Early stroke-related deep venous thrombosis: risk factors and influence on outcome

Deep venous thrombosis (DVT) is a serious complication of various medical conditions including acute stroke. Our aim was to identify the occurrence of early stroke-related DVT, risk factors for its development and the influence on outcome. The study involved consecutive patients admitted to our center due to acute ischaemic (n = 278) or haemorrhagic (n = 12) stroke during a 16-month period. We collected data on their pre-stroke health status, neurological deficit on admission and baseline serum CRP and fibrinogen level. Ultrasonographic imaging was performed at the 3rd (IQR: 2–4) and 9th (IQR: 8–9) day after stroke. Patients thrombosis occurring between the first and second examination comprised the newly developed early stroke-related DVT group. We found DVT in 8.0% (24/299) of patients at initial evaluation. Newly developed DVT was present in 3.0% (9/299) of patients, and was predominantly distal (7 of 9 cases). It was associated with elevated serum CRP level (OR 8.75; 95%CI: 1.61–47.6), which was verified in a model adjusted for stroke severity and pre-stroke dependency (3–5 pts. in mRS). In a multivariate model, newly developed DVT significantly increased the risk of 3-month mortality (OR 12.4; 95%CI: 1.72–89.4), without affecting the combined risk of dependency and death (OR 2.57; 95%CI: 0.39–17.0). Early stroke-related DVT is an infrequent complication. However, it may be an independent risk factor for 3-month mortality. Increased serum CRP level combined with normal fibrinogen level seems predictive for development of DVT. It may be reasonable to provide those patients with additional DVT prophylaxis

Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo

Deep vein thrombosis (DVT) is a major cause of cardiovascular death. The sequence of events that promote DVT remains obscure, largely as a result of the lack of an appropriate rodent model. We describe a novel mouse model of DVT which reproduces a frequent trigger and resembles the time course, histological features, and clinical presentation of DVT in humans. We demonstrate by intravital two-photon and epifluorescence microscopy that blood monocytes and neutrophils crawling along and adhering to the venous endothelium provide the initiating stimulus for DVT development. Using conditional mutants and bone marrow chimeras, we show that intravascular activation of the extrinsic pathway of coagulation via tissue factor (TF) derived from myeloid leukocytes causes the extensive intraluminal fibrin formation characteristic of DVT. We demonstrate that thrombus-resident neutrophils are indispensable for subsequent DVT propagation by binding factor XII (FXII) and by supporting its activation through the release of neutrophil extracellular traps (NETs). Correspondingly, neutropenia, genetic ablation of FXII, or disintegration of NETs each confers protection against DVT amplification. Platelets associate with innate immune cells via glycoprotein Ibα and contribute to DVT progression by promoting leukocyte recruitment and stimulating neutrophil-dependent coagulation. Hence, we identified a cross talk between monocytes, neutrophils, and platelets responsible for the initiation and amplification of DVT and for inducing its unique clinical features

Aging-Aware Request Scheduling for Non-Volatile Main Memory

Modern computing systems are embracing non-volatile memory (NVM) to implement high-capacity and low-cost main memory. Elevated operating voltages of NVM accelerate the aging of CMOS transistors in the peripheral circuitry of each memory bank. Aggressive device scaling increases power density and temperature, which further accelerates aging, challenging the reliable operation of NVM-based main memory. We propose HEBE, an architectural technique to mitigate the circuit aging-related problems of NVM-based main memory. HEBE is built on three contributions. First, we propose a new analytical model that can dynamically track the aging in the peripheral circuitry of each memory bank based on the bank's utilization. Second, we develop an intelligent memory request scheduler that exploits this aging model at run time to de-stress the peripheral circuitry of a memory bank only when its aging exceeds a critical threshold. Third, we introduce an isolation transistor to decouple parts of a peripheral circuit operating at different voltages, allowing the decoupled logic blocks to undergo long-latency de-stress operations independently and off the critical path of memory read and write accesses, improving performance. We evaluate HEBE with workloads from the SPEC CPU2017 Benchmark suite. Our results show that HEBE significantly improves both performance and lifetime of NVM-based main memory.Comment: To appear in ASP-DAC 202

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

The results of performance test regarding to fat and meat traits of crossbred gilts of different growth rate

Celem pracy była analiza wyników oceny przyżyciowej z uwzględnieniem cech otłuszczenia i umięśnienia 51 802 loszek mieszańców o zróżnicowanym tempie wzrostu, pochodzących z dwóch wariantów krzyżowania: wbp x pbz oraz pbz x wbp (rasę lochy podano w pierwszej pozycji). Zwierzęta pochodziły z bydgoskiego okręgu hodowlanego i zostały poddane ocenie przyżyciowej na przestrzeni lat 2004-2008. W zależności od wielkości przyrostów dobowych masy ciała standaryzowanych na 180. dzień życia, loszki mieszańce podzielono na dwie grupy charakteryzujące się zróżnicowanym tempem wzrostu, tj. niskimi i wysokimi przyrostami dobowymi masy ciała w każdym analizowanym roku. Wpływ tempa wzrostu na kształtowanie się cech dotyczących otłuszczenia i umięśnienia loszek mieszańców w poszczególnych latach był zróżnicowany. W łącznym zestawieniu wyników z lat 2004-2008 wykazano jednoznacznie, że badane loszki mieszańce o wysokich przyrostach dobowych masy ciała charakteryzowały się cieńszą słoniną w punkcie P2 oraz grubszą słoniną w punkcie P4 w porównaniu ze zwierzętami o wolniejszym tempie wzrostu. Stwierdzono korzystniejszy wynik dotyczący wysokości oka polędwicy u świń charakteryzujących się wysokimi przyrostami dobowymi masy ciała w porównaniu ze zwierzętami o wolniejszym tempie wzrostu, wyższą natomiast zawartość mięsa w ciele u loszek o niskim tempie wzrostu wobec świń odznaczających się wysokimi przyrostami dobowymi masy ciała. Loszki z obu badanych wariantów krzyżowania odznaczające się szybkim tempem wzrostu osiągnęły wysoko istotnie wyższą wartość indeksu selekcyjnego oceny przyżyciowej, czyli lepszą wartość hodowlaną od zwierząt o niskich przyrostach dobowych masy ciała.The aim of the paper was to analyze the performance test results regarding to fat and meat traits of 51.802 crossbred gilts of different growth rate, coming from two following crossing variants, where the sow breed was given in the first position: PLW x PL and PL x PLW. The animals came from The Bydgoszcz Breeding Region and they were performance- tested within the years 2004-2008. Depending on the level of daily body weight gains standardized on 180th day of life, the young crossbred gilts were divided into two groups of different growth rate, i.e. low and high daily gains of body weight in each analyzed year. The impact of growth rate on shaping fat and meat traits of crossbred gilts in particular years was diverse. In total results’ summary from years 2004-2008 it was clearly proved that the tested crossbred gilts PLW x PL and PL x PLW of high daily gains of body weight had thinner backfat in P2 point and thicker backfat in P4 point as compared to the animals of lower growth rate. More favourable result of the height of loin eye was observed in the pigs with high daily gains of body weight as compared to the animals of lower grow rate. Higher body meat content was recorded in gilts of low growth rate as compared to the pigs of high daily gains of body weight. The gilts coming from the both tested crossing variants of high growth rate had significantly higher value of performance test selection index, thus higher breeding value than the animals with low daily gains of body weight

Analiza wyników testu wydajności loszek mieszańców wyprodukowanych w Bydgoskim Regionie Hodowli

The aim of this study was to analyse the results of performance test of crossbred gilts of Polish Large White and Polish Landrace breed conducted in years 2009–2013 in the Bydgoszcz Breeding Region. They came from two crossing variants (sows breed at first position): [PLW×PL] and [PL×PLW]. Crossbred gilts [PL×PLW] in all analysed years (except for 2001) had higher daily gain of body weight standardised on 180th day than [PLW×PL] animals. From 2009 till 2013 the growth rate of tested crossbred gilts, i.e. [PLW×PL] and [PL×PLW] increased by 10 and 8 g, respectively. Within the span of 5 years (2009–2013) an improvement of breeding value of animals determined as selection index value, which increased by 7 points in [PLW×PL] gilts and by 4 points in [PL×PLW] pigs. This proves the effective improvement of growth and slaughter performance of crossbred gilts coming from the Bydgoszcz Breeding Region within the space of years 2009–2013, being maternal component used in breeding and commercial crossing, which should be monitored in following years

Effect of dilution on compressibility of naproxen in acetonitrile studied by ultrasonic method

Naproxen, ibuprofen, and ketoprofen are non-steroidal anti-inflammatory drugs. All of them belong to chiral 2-arylpropionic acids (2-APAs). Chiral compounds may remain in a patient's body as two antimers, even if administered as a single one, due to transenantiomerization. That is dangerous if therapeutic enantiomer has a toxic antipode. Chromatographic data suggest that solutions of $S$-(+)-naproxen in acetonitrile are stiffer than the pure solvent that favours oscillatory transenantiomerisation. Acoustic and volumetric studies of dilute solutions of naproxen in acetonitrile have been undertaken to verify that supposition. The molar adiabatic compressibility and volume depend linearly on the molar percent of naproxen at temperatures from 298.15 K to 313.15 K. Limiting partial compressibility of naproxen is close to zero and decreases slightly with increasing temperature. Thus, the compressibility of dilute solutions is mainly due to compressibility of acetonitrile, while naproxen is virtually incompressible. The hydrogen-bonded dimers of naproxen probably remain intact, even at infinite dilution