A novel presenilin 1 mutation (L174M) in a large Cuban family with early onset Alzheimer disease.

We studied a Cuban family with presenile dementia (autosomal dominant) consisting of 281 members within six generations, the proband descended from a Spanish founder. Mean age at onset was 59 years of age. Memory impairment was the main symptom in all patients, additionally, ischemic episodes were described in 4 (n = 18) patients. Neuropathological examination of brain material (1 patient) revealed neuronal loss, amyloid plaques, and neurofibrillary tangles. Thirty DNA samples were genotyped (regions on chromosome 1, 3, 10, 12, 14, 17, 19, 20, and 21). A maximum Lod score of 3.79 at theta = 0 was obtained for marker D14S43, located in a 9-cM interval in which all patients shared the same haplotype. Sequencing of the PSEN1 gene revealed a heterozygous base substitution, C520A (exon 6), which is predicted to cause an amino acid change from leucine to methionine in the TMIII of the presenilin 1 protein. The mutation was found to co-segregate with the disease phenotype and the associated disease haplotype. The C --> A change was not observed in 80 control chromosomes from the Cuban population. Leucine at position 174 is highly conserved among species and is identical in prese

Estimated GFR reporting is not sufficient to allow detection of chronic kidney disease in an Italian regional hospital

<p>Abstract</p> <p>Background</p> <p>Chronic kidney disease (CKD) is an emerging worldwide problem. The lack of attention paid to kidney disease is well known and has been described in previous publications. However, little is known about the magnitude of the problem in highly specialized hospitals where serum creatinine values are used to estimate GFR values.</p> <p>Methods</p> <p>We performed a cross-sectional evaluation of hospitalized adult patients who were admitted to the medical or surgical department of Santa Maria della Misericordia Hospital in 2007. Information regarding admissions was derived from a database. Our goal was to assess the prevalence of CKD (defined as an estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m²) and detection of CKD using diagnostic codes (Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]). To reduce the impact of acute renal failure on the study, the last eGFR obtained during hospitalization was the value used for analysis, and intensive care and nephrology unit admissions were excluded. We also excluded patients who had ICD-9-CM codes for renal replacement therapy, acute renal failure, and contrast administration listed as discharge diagnoses.</p> <p>Results</p> <p>Of the 18,412 patients included in the study, 4,748 (25.8%) had reduced eGFRs, falling into the category of Kidney Disease Outcomes Quality Initiative (KDOQI) stage 3 (or higher) CKD. However, the diagnosis of CKD was only reported in 19% of these patients (904/4,748). It is therefore evident that there was a "gray area" corresponding to stage 3 CKD (eGFR 30-59 ml/min), in which most CKD diagnoses are missed. The ICD-9 code sensitivity for detecting CKD was significantly higher in patients with diabetes, hypertension, and cardiovascular disease (26.8%, 22.2%, and 23.7%, respectively) than in subjects without diabetes, hypertension, or cardiovascular disease (p < 0.001), but these values are low when the widely described relationship between such comorbidities and CKD is considered.</p> <p>Conclusion</p> <p>Although CKD was common in this patient population at a large inpatient regional hospital, the low rates of CKD detection emphasize the primary role nephrologists must play in continued medical education, and the need for ongoing efforts to train physicians (particularly primary care providers) regarding eGFR interpretation and systematic screening for CKD in high-risk patients (i.e., the elderly, diabetics, hypertensives, and patients with CV disease).</p

The QUIJOTE experiment: project status and first scientific results

We present the current status of the QUIJOTE (Q-U-I JOint TEnerife) experiment, a new polarimeter with the aim of characterizing the polarization of the Cosmic Microwave Background, and other galactic or extra-galactic physical processes that emit in microwaves in the frequency range 10–42 GHz, and at large angular scales (around 1 degree resolution). The experiment has been designed to reach the required sensitivity to detect a primordial gravitational wave component in the CMB, provided its tensor-to-scalar ratio is larger than r ∼ 0.05. The project consists of two telescopes and three instruments which will survey a large sky area from the Teide Observatory to provide I, Q and U maps of high sensitivity. The first QUIJOTE instrument, known as Multi-Frequency Instrument (MFI), has been surveying the northern sky in four individual frequencies between 10 and 20 GHz since November 2012, providing data with an average sensitivity of 80 µK beam−1 in Q and U in a region of 20, 000 square-degrees. The second instrument, or Thirty-GHz Instrument (TGI), is currently undergoing the commissioning phase, and the third instrument, or Forty-GHz Instrument (FGI), is in the final fabrication phase. Finally, we describe the first scientific results obtained with the MFI. Some specific regions, mainly along the Galactic plane, have been surveyed to a deeper depth, reaching sensitivities of around 40 µK beam−1. We present new upper limits on the polarization of the anomalous dust emission, resulting from these data, in the Perseus molecular complex and in the W43 molecular complex

The status of the Quijote multi-frequency instrument

The QUIJOTE-CMB project has been described in previous publications. Here we present the current status of the QUIJOTE multi-frequency instrument (MFI) with five separate polarimeters (providing 5 independent sky pixels): two which operate at 10-14 GHz, two which operate at 16-20 GHz, and a central polarimeter at 30 GHz. The optical arrangement includes 5 conical corrugated feedhorns staring into a dual reflector crossed-draconian system, which provides optimal cross-polarization properties (designed to be < -35 dB) and symmetric beams. Each horn feeds a novel cryogenic on-axis rotating polar modulator which can rotate at a speed of up to 1 Hz. The science driver for this first instrument is the characterization of the galactic emission. The polarimeters use the polar modulator to derive linear polar parameters Q, U and I and switch out various systematics. The detection system provides optimum sensitivity through 2 correlated and 2 total power channels. The system is calibrated using bright polarized celestial sources and through a secondary calibration source and antenna. The acquisition system, telescope control and housekeeping are all linked through a real-time gigabit Ethernet network. All communication, power and helium gas are passed through a central rotary joint. The time stamp is synchronized to a GPS time signal. The acquisition software is based on PLCs written in Beckhoffs TwinCat and ethercat. The user interface is written in LABVIEW. The status of the QUIJOTE MFI will be presented including pre-commissioning results and laboratory testing

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

The QUIJOTE experiment: project status and first scientific results

We present the current status of the QUIJOTE (Q-U-I JOint TEnerife) experiment, a new polarimeter with the aim of characterizing the polarization of the Cosmic Microwave Background, and other galactic or extra-galactic physical processes that emit in microwaves in the frequency range 10–42 GHz, and at large angular scales (around 1 degree resolution). The experiment has been designed to reach the required sensitivity to detect a primordial gravitational wave component in the CMB, provided its tensor-to-scalar ratio is larger than r ∼ 0.05. The project consists of two telescopes and three instruments which will survey a large sky area from the Teide Observatory to provide I, Q and U maps of high sensitivity. The first QUIJOTE instrument, known as Multi-Frequency Instrument (MFI), has been surveying the northern sky in four individual frequencies between 10 and 20 GHz since November 2012, providing data with an average sensitivity of 80 µK beam−1 in Q and U in a region of 20, 000 square-degrees. The second instrument, or Thirty-GHz Instrument (TGI), is currently undergoing the commissioning phase, and the third instrument, or Forty-GHz Instrument (FGI), is in the final fabrication phase. Finally, we describe the first scientific results obtained with the MFI. Some specific regions, mainly along the Galactic plane, have been surveyed to a deeper depth, reaching sensitivities of around 40 µK beam−1. We present new upper limits on the polarization of the anomalous dust emission, resulting from these data, in the Perseus molecular complex and in the W43 molecular complex

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)