Search for the associated production of a b quark and a neutral supersymmetric Higgs boson which decays to tau pairs

We report results from a search for production of a neutral Higgs boson in association with a $b$ quark. We search for Higgs decays to $\tau$ pairs with one $\tau$ subsequently decaying to a muon and the other to hadrons. The data correspond to 2.7fb$^{-1}$ of \ppbar collisions recorded by the D0 detector at $\sqrt{s} = 1.96$TeV. The data are found to be consistent with background predictions. The result allows us to exclude a significant region of parameter space of the minimal supersymmetric model.Comment: Submitted to Phys. Rev. Letter

A novel method for classifying cortical state to identify the accompanying changes in cerebral hemodynamics

Background: Many brain imaging techniques interpret the haemodynamic response as an indirect indicator of underlying neural activity. However, a challenge when interpreting this blood based signal is how changes in brain state may affect both baseline and stimulus evoked haemodynamics. New method: We developed an Automatic Brain State Classifier (ABSC), validated on data from anaesthetised rodents. It uses vectorised information obtained from the windowed spectral frequency power of the Local Field Potential. Current state is then classified by comparing this vectorised information against that calculated from state specific training datasets. Results: The ABSC identified two user defined brain states (synchronised and desynchronised), with high accuracy (~90%). Baseline haemodynamics were found to be significantly different in the two identified states. During state defined periods of elevated baseline haemodynamics we found significant decreases in evoked haemodynamic responses to somatosensory stimuli. Comparison to existing methods: State classification - The ABSC (~90%) demonstrated greater accuracy than clustering (~66%) or 'power threshold' (~64%) methods of comparison.Haemodynamic averaging - Our novel approach of selectively averaging stimulus evoked haemodynamic trials by brain state yields higher quality data than creating a single average from all trials. Conclusions: The ABSC can account for some of the commonly observed trial-to-trial variability in haemodynamic responses which arises from changes in cortical state. This variability might otherwise be incorrectly attributed to alternative interpretations. A greater understanding of the effects of cortical state on haemodynamic changes could be used to inform techniques such as general linear modelling (GLM), commonly used in fMRI

Therapeutic implications of improved molecular diagnostics for rare CNS-embryonal tumor entities: results of an international, retrospective study

BACKGROUND: Only few data are available on treatment-associated behavior of distinct rare CNS-embryonal tumor entities previously treated as "CNS-primitive neuroectodermal tumors" (CNS-PNET). Respective data on specific entities, including CNS neuroblastoma, FOXR2 activated (CNS NB-FOXR2), and embryonal tumor with multi-layered rosettes (ETMR) are needed for development of differentiated treatment strategies. METHODS: Within this retrospective, international study, tumor samples of clinically well-annotated patients with the original diagnosis of CNS-PNET were analyzed using DNA methylation arrays (n=307). Additional cases (n=66) with DNA methylation pattern of CNS NB-FOXR2 were included irrespective of initial histological diagnosis. Pooled clinical data (n=292) were descriptively analyzed. RESULTS: DNA methylation profiling of "CNS-PNET" classified 58(19%) cases as ETMR, 57(19%) as HGG, 36(12%) as CNS NB-FOXR2, and 89(29%) cases were classified into 18 other entities. Sixty-seven (22%) cases did not show DNA methylation patterns similar to established CNS tumor reference classes. Best treatment results were achieved for CNS NB-FOXR2 patients (5-year PFS: 63%±7%, OS: 85%±5%, n=63), with 35/42 progression-free survivors after upfront craniospinal irradiation (CSI) and chemotherapy. The worst outcome was seen for ETMR and HGG patients with 5-year PFS of 18%±6% and 22%±7%, and 5-year OS of 24%±6% and 25%±7%, respectively. CONCLUSION: The historically reported poor outcome of CNS-PNET patients becomes highly variable when tumors are molecularly classified based on DNA methylation profiling. Patients with CNS NB-FOXR2 responded well to current treatments and a standard-risk-CSI based regimen may be prospectively evaluated. The poor outcome of ETMR across applied treatment strategies substantiates the necessity for evaluation of novel treatments

Брахитерапия ретинобластомы: результаты 13 лет применения

Brachytherapy (BT) is a method of radiation therapy with radioactive source contacting the tumor. It was proposed by P. Moore and H. Stallard in 1929. Despite those 50 years of experience with the use of BT in ophthalmic oncology, there are only a few studies on the use of Ru-106 BT for retinoblastoma (RB), and no publications on the use of Sr-90 BT have been found.Purpose. To present our own experience with the use of ruthenium and strontium ophthalmic applicators for BT in retinoblastoma.Materials and methods. 120 patients (137 eyes and 194 RB foci) received BT as a local treatment in the period from 2007 to 2020. At the time of treatment the age of the patients varied from 4 to 109 months (mean age 26 months). In 32% of cases (44 eyes) there were monofocal lesions, and in 68% of cases (93 eyes) — multifocal. In 36 cases (30%) BT was performed in the single eye. 79 patients (87 eyes) were treated with the use of ruthenium ophthalmic applicators (OAs), 25 patients (26 eyes) — with the use of strontium OAs, and for the treatment of 16 patients (24 eyes) both ruthenium and strontium OAs were used.Results. Clinically complete tumor regression was achieved in 62 % of cases (120 foci), partial tumor regression — in 31% of cases (60 foci). In 6% of cases (12 foci) continuous tumor growth was observed, and tumor recurrence occurred in 1% of cases (2 foci) within 4 to 6 months after BT. Local tumor control was achieved in 93% of cases.The single eyes were preserved in 92% of cases. BT complications of different intensity were reported in 38% of cases (46 patients — 49 eyes) with the mean follow-up duration of 55 months (3 to 157 months). In 92 % of cases (42 patients — 45 eyes) complications were associated with the use of ruthenium OAs, and only in 8% of cases (4 patients — 4 eyes) — with the use of strontium OAs. Risk factors for radiation-induced complications were identified: focus size (height more than 2.5 mm [P =0.0005], extension more than 7.3 mm [P <0,0001]), sclera dose more than 626 Gr (P = 0,0002), and the central localization of the tumor (P <0.0001).Conclusions. Ruthenium-106 and strontium-90 brachytherapy is a highly effective treatment modality for the management of RB.Брахитерапия (БТ)— метод контактного облучения опухоли радиоактивными пластинками, предложенный Moore P. и Stallard H. в 1929 году. Несмотря на более чем полувековую историю применения метода в офтальмоонкологии, представленные в литературе исследования, посвященные БТ с Ru106 при ретинобластоме (РБ), немногочисленны, а БТ со Sr90 не найдены.Цель работы. Представить собственный опыт БТ ретинобластомы с рутениевыми и стронциевыми офтальмоаппликаторами.Материалы и методы. В период с 2007 по 2020 годы БТ в качестве локального метода лечения РБ проведена 120 пациентам (137 глаз— 194 очага РБ). Возраст пациентов на момент лечения варьировал от 4 до 109 месяцев (в среднем— 26 мес.). Монофокальное поражение наблюдалось в 32% случаев (44 глаза), мультифокальное — в 68% случаев (93 глаза). БТ проводилась на единственном глазу в 36 случаях (30%). С использованием рутениевых офтальмоаппликаторов (ОА) пролечено 79 пациентов (87 глаз), стронциевых ОА — 25 пациентов (26 глаз), 16 пациентов (24 глаза) пролечено с использованием как рутениевых, так и стронциевых ОА.Результаты. Клинически полная регрессия опухоли была достигнута в62% случаев (120 очагов), частичная регрессия опухоли наблюдалась в31% случаев (60 очагов). В 6% случаев (12 очагов) наблюдался продолженный рост опухоли, в 1% случаев (2 очага) наблюдался рецидив опухоли в сроки от 4-6 месяцев после БТ. Локальный контроль над опухолью был достигнут в 93% случаев. Единственные глаза были сохранены в 92% случаев. Осложнения различной степени выраженности после БТ наблюдались в 38% случаев (46 пациентов— 49 глаз) при среднем сроке наблюдения 55 месяцев (от 3 до 157 мес.). В 92% случаев (42 пациента — 45 глаз) осложнения были ассоциированы с использованием рутениевых ОА и лишь в 8% случаев (4 пациента — 4 глаза) со стронциевыми. Были определены факторы риска развития радиоиндуцированных осложнений: размеры очага (высота более 2,5мм (Р =0,0005), протяженность более 7,3 мм (Р <0,0001), склеральная доза более 626 Гр (Р =0,0002) и центральная локализация опухоли (Р <0, 0001 ) .Выводы. Брахитерапия c рутением-106 и стронцием-90 является высокоэффективным методом лечения РБ

Clinical outcomes and patient-matched molecular composition of relapsed medulloblastoma

© 2021 by American Society of Clinical Oncology. Creative Commons Attribution Non-Commercial No Derivatives 4.0 License: https://creativecommons.org/licenses/by-nc-nd/4.0/Purpose: We sought to investigate clinical outcomes of relapsed medulloblastoma and to compare molecular features between patient-matched diagnostic and relapsed tumors. Methods: Children and infants enrolled on either SJMB03 (NCT00085202) or SJYC07 (NCT00602667) trials who experienced medulloblastoma relapse were analyzed for clinical outcomes, including anatomic and temporal patterns of relapse and postrelapse survival. A largely independent, paired molecular cohort was analyzed by DNA methylation array and next-generation sequencing. Results: A total of 72 of 329 (22%) SJMB03 and 52 of 79 (66%) SJYC07 patients experienced relapse with significant representation of Group 3 and wingless tumors. Although most patients exhibited some distal disease (79%), 38% of patients with sonic hedgehog tumors experienced isolated local relapse. Time to relapse and postrelapse survival varied by molecular subgroup with longer latencies for patients with Group 4 tumors. Postrelapse radiation therapy among previously nonirradiated SJYC07 patients was associated with long-term survival. Reirradiation was only temporizing for SJMB03 patients. Among 127 patients with patient-matched tumor pairs, 9 (7%) experienced subsequent nonmedulloblastoma CNS malignancies. Subgroup (96%) and subtype (80%) stabilities were largely maintained among the remainder. Rare subgroup divergence was observed from Group 4 to Group 3 tumors, which is coincident with genetic alterations involving MYC, MYCN, and FBXW7. Subgroup-specific patterns of alteration were identified for driver genes and chromosome arms. Conclusion: Clinical behavior of relapsed medulloblastoma must be contextualized in terms of up-front therapies and molecular classifications. Group 4 tumors exhibit slower biological progression. Utility of radiation at relapse is dependent on patient age and prior treatments. Degree and patterns of molecular conservation at relapse vary by subgroup. Relapse tissue enables verification of molecular targets and identification of occult secondary malignancies.info:eu-repo/semantics/publishedVersio

The role of ultrastructural abnormalities of the blood-brain barrier in the development of brain glioblastoma radioresistance

Background: Glioblastoma (GB) is the most commonly diagnosed brain tumor. Its management involves adjuvant therapies, such as radiation. The cause of high probability of GB local relapse is its radioresistance related to hypoxia arising from abnormal blood-brain barrier permeability in GB vessels and in the peritumoral zone (PZ).Aim: To study pathophysiology of hypoxia in the residual GB based on the abnormalities of the morphological elements of the capillary walls building up the blood-brain barrier in GB and PZ capillaries.Materials and methods: Samples for morphological evaluation were taken during surgery for GB in 5 patients. The samples were prepared for transmission electron microscopy according to the standard technique with fixation in 2% glutaraldehyde in phosphate buffer, post-fixation with osmium tetroxide, embedding in the epon-araldite mixture, and contrast staining of ultrathin sections with uranylacetate and lead citrate. Abnormalities of the capillary cells (mitochondrial vacuolization and vacuolization of endoplasmic reticulum in endothelial cells, pericytes and astrocytes), as well as of the acellular element of the capillary wall, i.e. basement membrane, were assessed in two groups of capillaries – those of GB (n = 38) and those of PZ (n = 32).Results: Abnormalities characteristic for apoptosis and oncosis were found in the cells of the GB and PZ capillaries of the blood-brain barrier, such as endothelial cells and pericytes. However, in the GB capillaries these abnormalities were signifcantly more frequent (р < 0.001). Only half (52.6%) of the GB capillaries had an edematous pericapillary astrocyte layer. In all other capillaries, astrocyte sprouts either were visualized as separate morphological elements (13.2%) or were not visualized at all (34.2%). All PZ capillaries had the astrocyte layer, being edematous in 68.8% of the capillaries and totally edematous only in 25%. Thickened basement membrane was found in the vast majority (89.5%) of the GB capillaries and only in 25% of the PZ capillaries (р < 0.001).Conclusion: Findings of abnormal cell elements in the GB capillaries leading to peritumoral edema and consequent hypoxia are highly likely to be the cause of the remnant GB radioresistance

Brain Region-specific Alterations in the Gene Expression of Cytokines, Immune Cell Markers and Cholinergic System Components During Peripheral Endotoxin-induced Inflammation

Inflammatory conditions characterized by excessive peripheral immune responses are associated with diverse alterations in brain function, and brain-derived neural pathways regulate peripheral inflammation. Important aspects of this bidirectional peripheral immune - brain communication, including the impact of peripheral inflammation on brain region-specific cytokine responses, and brain cholinergic signaling (which plays a role in controlling peripheral cytokine levels) remain unclear. To provide insight, we studied gene expression of cytokines, immune cell markers and brain cholinergic system components in the cortex, cerebellum, brainstem, hippocampus, hypothalamus, striatum, and thalamus in mice following an intraperitoneal lipopolysaccharide injection. Endotoxemia was accompanied by elevated serum levels of IL-1beta, IL-6 and other cytokines, and brain region-specific increases in Il1b (highest, relative to basal level increase - in cortex, lowest increase- in cerebellum) and Il6 (highest increase - in cerebellum, lowest increase - in striatum) mRNA expression. Gene expression of brain Gfap (astrocyte marker) was also differentially increased. However, Iba1 (microglia marker) mRNA expression was decreased in the cortex, hippocampus and other brain regions in parallel with morphological changes, indicating microglia activation. Brain choline acetyltransferase (Chat) mRNA expression was decreased in the striatum; acetylcholinesterase (Ache) mRNA expression was decreased in the cortex and increased in the hippocampus; and M1 muscarinic acetylcholine receptor (Chrm1) mRNA expression was decreased in the cortex and the brainstem. These results reveal a previously unrecognized regional specificity in brain immunoregulatory and cholinergic system gene expression in the context of peripheral inflammation, and are of interest for designing future anti-inflammatory approaches