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Background Global longitudinal strain (GLS) is a sensitive measure of left ventricular function and a risk marker in severe aortic stenosis. We sought to determine whether biomarkers of cardiac damage (cardiac troponin) and stress (NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide]) could complement GLS to identify patients with severe aortic stenosis at highest risk. Methods and Results From a multicenter prospective cohort of patients with symptomatic severe aortic stenosis who underwent transcatheter aortic valve implantation, we measured absolute GLS (aGLS), cardiac troponin, and NT‐proBNP at baseline in 499 patients. Left ventricular ejection fraction 2; P≤0.002 for each) when the other biomarker was elevated, but not when the other biomarker was normal (interaction P=0.015). Conclusions Among patients with symptomatic severe aortic stenosis undergoing transcatheter aortic valve implantation, elevations in circulating cardiac troponin and NT‐proBNP are more common as GLS worsens. Biomarkers of cardiac damage and stress are independently associated with mortality after transcatheter aortic valve implantation, whereas GLS is not. These findings may have implications for risk stratification of asymptomatic patients to determine optimal timing of valve replacement.

Escherichia coli serotype O157:H7 is a zoonotic food- and waterborne bacterial pathogen that causes a high hospitalization rate and can cause life-threatening complications. Increasingly, E. coli O157:H7 infections appear to originate from fresh produce. Ruminants, such as cattle, are a prominent reservoir of E. coli O157:H7 in the United States. California is one of the most agriculturally productive regions in the world for fresh produce, beef, and milk. The close proximity of fresh produce and cattle presents food safety challenges on a uniquely large scale. We performed a survey of E. coli O157:H7 on 20 farms in California to observe the regional diversity and prevalence of E. coli O157:H7. Isolates were obtained from enrichment cultures of cow feces. Some farms were sampled on two dates. Genomes from isolates were sequenced to determine their relatedness and pathogenic potential. E. coli O157:H7 was isolated from approximately half of the farms. The point prevalence of E. coli O157:H7 on farms was highly variable, ranging from zero to nearly 90%. Within farms, generally one or a few lineages were found, even when the rate of isolation was high. On farms with high isolation rates, a single clonal lineage accounted for most of the isolates. Farms that were visited months after the first visit might have had the same lineages of E. coli O157:H7. Strains of E. coli O157:H7 may be persistent for months on farms.IMPORTANCE This survey of 20 cow-calf operations from different regions of California provides an in depth look at resident Escherichia coli O157:H7 populations at the molecular level. E. coli O157:H7 is found to have a highly variable prevalence, and with whole-genome sequencing, high prevalences in herds were found to be due to a single lineage shed from multiple cows. Few repeat lineages were found between farms in this area; therefore, we predict that E. coli O157:H7 has significant diversity in this area beyond what is detected in this survey. All isolates from this study were found to have pathogenic potential based on the presence of key virulence gene sequences. This represents a novel insight into pathogen diversity within a single subtype and will inform future attempts to survey regional pathogen populations.

Antigen-activated lymphocytes undergo extraordinarily rapid cell division in the course of immune responses. We hypothesized that this unique aspect of lymphocyte biology leads to unusual genomic stress in recently antigen-activated lymphocytes and that targeted manipulation of DNA damage-response (DDR) signaling pathways would allow for selective therapeutic targeting of pathological T cells in disease contexts. Consistent with these hypotheses, we found that activated mouse and human T cells display a pronounced DDR in vitro and in vivo. Upon screening a variety of small-molecule compounds, we found that potentiation of p53 (via inhibition of MDM2) or impairment of cell cycle checkpoints (via inhibition of CHK1/2 or WEE1) led to the selective elimination of activated, pathological T cells in vivo. The combination of these strategies [which we termed "p53 potentiation with checkpoint abrogation" (PPCA)] displayed therapeutic benefits in preclinical disease models of hemophagocytic lymphohistiocytosis and multiple sclerosis, which are driven by foreign antigens or self-antigens, respectively. PPCA therapy targeted pathological T cells but did not compromise naive, regulatory, or quiescent memory T-cell pools, and had a modest nonimmune toxicity profile. Thus, PPCA is a therapeutic modality for selective, antigen-specific immune modulation with significant translational potential for diverse immune-mediated diseases.

The cerebellum is a large hindbrain structure that is increasingly recognized for its contribution to diverse domains of cognitive and affective processing in human health and disease. Although several of these domains are sex biased, our fundamental understanding of cerebellar sex differences-including their spatial distribution, potential biological determinants, and independence from brain volume variation-lags far behind that for the cerebrum. Here, we harness automated neuroimaging methods for cerebellar morphometrics in 417 individuals to (1) localize normative male-female differences in raw cerebellar volume, (2) compare these to sex chromosome effects estimated across five rare sex (X/Y) chromosome aneuploidy (SCA) syndromes, and (3) clarify brain size-independent effects of sex and SCA on cerebellar anatomy using a generalizable allometric approach that considers scaling relationships between regional cerebellar volume and brain volume in health. The integration of these approaches shows that (1) sex and SCA effects on raw cerebellar volume are large and distributed, but regionally heterogeneous, (2) human cerebellar volume scales with brain volume in a highly nonlinear and regionally heterogeneous fashion that departs from documented patterns of cerebellar scaling in phylogeny, and (3) cerebellar organization is modified in a brain size-independent manner by sex (relative expansion of total cerebellum, flocculus, and Crus II-lobule VIIIB volumes in males) and SCA (contraction of total cerebellar, lobule IV, and Crus I volumes with additional X- or Y-chromosomes; X-specific contraction of Crus II-lobule VIIIB). Our methods and results clarify the shifts in human cerebellar organization that accompany interwoven variations in sex, sex chromosome complement, and brain size.SIGNIFICANCE STATEMENT Cerebellar systems are implicated in diverse domains of sex-biased behavior and pathology, but we lack a basic understanding of how sex differences in the human cerebellum are distributed and determined. We leverage a rare neuroimaging dataset to deconvolve the interwoven effects of sex, sex chromosome complement, and brain size on human cerebellar organization. We reveal topographically variegated scaling relationships between regional cerebellar volume and brain size in humans, which (1) are distinct from those observed in phylogeny, (2) invalidate a traditional neuroimaging method for brain volume correction, and (3) allow more valid and accurate resolution of which cerebellar subcomponents are sensitive to sex and sex chromosome complement. These findings advance understanding of cerebellar organization in health and sex chromosome aneuploidy.

Bandgap engineering is controlled manipulation of the bandgap of materials/meta-materials to achieve desired properties. The electrical and optical properties of materials are significantly affected by bandgap tuning; therefore, bandgap engineering is a powerful technique for designing electronic and optoelectronic devices. Compositional engineering, strain engineering, and nanoscience and technology are the three major fields associated with bandgap engineering. Any unique combination of this engineering can provide novel strategies to produce novel band-structured devices. In this method article, we have demonstrated how solvation energy can alter the bandgap energy, a fact that is generally ignored due to misconceptions about quantum/size confinement. Here, we prepare nanostructured transition metal oxides (Co3O4, CuO, and ZnO) with polyethylene glycol (PEG), and the method is termed PEGylation. We investigate the influence of PEGylation on the structural, electrochemical, and electronic nature of these oxides. It is observed that the bandgap tunability (7.33%) is maximum for ZnO. Our study suggests that band alteration is significantly correlated with the change in lattice parameters; however, it is orientation dependent as the correlation coefficient reduces to 0.85 from 1 for the change in lattice parameter b along the y -axis compared to the other two lattice parameters. Similarly, band alteration is also known to have some correlation with the electrochemical potential, but is surprisingly almost independent of size confinement. [ABSTRACT FROM AUTHOR]

Zombies are the walking dead. In scientific literature, the Zombie Papers continue to exist and do not die even after the retraction which in itself is a slow process, inconsistent, and inadequate. The top-level evidence and practice guidelines based upon systematic review and meta-analysis get contaminated by the false data from paper mills and Zombie Papers. Science relies on trust. The research and publication of evidence must be ethical and trustworthy. The research publication is a transnational process. It requires the collaboration of stakeholders including readers, editors, institutions, and society beyond the national boundaries. Awareness of Zombie Papers and misconduct is necessary to maintain the integrity of science.

Solids such as soils and sediments contaminated with per- and polyfluorinated alkyl substances (PFAS) from exposure to impacted media, e.g., landfill leachate or biosolids, direct contaminated discharge, and contaminant transport from atmospheric deposition, have caused significant environmental pollution. Such solids can act as secondary sources of PFAS for groundwater and surface water contamination. There are currently no proven technologies that can degrade PFAS in soil and sediments in a cost-effective, environmentally-friendly, and energy-efficient manner. This study examines the use of coupled high and low-frequency ultrasound in desorbing and degrading PFAS in soil, thereby achieving concurrent treatment and destruction of PFAS in soil. Two common PFAS, namely perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), were used to evaluate treatment performance in soils with both low and high organic matter contents. The test results showed that the ultrasound treatment could significantly reduce PFAS concentrations in artificially contaminated soil; however, no significant degradation was achieved. Ultrasound treatment did improve desorption of PFAS from solid particles, particularly from the highly absorbent organic soil; 68.8 ± 1.8% of PFOA and 45.4 ± 4.1% of PFOS were leached from the soil after ultrasound treatment compared to only 28 ± 0.2% of PFOA and 1 ± 3.1% of PFOS after desorption in water. This work shows that sonication treatment is an effective technology for the removal of PFAS from solids, however, the presence of solids in the solid–liquid slurry can negatively impact ultrasonic cavitation, inhibiting the sonolytic degradation of desorbed PFAS.

Background: As primary total knee arthroplasty volume continues to increase, so will the number of revision total knee arthroplasty (rTKA) procedures. The purpose of this study is to provide an updated perspective on the incidence, indications, and financial burden of rTKA in the United States. Material and methods: This was a retrospective epidemiologic analysis using the National Inpatient Sample. International Classification of Diseases ninth and tenth revision codes were used to identify patients who underwent rTKA and create cohorts based on rTKA indications from 2012 to 2019. National and regional trends for length of stay, cost, and discharge location were evaluated. Results: A total of 505,160 rTKA procedures were identified. The annual number of rTKA procedures increased by 29.6% over the study period (56,490 to 73,205). The top 3 indications for rTKA were aseptic loosening (23.1%), periprosthetic joint infection (PJI) (20.4%), and instability (11.0%). Over the study period, the proportion of patients discharged to skilled nursing facility decreased from 31.7% to 24.1% (P < .001). Hospital length of stay decreased from 4.0 days in 2012 to 3.8 days in 2019 (P < .001). Hospital costs increased by $1300 from $25,730 to $27,077 (P < .001). The proportion of rTKA cases performed at urban academic centers increased (52.1% to 74.3%, P < .001) while that at urban nonacademic centers decreased (39.0% to 19.2%, P < .001). Conclusion: The top 3 indications for rTKA were aseptic loosening, PJI, and instability, with PJI becoming the most common indication in 2019. These cases are increasingly being performed at urban academic centers and away from urban nonacademic centers. Level of Evidence: 3 (Retrospective cohort study).

Abstract The permeability of shale is a significant and important design parameter for shale gas extraction. The shale gas permeability is usually obtained based on Darcy flow using standard laboratory permeability tests done on core samples, that do not account for different transport mechanisms at high pressures and anisotropic effects in shales due to nano-scale pore structure. In this study, the permeability of shale is predicted using a pore network model. The characteristics of pore structure can be described by specific parameters, including porosity, pore body and pore throat sizes and distributions and coordination numbers. The anisotropy was incorporated into the model using a coordination number ratio, and an algorithm that was developed for connections of pores in the shale formation. By predicting hydraulic connectivity and comparing it with several high-pressure permeability tests, the proposed three-dimensional pore network model was verified. Results show that the prediction from the anisotropic pore network model is closer to the test results than that based on the isotropic pore network model. The predicted permeability values from numerical simulation using anisotropic pore network model for four shales from Qaidam Basin, China are quite similar to those measured from laboratory tests. This study confirmed that the developed anisotropic three-dimensional pore network model could reasonably represent the natural gas flow in the actual shale formation so that it can be used as a prediction tool.

Undergraduates learn that gene editing in diverse organisms is now possible. How targeted manipulation of genes and genomes is utilized in basic science and biomedicine to address biological questions is challenging for undergraduates to conceptualize. Thus, we developed a lab experience that would allow students to be actively engaged in the full process of design, implementation of a gene editing strategy, and interpretation of results within an 8-week lab period of a Genetics course. The laboratory experience combines two transformative biotechnology tools; the utilization of green fluorescent protein (GFP) as a diagnostic marker of gene expression and the fundamentals and specificity of Clustered Regularly Interspaced Short Palindromic Repeats-cas9 (CRISPR-cas9) gene editing in bacterial cells. The students designed and constructed plasmids that express single guide RNA targeted to GFP, expressed the sgRNA and cas9 in bacteria cells, and successfully deactivated GFP gene expression in the bacterial cells with their designed CRISPR-cas9 tools. Student assessment revealed most students achieved student learning objectives. We conclude this lab experience is an effective and accessible method for engaging students in the scientific practices, knowledge and challenges revolving targeted CRISPR-cas9 gene manipulation.

Use of manipulatives in mathematics classes has yielded compelling evidence of their value in improving several aspects of mathematics education. This report endeavored to gain a clearer picture of their benefits by using a meta-synthesis technique by integrating findings from 12 previous qualitative or mixed methods studies. They were evaluated using the Critical Appraisal Skills Programme and summarized using a PRISMA diagram. Content analysis identified five main themes: (a) activation of classroom engagement and participation, (b) building of confidence and motivation, (c) enhancement of mathematical proficiency, (d) availability and accessibility of varied resources as manipulative, and (e) teachers' competency and careful planning. A meta-theme that emerged was Optimizing Mathematics Learning with Effective Classroom Resources through Manipulatives. Thematic study revealed that strategically integrating manipulatives into classroom instruction has a favorable influence on student engagement, confidence, motivation, and mathematical ability. By incorporating manipulatives into mathematics instruction, educators may create inclusive, engaging, and dynamic learning environments that encourage deeper conceptual comprehension. [ABSTRACT FROM AUTHOR]

Pollution prevention is an approach for generating less waste using fewer toxic chemicals while conserving water and energy. Even though pollution prevention practices have been encouraged for over thirty years, many smaller businesses have not considered or adopted such techniques. This study examines the effect of a community-based approach designed to emphasize the benefits to the health and economic well-being of urban communities when source reduction practices are implemented by businesses in the community. Partnering with existing community groups in Newark and Jersey City, NJ, technical assistance was provided to small and medium-sized businesses under grant funding from Region 2 of the US Environmental Protection Agency. In this research, 32 small and medium-sized businesses were evaluated for source reduction opportunities and implementation plans were drawn up. After these businesses implemented operational changes, emission and cost savings were determined and reported back to respective small business owners as well as to the communities during community meetings designed to encourage additional participation. Based on 32 case studies, several measurable benefits were achieved, including the yearly saving of 932 pounds of hazardous waste, 3917 pounds of non-hazardous waste, 13.62 metric tons of carbon equivalent (MTCE) of greenhouse gases and $5335 USD. The initial findings suggest that community-based programs such as this can be beneficial but must be sustained over a period of time. One issue that was repeatedly observed, and is likely widely believed, is the concern of small business operators that cooperation with any group funded by a government program may lead to the assessment of fines or penalties for environmental violations. This concern limits the willingness of many smaller businesses to participate. The findings of this study suggest that a sustained community-based program may overcome that concern through demonstration of the benefit to the business and the community, and through credibility building achieved by regular community reporting and the absence of official intervention.

Background Left ventricular hypertrophy (LVH) is associated with increased mortality risk and rehospitalization after transcatheter aortic valve replacement among those with severe aortic stenosis. Whether cardiac troponin (cTnT) and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) risk stratify patients with aortic stenosis and without LVH is unknown. Methods and Results In a multicenter prospective registry of 923 patients with severe aortic stenosis undergoing transcatheter aortic valve replacement, we included 674 with core‐laboratory‐measured LV mass index, cTnT, and NT‐proBNP. LVH was defined by sex‐specific guideline cut‐offs and elevated biomarker levels were based on age and sex cut‐offs. Adjusted Cox proportional hazards models evaluated associations between LVH and biomarkers and all‐cause death out to 5 years. Elevated cTnT and NT‐proBNP were present in 82% and 86% of patients with moderate/severe LVH, respectively, as compared with 66% and 69% of patients with no/mild LVH, respectively (P

Detailed descriptions of cortical anatomy in youth with Down syndrome (DS), the most common genetic cause of intellectual disability (ID), are scant. Thus, the current study examined deviations in cortical thickness (CT) and surface area (SA), at high spatial resolution, in youth with DS, to identify focal differences relative to typically developing (TD) youth. Participants included 31 youth with DS and 45 age- and sex-matched TD controls (mean age ∼16 years; range = 5-24 years). All participants completed T1-weighted ASSET-calibrated magnetization prepared rapid gradient echo scans on a 3-T magnetic resonance imaging scanner. Replicating prior investigations, cortical volume was reduced in DS compared with controls. However, a novel dissociation for SA and CT was found-namely, SA was reduced (predominantly in frontal and temporal regions) while CT was increased (notably in several regions thought to belong to the default mode network; DMN). These findings suggest that reductions in SA rather than CT are driving the cortical volume reductions reported in prior investigations of DS. Moreover, given the link between DMN functionality and Alzheimer's symptomatology in chromosomally typical populations, future DS studies may benefit from focusing on the cortex in DMN regions, as such investigations may provide clues to the precocious onset of Alzheimer's disease in this at-risk group.

Structural neuroimaging of humans with typical and atypical sex-chromosome complements has established the marked influence of both Yand X-/Y-chromosome dosage on total brain volume (TBV) and identified potential cortical substrates for the psychiatric phenotypes associated with sex-chromosome aneuploidy (SCA). Here, in a cohort of 354 humans with varying karyotypes (XX, XY, XXX, XXY, XYY, XXYY, XXXXY), we investigate sex and SCA effects on subcortical size and shape; focusing on the striatum, pallidum and thalamus. We find large effect-size differences in the volume and shape of all three structures as a function of sex and SCA. We correct for TBV effects with a novel allometric method harnessing normative scaling rules for subcortical size and shape in humans, which we derive here for the first time. We show that all three subcortical volumes scale sublinearly with TBV among healthy humans, mirroring known relationships between subcortical volume and TBV among species. Traditional TBV correction methods assume linear scaling and can therefore invert or exaggerate sex and SCA effects on subcortical anatomy. Allometric analysis restricts sex-differences to: (1) greater pallidal volume (PV) in males, and (2) relative caudate head expansion and ventral striatum contraction in females. Allometric analysis of SCA reveals that supernumerary X- and Y-chromosomes both cause disproportionate reductions in PV, and coordinated deformations of striatopallidal shape. Our study provides a novel understanding of sex and sex-chromosome dosage effects on subcortical organization, using an allometric approach that can be generalized to other basic and clinical structural neuroimaging settings.

Owing to their unique evolutionary history, modern mammalian X- and Y-chromosomes have highly divergent gene contents counterbalanced by regulatory features, which preferentially restrict expression of X- and Y-specific genes. These 2 characteristics make opposing predictions regarding the expected dissimilarity of X- vs. Y-chromosome influences on biological structure and function. Here, we quantify this dissimilarity using in vivo neuroimaging within a rare cohort of humans with diverse sex chromosome aneuploidies (SCAs). We show that X- and Y-chromosomes have opposing effects on overall brain size but exert highly convergent influences on local brain anatomy, which manifest across biologically distinct dimensions of the cerebral cortex. Large-scale online meta-analysis of functional neuroimaging data indicates that convergent sex chromosome dosage effects preferentially impact centers for social perception, communication, and decision-making. Thus, despite an almost complete lack of sequence homology, and opposing effects on overall brain size, X- and Y-chromosomes exert congruent effects on the proportional size of cortical systems involved in adaptive social functioning. These convergent X-Y effects (i) track the dosage of those few genes that are still shared by X- and Y-chromosomes, and (ii) may provide a biological substrate for the link between SCA and increased rates of psychopathology.

Studies suggest marijuana impacts gray and white matter neural tissue development, however few prospective studies have determined the relationship between cortical thickness and cannabis use spanning adolescence to young adulthood. This study aimed to understand how heavy marijuana use influences cortical thickness trajectories across adolescence. Subjects were adolescents with heavy marijuana use and concomitant alcohol use (MJ+ALC, n=30) and controls (CON, n=38) with limited substance use histories. Participants underwent magnetic resonance imaging and comprehensive substance use assessment at three independent time points. Repeated measures analysis of covariance was used to look at main effects of group, time, and Group × Time interactions on cortical thickness. MJ+ALC showed thicker cortical estimates across the brain (23 regions), particularly in frontal and parietal lobes (ps

A 54-year-old male with history of end-stage renal disease secondary to hypertension on hemodialysis with moderate aortic valve insufficiency presented with progressive exertional dyspnea and lower extremity edema over several weeks. Relevant history included hospitalization for Staphylococcus epidermidis bacteremia secondary to dialysis catheter line infection 6 months prior. (Level of Difficulty: Advanced.)

In this paper, nonlinearity associated with intense ultrasound is studied by using the one-dimensional motion of nonlinear shock wave in an ideal fluid. In nonlinear acoustics, the wave speed of different segments of a waveform is different, which causes distortion in the waveform and can result in the formation of a shock (discontinuity). Acoustic pressure of high-intensity waves causes particles in the ideal fluid to vibrate forward and backward, and this disturbance is of relatively large magnitude due to high-intensities, which leads to nonlinearity in the waveform. In this research, this vibration of fluid due to the intense ultrasonic wave is modeled as a fluid pushed by one complete cycle of piston. In a piston cycle, as it moves forward, it causes fluid particles to compress, which may lead to the formation of a shock (discontinuity). Then as the piston retracts, a forward-moving rarefaction, a smooth fan zone of continuously changing pressure, density, and velocity is generated. When the piston stops at the end of the cycle, another shock is sent forward into the medium. The variation in wave speed over the entire waveform is calculated by solving a Riemann problem. This study examined the interaction of shocks with a rarefaction. The flow field resulting from these interactions shows that the shock waves are attenuated to a Mach wave, and the pressure distribution within the flow field shows the initial wave is dissipated. The developed theory is applied to waves generated by 20 KHz, 500 KHz, and 2 MHz transducers with 50, 150, 500, and 1500 W power levels to explore the effect of frequency and power on the generation and decay of shock waves. This work enhances the understanding of the interactions of high-intensity ultrasonic waves with fluids.

ObjectivePrior reports suggest that autism spectrum disorder (ASD) is associated with atypically excessive early brain growth. Recent cross-sectional studies suggest that later cortical development during adolescence/adulthood might also be aberrant, although longitudinal designs are required to evaluate atypical growth trajectories. The present study sought to examine longitudinal changes in cortical thickness and surface area among adolescents and young adults with ASD.MethodTwo high-resolution anatomic magnetic resonance imaging scans approximately 2 years apart were acquired from 17 adolescents with ASD and 18 typically developing (TD) adolescents, matched on age (range = 14-24 years), IQ, sex ratio, and handedness (70 scans total). The FreeSurfer image analysis suite was used to quantify longitudinal changes in cortical thickness and surface area.ResultsAccelerated cortical thinning for the ASD group as compared to the TD group was found in 2 areas in the left hemisphere, the posterior portion of ventral temporal cortex and superior parietal cortex (cluster corrected p < .01). For ventral temporal cortex, cortical thinning was associated with everyday executive function impairments, and thinner cortex at time 2 was correlated with ASD social symptoms. Differences in surface area changes were not detected.ConclusionThe present longitudinal study extends prior cross-sectional research by demonstrating increased cortical thinning (in portions of temporal and parietal cortex) but comparable surface area growth rates in participants with ASD compared to TD controls during adolescence and into young adulthood. These findings provide further evidence for atypical cortical development beyond the early years in ASD, marked by increased cortical thinning in late adolescence/young adulthood.

There are varying, often conflicting, reports with respect to altered striatal volume and morphometry in the major psychoses due to the influences of antipsychotic medications on striatal volume. Thus, disassociating disease effects from those of medication become exceedingly difficult. For the first time, using a longitudinally studied sample of structural magnetic resonance images from patients with childhood onset schizophrenia (COS; neurobiologically contiguous with the adult onset form of schizophrenia), their nonpsychotic siblings (COSSIBs), and novel shape mapping algorithms that are volume independent, we report the familial contribution of striatal morphology in schizophrenia. The results of our volumetric analyses demonstrate age-related increases in overall striatal volumes specific only to COS. However, both COS and COSSIBs showed overlapping shape differences in the striatal head, which normalized in COSSIBs by late adolescence. These results mirror previous studies from our group, demonstrating cortical thickness deficits in COS and COSSIBs as these deficits normalize in COSSIBs in the same age range as our striatal findings. Finally, there is a single region of nonoverlapping outward displacement in the dorsal aspect of the caudate body, potentially indicative of a response to medication. Striatal shape may be considered complimentary to volume as an endophenotype, and, in some cases may provide information that is not detectable using standard volumetric techniques. Our striatal shape findings demonstrate the striking localization of abnormalities in striatal the head. The neuroanatomical localization of these findings suggest the presence of abnormalities in the striatal-prefrontal circuits in schizophrenia and resilience mechanisms in COSSIBs with age dependent normalization.

The human brain displays stereotyped and early emerging patterns of cortical asymmetry in health. It is unclear if these asymmetries are highly sensitive to genetic and environmental variation or fundamental features of the brain that can survive severe developmental perturbations. To address this question, we mapped cortical thickness (CT) asymmetry in a group of genetically defined disorders known to impact CT development. Participants included 137 youth with one of five sex-chromosome aneuploidies [SCAs; XXX (n = 28), XXY (n = 58), XYY (n = 26), XXYY (n = 20), and XXXXY (n = 5)], and 169 age-matched typically developing controls (80 female). In controls, we replicated previously reported rightward inferior frontal and leftward lateral parietal CT asymmetry. These opposing frontoparietal CT asymmetries were broadly preserved in all five SCA groups. However, we also detected foci of shifting CT asymmetry with aneuploidy, which fell almost exclusively within regions of significant CT asymmetry in controls. Specifically, X-chromosome aneuploidy accentuated normative rightward inferior frontal asymmetries, while Y-chromosome aneuploidy reversed normative rightward medial prefrontal and lateral temporal asymmetries. These findings indicate that (1) the stereotyped normative pattern of opposing frontoparietal CT asymmetry arises from developmental mechanisms that can withstand gross chromosomal aneuploidy and (2) X and Y chromosomes can exert focal, nonoverlapping and directionally opposed influences on CT asymmetry within cortical regions of significant asymmetry in health. Our study attests to the resilience of developmental mechanisms that support the global patterning of CT asymmetry in humans, and motivates future research into the molecular bases and functional consequences of sex chromosome dosage effects on CT asymmetry.

Executive functions (EF) are thought to be impaired in Down syndrome (DS) and sex chromosome trisomy (Klinefelter and Trisomy X syndromes; +1X). However, the syndromic specificity and developmental trajectories associated with EF difficulties in these groups are poorly understood. The current investigation (a) compared everyday EF difficulties in youth with DS, +1X, and typical development (TD); and (b) examined relations between age and EF difficulties in these two groups and a TD control group cross-sectionally. Study 1 investigated the syndromic specificity of EF profiles on the Behavior Rating Inventory of Executive Function (BRIEF) in DS (n = 30), +1X (n = 30), and a TD group (n = 30), ages 5-18 years. Study 2 examined age effects on EF in the same cross-sectional sample of participants included in Study 1. Study 3 sought to replicate Study 2's findings for DS by examining age-EF relations in a large independent sample of youth with DS (n = 85) and TD (n = 43), ages 4-24 years. Study 1 found evidence for both unique and shared EF impairments for the DS and +1X groups. Most notably, youth with +1X had relatively uniform EF impairments on the BRIEF scales, while the DS group showed an uneven BRIEF profile with relative strengths and weaknesses. Studies 2 and 3 provided support for fairly similar age-EF relations in the DS and TD groups. In contrast, for the +1X group, findings were mixed; 6 BRIEF scales showed similar age-EF relations to the TD group and 2 showed greater EF difficulties at older ages for +1X. These findings will be discussed within the context of efforts to identify syndrome specific cognitive-behavioral profiles for youth with different genetic syndromes in order to inform basic science investigations into the etiology of EF difficulties in these groups and to develop treatment approaches that are tailored to the needs of these groups.

The phenotype of 48, XXYY syndrome (referred to as XXYY) is associated with characteristic but variable developmental, cognitive, behavioral and physical abnormalities. To discern the neuroanatomical phenotype of the syndrome, we conducted quantitative and qualitative analyses on MRI brain scans from 25 males with XXYY and 92 age and SES matched typically developing XY males. Quantitatively, males in the XXYY group had smaller gray and white matter volumes of the frontal and temporal lobes. Conversely, both gray and white matter volumes of the parietal lobe as well as lateral ventricular volume were larger in the XXYY group. Qualitatively, males in the XXYY group had a higher incidence of colpocephaly (84% vs. 34%, p ≤ 0.001), white matter lesions (25% vs. 5%, p = 0.007), and thin posterior body of the corpus callosum (28% vs. 3%, p = 0.001). The specificity of these findings may shed light on the role of the X and Y chromosomes in typical and atypical brain development and help provide direction for future studies of brain-behavior relationships in males with XXYY syndrome.

The advent of magnetic resonance imaging, which safely allows in vivo quantification of anatomical and physiological features of the brain, has revolutionized pediatric neuroscience. Longitudinal studies are useful for the characterization of developmental trajectories (ie, changes in imaging measures by age). Developmental trajectories (as opposed to static measures) have proven to have greater power in discriminating healthy from clinical groups and in predicting cognitive/behavioral measures, such as IQ. Here we summarize results from an ongoing longitudinal pediatric neuroimaging study that has been conducted at the Child Psychiatry Branch of the National Institute of Mental Health since 1989. Developmental trajectories of structural MRI brain measures from healthy youth are compared and contrasted with trajectories in attention-deficit/hyperactivity disorder (ADHD) and childhood-onset schizophrenia. Across ages 5-25 years, in both healthy and clinical populations, white matter volumes increase and gray matter volumes follow an inverted U trajectory, with peak size occurring at different times in different regions. At a group level, differences related to psychopathology are seen for gray and white matter volumes, rates of change, and for interconnectedness among disparate brain regions.

Good research writing and publication practices are important to identify, acknowledge, and generate awareness for ethical and credible science. Academic requirement for research thesis, and ‘publish or perish’ culture of academia for career evaluation of faculties contribute to authorship misconducts. The authorship criteria have been clearly outlined by international guidelines like International Committee of Medical Journals Editors, Committee on Publication Ethics, Council of Science Editors, World Association of Medical Editors. However, the practice of guide, co-guide as authors in students’ thesis articles continues as inappropriate authorship. This is a topic which requires more debate in academia. Historical practices of academia, the power dynamics, and the guidelines of the journals vary and make this dispute even more complicated. In Nepal, we need to expand the discussion among stakeholders from academia, universities, monitoring bodies, ethical committees to journals for a consensus; to ‘put to rest’ this issue and be in line with the international guidelines. Keywords: Authorship guideline; journal article publication; research thesis guide co-guide supervisor

BackgroundSupernumerary sex chromosome aneuploidies (sSCA) are characterized by the presence of one or more additional sex chromosomes in an individual's karyotype; they affect around 1 in 400 individuals. Although there is high variability, each sSCA subtype has a characteristic set of cognitive and physical phenotypes. Here, we investigated the differences in the morphometry of the human corpus callosum (CC) between sex-matched controls 46,XY (N =99), 46,XX (N =93), and six unique sSCA karyotypes: 47,XYY (N =29), 47,XXY (N =58), 48,XXYY (N =20), 47,XXX (N =30), 48,XXXY (N =5), and 49,XXXXY (N =6).MethodsWe investigated CC morphometry using local and global area, local curvature of the CC boundary, and between-landmark distance analysis (BLDA). We hypothesized that CC morphometry would vary differentially along a proposed spectrum of Y:X chromosome ratio with supernumerary Y karyotypes having the largest CC areas and supernumerary X karyotypes having significantly smaller CC areas. To investigate this, we defined an sSCA spectrum based on a descending Y:X karyotype ratio: 47,XYY, 46,XY, 48,XXYY, 47,XXY, 48,XXXY, 49,XXXXY, 46,XX, 47,XXX. We similarly explored the effects of both X and Y chromosome numbers within sex. Results of shape-based metrics were analyzed using permutation tests consisting of 5,000 iterations.ResultsSeveral subregional areas, local curvature, and BLDs differed between groups. Moderate associations were found between area and curvature in relation to the spectrum and X and Y chromosome counts. BLD was strongly associated with X chromosome count in both male and female groups.ConclusionsOur results suggest that X- and Y-linked genes have differential effects on CC morphometry. To our knowledge, this is the first study to compare CC morphometry across these extremely rare groups.