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Abstract: (Pr0.55Ca0.45)(Mn1−y Cr y )O3 (with y =0.00, 0.03 and 0.06) have been prepared by means of a solid-state reaction from stoichiometric powder mixtures of binary oxides. XRPD reveals the formation of the perovskite-type compound for the whole compositions; no evidence for secondary phases may be detected. The structural refinements have been carried out using XRPD data applying the Rietveld method; the lattice parameters of the orthorhombic cell faintly change with composition. On the contrary the tilting of the octahedra results strongly dependent on the concentration of Cr in the 4b site. DC magnetic measurements have been performed as a function of temperature and magnetic field. [Copyright &y& Elsevier]

Abstract: We have studied the effect of thickness on the structure and superconductivity of Nd1.2Ba1.8Cu3O7+x (NdBCO) epitaxial films deposited on SrTiO3 (100) substrates. High quality NdBCO films were deposited by high oxygen pressure sputtering. The samples have been carefully characterized by transport measurements and X-ray diffraction using conventional and synchrotron radiation sources. Two structural transformations are observed. The first one is a crossover from the orthorhombic and twinned structure, typical of thick samples, to a pseudotetragonal phase at thickness lower than 60 unit cells. The pseudotetragonal phase exhibits peculiar X-ray diffuse scattering around the Bragg reflections, associated to nanostructured twinned domains. The second one appears at thickness lower than 20 unit cells and is assigned to a pseudotetragonal–tetragonal transition. The transport properties are not modified at the first crossover, while a substantial decrease of T c and of the number of holes is observed at the pseudotetragonal–tetragonal transformation. Our results suggest that the structural rearrangement and the transport properties are explained by the ordering of Cu(1)O chains. [Copyright &y& Elsevier]

Background:  We evaluate the feasibility of a single-stage posterior corpectomy and circumferential arthrodesis with the aid of spinal navigation for the treatment of traumatic thoracolumbar burst fractures., Methods:  This was a single-center, retrospective study. Demographics, clinical, and radiologic data of 19 patients who underwent surgery at our institution for thoracolumbar burst fractures between 2016 and 2019 were collected. All patients enrolled in the present study underwent surgery by means of posterior fixation and transpedicular corpectomy with the aid of an intraoperative image-guided neuronavigation system., Results:  Postoperative correction of the vertebral height ratio was achieved in all cases, with an average increase of 23.6% ( p  = 0.0005). No statistical differences ( p  = 0.9) were found comparing 1- and 3-month postoperative CT scans, in relation to vertebral height ratio. A statistically significant difference was found between the pre- and postoperative kyphotic angles for the thoracolumbar and lumbar segments ( p  = 0.0018 and 0.005, respectively), but no difference was found between kyphotic angles at the 3-month follow-up. A unilateral approach was performed on 15 patients (79%), while 4 cases (21%) required a bilateral laminectomy. We did not observe any significant intraoperative complication., Conclusion:  Single-stage posterior corpectomy and fixation is a safe and effective approach for thoracic and lumbar burst fractures. It provides excellent 360-degree reconstruction in a single surgical stage with satisfactory results in terms of kyphosis reduction, biomechanical stability, and reduced invasiveness. Spinal navigation represents a fundamental tool to overcome some anatomical limits of the presented technique., Competing Interests: None declared., (Thieme. All rights reserved.)

Despite the recent progress in surgical technology in the last decades, the surgical treatment of skull base lesions still remains a challenge. The purpose of this study was to assess the anatomy of the tentorial and cavernous segment of the fourth cranial nerve as it appears in two different surgical approaches to the skull base: subtemporal transtentorial approach and pretemporal fronto-orbito-zygomatic approach. Four human cadaveric fixed heads were used for the dissection. Using both sides of each cadaveric head, we made 16 dissections: 8 with subtemporal transtentorial technique and 8 with pretemporal fronto-orbito-zygomatic approach. The first segment that extends from the initial point of contact of the fourth cranial nerve with the tentorium (point Q) to its point of entry into its dural channel (point D) presents an average length of 13.5 mm with an extremely wide range and varying between 3.20 and 9.3 mm. The segment 2, which extends from point D to the point of entry into the lateral wall of the cavernous sinus, presents a lesser interindividual variability (mean 10.4 mm, range 15.1-5.9 mm). A precise knowledge of the surgical anatomy of the fourth cranial nerve and its neurovascular relationships is essential to safely approach. The recognition of some anatomical landmarks allows to treat pathologies located in regions of difficult surgical access even when there is an important subversion of the anatomy.

Background: The pseudoautosomal short stature homeobox-containing (SHOX) gene encodes a homeodomain transcription factor involved in cell-cycle and growth regulation. SHOX/SHOX enhancers deletions cause short stature and skeletal abnormalities in a female-dominant fashion; duplications appear to be rare. Neurodevelopmental disorders (NDDs), such as autism spectrum disorders (ASDs), are complex disorders with high heritability and skewed sex ratio; several rare (<1% frequency) CNVs have been implicated in risk., Methods: We analysed data from a discovery series of 90 adult ASD cases, who underwent clinical genetic testing by array-comparative genomic hybridisation (CGH). Twenty-seven individuals harboured CNV abnormalities, including two unrelated females with microduplications affecting SHOX. To determine the prevalence of SHOX duplications and delineate their associated phenotypic spectrum, we subsequently examined array-CGH data from a follow-up sample of 26 574 patients, including 18 857 with NDD (3541 with ASD)., Results: We found a significant enrichment of SHOX microduplications in the NDD cases (p=0.00036; OR 2.21) and, particularly, in those with ASD (p=9.18×10(-7); OR 3.63) compared with 12 594 population-based controls. SHOX duplications affecting the upstream or downstream enhancers were enriched only in females with NDD (p=0.0043; OR 2.69/p=0.00020; OR 7.20), but not in males (p=0.404; OR 1.38/p=0.096; OR 2.21)., Conclusions: Microduplications at the SHOX locus are a low penetrance risk factor for ASD/NDD, with increased risk in both sexes. However, a concomitant duplication of SHOX enhancers may be required to trigger a NDD in females. Since specific SHOX isoforms are exclusively expressed in the developing foetal brain, this may reflect the pathogenic effect of altered SHOX protein dosage on neurodevelopment., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

The XXII World Congress of Psychiatric Genetics, sponsored by the International Society of Psychiatric Genetics, took place in Copenhagen, Denmark, on 12-16 October 2014. A total of 883 participants gathered to discuss the latest findings in the field. The following report was written by student and postdoctoral attendees. Each was assigned one or more sessions as a rapporteur. This manuscript represents topics covered in most, but not all of the oral presentations during the conference, and contains some of the major notable new findings reported.

There have been several reports on the association between the Val(158)Met genetic polymorphism of the catechol-O-methyltransferase (COMT) gene, as well as the serotonin transporter-linked polymorphic region (5-HTTLPR) of the serotonin transporter gene (SLC6A4), and frontolimbic region volumes, which have been suggested to underlie individual differences in emotion processing or susceptibility to emotional disorders. However, findings have been somewhat inconsistent. This study used diffeomorphic anatomic registration through exponentiated Lie algebra (DARTEL) whole-brain voxel-based morphometry to study the genetic effects of COMT Val(158)Met and SLC6A4 5-HTTLPR, as well as their interaction, on the regional gray matter volumes of a sample of 91 healthy volunteers. An interaction of COMT Val(158)Met × SLC6A4 5-HTTLPR genotypes with gray matter volume was found in bilateral parahippocampal gyrus, amygdala, hippocampus, vermis of cerebellum and right putamen/insula. In particular, the gray matter volume in these regions was smaller in individuals who were both COMT-Met and 5-HTTLPR-S carriers, or both COMT-Val and 5-HTTLPR-L homozygotes, as compared with individuals with intermediate combinations of alleles. The interaction of COMT Val(158)Met and SLC6A4 5-HTTLPR adds to the understanding of individual differences in emotion processing., (© The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.)

A number of rare copy number variants (CNVs), including both deletions and duplications, have been associated with developmental disorders, including schizophrenia, autism, intellectual disability, and epilepsy. Pathogenicity may derive from dosage sensitivity of one or more genes contained within the CNV locus. To understand pathophysiology, the specific disease-causing gene(s) within each CNV need to be identified. In the present study, we test the hypothesis that ohnologs (genes retained after ancestral whole-genome duplication events, which are frequently dosage sensitive) are overrepresented in pathogenic CNVs. We selected three sets of genes implicated in copy number pathogenicity: (i) genes mapping within rare disease-associated CNVs, (ii) genes within de novo CNVs under negative genetic selection, and (iii) genes identified by clinical array comparative genome hybridization studies as potentially pathogenic. We compared the proportion of ohnologs between these gene sets and control genes, mapping to CNVs not known to be disease associated. We found that ohnologs are significantly overrepresented in genes mapping to pathogenic CNVs, irrespective of how CNVs were identified, with over 90% containing an ohnolog, compared with control CNVs >100 kb, where only about 30% contained an ohnolog. In some CNVs, such as del15p11.2 (CYFIP1) and dup/del16p13.11 (NDE1), the most plausible prior candidate gene was also an ohnolog, as were the genes VIPR2 and NRXN1, each found in short CNVs containing no other genes. Our results support the hypothesis that ohnologs represent critical dosage-sensitive elements of the genome, possibly responsible for some of the deleterious phenotypes observed for pathogenic CNVs and as such are readily identifiable candidate genes for further study.

Background: Within a therapeutic gene by environment (G × E) framework, we recently demonstrated that variation in the Serotonin Transporter Promoter Polymorphism; 5HTTLPR and marker rs6330 in Nerve Growth Factor gene; NGF is associated with poorer outcomes following cognitive behaviour therapy (CBT) for child anxiety disorders. The aim of this study was to explore one potential means of extending the translational reach of G × E data in a way that may be clinically informative. We describe a 'risk-index' approach combining genetic, demographic and clinical data and test its ability to predict diagnostic outcome following CBT in anxious children., Method: DNA and clinical data were collected from 384 children with a primary anxiety disorder undergoing CBT. We tested our risk model in five cross-validation training sets., Results: In predicting treatment outcome, six variables had a minimum mean beta value of 0.5:5HTTLPR, NGF rs6330, gender, primary anxiety severity, comorbid mood disorder and comorbid externalising disorder. A risk index (range 0-8) constructed from these variables had moderate a predictive ability (AUC = .62-.69) in this study. Children scoring high on this index (5-8) were approximately three times as likely to retain their primary anxiety disorder at follow-up as compared with those children scoring 2 or less., Conclusion: Significant genetic, demographic and clinical predictors of outcome following CBT for anxiety-disordered children were identified. Combining these predictors within a risk index could be used to identify which children are less likely to be diagnosis-free following CBT alone and require longer or enhanced treatment. The 'risk-index' approach represents one means of harnessing the translational potential of G × E data., (© 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.)

Both childhood maltreatment and adult stressful life events are established risk factors for the onset of depression in adulthood. However, the interaction between them can be viewed through two conflicting frameworks. Under a mismatch hypothesis stressful childhoods allow 'adaptive programming' for a stressful adulthood and so can be protective. Only when childhood and adulthood do not match is there a risk of behavioural problems. Alternatively, under the cumulative stress hypothesis we expect increased risk with each additional stressor. It has also been suggested that an individual's genetic background may determine the extent they undergo adaptive programming, and so which of these two hypotheses is relevant. In this study we test for an interaction between exposure to childhood maltreatment and adult stressful life events in a retrospective sample of 455 individuals, using major depression as the outcome. We also test whether this interaction differs by genotype at the 5-HTTLPR, a candidate for an individual's plasticity to adaptive programming. Early maltreatment and stressful life events in adulthood interacted to produce increased risk for depression over each individually (p = 0.055). This supports the cumulative stress hypothesis over the mismatch hypothesis, at least with respect to severe environmental risk factors. This effect was not altered by 5-HTTLPR allele, suggesting there was no difference by genotype in adaptive programming to these events. We suggest that the apparent additional vulnerability to stressful events of those who have experienced maltreatment has clinical relevance, highlighting the importance of providing support beyond the immediate aftermath of maltreatment into adulthood., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Copy number variants (CNVs) at chromosome 16p13.11 have been associated with a range of neurodevelopmental disorders including autism, ADHD, intellectual disability and schizophrenia. Significant sex differences in prevalence, course and severity have been described for a number of these conditions but the biological and environmental factors underlying such sex-specific features remain unclear. We tested the burden and the possible sex-biased effect of CNVs at 16p13.11 in a sample of 10,397 individuals with a range of neurodevelopmental conditions, clinically referred for array comparative genomic hybridisation (aCGH); cases were compared with 11,277 controls. In order to identify candidate phenotype-associated genes, we performed an interval-based analysis and investigated the presence of ohnologs at 16p13.11; finally, we searched the DECIPHER database for previously identified 16p13.11 copy number variants. In the clinical referral series, we identified 46 cases with CNVs of variable size at 16p13.11, including 28 duplications and 18 deletions. Patients were referred for various phenotypes, including developmental delay, autism, speech delay, learning difficulties, behavioural problems, epilepsy, microcephaly and physical dysmorphisms. CNVs at 16p13.11 were also present in 17 controls. Association analysis revealed an excess of CNVs in cases compared with controls (OR = 2.59; p = 0.0005), and a sex-biased effect, with a significant enrichment of CNVs only in the male subgroup of cases (OR = 5.62; p = 0.0002), but not in females (OR = 1.19, p = 0.673). The same pattern of results was also observed in the DECIPHER sample. Interval-based analysis showed a significant enrichment of case CNVs containing interval II (OR = 2.59; p = 0.0005), located in the 0.83 Mb genomic region between 15.49-16.32 Mb, and encompassing the four ohnologs NDE1, MYH11, ABCC1 and ABCC6. Our data confirm that duplications and deletions at 16p13.11 represent incompletely penetrant pathogenic mutations that predispose to a range of neurodevelopmental disorders, and suggest a sex-limited effect on the penetrance of the pathological phenotypes at the 16p13.11 locus.

Objective: To characterize the diagnosis of pancreatic trauma in an athletic population and to raise awareness among health care providers of the possibility of this life- and organ-threatening injury., Background: An 18-year-old, previously healthy female collegiate soccer athlete sustained a direct blow from an opponent's knee between the left and right upper abdominal quadrants while attempting to head the ball. She initially presented with only minimal nausea and discomfort, but this progressed to abdominal pain, tenderness, spasm, and vomiting. She was referred to the emergency department, where she was diagnosed with a pancreatic laceration., Differential Diagnosis: Duodenal, hepatic, or splenic contusion or laceration; hemorrhagic ovarian cyst., Treatment: The patient underwent a distal pancreatectomy and total splenectomy., Uniqueness: Pancreatic injuries, particularly those severe enough to warrant surgical intervention, are extremely rare in athletes., Conclusions: Recognition of a pancreatic injury can be very challenging outside the hospital setting. This is problematic, because a delay in diagnosis is a significant source of preventable morbidity and mortality after this rare injury. Thus, early identification depends on a high index of suspicion, a thorough examination, and close observation. It is imperative that athletic trainers and other health care professionals be able to identify this condition so that referral and management can occur without delay.

Objectives: To examine the association of genetic variants in the syntaxin 1A gene (STX1A) with common forms of migraine, and perform a combined analysis of the data from the current study and previously published reports., Methods: We investigated the parent-to-offspring transmission of rs6951030, rs4363087 and rs2293489 in 191 family trios, each with a proband with childhood-onset migraine, and performed a case-control analysis between the probands and 223 unrelated controls. In addition, we performed a combined data analysis with an overall sample of 567 migraine patients and 720 unrelated controls and performed a migraine-specific gene-network analysis., Results: The transmission disequilibrium test revealed significant transmission distortion of rs4363087 in migraine overall (OR = 1.56, p = 0.006; p = 0.01 after correction for multiple testing) and migraine without aura (OR = 1.58, p = 0.01; corrected p = 0.04). Two-marker haplotype analysis revealed transmission distortion of A-G (rs6951030-rs4363087; OR = 1.47, p = 0.01) and A-C (rs4363087-rs2293489; OR = 0.66, p = 0.01). Combined analysis showed significant association of rs941298 with migraine overall (OR = 1.28, p = 0.004) and migraine without aura (OR = 1.3, p = 0.008). Network analysis identified 24 genes relating STX1A to other migraine candidate genes, including KCNK18 (TRESK channel) involved in the cytoplasmatic calcium signalling together with syntaxin 1A., Conclusion: Our results provide support for the hypothesis that STX1A represents a susceptibility gene for migraine.

Background: An interaction between recent stressful life events (SLEs) and a serotonin transporter promoter polymorphism (5-HTTLPR) in depression has been inconsistently reported. Some of this variability may be due to a previous focus on sub-clinical depression, inclusion of individuals at the lower or upper ends of the age-span, or assumptions concerning the degree of dominance of the low expressing allele. Therefore, a large sample of patients with recurrent clinically diagnosed depression and controls screened for absence of depression was utilised to examine the moderating effect of each 5-HTTLPR genetic model on the association between SLEs and severe depressive episodes., Method: A sample of 1236 recurrent unipolar depression cases and 598 age-matched, never psychiatrically ill controls completed the List of Threatening Experiences Questionnaire to assess the number of SLEs experienced in the 6 months prior to the most severe depressive episode (cases) or interview (controls). DNA extracted from blood or cheek swabs was genotyped for the short (s) and long (l) alleles of 5-HTTLPR., Results: A greater number of SLEs were reported by cases than controls and this held across all genotypic groups. There was no main effect of 5-HTTLPR on depression and no evidence of interaction between total SLEs and any of the 5-HTTLPR genetic models. The results were the same for men and women., Limitations: Utilisation of retrospective self-reported SLEs may have reduced the accuracy of the findings and the cross-sectional design prevents causal inference., Conclusions: This study failed to find evidence of gene-environment interplay in recurrent clinical depression., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Cognitive deficits are rate limiters on recovery in schizophrenia that respond poorly to pharmacotherapy. Cognitive remediation therapy (CRT), a novel psychological therapy, has produced promising outcomes for cognition. However, little is known about the biological mechanisms that might underlie individual differences in CRT response. Catechol-O-Methyltransferase (COMT) is associated specifically with prefrontal cognition. The COMT Val158Met polymorphism is known to have a functional effect on the rate of dopamine degradation, which may be related to cognitive treatment response. This study aimed to determine whether COMT genotype influences cognitive improvement following CRT in schizophrenia. Participants with schizophrenia were recruited from three randomised controlled trials of CRT compared to treatment as usual, and one CRT treatment only trial, each providing 40 CRT sessions. Eighty-seven participants (40%) agreed to participate in the genetic study, and provided DNA for COMT genotyping. Cognitive function and psychopathology were assessed at baseline, post-treatment and 3-6-month follow-up. People with the COMT Val/Met genotype performed more poorly on categories achieved at baseline on the Wisconsin Card Sorting Test (WCST) than those homozygous for the Val or Met allele. Cognitive function improved with CRT but there was no association between this cognitive improvement and COMT genotype, either in the CRT group or in the total sample. The COMT val158Met polymorphism does not appear to be a clinically useful biomarker of cognitive improvement following CRT in schizophrenia. A complex set of factors may influence cognitive change, however, such that the COMT genotype might still have a subtle effect on response to CRT or similar interventions., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Migraine and bipolar disorder are characterized by a high level of co-morbidity, and a common familial-genetic basis has recently been hypothesized for the 2 disorders. Genome-wide association studies have reported strong evidence of association between the polymorphisms rs10994336[T] in the ANK3 gene and rs1006737[A] in the CACNA1C gene and risk of bipolar disorder., Objective: The aim of this study was to evaluate the hypothesis of a genetic linkage between migraine and bipolar disorder by investigating the familial transmission of the 2 bipolar disorder risk polymorphisms, in a sample of family trios with probands with childhood migraine, and unrelated controls., Methods: Our sample comprised 192 family trios, each with a proband with childhood migraine (137 migraine without aura, 44 migraine with aura) and 228 unrelated controls. The markers rs10994336 and rs1006737 were genotyped using a TaqMan single nucleotide polymorphism Genotyping Assay. The transmission disequilibrium test analysis for the family trios and the case-control analysis were performed using the program UNPHASED., Results: The allelic and genotypic transmission disequilibrium test analysis did not show any evidence of transmission distortion of the 2 markers in both migraine overall (rs10994336: OR = 1.61, P = .11; rs1006737: OR = 1.12, P = .49) and in the migraine without aura and migraine with aura subgroups. Likewise, the case-control analysis of alleles and genotypes frequencies did not show any evidence of association., Conclusion: In the present study, we did not find evidence for association between the bipolar disorder risk polymorphisms rs10994336 in the ANK3 gene and rs1006737 in the CACNA1C gene in migraine. However, as these are variants that have a small effect on the risk of bipolar disorder (OR < 1.5), we cannot exclude a similar small effect on migraine susceptibility with the present sample size., (© 2011 American Headache Society.)