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Complement factor D (FD) is a rate-limiting enzyme of the alternative pathway (AP). Recent studies have suggested that it is synthesized as an inactive precursor and that its conversion to enzymatically active FD is catalyzed by mannan-binding lectin-associated serine protease 3 (MASP3). However, whether MASP3 is essential for AP complement activity remains uncertain. It has been shown that Masp1/3 gene knockout did not prevent AP complement overactivation in a factor H–knockout mouse, and a human patient lacking MASP3 still retained AP complement activity. In this study, we have assessed AP complement activity in a Masp3-knockout mouse generated by CRISPR/Cas9 editing of the Masp1/3 gene. We confirmed specific Masp3 gene inactivation by showing intact MASP1 protein expression and absence of mature FD in the mutant mice. Using several assays, including LPS- and zymosan-induced C3b deposition and rabbit RBC lysis tests, we detected plasma concentration–dependent AP complement activity in Masp3 gene–inactivated mice. Thus, although not measurable in 5% plasma, significant AP complement activity was detected in 20–50% plasma of Masp3 gene–inactivated mice. Furthermore, whereas FD gene deletion provided more than 90% protection of CD55/Crry-deficient RBCs from AP complement-mediated extravascular hemolysis, Masp3 gene deletion only provided 30% protection in the same study. We also found pro-FD to possess intrinsic catalytic activity, albeit at a much lower level than mature FD. Our data suggest that MASP3 deficiency reduces but does not abrogate AP complement activity and that this is explained by intrinsic pro-FD activity, which can be physiologically relevant in vivo.

Purpose The individual placement and support (IPS) model of supported employment is a leading evidence-based practice in community mental health services. In Japan, individualized supported employment that is highly informed by the philosophy of the IPS model has been implemented. While there is a body of evidence demonstrating the association between program fidelity and the proportion of participants gaining competitive employment, the association between fidelity and a wider set of vocational and individual outcomes has received limited investigation. This study aimed to assess whether high-fidelity individualized supported employment programs were superior to low-fidelity programs in terms of vocational outcomes, preferred job acquisition, and patient-reported outcome measures (PROMs). Methods A prospective longitudinal study with 24-month follow-up analyzed 16 individualized supported employment programs. The Japanese version of the individualized Supported Employment Fidelity scale (JiSEF) was used to assess the structural quality of supported employment programs (scores: low-fidelity program, ≤ 90; high-fidelity program, ≥ 91). Job acquisition, work tenure, work earnings, job preference matching (e.g., occupation type, salary, and illness disclosure), and PROMs such as the INSPIRE and WHO-Five Well-being index were compared between groups. Results There were 75 and 127 participants in the low-fidelity group (k = 6) and high-fidelity group (k = 10), respectively. The high-fidelity group demonstrated better vocational outcomes than the low-fidelity group, i.e., higher competitive job acquisition (71.7% versus 38.7%, respectively, adjusted odds ratio (aOR) = 3.6, p = 0.002), longer work tenure (adjusted mean difference = 140.8, p Conclusion High-fidelity individualized supported employment programs resulted in good vocational outcomes in a real-world setting. However, enhancing service quality to increase desired job acquisition and improve PROMs will be important in the future. Clinical Trial Registration UMIN000025648

This study examined the association between job tenure and job preference matching for five job preference domains for people with mental disorders enrolled in Individual Placement and Support (IPS) programs in Japan. The domains include occupation type, monthly income, weekly work hours, commute time, and illness disclosure.We conducted secondary analysis of participants who obtained employment in a longitudinal study during the 24-month follow-up period at 16 agencies routinely providing IPS programs. We included 112 participants who expressed job preferences and were employed at least once. A total of 130 employment cases were analyzed. Matches in the five domains were determined using participants' job preferences and employment information. The Match Level (0-5) indicates the number of domains that match the participant's job preferences. Job tenure (weeks worked) was compared between the matched and unmatched groups in each domain and between each match levels using linear regression mixed-effects models.A match for a given domain did not show a significant relationship with job tenure, whereas Match Levels 3 (A higher match level may be related to a longer job tenure. The results suggest that employment specialists should prioritize clients' preferences in job searches. Further replication studies in other settings and countries should be conducted to verify the findings in this study. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Objective In an effort to reduce mortality from gastric cancer, endoscopic screening was introduced in 2016 as a nationwide screening program in Japan. Recent developments in high-definition endoscopic imaging and diagnostic strategies have enabled the simultaneous detection of other upper gastrointestinal (U-GI) malignancies. Therefore, we conducted a study to evaluate the feasibility of endoscopic screening for U-GI malignancy in a comprehensive health checkup. Methods We retrospectively reviewed the data of 13,120 participants who had received a comprehensive health checkup in a single institution between April 2012 and March 2018. Participants were divided into two groups [gastrointestinal endoscopy (GIE) group (n=9,142) and gastrointestinal X-ray (X-ray) group (n=3,978)] and compared with regards to the screening results, adverse events, and detection rate of U-GI malignancies (gastric cancer or other) using a propensity-score matched analysis. Results The gastric cancer detection rate was significantly higher in the GIE group [34/9,142 (0.48%)] than in the X-ray group [3/3,978 (0.08%)] (p=0.003). Other U-GI malignancies were found only in the GIE group and comprised two hypopharyngeal cancers, five esophageal cancers, two duodenal cancers, and one duodenal gastrointestinal stromal tumor. Adverse events occurred in 6/9,142 (0.07%) participants in the GIE group and 18/3,978 (0.45%) participants in the X-ray group (p

The growing literature on gender inequality in academia attests to the challenge that awaits female researchers during their academic careers. However, research has not yet conclusively resolved whether these biases persist during the peer review process of research grant funding and whether they impact respective funding decisions. Whereas many have argued for the existence of gender inequality in grant peer reviews and outcomes, others have demonstrated that gender equality is upheld during these processes. In the present paper, we illustrate how these opinions have come to such opposing conclusions and consider methodological and contextual factors that render these findings inconclusive. More specifically, we argue that a more comprehensive approach is needed to further the debate, encompassing individual and systemic biases as well as more global social barriers. We also argue that examining gender biases during the peer review process of research grant funding poses critical methodological challenges that deserve special attention. We conclude by providing directions for possible future research and more general considerations that may improve grant funding opportunities and career paths for female researchers.

Purpose: Endoscopic submucosal dissection is a promising method for the resection of superficial gastric neoplasms. To date, several institutions have used proton pump inhibitor injections over the perioperative period. However, there is very little evidence regarding their efficacy. To overcome this limitation, we compared procedural outcomes and the prevention of adverse events of proton pump inhibitor injection with an orally administered active potassium-competitive acid blocker alone. Participants and Methods: We enrolled a total of 150 patients treated for superficial gastric neoplasms at a single institution between April 2015 and December 2018. Patients treated for 2 days with proton pump inhibitor injections following 12 days of oral potassium-competitive acid blocker (proton pump inhibitor group=80) were compared with patients treated for 14 days orally with potassium-competitive acid blocker alone (potassium-competitive acid blocker group=70) using propensity score analysis. We evaluated intragastric pH levels prior to endoscopic submucosal dissection, frequency of intraoperative major bleeding, procedure time, en bloc resection rate, curability, ulcer reduction rate 14 days after endoscopic submucosal dissection, and adverse events (including perforation and postoperative bleeding). Results: Propensity score analysis yielded 43 matched pairs. The comparison demonstrated similar values for the outcomes. For all cases, we observed intragastric pH levels >6.4 prior to endoscopic submucosal dissection. Postoperative bleeding rates were 2.3% (1/43) in the proton pump inhibitor group and 0.0% (0/43) in the potassium-competitive acid blocker group (P=0.315). Conclusions: Oral potassium-competitive acid blocker alone was as effective as proton pump inhibitor injection, with a low incidence of adverse events. Based on these results, proton pump inhibitor injection might be omitted during gastric endoscopic submucosal dissection.

SummaryPlant nucleotide-binding leucine-rich repeat receptors (NLRs) initiate immune responses and the hypersensitive response by recognizing pathogen effectors. Xa1 encodes an NLR with an N-terminal BED domain, and recognizes transcription activator-like (TAL) effectors of Xanthomonas oryzae pv. oryzae (Xoo). The molecular mechanisms controlling the recognition of TAL effectors by Xa1 and the subsequent induction of immunity remain poorly understood.Xa1 interacts in the nucleus with two TAL effectors via the BED domain. We identified the AP2/ERF-type transcription factor OsERF101/OsRAP2.6 as an interactor with Xa1, and found that it also interacts with the TAL effectors.Overexpression of OsERF101 exhibited an enhanced resistance to an incompatible Xoo strain only in the presence of Xa1, indicating that OsERF101 functions as a positive regulator of Xa1-mediated immunity. Unexpectedly, oserf101 mutants also showed enhanced Xa1-dependent resistance, but in a different manner from the overexpressing plants. This result revealed an additional Xa1-mediated immune pathway that is negatively regulated by OsERF101. Furthermore, OsERF101 directly interacted with the TAL effectors.Our results show that OsERF101 regulates the recognition of TAL effectors and the Xa1-mediated activation of the immune response. These data provide new insights into the molecular mechanism of NLR-mediated immunity in plants.

Simple Summary Stimulator of interferon genes (STING) is currently recognized as a driver for anti-tumor immunity against various malignancies and is expected to enhance the anti-tumor effects. In this review, we summarized recent knowledges gained from epigenetics-mediated skin cancer development and discussed the clinical application of STING agonists in the treatment of skin cancer. Abstract Recent developments in immunotherapy against malignancies overcome the disadvantages of traditional systemic treatments; however, this immune checkpoint treatment is not perfect and cannot obtain a satisfactory clinical outcome in all cases. Therefore, an additional therapeutic option for malignancy is needed in oncology. Stimulator of interferon genes (STING) has recently been highlighted as a strong type I interferon driver and shows anti-tumor immunity against various malignancies. STING-targeted anti-tumor immunotherapy is expected to enhance the anti-tumor effects and clinical outcomes of immunotherapy against malignancies. In this review, we focus on recent advancements in the knowledge gained from research on STING signaling in skin cancers. In addition to the limitations of STING-targeted immunotherapy, we also discuss the clinical application of STING agonists in the treatment of skin cancer.

Atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy (TMA) caused by dysregulated complement activation. Clinically, aHUS is effectively treated by an anti-C5 monoclonal antibody (mAb) but whether the disease is mediated by the C5a receptor (C5aR) or C5b-9 pathway, or both, is unknown. Here we address this in a factor H mutant mouse (FHR/R) which developed complement-mediated TMA as well as macrovascular thrombosis caused by an aHUS-related factor H point mutation (mouse W1206R, corresponding to human W1183R). C5 deficiency and anti-C5 mAb treatment blocked all disease manifestations in FHR/R mice. C5aR1 gene deficiency prevented macrovascular thrombosis in various organs but did not improve survival or reduce renal TMA. Conversely, C6 or C9 deficiency significantly improved survival and markedly diminished renal TMA but did not prevent macrovascular thrombosis. Interestingly, as they aged both FHR/R C6−/− and FHR/R C9−/− mice developed glomerular disease reminiscent of C3 glomerulonephritis. Thus, C5aR and C5b-9 pathways drove different aspects of disease in FHR/R mice with the C5aR pathway being responsible for macrovascular thrombosis and chronic inflammatory injury while the C5b-9 pathway caused renal TMA. Our data provide new understanding of the pathogenesis of complement-mediated TMA and macrovascular thrombosis in FHR/R mice and suggest that C5 blockade is more effective for the treatment of aHUS than selectively targeting the C5aR or C5b-9 pathway alone.

Plant nucleotide-binding leucine-rich repeat receptors (NLRs) initiate immune responses by recognizing pathogen effectors. The rice gene Xa1 encodes an NLR with an N-terminal BED domain, and recognizes transcription activator-like (TAL) effectors of Xanthomonas oryzae pv. oryzae (Xoo). Our goal is to elucidate the molecular mechanisms controlling the induction of immunity by Xa1. We used yeast two-hybrid assays to screen for host factors that interact with Xa1 and identified the AP2/ERF-type transcription factor OsERF101/OsRAP2.6. Molecular complementation assays were used to confirm the interactions among Xa1, OsERF101, and two TAL effectors. We created OsERF101-overexpressing and knockout mutant lines in rice and identified genes differentially regulated in these lines, many of which are predicted to be involved in regulation of response to stimulus. Xa1 interacts in the nucleus with the TAL effectors and OsERF101 via the BED domain. Unexpectedly, both the overexpression and knockout lines of OsERF101 displayed Xa1-dependent, enhanced resistance to an incompatible Xoo strain. Different sets of genes were up- or down-regulated in the overexpression and knockout lines. Our results indicate that OsERF101 regulates the recognition of TAL effectors by Xa1, and functions as a positive regulator of Xa1-mediated immunity. Further, an additional Xa1-mediated immune pathway is negatively regulated by OsERF101., イネが病原菌の感染力の源を検出して免疫を誘導する仕組みを解明 --病気に強い植物の開発に期待--. 京都大学プレスリリース. 2022-09-07.

We present a preliminary validation of a newly built questionnaire aimed at evaluating people’s openness towards the notion of non-binary gender. To explore the validity of our questionnaire, we ran a principal component analysis to evaluate the existence of three overarching dimensions (Gender Categories, Gender Fluidity, and Gender Definitions) that were at the very foundation of our questionnaire. We also explored the link between our questionnaire and measures of one’s political orientation and feminist identification. In all, our questionnaire was found to have an acceptable level of reliability, and as such, constitutes an important tool for better understanding people’s attitudes towards non-binary gender.

In the field of organic syntheses, the development of environmentally friendly methods based on the concept of green chemistry has been always required. In response to this requirement, we reported solvent- and catalyst-free syntheses of imines using the pressure reduction technique as a key technology. We found that this reaction proceeded very rapidly in the initial stage, but its rate decreased with the passage of time. It was also found that the reaction of benzaldehyde with aniline had a specificity that the phase transition occurred. In this method, the desired imines could be obtained in good to excellent yields, but target compounds had to be given by purifications using organic solvents. Therefore, we tried to develop the perfect synthetic method of imine derivatives without organic or inorganic solvents. We selected two methods and took them into this investigation. One was exactly mixing (1:1, substance ratio) aldehydes and amines and the other was employing lower pressure (>0.1 mmHg, previous method: 1.0 mmHg) at the pressure reducing technique. When this improved synthetic method was performed, it was revealed that pure target imines were obtained in excellent yields without any purification.

Background: The use of antithrombotic agents for the prevention of cerebro-cardioembolic events has increased, and recent guidelines have recommended the continued administration of low-dose aspirin (LDA) during endoscopic procedures with a high risk of bleeding. However, the influence of LDA on intraoperative bleeding control status during Endoscopic submucosal dissection (ESD) remains unclear. Methods: We examined 293 consecutive patients who underwent ESD for gastric cancers between January 2014 and February 2018. Patients administered with LDA (n = 52) were compared with those without antithrombotic therapy (n = 241; control) by propensity-score matching (PSM) concerning outcomes of ESD. Results: PSM analysis yielded 50 matched pairs. Comparison showed similar values for frequency of intraoperative major bleeding: 1 (0–4) times (median [range]) in the LDA group and 0 (0–5) in the control group respectively (p = 0.710). Others (frequency of preventive coagulation, procedure time, decrease of hemoglobin levels, en bloc resection, complete resection) were the same with a few adverse events including perforation (0%), and thromboembolism (0%). Postoperative bleeding rate was 1.9% in LDA group. Multivariate analysis indicated that location U and circumference on the posterior wall were associated with for multiple major intraoperative bleeding. Conclusion: The study suggests that gastric ESD can be safely accomplished without cessation of LDA.

Background Properdin (P) is a positive regulator of the alternative pathway of complement activation. Although P inhibition is expected and has been shown to ameliorate the alternative pathway of complement-mediated tissue injury in several disease models, it unexpectedly exacerbated renal injury in a murine model of C3 glomerulopathy. The role of P in atypical hemolytic uremic syndrome (aHUS) is uncertain.Methods We blocked P function by genetic deletion or mAb-mediated inhibition in mice carrying a factor H (FH) point mutation, W1206R (FHR/R), that causes aHUS and systemic thrombophilia with high mortality.Results P deficiency completely rescued FHR/R mice from premature death and prevented thrombocytopenia, hemolytic anemia, and renal disease. It also eliminated macrovessel thrombi that were prevalent in FHR/R mice. All mice that received a function-blocking anti-P mAb for 8 weeks survived the experimental period and appeared grossly healthy. Platelet counts and hemoglobin levels were significantly improved in FHR/R mice after 4 weeks of anti-P mAb treatment. One half of the FHR/R mice treated with an isotype control mAb but none of the anti-P mAb-treated mice developed stroke-related neurologic disease. Anti-P mAb-treated FHR/R mice showed largely normal renal histology, and residual liver thrombi were detected in only three of 15 treated mice.Conclusions These results contrast with the detrimental effect of P inhibition observed in a murine model of C3 glomerulopathy and suggest that P contributes critically to aHUS pathogenesis. Inhibition of P in aHUS may be of therapeutic benefit.

Endoscopic submucosal dissection (ESD) is a promising method for the resection of superficial gastric neoplasms. Vonoprazan is a novel potassium-competitive acid blocker (P-CAB) that is currently considered as a potential alternative to proton pump inhibitors (PPIs) for the treatment of acid-related diseases. However, the utility of vonoprazan in ESD-related ulcers is unclear. Therefore, we compared the short-term efficacies of vonoprazan and the PPI lansoprazole in ESD-related ulcer healing during the first two weeks following intervention.This study included 115 superficial gastric neoplasms that were treated by ESD at Hiraka General Hospital between April 2015 and January 2017. Patients treated with P-CAB (20 mg vonoprazan, n = 62) or PPI (30 mg lansoprazole, n = 53) were compared using propensity-score matching analysis. Primary outcome was rate of ulcer reduction at two weeks after ESD. Secondary outcomes were coverage ratio of ulcer base by granulation tissue and incidence of postoperative bleeding.The rate of ulcer reduction was significantly higher (median [range], 80.6% [67.6%-94.5%] vs. 62.7% [33.4%-85.2%]; p .0001) and coverage ratio of the ulcer base by granulation tissue was significantly accelerated (median [range], 84.1% [67.7%-95.3%] vs. 61.9% [12.1%-90.1%]; P 0.0001) in the P-CAB group compared with the PPI group. Postoperative bleeding was not observed in either group.P-CAB achieved rapid artificial ulcer healing with promotion of granulation tissue formation. However, conventional PPI with initial intravenous infusion might be sufficient for prevention of postoperative bleeding following gastric ESD.

The Individual Placement and Support (IPS) model of supported employment is an evidence based practice. Although several agencies have been trying to implement the IPS-model since 2005 in Japan, there was no tool to assess the quality. This study developed a Japanese version of the 25-item Individualized Supported Employment Fidelity Scale (J-ISEF), a new Japanese fidelity tool for supported employment based on the IPS model. A working group consisting of researchers and practitioners was formed to develop J-ISEF based on IPS-25. Some experts of the group visited the community agencies in Vermont before the development process. Twenty-six eligible agencies were identified using snowball sampling, and 14 agencies of them agreed and participated at T1. We conducted three cross-sectional surveys (T1, T2 and T3), using the new scale. The first evaluation period (T1) was between September 2013 and February 2014, the second (T2) between September 2014 and February 2015, and the third (T3) between October 2015 and February 2016. High inter-rater reliability (ICC = 0.98 for the entire scale) was confirmed from T1 data. The total score and the service subscale total were positively correlated with employment rate (P

Complement plays a key role in host defense, but its dysregulation can cause autologous tissue injury. Complement activation is normally controlled by regulatory proteins, including factor H (FH) in plasma and membrane cofactor protein (MCP) on the cell surface. Mutations in FH and MCP are linked to atypical hemolytic uremic syndrome, a type of thrombotic microangiopathy (TMA) that causes renal failure. We describe here that disruption of FH function on the cell surface can also lead to disseminated complement-dependent macrovascular thrombosis. By gene targeting, we introduced a point mutation (W1206R) into murine FH that impaired its interaction with host cells but did not affect its plasma complement-regulating activity. Homozygous mutant mice carrying this mutation developed renal TMA as well as systemic thrombophilia involving large blood vessels in multiple organs, including liver, lung, spleen, and kidney. Approximately 30% of mutant mice displayed symptoms of stroke and ischemic retinopathy, and 48% died prematurely. Genetic deficiency of complement C3 and factor D prevented both the systemic thrombophilia and renal TMA phenotypes. These results demonstrate a causal relationship between complement dysregulation and systemic angiopathy and suggest that complement activation may contribute to various human thrombotic disorders involving both the micro- and macrovasculature.

Little is known about the association between service intensity and fidelity scale score in supported employment programs. This study compares service contents and intensity in low- and high-fidelity programs and examines the validity of the Japanese version of the individualized Supported Employment Fidelity Scale.The vocational outcomes and service provision data for 51 individuals with schizophrenia in 13 supported employment programs were collected over a 12-month study period. Outcomes, service contents, and service intensity were compared between the low-fidelity group (seven programs; N=29) and the high-fidelity group (six programs; N=22).In both groups, 70% of the total services (hours) were provided in the first 6 months. The high-fidelity group, which was associated with better vocational outcomes than the low-fidelity group (employment rate, 68% versus 38%, respectively), made the greatest effort in job development outside of the agency, whereas the low-fidelity group spent more time on group services. In addition, before the client obtained a job, high-fidelity programs provided outreach services (B=7.2, p=0.043) and agency-based individual services (B=5.7, p0.001) at greater intensity than did low-fidelity programs. However, no significant between-group difference was found in service intensity once clients were employed.Supported employment programs with a high fidelity score focus more intensely on providing individual services in and outside of the agency, particularly before clients obtain a job. However, clarification of the relationships among service quality at the structure level, amount of follow-up services, and individual needs in supported employment programs is a future issue.

Objective In spite of the effectiveness of the individual placement and support model of supported employment (IPS) for the recovery of people with mental illness, the implementation and dissemination of IPS in Japan have not been straightforward. This paper summarizes barriers against the implementation of IPS in Japan and discusses potential strategies to overcome them. Method We reviewed IPS research performed in Japan through literature search, and summarized current employment services and policies in Japan along with a practice report of an ongoing IPS program in a local city in Japan. Results Barriers against the implementation of IPS in Japan included: (a) systems designed mainly for group-based services, (b) weak recognition of IPS, and (c) cultural background. Nevertheless, we identified 4 intervention studies of IPS in Japanese settings, and all found that more than 40% of the participants gained their employment through IPS. By utilizing available services, the IPE program in Hamada City achieved ∼50% employment rate and sufficient fidelity. Conclusions and implications for practice The present data indicate that, by combining currently available services, IPS can be implemented successfully in Japan. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Aim The aim of this study was to clarify whether improvement of cognitive functioning by cognitive remediation therapy can improve work outcome in schizophrenia and other severe mental illnesses when combined with supported employment. Methods The subjects of this study were persons with severe mental illness diagnosed with schizophrenia, major depression, or bipolar disorder (ICD-10) and cognitive dysfunction who participated in both cognitive remediation using the Thinking Skills for Work program and a supported employment program in a multisite, randomized controlled study. Logistic and multiple linear regression analyses were performed to clarify the influence of cognitive functioning on vocational outcomes, adjusting for demographic and clinical variables. Results Improvement of cognitive functioning with cognitive remediation significantly contributed to the total days employed and total earnings of competitive employment in supported employment service during the study period. Any baseline demographic and clinical variables did not significantly contribute to the work-related outcomes. Conclusion A cognitive remediation program transferring learning skills into the real world is useful to increase the quality of working life in supported employment services for persons with severe mental illness and cognitive dysfunction who want to work competitively.

The generic use of masculine plural forms in grammatical gender languages has been criticized for activating unequal gender representations that are male dominant. The present study examined whether the recently introduced gender-neutral forms of nominalized adjectives and participles in German provide references that induce more balanced representations. We used cross-linguistic differences as a means to illustrate the flexibility of the gender representation system and investigated both native and nonnative (French–German bilinguals) speakers of German. Although a masculine bias persisted when participants read role nouns in the masculine plural form, the study suggests that the usage of nominalized forms can attenuate this male bias, even for nonnative speakers. The results of the study provide further support for the use of gender-neutral language.

Devising new methods to improve neurocognitive impairment through cognitive remediation is an important research goal. We developed an original computer programme termed the Japanese Cognitive Rehabilitation Programme for Schizophrenia (JCORES) that provides cognitive practice across a broad range of abilities. The current study examined for the first time whether a cognitive remediation programme, including both computerised cognitive training using JCORES and group intervention such as enhancing meta-cognition and teaching strategies, is more effective than treatment as usual for improving neurocognitive and social functioning. Sixty-two outpatients with schizophrenia were randomised to either a cognitive remediation group or a control group. Participants engaged in two computerised cognitive training sessions and one group meeting per week for 12 weeks. The average number of total sessions attended (computerised cognitive practice + group intervention) was 32.3 (89.7%). The cognitive remediation group showed significantly more improvements in verbal memory, composite score of the Brief Assessment of Cognition in Schizophrenia, Japanese version (BACS-J), and general psychopathology on the Positive and Negative Syndrome Scale (PANSS) than the control group. These findings demonstrate that a cognitive remediation programme is feasible in Japan and is a more effective way to improve neurocognitive functioning and psychiatric symptoms.

We analyze the semantic ambiguity of the grammatically masculine form in languages where this form has more than one meaning (e.g., French, German, English to some extent) when used to refer to human beings. We discuss this ambiguity in terms of inference processing, meaning activation, and the link between language and the way we perceive reality. Importantly, we attempt to identify and explain the cognitive mechanisms at the very heart of gender biases when readers (and speakers) construct mental representations of gender through language. We ground our argument in memory-based approaches to reading, the meaning activation selection model and the thinking-for-speaking hypothesis. This paper provides a cognitive perspective to understanding why, in grammatical gender languages, gender representations are male biased.