16 research outputs found
ARCHITECTURAL INNOVATION AND EDUCATIONAL PHILOSOPHY IN EARLY CHILDHOOD EDUCATION AND CARE: THE CASE OF FUJI KINDERGARTEN IN JAPAN: Received: 24th April 2025 Revised: 30th April 2025 &1st May 2025 Accepted: 1st May 2025 Date of Publication: 7th May 2025
No full textThis case study explores Fuji Kindergarten, located in Tachikawa City, Tokyo, Japan, renowned for its innovative architecture and design. Rooted in Montessori philosophy, the kindergarten emphasizes free play, children's connection with nature, and autonomy. Designed by architects Takaharu and Yui Tezuka, the building features a distinctive circular layout, offering a 360-degree experience when standing at the center of the grassy playground. This paper examines Fuji Kindergarten's unique architectural features, its educational principles in alignment with Montessori education, and its broader implications for early childhood education. The success of Fuji Kindergarten not only challenges traditional educational practices but also introduces a new paradigm for integrating architectural innovation with child-centered pedagogies. By blending traditional Japanese architecture with contemporary educational philosophies, it demonstrates how thoughtful design can significantly impact young children's developmental outcomes and educational experiences. This study highlights the importance of creating educational environments that align with pedagogical goals, fostering spaces that support the holistic development of children
Generation of Functional CLL-Specific Cord Blood CTL Using CD40-Ligated CLL APC
No full textPMCID: PMC3526610This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
MAN IN THOUGHTS OF A GENIUS Psychological-analytical approach to Pascal’s anthropology
No full textCovjek – ta “misleca trska” to stvorenje koje se može
definirati kao “inzistirajuce, mislece, paradoksalno bice”, koja se
paradoksalnost ocituje u spoznaji da je istovremeno “sve i ništa”..,
leitmotiv je Pascalovih promišljanja u “Mislima”.
Pascal je jezicni i intelektualni virtuoz, koji ne mari za
sustavnost i metodologijski okvir promišljanja. On zalazi u najdublje
sfere covjekove mislece, ali i osjecajuce egzistencije, nastojeci
neizravno i spontano ’pomiriti’ višestoljetni “dvoboj” izme$u vjere
i razuma. Njegov je covjek “pâtos osjecaja i mišljenja” (op. a.),
kojim hodi beskonacno, nespoznatljivo i nedohvatljivo bice, njegov
Stvoritelj...
Prethodno navedene formulacije nastojat cu izložiti u ovome
elaboratu u tri koraka:
Prvi dio elaborata referira se na analizu samog Pascala,
kreirajuci njegov svojevrsni psihološki profil, koji autorica ovog
clanka smatra pregnantnim i presudnim za Pascalov put spoznaje
covjeka i Boga
Drugi dio elaborata tematski je fokusiran na pitanje zašto
covjek (ni)je kadar “osobno” spoznati Boga
Treci dio elaborata sadržajno nastoji približiti i pojasniti
problematiku Pascalovog aksioma “credo, ergo sum”.
U zakljucku autorica clanka pojašnjava dileme oko citiranja
temeljem dvaju razlicitih izdanja Pascalovih “Misli” na hrvatskom
jeziku.Man – that “thinking cane”, that creature who can be defined as
a “persistent, thinking, paradoxical being”, who paradoxically reveals
himself in the cognition that he is at the same time “everything and
nothing” …, is the leitmotiv of Pascal’s reflections in his “Pénsees”
(“Thoughts”).
Pascal is a linguistic and intellectual wizard, who does not care for
a systematic and methodological framework of reflections. He enters
into the deepest spheres of man’s mental and emotional existence,
trying to restore, indirectly and spontaneously, the harmony between
faith and reason. His man is the “floor of feelings and thoughts” over
which an infinite, incomprehensible and unattainable being, his
Creator, is walking.
I will try to present the formulations mentioned above in three
steps. The first part of the study refers to the analysis of Pascal himself,
shaping a kind of his psychological profile, which the author of the
study holds to be pregnant and crucial for Pascal’s understanding of
man and God. The second part of the study focuses on the question
why man is not able to conceive God “personally”. The third part of
the study is trying to bring nearer and explain the issue of Pascal’s
axiom “credo, ergo sum”. In conclusion the author explains the
dilemma related to quotations on the basis of two different editions
of Pascal’s “Thoughts” in Croatian language
Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma
No full textBACKGROUND Nivolumab plus ipilimumab or nivolumab alone resulted in longer progression-free and overall survival than ipilimumab alone in a trial involving patients with advanced melanoma. We now report 5-year outcomes in the trial.
METHODS We randomly assigned patients with previously untreated advanced melanoma to receive one of the following regimens: nivolumab (at a dose of 1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram every 2 weeks); nivolumab (3 mg per kilogram every 2 weeks) plus ipilimumab-matched placebo; or ipilimumab (3 mg per kilogram every 3 weeks for four doses) plus nivolumab-matched placebo. The two primary end points were progression-free survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group, as compared with the ipilimumab group.
RESULTS At a minimum follow-up of 60 months, the median overall survival was more than 60.0 months (median not reached) in the nivolumab-plus-ipilimumab group and 36.9 months in the nivolumab group, as compared with 19.9 months in the ipilimumab group (hazard ratio for death with nivolumab plus ipilimumab vs. ipilimumab, 0.52; hazard ratio for death with nivolumab vs. ipilimumab, 0.63). Overall survival at 5 years was 52% in the nivolumab-plus-ipilimumab group and 44% in the nivolumab group, as compared with 26% in the ipilimumab group. No sustained deterioration of health-related quality of life was observed during or after treatment with nivolumab plus ipilimumab or with nivolumab alone. No new late toxic effects were noted.
CONCLUSIONS Among patients with advanced melanoma, sustained long-term overall survival at 5 years was observed in a greater percentage of patients who received nivolumab plus ipilimumab or nivolumab alone than in those who received ipilimumab alone, with no apparent loss of quality of life in the patients who received regimens containing nivolumab. (Funded by Bristol-Myers Squibb and others; CheckMate 067 ClinicalTrials.gov number, NCT01844505.)
Improved endpoints for cancer immunotherapy trials
No full textUnlike chemotherapy, which acts directly on the tumor, cancer immunotherapies exert their effects on the immune system and demonstrate new kinetics that involve building a cellular immune response, followed by changes in tumor burden or patient survival. Thus, adequate design and evaluation of some immunotherapy clinical trials require a new development paradigm that includes reconsideration of established endpoints. Between 2004 and 2009, several initiatives facilitated by the Cancer Immunotherapy Consortium of the Cancer Research Institute and partner organizations systematically evaluated an immunotherapy-focused clinical development paradigm and created the principles for redefining trial endpoints. On this basis, a body of clinical and laboratory data was generated that supports three novel endpoint recommendations. First, cellular immune response assays generate highly variable results. Assay harmonization in multicenter trials may minimize variability and help to establish cellular immune response as a reproducible biomarker, thus allowing investigation of its relationship with clinical outcomes. Second, immunotherapy may induce novel patterns of antitumor response not captured by Response Evaluation Criteria in Solid Tumors or World Health Organization criteria. New immune-related response criteria were defined to more comprehensively capture all response patterns. Third, delayed separation of Kaplan-Meier curves in randomized immunotherapy trials can affect results. Altered statistical models describing hazard ratios as a function of time and recognizing differences before and after separation of curves may allow improved planning of phase III trials. These recommendations may improve our tools for cancer immunotherapy trials and may offer a more realistic and useful model for clinical investigation. © 2010 The Author
Author Correction: Subsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade
No full textHealth-related quality of life with nivolumab plus relatlimab versus nivolumab monotherapy in patients with previously untreated unresectable or metastatic melanoma: RELATIVITY-047 trial
No full textBackground: In the phase II/III RELATIVITY-047 trial, a novel fixed-dose combination (FDC) of nivolumab plus relatlimab (NIVO + RELA; a programmed death-1 and a lymphocyte-activation gene 3 inhibitor, respectively) significantly improved progression-free survival (PFS) versus NIVO in patients with previously untreated unresectable or metastatic melanoma (median follow-up, 13.2 months) with stable health-related quality of life (HRQoL), although grade three or four treatment-related adverse events (TRAEs) were more frequent with the combination. Updated HRQoL results (median follow-up, 19.3 months) are presented. Methods: Patients were randomised to receive intravenous NIVO + RELA (480 mg and 160 mg, respectively) or NIVO (480 mg) every 4 weeks. HRQoL was assessed using the Functional Assessment of Cancer Treatment-Melanoma (FACT-M) and EQ-5D-3L questionnaires at baseline, before dosing at each treatment cycle, and at follow-up (posttreatment) visits. Results: Consistent with the initial analysis, HRQoL remained stable with NIVO + RELA on treatment and was similar to that with NIVO. Mean changes from baseline did not exceed clinically meaningful thresholds. HRQoL results were consistent across instruments and scales/subscales. Despite an increased rate of grade three or four TRAEs with NIVO + RELA versus NIVO, the proportion of patients reporting that they were bothered 'quite a bit' or 'very much' by TRAEs was low and comparable between treatments. Conclusion: Results from the RELATIVITY-047 trial show that the PFS benefit with NIVO + RELA FDC over NIVO was obtained with stable patient-reported HRQoL, supporting NIVO + RELA as a first-line treatment option for patients with advanced melanoma. © 2023 The Author(s
Never be silent : publishing & imperialism in Kenya, 1884-1963
No full textSocial communications are central to any social struggle. There is a sizable body of literature from other countries on the use of oral medium, newspapers, books and other forms of communications being used as tools for organising against a powerful enemy, as a training ground for cadres and for clarifying and developing revolutionary theory, ideology, organisation and practice. All this ensures a greater unity among those resisting oppression and exploitation. Thus revolutionary and liberation forces of Bolsheviks in the Soviet Union, the Communist Party of China, and in Vietnam had developed theories and practices of revolutionary publishing as part of their revolutionary work. This has also been the case during anti-colonial and anti-imperialist struggles in Africa, but very little of this has been systematically documented as an aspect of revolutionary communications policy and practice. While the
colonial communications systems have been reasonably well documented, the resistance communication systems remain largely undocumented and ignored. This book is an initial attempt to document this dynamic communications process in Kenya with its external struggles against colonialism and its complex internal struggles with overlaying divisions of race and class, Kenyan and foreign peoples. The main theme emerging from this experience is that people struggling to change their society always find ways of establishing their own system of communicating with the people they lead
and by whom they are led. Their mission of revolution, of change, of peace, of social and economic justice requires that they should never be silent. This was well understood and practised by the liberation forces in Kenya. They
were never silent
Efficacy and safety of nilotinib in patients with KIT-mutated metastatic or inoperable melanoma: final results from the global, single-arm, phase II TEAM trial
No full textBackground: The single-arm, phase II Tasigna Efficacy in Advanced Melanoma (TEAM) trial evaluated the KIT-selective tyrosine kinase inhibitor nilotinib in patients with KIT-mutated advanced melanoma without prior KIT inhibitor treatment. Patients and methods: Forty-two patients with KIT-mutated advanced melanoma were enrolled and treated with nilotinib 400mg twice daily. TEAM originally included a comparator arm of dacarbazine (DTIC)-treated patients; the design was amended to a single-arm trial due to an observed low number of KIT-mutated melanomas. Thirteen patients were randomized to DTIC before the protocol amendment removing this study arm. The primary endpoint was objective response rate (ORR), determined according to Response Evaluation Criteria In Solid Tumors. Results: ORR was 26.2% (n = 11/42; 95% CI, 13.9%-42.0%), sufficient to reject the null hypothesis (ORR <= 10%). All observed responses were partial responses (PRs; median response duration, 7.1 months). Twenty patients (47.6%) had stable disease and 10 (23.8%) had progressive disease; 1 (2.4%) response was unknown. Ten of the 11 responding patients had exon 11 mutations, four with an L576P mutation. The median progression-free survival and overall survival were 4.2 and 18.0 months, respectively. Three of the 13 patients on DTIC achieved a PR, and another patient had a PR following switch to nilotinib. Conclusion: Nilotinib activity in patients with advanced KIT-mutated melanoma was similar to historical data from imatinib-treated patients. DTIC treatment showed potential activity, although the low patient number limits interpretation. Similar to previously reported results with imatinib, nilotinib showed greater activity among patients with an exon 11 mutation, including L576P, suggesting that nilotinib may be an effective treatment option for patients with specific KIT mutations.Novartis Pharmaceuticals CorporationSCI(E)ARTICLE61380-13872
Author Correction: A single-cell and single-nucleus RNA-Seq toolbox for fresh and frozen human tumors
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