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Brain stimulation has emerged as a powerful tool in human neuroscience, becoming integral to next-generation psychiatric and neurologic therapeutics. Theta-burst stimulation (TBS), in which electrical pulses are delivered in rhythmic bouts of 3–8 Hz, seeks to recapitulate neural activity seen endogenously during cognitive tasks. A growing literature suggests that TBS can be used to alter or enhance cognitive processes, but little is known about how these stimulation events influence underlying neural activity. Our study sought to investigate the effect of direct electrical TBS on mesoscale neural activity in humans by asking (1) whether TBS evokes persistent theta oscillations in cortical areas, (2) whether these oscillations occur at the stimulated frequency, and (3) whether stimulation events propagate in a manner consistent with underlying functional and structural brain architecture. We recruited 20 neurosurgical epilepsy patients with indwelling electrodes and delivered direct cortical TBS at varying locations and frequencies. Simultaneous iEEG was recorded from non-stimulated electrodes and analyzed to understand how TBS influences mesoscale neural activity. We found that TBS rapidly evoked theta rhythms in widespread brain regions, preferentially at the stimulation frequency, and that these oscillations persisted for hundreds of milliseconds post stimulation offset. Furthermore, the functional connectivity between recording and stimulation sites predicted the strength of theta response, suggesting that underlying brain architecture guides the flow of stimulation through the brain. By demonstrating that cortical TBS induces frequency-specific oscillatory responses, our results suggest this technology can be used to directly and predictably influence the activity of cognitively-relevant brain networks. • Theta-burst stimulation of human cortex induces theta oscillations elsewhere in the brain. • Induced rhythms are specific to the stimulation frequency between 3 and 8 Hz. • Functional connections predict how stimulation flows from a target site to other regions. [ABSTRACT FROM AUTHOR]

Study Objective: Compare clinical outcomes and physician attitudes toward tubal occlusion and salpingectomy during cesarean section.Design: Retrospective cohort study with survey.Setting: Private hospital in Cincinnati, Ohio.Patients: Women aged ≥18 years undergoing permanent contraception during cesarean delivery with and without salpingectomy from January 2016 to December 2017.Interventions: Rate measurements of permanent contraception during cesarean section by salpingectomy versus tubal occlusion. Online survey assessment of study population physicians' attitudes toward salpingectomy.Measurements and Main Results: Study subjects identified using Current Procedural Terminology codes. Subject demographics, operative details, and perioperative morbidity indicators were identified by chart review. A total of 363 subjects were included: 116 (32%) had salpingectomies, and 247 (68%) had tubal occlusions. Study variables were compared using Wilcoxon rank sum and Fisher exact tests. Despite similar cohort demographics, salpingectomy increased mean operative time by 6.5 minutes compared with tubal occlusion (p = .001). Compared with subjects who had a salpingectomy, those who had a tubal occlusion had more postoperative symptomatic anemia (5.7% vs 0.9%) and infection (6.9% vs 1.7%). The primary surgeon was identified by logistic regression as the factor most predictive of salpingectomy (p <.001). Of 30 physicians, 23 (77%) completed the survey, and these physicians performed 80% of procedures. Physicians did not differ by sex, age, years of practice, solo vs group practice, or hospital-employed vs private practice when compared with the number or rate of salpingectomies performed. Cancer risk reduction was the most common physician-identified salpingectomy benefit (17 of 23, 74%). A total of 65% believed that salpingectomy posed additional risks, but 70% believed the benefits were equal to or greater than the risks. Of the 23 (87%) who completed the survey, 20 believed that salpingectomy added no additional operative time and was cost-neutral.Conclusion: Relative to tubal ligation, salpingectomy during cesarean section increases operative time but not perioperative morbidity. Physicians do not seem biased against salpingectomy and express awareness of published benefits and risks, yet it is not the dominant surgical approach. [ABSTRACT FROM AUTHOR]

Globally, building codes tend to focus on life safety without consideration for the continuous use of buildings after a disaster. Post-earthquake functional recovery is an emerging concept in the built environment that aims at incorporating recovery-based objectives into building codes. However, to date, post-earthquake functional recovery is predominantly recognised from engineering perspectives with minimal inclusion of users' input. To enhance post-earthquake functional recovery for effective risk reduction, this study introduces conceptual frameworks that expand the scope of building functionality through socio-technical systems (STS) thinking. While engineers focus on the technical aspects of buildings, users emphasise additional facets that include social context. The adoption of the STS theory guides the development of building-system functionality frameworks, examining perspectives at both the micro and macro levels. At the micro level, users prioritise essential building services, while on the macro level, externalities that can impact the overarching functionality of a building are taken into consideration. The building-system functionality frameworks have a significant impact on both functionality and functional recovery following a disaster. By prioritising users' perspectives, the objective of the building-system functionality is to enhance societal engagement in integrating functional recovery criteria into building codes. [ABSTRACT FROM AUTHOR]

Abstract: Thought disorder as well as language and communication disturbances are associated with schizophrenia and are over-represented in clinically unaffected relatives of schizophrenics. All three kinds of dysfunction involve some element of deviant verbalizations, most notably, semantic anomalies. Of particular importance, thought disorder characterized primarily by deviant verbalizations has a higher recurrence in relatives of schizophrenic patients than schizophrenia itself. These findings suggest that deviant verbalizations may be more penetrant expressions of schizophrenia susceptibility genes than schizophrenia. This paper reviews the evidence documenting the presence of thought, language and communication disorders in schizophrenic patients and in their first-degree relatives. This familial aggregation potentially implicates genetic factors in the etiology of thought disorder, language anomalies, and communication disturbances in schizophrenia families. We also present two examples of ways in which thought, language and communication disorders can enrich genetic studies, including those involving schizophrenia. [Copyright &y& Elsevier]

Objective: To describe the course of patients with juvenile dermatomyositis (JDM) treated effectively without systemic corticosteroids. Study design: A retrospective study of 38 patients with JDM treated at a tertiary care children''s hospital identified 8 patients who had never received corticosteroids. Disease presentation and course, pharmacologic, and ancillary treatments were recorded. Results: Patients in the no corticosteroid group were followed for a median of 2.8 years (range, 2.1 to 9.5 years). Treatment was primarily with intravenous immunoglobulin (IVIG) (75%) and methotrexate (50%), with favorable response in all. No serious treatment complications were observed; headaches were reported by 3 patients receiving IVIG. Two patients had a myositis flare after discontinuing all medications for more than 1 year; complete resolution of symptoms was observed after either 1 or 2 further doses of IVIG. Two patients had calcinosis (at 1 and 9 years of disease); however, no patient had joint contractures, muscle atrophy, lipodystrophy, or functional limitations. Conclusions: Systemic corticosteroids can be avoided in a select group of patients with JDM. Alternative agents such as methotrexate and IVIG may be prescribed to effectively treat JDM and prevent complications. [Copyright &y& Elsevier]

Recent studies have established an important role for rare genomic deletions and duplications in the etiology of schizophrenia. This research suggests that the genetic architecture of neuropsychiatric disorders includes a constellation of rare mutations in many different genes. Mutations that confer substantial risk for schizophrenia have been identified at several loci, most of which have also been implicated in other neurodevelopmental disorders, including autism. Genetic heterogeneity is a characteristic of schizophrenia; conversely, phenotypic heterogeneity is a characteristic of all schizophrenia-associated mutations. Both kinds of heterogeneity probably reflect the complexity of neurodevelopment. Research strategies must account for both genetic and clinical heterogeneity to identify the genes and pathways crucial for the development of neuropsychiatric disorders. [Copyright &y& Elsevier]

Deficiency of adenosine deaminase 2 (DADA2) is a recessively inherited autoinflammatory disorder caused by a loss of functional ADA2 protein. TNF inhibition (TNFi) has proven to be highly effective in treating inflammatory manifestations. We sought to explore the pathophysiology and the underlying mechanisms of TNF-inhibitor response in these patients. We performed Sanger sequencing of the ADA2 gene. We used flow cytometry, intracellular cytokine staining, transcriptome analysis, immunohistochemistry, and cell differentiation experiments to define an inflammatory signature in patients with DADA2 and studied their response to TNF-inhibitor treatment. We demonstrated increased inflammatory signals and overproduction of cytokines mediated by IFN and nuclear factor kappa B pathways in patients' primary cells. Treatment with TNFi led to reduction in inflammation, rescued the skewed differentiation toward the proinflammatory M1 macrophage subset, and restored integrity of endothelial cells in blood vessels. We also report 8 novel disease-associated variants in 7 patients with DADA2. Our data explore the cellular mechanism underlying effective treatment with TNFi therapies in DADA2. DADA2 vasculitis is strongly related to the presence of activated myeloid cells, and the endothelial cell damage is rescued with anti-TNF treatment. [ABSTRACT FROM AUTHOR]

: BackgroundVisual motion processing is compromised in schizophrenia, as shown in deficient velocity discrimination. Processing of motion signals comprises progressive stages along the geniculate-striate-extrastriate-cortex pathway. Based on neurophysiologic and brain lesion studies, a velocity discrimination deficit can implicate early-stage motion processing if it is contrast-dependent or late-stage motion processing if it is contrast-independent.: MethodsTo determine which stage underlies the deficient velocity discrimination in schizophrenia, we examined the effects of visual contrast on velocity discrimination. We measured velocity discrimination thresholds in schizophrenia patients (n = 34) and normal control subjects (n = 17) at both low and high contrasts, using each subject''s contrast detection threshold to equate contrast levels.: ResultsSchizophrenia patients showed poor velocity discrimination that improved little with high contrast, whereas normal control subjects showed enhanced velocity discrimination with increased contrast.: ConclusionsThe finding that the velocity discrimination deficit in schizophrenia is independent of contrast modulation implicates the later, rather than the earlier, stages of motion processing, which is mediated in the extrastriate cortex. [Copyright &y& Elsevier]

Derived from a wider study of place-based economic, social, cultural and environmental regeneration initiatives in small regional New Zealand towns, and reflecting on international research that emphasises the importance of long-term collaborative effort, effective governance and locally-based leadership in regional regeneration, this paper examines the ways locally-based benevolent property development entrepreneurs are attempting to contribute to their regional town-centres. The experience of towns in mid and South Canterbury in the South Island of New Zealand, where national and global commercial property developers are reluctant to invest, are used as case studies. We discuss how property-led town-centre regeneration in small regional towns in New Zealand such as these may best be characterised. This work is then used to outline a policy agenda that would help local government and allied stakeholders to engage more effectively and cooperatively with local property developers. This work has relevance for an international audience interested in the town-centre regeneration challenges faced by the residents and local governments of small regional towns in neo-liberal polities. • Local benevolent entrepreneurs are investing in regional town-centre regeneration in New Zealand. • These investors are often property development neophytes and underestimate the complexity of the development process. • Local councils are unable and unwilling to work with these entrepreneurs to make the most of the investment offer. • An agenda to help local government and benevolent property entrepreneurs work cooperatively in New Zealand as outlined. [ABSTRACT FROM AUTHOR]

Abstract: Double-blinded trials are often considered the gold standard for research, but significant bias may result from unblinding of participants and investigators. Although the CONSORT guidelines discuss the importance of reporting “evidence that blinding was successful”, it is unclear what constitutes appropriate evidence. Among studies reporting methods to evaluate blinding effectiveness, many have compared groups with respect to the proportions correctly identifying their intervention at the end of the trial. Instead, we reasoned that participants'' beliefs, and not their correctness, are more directly associated with potential bias, especially in relation to self-reported health outcomes. During the Water Evaluation Trial performed in northern California in 1999, we investigated blinding effectiveness by sequential interrogation of participants about their “blinded” intervention assignment (active or placebo). Irrespective of group, participants showed a strong tendency to believe they had been assigned to the active intervention; this translated into a statistically significant intergroup difference in the correctness of participants'' beliefs, even at the start of the trial before unblinding had a chance to occur. In addition, many participants (31%) changed their belief during the trial, suggesting that assessment of belief at a single time does not capture unblinding. Sequential measures based on either two or all eight questionnaires identified significant group-related differences in belief patterns that were not identified by the single, cross-sectional measure. In view of the relative insensitivity of cross-sectional measures, the minimal additional information in more than two assessments of beliefs and the risk of modifying participants'' beliefs by repeated questioning, we conclude that the optimal means of assessing unblinding is an intergroup comparison of the change in beliefs (and not their correctness) between the start and end of a randomized controlled trial. [Copyright &y& Elsevier]

d -Serine is a co-agonist at forebrain N -methyl- d -aspartate receptors (NMDAR) and is synthesized by serine racemase (SR). Although d -serine and SR were originally reported to be localized to glia, recent studies have provided compelling evidence that under healthy physiologic conditions both are localized primarily in neurons. However, in pathologic conditions, reactive astrocytes can also express SR and synthesize d -serine. Since cultured astrocytes exhibit features of reactive astrocytes, we have characterized d -serine synthesis and the expression of enzymes involved in its disposition in primary glial cultures. The levels of SR were quite low early in culture and increased markedly in all astrocytes with the duration in vitro . The concentration of d -serine in the culture medium increased in parallel with SR expression in the astrocytes. Microglia, identified by robust expression of Iba1, did not express SR. While the levels of glial fibrillary acidic protein (GFAP), glycine decarboxylase (GLDC) and phosphoglycerate dehydrogenase (PHGDH), the initial enzyme in the pathway converting glycine to l -serine, remained constant in culture, the expression of lipocalin-2, a marker for pan-reactive astrocytes, increased several-fold. The cultured astrocytes also expressed Complement-3a, a marker for a subpopulation of reactive astrocytes (A1). Astrocytes grown from mice with a copy number variant associated with psychosis, which have four copies of the GLDC gene, showed a more rapid production of d -serine and a reduction in glycine in the culture medium. These results substantiate the conclusion that A1 reactive astrocytes express SR and release d -serine under pathologic conditions, which may contribute to their neurotoxic effects by activating extra-synaptic NMDARs. [ABSTRACT FROM AUTHOR]

Objective To evaluate the performance of two glossoptosis airway obstruction classifications in predicting symptom severity and laryngeal exposure difficulty in Robin Sequence (RS) patients. Setting: Public tertiary hospital otolaryngology section (Hospital de Clínicas de Porto Alegre - HCPA). Patients All RS patients diagnosed at HCPA from October 2012 to February 2015 were enrolled, a total of 58 individuals. They were classified in isolated RS, RS-Plus and syndromic RS. Intervention Patients were submitted to sleep endoscopy and a score was attributed according to Yellon and de Sousa by a blinded researcher. Symptom severity evaluation was performed as defined by Cole classification. Main outcome measure Association between endoscopic findings and clinical symptoms severity and laryngeal exposure difficulty. Results Twenty four patients were identified as isolated RS (41.4%), 19 patients presented as RS-Plus (32.7%) and 15 patients had well defined diagnosed syndromes (25.9%). Concomitant airway anomalies were found in 18 patients (31%). Specifically 17.4% in isolated RS, 55.6% in RS- Plus and 28.6% in the syndromic group had such anomalies (P = 0,03). Probability of presenting severe clinical symptoms as graded by Cole was higher in grade 3 Yellon classification (68.4%, P = 0.012) and in moderate and severe de Sousa classification (61.5% and 62.5%, respectively, P = 0.015) than in milder grades of obstruction. This findings were considered significant even after controlling for patient age. Laryngeal exposure difficulty was correlated with de Sousa and Yellon (Rho = 0,41 and Rho = 0,43, respectively; P < 0,05). Conclusion Patients with higher degrees of obstruction in sleep endoscopy had a higher probability of presenting a more severe clinical manifestation and a more difficult laryngeal exposure. Since the number of patients included in this study was small for subgroup analyses, it is not clear if this association is restricted to a specific group of RS. [ABSTRACT FROM AUTHOR]

Abstract: Historically, bipolar disorder and schizophrenia have been considered distinct disorders with different etiologies. Growing evidence suggests that overlapping genetic influences contribute to risk for these disorders and that each disease is genetically heterogeneous. Using cluster analytic methods, we empirically identified homogeneous subgroups of patients, their relatives, and controls based on distinct neurophysiologic profiles. Seven phenotypes were collected from two independent cohorts at two institutions. K-means clustering was used to identify neurophysiologic profiles. In the analysis of all participants, three distinct profiles emerged: “globally impaired”, “sensory processing”, and “high cognitive”. In a secondary analysis, restricted to patients only, we observed a similar clustering into three profiles. The neurophysiological profiles of the Schizophrenia (SZ) and Bipolar Disorder (BPD) patients did not support the Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic distinction between these two disorders. Smokers in the globally impaired group smoked significantly more cigarettes than those in the sensory processing or high cognitive groups. Our results suggest that empirical analyses of neurophysiological phenotypes can identify potentially biologically relevant homogenous subgroups independent of diagnostic boundaries. We hypothesize that each neurophysiology subgroup may share similar genotypic profiles, which may increase statistical power to detect genetic risk factors. [Copyright &y& Elsevier]

Abstract: Semantic priming has long been used to investigate how concepts and ideas are related at the level of language, and has become a convenient tool for assessing conceptual and semantic dysfunction in cognitive disorders, including schizophrenia. The study of semantic priming in schizophrenia has led to diverse results: enhanced priming, reduced priming, and priming equivalent to that found in nonpsychiatric comparison groups. A number of hypotheses have been proposed to explain some of the observed deficits in schizophrenia patients. For example, difficulties in word recognition may be due to hyperactivation of too many lexical representations or to a failure to inhibit lexical competitors. One way to distinguish between these possible explanations is to move beyond reliance on behavior alone and to examine the neural processes involved in lexical recognition. Here we present a magnetoencephalographic study of semantic priming in schizophrenia. Importantly, schizophrenia patients and healthy controls did not differ in performance on a priming task. We show that normal behavioral performance can occur in a context of aberrant neural responses. These findings suggest that normal behavioral responses in schizophrenia can be achieved through neural mechanisms that differ from those seen in the psychiatrically well brain. [Copyright &y& Elsevier]

Abstract: This study employed a conceptual combination task based on Estes and Glucksberg [(2000). Interactive property attribution in concept combination. Memory & Cognition, 28(1), 28–34] to address the question of whether semantic processing abnormalities in schizophrenia arise from deficits in semantic storage or access, or the controlled use of semantic memory representations. High thought disorder schizophrenia patients (), low thought disorder schizophrenia patients (), and controls () read and interpreted noun–noun combinations that varied with respect to whether the modifier noun had a salient semantic feature that could be mapped to a relevant dimension of a head noun. The percentages of property attributions, relational interpretations, and “other” interpretations were determined for each combination type. Subjective difficulty ratings were also collected for each response. Neither high nor low thought disorder patients differed from controls in the production of property interpretations. High thought disorder patients were significantly less likely to generate relational interpretations and significantly more likely to generate “other” interpretations. Subjective difficulty ratings were low for all groups, suggesting that differences in the ease of generating interpretations does not account for the results. The finding of intact property interpretations suggests that the integrity and initial access of semantic memory is spared in schizophrenia. In contrast, the reduced production of relational interpretations and increased production of “other” interpretations in schizophrenia suggests a compromised ability to engage in the controlled processing operations necessary to make flexible use of semantic material. [Copyright &y& Elsevier]

Objective: Uveitis in children most commonly is associated with juvenile idiopathic arthritis. In addition to topical glucocorticoids, treatment may include systemic immunosuppressive agents. Tumor necrosis factor α (TNF-α) has been implicated in the pathogenesis of uveitis; therefore, TNF-α blockade seems to be a reasonable therapeutic option to investigate. We report successful treatment of children with uveitis using infliximab. Study Design: A retrospective study of our complete experience using infliximab for the treatment of childhood uveitis was conducted. Participants: Seventeen children (14 females, 3 males) with chronic uveitis were administered high-dose infliximab (10–20 mg/kg/dose). Main Outcome Measures: Our main outcome measure was the ability to eliminate all signs of intraocular inflammation. Results: All 17 patients demonstrated a dramatic, rapid response, with no observed inflammation in 13 patients after the second infusion, and 4 patients requiring 3 to 7 infusions to achieve disease quiescence. Additional immunosuppressives and topical glucocorticoids were tapered when patients achieved no intraocular inflammation. Conclusions: In this series, high-dose infliximab was a rapidly effective, well-tolerated therapeutic agent for the treatment of chronic, medically refractory, noninfectious uveitis. [Copyright &y& Elsevier]