Ranibizumab 0.5 mg for diabetic macular edema with bimonthly monitoring after a phase of initial treatment:18-month, multicenter, phase IIIB RELIGHT study

Abstract PURPOSE: To evaluate ranibizumab 0.5 mg using bimonthly monitoring and individualized re-treatment after monthly follow-up for 6 months in patients with visual impairment due to diabetic macular edema (DME). DESIGN: A phase IIIb, 18-month, prospective, open-label, multicenter, single-arm study in the United Kingdom. PARTICIPANTS: Participants (N = 109) with visual impairment due to DME. METHODS: Participants received 3 initial monthly ranibizumab 0.5 mg injections (day 0 to month 2), followed by individualized best-corrected visual acuity (BCVA) and optical coherence tomography-guided re-treatment with monthly (months 3-5) and subsequent bimonthly follow-up (months 6-18). Laser was allowed after month 6. MAIN OUTCOME MEASURES: Mean change in BCVA from baseline to month 12 (primary end point), mean change in BCVA and central retinal thickness (CRT) from baseline to month 18, gain of ≥10 and ≥15 letters, treatment exposure, and incidence of adverse events over 18 months. RESULTS: Of 109 participants, 100 (91.7%) and 99 (90.8%) completed the 12 and 18 months of the study, respectively. The mean age was 63.7 years, the mean duration of DME was 40 months, and 77.1% of the participants had received prior laser treatment (study eye). At baseline, mean BCVA was 62.9 letters, 20% of patients had a baseline BCVA of >73 letters, and mean baseline CRT was 418.1 μm, with 32% of patients having a baseline CRT <300 μm. The mean change in BCVA from baseline to month 6 was +6.6 letters (95% confidence interval [CI], 4.9-8.3), and after institution of bimonthly treatment the mean change in BCVA at month 12 was +4.8 letters (95% CI, 2.9-6.7; P < 0.001) and +6.5 letters (95% CI, 4.2-8.8) at month 18. The proportion of participants gaining ≥10 and ≥15 letters was 24.8% and 13.8% at month 12 and 34.9% and 19.3% at month 18, respectively. Participants received a mean of 6.8 and 8.5 injections over 12 and 18 months, respectively. No new ocular or nonocular safety findings were observed during the study. CONCLUSIONS: The BCVA gain achieved in the initial 6-month treatment period was maintained with an additional 12 months of bimonthly ranibizumab PRN treatment.

Differing effects of two synthetic phonics programmes on early reading development

Background: Synthetic phonics is the widely accepted approach for teaching reading in English: children are taught to sound out the letters in a word then blend these sounds together. Aims: We compared the impact of two synthetic phonics programmes on early reading.SampleChildren received Letters and Sounds (L&S; 7 schools) which teaches multiple letter-sound mappings or Early Reading Research (ERR; 10 schools) which teaches only the most consistent mappings plus frequent words by sight.MethodWe measured phonological awareness (PA) and reading from school entry to the end of the second (all schools) or third school year (4 ERR, 3 L&S schools). Results: PA was significantly related to all reading measures for the whole sample. However, there was a closer relationship between PA and exception word reading for children receiving the L&S programme. The programmes were equally effective overall, but their impact on reading significantly interacted with school-entry PA: children with poor PA at school entry achieved higher reading attainments under ERR (significant group difference on exception word reading at the end of the first year), whereas children with good PA performed equally well under either programme. Conclusions: The more intensive phonics programme (L&S) heightened the association between PA and exception word reading. Although the programmes were equally effective for most children, results indicate potential benefits of ERR for children with poor PA. We suggest that phonics programmes could be simplified to teach only the most consistent mappings plus frequent words by sight.

Patterns and effects of notetaking by learning -disabled and nondisabled adolescents: A comparative study

This study analyzes the qualitative and quantitative patterns of notetaking by learning disabled (LD) and nondisabled (ND) adolescents and the effectiveness of notetaking and review as measured by the subjects' ability to recall information presented during a lecture. The study also examines relationships between certain learner characteristics and notetaking. The following notetaking variables were investigated: note completeness, number of critical ideas recorded, levels of processing information, organizational strategies, fluency of notes, and legibility of notes. The learner characteristics examined pertained to measures on achievement, short-term memory, listening comprehension, and verbal ability.^ Students from the 11th and 12th grades were randomly selected from four senior high schools in Dade County, Florida. Seventy learning disabled and 79 nondisabled subjects were shown a video tape lecture and required to take notes. The lecture conditions controlled for presentation rate, prior knowledge, information density, and difficulty level. After 8 weeks, their notes were returned to the subjects for a review period, and a posttest was administered.^ Results of this study suggest significant differences (p $\le$.01) in the patterns of notetaking between LD and ND groups not due to differences in the learner characteristics listed above. In addition, certain notetaking variables such as process levels, number of critical ideas, and note completeness were found to be significantly correlated to learning outcome. Further, deficiencies in the spontaneous use of organizational strategies and abbreviations adversely affected the notetaking effectiveness of learning disabled students.^ Both LD and ND subjects recalled more information recorded in their notes than not recorded. This difference was significant only for the ND group. By contrast, LD subjects compensated for their poor notetaking skills and recalled significantly more information not recorded on their notes than did ND subjects. The major implications of these findings suggest that LD and ND subjects exhibit very different entry behaviors when asked to perform a notetaking task; hence, teaching approaches to notetaking must differ as well. ^

Noble States Managed by Women. Doña Teresa de Saavedra y Zúñiga, Countess of Villalonso: an Aristocrat during Philip II and Philip III’s Reign

This work intends to analyze the letters exchanged between doña Teresa de Saavedra y Zúñiga, countess of Villalonso, and Bartolomé de Cartagena, a merchant who lived in Seville. Those letters are a very detailed account of their financial relationship during two decades; but they also give us important information about the countess’ life. In her letters the countess discussed her domestic familial life but also made reference to her social position at Court, so we can reconstruct the strategies used by doña Teresa in order to accomplish all her objectives and the ways she used to present these goals to the others.

Of Marx and Makers: an Historical Perspective on Generative Justice

In Marxist frameworks “distributive justice” depends on extracting value through a centralized state. Many new social movements—peer to peer economy, maker activism, community agriculture, queer ecology, etc.—take the opposite approach, keeping value in its unalienated form and allowing it to freely circulate from the bottom up. Unlike Marxism, there is no general theory for bottom-up, unalienated value circulation. This paper examines the concept of “generative justice” through an historical contrast between Marx’s writings and the indigenous cultures that he drew upon. Marx erroneously concluded that while indigenous cultures had unalienated forms of production, only centralized value extraction could allow the productivity needed for a high quality of life. To the contrary, indigenous cultures now provide a robust model for the “gift economy” that underpins open source technological production, agroecology, and restorative approaches to civil rights. Expanding Marx’s concept of unalienated labor value to include unalienated ecological (nonhuman) value, as well as the domain of freedom in speech, sexual orientation, spirituality and other forms of “expressive” value, we arrive at an historically informed perspective for generative justice. 

Effects of efficient fronto-temporal circuitry on lexical ambiguity resolution: converging evidence from cross-age comparisons in eye-tracking and ERP data

Eye-tracking was used to examine how younger and older adults use syntactic and semantic information to disambiguate noun/verb (NV) homographs (e.g., park). We find that young adults exhibit inflated first fixations to NV-homographs when only syntactic cues are available for disambiguation (i.e., in syntactic prose). This effect is eliminated with the addition of disambiguating semantic information. Older adults (60+) as a group fail to show the first fixation effect in syntactic prose; they instead reread NV homographs longer. This pattern mirrors that in prior event-related potential work (Lee & Federmeier, 2009, 2011), which reported a sustained frontal negativity to NV-homographs in syntactic prose for young adults, which was eliminated by semantic constraints. The frontal negativity was not observed in older adults as a group, although older adults with high verbal fluency showed the young-like pattern. Analyses of individual differences in eye-tracking patterns revealed a similar effect of verbal fluency in both young and older adults: high verbal fluency groups of both ages show larger first fixation effects, while low verbal fluency groups show larger downstream costs (rereading and/or refixating NV homographs). Jointly, the eye-tracking and ERP data suggest that effortful meaning selection recruits frontal brain areas important for suppressing contextually inappropriate meanings, which also slows eye movements. Efficacy of fronto-temporal circuitry, as captured by verbal fluency, predicts the success of engaging these mechanisms in both young and older adults. Failure to recruit these processes requires compensatory rereading or leads to comprehension failures (Lee & Federmeier, in press).

Improvement of Virtual Screening Predictions using Computational Intelligence Methods

Virtual Screening (VS) methods can considerably aid clinical research, predicting how ligands interact with drug targets. However, the accuracy of most VS methods is constrained by limitations in the scoring function that describes biomolecular interactions, and even nowadays these uncertainties are not completely understood. In order to improve accuracy of scoring functions used in most VS methods we propose a hybrid novel approach where neural networks (NNET) and support vector machines (SVM) methods are trained with databases of known active (drugs) and inactive compounds, this information being exploited afterwards to improve VS predictions.

Letters to Secretary General Drummond from Thomas Scott, July 1814

Thomas Scott (1746-1824) was a politician and judge originally from Scotland. He came to Canada in 1800 after accepting the appointment of Attorney General of Upper Canada, and in 1806 was promoted to Chief Justice of Upper Canada. The declaration of war in 1812 brought into question the loyalty of the colony’s population, who were largely born in America. As concerns over allegiance intensified, the government sought out traitors in an attempt to make an example of them and deter others. The subsequent trials of citizens accused of treason resulted in 15 convictions, including Jacob Overholser. These trials were intended to assert the authority of the state, but also to demonstrate clemency. Only 8 of the convicts were executed, with the rest being banished from the colony. Scott supported these measures, although they were largely initiated by Attorney General John Beverly Robinson. Thomas Scott retired in 1816 and died in 1824.

By-Law No. 56

The by-law reads: "Be it enacted as a By-Law of the Ontario Grape Growing & Wine Manufacturing Company Limited that the Directors be and they are hereby authorized to make application to the lieutenant-Governor of the Province of Ontario, for issuance of Supplementary letters Patent providing for, 1) Changing the name of the said Company to Barnes Wines, Limited. 2) The Management of the affairs of the Company by a Board of 7 Directors. 3) Re-dividing the Capitol Stock of the Company from 60 shares of par value of $500.00 each, to 6000 shares of par value of $5.00 each. Passed this 5th day of February A.D. 1934."

Beckett's Letters

Review article: The Letters of Samuel Beckett 1929–1940, edited by Martha Dow Fehsenfeld and Lois More Overbeck, Cambridge: Cambridge University Press, 2009, pp. xcix, 782, £30.00. ISBN: 978-0521867931.

Referral letters in oral medicine: standard versus non-standard letters

Usually referral letters are the only means of communication between general practitioners and specialists in the health area. However, they are inadequate if important basic data are omitted. The aim of this study was to compare the content of standard and non-standard letters. A total of 1956 files from the Oral Medicine Service were consecutively evaluated (March 1996 to September 2000). Key items were considered for analysis and the results were stored in a database using the Epinfo 6.04 program. The X-2 test (a=0.05) was applied to the results. of the 1956 files examined, 34% (662) had a referral letter, 31% of them being standard letters and 69% non-standard letters. Most standard letters (87%) were from professionals of public health institutions. Most percent discrepancies between standard and non-standard letters were observed for patient address (14.90 vs 1.32%), patient age (54.81 vs 9.47%), chief complaint (32.21 vs 8.37%), fundamental lesion (29.33 vs 13.66%), and symptoms (27.81 vs 15.42%,,). Statistically significant differences were observed for patient age, professional referring the patient, chief complaint, and site of the lesion. The quality and quantity of the information differed significantly between the two types of letters. The standard letters were more complete and contained information commonly absent in the non-standard letters. We suggest the use of standard letters for improving the quality of communication among professionals.

Letters from Daniel White to Andrew Hall, March 23, 1799

These two letters, both written on the same document, appear to be White's response to accusations from the father of one of his students at the Medford grammar school. Andrew Hall appears to have accused White of punishing his son too severely. In the letters, White denies Hall's accusations while defending his apparently strict approach to discipline. It is not certain whether both these letters were intended for Hall, or if one was written to another (unnamed) upset parent.

Letters to family members, 1799

Four letters dated March 11, 1799, written from debtors' prison ("Debtors' Apartment") in Philadelphia. Includes descriptions of his life in the prison and fellow prisoners.

Letters from William Tudor to his mother, Delia Jarvis Tudor,

Four letters written from Paris, in which he describes his capture by a French privateer and discusses virtues and vices of French society and culture. He also relays details about social visits, including a meeting with the Marquis de Lafayette. Included is an undated list of packages and trunks he was sending home. Content is obscured in some places from loss, and dates are missing from two of the letters, but presumably they were sent in the summer of 1800.

Letters from John Hubbard Church to William Jenks, 1795-1798

John Hubbard Church wrote these twelve letters to his friend and classmate William Jenks between 1795 and 1798. Church wrote the letters from Boston, Rutland, Cambridge, and Chatham in Massachusetts and from Somers, Connecticut; they were sent to Jenks in Cambridge and Boston, where for a time he worked as an usher in Mr. Vinall's school and Mr. Webb's school. Church's letters touch on various subjects, ranging from his increased interest in theology and his theological studies under Charles Backus to his seasickness during a sailing voyage to Cape Cod. Church also informs Jenks of what he is reading, including works by John Locke, P. Brydone, James Beattie, John Gillies, Plutarch, and Alexander Pope. He describes his work teaching that children of the Sears family in Chatham, Massachusetts, where he appears to have spent a significant amount of time between 1795 and 1797. Church's letters are at times very personal, and he often expresses great affection for Jenks and their friendship.