Schizophrenia Genetic Variants are not Associated with Intelligence

Background Schizophrenia is associated with lower pre-morbid intelligence (IQ) in addition to (pre-morbid) cognitive decline. Both schizophrenia and IQ are highly heritable traits. Therefore, we hypothesized that genetic variants associated with schizophrenia, including copy number variants (CNVs) and a polygenic schizophrenia (risk) score (PSS), may influence intelligence. Method IQ was estimated with the Wechsler Adult Intelligence Scale (WAIS). CNVs were determined from single nucleotide polymorphism (SNP) data using the QuantiSNP and PennCNV algorithms. For the PSS, odds ratios for genome-wide SNP data were calculated in a sample collected by the Psychiatric Genome-Wide Association Study (GWAS) Consortium (8690 schizophrenia patients and 11 831 controls). These were used to calculate individual PSSs in our independent sample of 350 schizophrenia patients and 322 healthy controls. Results Although significantly more genes were disrupted by deletions in schizophrenia patients compared to controls (p = 0.009), there was no effect of CNV measures on IQ. The PSS was associated with disease status (R 2 = 0.055, p = 2.1 × 10 -7) and with IQ in the entire sample (R 2 = 0.018, p = 0.0008) but the effect on IQ disappeared after correction for disease status. Conclusions Our data suggest that rare and common schizophrenia-associated variants do not explain the variation in IQ in healthy subjects or in schizophrenia patients. Thus, reductions in IQ in schizophrenia patients may be secondary to other processes related to schizophrenia risk. © Cambridge University Press 2013.

Genome-wide association analysis identifies 13 new risk loci for schizophrenia

Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-Analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.

Genome-wide association study identifies five new schizophrenia loci

We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10 -11) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10 -9), ANK3 (rs10994359, P = 2.5 × 10 -8) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10 -9).

More than just food: Field visits to an emergency relief centre

Emergency relief centres provide financial, housing, food and other types of support to families and individuals who experience financial hardship. These centres are non-profit, often government supported organizations that rely on the help of their volunteers and social workers. This paper reports on our preliminary findings from field visits to one such centre called Communify, in the inner west of Brisbane, Australia. Communify runs an emergency food relief facility for people who find themselves in a crisis or temporarily unable to afford groceries. Over a period of five months, we did several field visits to the centre and carried out 21 short in-situ interviews, with a mix of Communify clients and volunteers. Our results shed light on people’s experiences of financial hardship and their interactions with the emergency relief centre. In particular, issues related to their perceived values and stigmas associated with their experiences are highlighted in our findings. We identify opportunities for design that can empower people struggling with financial hardship.

Investigating the effectiveness of an ecological approach to learning design in a first year mathematics for engineering unit

This is presentation of the refereed paper accepted for the Conferences' proceedings. The presentation was given on Tuesday, 1 December 2015.

The Connected Learning Analytics toolkit

This demonstration introduces the Connected Learning Analytics (CLA) Toolkit. The CLA toolkit harvests data about student participation in specified learning activities across standard social media environments, and presents information about the nature and quality of the learning interactions.

Long-term results of obstetric brachial plexus surgery

Background: Brachial plexus birth palsy (BPBP) most often occurs as a result of foetal-maternal disproportion. The C5 and C6 nerve roots of the brachial plexus are most frequently affected. In contrast, roots from the C7 to Th1 that result in total injury together with C5 and C6 injury, are affected in fewer than half of the patients. BPBP was first described by Smellie in 1764. Erb published his classical description of the injury in 1874 and his name became linked with the paralysis that is associated with upper root injury. Since then, early results of brachial plexus surgery have been reasonably well documented. However, from a clinical point of view not all primary results are maintained and there is also a need for later follow-up results. In addition most of the studies that are published emanate from highly specialized clinics and no nation wide epidemiological reports are available. One of the plexus injuries is the avulsion type, in which the nerve root or roots are ruptured at the neural cord. It has been speculated whether this might cause injury to the whole neural system or whether shoulder asymmetry and upper limb inequality results in postural deformities of the spine. Alternatively, avulsion could manifest as other signs and symptoms of the whole musculoskeletal system. In addition, there is no available information covering activities of daily living after obstetric brachial plexus surgery. Patients and methods: This was a population-based cross-sectional study on all patients who had undergone brachial plexus surgery with at least 5 years of follow-up. An incidence of 3.05/1000 for BPBP was obtained from the registers for this study period. A total of 1706 BPBP patients needing hospital treatment out of 1 717 057 newborns were registered in Finland between 1971 and 1997 inclusive. Of these BPBP patients, 124 (7.3%) underwent brachial plexus surgery at a mean age of 2.8 months (range: 0.4―13.2 months). Surgery was most often performed by direct neuroraphy after neuroma resection (53%). Depending on the phase of the study, 105 to 112 patients (85-90%) participated in a clinical and radiological follow-up assessment. The mean follow up time exceeded 13 years (range: 5.0―31.5 years). Functional status of the upper extremity was evaluated using Mallet, Gilbert and Raimondi scales. Isometric strength of the upper limb, sensation of the hand and stereognosis were evaluated for both the affected and unaffected sides then the differences and their ratios were calculated and recorded. In addition to the upper extremity, assessment of the spine and lower extremities were performed. Activities of daily living (ADL), participation in normal physical activities, and the use of physiotherapy and occupational therapy were recorded in a questionnaire. Results: The unaffected limb functioned as the dominant hand in all, except four patients. The mean length of the affected upper limb was 6 cm (range: 1-13.5 cm) shorter in 106 (95%) patients. Shoulder function was recorded as a mean Mallet score of 3 (range: 2―4) which was moderate. Both elbow function and hand function were good. The mean Gilbert elbow scale value was 3 (range: -1―5) and the mean Raimondi hand scale was 4 (range:1―5). One-third of the patients experienced pain in the affected limb including all those patients (n=9) who had clavicular non-union resulting from surgery. A total of 61 patients (57%) had an active shoulder external rotation of less than 0° and an active elbow extension deficiency was noted in 82 patients (77%) giving a mean of 26° (range: 5°―80°). In all, expect two patients, shoulder external rotation strength at a mean ratio 35% (range: 0―83%) and in all patients elbow flexion strength at a mean ratio of 41% (range: 0―79%) were impaired compared to the unaffected side. According to radiographs, incongruence of the glenohumeral joint was noted in 15 (16%) patients, whereas incongruence of the radiohumeral joint was found in 20 (21%) patients. Fine sensation was normal for 34/49 (69%) patients with C5-6 injury, for 15/31 (48%) with C5-7 and for only 8/25 (32%) of patients with total injury. Loss of protective sensation or absent sensation was noted in some palmar areas of the hand for 12/105 patients (11%). Normal stereognosis was recorded for 88/105 patients (84%). No significant inequalities in leg length were found and the incidence of structural scoliosis (1.7%) did not differ from that of the reference population. Nearly half of the patients (43%) had asynchronous motion of the upper limbs during gait, which was associated with impaired upper limb function. Data obtained from the completed questionnaires indicated that two thirds (63%) of the patients were satisfied with the functional outcome of the affected hand although one third of all patients needed help with ADL. Only a few patients were unable to participate in physical activities such as: bicycling, cross-country skiing or swimming. However, 71% of the patients reported problems related to the affected upper limb, such as muscle weakness and/or joint stiffness during the aforementioned activities. Incongruity of the radiohumeral joints, extent of the injury, avulsion type injury, age less than three months of age at the time of plexus surgery and inexperience of the surgeon was related to poor results as determined by multivariate analyses. Conclusions: Most of the patients had persistent sequelae, especially of shoulder function. Almost all measurements for the total injury group were poorer compared with those of the C5-6 type injury group. Most of the patients had asymmetry of the shoulder region and a shorter affected upper limb, which is a probable reason for having an abnormal gait. However, BPBP did not have an effect on normal growth of the lower extremities or the spine. Although, participation in physical activities was similar to that of the normal population, two-thirds of the patients reported problems. One-third of the patients needed help with ADL. During the period covered by this study, 7.3% BPBP of patients that needed hospital treatment had a brachial plexus operation, which amounts to fewer than 10 operations per year in Finland. It seems that better results of obstetric plexus surgery and more careful follow-up including opportunities for late reconstructive procedures will be expected, if the treatment is solely concentrated on by a few specialised teams.

The ambient aerosol characterization during the prescribed bushfire season in Brisbane 2013

Prescribed burnings are conducted in Queensland each year from August until November aiming to decrease the impact of bushfire hazards and maintain the health of vegetation. This study reports chemical characteristics of the ambient aerosol, with a focus on source apportionment of the organic aerosol (OA)fraction, during the prescribed biomass burning (BB) season in Brisbane 2013. All measurements were conducted within the International Laboratory for Air Quality and Health (ILAQH) located in Brisbane’s Central Business District. Chemical composition, degree of ageing and the influence of BB emission on the air quality of central Brisbane were characterized using a compact Time of Flight Aerosol Mass Spectrometer (cToF-AMS). AMS loadings were dominated by OA (64 %), followed by, sulfate (17 %), ammonium (14 %) and nitrates (5 %). Source apportionment was applied on the AMS OA mass spectra via the multilinear engine solver (ME-2) implementation within the recently developed Source Finder (SoFi) interface. Six factors were extracted including hydrocarbon-like OA (HOA), cooking-related OA (COA), biomass burning OA (BBOA), low-volatility oxygenated OA (LV-OOA), semivolatile oxygenated OA (SV-OOA), and nitrogen-enriched OA (NOA). The aerosol fraction that was attributed to BB factor was 9 %, on average over the sampling period. The high proportion of oxygenated OA (72 %), typically representing aged emissions, could possess a fraction of oxygenated species transformed from BB components on their way to the sampling site.

High levels of catalytic antibodies correlate with favorable outcome in sepsis

Sepsis is the leading cause of death in intensive care units and results from a deleterious systemic host response to infection. Although initially perceived as potentially deleterious, catalytic antibodies have been proposed to participate in removal of metabolic wastes and protection against infection. Here we show that the presence in plasma of IgG endowed with serine protease-like hydrolytic activity strongly correlates with survival from sepsis. Variances of catalytic rates of IgG were greater in the case of patients with severe sepsis than healthy donors (P < 0.001), indicating that sepsis is associated with alterations in plasma levels of hydrolytic IgG. The catalytic rates of IgG from patients who survived were significantly greater than those of IgG from deceased patients (P < 0.05). The cumulative rate of survival was higher among patients exhibiting high rates of IgG-mediated hydrolysis as compared with patients with low hydrolytic rates (P < 0.05). An inverse correlation was also observed between the markers of severity of disseminated intravascular coagulation and rates of hydrolysis of patients' IgG. Furthermore, IgG from three surviving patients hydrolyzed factor VIII, one of which also hydrolyzed factor IX, suggesting that, in some patients, catalytic IgG may participate in the control of disseminated microvascular thrombosis. Our observations provide the first evidence that hydrolytic antibodies might play a role in recovery from a disease.

As garantias do processo do trabalho

Este trabalho se propõe a uma releitura da atual concepção do Direito Processual do Trabalho, seus institutos, princípios e regras. A partir da constatação da autonomia do processo do trabalho e da inaptidão de seus mecanismos para a realização dos direitos materiais subjacentes, passam a ser diagnosticados fatores que o distanciam dos valores constitucionais e das garantias processuais fundamentais reconhecidas nos textos supranacionais, para a construção de principiologia própria e coerente com a Teoria Geral do Processo. Destacadas as seis garantias processuais fundamentais, quais sejam (i) tribunal competente; (ii) acesso à justiça; (iii) órgão julgador imparcial; (iv) ampla possibilidade de participação no processo; (v) prazo razoável e (vi) efetividade da decisão, cada uma passa a ser apresentada inicialmente sob uma ótica abstrata e geral, para, em seguida, serem considerados os pontos em que se chocam com as práticas processuais trabalhistas. Sobre tais premissas são desenvolvidas teses em prol da construção de um justo processo do trabalho.

Efeito de ExoU na ativação de NF-κB e na secreção de IL-8 por células humanas infectadas por Pseudomonas aeruginosa

ExoU, uma citotoxina produzida pelo patógeno oportunista Pseudomonas aeruginosa e translocada para o citossol de células hospedeiras via sistema de secreção do tipo III, é associada à gravidade de infecções agudas. Estudos anteriores realizados em nosso laboratório relataram a potente atividade pró-inflamatória de ExoU, responsável por um intenso recrutamento de neutrófilos para o sítio de infecção. No presente trabalho, o efeito de ExoU na modulação da ativação do fator transcricional NF-κB e na regulação da expressão e da secreção da quimiocina para neutrófilos IL-8 foi avaliado em culturas de células epiteliais respiratórias e endoteliais humanas infectadas com a cepa PA103 de P. aeruginosa (produtora de ExoU) ou com a mutante deletada no gene exoU, PA103κexoU. Análises por RT-PCR semi-quantitativo mostraram que a infecção pela cepa produtora de ExoU levou ao aumento dos níveis de mRNA de IL-8, enquanto ensaios de alteração da mobilidade eletroforética (EMSA), supershift e com gene repórter mostraram que ExoU induziu a translocação nuclear do heterodímero transativador p65/p50 de NF-κB e a ativação da transcrição de genes dependente deste fator transcricional. Adicionalmente, o tratamento das culturas celulares com um inibidor de NF-κB antes da infecção bacteriana reduziu significativamente os níveis de mRNA de IL-8 e da secreção desta quimiocina. Em conjunto, estes resultados mostram que ExoU ativa NF-κB e, consequentemente, estimula a expressão e a secreção de IL-8 por células epiteliais respiratórias e células endoteliais infectadas com P. aeruginosa

The effect of timing of tagging on streamer-tag recapture rates for American lobster (Homarus americanus)

Streamer tags are commonly used to study the ecology and population biology of the American lobster (Homarus americanus). Aquarium observations suggest that streamer tag loss, either through tag-induced mortality or tag shedding, is related to the molt stage of the lobster at the time of tagging, and the molting event itself. Tag-induced mortality, where lobsters did not molt, occurred within eleven and sixteen days following tagging for lobsters tagged in postmolt (4%) and late premolt (10%) stages, respectively; whereas no lobsters tagged in early premolt or intermolt stages died. Taginduced mortality at time of molting was observed for lobsters tagged in late premolt stage (11%), and tag shedding was observed for lobsters tagged both in early (25%) and late premolt (11%) stages, but was significantly higher (P=0.014) for lobsters tagged in early premolt stages. Autopsies revealed that lobsters died mainly of organ perforations (hepato-pancreas and pericardial sac) following the tagging process, and rupture of the dorsal thoraco-abdominal membrane during the molting process. The total tag loss was estimated at 4% for lobsters tagged after molting, and 27% and 31% for lobsters tagged in early and late premolt stages, respectively. There was no tag loss for lobsters tagged in the intermolt stage during four months of laboratory observations (July−October). To minimize streamer tag loss, lobsters should be tagged during the intermolt or postmolt stage. Based on field studies, recapture rates for lobsters tagged in premolt stage are always lower than those of lobsters tagged in postmolt stage. Furthermore, recapture rates during the second year, for lobsters that molt in the year following tagging, were drastically reduced, and no lobster was recaptured after four years at large. Finally, to account for tag loss during the first year at large, a minimal adjustment of 24.9% (SD 2.9%) and 4.4% (SD 1.6%) for the recapture rate of lobsters tagged immediately before and after the molting season, respectively, is recommended. Adjustments beyond one year at large are not recommended for the American lobster at this time.

Developing Quantitative Methodologies for the Digital Humanities: A Case Study of 20th Century American Commentary on Russian Literature

Using scientific methods in the humanities is at the forefront of objective literary analysis. However, processing big data is particularly complex when the subject matter is qualitative rather than numerical. Large volumes of text require specialized tools to produce quantifiable data from ideas and sentiments. Our team researched the extent to which tools such as Weka and MALLET can test hypotheses about qualitative information. We examined the claim that literary commentary exists within political environments and used US periodical articles concerning Russian literature in the early twentieth century as a case study. These tools generated useful quantitative data that allowed us to run stepwise binary logistic regressions. These statistical tests allowed for time series experiments using sea change and emergency models of history, as well as classification experiments with regard to author characteristics, social issues, and sentiment expressed. Both types of experiments supported our claim with varying degrees, but more importantly served as a definitive demonstration that digitally enhanced quantitative forms of analysis can apply to qualitative data. Our findings set the foundation for further experiments in the emerging field of digital humanities.

Triterpenoid saponins from a cytotoxic root extract of Sideroxylon foetidissimum subsp. gaumeri

Evaluation of the cytotoxicity of an ethanolic root extract of Sideroxylonfoetidissimum subsp. gaumeri (Sapotaceae) revealed activity against the murine macrophage-like cell line RAW 264.7. Systematic bioassay-guided fractionation of this extract gave an active saponin-containing fraction from which four saponins were isolated. Use of 1D ((1)H, (13)C, DEPT135) and 2D (COSY, TOCSY, HSQC, and HMBC) NMR, mass spectrometry and sugar analysis gave their structures as 3-O-(beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl)-28-O-(alpha-L-rhamnopyranosyl-(1-->3)[beta-D-xylopyranosyl-(1-->4)]-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl)-16alpha-hydroxyprotobassic acid, 3-O-beta-D-glucopyranosyl-28-O-(alpha-L-rhamnopyranosyl-(1-->3)[beta-D-xylopyranosyl-(1-->4)]-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl)-16alpha-hydroxyprotobassic acid, 3-O-(beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl)-28-O-(alpha-L-rhamnopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)[beta-D-apiofuranosyl-(1-->3)]-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl)-16alpha-hydroxyprotobassic acid, and the known compound, 3-O-beta-D-glucopyranosyl-28-O-(alpha-L-rhamnopyranosyl-(1-->3)[beta-D-xylopyranosyl-(1-->4)]-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl)-protobassic acid. Two further saponins were obtained from the same fraction, but as a 5:4 mixture comprising 3-O-(beta-D-glucopyranosyl)-28-O-(alpha-L-rhamnopyranosyl-(1-->3)-beta-D-xylopyranosyl-(1-->4)[beta-D-apiofuranosyl-(1-->3)]-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl)-16alpha-hydroxyprotobassic acid and 3-O-(beta-D-apiofuranosyl-(1-->3)-beta-D-glucopyranosyl)-28-O-(alpha-L-rhamnopyranosyl-(1-->3)[beta-D-xylopyranosyl-(1-->4)]-beta-D-xylopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranosyl)-16alpha-hydroxyprotobassic acid, respectively. This showed greater cytotoxicity (IC(50)=11.9+/-1.5 microg/ml) towards RAW 264.7 cells than the original extract (IC(50)=39.5+/-4.1 microg/ml), and the saponin-containing fraction derived from it (IC(50)=33.7+/-6.2 microg/ml).

Triterpenoid saponins from the cytotoxic root extract of Sideroxylon foetidissimum, an endemic Yucatecan medicinal plant

The flora of the Yucatan peninsula (Mexico) includes approximately 3000 plant species. Sideroxylon foetidissimum Jacq. subsp. gaumeri (Sapotaceae) is an endemic plant to the Yucatan peninsula; its fruit is edible and local people use the plant for medicinal purposes, although no details on its preparation or application are available [1,2]. A preliminary cytotoxic evaluation of the ethanolic root extract of S. foetidissimum revealed a potent activity against murine macrophage like cell line RAW 264.7 (IC50=39.54±4.11µg/mL). The systematic bioassay-guided fractionation of the extract resulted in the identification of the active saponin-containing fraction (IC50=33.69±6.19µg/mL). Four new triterpenoid saponins and a 1:1 mixture of two saponins were isolated from the active saponin- containing fraction. The evaluation of their cytotoxic activity revealed no activity for the tested pure saponins; however, the 1:1 mixture of saponins showed a potent activity (IC50=11.91±1.49µg/mL). The isolation of the saponins was carried out using semi-preparative HPLC. The structural assignments of the pure saponins were based on 1D (1H and 13C and DEPT-135) and 2D (COSY, HMBC, HSQC and TOCSY) NMR and mass spectrometry analyses. In this presentation, the isolation, identification and cytotoxic activity of the isolated compounds is discussed in more detail.