The impact of the 1999 education reform in Poland

Increasing the share of vocational secondary schooling has been a mainstay of development policy for decades, perhaps nowhere more so than in formerly socialist countries. The transition, however, led to significant restructuring of school systems, including a declining share of vocational students. Exposing more students to a general curriculum could improve academic abilities. This paper analyzes Poland’s significant improvement in international achievement tests and the restructuring of the education system that expanded general schooling to test the hypothesis that delayed vocational streaming improves outcomes. Using propensity score matching and differences-in-differences estimates, the authors show that delayed vocationalization had a positive and significant impact on student performance on the order of one standard deviation.Tertiary Education,Secondary Education,Education For All,Primary Education,Teaching and Learning

The Effects of Insurance Status on Pediatric Traumatic Brain Injury Outcomes: A Literature Review

Objective: To review the literature that describes the effects of insurance status on traumatic brain injury (TBI) outcomes among pediatric patients to understand how policies related to access to health insurance changes TBI outcomes. Method: This review was conducted using the Preferred Reporting Items of Systematic Reviews and Meta-Analysis (PRISMA). A search of OVID Medline was conducted in May of 2016 for all years for peer-reviewed articles that included keywords related to “brain injuries” and “insurance status”. Articles were included if authors conducted a separate analysis of children aged 0 to 18. Articles were excluded if the TBI was the result of abuse. Results: After screening for inclusion and exclusion criteria, a total of 12 articles were analyzed. Discussion/Summary: The findings of this review indicate that insurance status has a significant effect on the health outcomes of pediatric patients who experience TBI, with insured children having lower mortality rates than those with insurance from the government or uninsured. In addition, those insured from the government had a survival benefit when compared to those without insurance. We found evidence that insurance status plays a role in long term outcomes such as rates of placement into rehabilitation facilities and level of disability

V838 Monocerotis: the central star and its environment a decade after outburst

Aims. V838 Monocerotis erupted in 2002, brightened in a series of outbursts, and eventually developed a spectacular light echo. A very red star emerged a few months after the outburst. The whole event has been interpreted as the result of a merger. Methods. We obtained near-IR and mid-IR interferometric observations of V838 Mon with the AMBER and MIDI recombiners located at the Very Large Telescope Interferometer (VLTI) array. The MIDI two-beam observations were obtained with the 8m Unit Telescopes between October 2011 and February 2012. The AMBER three-beam observations were obtained with the compact array (B$\leq$m) in April 2013 and the long array (B$\leq$140m) in May 2014, using the 1.8m Auxiliary Telescopes. Results. A significant new result is the detection of a compact structure around V838 Mon, as seen from MIDI data. The extension of the structure increases from a FWHM of 25 mas at 8 {\mu}m to 70 mas at 13 {\mu}m. At the adopted distance of D = 6.1 $\pm$ 0.6 kpc, the dust is distributed from about 150 to 400 AU around V838 Mon. The MIDI visibilities reveal a flattened structure whose aspect ratio increases with wavelength. The major axis is roughly oriented around a position angle of -10 degrees, which aligns with previous polarimetric studies reported in the literature. This flattening can be interpreted as a relic of the 2002 eruption or by the influence of the currently embedded B3V companion. The AMBER data provide a new diameter for the pseudo-photosphere, which shows that its diameter has decreased by about 40% in 10yrs, reaching a radius R$_*$ = 750 $\pm$ 200 R$_{\odot}$ (3.5 $\pm$ 1.0 AU). Conclusions. After the 2002 eruption, interpreted as the merging of two stars, it seems that the resulting source is relaxing to a normal state. The nearby environment exhibits an equatorial over-density of dust up to several hundreds of AU.Comment: Astronomy and Astrophysics (2014) Will be set by the publishe

CheckMate 040 cohort 5: A phase I/II study of nivolumab in patients with advanced hepatocellular carcinoma and Child-Pugh B cirrhosis.

Background & Aims Patients with advanced hepatocellular carcinoma (aHCC) and Child-Pugh B liver function are often excluded from clinical trials. In previous studies, overall survival for these patients treated with sorafenib was ∼3–5 months; thus, new treatments are needed. Nivolumab, alone or in combination with ipilimumab, is conditionally approved in the United States to treat patients with aHCC who previously received sorafenib. We describe nivolumab monotherapy outcomes in patients with Child-Pugh B status. Methods This phase I/II, open-label, non-comparative, multicentre trial (27 centres) included patients with Child-Pugh B (B7–B8) aHCC. Patients received intravenous nivolumab 240 mg every 2 weeks until unacceptable toxicity or disease progression. Primary endpoints were objective response rate (ORR) by investigator assessment (using Response Evaluation Criteria in Solid Tumors v1.1) and duration of response. Safety was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events v4.0. Results Twenty-five sorafenib-naive and 24 sorafenib-treated patients began treatment between November 2016 and October 2017 (median follow-up, 16.3 months). Investigator-assessed ORR was 12% (95% CI 5–25%) with 6 patients responding; disease control rate was 55% (95% CI 40–69%). Median time to response was 2.7 months (interquartile range, 1.4–4.2), and median duration of response was 9.9 months (95% CI 9.7–9.9). Treatment-related adverse events (TRAEs) were reported in 25 patients (51%) and led to discontinuation in 2 patients (4%). The most frequent grade 3/4 TRAEs were hypertransaminasemia (n = 2), amylase increase (n = 2), and aspartate aminotransferase increase (n = 2). The safety of nivolumab was comparable to that in patients with Child-Pugh A aHCC. Conclusions Nivolumab showed clinical activity and favourable safety with manageable toxicities, suggesting it could be suitable for patients with Child-Pugh B aHCC. Lay summary In patients with advanced hepatocellular carcinoma, almost all systemic therapies require very good liver function, i.e. Child-Pugh A status. The evidence from this study suggests that nivolumab shows clinical activity and an acceptable safety profile in patients with hepatocellular carcinoma with Child-Pugh B status who have mild to moderate impairment of liver function or liver decompensation that might rule out other therapies. Further studies are warranted to assess the safety and efficacy of nivolumab in this patient population. Clinical trial number NCT01658878

Brain imaging predictors and the international study to predict optimized treatment for depression: study protocol for a randomized controlled trial

BACKGROUND: Approximately 50% of patients with major depressive disorder (MDD) do not respond optimally to antidepressant treatments. Given this is a large proportion of the patient population, pretreatment tests that predict which patients will respond to which types of treatment could save time, money and patient burden. Brain imaging offers a means to identify treatment predictors that are grounded in the neurobiology of the treatment and the pathophysiology of MDD. METHODS/DESIGN: The international Study to Predict Optimized Treatment in Depression is a multi-center, parallel model, randomized clinical trial with an embedded imaging sub-study to identify such predictors. We focus on brain circuits implicated in major depressive disorder and its treatment. In the full trial, depressed participants are randomized to receive escitalopram, sertraline or venlafaxine-XR (open-label). They are assessed using standardized multiple clinical, cognitive-emotional behavioral, electroencephalographic and genetic measures at baseline and at eight weeks post-treatment. Overall, 2,016 depressed participants (18 to 65 years old) will enter the study, of whom a target of 10% will be recruited into the brain imaging sub-study (approximately 67 participants in each treatment arm) and 67 controls. The imaging sub-study is conducted at the University of Sydney and at Stanford University. Structural studies include high-resolution three-dimensional T1-weighted, diffusion tensor and T2/Proton Density scans. Functional studies include standardized functional magnetic resonance imaging (MRI) with three cognitive tasks (auditory oddball, a continuous performance task, and Go-NoGo) and two emotion tasks (unmasked conscious and masked non-conscious emotion processing tasks). After eight weeks of treatment, the functional MRI is repeated with the above tasks. We will establish the methods in the first 30 patients. Then we will identify predictors in the first half (n = 102), test the findings in the second half, and then extend the analyses to the total sample. TRIAL REGISTRATION: International Study to Predict Optimized Treatment - in Depression (iSPOT-D). ClinicalTrials.gov, NCT00693849

Direct images and spectroscopy of a giant protoplanet driving spiral arms in MWC 758

Understanding the driving forces behind spiral arms in protoplanetary disks remains a challenge due to the faintness of young giant planets. MWC 758 hosts such a protoplanetary disk with a two-armed spiral pattern that is suggested to be driven by an external giant planet. We present new thermal infrared observations that are uniquely sensitive to redder (i.e., colder or more attenuated) planets than past observations at shorter wavelengths. We detect a giant protoplanet, MWC 758c, at a projected separation of ~100 au from the star. The spectrum of MWC 758c is distinct from the rest of the disk and consistent with emission from a planetary atmosphere with Teff = 500 +/- 100 K for a low level of extinction (AV<30), or a hotter object with a higher level of extinction. Both scenarios are commensurate with the predicted properties of the companion responsible for driving the spiral arms. MWC 758c provides evidence that spiral arms in protoplanetary disks can be caused by cold giant planets or by those whose optical emission is highly attenuated. MWC 758c stands out both as one of the youngest giant planets known, and also as one of the coldest and/or most attenuated. Furthermore, MWC 758c is among the first planets to be observed within a system hosting a protoplanetary disk.Comment: Published in Nature Astronom

JWST/NIRCam Coronagraphy of the Young Planet-hosting Debris Disk AU Microscopii

High-contrast imaging of debris disk systems permits us to assess the composition and size distribution of circumstellar dust, to probe recent dynamical histories, and to directly detect and characterize embedded exoplanets. Observations of these systems in the infrared beyond 2--3 $\mu$m promise access to both extremely favorable planet contrasts and numerous scattered-light spectral features -- but have typically been inhibited by the brightness of the sky at these wavelengths. We present coronagraphy of the AU Microscopii (AU Mic) system using JWST's Near Infrared Camera (NIRCam) in two filters spanning 3--5 $\mu$m. These data provide the first images of the system's famous debris disk at these wavelengths and permit additional constraints on its properties and morphology. Conducting a deep search for companions in these data, we do not identify any compelling candidates. However, with sensitivity sufficient to recover planets as small as $\sim 0.1$ Jupiter masses beyond $\sim 2^{\prime\prime}$ ($\sim 20$ au) with $5\sigma$ confidence, these data place significant constraints on any massive companions that might still remain at large separations and provide additional context for the compact, multi-planet system orbiting very close-in. The observations presented here highlight NIRCam's unique capabilities for probing similar disks in this largely unexplored wavelength range, and provide the deepest direct imaging constraints on wide-orbit giant planets in this very well studied benchmark system.Comment: 27 pages, 14 figure

Incorporation of Pentraxin 3 into Hyaluronan Matrices Is Tightly Regulated and Promotes Matrix Cross-linking

Mammalian oocytes are surrounded by a highly hydrated hyaluronan (HA)-rich extracellular matrix with embedded cumulus cells, forming the cumulus cell·oocyte complex (COC) matrix. The correct assembly, stability, and mechanical properties of this matrix, which are crucial for successful ovulation, transport of the COC to the oviduct, and its fertilization, depend on the interaction between HA and specific HA-organizing proteins. Although the proteins inter-α-inhibitor (IαI), pentraxin 3 (PTX3), and TNF-stimulated gene-6 (TSG-6) have been identified as being critical for COC matrix formation, its supramolecular organization and the molecular mechanism of COC matrix stabilization remain unknown. Here we used films of end-grafted HA as a model system to investigate the molecular interactions involved in the formation and stabilization of HA matrices containing TSG-6, IαI, and PTX3. We found that PTX3 binds neither to HA alone nor to HA films containing TSG-6. This long pentraxin also failed to bind to products of the interaction between IαI, TSG-6, and HA, among which are the covalent heavy chain (HC)·HA and HC·TSG-6 complexes, despite the fact that both IαI and TSG-6 are ligands of PTX3. Interestingly, prior encounter with IαI was required for effective incorporation of PTX3 into TSG-6-loaded HA films. Moreover, we demonstrated that this ternary protein mixture made of IαI, PTX3, and TSG-6 is sufficient to promote formation of a stable (i.e. cross-linked) yet highly hydrated HA matrix. We propose that this mechanism is essential for correct assembly of the COC matrix and may also have general implications in other inflammatory processes that are associated with HA cross-linking

Efficacy and Safety of Nivolumab Plus Ipilimumab in Patients With Advanced Hepatocellular Carcinoma Previously Treated With Sorafenib The CheckMate 040 Randomized Clinical Trial

IMPORTANCE Most patients with hepatocellular carcinoma (HCC) are diagnosed with advanced disease not eligible for potentially curative therapies; therefore, new treatment options are needed. Combining nivolumab with ipilimumab may improve clinical outcomes compared with nivolumab monotherapy. OBJECTIVE To assess efficacy and safety of nivolumab plus ipilimumab in patients with advanced HCC who were previously treated with sorafenib. DESIGN, SETTING, AND PARTICIPANTS CheckMate 040 is a multicenter, open-label, multicohort, phase 1/2 study. In the nivolumab plus ipilimumab cohort, patients were randomized between January 4 and September 26, 2016. Treatment group information was blinded after randomization. Median follow-up was 30.7 months. Data cutoff for this analysis was January 2019. Patients were recruited at 31 centers in 10 countries/territories in Asia, Europe, and North America. Eligible patients had advanced HCC (with/without hepatitis B or C) previously treated with sorafenib. A total of 148 patients were randomized (50 to arm A and 49 each to arms B and C). INTERVENTIONS Patients were randomized 1:1:1 to either nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, administered every 3 weeks (4 doses), followed by nivolumab 240 mg every 2 weeks (arm A); nivolumab 3 mg/kg plus ipilimumab 1 mg/kg, administered every 3 weeks (4 doses), followed by nivolumab 240 mg every 2 weeks (arm B); or nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks (arm C). MAIN OUTCOMES AND MEASURES Coprimary end points were safety, tolerability, and objective response rate. Duration of response was also measured (investigator assessed with the Response Evaluation Criteria in Solid Tumors v1.1). RESULTS Of 148 total participants, 120 were male (81%). Median (IQR) age was 60 (52.5-66.5). At data cutoff (January 2019), the median follow-up was 30.7 months (IQR, 29.9-34.7). Investigator-assessed objective response rate was 32% (95% CI, 20%-47%) in arm A, 27% (95% CI, 15%-41%) in arm B, and 29% (95% CI, 17%-43%) in arm C. Median (range) duration of response was not reached (8.3-33.7+) in arm A and was 15.2 months (4.2-29.9+) in arm B and 21.7 months (2.8-32.7+) in arm C. Any-grade treatment-related adverse events were reported in 46 of 49 patients (94%) in arm A, 35 of 49 patients (71%) in arm B, and 38 of 48 patients (79%) in arm C; there was 1 treatment-related death (arm A; grade 5 pneumonitis). CONCLUSIONS AND RELEVANCE In this randomized clinical trial, nivolumab plus ipilimumab had manageable safety, promising objective response rate, and durable responses. The arm A regimen (4 doses nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks then nivolumab 240 mg every 2 weeks) received accelerated approval in the US based on the results of this study. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0165887

The pattern of amyloid accumulation in the brains of adults with Down syndrome.

INTRODUCTION: Adults with Down syndrome (DS) invariably develop Alzheimer's disease (AD) neuropathology. Understanding amyloid deposition in DS can yield crucial information about disease pathogenesis. METHODS: Forty-nine adults with DS aged 25-65 underwent positron emission tomography with Pittsburgh compound-B (PIB). Regional PIB binding was assessed with respect to age, clinical, and cognitive status. RESULTS: Abnormal PIB binding became evident from 39 years, first in striatum followed by rostral prefrontal-cingulo-parietal regions, then caudal frontal, rostral temporal, primary sensorimotor and occipital, and finally parahippocampal cortex, thalamus, and amygdala. PIB binding was related to age, diagnostic status, and cognitive function. DISCUSSION: PIB binding in DS, first appearing in striatum, began around age 40 and was strongly associated with dementia and cognitive decline. The absence of a substantial time lag between amyloid accumulation and cognitive decline contrasts to sporadic/familial AD and suggests this population's suitability for an amyloid primary prevention trial.This research was generously supported by a grant from the Medical Research Council (grant ID number: 98480). Additional support came from the NIHR Cambridge Biomedical Research Centre, the NIHR Collaborations in Leadership for Applied Health Research and Care (CLAHRC) for the East of England, the NIHR Cambridge Dementia Biomedical Research Unit, The Down Syndrome Association, and The Health Foundation.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.jalz.2015.07.49