Cargo adaptors regulate stepping and force generation of mammalian dynein-dynactin.

Cytoplasmic dynein is an ATP-driven motor that transports intracellular cargos along microtubules. Dynein adopts an inactive conformation when not attached to a cargo, and motility is activated when dynein assembles with dynactin and a cargo adaptor. It was unclear how active dynein-dynactin complexes step along microtubules and transport cargos under tension. Using single-molecule imaging, we showed that dynein-dynactin advances by taking 8 to 32-nm steps toward the microtubule minus end with frequent sideways and backward steps. Multiple dyneins collectively bear a large amount of tension because the backward stepping rate of dynein is insensitive to load. Recruitment of two dyneins to dynactin increases the force generation and the likelihood of winning against kinesin in a tug-of-war but does not directly affect velocity. Instead, velocity is determined by cargo adaptors and tail-tail interactions between two closely packed dyneins. Our results show that cargo adaptors modulate dynein motility and force generation for a wide range of cellular functions

Impact of prior hospital mortality versus surgical volume on mortality following surgery for congenital heart disease

ObjectiveOur objective was to assess the relationships of a hospital’s past adjusted in-hospital mortality and surgical volume with future in-hospital mortality after surgery for congenital heart disease.MethodsUsing the Pediatric Health Information Systems database, we (1) calculated hospital surgical volume and standardized mortality ratio (= observed number of deaths/expected number of deaths adjusted for surgery type) for January 2004 through June 2006 for children (0-18 years) after surgery for congenital heart disease at 38 hospitals and (2) assessed the relationship between these values and subsequent mortality during July 2006 through December 2008. We constructed Poisson regression models to estimate risk of mortality, adjusting for age, race, sex, genetic syndrome, insurance type, and surgery type (using the Risk Adjustment in Congenital Heart Surgery method).ResultsThere were 49,792 hospital encounters during 2004 through 2008 for pediatric patients having surgery for congenital heart disease, with an overall in-hospital mortality of 3.45%. For the 24,112 eligible encounters during July 2006 through December 2008, a hospital’s prior standardized mortality ratio was significantly associated with postoperative in-hospital mortality (P < .0001), and a hospital’s prior surgical volume had only borderline significance (P = .0792). On stratified analysis, past standardized mortality ratio was associated with mortality for both lower- and higher-risk surgical risk categories (P = .0105 and .0015, respectively). Hospital surgical volume was not significantly associated with mortality for lower-risk categories (P = .4122), but it was borderline significant for higher-risk categories (P = .0678).ConclusionsIn this data set, prior hospital surgical volume tended to be associated with improved mortality after higher-risk operations in pediatric patients with congenital heart disease, whereas prior hospital postoperative mortality was significantly associated with mortality across all risk strata of congenital heart surgery

Emerging Longitudinal Trends in Health Indicators for Rural Residents Participating in a Diabetes and Cardiovascular Screening Program in Northern Alberta, Canada

Background. Geographic isolation, poverty, and loss of culture/tradition contribute to “epidemic” rates of diabetes amongst indigenous Canadians. The Mobile Diabetes Screening Initiative travels to rural indigenous and other remote communities in Alberta to screen for diabetes and cardiovascular risk. We sought to examine risk factors longitudinally. Methods. Clinical and anthropometric measurements were undertaken for 809 adults (aged 20–91) between November 2003 and December 2009. For those who had more than one MDSi visit, trend estimates (actual changes) were calculated for body mass index (BMI), weight, waist circumference, hemoglobin A1c (A1c), total cholesterol, and blood pressure. Results. Among those without diabetes (N = 629), BMI and weight increased (P < .01) and blood pressure decreased (P < .05). For those with diabetes (N = 180), significant improvements (P < .05) were observed for all indicators except waist circumference. Conclusion. Improvements observed suggest that MDSi's model may effectively mediate some barriers and support subjects in managing their health

Pemanfaatan Completeness Sebagai Koreksi Angka Kematian Hasil Registrasi Kematian Dan Sp-2010

Angka kematian merupakan indikator yang sensitif untuk menilai keberhasilan program kesehatan. Angka ini didapat dari berbagai sumber data termasuk dari survei, registrasi, dan sensus penduduk, namun umumnya perhitungan secara langsung tersebut akan mendapatkan angka kematian yang under reported, untuk itu perlu dilakukan koreksi. Completeness dapat menjadi angka koreksi yang merupakan perhitungan dari dua metode pengumpulan data yang saling independen, dalam hal ini registrasi dan sensus penduduk. Penelitian ini dilakukan dengan mengumpulkan data registrasi kematian di empat daerah yaitu Kota Metro, Surakarta, Kabupaten Pekalongan, dan Gorontalo, yang kemudian dilakukan pula matching dengan Sensus Penduduk 2010 untuk mendapatkan completeness. Diketahui bahwa completeness dari sistem registrasi kematian di empat daerah tersebut bervariasi, untuk Kota Metro 66% sehingga angka kematian harus dikoreksi dengan 1,5, Kota Surakarta 74% (koreksi 1,35), Kabupaten Pekalongan 40% (koreksi 2,5) dan Kabupaten Gorontalo sebesar 53% (koreksi 1,9). Pada kelompok umur 50 tahun ke atas nilai completeness semakin tinggi, yang berarti sistem pelaporan dan pencatatan kematian lebih baik dari kelompok umur yang lain. Penggunaan angka koreksi dalam melakukan kajian angka kematian masih perlu dilakukan, upaya lebih lanjut perlu dilakukan pula pada kajian angka kematian karena sebab yang spesifik

Association of Digoxin With Interstage Mortality: Results From the Pediatric Heart Network Single Ventricle Reconstruction Trial Public Use Dataset

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139107/1/jah31279.pd

The subpulse modulation properties of pulsars at 92 cm and the frequency dependence of subpulse modulation

A large sample of pulsars has been observed to study their subpulse modulation at an observing wavelength (when achievable) of both 21 and 92 cm using the Westerbork Synthesis Radio Telescope. In this paper we present the 92-cm data and a comparison is made with the already published 21-cm results. We analysed 191 pulsars at 92 cm using fluctuation spectra. The sample of pulsars is as unbiased as possible towards any particular pulsar characteristics. For 15 pulsars drifting subpulses are discovered for the first time and 26 of the new drifters found in the 21-cm data are confirmed. We discovered nulling for 8 sources and 8 pulsars are found to intermittently emit single pulses that have pulse energies similar to giant pulses. It is estimated that at least half of the total population of pulsars have drifting subpulses when observations with a high enough signal-to-noise ratio would be available. It could well be that the drifting subpulse mechanism is an intrinsic property of the emission mechanism itself, although for some pulsars it is difficult or impossible to detect. Drifting subpulses are in general found at both frequencies, although the chance of detecting drifting subpulses is possibly slightly higher at 92 cm. It appears that the youngest pulsars have the most disordered subpulses and the subpulses become more and more organized into drifting subpulses as the pulsar ages. The correlations with the modulation indices are argued to be consistent with the picture in which the radio emission can be divided in a drifting subpulse signal plus a quasi-steady signal which becomes, on average, stronger at high observing frequencies. The measured values of P3 at the two frequencies are highly correlated, but there is no evidence for a correlation with other pulsar parameters.Comment: 30 pages, 10 figures, accepted for publication in A&A, astro-ph version is missing 191 figures due to file size restrictions. Please download the appendix from http://www.astron.nl/~stappers/wiki/doku.php?id=resources:publication

OCULAR CHANGES IN MONGOLISM

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75455/1/j.1749-6632.1970.tb39372.x.pd