Evaluation of radiological and clinical efficacy of ^{90}Y-DOTATATE} therapy in patients with progressive metastatic midgut neuroendocrine carcinomas

Background: To evaluate the radiological and clinical therapeutic effectiveness of ^{90}Y-octreotate [DOTATATE] inpatients with progressive somatostatin receptor-positive midgut neuroendocrine carcinomas (GEPNETs). Material/Methods: The study group: 34 patients, with histological proven extensive non-resectable and progressive midgut GEP-NETs. Radionuclide therapy (^{90}Y-DOTATATE) was given i.v. with a mean activity per administration 3,82 GBq. Initial clinical tumor responses were assessed 6-7 weeks after therapy completion and then once 3-monthly. The objective tumor response was classified according to the RECIST, initially between 4-6 months and then after each of the 6 months interval. Results: At 6 months after treatment completion, radiological tumor response was observed in 6 subjects with PR (19%), 25 presented SD (78%) and single had PD (3%). Overall clinical response to therapy at 6 months follow-up was observed in 23 patients (68%), SD in 5 patients (15%) and PD in 6 (18%). A year after therapy radiological tumour response was seen in 11 patients (44%), SD had 12 subjects (44%) and DP was noted in 2 patients. Two years after completed therapy PR was seen in 6 patients (33%), SD in additional 11 subjects (61%), single patient had PD. Clinical response to treatment in terms of PR and SD were noted in 22 patients (88%) after 1 year and in 14 patients (87%) after 2 years. Median PFS was 20 months, while the median OS was 23 months. In the 6 patients with clinical PD within initial 6 months the median PFS was 6 months and OS 11 months, while in those with SD or PR PFS was 22 months and OS 26 months (P<0.05). Conclusions: Therapy with ^{90}Y-DOTATATE} is effective in terms of clinical response, however the radiological response measured by the RECIST criteria underestimates benefits of this type of therapy in patients with progressive somatostatin receptor-positive midgut neuroendocrine carcinomas

Normative Data and Minimally Detectable Change for Inner Retinal Layer Thicknesses Using a Semi-automated OCT Image Segmentation Pipeline

Neurodegenerative and neuroinflammatory diseases regularly cause optic nerve and retinal damage. Evaluating retinal changes using optical coherence tomography (OCT) in diseases like multiple sclerosis has thus become increasingly relevant. However, intraretinal segmentation, a necessary step for interpreting retinal changes in the context of these diseases, is not standardized and often requires manual correction. Here we present a semi-automatic intraretinal layer segmentation pipeline and establish normative values for retinal layer thicknesses at the macula, including dependencies on age, sex, and refractive error. Spectral domain OCT macular 3D volume scans were obtained from healthy participants using a Heidelberg Engineering Spectralis OCT. A semi-automated segmentation tool (SAMIRIX) based on an interchangeable third-party segmentation algorithm was developed and employed for segmentation, correction, and thickness computation of intraretinal layers. Normative data is reported froma 6mmEarly Treatment Diabetic Retinopathy Study (ETDRS) circle around the fovea. An interactive toolbox for the normative database allows surveying for additional normative data. We cross-sectionally evaluated data from218 healthy volunteers (144 females/74males, age 36.5 ± 12.3 years, range 18–69 years). Average macular thickness (MT) was 313.70 ± 12.02 μm, macular retinal nerve fiber layer thickness (mRNFL) 39.53 ± 3.57 μm, ganglion cell and inner plexiform layer thickness (GCIPL) 70.81 ± 4.87 μm, and inner nuclear layer thickness (INL) 35.93 ± 2.34 μm. All retinal layer thicknesses decreased with age. MT and GCIPL were associated with sex, with males showing higher thicknesses. Layer thicknesses were also positively associated with each other. Repeated-measurement reliability for the manual correction of automatic intraretinal segmentation results was excellent, with an intra-class correlation coefficient >0.99 for all layers. The SAMIRIX toolbox can simplify intraretinal segmentation in research applications, and the normative data application may serve as an expandable reference for studies, in which normative data cannot be otherwise obtained

Fibroblast growth factor 10 is a negative regulator of postnatal neurogenesis in the mouse hypothalamus

New neurons are generated in the postnatal rodent hypothalamus, with a subset of tanycytes in the third ventricular (3V) wall serving as neural stem/progenitor cells. However, the precise stem cell niche organization, the intermediate steps and the endogenous regulators of postnatal hypothalamic neurogenesis remain elusive. Quantitative lineage-tracing in vivo revealed that conditional deletion of fibroblast growth factor 10 (Fgf10) from Fgf10-expressing beta-tanycytes at postnatal days (P)4-5 results in the generation of significantly more parenchymal cells by P28, composed mostly of ventromedial and dorsomedial neurons and some glial cells, which persist into adulthood. A closer scrutiny in vivo and ex vivo revealed that the 3V wall is not static and is amenable to cell movements. Furthermore, normally beta-tanycytes give rise to parenchymal cells via an intermediate population of alpha-tanycytes with transient amplifying cell characteristics. Loss of Fgf10 temporarily attenuates the amplification of beta-tanycytes but also appears to delay the exit of their alpha-tanycyte descendants from the germinal 3V wall. Our findings suggest that transience of cells through the alpha-tanycyte domain is a key feature, and Fgf10 is a negative regulator of postnatal hypothalamic neurogenesis.Peer reviewe

Development and validation of PozQoL: A scale to assess quality of life of PLHIV

Background: Advances in medical treatment for HIV are driving major changes in HIV policy and practice, including the encouragement of intake and adherence to HIV antiretroviral treatment (ART) by people living with HIV (PLHIV) for both personal and public health benefits. However, there is increasing recognition that achieving these goals will require a concurrent focus on the broader psychological and social wellbeing of PLHIV. Increasingly calls are being been made to incorporate a stronger focus on quality of life (QoL) of PLHIV into HIV prevention policy. In order to achieve this goal, HIV community, support and healthcare services need a valid, short and practical way to evaluate QoL of PLHIV accessing their programs. Current QoL measures are either long, complex, restricted in their use, or expensive. To address these shortcomings, the PozQoL study aimed to develop, test and validate a short and freely available scale assessing QoL among PLHIV. Methods: Drawing on a literature review, the prioritisation of domains and development of the initial pool of items was conducted in consultation with PLHIV community organisations in Australia. The items covered health concerns, psychological, social, and functional wellbeing. Testing involved a baseline and a follow-up survey of 465 adult Australians living with HIV. Participants were recruited through social media and various community organizations nationwide. The survey included the pilot PozQoL scale and other validated measures of health and wellbeing. Results: Guided by an Exploratory Factor Analysis and conceptual considerations, a 13-item scale was developed. The PozQoL scale demonstrated high levels of fit in a Confirmatory Factor Analysis, very good internal consistency, test-retest reliability, and concurrent validity with other measures that approximated different aspects of QoL. Conclusion: The PozQoL scale has been tested in a diverse sample of adult PLHIV living in Australia, demonstrating very good reliability and validity. The insights from PLHIV and other stakeholders supported the balancing of statistical rigour and conceptual accuracy. The scale is now ready to be implemented and field-tested across a range of community, support and healthcare programs for PLHIV. This will make a significant contribution to the evaluation and enhancement of programs for PLHIV

Emotional intelligence buffers the effect of physiological arousal on dishonesty

We studied the emotional processes that allow people to balance two competing desires: benefitting from dishonesty and keeping a positive self-image. We recorded physiological arousal (skin conductance and heart rate) during a computer card game in which participants could cheat and fail to report a certain card when presented on the screen to avoid losing their money. We found that higher skin conductance corresponded to lower cheating rates. Importantly, emotional intelligence regulated this effect; participants with high emotional intelligence were less affected by their physiological reactions than those with low emotional intelligence. As a result, they were more likely to profit from dishonesty. However, no interaction emerged between heart rate and emotional intelligence. We suggest that the ability to manage and control emotions can allow people to overcome the tension between doing right or wrong and license them to bend the rules

\u201cGive, but Give until It Hurts\u201d: The Modulatory Role of Trait Emotional Intelligence on the Motivation to Help

Two studies investigated the effect of trait Emotional Intelligence (trait EI) on people\u2019s moti- vation to help. In Study 1, we developed a new computer-based paradigm that tested partic- ipants\u2019 motivation to help by measuring their performance on a task in which they could gain a hypothetical amount of money to help children in need. Crucially, we manipulated partici- pants\u2019 perceived efficacy by informing them that they had been either able to save the chil- dren (positive feedback) or unable to save the children (negative feedback). We measured trait EI using the Trait Emotional Intelligence Questionnaire\u2013Short Form (TEIQue-SF) and assessed participants\u2019 affective reactions during the experiment using the PANAS-X. Results showed that high and low trait EI participants performed differently after the presen- tation of feedback on their ineffectiveness in helping others in need. Both groups showed increasing negative affective states during the experiment when the feedback was negative; however, high trait EI participants better managed their affective reactions, modulating the impact of their emotions on performance and maintaining a high level of motivation to help. In Study 2, we used a similar computerized task and tested a control situation to explore the effect of trait EI on participants\u2019 behavior when facing failure or success in a scenario unre- lated to helping others in need. No effect of feedback emerged on participants\u2019 emotional states in the second study. Taken together our results show that trait EI influences the impact of success and failure on behavior only in affect-rich situation like those in which people are asked to help others in need

Sources of information-seeking on sexually transmitted infections and safer sex by older heterosexual Australian men and women

Sexually transmitted infections (STIs) have risen among older people in Australia and other countries. To guide future initiatives, we examined sources of information that older people use or are willing to use for knowledge about safer sex and STIs, including whether there are any gender differences. A total of 2137 Australian adults aged 60+ years completed a nationwide survey. Analyses focused on participants who were at risk of an STI (n = 686; 220 women and 466 men). Overall, information-seeking on STIs in the last year was low (18% men; 15% women). When sought, common sources included general media outlets (e.g., magazines, TV), healthcare providers (HCPs), and the Internet. HCPs were the most relied upon source among both women and men. Brochures, websites, and HCPs were rated highest as future sources; however, women indicated they were more willing than men to have information provided by brochures and websites. STI information-seeking was generally low, but there was willingness among both men and women to use a range of sources for gaining future information

Network structure and taxonomic composition of tritrophic communities of Fagaceae, cynipid gallwasps and parasitoids in Sichuan, China

A key question in insect community ecology is whether parasitoid assemblages are structured by the food plants of their herbivore hosts. Tritrophic communities centred on oak-feeding cynipid gallwasps are one of the best-studied tritrophic insect communities. Previous work suggests that host plant identity is a much stronger predictor of oak–cynipid interactions than of cynipid–parasitoid interactions. However, these relationships have not been formally quantified. We reason that the potential for ‘bottom-up’ effects should increase with host plant phylogenetic diversity. We, therefore, generated quantified interaction network data for previously unstudied tritrophic cynipid communities in Sichuan, China, where, in addition to Quercus, cynipid host plants include Castanea, Castanopsis and Lithocarpus. We characterise these communities taxonomically and compare the extent to which host plant taxonomy predicts plant–herbivore and plant–parasitoid associations. We sampled 42,620 cynipid galls of 176 morphotypes from 23 host plant species, yielding over 4500 specimens of 64 parasitoid morphospecies. Many parasitoids were identifiable to chalcidoid taxa present in other Holarctic oak cynipid communities, with the addition of Cynipencyrtus (Cynipencyrtidae). As elsewhere, Sichuan parasitoid assemblages were dominated by generalists. Gallwasp–plant interaction networks were significantly more modular than parasitoid–plant association networks. Gallwasps were significantly more specialised to host plants (i.e. had higher mean d' values) than parasitoids. Parasitoid assemblages nevertheless showed significant plant-associated beta diversity, with a dominant turnover component. We summarise parallels between our study and other Fagaceae-associated cynipid communities and discuss our findings in light of the processes thought to structure tritrophic interactions centred on endophytic insect herbivores

Network structure and taxonomic composition of tritrophic communities of Fagaceae, cynipid gallwasps and parasitoids in Sichuan, China

A key question in insect community ecology is whether parasitoid assemblages are structured by the food plants of their herbivore hosts. Tritrophic communities centred on oak‐feeding cynipid gallwasps are one of the best‐studied tritrophic insect communities. Previous work suggests that host plant identity is a much stronger predictor of oak–cynipid interactions than of cynipid–parasitoid interactions. However, these relationships have not been formally quantified. We reason that the potential for ‘bottom‐up’ effects should increase with host plant phylogenetic diversity. We, therefore, generated quantified interaction network data for previously unstudied tritrophic cynipid communities in Sichuan, China, where, in addition to Quercus, cynipid host plants include Castanea, Castanopsis and Lithocarpus. We characterise these communities taxonomically and compare the extent to which host plant taxonomy predicts plant–herbivore and plant–parasitoid associations. We sampled 42,620 cynipid galls of 176 morphotypes from 23 host plant species, yielding over 4500 specimens of 64 parasitoid morphospecies. Many parasitoids were identifiable to chalcidoid taxa present in other Holarctic oak cynipid communities, with the addition of Cynipencyrtus (Cynipencyrtidae). As elsewhere, Sichuan parasitoid assemblages were dominated by generalists. Gallwasp–plant interaction networks were significantly more modular than parasitoid–plant association networks. Gallwasps were significantly more specialised to host plants (i.e. had higher mean d' values) than parasitoids. Parasitoid assemblages nevertheless showed significant plant‐associated beta diversity, with a dominant turnover component. We summarise parallels between our study and other Fagaceae‐associated cynipid communities and discuss our findings in light of the processes thought to structure tritrophic interactions centred on endophytic insect herbivores