Cardiovascular risk prediction in type 2 diabetes: a comparison of 22 risk scores in primary care settings

AIMS/HYPOTHESIS: We aimed to compare the performance of risk prediction scores for CVD (i.e., coronary heart disease and stroke), and a broader definition of CVD including atrial fibrillation and heart failure (CVD+), in individuals with type 2 diabetes. METHODS: Scores were identified through a literature review and were included irrespective of the type of predicted cardiovascular outcome or the inclusion of individuals with type 2 diabetes. Performance was assessed in a contemporary, representative sample of 168,871 UK-based individuals with type 2 diabetes (age ≥18 years without pre-existing CVD+). Missing observations were addressed using multiple imputation. RESULTS: We evaluated 22 scores: 13 derived in the general population and nine in individuals with type 2 diabetes. The Systemic Coronary Risk Evaluation (SCORE) CVD rule derived in the general population performed best for both CVD (C statistic 0.67 [95% CI 0.67, 0.67]) and CVD+ (C statistic 0.69 [95% CI 0.69, 0.70]). The C statistic of the remaining scores ranged from 0.62 to 0.67 for CVD, and from 0.64 to 0.69 for CVD+. Calibration slopes (1 indicates perfect calibration) ranged from 0.38 (95% CI 0.37, 0.39) to 0.74 (95% CI 0.72, 0.76) for CVD, and from 0.41 (95% CI 0.40, 0.42) to 0.88 (95% CI 0.86, 0.90) for CVD+. A simple recalibration process considerably improved the performance of the scores, with calibration slopes now ranging between 0.96 and 1.04 for CVD. Scores with more predictors did not outperform scores with fewer predictors: for CVD+, QRISK3 (19 variables) had a C statistic of 0.68 (95% CI 0.68, 0.69), compared with SCORE CVD (six variables) which had a C statistic of 0.69 (95% CI 0.69, 0.70). Scores specific to individuals with diabetes did not discriminate better than scores derived in the general population: the UK Prospective Diabetes Study (UKPDS) scores performed significantly worse than SCORE CVD (p value <0.001). CONCLUSIONS/INTERPRETATION: CVD risk prediction scores could not accurately identify individuals with type 2 diabetes who experienced a CVD event in the 10 years of follow-up. All 22 evaluated models had a comparable and modest discriminative ability

Regioselective thioacetylation of chitosan end-groups for nanoparticle gene delivery systems

Chitosan (CS) end-group chemistry is a conjugation strategy that has been minimally exploited in the literature to date. Although the open-chain form of the CS reducing extremity bears a reactive aldehyde moiety, the most common method to generate a reactive end-group on CS is nitrous acid depolymerization, which produces a 2,5-anhydro-D-mannose unit (M-Unit) bearing also an aldehyde moiety. However, the availability of the latter might be low, since previous literature suggests that its hydrated and non-reactive form, namely the gem-diol form, is predominant in acidic aqueous conditions. Oxime-click chemistry has been used to react on such aldehydes with various degrees of success, but the use of a co-solvent and additional chemical reagents remain necessary to obtain the desired and stable covalent linkage. In this study, we have assessed the availability of the aldehyde reactive form on chitosan treated with nitrous acid. We have also assessed its reactivity towards thiol-bearing molecules in acidic conditions where CS amino groups are fully protonated and thus unreactive towards aldehyde. LC-MS and NMR spectroscopy methods (H-1 and DOSY, respectively) confirmed the regioselective thioacetylation of the reactive aldehyde with conversion rates between 55 and 70% depending on the thiol molecule engaged. The stabilization of the hemithioacetal intermediates into the corresponding thioacetals was also found to be facilitated upon freeze-drying of the reaction medium. The PEGylation of the CS M-Unit aldehyde by thioacetylation was also performed as a direct application of the proposed conjugation approach. CS-b-PEG(2) block copolymers were successfully synthesized and were used to prepare block ionomer complexes with plasmid DNA, as revealed by their spherical morphology vs. the rod-like/globular/toroidal morphology observed for polyplexes prepared using native unmodified chitosan. This novel aqueous thiol-based conjugation strategy constitutes an alternative to the oxime-click pathway; it could be applicable to other polymers

Exploring subjective constructions of health in China: a Q-methodological investigation

Background: With an increasing awareness of people’s satisfaction and feeling, health-related quality of life (HRQoL) has become an essential aspect of measuring health. HRQoL is fundamentally a foreign concept introduced to China from the West. While a growing number of studies applied western HRQoL measures, few content validity tests examined the legitimacy of applying Western developed HRQoL measures in a Chinese cultural setting. If there are distinct differences in health conceptualisation between China and the West, it can be argued that those western measures may fail to ask the most appropriate and important questions among a Chinese population in assessing health. As a limited number of studies have investigated Chinese people’s understandings of health, this study aimed to explore how health is defined and described in China. Methods: A Q-methodological study was conducted to explore subjective constructions of health among Chinese participants. A scoping review of Chinese generic HRQoL measures, supplemented by a series of qualitative interviews conducted in China, produced a list of 42 statements representing aspects of health considered as being important in a Chinese cultural setting. Chinese participants in face-to-face interviews ranked and sorted these statements. Data were analysed to identify clusters of participants who shared a similar perspective, using a by-person factor analysis procedure. Results: 110 Chinese participants with various demographics characteristics completed sorting interviews. Five independent factors emerged: (I) “Physical independence and social interaction skills”; (II) “Physical health”; (III) “Sensations and feelings”; (IV) “Lifestyles”; (V) “Learning and working abilities”. Conclusions: The Q-study showed that many health statements were rated highly as most important by a diverse range of Chinese participants but were not covered in the commonly used Western HRQoL measure EQ-5D. It then suggests that the EQ-5D descriptive system might need modification to improve its capacity to measure health status in China. The study thus raises a general question as to how appropriate the Western-developed HRQoL measures are when used to assess health in a significantly different cultural setting

Flight estimation of four bullets of serial firing from the Glauberyt submachine gun

Na strzelnicy firmy EMJOT przeprowadzono rejestrację procesu wystrzelenia z pistoletu maszynowego Glauberyt ogniem seryjnym czterech pocisków. Do badań empirycznych użyto amunicji 9x19 mm FMJ Luger (Parabellum) produkcji czeskiej z 2017 r. Strzały zostały oddane przez antyterrorystę. Ich rejestrację przeprowadzono z zastosowaniem szybkiej kamery cyfrowej Phantom v.9.1 wraz z niezbędnym oprzyrządowaniem. Na podstawie zarejestrowanego obrazu określono początkowe kinematyczne parametry lotu każdego z pocisków. Korzystając z zasad mechaniki lotu, opracowano model balistyczny pocisku, a na jego podstawie zredagowano program symulacyjny. Zweryfikowano wyniki lotu uzyskane w przestrzeni wirtualnej, porównując je z wynikami badań doświadczalnych. Po dopracowaniu modelu teoretycznego przeprowadzono estymację lotu czterech pocisków wystrzeliwanych ogniem seryjnym z pistoletu maszynowego Glauberyt do tarczy znajdującej się w odległości 25 m. W artykule przedstawiono reprezentatywny przykład wystrzeliwania ogniem seryjnym czterech pocisków. W badaniach wykonano 50 takich strzelań.At the EMJOT firing range, the process of firing the Glauberite machine gun was recorded with serial fire of four bullets. 9x19 mm FMJ Parabellum Luger Czech production from 2017 was used for empirical research. The shots were given by an anti-terrorist. Their registration was carried out using the high-speed Phantom v.9.1 digital camera, together with the necessary equipment. Based on the recorded image, the initial kinematic flight parameters of each of the missiles were determined. Using the principles of flight mechanics, a ballistic model of the projectile was developed, and on its basis a simulation program was prepared. Flight results obtained in the virtual space were verified by comparing them with the results of experimental tests. After finetuning the theoretical model, four flight bullets from the Glauberite machine pistol were estimated to be placed at the distance of 30 m. The article presents a representative example of serial firing of four missiles. Fifty such shots were made in the tests

Wpływ układu człowiek-broń na lot pocisku wystrzelonego z pistoletu maszynowego

The process of burst-firing two projectiles from a Skorpion vz. 61 7.65 mm calibre machine pistol was recorded during a test at a firing range operated by the Polish Police. This experimental test involved Browning 7.65 x 17 mm SR ammunition rounds. The shots were fired by a Police Special Forces operative. The shots were recorded with a Phantom v.9.1 slow-motion video camera, complete with the essential accessories. TEMA, a software suite dedicated to video recording analyses, was used to determine the initial kinematic parameters of flight for each of the two projectiles. By applying the theorem of momentum and spin change, a theoretical projectile flight model was developed with a respective simulation runtime in SciLab. The projectile flight results were verified with the experimental test results to validate the developed model. Having delivered a reliable projectile flight model, an analysis was carried out to study the effectiveness of the shots fired by the Police Special Forces operative towards a target 30 metres away. This paper presents a determined process of burst firing of two projectiles. It is also a representative example of repetitive shooting. The ultimate task of this research is to develop guidelines for the design of machine pistol dynamic properties that reduce the scatter of projectiles shot in series.Na strzelnicy policyjnej przeprowadzono rejestrację procesu wystrzelenia z pistoletu maszynowego Skorpion wz. 61 kal.7.65 mm ogniem seryjnym dwóch pocisków. Do badań empirycznych użyto amunicji 7.65 x 17 mm SR Browning. Strzały oddane zostały przez policjanta ze służb specjalnych. Ich rejestrację przeprowadzono przy wykorzystaniu szybkiej kamery cyfrowej Phantom v.9.1 wraz z niezbędnym oprzyrządowaniem. Przy wykorzystaniu specjalistycznego programu TEMA służącego do analizy zarejestrowanego obrazu, określono początkowe kinematyczne parametry lotu każdego z pocisków. Wykorzystując twierdzenie o zmianie pędu i krętu opracowano model teoretyczny lotu pocisku oraz program symulacyjny w systemie Scilab. Zweryfikowano wyniki lotu na podstawie danych z badań empirycznych, co pozwoliło na walidację opracowanego modelu. Dysponując wiarygodnym modelem lotu pocisku, przeprowadzono analizę skuteczności strzelania wykonanego przez policjanta ze służb specjalnych do celu znajdującego się w odległości 30 m. W artykule przedstawiony jest proces zdeterminowany wystrzeliwania ogniem seryjnym dwóch pocisków. Stanowi on reprezentatywny przykład wielokrotnego procesu wystrzeliwania. Docelowym zadaniem podjętych rozważań jest opracowanie wytycznych zmierzających do takiego kształtowania właściwości dynamicznych pistoletów automatycznych, aby zmniejszyć rozrzut wystrzeliwanych ogniem seryjnym pocisków

Model teoretyczny układu człowiek — broń

Rapid firing of two bullets from the Skorpion submachine gun vz. 61 cal. 7,65 mm towards the target located at a distance of 25 [m] was registered at a police shooting range. The tests confirmed the opinion of the users regarding the presence of significant weapon dispersion. This undesirable effect prompted the authors to undertake work in order to improve the dynamic properties of weapons. Experimental studies provided information on the kinematics of movement of human — weapon system. On the basis of the courses of variation of displacement, velocity and acceleration over time, the behaviour of a machine gun in thirteen characteristic points of its operation was specified. The verification of bullet holes and analysis of recorded images showed a slight deviation of movement of the objects under examination from the vertical plane. Therefore, a physical model of human — weapon system with five degrees of freedom in the vertical plane was formulated. On the basis of the physical model, a mathematical model of human — weapon system was derived, which can be classified as linear, determined, variable over time, dissipative and constrained.Na strzelnicy policyjnej przeprowadzono rejestrację procesu wystrzelenia z pistoletu maszynowego Skorpion wz. 61 kal. 7,65 mm ogniem seryjnym dwóch pocisków do tarczy znajdującej się w odległości 25 [m]. Przeprowadzone próby potwierdziły opinię użytkowników o występowaniu znacznego rozrzutu broni. Występowanie niepożądanego zjawiska skłoniło autorów do podjęcia prac zmierzających do poprawienia właściwości dynamicznych broni. Badania doświadczalne dostarczyły informacji na temat kinematyki ruchu układu człowiek — broń. Na podstawie otrzymanych przebiegów zmienności przemieszczenia, prędkości i przyspieszenia w funkcji czasu określono zachowanie się pistoletu maszynowego w trzynastu charakterystycznych punktach jego działania. Weryfikacja przestrzelin i analiza zarejestrowanych obrazów wykazała nieznaczne odstępstwo ruchu badanych obiektów od płaszczyzny pionowej. W związku z tym sformułowano w płaszczyźnie pionowej model fizyczny układu człowiek — broń o pięciu stopniach swobody. Na podstawie modelu fizycznego wyprowadzono model matematyczny układu człowiek — broń, który można zakwalifikować do liniowych, zdeterminowanych, zmiennych w czasie, dyssypatywnych i nieswobodnych