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Though zoos and aquariums have become increasingly focused on conservation education, their menageries of unique and diverse learning opportunities have been underused. This practical "NGSS"-aligned guide to field trips at zoos and aquariums is written specifically for science teachers to support broader utilization of zoos and aquariums as educational resources. Common challenges for education at zoos and aquariums are discussed through the context of "ZooU," a new postsecondary-level animal behavior laboratory experience at an aquarium. Recent research using ZooU demonstrated that active learning pedagogy aligned with the "Next Generation Science Standards" ("NGSS") could facilitate expansion of education at zoos and aquariums beyond their conservation education niche. Generally, students indicated that ZooU provided new opportunities for them to explore their own interests, demonstrate their learning, and augment their previous laboratory and aquarium experiences. Following both student self-assessments and researcher assessments of the students' work, integrated analyses revealed that students who engaged in more active learning activities at the aquarium demonstrated a greater increase in skills aligned with the "NGSS." This guide introduces zoos and aquariums as educational resources before focusing on meaningful connections to curricula, creation of active learning activities, differentiation and scaffolding strategies, and assessment for both students and field trips.

While walnut trees on Juglans hindsiix J. regia ‘Paradox’ rootstocks are highly susceptible to crown gall, it is unknown whether this bacterial disease is acquired in the nursery or the orchard. We selected two groups of gall-free trees in nurseries, those adjacent to trees with and without galls. Two years after being transplanted in the orchard, trees in the group adjacent to those with galls had significantly greater — more than four times more — crown gall incidence than those adjacent to trees without galls (14% versus 3%). In addition, trees in prolonged (17-day), bare-root, unrefrigerated storage before transplanting were associated with higher crown-gall incidence. We also found that crown gall can decrease walnut tree productivity. For every quarter of trunk circumference that was galled, there was a 12% decrease in cumulative nut yield over the first 4 years of production.

We reveal surprisingly high kinetic energy release in the intense-field fragmentation of D _3 ^+ to D ^+ + D ^+ + D with 10 ^16 W cm ^−2 , 790 nm, 40 fs (and 7 fs) laser pulses. This feature strongly mimics the behaviour of the D ^+ + D ^+ + D ^+ channel. From the experimental evidence, we conclude that the origin of the feature is due to frustrated tunnelling ionization, the first observation of this mechanism in a polyatomic system. Furthermore, we unravel evidence of frustrated tunnelling ionization in dissociation, both two-body breakup to D + D _2 ^+ and D ^+ + D _2 , and three-body breakup to D ^+ + D + D.

Abstract The finding of a genotype-negative hypertrophic cardiomyopathy (HCM) pedigree with several affected members indicating a familial origin of the disease has driven this study to discover causative gene variants. Genetic testing of the proband and subsequent family screening revealed the presence of a rare variant in the MYBPC3 gene, c.3331−26T>G in intron 30, with evidence supporting cosegregation with the disease in the family. An analysis of potential splice-altering activity using several splicing algorithms consistently yielded low scores. Minigene expression analysis at the mRNA and protein levels revealed that c.3331−26T>G is a spliceogenic variant with major splice-altering activity leading to undetectable levels of properly spliced transcripts or the corresponding protein. Minigene and patient mRNA analyses indicated that this variant induces complete and partial retention of intron 30, which was expected to lead to haploinsufficiency in carrier patients. As most spliceogenic MYBPC3 variants, c.3331−26T>G appears to be non-recurrent, since it was identified in only two additional unrelated probands in our large HCM cohort. In fact, the frequency analysis of 46 known splice-altering MYBPC3 intronic nucleotide substitutions in our HCM cohort revealed 9 recurrent and 16 non-recurrent variants present in a few probands (≤ 4), while 21 were not detected. The identification of non-recurrent elusive MYBPC3 spliceogenic variants that escape detection by in silico algorithms represents a challenge for genetic diagnosis of HCM and contributes to solving a fraction of genotype-negative HCM cases.

Abstract The DISC1 gene is one of the most relevant susceptibility genes for psychosis. However, the complex genetic landscape of this locus, which includes protective and risk variants in interaction, may have hindered consistent conclusions on how DISC1 contributes to schizophrenia (SZ) liability. Analysis from haplotype approaches and brain-based phenotypes can contribute to understanding DISC1 role in the neurobiology of this disorder. We assessed the brain correlates of DISC1 haplotypes associated with SZ through a functional neuroimaging genetics approach. First, we tested the association of two DISC1 haplotypes, the HEP1 (rs6675281-1000731-rs999710) and the HEP3 (rs151229-rs3738401), with the risk for SZ in a sample of 138 healthy subjects (HS) and 238 patients. This approach allowed the identification of three haplotypes associated with SZ (HEP1-CTG, HEP3-GA and HEP3-AA). Second, we explored whether these haplotypes exerted differential effects on n-back associated brain activity in a subsample of 70 HS compared to 70 patients (diagnosis × haplotype interaction effect). These analyses evidenced that HEP3-GA and HEP3-AA modulated working memory functional response conditional to the health/disease status in the cuneus, precuneus, middle cingulate cortex and the ventrolateral and dorsolateral prefrontal cortices. Our results are the first to show a diagnosis-based effect of DISC1 haplotypes on working memory-related brain activity, emphasising its role in SZ.

Gene therapy using Adeno-associated viral vectors (AAV) rescues hearing and balance deficits in mouse models of human disorders. Here, the authors show that AAVAnc80L65 allows efficient cochlear gene transfer in nonhuman primates, and motivate future studies to evaluate gene therapy for hearing and balance disorders.

Abstract Background Osteoarthritis (OA) is a chronic, progressive condition that can be effectively managed via conservative treatments including exercise, weight management and education. Offering these treatments contemporaneously and digitally may increase adherence and engagement due to the flexibility and cost-effectiveness of digital program delivery. The objective of this review was to summarise the characteristics of current digital self-management interventions for individuals with OA and synthesise adherence and attrition outcomes. Methods Electronic databases were searched for randomised controlled trials utilising digital self-management interventions in individuals with OA. Two reviewers independently screened the search results and extracted data relating to study characteristics, intervention characteristics, and adherence and dropout rates. Results Eleven studies were included in this review. Intervention length ranged from 6 weeks to 9 months. All interventions were designed for individuals with OA and mostwere multi-component and were constructed around physical activity. The reporting of intervention adherence varied greatly between studies and limited the ability to form conclusions regarding the impact of intervention characteristics. However, of the seven studies that quantified adherence, six reported adherence > 70%. Seven of the included studies reported attrition rates

Abstract Auditory verbal hallucinations (AVH, ‘hearing voices’) are an important symptom of schizophrenia but their biological basis is not well understood. One longstanding approach proposes that they are perceptual in nature, specifically that they reflect spontaneous abnormal neuronal activity in the auditory cortex, perhaps with additional ‘top down’ cognitive influences. Functional imaging studies employing the symptom capture technique—where activity when patients experience AVH is compared to times when they do not—have had mixed findings as to whether the auditory cortex is activated. Here, using a novel variant of the symptom capture technique, we show that the experience of AVH does not induce auditory cortex activation, even while real speech does, something that effectively rules out all theories that propose a perceptual component to AVH. Instead, we find that the experience of AVH activates language regions and/or regions that are engaged during verbal short-term memory.

Summary: Investigator-generated transcriptomic datasets interrogating circulating immune cell (CIC) gene expression in clinical type 1 diabetes (T1D) have underappreciated re-use value. Here, we repurposed these datasets to create an open science environment for the generation of hypotheses around CIC signaling pathways whose gain or loss of function contributes to T1D pathogenesis. We firstly computed sets of genes that were preferentially induced or repressed in T1D CICs and validated these against community benchmarks. We then inferred and validated signaling node networks regulating expression of these gene sets, as well as differentially expressed genes in the original underlying T1D case:control datasets. In a set of three use cases, we demonstrated how informed integration of these networks with complementary digital resources supports substantive, actionable hypotheses around signaling pathway dysfunction in T1D CICs. Finally, we developed a federated, cloud-based web resource that exposes the entire data matrix for unrestricted access and re-use by the research community.

The data generated here in relates to the research article “CaV1.3 enhanced store operated calcium promotes resistance to androgen deprivation in prostate cancer”. A model of prostate cancer (PCa) progression to castration resistance was employed, with untreated androgen sensitive LNCaP cell line alongside two androgen deprived (bicalutamide) sublines, either 10 days (LNCaP-ADT) or 2 years (LNCaP-ABL) treatment, in addition to androgen insensitive PC3. With this PCa model, qPCR was used to examined fold change in markers linked to androgen resistance, androgen receptor (AR) and neuron specific enolase (NSE), observing an increase under androgen deprivation. In addition, the gene expression of a range of calcium channels was measured, with only the L-type Voltage gated calcium channel, CACNA1D, demonstrating an increase during androgen deprivation. With CACNA1D knockdown the channel was found not to influence the gene expression of calcium channels, ORAI1 and STIM1. The calcium channel blocker (CCB), nifedipine, was employed to determine the impact of CaV1.3 on the observed store release and calcium entry measured via Fura-2AM ratiometric dye in our outlined PCa model. In both the presence and absence of androgen deprivation, nifedipine was found to have no impact on store release induced by thapsigargin (Tg) in 0mM Ca2+ nor store operated calcium entry (SOCE) following the addition of 2mM Ca2+. However, CACNA1D siRNA knockdown was able to reduce SOCE in PC3 cells. The effect of nifedipine on CaV1.3 in PCa biology was measured through cell proliferation assay, with no observed change in the presence of CCB. While siCACNA1D reduced PC3 cell proliferation. This data can be reused to inform new studies investigating altered calcium handling in androgen resistant prostate cancer. It provides insight into the mechanism of CaV1.3 and its functional properties in altered calcium in cancer, which can be of use to researchers investigating this channel in disease. Furthermore, it could be helpful in interpreting studies investigating CCB's as a therapeutic and in the development of future drugs targeting CaV1.3.

Abstract A subset of CD4 + lymphocytes, regulatory T cells (Tregs), are necessary for central tolerance and function as suppressors of autoimmunity against self-antigens. The SRC-3 coactivator is an oncogene in multiple cancers and is capable of potentiating numerous transcription factors in a wide variety of cell types. Src-3 knockout mice display broad lymphoproliferation and hypersensitivity to systemic inflammation. Using publicly available bioinformatics data and directed cellular approaches, we show that SRC-3 also is highly enriched in Tregs in mice and humans. Human Tregs lose phenotypic characteristics when SRC-3 is depleted or pharmacologically inhibited, including failure of induction from resting T cells and loss of the ability to suppress proliferation of stimulated T cells. These data support a model for SRC-3 as a coactivator that actively participates in protection from autoimmunity and may support immune evasion of cancers by contributing to the biology of Tregs.

BackgroundAlmost 50,000 men in the United Kingdom (UK) are diagnosed each year with prostate cancer (PCa). Secondary referrals for investigations rely on serum prostate-specific antigen (PSA) levels and digital rectal examination. However, both tests lack sensitivity and specificity, resulting in unnecessary referrals to secondary care for costly and invasive biopsies.Materials and MethodsSerum samples and clinical information were collected from N = 125 age-matched patients (n = 61 non-PCa and n = 64 PCa) and analyzed using Biochip Array Technology on high-sensitivity cytokine array I (IL-2, IL-4, IL-6, IL-8, IL-10, IL-1α, IL-1β, TNFα, MCP-1, INFγ, EGF, and VEGF), cerebral array II (CRP, D-dimer, neuron-specific enolase, and sTNFR1), and tumor PSA oncology array (fPSA, tPSA, and CEA).ResultsThe data showed that 11/19 (68.8%) markers were significantly different between the non-PCa and the PCa patients. A combination of EGF, log10 IL-8, log10 MCP-1, and log10 tPSA significantly improved the predictive potential of tPSA alone to identify patients with PCa (DeLong, p < 0.001). This marker combination had an increased area under the receiver operator characteristic (0.860 vs. 0.700), sensitivity (78.7 vs. 68.9%), specificity (76.5 vs. 67.2%), PPV (76.2 vs. 66.7%), and NPV (79.0 vs. 69.4%) compared with tPSA.ConclusionsThe novel combination of serum markers identified in this study could be employed to help triage patients into “low-” and “high-risk” categories, allowing general practitioners to improve the management of patients in primary care settings and potentially reducing the number of referrals for unnecessary, invasive, and costly treatments.

Abstract Background Glucocorticoid therapy is the most common cause of iatrogenic osteoporosis. Less is known regarding the effect of glucocorticoids when used as replacement therapy on bone remodelling in patients with adrenal insufficiency. Enhanced intracellular conversion of inactive cortisone to active cortisol, by 11 beta-hydroxysteroid dehydrogenase type 1(11β-HSD1) and other enzymes leading to alterations in glucocorticoid metabolism, may contribute to a deleterious effect on bone health in this patient group. Methods Study design: An open crossover prospective study randomizing ten hypopituitary men, with severe ACTH deficiency, to three commonly used hydrocortisone dose regimens. Measurements: Following 6 weeks of each regimen, patients underwent 24-h serum cortisol/cortisone sampling, measurement of bone turnover markers, and a 24-h urine collection for measurement of urinary steroid metabolites by gas chromatography-mass spectrometry (GC-MS). Serum cortisone and cortisol were analysed by liquid chromatography-mass spectrometry (LC-MS). Results Dose-related and circadian variations in serum cortisone were seen to parallel those for cortisol, indicating conversion of ingested hydrocortisone to cortisone. The median area under the curve (AUC) of serum cortisone was significantly higher in patients on dose A (20 mg/10 mg) [670.5 (IQR 621–809.2)] compared to those on dose C (10 mg/5 mg) [562.8 (IQR 520.1–619.6), p = 0.01]. A negative correlation was observed between serum cortisone and bone formation markers, OC [1–49] (r = − 0.42, p = 0.03), and PINP (r = − 0.49, p = 0.01). There was a negative correlation between the AUC of night-time serum cortisone levels with the bone formation marker, OC [1–49] (r = − 0.41, p = 0.03) but there were no significant correlations between day-time serum cortisone or cortisol with bone turnover markers. There was a negative correlation between total urinary cortisol metabolites and the bone formation markers, PINP (r = − 0.39, p = 0.04), and OC [1–49] (r = − 0.35, p = 0.06). Conclusion Serum cortisol and cortisone and total urinary corticosteroid metabolites are negatively associated with bone turnover markers in patients receiving replacement doses of hydrocortisone, with nocturnal glucocorticoid exposure having a potentially greater influence on bone turnover. Trial registration Irish Medicines Board Clinical Trial Number – CT900/459/1 and EudraCT Number – 2007-005018-37 . Registration date: 07-09-2007.

Objective: Although PU.1/Spi1 is known as a master regulator for macrophage development and function, we have reported previously that it is also expressed in adipocytes and is transcriptionally induced in obesity. Here, we investigated the role of adipocyte PU.1 in the development of the age-associated metabolic syndrome.Methods: We generated mice with adipocyte-specific PU.1 knockout, assessed metabolic changes in young and older adult PU.1fl/fl (control) and AdipoqCre PU.1fl/fl (aPU.1KO) mice, including body weight, body composition, energy expenditure, and glucose homeostasis. We also performed transcriptional analyses using RNA-Sequencing of adipocytes from these mice.Results: aPU.1KO mice have elevated energy expenditure at a young age and decreased adiposity and increased insulin sensitivity in later life. Corroborating these observations, transcriptional network analysis indicated the existence of validated, adipocyte PU.1-modulated regulatory hubs that direct inflammatory and thermogenic gene expression programs.Conclusion: Our data provide evidence for a previously uncharacterized role of PU.1 in the development of age-associated obesity and insulin resistance.

Category: Ankle Introduction/Purpose: The traditional modified Brostrom-Gould has long been the procedure of choice for addressing chronic lateral ankle instability. However, more robust techniques including anatomic reconstruction are favored for larger deformity, poor tissue quality and revision surgery. Given the inherent disadvantages of allograft and non-elastic synthetic materials, material science has sought to impact the graft choice providing alternative load sharing, permeable materials with high strength. Our institution has performed anatomic lateral ligament stabilization, termed the 'ATLAS' procedure, using a novel synthetic graft (Artelon, Marietta, GA) with anecdotal success in recent years. In this study, we present our surgical technique and early experience. Methods: A retrospective cohort review was performed, evaluating the failure rate, complications and radiographic changes in anatomic alignment. A review of all patients undergoing the ATLAS procedure was performed, a total of 27 patients were included. The study included only those patients with at least 1 year follow up from the procedure. Results: Only one patient had symptoms of early failure of the procedure, while none of the patients required a revision procedure. The most common complication was minor wound dehiscence (11.1%). Overall, our short-term results with this procedure were excellent. Conclusion: We conclude that the ATLAS procedure is a predictable and effective lateral ligament reconstruction technique with no donor site morbidity, no donor tissue transmission risk, low risk of over-constraint and accomplished with a predictable technique.

Category: Ankle; Sports; Other Introduction/Purpose: Lateral ankle instability is not uncommon after osseous cuts and soft tissue releases are performed during Total Ankle Arthroplasty (TAA), particularly with varus malalignment. The purpose of the present study was to compare the outcomes of ankles that underwent TAA with concurrent Brostrom-Gould (BG) or Anatomic Lateral Ankle Stabilization (ATLAS) at a minimum of 1-year follow-up. Methods: Thirty-eight TAA's underwent BG (21 INFINITY, 4 CADENCE) or ATLAS (13 INBONE-2) between August 2015 and February 2019 at a single institution and were at least 1 year postoperative (mean 18.3 months, range 12-40). Baseline patient demographics, characteristics, and operative factors were assessed via medical record and chart reviews. Radiographs parameters were measured preoperatively, at 6 weeks postoperative, and during the latest follow-up. Revisions, reoperations, and complications were classified according to the criteria established by Vander Griend et al. and Glazebrook et el., respectively. Univariate and multivariate analyses were performed. Results: Survivorship for TAA with concurrent BG/ATLAS was 97%. Overall, TAA with concurrent BG had higher incidences of early TAA revision (4%), recurrent instability (4%), reoperation (16%), and complications (29%) compared to ATLAS. Postoperative coronal and sagittal tibiotalar alignment changes were significant for both groups (p< 0.001, p=0.014); however, the differences were greater for ATLAS (p= 0.045, p

Category: Ankle; Other Introduction/Purpose: More than 50% of patients undergoing Total Ankle Arthroplasty (TAA) have some degree of coronal deformity, which is the most common reason for additional procedures. The purpose of the present study was to assess the early clinical and radiographic outcomes for patients who underwent TAA and Anatomic Lateral Ankle Stabilization (ATLAS) using synthetic graft for instability in moderate and severe preoperative varus alignment. Methods: Seven ankles with moderate or severe varus alignment underwent TAA with a 3rd generation prosthesis (INBONE-2) and ATLAS using synthetic graft between September 2018 and February 2019 at a single institution, and were at least 1 year postoperative (mean 13.3 months, range 12-15). Medical records and charts were reviewed for any revisions, reoperations, or complications. Weight bearing radiographs were assessed using coronal and sagittal alignment parameters preoperatively, and during the latest follow-up. Results: Survivorship for INBONE-2 with ATLAS was 100%; recurrent instability was not observed. Symptomatic talonavicular joint arthritis was recorded for a single patient 12 months postoperatively; there were no revisions, or reoperations. Tibiotalar coronal alignment improved significantly from 17.7 +- 9.3 (range, 10.1-33.6) to 2.3 +- 1.2 (range, 0.9-4.4) degrees (p

Tumor-induced osteomalacia (TIO) is an ultrarare disorder that is caused by renal phosphate wasting due to uncontrolled tumoral production of fibroblast growth factor 23 (FGF23) from phosphaturic mesenchymal tumors. Surgical removal of the tumor is curative. There is limited information on the biochemical changes in mineral metabolism and bone remodeling activity after surgery, but it is reported that surgery is followed by a hungry bone syndrome (HBS) with hypocalcemia and secondary hyperparathyroidism. We report the biochemical response to surgery in two patients, who presented with severe TIO, as manifested by proximal myopathy, multiple stress fractures, high FGF23, low serum phosphate, low maximum renal phosphate reabsorption threshold (TmP/GFR), and low 1,25-dihydroxy-vitamin D (1,25(OH)2D). Prior to surgery, both patients developed secondary hyperparathyroidism and one case had progressed to tertiary hyperparathyroidism. After surgery there was normalization of FGF23, TmP/GFR, and phosphate. High 1,25(OH)2D was recorded. One patient had hypocalcaemia and worsening secondary hyperparathyroidism consistent with HBS; the other patient did not have hypocalcemia but had worsening tertiary hyperparathyroidism that only resolved with cinacalcet. There was a marked increase in bone remodeling markers, both resorption and formation, consistent with a high bone turnover state. There was a different pattern of change in bone specific alkaline phosphatase, reflecting healing of osteomalacia. Biochemical monitoring in the post-surgical management of TIO is warranted for guiding adjustments in medical intervention, both short-term and long-term. Future use of burosumab prior to surgery for TIO may ameliorate the immediate post-surgery effects.

BackgroundWhile multiple studies have examined the brain functional correlates of reward, meta-analyses have either focused on studies using the monetary incentive delay (MID) task, or have adopted a broad strategy, combining data from studies using both monetary and non-monetary reward, as probed using a wide range of tasks.ObjectiveTo meta-analyze fMRI studies that used monetary reward and in which there was a definable cue-reward contingency. Studies were limited to those using monetary reward in order to avoid potential heterogeneity from use of other rewards, especially social rewards. Studies using gambling or delay discounting tasks were excluded on the grounds that reward anticipation is not easily quantifiable.Study eligibilityEnglish-language fMRI studies (i) that reported fMRI findings on healthy adults; (ii) that used monetary reward; and (iii) in which a cue that was predictive of reward was compared to a no win (or lesser win) condition. Only voxel-based studies were included; those where brain coverage was incomplete were excluded.Data sourcesOvid, Medline and PsycInfo, from 2000 to 2020, plus checking of review articles and meta-analyses.Data synthesisData were pooled using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI). Heterogeneity among studies was examined using the I2 statistic. Publication bias was examined using funnel plots and statistical examination of asymmetries. Moderator variables including whether the task was pre-learnt, sex distribution, amount of money won and width of smoothing kernel were examined.ResultsPooled data from 45 studies of reward anticipation revealed activations in the ventral striatum, the middle cingulate cortex/supplementary motor area and the insula. Pooled data from 28 studies of reward delivery again revealed ventral striatal activation, plus cortical activations in the anterior and posterior cingulate cortex. There was relatively little evidence of publication bias. Among moderating variables, only whether the task was pre-learnt exerted an influence.ConclusionsAccording to this meta-analysis monetary reward anticipation and delivery both activate the ventral but not the dorsal striatum, and are associated with different patterns of cortical activation.

Category: Bunion; Midfoot/Forefoot; Other Introduction/Purpose: Potential shortening of the first ray is an important consideration when performing a first tarsometatarsal (TMTJ) fusion. However, no previous study has sought to directly quantify the resultant shortening after TMTJ fusion. The purpose of the present anatomic study was to directly assess and compare shortening of the first ray using two joint preparation techniques (curettage, planal resection) for first TMTJ fusion. Methods: Ten pairs of matched lower extremity cadaver specimens were divided into two groups. Preoperative length assessments were performed at the first TMTJ dorsally and plantarly using a digital caliper. In Group 1, joint preparation for first TMTJ fusion was performed with curettage, whereas specimens in Group 2 underwent planal resection. Post-operative length assessments were repeated. All data was analyzed using two-tailed Students t-tests. Results: Mean shortening of the first ray following curettage was 1.1 (range, 0.3 to 2.0) mm dorsally and 1.6 (range, 0.6 to 3.7) mm plantarly; while mean shortening following planal resection was 4.5 (range, 2.7 to 7.9) mm dorsally and 4.6 (range, 2.4 to 8.9) mm plantarly. The measured differences were statistically significant (p

Background This study assessed the prevalence of left ventricular (LV) involvement and characterized the clinical, electrocardiographic, and imaging features of LV phenotype in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Differential diagnosis between ARVC‐LV phenotype and dilated cardiomyopathy (DCM) was evaluated. Methods and Results The study population included 87 ARVC patients (median age 34 years) and 153 DCM patients (median age 51 years). All underwent cardiac magnetic resonance with quantitative tissue characterization. Fifty‐eight ARVC patients (67%) had LV involvement, with both LV systolic dysfunction and LV late gadolinium enhancement (LGE) in 41/58 (71%) and LV‐LGE in isolation in 17 (29%). Compared with DCM, the ARVC‐LV phenotype was statistically significantly more often characterized by low QRS voltages in limb leads, T‐wave inversion in the inferolateral leads and major ventricular arrhythmias. LV‐LGE was found in all ARVC patients with LV systolic dysfunction and in 69/153 (45%) of DCM patients. Patients with ARVC and LV systolic dysfunction had a greater amount of LV‐LGE (25% versus 13% of LV mass; P

Background: Up to 30% of patients with schizophrenia are resistant to antipsychotic drug treatment, with 60% of such cases also failing to respond to clozapine. Deep brain stimulation (DBS) has been used in treatment resistant patients with other psychiatric disorders, but there is a lack of trials in schizophrenia, partly due to uncertainties over where to site the electrodes. This trial aimed to examine the effectiveness of nucleus accumbens (NAcc) and subgenual anterior cingulate cortex (subgenual ACC) targeted DBS; the primary outcome measure was PANSS total score, as assessed fortnightly. Methods: Eight patients with schizophrenia, who met criteria for treatment resistance and were also resistant to/intolerant of clozapine, were randomly assigned using central allocation to receive DBS in the NAcc or subgenual ACC. An open stabilization phase lasting at least six months was followed by a randomized double-blind crossover phase lasting 24 weeks in those who met symptomatic improvement criteria. The primary end-point was a 25% improvement in PANSS total score. (ClinicalTrials.gov Identifier: NCT02377505; trial completed). Findings: One implanted patient did not receive DBS due to complications of surgery. Of the remaining 7 patients, 2/3 with NAcc and 2/4 with subgenual ACC electrode placements met the symptomatic improvement criteria (58% and 86%, and 37% and 68% improvement in PANSS total score, respectively). Three of these patients entered the crossover phase and all showed worsening when the stimulation was discontinued. The fourth patient worsened after the current was switched off accidentally without her or the investigators’ knowledge. Physical adverse events were uncommon, but two patients developed persistent psychiatric adverse effects (negative symptoms/apathy and mood instability, respectively). Interpretation: These preliminary findings point to the possibility of DBS having therapeutic effects in patients with schizophrenia who do not respond to any other treatment. Larger trials with careful attention to blinding will be necessary to establish the extent of the benefits and whether these can be achieved without psychiatric side-effects.

Background: An alteration in self/other differentiation has been proposed as a basis for several symptoms in schizophrenia, including delusions of reference and social functioning deficits. Dysfunction of the right temporo-parietal junction (TPJ), a region linked with social cognition, has been proposed as the basis of this alteration. However, imaging studies of self- and other-processing in schizophrenia have shown, so far, inconsistent results. Methods: Patients with schizophrenia and healthy controls underwent fMRI scanning while performing a task with three conditions: self-reflection, other-reflection and semantic processing. Results: Both groups activated similar brain regions for self- and other-reflection compared to semantic processing, including the medial prefrontal cortex, the precuneus and the TPJ. Compared to healthy subjects, patients hyperactivated the left lateral frontal cortex during self- and other-reflection. In other-reflection, compared to self-reflection, patients failed to increase right TPJ activity. Conclusions: Altered activity in the right TPJ supports a disturbance in self/other differentiation in schizophrenia, which could be linked with psychotic symptoms and affect social functioning in patients. Hyperactivity of the lateral frontal cortex for self- and other-reflection suggests the presence of greater cognitive demand to perform the task in the patient group. Keywords: Psychosis, Schizophrenia, Self-reflection, Other-reflection, fMRI, Temporo-parietal junction

Objectives: The profiles of cortical abnormalities in schizophrenia and bipolar disorder, and how far they resemble each other, have only been studied to a limited extent. The aim of this study was to identify and compare the changes in cortical morphology associated with these pathologies. Methods: A total of 384 subjects, including 128 patients with schizophrenia, 128 patients with bipolar disorder and 127 sex-age-matched healthy subjects, were examined using cortical surface-based morphology. Four cortical structural measures were studied: cortical volume (CV), cortical thickness (CT), surface area (SA) and gyrification index (GI). Group comparisons for each separate cortical measure were conducted. Results: At a threshold of P = 0.05 corrected, both patient groups showed significant widespread CV and CT reductions in similar areas compared to healthy subjects. However, the changes in schizophrenia were more pronounced. While CV decrease in bipolar disorder was exclusively explained by cortical thinning, in schizophrenia it was driven by changes in CT and partially by SA. Reduced GI was only found in schizophrenia. The direct comparison between both disorders showed significant reductions in all measures in patients with schizophrenia. Conclusions: Cortical volume and cortical thickness deficits are shared between patients with schizophrenia and bipolar disorder, suggesting that both pathologies may be affected by similar environmental and neurodegenerative factors. However, the exclusive alteration in schizophrenia of metrics related to the geometry and curvature of the brain cortical surface (SA, GI) suggests that this group is influenced by additional neurodevelopmental and genetic factors. Keywords: Neuroimaging, Schizophrenia, Bipolar disorder, Surface-based morphometry, Cortical thickness, Surface area, Gyrification index

Abstract Background The effect of cognitive behavioural therapy for psychosis (CBTp) on the core symptoms of schizophrenia has proven contentious, with current meta-analyses finding at most only small effects. However, it has been suggested that the effects of CBTp in areas other than psychotic symptoms are at least as important and potentially benefit from the intervention. Method We meta-analysed RCTs investigating the effectiveness of CBTp for functioning, distress and quality of life in individuals diagnosed with schizophrenia and related disorders. Data from 36 randomised controlled trials (RCTs) met our inclusion criteria- 27 assessing functioning (1579 participants); 8 for distress (465 participants); and 10 for quality of life (592 participants). Results The pooled effect size for functioning was small but significant for the end-of-trial (0.25: 95% CI: 0.14 to 0.33); however, this became non-significant at follow-up (0.10 [95%CI -0.07 to 0.26]). Although a small benefit of CBT was evident for reducing distress (0.37: 95%CI 0.05 to 0.69), this became nonsignificant when adjusted for possible publication bias (0.18: 95%CI -0.12 to 0.48). Finally, CBTp showed no benefit for improving quality of life (0.04: 95% CI: -0.12 to 0.19). Conclusions CBTp has a small therapeutic effect on functioning at end-of-trial, although this benefit is not evident at follow-up. Although CBTp produced a small benefit on distress, this was subject to possible publication bias and became nonsignificant when adjusted. We found no evidence that CBTp increases quality of life post-intervention.

The Open Source Geospatial Foundation’s (OSGeo) vision is to empower everyone, from pre-university students to professionals, with open source geospatial applications, tools and resources. In 2017, OSGeo decided to participate for the first time in the Code-in competition. Google Code-in (GCI) is an annual online competition aimed at introducing pre-university students (13–17 years) to open source projects, development and communities, through short 3–5 hour tasks. This is a unique opportunity to interact with pre-university students and to encourage them to become part of OSGeo. In this paper, we present OSGeo’s involvement in GCI with the purpose of establishing lessons learned to improve our approach in the next editions of GCI. Over the 51 days of the competition, 279 students completed 649 OSGeo tasks. Students consistently communicated with the mentors to discuss submission and receive inputs from the wide community of developers too. During the GCI, the mentors reviewed the students’ work and provided suggestions and feedback. Generally, the submissions were good and some of them are now part of the projects. As this was our first time participating in GCI these issues are seen as lessons learned and strategies to improve the process will be implemented based on the mentors’ experience. It is key to encourage these students to continue contributing to the OSGeo community, as they will bring new energy and ideas into the organisation; for many of these young students, this competition is a way to introduce them to the geospatial industry.

Public health is increasingly engaging with multi-faceted obesity prevention efforts. Although parks represent key community assets for broader public health, they may not be distributed equitably and associations with obesity are equivocal. We investigated park access and quality relative to deprivation and obesity with individual-level data from the Yorkshire Health Study. Compared to the least deprived areas, the moderately and most deprived areas had a greater park access and park quality in terms of features and amenities. However, parks in the moderately and most deprived areas also had the most safety concerns and incivilities. Although deprivation was associated with obesity, contrary to current policy guidance, both park access and quality appear less important for understanding variations in obesity within this study. Although sub-group analyses by deprivation tertile revealed that low quality park amenities in highly and moderately deprived areas may be important for understanding obesity prevalence, all other associations were non-significant.