologic improvement by up to six cycles of therapy.ResultsThe composite CR rates for cohorts A and B were 13.3% (95% confidence interval, 5.1%-26.8%) and 30.8% (95% confidence interval, 9.1%-61.4%), respectively. The median duration of response was 7.6 and 8.2 months, respectively, and the median overall survival was 6.5 and 11.5 months, respectively. The study was stopped because the futility boundary was crossed in both cohorts.ConclusionsThe combination of entospletinib and decitabine demonstrated activity and was acceptably tolerated in this patient population; however, the CR rates were low, and overall survival was short. Novel treatment strategies for older patients with TP53 mutations and complex karyotype remain an urgent need.

Striatal development is crucial for later motor, cognitive, and reward behavior, but age-related change in striatal physiology during the neonatal period remains understudied. An MRI-based measure of tissue iron deposition, T2*, is a non-invasive way to probe striatal physiology neonatally, linked to dopaminergic processing and cognition in children and adults. Striatal subregions have distinct functions that may come online at different time periods in early life. To identify if there are critical periods before or after birth, we measured if striatal iron accrued with gestational age at birth [range= 34.57-41.85 weeks] or postnatal age at scan [range= 5-64 days], using MRI to probe the T2* signal in N = 83 neonates in three striatal subregions. We found iron increased with postnatal age in the pallidum and putamen but not the caudate. No significant relationship between iron and gestational age was observed. Using a subset of infants scanned at preschool age (N = 26), we show distributions of iron shift between time points. In infants, the pallidum had the least iron of the three regions but had the most by preschool age. Together, this provides evidence of distinct change for striatal subregions, a possible differentiation between motor and cognitive systems, identifying a mechanism that may impact future trajectories.

BackgroundHealth promotion and growth-based interventions can effectively improve individual well-being; however, significant gaps in access and utilization still exist. ObjectiveThis study aims to develop and test the effectiveness and implementation of a new, widely targeted conversational agent prevention program (Zenny) designed to enhance well-being. MethodsA total of 1345 individuals in the United States were recruited online and randomly assigned to either (1) a self-help program intervention delivered via an automated conversational agent on WhatsApp or (2) an active control group that had access to evidence-based wellness resources available online. The primary outcomes were well-being (measured using the 5-item World Health Organization Well-being Scale), psychosocial flourishing (assessed with the Flourishing Scale), and positive psychological health (evaluated with the Mental Health Continuum-Short Form). Outcome measures were collected at baseline and again 1 month postassessment. All analyses were conducted using an intention-to-treat approach. ResultsBoth groups showed significant improvements in well-being (self-help program intervention group effect size: Cohen d=0.26, P

Background: Due to the multiorgan effects of liver disease, surgical patients with liver disease have an increased risk of perioperative complications. With revision total hip and knee arthroplasty surgeries increasing, it is important to determine the effects of liver disease in this patient population. The purpose of this study was to evaluate the impact of underlying liver disease on postoperative outcomes following revision total joint arthroplasty (TJA). Methods: The National Surgical Quality Improvement Program database was used to identify patients undergoing aseptic revision TJA from 2006-2019 and group them based on liver disease. The presence of liver disease was assessed by calculating the Model for End-Stage Liver Disease–Sodium score. Patients with a Model for End-Stage Liver Disease–Sodium score of > 10 were classified as having underlying liver disease. In this analysis, differences in demographics, comorbidities, and postoperative complications were assessed. Results: Of 7102 patients undergoing revision total hip arthroplasty, 11.6% of the patients had liver disease. Of 8378 patients undergoing revision total knee arthroplasty, 8.4% of the patients had liver disease. Following adjustment on multivariable regression analysis, patients with liver disease undergoing revision total hip arthroplasty or revision total knee arthroplasty had an increased risk of major complications, wound complications, septic complications, bleeding requiring transfusion, extended length of stay, and readmission compared to those without liver disease. Conclusions: Patients with liver disease have an increased risk of complications following revision TJA. A multidisciplinary team approach should be employed for preoperative optimization and postoperative management of these vulnerable patients to improve outcomes and decrease the incidence and severity of complications. Level of evidence: This is retrospective cohort study and is level 3 evidence.

Autistic meltdowns have been explored from the perspectives of parents, but there is a paucity of research on the experience of meltdowns from the autistic perspective. Little is known about how adults experience these events. In this descriptive phenomenological study, we conducted online interviews with 32 autistic adults on the experience of having a meltdown. Data were analyzed using Colaizzi's seven-step method. Six themes emerged from data that captured the essence of meltdowns, including "feeling overwhelmed" by informational, sensory, social, or emotional stressors; "experiencing extreme emotions," such as anger, sadness, and fear; "losing logic," including challenges with thinking and memory; "grasping for self-control," in which participants felt out of touch with themselves; "finding a release" for emotions, often described as an "explosion" of external behaviors or self-harm; and "minimizing social, emotional, or physical harm" by avoiding triggers or self-isolating when possible. Findings highlight the painful and distressing internalized experience of meltdowns beyond behavioral characteristics. Participants shared examples of internal meltdowns, in which external characteristics of meltdowns were camouflaged. Participants also suggested that meltdowns may serve a functional role in regulating emotions and making one's voice heard. Meltdowns are diverse experiences that hold different meaning to different people.

We report a new type of polymer blend electrolyte based on the principle of thermoplastic vulcanizates (TPV). TPV materials have been extensively used in the automotive and manufacturing sectors. However, to the best of our knowledge, TPV-based electrolytes have yet to be produced. These electrolytes, obtained via melt-processing, combine the high ionic conductivity and processibility of a thermoplastic phase with the improved mechanical strength of a crosslinked elastomeric phase. TPV electrolytes prepared with poly(caprolactone) (PCL) (thermoplastic phase) and hydrogenated nitrile butadiene rubber (HNBR) (elastomeric phase) are presented in this work. These materials deliver promising results in terms of ionic conductivity, electrochemical stability and mechanical strength. Further improvements in ionic conductivity are obtained by doping the TPV electrolyte with a flame-retardant solvent, triethyl phosphate. The crosslinked nature of the TPV allows both mechanical strength and electrochemical stability to be conserved upon doping which is not possible in non-crosslinked polymer blend electrolytes prepared with PCL and HNBR.

Abstract Purpose Loneliness may compromise health-related quality of life (HRQOL) outcomes and the immunological impacts of loneliness via neuroendocrinological mechanisms likely have consequences for patients who have undergone a hematopoietic stem cell transplantation (HSCT). Research approach and measures Loneliness (pre-transplant), immunological recovery (Day 30, Day 100, 1-year post-transplant), and HRQOL (Day 100, 1 year) were measured in a sample of 205 patients completing a HSCT (127 autologous, 78 allogenic). Results Greater levels of pre-transplant loneliness predicted poorer HRQOL at Day 100 and 1-year follow-up. Loneliness also was associated with higher absolute neutrophil to absolute lymphocyte (ANC/ALC) ratios in the entire sample at Day 30, which in turn was associated with Day 100 HRQOL. Conclusions Findings demonstrate that pretransplant loneliness predicts HRQOL outcomes and associates with inflammatory immunological recovery patterns in HSCT patients. The balance of innate neutrophils to adaptive lymphocytes at Day 30 present a distinct profile in lonely individuals, with this immunity recovery profile predicting reduced HRQOL 100 days after the transplant. Addressing perceptions of loneliness before HSCT may be an important factor in improving immunological recovery and HRQOL outcomes.

BackgroundMorphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life.MethodsInterregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed.ResultsAcross the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth.ConclusionsOur findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.

Background: Globally there are few countries facilitating undergraduate programmes to train nurses specifically to support people with intellectual disabilities. In Ireland, eight Higher Education Institutions (HEIs) in partnership with associated health care providers (AHCPs) facilitate undergraduate Nursing (Intellectual Disability) degree programmes. Practice placements are a core element of these programmes whereby students complete several hours in these learning environments as part fulfilment of their degree requirements. Because people with intellectual disability who traditionally accessed services in congregated settings, are now increasingly accessing mainstream services, new placement types are emerging. This study aimed to describe practice placements, areas of the registered nurse in intellectual disability (RNID) specialist support and other learning opportunities accessed by undergraduate students on Bachelor of Science Nursing (Intellectual Disability) programmes across eight HEIs in Ireland. Methods: A survey design involving a Placement Opportunities Tool (POT) developed through expert group meetings and consensus was utilised. Following ethical approval, Qualtrics XM software was enlisted to distribute the online survey to eight HEIs in Ireland. Excel and SPSS were engaged to undertake descriptive statistical analysis. Findings: A total of five fully complete and one partially complete POT were included in the data analysis. Findings demonstrate that majority of placements are accessed in traditional Intellectual Disability services with students having less access to placements either in mainstream services or with RNID specialists. Conclusions: This study details placement accessed by nursing students (Intellectual Disability) and associated areas of RNID specialist support. There is an urgent need to develop undergraduate student placements which reflect the contemporary lives of people with an intellectual disability. HEIs, AHCPs, nursing regulators, support persons and people with intellectual disabilities need to collaborate to develop practice placements enabling students to access learning experiences embedded in the realities of people living with intellectual disability who are integrating into their communities.

Approximately one-third of autistics report intimate relationship experience, but few studies have explored neuromixed relationships from the perspectives of non-autistic partners. Non-autistic partners increasingly use peer-led online groups to seek support. The purpose of this study was to capture a theory that reflects the basic social experience of individuals who use these support groups using classic Glaserian grounded theory methodology. Online interviews were conducted with 162 non-autistics who believed that they were in neuromixed relationships. Data were concurrently collected and analyzed using constant comparative analysis. Participants described varying views of autism, from a difference to a disorder, which defined the context of their relationships. Five relationship profiles emerged--mutual partnership: viewed partners as = companionship: viewed partners as friends but lacked a deeper connection; caregiving: viewed partners as dependents and compared relationships to parent-child dyads; detachment: viewed relationships as broken beyond repair and isolated selves from partners; and discriminatory: believed and circulated negative generalizations about autism. Many participants who were dissatisfied in their relationships shared that their partners were not formally evaluated and did not self-identify as autistic. Future research should explore ways that autism labels are (mis)applied by the general public based on negative stereotypes about autism.

The legalities around incidents in outdoor education (OE) are undeniable, and ignorance is not a defence. Using case study analysis specific to legal literacy, we extend this analysis to include the "7 Rights" framework and add two additional rights for consideration, referred to as the 9 Rights. This discussion organizes what is publicly available on the Toronto District School Board (TDSB) outing, and death of Jeremiah Perry, and draw insights from the decision of the Ontario Superior Court of Justice in the subsequent criminal negligence trial. We present our analysis and recommendations, based on the 9 Rights. By exploring pertinent legal terminology, relevant to this case, the 9 Rights guides risk analysis for trip planning, in-field risk assessment, and risk management. The unfortunate crux of this discussion, and many OE incidents in Canada, is that "the law" enters the learning equation only after something goes wrong.

Not available.

Health-related worries can be either self-directed or occur in close relationships by proxy (e.g., among parents, couples, or pet owners). Our aim was to test the feasibility of assessing health anxiety by proxy in parents and to examine the relationship of health anxiety with family well-being. Health anxiety by proxy was measured between parent-child and parent-partner relationships with adapted versions of the modified Short Health Anxiety Inventory. Parents reported significantly higher levels of health anxiety by proxy regarding their child than for themselves, t (585) = −3.61, p < .001. Exploratory factor analysis showed that each health anxiety questionnaire formed a distinct latent factor. Parenting stress and poorer family functioning had small associations with health anxiety towards one’s self, child, and partner ( r = 0.15 to r = 0.20). Further research is needed to determine clinical relevance and its impact on health behaviors and functioning within the family unit.

Summary:. Unlike other body parts, the upper extremity has critical structures close to the skin, making soft tissue injuries more complex. These injuries can result from various causes, including trauma and necrotizing soft tissue infections, necessitating reconstruction. Historically, pedicled flaps from the groin and abdomen were commonly used for upper extremity reconstruction, but they had limitations, such as the need for flap division and debulking, patient discomfort, and stiffness. Free flap reconstruction has become the preferred method, but it still faces challenges like patient and facility issues, the absence of recipient vessels after injury, and multi-surface wounds. This case report describes a 67-year-old patient with a severe necrotizing soft tissue infection in the right upper extremity. After multiple debridement procedures, the patient underwent hand amputation and soft tissue coverage using an abdominal wall-based flap. The objectives of achieving stable soft tissue coverage while preserving maximal length of the upper extremity were successfully achieved, and the patient expressed satisfaction with the outcomes. Inadequate management of upper extremity wounds can lead to amputation and psychological distress. The reconstructive ladder is used to approach upper extremity soft tissue defects, with free tissue transfer being the standard for larger defects. However, abdominal flaps still have indications when free tissue transfer is not feasible or contraindicated. It is imperative that plastic surgeons have these techniques in their armamentarium to provide a service to the ever more complex patient with an upper extremity wound.

Adolescence has been hypothesized to be a critical period for the development of human association cortex and higher-order cognition. A defining feature of critical period development is a shift in the excitation: inhibition (E/I) balance of neural circuitry, however how changes in E/I may enhance cortical circuit function to support maturational improvements in cognitive capacities is not known. Harnessing ultra-high field 7 T MR spectroscopy and EEG in a large, longitudinal cohort of youth (N = 164, ages 10–32 years old, 347 neuroimaging sessions), we delineate biologically specific associations between age-related changes in excitatory glutamate and inhibitory GABA neurotransmitters and EEG-derived measures of aperiodic neural activity reflective of E/I balance in prefrontal association cortex. Specifically, we find that developmental increases in E/I balance reflected in glutamate:GABA balance are linked to changes in E/I balance assessed by the suppression of prefrontal aperiodic activity, which in turn facilitates robust improvements in working memory. These findings indicate a role for E/I-engendered changes in prefrontal signaling mechanisms in the maturation of cognitive maintenance. More broadly, this multi-modal imaging study provides evidence that human association cortex undergoes physiological changes consistent with critical period plasticity during adolescence.

Abstract A BiFeO3 film is grown epitaxially on a PrScO3 single crystal substrate which imparts ~ 1.45% of biaxial tensile strain to BiFeO3 resulting from lattice misfit. The biaxial tensile strain effect on BiFeO3 is investigated in terms of crystal structure, Poisson ratio, and ferroelectric domain structure. Lattice resolution scanning transmission electron microscopy, precession electron diffraction, and X-ray diffraction results clearly show that in-plane interplanar distance of BiFeO3 is the same as that of PrScO3 with no sign of misfit dislocations, indicating that the biaxial tensile strain caused by lattice mismatch between BiFeO3 and PrScO3 are stored as elastic energy within BiFeO3 film. Nano-beam electron diffraction patterns compared with structure factor calculation found that the BiFeO3 maintains rhombohedral symmetry, i.e., space group of R3c. The pattern analysis also revealed two crystallographically distinguishable domains. Their relations with ferroelectric domain structures in terms of size and spontaneous polarization orientations within the domains are further understood using four-dimensional scanning transmission electron microscopy technique.

Abstract Theories of human neurobehavioral development suggest executive functions mature from childhood through adolescence, underlying adolescent risk-taking and the emergence of psychopathology. Investigations with relatively small datasets or narrow subsets of measures have identified general executive function development, but the specific maturational timing and independence of potential executive function subcomponents remain unknown. Integrating four independent datasets (N = 10,766; 8–35 years old) with twenty-three measures from seventeen tasks, we provide a precise charting, multi-assessment investigation, and replication of executive function development from adolescence to adulthood. Across assessments and datasets, executive functions follow a canonical non-linear trajectory, with rapid and statistically significant development in late childhood to mid-adolescence (10–15 years old), before stabilizing to adult-levels in late adolescence (18–20 years old). Age effects are well captured by domain-general processes that generate reproducible developmental templates across assessments and datasets. Results provide a canonical trajectory of executive function maturation that demarcates the boundaries of adolescence and can be integrated into future studies.

With advancements in multicomponent molecular biological tools, the need for versatile, rapid and cost-effective cloning that enables successful combinatorial assembly of DNA plasmids of interest is becoming increasingly important. Unfortunately, current cloning platforms fall short regarding affordability, ease of combinatorial assembly and, above all, the ability to iteratively remove individual cassettes at will. Herein we construct, implement and make available a broad set of cloning vectors, called PlayBack vectors, that allow for the expression of several different constructs simultaneously under separate promoters. Overall, this system is substantially cheaper than other multicomponent cloning systems, has usability for a wide breadth of experimental paradigms and includes the novel feature of being able to selectively remove components of interest at will at any stage of the cloning platform.