Survival following gamma knife radiosurgery for brain metastasis from breast cancer

BACKGROUND: Breast cancer is the second most common cause of brain metastases in the United States. Although breast cancer induced brain metastases represent an incurable condition, some patients experience prolonged survival. In this retrospective study, we examine a cohort of patients with brain metastases from breast cancer treated with Gamma Knife stereotactic radiosurgery to identify factors that predict better outcomes. METHODS: A retrospective database of 100 patients treated for brain metastases due to breast cancer via Gamma Knife radiosurgery (GKS) from July 1998 through March 2009 was reviewed. Patients who received radiosurgery as sole treatment, as a planned boost after whole brain radiotherapy or surgical resection, or as salvage after prior whole brain radiation therapy (WBRT) or surgical resection were included. Prognostic factors identified to be significant for survival in previous brain metastasis studies were analyzed for significance by univariate and multivariate Cox analysis. RESULTS: Overall, the median brain progression-free survival time was 7.1 months and the median survival time was 12.3 months. No prognostic variables were significant for brain progression-free survival. For patients treated with a planned GKS after WBRT, GKS as sole treatment, GKS salvage after WBRT, GKS boost after surgery, or GKS for surgical salvage the median survival times (MSTs) were as follows: 12.2 months, 12.4 months, 9.5 months, 27.6 months and 33.4 months respectively. Differences between the groups were not significant (p = 0.06); however, GKS boost after surgery and GKS for salvage after surgery did have a trend toward better overall survival. The MST for patients of age <65 years was 14.5 months, compared to age ≥65 which was 7.7 months (p = 0.06) and remained a significant prognostic factor for overall survival on multivariate analysis. The MST for patients with a single lesion was 16.9 months, not significantly different than the MST of 14.5 months for patients with 2–3 lesions. However patients with >3 lesions had a MST of 5.9 months, which was significantly worse. Breast cancer subtype as approximated by biomarkers and KPS were not significant predictors of overall survival and stage at initial diagnosis was inversely associated with survival. CONCLUSION: Stereotactic radiosurgery offers good local control and prolonged survival in selected patients. Age and number of lesions are strong predictors of overall survival

A retrospective analysis of survival and prognostic factors after stereotactic radiosurgery for aggressive meningiomas

BACKGROUND: While most meningiomas are benign, aggressive meningiomas are associated with high levels of recurrence and mortality. A single institution’s Gamma Knife radiosurgical experience with atypical and malignant meningiomas is presented, stratified by the most recent WHO classification. METHODS: Thirty-one patients with atypical and 4 patients with malignant meningiomas treated with Gamma Knife radiosurgery between July 2000 and July 2011 were retrospectively reviewed. All patients underwent prior surgical resection. Overall survival was the primary endpoint and rate of disease recurrence in the brain was a secondary endpoint. Patients who had previous radiotherapy or prior surgical resection were included. Kaplan-Meier and Cox proportional hazards models were used to estimate survival and identify factors predictive of recurrence and survival. RESULTS: Post-Gamma Knife recurrence was identified in 11 patients (31.4%) with a median overall survival of 36 months and progression-free survival of 25.8 months. Nine patients (25.7%) had died. Three-year overall survival (OS) and progression-free survival (PFS) rates were 78.0% and 65.0%, respectively. WHO grade II 3-year OS and PFS were 83.4% and 70.1%, while WHO grade III 3-year OS and PFS were 33.3% and 0%. Recurrence rate was significantly higher in patients with a prior history of benign meningioma, nuclear atypia, high mitotic rate, spontaneous necrosis, and WHO grade III diagnosis on univariate analysis; only WHO grade III diagnosis was significant on multivariate analysis. Overall survival was adversely affected in patients with WHO grade III diagnosis, prior history of benign meningioma, prior fractionated radiotherapy, larger tumor volume, and higher isocenter number on univariate analysis; WHO grade III diagnosis and larger treated tumor volume were significant on multivariate analysis. CONCLUSION: Atypical and anaplastic meningiomas remain difficult tumors to treat. WHO grade III diagnosis and treated tumor volume were significantly predictive of recurrence and survival on multivariate analysis in aggressive meningioma patients treated with radiosurgery. Larger tumor size predicts poor survival, while nuclear atypia, necrosis, and increased mitotic rate are risk factors for recurrence. Clinical and pathologic predictors may help identify patients that are at higher risk for recurrence

Mindfulness in schools: a health promotion approach to improving adolescent mental health.

Between 10 and 20% of adolescents worldwide experience a mental health problem within a given 12-month period. Mental health problems impact on an adolescent’s potential to live a fulfilling and productive life and lead to challenges such as stigma, isolation and discrimination. To address this need, in recent years, there has been growing interest into broad-based school-integrated health promotion interventions that seek to build resilience and augment protective factors in adolescents. Mindfulness-based interventions (MBIs) reflect one such approach that have been administered to adolescent populations in both resilience building and treatment contexts. This paper discusses the utility of school-based MBIs as an adolescent health promotion approach and makes recommendations for intervention design, delivery and evaluation. Emerging evidence indicates that school-integrated MBIs may be a cost-effective means of not only meeting government objectives relating to adolescent mental health, but also for improving the wellbeing of teachers and parents. Furthermore, there is growing evidence indicating that mindfulness can elicit improvements in student learning performance and general classroom behaviour. However, notwithstanding these beneficial properties, there remains a need to conduct large-scale empirical investigations that seek to evaluate the effectiveness of school-integrated MBIs at a regional or national level. A further challenge is the need to ensure that mindfulness instructors are able to impart to adolescents an experiential understanding of this ancient contemplative technique.N

Animal models for COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the aetiological agent of coronavirus disease 2019 (COVID-19), an emerging respiratory infection caused by the introduction of a novel coronavirus into humans late in 2019 (frst detected in Hubei province, China). As of 18 September 2020, SARS-CoV-2 has spread to 215 countries, has infected more than 30 million people and has caused more than 950,000 deaths. As humans do not have pre-existing immunity to SARS-CoV-2, there is an urgent need to develop therapeutic agents and vaccines to mitigate the current pandemic and to prevent the re-emergence of COVID-19. In February 2020, the World Health Organization (WHO) assembled an international panel to develop animal models for COVID-19 to accelerate the testing of vaccines and therapeutic agents. Here we summarize the fndings to date and provides relevant information for preclinical testing of vaccine candidates and therapeutic agents for COVID-19.info:eu-repo/semantics/acceptedVersio

Leiomodin-3 dysfunction results in thin filament disorganization and nemaline myopathy

Peer reviewe

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Myth or Memory? Recollections of Penal Times in Irish Folklore

Stories of priests being hunted down and murdered at Mass Rocks by priest catchers and soldiers during the Penal era in Ireland persist to the present day. Using Ó Ciosáin’s (2004) tripartite taxonomy of memory this paper explores the reasons why these images continue to dominate and reflect persecuted nature of Catholicism

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

The mechanism of speech processing in congenital amusia: Evidence from Mandarin speakers

Congenital amusia is a neuro-developmental disorder of pitch perception that causes severe problems with music processing but only subtle difficulties in speech processing. This study investigated speech processing in a group of Mandarin speakers with congenital amusia. Thirteen Mandarin amusics and thirteen matched controls participated in a set of tone and intonation perception tasks and two pitch threshold tasks. Compared with controls, amusics showed impaired performance on word discrimination in natural speech and their gliding tone analogs. They also performed worse than controls on discriminating gliding tone sequences derived from statements and questions, and showed elevated thresholds for pitch change detection and pitch direction discrimination. However, they performed as well as controls on word identification, and on statement-question identification and discrimination in natural speech. Overall, tasks that involved multiple acoustic cues to communicative meaning were not impacted by amusia. Only when the tasks relied mainly on pitch sensitivity did amusics show impaired performance compared to controls. These findings help explain why amusia only affects speech processing in subtle ways. Further studies on a larger sample of Mandarin amusics and on amusics of other language backgrounds are needed to consolidate these results