The Ursinus Weekly, December 6, 1973

ProTheatre to present “Second Shepherd’s Play” • Ursinus to comply with Nixon’s request to save energy • St. Andrew’s Society of New York announces graduate deadline • Professor Miller is elected to post • Christmas program to be first of kind • Women’s problems, schedule change aired at meeting • Economics club goes to New York • U.C. band to play on Monday • Editorial: The energy predicament; David Ben-Gurion • Wickersham publishes book, his first, on Greek history of fourth century B.C. • Letter to the editor: Mid-semester assessment • Arts Festival scheduled • Alumni corner: Class of ’73 active in many fields • The Zodiac: The signs and their compatibility discussed • Forum review: Longstreth speaks to forum audience on Megalopolis, 1984 • George Fago, of Psychology Department, delivers first Socratic Club lecture • Don’t think too hard • Hockey Bearettes go to nationals • Ursinus hoopla • Winter sports schedule • Swim team bows to Swarthmorehttps://digitalcommons.ursinus.edu/weekly/1007/thumbnail.jp

Predicting the Effect of Surface Texture on the Qualitative Form of Prehension

Reach-to-grasp movements change quantitatively in a lawful (i.e. predictable) manner with changes in object properties. We explored whether altering object texture would produce qualitative changes in the form of the precontact movement patterns. Twelve participants reached to lift objects from a tabletop. Nine objects were produced, each with one of three grip surface textures (high-friction, medium-friction and low-friction) and one of three widths (50 mm, 70 mm and 90 mm). Each object was placed at three distances (100 mm, 300 mm and 500 mm), representing a total of 27 trial conditions. We observed two distinct movement patterns across all trials—participants either: (i) brought their arm to a stop, secured the object and lifted it from the tabletop; or (ii) grasped the object ‘on-the-fly’, so it was secured in the hand while the arm was moving. A majority of grasps were on-the-fly when the texture was high-friction and none when the object was low-friction, with medium-friction producing an intermediate proportion. Previous research has shown that the probability of on-the-fly behaviour is a function of grasp surface accuracy constraints. A finger friction rig was used to calculate the coefficients of friction for the objects and these calculations showed that the area available for a stable grasp (the ‘functional grasp surface size’) increased with surface friction coefficient. Thus, knowledge of functional grasp surface size is required to predict the probability of observing a given qualitative form of grasping in human prehensile behaviour

Izloženost genotoksičnim agensima iz životnog okoliša tijekom prenatalnog razvoja i djetinjstva

Health disorders and diseases related to environmental exposure in children such as cancer and immunologic disturbances (asthma, allergies) are on the rise. However, complex transplacental and prepubertal genotoxicology is given very limited consideration, even though intrauterine development and early childhood may be critical for elucidating the cancer aetiology. The foetus is transplacentally exposed to contaminants in food and environment such as various chemicals, drugs, radiochemically contaminated water and air. Target organs of xenobiotic action may differ between the mother and the foetus due to specific stage of developmental physiology and enzyme distribution. This in turn may lead to different levels of clastogenic and aneugenic metabolites of the same xenobiotic in the mother and the foetus. Adult’s protective behaviour is not sufficient to isolate children from radioisotopes, pesticides, toxic metals and metalloids, environmental tobacco smoke, endocrine disrupting chemicals, and various food contaminants, which are just a part of the stressors present in a polluted environment. In order to improve legislation related to foetus and child exposure to genotoxic and possibly carcinogenic agents, oncologists, paediatricians, environmental health specialists, and genotoxicologists should work together much more closely to make a more effective use of accumulated scientific data, with the final aim to lower cancer incidence and mortality.Unatoč velikim naporima da se smanji okolišna izloženost u djece se dalje bilježi trend porasta pojavnosti karcinoma i imunosnih poremećaja (astma, alergije). Premda su intrauterini razvoj i rano djetinjstvo kritično razdoblje za tumačenje etiologije nastanka karcinoma, transplacentalna i prepubertetna genotoksikologija do danas su slabo istražene. Fetus je transplacentalno izložen brojnim fizikalnim i kemijskim čimbenicima: kontaminantima iz hrane i okoliša, radiokemijski kontaminiranoj vodi, zraku te lijekovima. Ciljna tkiva za djelovanje ksenobiotika mogu biti različita u majke i fetusa zbog različitosti u razvojnoj fiziologiji i distribuciji enzima. Zbog toga u organizmu majke i fetusa mogu nastati različite razine klastogenih i aneugenih metabolita istog ksenobiotika. Zaštitna uloga odraslih u namjeri da spriječe negativne utjecaje onečišćenog okoliša na djetetovo zdravlje često je ograničena jer su radioizotopi, olovo, PCB, pasivno pušenje, živa, endokrino aktivne tvari, pesticidi i kontaminanti prisutni u svim životnim područjima tijekom razvoja i rasta djeteta. Kako bi se poboljšalo zakonodavstvo vezano uz izloženost djece genotoksičnim i vjerojatno kancerogenim tvarima, tijekom razvoja potrebna je bolja suradnja onkologa, pedijatara, stručnjaka zdravstvene ekologije i genotoksikologa. Na taj način ostvarilo bi se uspješnije iskorištavanje postojećih znanstvenih podataka u cilju smanjenja incidencije karcinoma i mortaliteta

Telomerase inhibition abolishes the tumorigenicity of pediatric ependymoma tumor-initiating cells

Pediatric ependymomas are highly recurrent tumors resistant to conventional chemotherapy. Telomerase, a ribonucleoprotein critical in permitting limitless replication, has been found to be critically important for the maintenance of tumor-initiating cells (TICs). These TICs are chemoresistant, repopulate the tumor from which they are identified, and are drivers of recurrence in numerous cancers. In this study, telomerase enzymatic activity was directly measured and inhibited to assess the therapeutic potential of targeting telomerase. Telomerase repeat amplification protocol (TRAP) (n = 36) and C-circle assay/telomere FISH/ATRX staining (n = 76) were performed on primary ependymomas to determine the prevalence and prognostic potential of telomerase activity or alternative lengthening of telomeres (ALT) as telomere maintenance mechanisms, respectively. Imetelstat, a phase 2 telomerase inhibitor, was used to elucidate the effect of telomerase inhibition on proliferation and tumorigenicity in established cell lines (BXD-1425EPN, R254), a primary TIC line (E520) and xenograft models of pediatric ependymoma. Over 60 % of pediatric ependymomas were found to rely on telomerase activity to maintain telomeres, while no ependymomas showed evidence of ALT. Children with telomerase-active tumors had reduced 5-year progression-free survival (29 +/- A 11 vs 64 +/- A 18 %; p = 0.03) and overall survival (58 +/- A 12 vs 83 +/- A 15 %; p = 0.05) rates compared to those with tumors lacking telomerase activity. Imetelstat inhibited proliferation and self-renewal by shortening telomeres and inducing senescence in vitro. In vivo, Imetelstat significantly reduced subcutaneous xenograft growth by 40 % (p = 0.03) and completely abolished the tumorigenicity of pediatric ependymoma TICs in an orthotopic xenograft model. Telomerase inhibition represents a promising therapeutic approach for telomerase-active pediatric ependymomas found to characterize high-risk ependymomas.Canadian Institutes of Health Research [MOP 82727]info:eu-repo/semantics/publishedVersio

Novel Prognostic and Therapeutic Targets for Oral Squamous Cell Carcinoma

In oral squamous cell carcinoma (OSCC), metastasis to lymph nodes is associated with a 50% reduction in 5-year survival. To identify a metastatic gene set based on DNA copy number abnormalities (CNAs) of differentially expressed genes, we compared DNA and RNA of OSCC cells laser-microdissected from non-metastatic primary tumors (n = 17) with those from lymph node metastases (n = 20), using Affymetrix 250K Nsp single-nucleotide polymorphism (SNP) arrays and U133 Plus 2.0 arrays, respectively. With a false discovery rate (FDR)<5%, 1988 transcripts were found to be differentially expressed between primary and metastatic OSCC. Of these, 114 were found to have a significant correlation between DNA copy number and gene expression (FDR<0.01). Among these 114 correlated transcripts, the corresponding genomic regions of each of 95 transcripts had CNAs differences between primary and metastatic OSCC (FDR<0.01). Using an independent dataset of 133 patients, multivariable analysis showed that the OSCC-specific and overall mortality hazards ratio (HR) for patients carrying the 95-transcript signature were 4.75 (95% CI: 2.03-11.11) and 3.45 (95% CI: 1.84-6.50), respectively. To determine the degree by which these genes impact cell survival, we compared the growth of five OSCC cell lines before and after knockdown of over-amplified transcripts via a high-throughput siRNA-mediated screen. The expression-knockdown of 18 of the 26 genes tested showed a growth suppression ≥ 30% in at least one cell line (P<0.01). In particular, cell lines derived from late-stage OSCC were more sensitive to the knockdown of G3BP1 than cell lines derived from early-stage OSCC, and the growth suppression was likely caused by increase in apoptosis. Further investigation is warranted to examine the biological role of these genes in OSCC progression and their therapeutic potentials

Chaos, decoherence and quantum cosmology

In this topical review we discuss the connections between chaos, decoherence and quantum cosmology. We understand chaos as classical chaos in systems with a finite number of degrees of freedom, decoherence as environment induced decoherence and quantum cosmology as the theory of the Wheeler - DeWitt equation or else the consistent history formulation thereof, first in mini super spaces and later through its extension to midi super spaces. The overall conclusion is that consideration of decoherence is necessary (and probably sufficient) to sustain an interpretation of quantum cosmology based on the Wave function of the Universe adopting a Wentzel - Kramers - Brillouin form for large Universes, but a definitive account of the semiclassical transition in classically chaotic cosmological models is not available in the literature yet.Comment: 40 page

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362