To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
The scientific application of clinical evidence-based guidelines can reduce the variability of clinical practice, and standardize clinical diagnosis and treatment pathways. At present, many evidence-based guidelines on Chronic Obstructive Pulmonary Disease (COPD) prevention have been issued in countries around the world, but the procedures and evaluation strategies developed by different guidelines are not the same. This study aimed to evaluate the quality of published clinical practice guidelines (CPGs) relating to COPD using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument.
Databases were systematically searched PubMed, EMBASE, Wan Fang, and CNKI as well as guidelines websites on COPD prevention and treatment. The search period was from inception of the database up to May 2019. The inclusion criteria for this study are as follows: (i) published and in accordance with the definition of the practice guidelines; (ii)the main target population is COPD patients with the diagnostic criteria of the 2019 edition of the global initiative for COPD (GOLD), and the content of the guideline is related to the prevention and treatment practice of COPD; (ii) the same guide is included in the latest updated version; (iv) the published language is English or Chinese. Guidelines that met these inclusion criteria were evaluated for the quality of the AGREE II guidelines. Then, a descriptive analysis was made of the consensus that exists in the guidelines.
A total of fifteen guidelines/Consensuses Statements were included in the study. Two guidelines were assessed as recommended, eleven guidelines were assessed as recommended with modifications and two guidelines were not recommended. The mean scores of the included guidelines in the six domains (scope and purpose, personnel involved in guideline development, rigor of development, clarity, applicability, independence) were 90 percent, 72 percent, 49 percent, 96 percent, 60 percent, 69 percent, respectively. Thus, the study identified a consensus that disease risk factors and recommended interventions were mentioned in the guidelines, and that they comprehensively evaluated the quality of guideline reporting to provide reference for standardizing the development of practice guidelines for COPD in China.
The overall methodological quality of COPD CPGs should be improved. The key recommended areas for improvement include standardization of guideline report writing and synthesis of the latest and best evidence, to develop CPGs for COPD to improve the quality of clinical diagnosis and treatment for COPD.
Ankylosing spondylitis (AS) is a common disease that causes pain and affects productivity. Tumor necrosis factor-α (TNF-α) like adalimumab can bring better clinical efficacy and improve quality of life. Adalimumab is likely to be covered by health insurance. It is necessary to assess the impact of adalimumab for patients with AS on the medical insurance budget in China. Our research aims to give support evidence for policy-making.
From the perspective of medical insurance payers, a budget impact model was established to evaluate the impact of adalimumab for the treatment of adults with severe active AS that has responded inadequately to conventional therapy. The time horizon was 5 years (2020–2024). The cost of measurement included drug and treatment costs for adverse events. Scenario analysis was conducted to evaluate the results under different drug price reimbursement ratios and treatment ratios.
Based on the current price of adalimumab (CNY 3,160 [USD 446]/unit), under the reimbursement ratio of 70 percent, adalimumab will increase medical insurance expenditure by CNY 162 [USD 22] million, CNY 152 [USD 21] million, CNY 114 [USD 16] million, CNY 100 [USD 14] million and CNY 88.11 [USD 12] million in the next 1–5 years, respectively. The increased medical insurance expenditure accounts for 0.091, 0.085, 0.064, 0.056, and 0.049 percent of the annual medical insurance expenditure in the next 1–5 years, respectively, which is assumed to be equivalent to the expenditure in 2018 of CNY 1782.2 [USD 251] billion.
The budget impact of adalimumab for AS on medical insurance expenditure is limited, and including adalimumab in the medical insurance catalogue can reduce the burden on individuals, enrich treatment options, and satisfy clinical needs better.
Spinal muscular atrophy (SMA) is a rare, life-threatening, and seriously debilitating neuromuscular disorder, which has a heavy burden on patients, caregivers and the health system. Technological advances have improved clinical effect, but have also increased the financial burden. There is limited information in the literature on the resource utilization and economic burden of SMA. Our research aims to summarize the current literature on resource use, cost and economic evaluations of treatments for SMA, to inform further research and policy decision making.
Databases, including PubMed, Embase, Cochrane Library and CRD Database, were searched from inception. Two reviewers undertook title and abstract screening followed by full-text screening, and any disagreement was resolved in consensus. Data extraction was conducted using a customized form. Included studies were summarized using narrative synthesis structured around general and economic characteristics. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were adhered to where applicable.
We reviewed 552 abstracts and included twenty-six from 2015 to 2019. Four-fifths were published in the United States and Europe. Five full economic evaluations and one budget impact analysis compared nusinersen with AVXS-101 or best supportive care, and the remaining evaluated the economic burden of SMA. The most common outcomes were healthcare resource utilization and direct medical costs, only a few studies evaluated direct non-medical costs or indirect cost.
SMA patients have significant medical expenditures and high utilization of healthcare services, including nusinersen-treated patients. The results highlight the substantial burden of treatment for SMA, not only for patients but also for their caregivers. SMA represents a significant hidden cost that society should be made aware of, and that should be considered in the design, implementation and evaluation of support programs for people who suffer from this disease and their families, as well as in the economic evaluation of new treatments.
Lipopolysaccharides (LPS) could induce milk fat depression via regulating the body and blood fat metabolism. However, it is not completely clear how LPS might regulate triglyceride synthesis in dairy cow mammary epithelial cells (DCMECs). DCMECs were isolated and purified from dairy cow mammary tissue and treated with LPS. The level of triglyceride synthesis, the expression and activity of the liver X receptor α (LXRα), enzymes related to de novo fatty acid synthesis, and the expression of the fatty acid transporters were investigated. We found that LPS decreased the level of triglyceride synthesis via a down-regulation of the transcription, translation, and nuclear translocation level of the LXRα. The results also indicated that the transcription level of the LXRα target genes, sterol regulatory element binding protein 1 (SREBP1), fatty acid synthetase (FAS), acetyl-CoA carboxylase-1 (ACC1), were significantly down-regulated in DCMECs after LPS treatment. Our data may provide new insight into the mechanisms of milk fat depression caused by LPS.
The pathophysiology of obsessive-compulsive disorder (OCD) remains unclear despite extensive neuroimaging work on the disorder. Exposure to medication and comorbid mental disorders can confound the results of OCD studies. The goal of this study was to explore differences in brain functional connectivity (FC) within the cortico-striato-thalamo-cortical (CSTC) loop of drug-naïve and drug-free OCD patients and healthy controls (HCs).
A total of 29 drug-naïve OCD patients, 22 drug-free OCD patients, and 25 HCs matched on age, gender and education level underwent functional magnetic resonance imaging scanning at resting state. Seed-based connectivity analyses were conducted among the three groups. The Yale Brown Obsessive Compulsive Scale and clinical inventories were used to assess the clinical symptoms.
Compared with HCs, the drug-naïve OCD patients had reduced FC within the limbic CSTC loop. In the drug-naïve OCD participants, we also found hyperconnectivity between the supplementary motor area and ventral and dorsal putamen (p < 0.05, corrected for multiple comparisons).
Exposure to antidepressants such as selective serotonin reuptake inhibitors may affect the function of some brain regions. Future longitudinal studies could help to reveal the pharmacotherapeutic mechanisms in these loops.
In this work, a three-dimensional (3D) porous hybrid nickel/aluminum layered double hydroxide (Ni/Al-LDH)-carbon cloth (CC), the working electrode without binders or conductive additions for supercapacitor, was successfully synthesized via facile one-step hydrothermal method. The as-obtained Ni/Al-LDH/CC sample exhibited good charge storage performance (the specific capacitance was up to 359 F/g at a current density of 0.3 A/g), as well as superior cycling stability (5.9% capacitance increase after 3000 cycles at 1.0 A/g). Furthermore, an asymmetric supercapacitor, Ni/Al-LDH/CC as positive electrode and activated carbon (AC) as negative electrode (Ni/Al-LDH/CC//AC), achieved a high energy density (20.9 Wh/kg vs. the power density 262.5 W/kg) and good cycle lifetime (83.9% retention of the initial value after 3000 cycle tests at a current density of 0.5 A/g). The unique 3D porous structure and binder-free electrode display great potential in supercapacitors.
In this study, we chose a carnivorous fish, turbot (Scophthalmus maximus L.), to examine its nutrient-sensing and metabolic responses after ingestion of diets with fishmeal (FM), or 45 % of FM replaced by soyabean meal (34·6 % dry diet) balanced with or without essential amino acids (EAA) to match the amino acid profile of FM diet for 30 d. After a 1-month feeding trial, fish growth, feed efficiency and nutrient retention were markedly reduced by soyabean meal-incorporated (SMI) diets. Compared with the FM diet, SMI led to a reduction of postprandial influx of free amino acids, hypoactivated target of rapamycin signalling and a hyperactivated amino acid response pathway after refeeding, a status associated with reduced protein synthesis, impaired postprandial glycolysis and lipogenesis. These differential effects were not ameliorated by matching an EAA profile of soyabean meal to that of the FM diet through dietary amino acid supplementation. Therefore, this study demonstrated that the FM diet and SMI diets led to distinct nutrient-sensing responses, which in turn modulated metabolism and determined the utilisation efficiency of diets. Our results provide a new molecular explanation for the role of nutrient sensing in the inferior performance of aquafeeds in which FM is replaced by soyabean meal.
The merger of two supermassive black holes (SMBHs) imparts a gravitational-wave (GW) recoil kick to the remnant SMBH, which can even eject the SMBH from its host galaxy. An actively-accreting, recoiling SMBH may be observable as an offset quasar. Prior to the advent of a space-based GW observatory, detections of these offset quasars may offer the best chance for identifying recent SMBH mergers. Indeed, observational searches for recoiling quasars have already identified several promising candidates. However, systematic searches for recoils are currently hampered by large uncertainties regarding how often offset quasars should be observable and where they are most likely to be found. Motivated by this, we have developed a model for recoiling quasars in a cosmological framework, utilizing information about the progenitor galaxies from the Illustris cosmological hydrodynamic simulations. For the first time, we model the effects of BH spin alignment and recoil dynamics based on the gas-richness of host galaxies. We predict that if BH spins are not highly aligned, seeing-limited observations could resolve offset AGN, making them promising targets for all-sky surveys. The rarity of large broad-line offsets among SDSS quasars is likely due in part to selection effects but suggests that spin alignment plays a role in suppressing recoils. Nonetheless, in our most physically motivated model where alignment occurs only in gas-rich mergers, hundreds of offset AGN should be found in all-sky surveys. Our findings strongly motivate a dedicated search for recoiling AGN.
Lymphatic stomata are small openings of lymphatic capillaries on the surface of the mesothelium that lines the serous cavity and have the function of active absorption. They play an important role in physiological and pathological conditions. The cavity of the tunica vaginalis is a typical serous cavity of the testis, but the lymphatic stomata of the tunica vaginalis of humans have never been reported. Here, we studied their ultrastructure by scanning and transmission electron microscopy. The submesothelial connective tissue with foramina was investigated after the mesothelial cells were digested using NaOH solution. We found the lymphatic stomata in cuboidal mesothelial cell regions of the parietal layer of the tunica vaginalis of humans with a diameter of about 1–2 μm. Sometimes, closed lymphatic stomata could be observed. Our study is the first to report the existence of lymphatic stomata of the tunica vaginalis of humans. We found that the tunica vaginalis cavity is connected with the lymphatic system through the stomata, which might provide a morphological basis for the drainage of hydrocele and tumor metastasis of the tunica vaginalis of humans.
Significant conductive polymer-based composites consisting of immiscible semi-crystalline polymers PP and PVDF, at different volume ratios loaded with a certain concentration of CB were prepared by blending and sequent hot-pressing technology. The distributing status of CB in the polymers was evaluated through the micrographs of the composite. The percolation threshold of this kind of composite is much lower than those of the individual polymers. Even more, the composite at 1/1 volume ratio of PP and PVDF displays the best conductivity among different ratios at a certain concentration of CB, and it displays an outstanding PTC effect more than five orders of magnitude, and synchronously an enhanced dielectric permittivity about 24.9 at 100 Hz. These inimitable properties may owe to the formation of PP/PVDF co-continuous phases and a double-percolation effect in the composite. The novel polymer-based composite with ultra-low percolation threshold, enhanced PTC effect, as well as the significant dielectric permittivity is promising a potential application.
Email your librarian or administrator to recommend adding this to your organisation's collection.