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We report a large novel α-globin cluster deletion that we named –?–PG (NG_000006.1: g.93628_542759del450131), in a Chinese family. This large deletion is approximately 450?kb long, spanning from upstream of the PolR3k gene at the 5′ end to the RAB11FIP3 gene at the 3′ end of chromosome 16p13.3. This deletion removes all the globin distal regulatory elements as well as the whole α-globin gene cluster. Patients with heterozygous –?–PG/αα had red blood cell (RBC) indices consistent with α-thalassemia (α-thal) trait, but no apparent increase in a cancer tendency or mental disability, microcephaly, relative hypertelorism, unusual facies or genital anomalies. 相似文献
84.
Swingley WD Chen M Cheung PC Conrad AL Dejesa LC Hao J Honchak BM Karbach LE Kurdoglu A Lahiri S Mastrian SD Miyashita H Page L Ramakrishna P Satoh S Sattley WM Shimada Y Taylor HL Tomo T Tsuchiya T Wang ZT Raymond J Mimuro M Blankenship RE Touchman JW 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(6):2005-2010
Acaryochloris marina is a unique cyanobacterium that is able to produce chlorophyll d as its primary photosynthetic pigment and thus efficiently use far-red light for photosynthesis. Acaryochloris species have been isolated from marine environments in association with other oxygenic phototrophs, which may have driven the niche-filling introduction of chlorophyll d. To investigate these unique adaptations, we have sequenced the complete genome of A. marina. The DNA content of A. marina is composed of 8.3 million base pairs, which is among the largest bacterial genomes sequenced thus far. This large array of genomic data is distributed into nine single-copy plasmids that code for >25% of the putative ORFs. Heavy duplication of genes related to DNA repair and recombination (primarily recA) and transposable elements could account for genetic mobility and genome expansion. We discuss points of interest for the biosynthesis of the unusual pigments chlorophyll d and α-carotene and genes responsible for previously studied phycobilin aggregates. Our analysis also reveals that A. marina carries a unique complement of genes for these phycobiliproteins in relation to those coding for antenna proteins related to those in Prochlorococcus species. The global replacement of major photosynthetic pigments appears to have incurred only minimal specializations in reaction center proteins to accommodate these alternate pigments. These features clearly show that the genus Acaryochloris is a fitting candidate for understanding genome expansion, gene acquisition, ecological adaptation, and photosystem modification in the cyanobacteria. 相似文献
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Pharmacokinetics,clot strength and safety of a new fibrinogen concentrate: randomized comparison with active control in congenital fibrinogen deficiency
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C. Ross S. Rangarajan M. Karimi G. Toogeh S. Apte T. Lissitchkov S. Acharya M. J. Manco‐Johnson A. Srivastava B. Brand B. A. Schwartz S. Knaub F. Peyvandi 《Journal of thrombosis and haemostasis》2018,16(2):253-261
Essentials
- Congenital afibrinogenemia causes a potentially life‐threatening bleeding and clotting tendency.
- Two human fibrinogen concentrates (HFCs) were compared in a randomized pharmacokinetic study.
- Bioequivalence was not shown for AUCnorm, which was significantly larger for the new HFC.
- Increases in clot strength were comparable, and no thromboses or deaths occurred in the study.
Summary
Background
Human fibrinogen concentrate (HFC) corrects fibrinogen deficiency in congenital a‐/hypofibrinogenemia.Objectives
To assess pharmacokinetics (PK), effects on thromboelastometry maximum clot firmness (MCF), and safety of a new double virus‐inactivated/eliminated, highly purified HFC vs. active control.Patients/Methods
In this multinational, randomized, phase II, open‐label, crossover study in 22 congenital afibrinogenemia patients aged ≥ 12 years, 70 mg kg?1 of new HFC (FIBRYGA, Octapharma AG) or control (Haemocomplettan® P/RiaSTAP?, CSL Behring GmbH) were administered, followed by crossover to the other concentrate. Fibrinogen activity, PK and MCF in plasma were assessed.Results
The concentrates were not bioequivalent for the primary endpoint, AUCnorm (mean ratio, 1.196; 90% confidence interval [CI], 1.117, 1.281). Remaining PK parameters (Cmaxnorm, IVR, t1/2, MRT) reflected bioequivalence between concentrates, except for clearance (mean ratio, 0.836; 90% CI, 0.781, 0.895) and Vss (mean ratio, 0.886; 90% CI, 0.791, 0.994). Mean AUCnorm was significantly larger for the new HFC (1.62 ± 0.45 vs. 1.38 ± 0.47 h kg g L?1 mg?1, P = 0.0001) and mean clearance was significantly slower (0.665 ± 0.197 vs. 0.804 ± 0.255 mL h?1 kg?1, P = 0.0002). Mean MCF increased from 0 mm to 9.68 mm (new HFC) and 10.00 mm (control) 1‐hour post‐infusion (mean difference, ?0.32 mm; 95% CI, ?1.70, 1.07, n.s.). No deaths, thromboses, viral seroconversions or serious related adverse events occurred.Conclusions
Bioequivalence was not demonstrated for AUCnorm, clearance and Vss. Larger AUCnorm and slower clearance were observed for the new HFC. Remaining pharmacokinetic parameters reflected bioequivalence to control. Safety profiles and increases in clot strength were comparable between concentrates.87.
Hailan Jiang Heming Lu Hong Yuan Huixian Huang Yinglin Wei Yanxian Zhang Xu Liu 《Journal of radiation research》2015,56(1):114-121
This study aimed to evaluate whether placing dose constraints on the brachial plexus (BP) could provide dosimetric benefits in patients with nasopharyngeal carcinoma (NPC) undergoing intensity-modulated radiation therapy (IMRT). Planning CT images for 30 patients with NPC treated with definitive IMRT were retrospectively reviewed. Target volumes, the BP and other critical structures were delineated; two separate IMRT plans were designed for each patient: one set no restrictions for the BP; the other considered the BP as a critical structure for which a maximum dose limit of ≤66 Gy was set. No significant differences between the two plans were observed in the conformity index, homogeneity index, maximum dose to the planning target volumes (PTVs), minimum dose to the PTVs, percentages of the volume of the PTVnx and PTVnd receiving more than 110% of the prescribed dose, or percentages of the volume of the PTVs receiving 95% and > 93% of the prescribed dose. Dose constraints significantly reduced the maximum dose, mean dose, V45, V50, V54, V60, V66 and V70 to the BP. Dose constraints significantly reduced the maximum dose to the BP, V45, V60 and V66 in both N0–1 and N2–3 disease; however, the magnitude of the dosimetric gain for each parameter between N0–1 and N2–3 disease was not significantly different, except for the V60 and V66. In conclusion, placing dose constraints on the BP can significantly decrease the irradiated volume and dose, without compromising adequate dose delivery to the target volume. 相似文献
88.
Context
An aging population leads to a growing demand for long-term services and supports (LTSS). In 2002, France introduced universal, income-adjusted, public long-term care coverage for adults 60 and older, whereas the United States funds means-tested benefits only. Both countries have private long-term care insurance (LTCI) markets: American policies create alternatives to out-of-pocket spending and protect purchasers from relying on Medicaid. Sales, however, have stagnated, and the market''s viability is uncertain. In France, private LTCI supplements public coverage, and sales are growing, although its potential to alleviate the long-term care financing problem is unclear. We explore whether France''s very different approach to structuring public and private financing for long-term care could inform the United States’ long-term care financing reform efforts.Methods
We consulted insurance experts and conducted a detailed review of public reports, academic studies, and other documents to understand the public and private LTCI systems in France, their advantages and disadvantages, and the factors affecting their development.Findings
France provides universal public coverage for paid assistance with functional dependency for people 60 and older. Benefits are steeply income adjusted and amounts are low. Nevertheless, expenditures have exceeded projections, burdening local governments. Private supplemental insurance covers 11% of French, mostly middle-income adults (versus 3% of Americans 18 and older). Whether policyholders will maintain employer-sponsored coverage after retirement is not known. The government''s interest in pursuing an explicit public/private partnership has waned under President François Hollande, a centrist socialist, in contrast to the previous center-right leader, President Nicolas Sarkozy, thereby reducing the prospects of a coordinated public/private strategy.Conclusions
American private insurers are showing increasing interest in long-term care financing approaches that combine public and private elements. The French example shows how a simple, cheap, cash-based product can gain traction among middle-income individuals when offered by employers and combined with a steeply income-adjusted universal public program. The adequacy of such coverage, however, is a concern. 相似文献89.
Carolyn E. Schwartz Brian Stucky Carly S. Rivers Vanessa K. Noonan Joel A. Finkelstein 《Archives of physical medicine and rehabilitation》2018,99(8):1599-1608.e1
Objective
To investigate response shift effects in spinal cord injury (SCI) over 5 years postinjury.Design
Prospective cohort study observed at 1, 2, and 5 years post-SCI.Setting
Specialized SCI centers.Participants
Sample included 1125, 760, and 219 participants at 1, 2, and 5 years post-SCI (N = 2104). The study sample was 79% men; 39% were motor/sensory complete (mean age, 44.6±18.3y).Interventions
Not applicable.Main Outcome Measures
Patient-reported outcomes included the Medical Outcomes Study 36-Item Short-Form Health Survey version 2 and the Life Satisfaction-11 Questionnaire. Participant latent variable scores were adjusted for (1) potential attrition bias and (2) propensity scores reflecting risk of worse outcomes. The Oort structural equation modeling approach for detecting and accounting for response shift effects was used to test the hypothesis that people with SCI would undergo response shifts over follow-up.Results
The study data comprised the time after FIM scores, an objective measure of motor and cognitive function, had improved and stabilized. Three latent variables (Physical, Mental, and Symptoms) were modeled over time. The response shift model indicated uniform recalibration and reconceptualization response shift effects over time. When adjusted for these response shift effects, Physical showed small true change improvements at 2- and 5-year follow-up, despite FIM stability.Conclusions
We detected recalibration and reconceptualization response shift effects in 1- to 5-year follow-up of people with SCI. Despite stable motor and cognitive function, people with SCI are adapting to their condition. This adaptation reflects a progressive disconnection between symptoms and physical or mental health, and a real improvement in the Physical latent variable. 相似文献90.