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Haemodialysis is an extracorporeal process in which the blood is cleansed via removal of uraemic retention products by a semipermeable membrane. Traditionally, dialysis membranes have been broadly classified on the basis of their composition (cellulosic or noncellulosic) and water permeability (low flux or high flux). However, advances in materials technology and polymer chemistry have led to the development of membranes with specific characteristics and refined properties that mandate a reconsideration of traditional membrane classification systems. For adequate characterization of these newer types of membranes, additional parameters are now relevant, including new permeability indices, the hydrophilic or hydrophobic nature of membranes, adsorption capacity and electrical potential. In this Review, we provide clinicians with an updated analysis of dialysis membranes and dialysers. We discuss the basic mechanisms that underlie solute and water removal in dialysis (that is, diffusion, convection, adsorption and ultrafiltration) in the context of treatments that use highly permeable membranes. Specifically, we highlight online haemodiafiltration and new therapies (for example, expanded haemodialysis) that utilize membranes designed to produce a high degree of internal filtration. Finally, we discuss the considerations that govern the clinically acceptable balance between large-solute clearance and albumin loss for extracorporeal therapies.

تعاني عديد من الأسر من مشكلات سلوكية متنوعة تظهر لدى أبنائهم بمختلف أعمارهم، ينعكس أثرها على العلاقات الأسرية، وبناء شخصية الناشئة، وقد يمتد الأثر إلى التماسك الأسري العام. كما تجابه المعلمين في المدارس مشكلات شبيهة قد تعرقل سير العملية التعليمية. يمثل الكتاب الذي بين أيدينا دليلا عمليا شارحًا للمشكلات السلوكية الأكثر شيوعًا لدى الأطفال والمراهقين، فضلا عن تقديم برامج تدخلية بسيطة وواضحة ومثبتة علميا لكيفية التغلب على هذه المشكلات. يمثل هذا الكتاب فائدة عظيمة للأكاديميين والمحاضرين المهتمين بمجالات الإرشاد النفسي بوجه عام وتعديل السلوك بشكل خاص، فهو الكتاب الأول من نوعه في المنطقة العربية الذي يعرض لفنيات وطرائق تعديل السلوك من خلال تقديم أمثلة عملية، ووصف شامل لكيفية تنفيذها وتقويمها ؛ كما يشمل نماذج عملية ملحقة في النهاية خاصة بكل نشاط تدخلي مقترح. فهو بذلك كتاب علمي يمكن تدريسه في قاعات الجامعات على المستويين النظري والتطبيقي. يشكل الكتاب أيضًا أهمية متزايدة لدى المعنيين من مقدمي الرعاية مثل أولياء الأمور، والمعلمين في المدارس، والعاملين في مراكز تعديل السلوك. والكتاب على الرغم من لغته الأكاديمية، إلا أنه روعي في ترجمته تبسيط المصطلحات، وإدراج هوامش شارحة للمصطلحات التي قد تبدو تخصصية من قبل المترجمين.

Cell-penetrating peptides (CPPs) are capable of transporting molecules to which they are tethered across cellular membranes. Unsurprisingly, CPPs have attracted attention for their potential drug delivery applications, but several technical hurdles remain to be overcome. Chief among them is the so-called ‘endosomal escape problem,’ i.e. the propensity of CPP-cargo molecules to be endocytosed but remain entrapped in endosomes rather than reaching the cytosol. Previously, a CPP fused to calmodulin that bound calmodulin binding site-containing cargos was shown to efficiently deliver cargos to the cytoplasm, effectively overcoming the endosomal escape problem. The CPP-adaptor, “TAT-CaM,” evinces delivery at nM concentrations and more rapidly than we had previously been able to measure. To better understand the kinetics and mechanism of CPP-adaptor-mediated cargo delivery, a real-time cell penetrating assay was developed in which a flow chamber containing cultured cells was installed on the stage of a confocal microscope to allow for observation ab initio . Also examined in this study was an improved CPP-adaptor that utilizes naked mole rat ( Heterocephalus glaber ) calmodulin in place of human and results in superior internalization, likely due to its lesser net negative charge. Adaptor-cargo complexes were delivered into the flow chamber and fluorescence intensity in the midpoint of baby hamster kidney cells was measured as a function of time. Delivery of 400 nM cargo was observed within seven minutes and fluorescence continued to increase linearly as a function of time. Cargo-only control experiments showed that the minimal uptake which occurred independently of the CPP-adaptor resulted in punctate localization consistent with endosomal entrapment. A distance analysis was performed for cell-penetration experiments in which CPP-adaptor-delivered cargo showing wider dispersions throughout cells as compared to an analogous covalently-bound CPP-cargo. Small molecule endocytosis inhibitors did not have significant effects upon delivery. The real-time assay is an improvement upon static endpoint assays and should be informative in a broad array of applications.

Recent data indicate AKI is very common among hospitalized Chinese patients and continuous renal replacement therapy (CRRT) is increasingly offered for treatment. However, only anecdotal information regarding CRRT's use in relation to other modalities and the specific manner in which it is prescribed exists currently. This report summarizes the results of a comprehensive physician survey designed to characterize contemporary dialytic management of AKI patients in China, especially with respect to the utilization of CRRT. The survey queried both nephrologists and critical care physicians across a wide spectrum of hospitals about factors influencing initial RRT modality selection, especially patient clinical characteristics and willingness to receive RRT, treatment location, and institutional capabilities. For patients initially treated with CRRT, data related to indication, timing of treatment initiation, dose, anticoagulation technique, and duration of therapy were also collected. Among AKI patients considered RRT candidates, the survey indicated 15.1% (95% CI, 12.3%-17.9%) did not actually receive dialysis at Chinese hospitals. The finding was largely attributed to prohibitively high therapy costs in the view of patients or their families. The survey confirmed the dichotomy in RRT delivery in China, occurring both in the nephrology department (with nephrologists responsible) and the intensive care unit (with critical care physicians responsible). For all patients who were offered and received RRT, the survey participants reported 63.9% (56.4%-71.3%) were treated initially with CRRT and 24.8% (19.2%-30.3%) with intermittent hemodialysis (HD) (P<0.001). The mean percentage of patients considered hemodynamically unstable at RRT initiation was 36.2% (31.3%-41.1%), although this figure was two-fold higher in patients treated initially with CRRT (43.1%; 35.8%-50.4%) in comparison to those initially treated with HD (22.4%; 16.4%-28.4%)(P<0.001). An overwhelming majority of intensive care patients were treated initially with CRRT (86.6%; 79.8-93.4%) while it was the initial modality in only 44.6% (33.5-55.7%) of patients treated in a nephrology department (P<0.001). Approximately 70% of respondents overall reported prescribing a CRRT dose in the range of 20-30 mL/kg/hr while approximately 20% of prescriptions fell above this range. Daily prescribed therapy duration demonstrated a marked divergence from values reported in the literature and standard clinical practice. Overall, the most common average prescribed value (50% of respondents) fell in the 10-20 hr range, with only 18% in the 20-24 hr range. Moreover, 32% of respondents reported an average prescribed value of less than 10 hrs per day. While the percentages for the 10-20 hrs range were essentially the same for nephrology and ICU programs, a daily duration of less than 10 hrs was much more common in nephrology programs (48.0%; 38.3%-57.9%) versus ICU programs (16%; 10.0%-24.6%)(P<0.001). Our analysis demonstrates both similarities and differences between RRT practices for AKI in China and those in the developed world. While some differences are driven by non-medical factors, future studies should explore these issues further as Chinese RRT practices are harmonized with those in the rest of the world.

Since its inception four decades ago, both the clinical and technologic aspects of continuous renal replacement therapy (CRRT) have evolved substantially. Devices now specifically designed for critically ill patients with acute kidney injury are widely available and the clinical challenges associated with treating this complex patient population continue to be addressed. However, several important questions remain unanswered, leaving doubts in the minds of many clinicians about therapy prescription/delivery and patient management. Specifically, questions surrounding therapy dosing, timing of initiation and termination, fluid management, anticoagulation, drug dosing, and data analytics may lead to inconsistent delivery of CRRT and even reluctance to prescribe it. In this review, we discuss current limitations of CRRT and potential solutions over the next decade from both a patient management and a technology perspective. We also address the issue of sustainability for CRRT and related therapies beyond 2027 and raise several points for consideration.

Comparative evaluations of population dynamics in species with temporal and spatial variation in life-history traits are rare because they require long-term demographic time series from multiple populations. We present such an analysis using demographic data collected during the interval 1978-–1996 for six populations of western terrestrial garter snakes ( Thamnophis elegans ) from two evolutionarily divergent ecotypes. Three replicate populations from a slow-living ecotype, found in mountain meadows of northeastern California, were characterized by individuals that develop slowly, mature late, reproduce infrequently with small reproductive effort, and live longer than individuals of three populations of a fast-living ecotype found at lakeshore locales. We constructed matrix population models for each of the populations based on 8-–13 years of data per population and analyzed both deterministic dynamics based on mean annual vital rates and stochastic dynamics incorporating annual variation in vital rates. (1) Contributions of highly variable vital rates to fitness (λλ s ) were buffered against the negative effects of stochastic variation, and this relationship was consistent with differences between the meadow (M-slow) and lakeshore (L-fast) ecotypes. (2) Annual variation in the proportion of gravid females had the greatest negative effect among all vital rates on λλ s . The magnitude of variation in the proportion of gravid females and its effect on λλ s was greater in M-slow than L-fast populations. (3) Variation in the proportion of gravid females, in turn, depended on annual variation in prey availability, and its effect on λλ s was 4-–23 times greater in M-slow than L-fast populations. In addition to differences in stochastic dynamics between ecotypes, we also found higher mean mortality rates across all age classes in the L-fast populations. Our results suggest that both deterministic and stochastic selective forces have affected the evolution of divergent life-history traits in the two ecotypes, which, in turn, affect population dynamics. M-slow populations have evolved life-history traits that buffer fitness against direct effects of variation in reproduction and that spread lifetime reproduction across a greater number of reproductive bouts. These results highlight the importance of long-term demographic and environmental monitoring and of incorporating temporal dynamics into empirical studies of life-history evolution.

Variation in the size of home range of white-tailed deer (Odocoileus virginianus) has broad implications for managing populations, agricultural damage, and disease spread and transmission. Size of home range of deer also varies seasonally because plant phenology dictates the vegetation types that are used as foraging or resting sites. Knowledge of the landscape configuration and connectivity that contributes to variation in size of home range of deer for the region is needed to fully understand differences and similarities of deer ecology throughout the Midwest. We developed a research team from four Midwestern states to investigate how size of home range of deer in agro-forested landscapes is influenced by variations in landscape characteristics that provide essential habitat components. We found that for resident female deer, annual size of home range in Illinois (mean = 0.99 km²), Michigan (mean = 1.34 km²), Nebraska (mean = 1.20 km²), and Wisconsin (mean = 1.47 km²) did not differ across the region (F ₃,₁₇₅ = 0.42, P = 0.737), but differences between agricultural growing and nongrowing periods were apparent. Variables influencing size of home range included: distance to forests, roads, and urban development from the centroid of deer home range, and percent of crop as well as four landscape pattern indices (contrast-weighted edge density, mean nearest neighbor, area-weighted mean shape index, and patch size coefficient of variation). We also identified differences in model selection for four landscapes created hierarchically to reflect levels of landscape connectivity determined from perceived ability of deer to traverse the landscape. Connectivity of selected forested regions within agro-forested ecosystems across the Midwest plays a greater role in understanding the size of home ranges than traditional definitions of deer habitat conditions and landscape configuration.

According to the political business cycle literature, survival-maximizing leaders will manipulate whatever macroeconomic policy instruments they have at their disposal in order to retain power. However, an obvious implication of the political business cycle literature has not previously been adequately tested: does having the ability to manipulate macroeconomic policy instruments actually allow leaders to stay in office longer? We argue that elected leaders who have neither fiscal nor monetary instruments available for electoral purposes will find it more difficult to survive in office. We test this claim using data from 19 OECD countries in the latter part of the twentieth century when the degree of capital mobility in the international economy was high. We find that access to macroeconomic instruments does help leaders retain office, but that these instruments are only effective for leaders who have been in office for at least 7 years.

This article reports the conclusions of a consensus expert conference on the basic principles and nomenclature of renal replacement therapy (RRT) currently utilized to manage acute kidney injury (AKI). This multidisciplinary consensus conference discusses common definitions, components, techniques, and operations of the machines and platforms used to deliver extracorporeal therapies, utilizing a “machine-centric” rather than a “patient-centric” approach. We provide a detailed description of the performance characteristics of membranes, filters, transmembrane transport of solutes and fluid, flows, and methods of measurement of delivered treatment, focusing on continuous renal replacement therapies (CRRT) which are utilized in the management of critically ill patients with AKI. This is a consensus report on nomenclature harmonization for principles of extracorporeal renal replacement therapies. Devices and operations are classified and defined in detail to serve as guidelines for future use of terminology in papers and research.