The Lantern Vol. 35, No. 2, Spring 1969

• My Steps Alone • He Said He Hated Time • Communication • Evolution • Morning Almost Faded • Today I Looked • Gloucester • Have You Ever Tried • It\u27s Contact • The Galloping Camel • Life\u27s Flight • Haiku • Today is Monday • At the Waterfront • He Said to Me • Somewhere • A Darkened Window • The Stomach of the Sea • And When I Looked There Were Pinprick Holes in the Sky • Trinity • You Are a Goof • In Transit • Night Will Fall • Praise Be To...?https://digitalcommons.ursinus.edu/lantern/1095/thumbnail.jp

Distinctions Between Self-Report and Performance-Based Measures of Physical Function in Older Patients Prior to Chemotherapy

Under embargo until: 2022-04-02ABSTRACT Background: The maintenance of physical function (PF) is an extremely important outcome for older adults. Objective: The aims of this study were to, identify differences in subjective and objective measures of PF between younger older adults (YOA, 60-69 years of age) and older adults (OA, ≥70 years of age); compare the PF scores with age-matched samples from the general population; and evaluate for associations between subjective and objective measures of PF. Methods: Patients (n=139) were assessed using subjective (i.e., European Organization for Research and Treatment of Cancer Core Quality-of-Life Questionnaire (QLQ-C30)) and objective (i.e., Short Physical Performance Battery (SPPB)) measures prior to chemotherapy (CTX). Data were analyzed using parametric and nonparametric tests. Results: No differences were found between the two age groups in any of the subjective or objective measures of PF. Compared to the age-matched general population; both YOA and OA had significantly lower scores in both measures of PF. Large effect sizes were found for differences in QLQ-C30 role function, SPPB balance, and SPPB total scores between the YOA group and the age-matched general population samples. Correlations between the subjective and objective measures were low. Conclusions: Older patients with cancer have lower PF than their age matched general population prior to CTX. Longitudinal studies are warranted to evaluate for changes in PF during and following CTX. Implications for Practice: Nurses need to perform routine assessments of PF in older oncology patients prior to CTX. Our findings suggest that SPPB gait speed may be a useful screening measure for PF in older patients.acceptedVersio

Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study.

BackgroundInternal tandem duplication mutations in FLT3 are common in acute myeloid leukaemia and are associated with rapid relapse and short overall survival. The clinical benefit of FLT3 inhibitors in patients with acute myeloid leukaemia has been limited by rapid generation of resistance mutations, particularly in codon Asp835 (D835). We aimed to assess the highly selective oral FLT3 inhibitor gilteritinib in patients with relapsed or refractory acute myeloid leukaemia.MethodsIn this phase 1-2 trial, we enrolled patients aged 18 years or older with acute myeloid leukaemia who either were refractory to induction therapy or had relapsed after achieving remission with previous treatment. Patients were enrolled into one of seven dose-escalation or dose-expansion cohorts assigned to receive once-daily doses of oral gilteritinib (20 mg, 40 mg, 80 mg, 120 mg, 200 mg, 300 mg, or 450 mg). Cohort expansion was based on safety and tolerability, FLT3 inhibition in correlative assays, and antileukaemic activity. Although the presence of an FLT3 mutation was not an inclusion criterion, we required ten or more patients with locally confirmed FLT3 mutations (FLT3mut+) to be enrolled in expansion cohorts at each dose level. On the basis of emerging findings, we further expanded the 120 mg and 200 mg dose cohorts to include FLT3mut+ patients only. The primary endpoints were the safety, tolerability, and pharmacokinetics of gilteritinib. Safety and tolerability were assessed in the safety analysis set (all patients who received at least one dose of gilteritinib). Responses were assessed in the full analysis set (all patients who received at least one dose of study drug and who had at least one datapoint post-treatment). Pharmacokinetics were assessed in a subset of the safety analysis set for which sufficient data for concentrations of gilteritinib in plasma were available to enable derivation of one or more pharmacokinetic variables. This study is registered with ClinicalTrials.gov, number NCT02014558, and is ongoing.FindingsBetween Oct 15, 2013, and Aug 27, 2015, 252 adults with relapsed or refractory acute myeloid leukaemia received oral gilteritinib once daily in one of seven dose-escalation (n=23) or dose-expansion (n=229) cohorts. Gilteritinib was well tolerated; the maximum tolerated dose was established as 300 mg/day when two of three patients enrolled in the 450 mg dose-escalation cohort had two dose-limiting toxicities (grade 3 diarrhoea and grade 3 elevated aspartate aminotransferase). The most common grade 3-4 adverse events irrespective of relation to treatment were febrile neutropenia (97 [39%] of 252), anaemia (61 [24%]), thrombocytopenia (33 [13%]), sepsis (28 [11%]), and pneumonia (27 [11%]). Commonly reported treatment-related adverse events were diarrhoea (92 [37%] of 252]), anaemia (86 [34%]), fatigue (83 [33%]), elevated aspartate aminotransferase (65 [26%]), and increased alanine aminotransferase (47 [19%]). Serious adverse events occurring in 5% or more of patients were febrile neutropenia (98 [39%] of 252; five related to treatment), progressive disease (43 [17%]), sepsis (36 [14%]; two related to treatment), pneumonia (27 [11%]), acute renal failure (25 [10%]; five related to treatment), pyrexia (21 [8%]; three related to treatment), bacteraemia (14 [6%]; one related to treatment), and respiratory failure (14 [6%]). 95 people died in the safety analysis set, of which seven deaths were judged possibly or probably related to treatment (pulmonary embolism [200 mg/day], respiratory failure [120 mg/day], haemoptysis [80 mg/day], intracranial haemorrhage [20 mg/day], ventricular fibrillation [120 mg/day], septic shock [80 mg/day], and neutropenia [120 mg/day]). An exposure-related increase in inhibition of FLT3 phosphorylation was noted with increasing concentrations in plasma of gilteritinib. In-vivo inhibition of FLT3 phosphorylation occurred at all dose levels. At least 90% of FLT3 phosphorylation inhibition was seen by day 8 in most patients receiving a daily dose of 80 mg or higher. 100 (40%) of 249 patients in the full analysis set achieved a response, with 19 (8%) achieving complete remission, ten (4%) complete remission with incomplete platelet recovery, 46 (18%) complete remission with incomplete haematological recovery, and 25 (10%) partial remission INTERPRETATION: Gilteritinib had a favourable safety profile and showed consistent FLT3 inhibition in patients with relapsed or refractory acute myeloid leukaemia. These findings confirm that FLT3 is a high-value target for treatment of relapsed or refractory acute myeloid leukaemia; based on activity data, gilteritinib at 120 mg/day is being tested in phase 3 trials.FundingAstellas Pharma, National Cancer Institute (Leukemia Specialized Program of Research Excellence grant), Associazione Italiana Ricerca sul Cancro

Age-related differences in self-report and objective measures of cognitive function in older patients prior to chemotherapy

Aim: Evaluate for differences in demographic and clinical characteristics and subjective and objective measures of cognitive function (CF) between younger older adults (YOA, 60–69 years) and older adults (OA, ≥70 years). Design: Cross-sectional. Methods: Older oncology patients (n = 139) completed subjective (Attentional Function Index, European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC) CF scale) and objective (Montreal Cognitive Assessment, Trail Making Test (TMT) A & B) measures of CF prior to chemotherapy. Data were analyzed using parametric and nonparametric tests. Results: No differences were found between the two groups for any of the subjective or objective CF measures, except that OA patients had higher TMT B scores. Compared with the general population, OAs had significantly higher EORTC CF scores and YOAs had significantly worse scores for all of the objective tests. Clinically meaningful difference between group differences was found for the TMT B test

Adaptive optics tracking and pushing system for space debris manoeuvre

As space debris in lower Earth orbits are accumulating, techniques to lower the risk of space debris collisions must be developed. Within the context of the Space Environment Research Centre (SERC), the Australian National University (ANU) is developing an adaptive optics system for tracking and pushing space debris. The strategy is to pre-condition a laser launched from a 1.8 m telescope operated by Electro Optics Systems (EOS) on Mount Stromlo, Canberra and direct it at an object to perturb its orbit. Current progress towards implementing this experiment, which will ensure automated operation between the telescope and the adaptive optics system, will be presented.The authors would like to acknowledge the support of the Cooperative Research Centre for Space Environment Management (SERC Limited) through the Australian Government’s Cooperative Research Centre Programm

Sporadic Fatal Insomnia in Europe:Phenotypic features and diagnostic challenges

[Objective] Comprehensively describe the phenotypic spectrum of sporadic fatal insomnia (sFI) to facilitate diagnosis and management of this rare and peculiar prion disorder.[Methods] A survey among major prion disease reference centers in Europe identified 13 patients diagnosed with sFI in the past 20 years. We undertook a detailed analysis of clinical and histopathological features and the results of diagnostic investigations.[Results] Mean age at onset was 43 years, and mean disease duration 30 months. Early clinical findings included psychiatric, sleep, and oculomotor disturbances, followed by cognitive decline and postural instability. In all tested patients, video‐polysomnography demonstrated a severe reduction of total sleep time and/or a disorganized sleep. Cerebrospinal fluid (CSF) levels of proteins 14‐3‐3 and t‐tau were unrevealing, the concentration of neurofilament light protein (NfL) was more consistently increased, and the real‐time quaking‐induced conversion assay (RT‐QuIC) revealed a positive prion seeding activity in 60% of cases. Electroencephalography and magnetic resonance imaging showed nonspecific findings, whereas fluorodeoxyglucose positron emission tomography (FDG‐PET) demonstrated a profound bilateral thalamic hypometabolism in 71% of cases. Molecular analyses revealed PrPSc type 2 and methionine homozygosity at PRNP codon 129 in all cases.[Interpretation] sFI is a disease of young or middle‐aged adults, which is difficult to reconcile with the hypothesis of a spontaneous etiology related to stochastic, age‐related PrP misfolding. The combination of psychiatric and/or sleep‐related symptoms with oculomotor abnormalities represents an early peculiar clinical feature of sFI to be valued in the differential diagnosis. Video‐polysomnography, FDG‐PET, and especially CSF prion RT‐QuIC and NfL constitute the most promising supportive diagnostic tests in vivo.Peer reviewe

Caribbean Corals in Crisis: Record Thermal Stress, Bleaching, and Mortality in 2005

BACKGROUND The rising temperature of the world's oceans has become a major threat to coral reefs globally as the severity and frequency of mass coral bleaching and mortality events increase. In 2005, high ocean temperatures in the tropical Atlantic and Caribbean resulted in the most severe bleaching event ever recorded in the basin. METHODOLOGY/PRINCIPAL FINDINGS Satellite-based tools provided warnings for coral reef managers and scientists, guiding both the timing and location of researchers' field observations as anomalously warm conditions developed and spread across the greater Caribbean region from June to October 2005. Field surveys of bleaching and mortality exceeded prior efforts in detail and extent, and provided a new standard for documenting the effects of bleaching and for testing nowcast and forecast products. Collaborators from 22 countries undertook the most comprehensive documentation of basin-scale bleaching to date and found that over 80% of corals bleached and over 40% died at many sites. The most severe bleaching coincided with waters nearest a western Atlantic warm pool that was centered off the northern end of the Lesser Antilles. CONCLUSIONS/SIGNIFICANCE Thermal stress during the 2005 event exceeded any observed from the Caribbean in the prior 20 years, and regionally-averaged temperatures were the warmest in over 150 years. Comparison of satellite data against field surveys demonstrated a significant predictive relationship between accumulated heat stress (measured using NOAA Coral Reef Watch's Degree Heating Weeks) and bleaching intensity. This severe, widespread bleaching and mortality will undoubtedly have long-term consequences for reef ecosystems and suggests a troubled future for tropical marine ecosystems under a warming climate.This work was partially supported by salaries from the NOAA Coral Reef Conservation Program to the NOAA Coral Reef Conservation Program authors. NOAA provided funding to Caribbean ReefCheck investigators to undertake surveys of bleaching and mortality. Otherwise, no funding from outside authors' institutions was necessary for the undertaking of this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript