The adenomatous polyposis coli protein unambiguously localizes to microtubule plus ends and is involved in establishing parallel arrays of microtubule bundles in highly polarized epithelial cells

Loss of full-length adenomatous polyposis coli (APC) protein correlates with the development of colon cancers in familial and sporadic cases. In addition to its role in regulating β-catenin levels in the Wnt signaling pathway, the APC protein is implicated in regulating cytoskeletal organization. APC stabilizes microtubules in vivo and in vitro, and this may play a role in cell migration (Näthke, I.S., C.L. Adams, P. Polakis, J.H. Sellin, and W.J. Nelson. 1996. J. Cell Biol. 134:165–179; Mimori-Kiyosue, Y., N. Shiina, and S. Tsukita. 2000. J. Cell Biol. 148:505–517; Zumbrunn, J., K. Inoshita, A.A. Hyman, and I.S. Näthke. 2001. Curr. Biol. 11:44–49) and in the attachment of microtubules to kinetochores during mitosis (Fodde, R., J. Kuipers, C. Rosenberg, R. Smits, M. Kielman, C. Gaspar, J.H. van Es, C. Breukel, J. Wiegant, R.H. Giles, and H. Clevers. 2001. Nat. Cell Biol. 3:433–438; Kaplan, K.B., A. Burds, J.R. Swedlow, S.S. Bekir, P.K. Sorger, and I.S. Näthke. 2001. Nat. Cell Biol. 3:429–432). The localization of endogenous APC protein is complex: actin- and microtubule-dependent pools of APC have been identified in cultured cells (Näthke et al., 1996; Mimori-Kiyosue et al., 2000; Reinacher-Schick, A., and B.M. Gumbiner. 2001. J. Cell Biol. 152:491–502; Rosin-Arbesfeld, R., G. Ihrke, and M. Bienz. 2001. EMBO J. 20:5929–5939). However, the localization of APC in tissues has not been identified at high resolution. Here, we show that in fully polarized epithelial cells from the inner ear, endogenous APC protein associates with the plus ends of microtubules located at the basal plasma membrane. Consistent with a role for APC in supporting the cytoskeletal organization of epithelial cells in vivo, the number of microtubules is significantly reduced in apico-basal arrays of microtubule bundles isolated from mice heterozygous for APC

Functional status in ICU survivors and out of hospital outcomes: a cohort study

OBJECTIVES: Functional status at hospital discharge may be a risk factor for adverse events among survivors of critical illness. We sought to examine the association between functional status at hospital discharge in survivors of critical care and risk of 90-day all-cause mortality after hospital discharge. DESIGN: Single-center retrospective cohort study. SETTING: Academic Medical Center. PATIENTS: Ten thousand three hundred forty-three adults who received critical care from 1997 to 2011 and survived hospitalization. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The exposure of interest was functional status determined at hospital discharge by a licensed physical therapist and rated based on qualitative categories adapted from the Functional Independence Measure. The main outcome was 90-day post hospital discharge all-cause mortality. A categorical risk-prediction score was derived and validated based on a logistic regression model of the function grades for each assessment. In an adjusted logistic regression model, the lowest quartile of functional status at hospital discharge was associated with an increased odds of 90-day postdischarge mortality compared with patients with independent functional status (odds ratio, 7.63 [95% CI, 3.83-15.22; p < 0.001]). In patients who had at least 7 days of physical therapy treatment prior to hospital discharge (n = 2,293), the adjusted odds of 90-day postdischarge mortality in patients with marked improvement in functional status at discharge was 64% less than patients with no change in functional status (odds ratio, 0.36 [95% CI, 0.24-0.53]; p < 0.001). CONCLUSIONS: Lower functional status at hospital discharge in survivors of critical illness is associated with increased postdischarge mortality. Furthermore, patients whose functional status improves before discharge have decreased odds of postdischarge mortality.L30 TR001257 - NCATS NIH HH

Acute referral of patients from general practitioners: should the hospital doctor or a nurse receive the call?

<p>Abstract</p> <p>Background</p> <p>Surprisingly little is known about the most efficient organization of admissions to an emergency hospital. It is important to know, who should be in front when the GP requests an acute admission. The aim of the study was to analyse how experienced ED nurses perform when assessing requests for admissions, compared with hospital physicians.</p> <p>Methods</p> <p>Before- and after ED nurse assessment study, in which two cohorts of patients were followed from the time of request for admission until one month later. The first cohort of patients was included by the physicians on duty in October 2008. The admitting physicians were employed in the one of the specialized departments and only received request for admission within their speciality. The second cohort of patients was included by the ED in May 2009. They received all request from the GPs for admission, independent of the speciality in question.</p> <p>Results</p> <p>A total of 944 requests for admission were recorded. There was a non-significant trend towards the nurses admitting a smaller fraction of patients than the physicians (68 versus 74%). While the nurses almost never rejected an admission, the physicians did this in 7% of the requests. The nurses redirected 8% of the patients to another hospital, significantly more than the physicians with only 1%. (p < 0.0001). The nurses referred significantly more patients to the correct hospital than the doctors (78% vs. 70% p: 0.03). There were no differences in the frequency of unnecessary admissions between the groups. The self-reported use of time for assessment was twice as long for the physicians as for the nurses. (p < 0.0001).</p> <p>Conclusions</p> <p>We found no differences in the frequency of admitted patients or unnecessary admissions, but the nurses redirected significantly more patients to the right hospital according to the catchment area, and used only half the time for the assessment. We find, that nurses, trained for the assignment, are able to handle referrals for emergency admissions, but also advise the subject to be explored in further studies including other assessment models and GP satisfaction.</p

Detecting Determinacy in Prolog Programs: 22nd International Conference, ICLP 2006, Seattle, WA, USA, August 17-20, 2006. Proceedings

In program development it is useful to know that a call to a Prolog program will not inadvertently leave a choice-point on the stack. Determinacy inference has been proposed for solving this problem yet the analysis was found to be wanting in that it could not infer determinacy conditions for programs that contained cuts or applied certain tests to select a clause. This paper shows how to remedy these serious deficiencies. It also addresses the problem of identifying those predicates which can be rewritten in a more deterministic fashion. To this end, a radically new form of determinacy inference is introduced, which is founded on ideas in ccp, that is capable of reasoning about the way bindings imposed by a rightmost goal can make a leftmost goal deterministic

Follow-up of blood-pressure lowering and glucose control in type 2 diabetes.

BACKGROUND In the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) factorial trial, the combination of perindopril and indapamide reduced mortality among patients with type 2 diabetes, but intensive glucose control, targeting a glycated hemoglobin level of less than 6.5%, did not. We now report results of the 6-year post-trial follow-up. METHODS We invited surviving participants, who had previously been assigned to perindopril–indapamide or placebo and to intensive or standard glucose control (with the glucose-control comparison extending for an additional 6 months), to participate in a post-trial follow-up evaluation. The primary end points were death from any cause and major macrovascular events. RESULTS The baseline characteristics were similar among the 11,140 patients who originally underwent randomization and the 8494 patients who participated in the post-trial follow-up for a median of 5.9 years (blood-pressure–lowering comparison) or 5.4 years (glucose-control comparison). Between-group differences in blood pressure and glycated hemoglobin levels during the trial were no longer evident by the first post-trial visit. The reductions in the risk of death from any cause and of death from cardiovascular causes that had been observed in the group receiving active blood-pressure–lowering treatment during the trial were attenuated but significant at the end of the post-trial follow-up; the hazard ratios were 0.91 (95% confidence interval [CI], 0.84 to 0.99; P=0.03) and 0.88 (95% CI, 0.77 to 0.99; P=0.04), respectively. No differences were observed during follow-up in the risk of death from any cause or major macrovascular events between the intensive-glucose-control group and the standard-glucose-control group; the hazard ratios were 1.00 (95% CI, 0.92 to 1.08) and 1.00 (95% CI, 0.92 to 1.08), respectively. CONCLUSIONS The benefits with respect to mortality that had been observed among patients originally assigned to blood-pressure–lowering therapy were attenuated but still evident at the end of follow-up. There was no evidence that intensive glucose control during the trial led to long-term benefits with respect to mortality or macrovascular events

The simulations of sulfuric acid concentration and new particle formation in an urban atmosphere in China

Simulations of sulfuric acid concentration and new particle formation are performed by using the zero-dimensional version of the model MALTE (Model to predict new Aerosol formation in the Lower TropospherE) and measurements from the Campaign of Air Quality Research in Beijing and Surrounding areas (CAREBeijing) in 2008. Chemical reactions from the Master Chemical Mechanism Version 3.2 (MCM v3.2) are used in the model. High correlation (slope = 0.72, <i>R</i> = 0.74) between the modelled and observed sulfuric acid concentrations is found during daytime (06:00–18:00). The aerosol dynamics are simulated by the University of Helsinki Multicomponent Aerosol (UHMA) model including several nucleation mechanisms. The results indicate that the model is able to predict the on- and offset of new particle formation in an urban atmosphere in China. In addition, the number concentrations of newly formed particles in kinetic-type nucleation including homogenous homomolecular (<i>J=K</i>[H₂SO₄]²) and homogenous heteromolecular nucleation involving organic vapours (<i>J=K</i>_het[H₂SO₄][Org]) are in satisfactory agreement with the observations. However, the specific organic compounds possibly participate in the nucleation process should be investigated in further studies

Specializing Interpreters using Offline Partial Deduction

We present the latest version of the Logen partial evaluation system for logic programs. In particular we present new binding-types, and show how they can be used to effectively specialise a wide variety of interpreters.We show how to achieve Jones-optimality in a systematic way for several interpreters. Finally, we present and specialise a non-trivial interpreter for a small functional programming language. Experimental results are also presented, highlighting that the Logen system can be a good basis for generating compilers for high-level languages