Superior Episodic Memory Is Associated With Interhemispheric Processing

The dependence of episodic memories on interhemispheric processing was tested. In Experiment 1, positive familial sinistrality (FS+; e.g., the presence of left-handed relatives) was associated with superior episodic memory and inferior implicit memory in comparison with negative familial sinistrality (i.e., FS-). This reflected a greater degree of interhemispheric interaction in FS+ participants, which was hypothesized as facilitating episodic memory. In Experiment 2, the authors directly manipulated inter- versus intrahemispheric processing using tests of episodic (recognition) and semantic (lexical decision) memory in which letter strings were presented twice within trial blocks. Semantic memory was superior when the 2nd presentation went to the same hemisphere as the 1st. Episodic memory, however, was superior when the 2nd presentation of a stimulus went to the opposite hemisphere. Results support an interhemispheric processing basis for episodic memories

Child mental health and educational attainment: multiple observers and the measurement error problem

We examine the effect of survey measurement error on the empirical relationship between child mental health and personal and family characteristics, and between child mental health and educational progress. Our contribution is to use unique UK survey data that contain (potentially biased) assessments of each child's mental state from three observers (parent, teacher and child), together with expert (quasi-)diagnoses, using an assumption of optimal diagnostic behaviour to adjust for reporting bias. We use three alternative restrictions to identify the effect of mental disorders on educational progress. Maternal education and mental health, family income and major adverse life events are all significant in explaining child mental health, and child mental health is found to have a large influence on educational progress. Our preferred estimate is that a one-standard-deviation reduction in ?true? latent child mental health leads to a 2- to 5-month loss in educational progress. We also find a strong tendency for observers to understate the problems of older children and adolescents compared to expert diagnosi

Public service markets: their economics, institutional oversight and regulation

Public services in the UK have been transformed over the past 25 years with the introduction of market oriented solutions into their provision. This has been characterised by a shift away from state provision to independent providers, and by the introduction of competition and choice. This shift was partly ideologically motivated and partly driven by budget cutting considerations following the financial crisis. As such it has been lacking a comprehensive economic justification or method of analysis. It is now commonly accepted that the language of economic markets is essential to frame arguments about how effectively public services are achieving their intended outcomes. Using market language and concepts may not always be comfortable for those from a traditional policy-making background. It can nevertheless be very useful when designing investigations into the effectiveness and value for money in the mechanisms of delivery of such services, whenever these services entail a degree of user choice as is currently the case in large parts of health, social care and education (referred to as competition in the market). Our paper wants to provide a conceptual basis on the way of thinking in these terms. We provide a description of the current state and then comment on the desirability of this quasi market approach. Uniquely in the literature, we analyse the expected and desired developments by distinguishing between choice and compulsory merit goods. In choice merit goods markets many users are unable to choose effectively because of the existence of a number of demand side or supply side market failures. Moreover, conflicts may exist between how service users actually make choices, and policy objectives such as universality or equity which may not be achieved simply by ‘leaving it to the market’. The users of compulsory merit goods are typically a minority and unable to internalise the full social benefits of their actions; hence it may be welfare-enhancing for society to coerce them ‘consume’ these services. As choice cannot be an objective, the commissioning (competition for the market) or direct provision by the state of such goods may meet public policy objectives more effectively than the market mechanism alone. Building on these foundations the paper discusses when public service markets are likely to be an effective method of achieving public policy objectives, and when they may not be. Our paper analyses the implications for the institutional and legal framework, funding oversight and regulation of public service markets as a result of their transformation into quasi-markets. The paper concludes with some suggestions for those charged with overseeing public service markets in practice based on this analysis

Phase II study of TP300 in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma

Background: TP300, a recently developed synthetic camptothecin analogue, is a highly selective topoisomerase I inhibitor. A phase I study showed good safety and tolerability. As camptothecins have proven active in oesophago-gastric adenocarcinomas, in this phase II study we assessed the efficacy and safety of TP300 in patients with gastric or gastro-oesophageal junction (GOJ) adenocarcinomas. Methods: Eligible patients had metastatic or locally advanced gastric or Siewert Types II or III GOJ inoperable adenocarcinoma. Patients were chemotherapy naïve unless this had been administered in the perioperative setting. TP300 was administered as a 1-h intravenous infusion every 3 weeks (a cycle) for up to 6 cycles at a starting dose of 8 mg/m2 with intra-patient escalation to 10 mg/m2 from cycle 2 in the absence of dose-limiting toxicity. Tumour responses (RECIST 1.1) were assessed every 6 weeks. Toxicity was recorded by NCI-CTCAE version 3.0. Using a modified two-stage Simon design (Stage I and II), a total of 43 patients were to be included providing there were 3 of 18 patients with objective response in Stage I of the study. Results: In Stage I of the study 20 patients (14 males, 6 females), median age 67 years (range 40 − 82), performance status ECOG 0/1, with GC [14] or GOJ carcinoma [6] were enrolled. Of the 16 evaluable patients, 11 received the planned dose increase to 10 mg/m2 at cycle 2, 2 decreased to 6 mg/m2, and 3 continued on 8 mg/m2. There were no objective responses after 2 cycles of treatment. Twelve patients had stable disease for 1 − 5 months and 4 had progressive disease. Median progression free survival (PFS) was 4.1 months (CI [1.6 − 4.9]), median time to progression (TTP) was 2.9 months (CI [1.4 − 4.2]). Grade 3/4 toxicities (worst grade all cycles) included 7 patients (35 %) with neutropenia, 4 patients (20 %) with anaemia, 2 patients (10 %) with thrombocytopenia, and 3 patients (15 %) with fatigue. This study was terminated at the end of Stage I due to a lack of the required (3/18) responders. Conclusions: This study of TP300 showed good drug tolerability but it failed to demonstrate sufficient efficacy as measured by radiological response

Genetic markers as instrumental variables: an application to child fat mass and academic achievement

Working Pape

Asymmetry in Resting Alpha Activity: Effects of Handedness

Frontal electroencephalographic (EEG) alpha band power during rest shows increased right, and/or decreased left, hemisphere activity under conditions of state or trait withdrawal-associated effect. Non-right-handers (NRH) are more likely to have mental illnesses and dispositions that involve such withdrawal-related effect. The aim of the study was to examine whether NRH might be characterized by increased right, relative to left, hemisphere activity during rest. Methods: The present research investigated that hypothesis by examining resting EEG alpha power in consistently-right-handed (CRH) and NRH individuals. Results: In support of the hypothesis, NRH demonstrated decreased right hemisphere alpha power, and therefore increased right hemisphere activity, during rest, compared to CRH.Conclusions: The study demonstrates further support for an association between increased right hemisphere activity and negative affect via an association between such EEG activity and NRH

Analysis of colorectal cancers in British Bangladeshi identifies early onset, frequent mucinous histotype and a high prevalence of RBFOX1 deletion

PMCID: PMC3544714This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Role of Farmer Knowledge in Agroecosystem Science: Rice Farming and Amphibians in the Philippines

Rice (Oryza sativa) agriculture provides food and economic security for nearly half of the world’s population. Rice agriculture is intensive in both land and agrochemical use. However, rice fields also provide aquatic resources for wildlife, including amphibians. In turn, some species may provide ecosystem services back to the farmers working in the rice agroecosystem. The foundation for understanding the complexity of agroecosystem–human relationships requires garnering information regarding human perceptions and knowledge of the role of biodiversity in these rice agroecosystems. Understanding farmer knowledge and perceptions of the ecosystem services provided by wildlife in their fields, along with their understanding of the risks to wildlife associated with agrochemical exposure, can inform biodiversity preservation efforts. In June and July 2014, we used focus groups and structured and semi-structured interviews that engaged 22 individuals involved in rice agriculture operations in Laguna, Philippines, a village close to the International Rice Research Institute in Los Baños, Philippines, to learn more about farmer perceptions and knowledge of amphibians in their rice fields. We found that many, though not all farm workers (managers, tenants, and laborers) noted declines in amphibian populations over time, expressed how they incorporated frogs and toads (Anura) into their daily lives, and recognized the value of amphibians as ecosystem service providers. Specifically, farmers noted that amphibians provide pest-management through consumption of rice pests, act as biomonitors for pesticide-related health outcomes, and provide a local food and economic resource. Some farmers and farm workers noted the general cultural value of listening to the “frogs sing when it rains.” Overall, our findings demonstrate that farmers have an understanding of the value of amphibians in their fields. Future efforts can support how engagement with farmers and farm workers to evaluate the value of wildlife in their fields can lead to directed education efforts to support biodiversity conservation in agroecosystems

Phase II study of TP300 in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma

Background TP300, a recently developed synthetic camptothecin analogue, is a highly selective topoisomerase I inhibitor. A phase I study showed good safety and tolerability. As camptothecins have proven active in oesophago-gastric adenocarcinomas, in this phase II study we assessed the efficacy and safety of TP300 in patients with gastric or gastro-oesophageal junction (GOJ) adenocarcinomas. Methods Eligible patients had metastatic or locally advanced gastric or Siewert Types II or III GOJ inoperable adenocarcinoma. Patients were chemotherapy naïve unless this had been administered in the perioperative setting. TP300 was administered as a 1-h intravenous infusion every 3 weeks (a cycle) for up to 6 cycles at a starting dose of 8 mg/m2 with intra-patient escalation to 10 mg/m2 from cycle 2 in the absence of dose-limiting toxicity. Tumour responses (RECIST 1.1) were assessed every 6 weeks. Toxicity was recorded by NCI-CTCAE version 3.0. Using a modified two-stage Simon design (Stage I and II), a total of 43 patients were to be included providing there were 3 of 18 patients with objective response in Stage I of the study. Results In Stage I of the study 20 patients (14 males, 6 females), median age 67 years (range 40 − 82), performance status ECOG 0/1, with GC [14] or GOJ carcinoma [6] were enrolled. Of the 16 evaluable patients, 11 received the planned dose increase to 10 mg/m2 at cycle 2, 2 decreased to 6 mg/m2, and 3 continued on 8 mg/m2. There were no objective responses after 2 cycles of treatment. Twelve patients had stable disease for 1 − 5 months and 4 had progressive disease. Median progression free survival (PFS) was 4.1 months (CI [1.6 − 4.9]), median time to progression (TTP) was 2.9 months (CI [1.4 − 4.2]). Grade 3/4 toxicities (worst grade all cycles) included 7 patients (35 %) with neutropenia, 4 patients (20 %) with anaemia, 2 patients (10 %) with thrombocytopenia, and 3 patients (15 %) with fatigue. This study was terminated at the end of Stage I due to a lack of the required (3/18) responders. Conclusions This study of TP300 showed good drug tolerability but it failed to demonstrate sufficient efficacy as measured by radiological response. Trial registration EU-CTR 2009-012097-12 2009-09-0

Switchable CAR-T cells mediate remission in metastatic pancreatic ductal adenocarcinoma.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is a disease of unmet medical need. While immunotherapy with chimeric antigen receptor T (CAR-T) cells has shown much promise in haematological malignancies, their efficacy for solid tumours is challenged by the lack of tumour-specific antigens required to avoid on-target, off-tumour effects. Switchable CAR-T cells whereby activity of the CAR-T cell is controlled by dosage of a tumour antigen-specific recombinant Fab-based 'switch' to afford a fully tunable response may overcome this translational barrier. DESIGN: In this present study, we have used conventional and switchable CAR-T cells to target the antigen HER2, which is upregulated on tumour cells, but also present at low levels on normal human tissue. We used patient-derived xenograft models derived from patients with stage IV PDAC that mimic the most aggressive features of PDAC, including severe liver and lung metastases. RESULTS: Switchable CAR-T cells followed by administration of the switch directed against human epidermal growth factor receptor 2 (HER2)-induced complete remission in difficult-to-treat, patient-derived advanced pancreatic tumour models. Switchable HER2 CAR-T cells were as effective as conventional HER2 CAR-T cells in vivo testing a range of different CAR-T cell doses. CONCLUSION: These results suggest that a switchable CAR-T system is efficacious against aggressive and disseminated tumours derived from patients with advanced PDAC while affording the potential safety of a control switch