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The fraction of absorbed photosynthetically active radiation (FAPAR) is one of the bio-geophysical Essential Climate Variables assessed through remote sensing observations and distributed globally by space and environmental agencies. Any reliable remote sensing product should be benchmarked against a reference, which is normally determined by means of ground-based measurements. They should generally be aggregated spatially to be compared with remote sensing products at different resolutions. In this work, the effectiveness of various in situ sampling methods proposed to assess FAPAR from flux measurements was evaluated using a three-dimensional radiative transfer framework over eight virtual vegetated landscapes, including dense forests (leaf-on and leaf-off models), open canopies, sparse vegetation, and agricultural fields with a nominal extension of 1 hectare. The reference FAPAR value was determined by summing the absorbed PAR-equivalent photons by either all canopy components, both branches and leaves, or by only the leaves. The incoming and upwelling PAR fluxes were simulated in different illumination conditions and at a high spatial resolution (50 cm). They served to replicate in situ virtual FAPAR measurements, which were carried out using either stationary sensor networks or transects. The focus was on examining the inherent advantages and drawbacks of in situ measurement protocols against GCOS requirements. Consequently, the proficiency of each sampling technique in reflecting the distribution of incident and reflected PAR fluxes—essential for calculating FAPAR—was assessed. This study aims to support activities related to the validation of remote sensing FAPAR products by assessing the potential uncertainty associated with in situ determination of the reference values. Among the sampling schemes considered in our work, the cross shaped sampling schemes showed a particular efficiency in properly representing the pixel scale FAPAR over most of the scenario considered.

We present a genome assembly from an individual male Sphaerophoria taeniata (a hoverfly; Arthropoda; Insecta; Diptera; Syrphidae). The genome sequence is 609.3 megabases in span. Most of the assembly is scaffolded into 5 chromosomal pseudomolecules, including the X and Y sex chromosomes. The mitochondrial genome has also been assembled and is 16.42 kilobases in length. Gene annotation of this assembly on Ensembl identified 24,213 protein coding genes.

We present a genome assembly from an individual female Ophonus ardosiacus (a ground beetle; Arthropoda; Insecta; Coleoptera; Carabidae). The genome sequence is 911.9 megabases in span. Most of the assembly is scaffolded into 19 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled and is 16.61 kilobases in length. Gene annotation of this assembly on Ensembl identified 40,995 protein coding genes.

We present a genome assembly from an individual male Agrypnus murinus (a click beetle; Arthropoda; Insecta; Coleoptera; Elateridae). The genome sequence is 1,578.5 megabases in span. Most of the assembly is scaffolded into 9 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled and is 18.23 kilobases in length. Gene annotation of this assembly on Ensembl identified 42,204 protein coding genes.

Abstract Members of the highly polymorphic Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family expressed on the surface of infected erythrocytes (IEs) are important virulence factors, which mediate vascular adhesion of IEs via endothelial host receptors and are targets of naturally acquired immunity. The PfEMP1 family can be divided into clinically relevant subgroups, of which some bind intercellular adhesion molecule 1 (ICAM-1). While the acquisition of IgG specific for ICAM-1-binding DBLβ domains is known to differ between PfEMP1 groups, its ability to induce antibody-dependent cellular phagocytosis (ADCP) is unclear. We therefore measured plasma levels of DBLβ-specific IgG, the ability of such IgG to inhibit PfEMP1-binding to ICAM-1, and its ability to opsonize IEs for ADCP, using plasma from Beninese children with severe (SM) or uncomplicated malaria (UM). IgG specific for DBLβ from group A and B ICAM-1-binding PfEMP1 were dominated by IgG1 and IgG3, and were similar in SM and UM. However, levels of plasma IgG inhibiting ICAM-1-binding of group A DBLβ of PFD1235w was significantly higher in children with UM than SM, and acute UM plasma induced a higher ADCP response than acute SM plasma.

Abstract Thin film-based optical sensors have been attracting increasing interest for use in developing technologies such as biometrics. Multilayered dielectric thin films with different refractive indices have been utilized to modulate the optical properties in specific wavelength bands for spectral selectivity of Thin Film Narrow Bandpass Filters (TFNBFs). Progress in TFNBF design has been made with the incorporation of metallic thin films. Narrower bandwidths with higher transmittance have been achieved in specific spectral bands. In this work, Ti/TiO2/SiO2 based multilayer thin films were prepared using pulsed-DC reactive sputtering. Computer simulations using the Essential Macleod Program allowed the optimal number of layers and thickness of the multilayer thin films to be determined to efficiently tailor the optical path transmitting specific wavelength bands. The addition of Ti metal layers within dielectric (TiO2/SiO2) multilayer thin films significantly changes the cutoff frequency of transmittance at specific wavelengths. Representative 26 multilayer films consisting of Ti, TiO2, and SiO2 show lower transmittance of 10.29% at 400 nm and 10.48% at 680 nm. High transmittance of 80.42% at 485 nm was observed, which is expected to improve the spectral selectivity of the TFNBF. This work provides a contribution to future simulation based design strategy based on experimental thin film engineering for potential industrial development opportunities such as optical biometrics.

Abstract To avoid collisions, pedestrians depend on their ability to perceive and interpret the visual motion of other road users. Eye movements influence motion perception, yet pedestrians’ gaze behavior has been little investigated. In the present study, we ask whether observers sample visual information differently when making two types of judgements based on the same virtual road-crossing scenario and to which extent spontaneous gaze behavior affects those judgements. Participants performed in succession a speed and a time-to-arrival two-interval discrimination task on the same simple traffic scenario—a car approaching at a constant speed (varying from 10 to 90 km/h) on a single-lane road. On average, observers were able to discriminate vehicle speeds of around 18 km/h and times-to-arrival of 0.7 s. In both tasks, observers placed their gaze closely towards the center of the vehicle’s front plane while pursuing the vehicle. Other areas of the visual scene were sampled infrequently. No differences were found in the average gaze behavior between the two tasks and a pattern classifier (Support Vector Machine), trained on trial-level gaze patterns, failed to reliably classify the task from the spontaneous eye movements it elicited. Saccadic gaze behavior could predict time-to-arrival discrimination performance, demonstrating the relevance of gaze behavior for perceptual sensitivity in road-crossing.

Abstract Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of cardiometabolic diseases in overweight individuals. While liver biopsy is the current gold standard to diagnose NAFLD and magnetic resonance imaging (MRI) is a non-invasive alternative still under clinical trials, the former is invasive and the latter costly. We demonstrate electrical impedance tomography (EIT) as a portable method for detecting fatty infiltrate. We enrolled 19 overweight subjects to undergo liver MRI scans, followed by EIT measurements. The MRI images provided the a priori knowledge of the liver boundary conditions for EIT reconstruction, and the multi-echo MRI data quantified liver proton-density fat fraction (PDFF%) to validate fat infiltrate. Using the EIT electrode belts, we circumferentially injected pairwise current to the upper abdomen, followed by acquiring the resulting surface-voltage to reconstruct the liver conductivity. Pearson’s correlation analyses compared EIT conductivity or MRI PDFF with body mass index, age, waist circumference, height, and weight variables. We reveal that the correlation between liver EIT conductivity or MRI PDFF with demographics is statistically insignificant, whereas liver EIT conductivity is inversely correlated with MRI PDFF (R = −0.69, p = 0.003, n = 16). As a pilot study, EIT conductivity provides a portable method for operator-independent and cost-effective detection of hepatic steatosis.

Abstract Cancer patients undergo detrimental toxicities and ineffective treatments especially in the relapsed setting, due to failed treatment attempts. The development of a tool that predicts the clinical response of individual patients to therapy is greatly desired. We have developed a novel patient-derived 3D tissue engineered bone marrow (3DTEBM) technology that closely recapitulate the pathophysiological conditions in the bone marrow and allows ex vivo proliferation of tumor cells of hematologic malignancies. In this study, we used the 3DTEBM to predict the clinical response of individual multiple myeloma (MM) patients to different therapeutic regimens. We found that while no correlation was observed between in vitro efficacy in classic 2D culture systems of drugs used for MM with their clinical efficacious concentration, the efficacious concentration in the 3DTEBM were directly correlated. Furthermore, the 3DTEBM model retrospectively predicted the clinical response to different treatment regimens in 89% of the MM patient cohort. These results demonstrated that the 3DTEBM is a feasible platform which can predict MM clinical responses with high accuracy and within a clinically actionable time frame. Utilization of this technology to predict drug efficacy and the likelihood of treatment failure could significantly improve patient care and treatment in many ways, particularly in the relapsed and refractory setting. Future studies are needed to validate the 3DTEBM model as a tool for predicting clinical efficacy.

Historical climate adaptation can give insight into the potential for adaptation to contemporary changing climates. Here Bennett et al. investigate thermal tolerance evolution across much of the tree of life and find different effects of ancestral climate on the subsequent evolution of ectotherms vs. endotherms.

The tumour microenvironment (TME) has a major role in chemoresistance in multiple myeloma. The authors show that a nanoparticle targeted to TME and loaded with bortezomib (BTZ) and Y27632 is more effective than free drugs, non-targeted and single-agent controls and reduces BTZ-related side effects.

Changes in life-history requirements drive trophic variations, particularly in large marine predators. The life history of many shark species is still poorly known and understanding their dietary ontogeny is a challenging task, especially for highly migratory species. Stable isotope analysis has proven as a useful method for examining the foraging strategies of sharks and other marine predators. We assessed the foraging strategies and ontogenetic changes of scalloped hammerhead sharks, Sphyrna lewini, at Galapagos Marine Reserve (GMR), by analysing δ13C and δ15N signatures in different maturity stages. Our isotopic results suggest ontogenetic shifts in resource use between sub-adult and adult stages, but not between adult and juvenile stages. Carbon isotopic signatures found in the juvenile stage were enriched in contrast to sub-adults (~0.73‰) suggesting a combination of the maternal input and the use of coastal resources around the Galapagos Islands. Adult female sharks also showed enrichment in δ13C (~0.53‰) in comparison to sub-adult stages that suggest feeding in high primary productivity areas, such as the GMR. This study improves the understanding of the trophic ecology and ontogenetic changes of a highly migratory shark that moves across the protected and unprotected waters of the Eastern Tropical Pacific.

Changes in life-history requirements drive trophic variations, particularly in large marine predators. The life history of many shark species is still poorly known and understanding their dietary ontogeny is a challenging task, especially for highly migratory species. Stable isotope analysis has proven as a useful method for examining the foraging strategies of sharks and other marine predators. We assessed the foraging strategies and ontogenetic changes of scalloped hammerhead sharks, Sphyrna lewini, at Galapagos Marine Reserve (GMR), by analysing δ13C and δ15N signatures in different maturity stages. Our isotopic results suggest ontogenetic shifts in resource use between sub-adult and adult stages, but not between adult and juvenile stages. Carbon isotopic signatures found in the juvenile stage were enriched in contrast to sub-adults (~0.73‰) suggesting a combination of the maternal input and the use of coastal resources around the Galapagos Islands. Adult female sharks also showed enrichment in δ13C (~0.53‰) in comparison to sub-adult stages that suggest feeding in high primary productivity areas, such as the GMR. This study improves the understanding of the trophic ecology and ontogenetic changes of a highly migratory shark that moves across the protected and unprotected waters of the Eastern Tropical Pacific.

BackgroundOritavancin is a lipoglycopeptide antibiotic with in vitro bactericidal activity against gram-positive pathogens indicated for use in adults with acute bacterial skin and skin structure infections (ABSSSI). Its concentration-dependent activity and prolonged half-life provide a convenient single-dose alternative to multi-dose daily therapies for ABSSSI. This retrospective cohort study was conducted to quantify the clinical and economic advantages of using oritavancin compared to other antibiotic agents that have been historically effective for ABSSSI.MethodsSeventy-nine patients received oritavancin who had failed previous outpatient antibiotic therapy (OPAT) for cellulitis or abscess and were subsequently readmitted to the hospital as an inpatient between 2016 and 2018. These patients were compared to a cohort of 28 patients receiving other antibiotics following OPAT failure and subsequent hospitalization for these two infection types. The primary clinical end point was average length of stay (aLOS) and secondary endpoints included readmission rates for the same indication at 30 and 90 days after discharge and the average hospital cost (aHC).ResultsA total of 107 patients were hospitalized for treatment of cellulitis or abscess. Demographic characteristics of both the oritavancin and comparator groups were similar except for the presence of diabetes. The primary clinical endpoint showed a non-significant decrease in aLOS between the oritavancin group versus comparator (2.12 days versus 2.59 days; p = 0.097). The secondary endpoints revealed lower readmission rates associated with oritavancin treatment at 30 and 90 days; the average hospital cost was 5.9% lower for patients that received oritavancin.ConclusionThe results of this study demonstrate that oritavancin provides not only a single-dose alternative to multi-day therapies for skin and skin structure infections, but also a clinical and economic advantage compared to other antibiotic agents.

Study objectivesHeightened immigration enforcement may induce fear in undocumented patients when coming to the Emergency Department (ED) for care. Limited literature examining health system policies to reduce immigrant fear exists. In this multi-site qualitative study, we sought to assess provider and system-level policies on caring for undocumented patients in three California EDs.MethodsWe recruited 41 ED providers and administrators from three California EDs (in San Francisco, Oakland, and Sylmar) with large immigrant populations. Participants were recruited using a trusted gatekeeper and snowball sampling. We conducted semi-structured interviews and analyzed the transcripts using constructivist grounded theory.ResultsWe interviewed 10 physicians, 11 nurses, 9 social workers, and 11 administrators, and identified 7 themes. Providers described existing policies and recent policy changes that facilitate access to care for undocumented patients. Providers reported that current training and communication around policies is limited, there are variations between who asks about and documents status, and there remains uncertainty around policy details, laws, and jurisdiction of staff. Providers also stated they are taking an active role in building safety and trust and see their role as supporting undocumented patients.ConclusionsThis study introduces ED-level health system perspectives and recommendations for caring for undocumented patients. There is a need for active, multi-disciplinary ED policy training, clear policy details including the extent of providers' roles, protocols on the screening and documentation of status, and continual reassessment of our health systems to reduce fear and build safety and trust with our undocumented communities.

Patients often do not disclose domestic violence (DV) to healthcare providers in emergency departments and other healthcare settings. Barriers to disclosure may include fears and misconceptions about whether, and under what circumstances, healthcare providers report DV to law enforcement and immigration authorities. We sought to assess undocumented Latino immigrants (UDLI), Latino legal residents/citizens (LLRC) and non-Latino legal residents/citizens (NLRC) beliefs about disclosure of DV victimization to healthcare providers and healthcare provider reporting of DV to law enforcement and immigration authorities. From 10/2018-2/2020, we conducted this survey study at two urban emergency departments (EDs) in California. Participants, enrolled by convenience sampling, responded to survey questions adapted from a previously published survey instrument that was developed to assess undocumented immigrant fears of accessing ED care. Our primary outcomes were the proportions of UDLI, LLRC and NLRC who knew of someone who had experienced DV in the past year, whether these DV victims were afraid to access ED care, reasons DV victims were afraid to access ED care, and rates of misconceptions (defined according to current California law) about the consequences of disclosing DV to healthcare providers. Of 667 patients approached, 531 (80%) agreed to participate: 32% UDLI, 33% LLRC, and 35% NLRC. Of the 27.5% of respondents who knew someone who experienced DV in the past year, 46% stated that the DV victim was afraid to seek ED care; there was no significant difference in this rate between groups. The most common fears reported as barriers to disclosure were fear the doctor would report DV to police (31%) and fear that the person perpetrating DV would find out about the disclosure (30.3%). Contrary to our hypothesis, UDLI had lower rates of misconceptions about healthcare provider and law enforcement responses to DV disclosure than LLRC and NLRC. Fear of disclosing DV and misconceptions about the consequences of disclosure of DV to healthcare providers were common, indicating a need for provider, patient, and community education and changes that lower barriers to help-seeking.

OBJECTIVES:Selective dorsal rhizotomy (SDR) has gained interest as an intervention to reduce spasticity and pain, and improve quality of life and mobility in children with cerebral palsy mainly affecting the legs (diplegia). We evaluated the cost-effectiveness of SDR in England. METHODS:Cost-effectiveness was quantified with respect to Gross Motor Function Measure (GMFM-66) and the pain dimension of the Cerebral Palsy Quality of Life questionnaire for Children (CPQOL-Child). Data on outcomes following SDR over two years were drawn from a national evaluation in England which included 137 children, mean age 6.6 years at surgery. The incremental impact of SDR on GMFM-66 was determined through comparison with data from a historic Canadian cohort not undergoing SDR. Another single centre provided data on hospital care over ten years for 15 children undergoing SDR at a mean age of 7.0 years, and a comparable cohort managed without SDR. The incremental impact of SDR on pain was determined using a before and after comparison using data from the national evaluation. Missing data were imputed using multiple imputation. Incremental costs of SDR were determined as the difference in costs over 5 years for the patients undergoing SDR and those managed without SDR. Uncertainty was quantified using bootstrapping and reported as the cost-effectiveness acceptability curve. RESULTS:In the base case, the incremental cost-effectiveness ratios (ICERs) for SDR are £1,382 and £903 with respect to a unit improvement in GMFM-66 and the pain dimension of CPQOL-Child, respectively. Inclusion of data to 10 years indicates SDR is cheaper than management without SDR. Incremental costs and ICERs for SDR rose in sensitivity analysis applying an alternative regression model to cost data. CONCLUSIONS:Data on outcomes from a large observational study of SDR and long-term cost data on children who did and did not receive SDR indicates SDR is cost-effective.

Sharks are top predators across ocean food webs and have a major ecological role in marine ecosystems. Investigating the trophic ecology of this group of species is thus essential to understand ecosystem functioning and inform specific management actions aimed at shark conservation. The Galapagos Islands represent one of the last ocean wildernesses, where populations of sharks and other top marine predators come close to a pristine status. Here we provide the first study on the trophic ecology of the tiger shark (Galeocerdo cuvier) within the Galapagos Marine Reserve (GMR), using a combination of stable isotope analysis, satellite tracking, and passive acoustic telemetry to investigate ontogenetic and spatial variations at two regions. The mean estimated δ13C and δ15N at Isabela island (western region) were -13.9 ± 0.5‰ and 13.7 ± 0.7‰; and for Santa Cruz island (central region) were -13.8 ± 0.3‰ and 13.4 ± 0.7‰, respectively. Green sea turtles (Chelonia mydas) were the main prey item for large tiger sharks (>280 cm TL), while smaller sharks mainly fed on squid and pelagic fish. Tiger sharks exhibited a high degree of philopatry around green sea-turtle nesting areas, with the majority of sharks detected around green sea-turtle nesting areas for at least 10 months after their capture date, and some individuals were even present during the entire three-year study period. Although we did not report statistically significant differences between the two regions, isotopic and electronic tagging data suggest that tiger sharks in the Galapagos could be segregated into specific populations separated by geographical scales of

Statements about building walls, deportation and denying services to undocumented immigrants made during President Trump's presidential campaign and presidency may induce fear in Latino populations and create barriers to their health care access. To assess how these statements relate to undocumented Latino immigrants' (UDLI) and Latino legal residents/citizens' (LLRC) perceptions of safety and their presentations for emergency care, we conducted surveys of adult patients at three county emergency departments (EDs) in California from June 2017 to December 2018. Of 1,684 patients approached, 1,337 (79.4%) agreed to participate: 34.3% UDLI, 36.9% LLRC, and 29.8% non-Latino legal residents/citizens (NLRC). The vast majority of UDLI (95%), LLRC (94%) and NLRC (85%) had heard statements about immigrants. Most UDLI (89%), LLRC (88%) and NLRC (87%) either thought that these measures were being enacted now or will be enacted in the future. Most UDLI and half of LLRC reported that these statements made them feel unsafe living in the US, 75% (95% CI 70-80%) and 51% (95% CI 47-56%), respectively. More UDLI reported that these statements made them afraid to come to the ED (24%, 95% CI 20-28%) vs LLRC (4.4%, 95% CI 3-7%) and NLRC (3.5%, 95% CI 2-6%); 55% of UDLI with this fear stated it caused them to delay coming to the ED (median delay 2-3 days). The vast majority of patients in our California EDs have heard statements during the 2016 presidential campaign or from President Trump about measures against undocumented immigrants, which have induced worry and safety concerns in both UDLI and LLRC patients. Exposure to these statements was also associated with fear of accessing emergency care in some UDLIs. Given California's sanctuary state status, these safety concerns and ED access fears may be greater in a nationwide population of Latinos.

BACKGROUND:We conducted a systematic review to assess the effectiveness of smoking cessation, physical activity (PA), diet, and alcohol reduction interventions delivered by mobile technology to prevent non-communicable diseases (NCDs). METHODS:We searched for randomised controlled trials (RCTs) of mobile-based NCD prevention interventions using MEDLINE, EMBASE, Global Health, CINAHL (Jan 1990-Jan 2016). Two authors extracted data. FINDINGS:71 trials were included: smoking cessation (n = 18); PA (n = 15), diet (n = 3), PA and diet (n = 25); PA, diet, and smoking cessation (n = 2); and harmful alcohol consumption (n = 8). 4 trials had low risk of bias. The effect of SMS-based smoking cessation support on biochemically verified continuous abstinence was pooled relative risk [RR] 2.19 [95% CI 1.80-2.68], I2 = 0%) and on verified 7 day point prevalence of smoking cessation was pooled RR 1.51 [95% CI 1.06-2.15], I2 = 0%, with no reported adverse events. There was no difference in peak oxygen intake at 3 months in a trial of an SMS-based PA intervention. The effect of SMS-based diet and PA interventions on: incidence of diabetes was pooled RR 0.67 [95% CI 0.49, 0.90], I2 = 0.0%; end-point weight was pooled MD -0.99Kg [95% CI -3.63, 1.64] I2 = 29.4%; % change in weight was pooled MD -3.1 [95%CI -4.86- -1.3] I2 0.3%; and on triglyceride levels was pooled MD -0.19 mmol/L [95% CI -0.29, -0.08], I2 = 0.0%. The results of other pooled analyses of the effect of SMS-based diet and PA interventions were heterogenous (I2 59-90%). The effects of alcohol reduction interventions were inconclusive. CONCLUSIONS:Smoking cessation support delivered by SMS increases quitting rates. Trials of PA interventions reporting outcomes ≥3 months showed no benefits. There were at best modest benefits of diet and PA interventions. The effects of the most promising SMS-based smoking, diet and PA interventions on morbidity and mortality in high-risk groups should be established in adequately powered RCTs.

BACKGROUND:The beneficial effects of cardiac rehabilitation (CR) have been challenged in recent years and there is now a need to investigate whether current CR programmes, delivered in the context of modern cardiology, still benefit patients. METHODS:A systematic review of non-randomised controlled studies was conducted. Electronic searches of Medline, Embase, CINAHL, science citation index (web of science), CIRRIE and Open Grey were undertaken. Non-randomised studies investigating the effects of CR were included when recruitment occurred from the year 2000 onwards in accordance with significant CR guidance changes from the late 1990's. Adult patients diagnosed with acute myocardial infarction (AMI) were included. Non-English articles were considered. Two reviewers independently screened articles according to pre-defined selection criteria as reported in the PROSPERO database (CRD42015024021). RESULTS:Out of 2,656 articles, 8 studies involving 9,836 AMI patients were included. Studies were conducted in 6 countries. CR was found to reduce the risk of all-cause and cardiac-related mortality and improve Health-Related Quality of Life (HRQOL) significantly in at least one domain. The benefits of CR in terms of recurrent MI were inconsistent and no significant effects were found regarding re-vascularisation or re-hospitalisation following AMI. CONCLUSION:Recent observational evidence draws different conclusions to the most current reviews of trial data with respect to total mortality and re-hospitalisation, questioning the representativeness of historic data in the modern cardiological era. Future work should seek to clarify which patient and service level factors determine the likelihood of achieving improved all-cause and cardiac mortality and reduced hospital re-admissions.

BackgroundReciprocal interactions between epithelium and stroma play vital roles for prostate cancer development and progression. Enhanced secretions of cytokines and growth factors by cancer associated fibroblasts in prostate tumors create a favorable microenvironment for cancer cells to grow and metastasize. Our previous work showed that the progesterone receptor (PR) was expressed specifically in prostate stromal fibroblasts and smooth muscle cells. However, the expression levels of PR and its impact to tumor microenvironment in prostate tumors are poorly understood.MethodsImmunohistochemistry assays are applied to human prostate tissue biopsies. Cell migration, invasion and proliferation assays are performed using human prostate cells. Real-time PCR and ELISA are applied to measure gene expression at molecular levels.ResultsImmunohistochemistry assays showed that PR protein levels were decreased in cancer associated stroma when compared with paired normal prostate stroma. Using in vitro prostate stromal cell models, we showed that conditioned media collected from PR positive stromal cells inhibited prostate cancer cell migration and invasion, but had minor suppressive impacts on cancer cell proliferation. PR suppressed the secretion of stromal derived factor-1 (SDF-1) and interlukin-6 (IL-6) by stromal cells independent to PR ligands. Blocking PR expression by siRNA or supplementation of exogenous SDF-1 or IL-6 to conditioned media from PR positive stromal cells counteracted the inhibitory effects of PR to cancer cell migration and invasion.ConclusionsDecreased expression of the PR in cancer associated stroma may contribute to the elevated SDF-1 and IL-6 levels in prostate tumors and enhance prostate tumor progression.

BackgroundRecently, much attention has been paid to the role of cooperative breeding in the evolution of behavior. In many measures, cooperative breeders are more prosocial than non-cooperatively breeding species, including being more likely to actively share food. This is hypothesized to be due to selective pressures specific to the interdependency characteristic of cooperatively breeding species. Given the high costs of finding a new mate, it has been proposed that cooperative breeders, unlike primates that cooperate in other contexts, should not respond negatively to unequal outcomes between themselves and their partner. However, in this context such pressures may extend beyond cooperative breeders to other species with pair-bonding and bi-parental care.MethodsHere we test the response of two New World primate species with different parental strategies to unequal outcomes in both individual and social contrast conditions. One species tested was a cooperative breeder (Callithrix spp.) and the second practiced bi-parental care (Aotus spp.). Additionally, to verify our procedure, we tested a third confamilial species that shows no such interdependence but does respond to individual (but not social) contrast (Saimiri spp.). We tested all three genera using an established inequity paradigm in which individuals in a pair took turns to gain rewards that sometimes differed from those of their partners.ConclusionsNone of the three species tested responded negatively to inequitable outcomes in this experimental context. Importantly, the Saimiri spp responded to individual contrast, as in earlier studies, validating our procedure. When these data are considered in relation to previous studies investigating responses to inequity in primates, they indicate that one aspect of cooperative breeding, pair-bonding or bi-parental care, may influence the evolution of these behaviors. These results emphasize the need to study a variety of species to gain insight in to how decision-making may vary across social structures.

Predicting others' actions is crucial to successful social interaction. Previous research on joint action, based on a reaction-time paradigm called the Joint Simon Task, suggests that successful joint action stems from the simultaneous representation of the self with the other. Performance on this task provides a read-out of the degree of intrusion from a partner that participants experience from acting jointly compared to acting alone, which in turn is a measure of the degree to which participants mentally represent their co-actors during the task. To investigate the role of perceived group membership in this type of joint action and its influence on the representation of others, we first subjected participants to a minimal group paradigm while manipulating differences in social competition. We then asked participants to do the Joint Simon Task in pairs with an in-group or out-group member. Only participants who acted with an "in-group" partner on the joint task showed altered reaction times compared to when acting alone, presumably a change caused by the simultaneous and automatic representation of their in-group partner. In contrast, participants who acted with an out-group partner were unaffected in their reactions when doing the joint task, showing no evidence of representation of their out-group partner. This effect was present in both the high-competition and low-competition conditions, indicating that the differential effects of group membership on representation during joint action were driven by perceived group membership and independent of the effects of social competition. We concluded that participants failed to represent out-group members as socially relevant agents not based on any personality or situational characteristics, but in reaction only to their status as "other". In this way group membership appears to affect cognition on a very immediate and subconscious level.

Fatigue is a significant symptom in multiple sclerosis (MS) patients. First-generation disease modifying therapies (DMTs) are at best moderately effective to improve fatigue. Observations from small cohorts have indicated that natalizumab, an antibody targeting VLA-4, may reduce MS-related fatigue. The TYNERGY study aimed to further evaluate the effects of natalizumab treatment on MS-related fatigue. In this one-armed clinical trial including 195 MS patients, natalizumab was prescribed in a real-life setting, and a validated questionnaire, the Fatigue Scale for Motor and Cognitive functions (FSMC), was used both before and after 12 months of treatment to evaluate a possible change in the fatigue experienced by the patients. In the treated cohort all measured variables, that is, fatigue score, quality of life, sleepiness, depression, cognition, and disability progression were improved from baseline (all p values