Aldo van Eyck y Louis I. Kahn: Paralelos en la otra tradición de la arquitectura moderna

In September 1959, at the invitation of Alison and Peter Smithson, the American architect Louis I. Kahn (1901-1974) attended the 11th and last Congrés Internationaux d’Architecture Moderne (CIAM) conference held at Henry van de Velde’s Kroller-Muller Museum in Otterlo, the Netherlands. There he met the Dutch architect Aldo van Eyck (1918-1999), founding member of Team 10, the successor of CIAM that emerged at the end of this conference. The paths of these two architects – the Second-Generation modernist Kahn, then 58 years old, and the Third-Generation modernist Van Eyck, then 40 years old – parallel in so astonishingly many ways, crossed here for the first time, deeply affecting them both at a time of critical transition in their respective practices and thought.En septiembre de 1959, por invitación de Alison y Peter Smithson, el arquitecto estadounidense Louis I. Kahn (1901-1974) asistió a la 11ª y última conferencia del Congrés Internationaux d'Architecture Moderne (CIAM) celebrada en el Museo Kroller-Muller de Henry van de Velde. en Otterlo, Países Bajos. Allí conoció al arquitecto holandés Aldo van Eyck (1918-1999), miembro fundador del Team10, sucesor del CIAM que surgió al final de esta conferencia. Los caminos de estos dos arquitectos – Kahn, de la Segunda Generación, que entonces tenía 58 años, y Van Eyck, de la Tercera Generación, que entonces tenía 40 año – se desarrollan en paralelo de manera asombrosa en muchos sentidos. Se cruzan aquí por primera vez, quedando profundamente afectados en un momento de transición crítica en sus respectivas prácticas y pensamiento

Randomized and non-randomized designs for causal inference with longitudinal data in rare disorders.

In the United States, approximately 7000 rare diseases affect 30 million patients, and only 10% of these diseases have existing therapies. Sound study design and causal inference methods are essential to demonstrate the therapeutic efficacy, safety, and effectiveness of new therapies. In the rare diseases setting, several factors challenge the use of typical parallel control designs: the small patient population size, genotypic and phenotypic diversity, and the complexity and incomplete understanding of the disorder\u27s progression. Repeated measures, when spaced appropriately relative to disease progression and exploited in design and analysis, can increase study power and reduce variability in treatment effect estimation. This paper reviews these longitudinal designs and draws the parallel between some new and existing randomized studies in rare diseases and their less well-known controlled observational study designs. We show that self-controlled randomized crossover and N-of-1 designs have similar considerations as the observational case series and case-crossover designs. Also, randomized sequential designs have similar considerations to longitudinal cohort studies using sequential matching or weighting to control confounding. We discuss design and analysis considerations for valid causal inference and illustrate them with examples of analyses in multiple rare disorders, including urea cycle disorder and cystic fibrosis

Survey of California Pharmacists\u27 Awareness of and Readiness for the New Authorities Granted by SB 493: A Pilot Study

The recent passing of Senate Bill (SB) 493 – effective on January 1, 2014 – addresses a primary care provider shortage in California by declaring pharmacists as health care providers and authorizing new roles for them in patient care. The aims of this pilot study were to examine California registered pharmacists’ awareness and knowledge of the expanded authorities granted by SB 493 as well as to assess their perception of their own readiness to exercise these new authorities. A cross-sectional, observational study was designed, and a 40-question survey was administered electronically through Qualtrics to adjunct faculty, clinical faculty, and alumni of Touro University California College of Pharmacy. All participants were aware of this new legislation. Through their responses to Likert-scale questions, pharmacists’ self-perceived readiness for each new authority was discovered. A Kruskal-Wallis test revealed no statistically significant difference among the three subgroups’ self-perceived readiness to exercise most of the new authorities, except initiating and administering vaccinations independently to those older than three years old without a physician’s collaborative practice protocol (p = 0.0123). The lower degree of self-perceived readiness to provide immunizations independently reported by adjunct faculty might have been due to not being certified as immunizers, reflecting the need to be educated on administration of vaccinations

Is it safe? Talking to teens with HIV/AIDS about death and dying: a 3-month evaluation of Family Centered Advance Care (FACE) planning ? anxiety, depression, quality of life

Purpose To determine the safety of engaging HIV-positive (HIV+) adolescents in a Family Centered Advance Care (FACE) planning intervention. Patients and methods We conducted a 2-armed, randomized controlled clinical trial in 2 hospital-based outpatient clinics from 2006?2008 with HIV+ adolescents and their surrogates (n = 76). Three 60?90 minutes sessions were conducted weekly. FACE intervention groups received: Lyon FCACP Survey©, the Respecting Choices¬ interview, and completion of The Five Wishes©. The Healthy Living Control (HLC) received: Developmental History, Healthy Tips, Future Planning (vocational, school or vocational rehabilitation). Three-month post-intervention outcomes were: completion of advance directive (Five Wishes©); psychological adjustment (Beck Depression, Anxiety Inventories); quality of life (PedsQL?); and HIV symptoms (General Health Self-Assessment). Results Adolescents had a mean age, 16 years; 40% male; 92% African-American; 68% with perinatally acquired HIV, 29% had AIDS diagnosis. FACE participants completed advance directives more than controls, using time matched comparison (P \u3c 0.001). Neither anxiety, nor depression, increased at clinically or statistically significant levels post-intervention. FACE adolescents maintained quality of life. FACE families perceived their adolescents as worsening in their school (P = 0.018) and emotional (P = 0.029) quality of life at 3 months, compared with controls. Conclusions Participating in advance care planning did not unduly distress HIV+ adolescents

Codon usage patterns in Nematoda: analysis based on over 25 million codons in thirty-two species

BACKGROUND: Codon usage has direct utility in molecular characterization of species and is also a marker for molecular evolution. To understand codon usage within the diverse phylum Nematoda, we analyzed a total of 265,494 expressed sequence tags (ESTs) from 30 nematode species. The full genomes of Caenorhabditis elegans and C. briggsae were also examined. A total of 25,871,325 codons were analyzed and a comprehensive codon usage table for all species was generated. This is the first codon usage table available for 24 of these organisms. RESULTS: Codon usage similarity in Nematoda usually persists over the breadth of a genus but then rapidly diminishes even within each clade. Globodera, Meloidogyne, Pristionchus, and Strongyloides have the most highly derived patterns of codon usage. The major factor affecting differences in codon usage between species is the coding sequence GC content, which varies in nematodes from 32% to 51%. Coding GC content (measured as GC3) also explains much of the observed variation in the effective number of codons (R = 0.70), which is a measure of codon bias, and it even accounts for differences in amino acid frequency. Codon usage is also affected by neighboring nucleotides (N1 context). Coding GC content correlates strongly with estimated noncoding genomic GC content (R = 0.92). On examining abundant clusters in five species, candidate optimal codons were identified that may be preferred in highly expressed transcripts. CONCLUSION: Evolutionary models indicate that total genomic GC content, probably the product of directional mutation pressure, drives codon usage rather than the converse, a conclusion that is supported by examination of nematode genomes

Biological variation in HbA1c predicts risk of retinopathy and nephropathy in type 1 diabetes

WSTĘP. Autorzy niniejszej pracy założyli, że ryzyko powikłań mikronaczyniowych w badaniu Diabetes Control and Complications Trial (DCCT) jest uwarunkowane zarówno zmiennością hemoglobiny glikowanej (HbA1c), zależną od średniego stężenia glukozy we krwi (MBG, mean blood glucose), jak i biologiczną zmiennością osobniczą HbA1c. MATERIAŁ I METODY. Wartości MBG i HbA1c, oznaczone u uczestników badania DCCT (n = 1441) podczas wizyt odbywających się co 3 miesiące, poddano analizie według modelu liniowej regresji wieloczynnikowej. W celu oceny zmienności biologicznej podczas każdej wizyty obliczono indeks glikacji hemoglobiny (HGI, hemoglobin glycation index = wartość zmierzona HbA1c&#8211; wartość przewidywana HbA1c), aby ocenić biologiczną zmienność, opierając się na kierunkowych odchyleniach zmierzonej HbA1c od wartości przewidywanej na podstawie MBG. Populację podzielono w zależności od średnich wartości HGI podczas trwania badania na 3 części: o wysokim, średnim i niskim HGI. Dla poszczególnych grup przeprowadzono analizę z zastosowaniem modelu proporcjonalnego hazardu Coxa w celu porównania ryzyka wystąpienia oraz rozwoju retinopatii i nefropatii w zależności od MBG, wieku, sposobu leczenia, grupy prewencji pierwotnej lub interwencji i czasu trwania cukrzycy. WYNIKI. Współczynnik prawdopodobieństwa oraz analizy HGI w testach t podważają twierdzenie, że wartość HbA1c zależy jedynie od MBG. Podczas 7-letniej obserwacji u pacjentów z wysokimi wartościami HbA1c (wyższymi niż oczekiwane) było 3-krotnie wyższe ryzyko retinopatii (30 vs. 9%; p < 0,001) i 6-krotnie wyższe ryzyko nefropatii (6 vs. 1%, p < 0,001) w porównaniu z grupą o niskim HGI. WNIOSKI. Osobnicza biologiczna zmienność HbA1c, odmienna i niezależna od zmienności HbA1c warunkowanej średnią glikemią, występuje niewątpliwie u chorych na cukrzycę typu 1 biorących udział w badaniu DCCT. Ponadto jest silnym czynnikiem ryzyka rozwoju cukrzycy. Określenie procesów odpowiedzialnych za biologiczną zmienność HbA1c mogłoby prowadzić do stworzenia nowych kierunków leczenia hipoglikemizującego oraz opóźniającego powikłania i postęp choroby.INTRODUCTION. We hypothesized that biological variation in HbA1c, distinct from variation attributable to mean blood glucose (MBG), would predict risk for microvascular complications in the Diabetes Control and Complications Trial (DCCT). MATERIAL AND METHODS. A longitudinal multiple regression model was developed from MBG and HbA1c measured in the 1,441 DCCT participants at quarterly visits. A hemoglobin glycation index (HGI = observed HbA1c&#8211;predicted HbA1c) was calculated for each visit to assess biological variation based on the directional deviation of observed HbA1c from that predicted by MBG in the model. The population was subdivided by thirds into high-, moderate-, and low- HGI groups based on mean participant HGI during the study. Cox proportional hazard analysis compared risk for development or progression of retinopathy and nephropathy between HGI groups controlled for MBG, age, treatment group, strata, and duration of diabetes. RESULTS. Likelihood ratio and t tests on HGI rejected the assumption that HbA1c levels were determined by MBG alone. At 7 years&#8217; follow-up, patients in the high-HGI group (higher than-predicted HbA1c) had three times greater risk of retinopathy (30 vs. 9%; P < 0.001) and six times greater risk of nephropathy (6 vs. 1%; P < 0.001) compared with the low- HGI group. CONCLUSIONS. Between-individual biological variation in HbA1c, which is distinct from that attributable to MBG, was evident among type 1 diabetic patients in the DCCT and was a strong predictor of risk for diabetes complications. Identification of the processes responsible for biological variation in HbA1c could lead to novel therapies to augment treatments directed at lowering blood glucose levels and preventing diabetes complications

The hemoglobin glycation index identifies subpopulations with harms or benefits from intensive treatment in the ACCORD Trial. Diabetes care 2015;38:1067-1074

This study tested the hypothesis that intensive treatment in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial disproportionately produced adverse outcomes in patients with diabetes with a high hemoglobin glycation index (HGI = observed HbA1c − predicted HbA1c)