Jenkins, Stan*
Dotaz
Zobrazit nápovědu
1st ed. viii, 110 s.
- Klíčová slova
- Knihovnictví,
- MeSH
- lékařské knihovny MeSH
- Publikační typ
- příručky MeSH
- Geografické názvy
- Spojené království MeSH
- Konspekt
- Knihovny
- NLK Obory
- knihovnictví, informační věda a muzeologie
1. elektronické vydání 1 online zdroj (264 stran)
Když se Matthew Lewis a jeho přítelkyně Stacey vracejí z večírku domů, na opuštěné silničce mezi pastvinami zjistí, že v autě dochází benzín. Matthew nechá čekat Stacey v autě a sám se vydává hledat pomoc. V dálce zahlédne světlo a zamíří k němu v domnění, že zde najde pomoc. Stane se však nechtěným svědkem něčeho, co vidět neměl. Když si to uvědomí, je už příliš pozdě. Ráno je Stacey nalezena v autě mrtvá a Matthew je pryč.Policie se zpočátku domnívá, že Matthew Stacey zabil a utekl. Záhy je však nahlášeno zmizení dalšího mladíka jménem Kieran Robinson a v zahradě rodinného domu je nalezeno tělo. Nepatří však ani jednomu z nich, tuto oběť někdo zavraždil před více než třiceti lety.Policie zprvu nemá důvod předpokládat, že spolu všechny tři případy nějak souvisí. Je to však opravdu jen náhoda? Jakou děsivou minulost skrývá nenápadná zahrada a jak může její tajemství souviset s novými případy, když je odděluje nejméně třicet let?Detektivové Alex Kingová a Chloe Laneová tak mají plné ruce práce. Vrásky jim však nepřidělávají jen nové případy, ale i někteří členové vyšetřovacího týmu, kteří mají svá vlastní tajemství. Závod s časem začíná.; Krimithriller ze série o dvou vyšetřovatelkách Kingové a Laneové. Jak souvisí zmizení dvou mužů a hrdelní zločin, který se odehrál před třiceti lety?Když se Matthew a Stacey vracejí z večírku, na silničce mezi pastvinami zjistí, že dochází benzín. Matthew nechá čekat Stacey v autě a sám se vydává hledat pomoc. Stane se nechtěným svědkem něčeho, co vidět neměl. Ráno je Stacey nalezena v autě mrtvá a Matthew je pryč. Záhy je nahlášeno zmizení dalšího mladíka jménem Kieran a v zahradě rodinného domu je nalezeno tělo. Nepatří však ani jednomu z nich, tuto oběť někdo zavraždil před více než třiceti lety. Dva mrtví a dva pohřešovaní. Jakou děsivou minulost skrývá nenápadná zahrada a jak může její tajemství souviset s novými případy, když je odděluje nejméně třicet let? Detektivové Kingová a Laneová mají plné ruce práce. Vrásky jim však nepřidělávají jen nové případy, ale i někteří členové vyšetřovacího týmu, kteří mají svá vlastní tajemství.
When a tree dies, it continues to play an important ecological role within forests. Coarse woody debris (CWD), including standing deadwood (SDW) and downed deadwood (DDW), is an important functional component of forest ecosystems, particularly for many dispersal-limited saproxylic taxa and for metapopulation dynamics across landscapes. Processes, such as natural disturbance or management, modify forest composition and structure, thereby influencing CWD abundance and distribution. Many studies have compared older forests to forests managed with even-aged silvicultural systems and observed a prolonged period of low CWD occurrence after harvesting. With fine-scale spatial data, our study compares the long-term impacts of light partial harvesting on the CWD structure of eastern deciduous hardwood forests. We mapped and inventoried DDW and SDW using variable radius plots based on a 10 m × 10 m grid throughout an unmanaged, structurally-complex relict forest and two nearby forests that were partially harvested over 46 years ago. The relict stand had significantly larger individual pieces and higher accumulations of DDW and SDW than both of the partially harvested stands. Connectivity of CWD was much higher in the relict stand, which had fewer, larger patches. Larger pieces and higher proportion of decay-resistant species (e.g. Quercus spp.) in the relict forest resulted in slower decomposition, greater accumulation and increased connectivity of CWD. Partial harvests, such that occur with selection forestry, are generally considered less disruptive of ecosystem services, but this study highlights the long-term impacts of even light partial harvests on CWD stocks and distribution. When planning harvesting events, forest managers should also consider alternative methods to ensure the sustainability of deadwood resources and function.
- MeSH
- biodiverzita MeSH
- dřevo chemie metabolismus MeSH
- ekosystém MeSH
- lesy * MeSH
- stromy fyziologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Pulmonary endarterectomy is the gold standard treatment for chronic thromboembolic pulmonary hypertension and is potentially curative, although some patients are unsuitable for pulmonary endarterectomy and require alternative management. Lack of standardized assessment of pulmonary endarterectomy eligibility risks suboptimal treatment in some patients. We discuss the implications for future clinical trials and practice of a unique operability assessment in patients who have chronic thromboembolic pulmonary hypertension and were initially screened for inclusion in the CHEST-1 (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase Stimulator Trial-1) study. The CHEST-1 study evaluated riociguat for the treatment of inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy. Screened patients who were initially considered "inoperable" underwent central independent adjudication by a committee of experienced surgeons, or local adjudication in collaboration with an experienced surgeon. Operability decisions were based on accessibility of thrombi and the association between pulmonary vascular resistance (PVR) and the extent of obstruction, using pulmonary angiography/computed tomography with ventilation/perfusion scintigraphy as the minimum diagnostic tests. Of 446 patients screened for CHEST-1, a total of 188 and 124 underwent central and local adjudication, respectively, after being initially considered to be "inoperable." After a second assessment by an experienced surgeon, 69 of these 312 "inoperable" patients were deemed operable. Rigorous measures in CHEST-1 guaranteed that only technically inoperable patients, or patients who had persistent/recurrent pulmonary hypertension, were enrolled, thus ensuring that only patients for whom surgery was not an option were enrolled. This study design sets new standards for future clinical trials and practice in CTEPH, helping to ensure that patients who have CTEPH receive optimal treatment.
Following advancements in the field of genotoxicology, it has become widely accepted that 3D models are not only more physiologically relevant but also have the capacity to elucidate more complex biological processes that standard 2D monocultures are unable to. Whilst 3D liver models have been developed to evaluate the short-term genotoxicity of chemicals, the aim of this study was to develop a 3D model that could be used with the regulatory accepted in vitro micronucleus (MN) following low-dose, longer-term (5 days) exposure to engineered nanomaterials (ENMs). A comparison study was carried out between advanced models generated from two commonly used liver cell lines, namely HepaRG and HepG2, in spheroid format. While both spheroid systems displayed good liver functionality and viability over 14 days, the HepaRG spheroids lacked the capacity to actively proliferate and, therefore, were considered unsuitable for use with the MN assay. This study further demonstrated the efficacy of the in vitro 3D HepG2 model to be used for short-term (24 h) exposures to genotoxic chemicals, aflatoxin B1 (AFB1) and methyl-methanesulfonate (MMS). The 3D HepG2 liver spheroids were shown to be more sensitive to DNA damage induced by AFB1 and MMS when compared to the HepG2 2D monoculture. This 3D model was further developed to allow for longer-term (5 day) ENM exposure. Four days after seeding, HepG2 spheroids were exposed to Zinc Oxide ENM (0-2 µg/ml) for 5 days and assessed using both the cytokinesis-block MN (CBMN) version of the MN assay and the mononuclear MN assay. Following a 5-day exposure, differences in MN frequency were observed between the CBMN and mononuclear MN assay, demonstrating that DNA damage induced within the first few cell cycles is distributed across the mononucleated cell population. Together, this study demonstrates the necessity to adapt the MN assay accordingly, to allow for the accurate assessment of genotoxicity following longer-term, low-dose ENM exposure.
- MeSH
- aflatoxin B1 toxicita MeSH
- biologické modely MeSH
- buněčné kultury metody MeSH
- buněčné linie MeSH
- buněčné sféroidy * MeSH
- buňky Hep G2 MeSH
- hepatocyty účinky léků MeSH
- játra účinky léků MeSH
- lidé MeSH
- methylmethansulfonát toxicita MeSH
- mikrojaderné testy metody MeSH
- mutageny toxicita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Lenz-Majewski syndrome (LMS) is a syndrome of intellectual disability and multiple congenital anomalies that features generalized craniotubular hyperostosis. By using whole-exome sequencing and selecting variants consistent with the predicted dominant de novo etiology of LMS, we identified causative heterozygous missense mutations in PTDSS1, which encodes phosphatidylserine synthase 1 (PSS1). PSS1 is one of two enzymes involved in the production of phosphatidylserine. Phosphatidylserine synthesis was increased in intact fibroblasts from affected individuals, and end-product inhibition of PSS1 by phosphatidylserine was markedly reduced. Therefore, these mutations cause a gain-of-function effect associated with regulatory dysfunction of PSS1. We have identified LMS as the first human disease, to our knowledge, caused by disrupted phosphatidylserine metabolism. Our results point to an unexplored link between phosphatidylserine synthesis and bone metabolism.
- MeSH
- dánio pruhované embryologie genetika MeSH
- dítě MeSH
- embryo nesavčí MeSH
- fibroblasty metabolismus MeSH
- fosfatidylseriny biosyntéza genetika MeSH
- hyperostóza MeSH
- kultivované buňky MeSH
- lidé MeSH
- mladiství MeSH
- mnohočetné abnormality genetika MeSH
- molekulární sekvence - údaje MeSH
- mutace * MeSH
- nanismus MeSH
- syndrom MeSH
- transferasy dusíkatých skupin genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
PURPOSE: To investigate combined MRI and 18F-FDG PET for assessing breast tumor metabolism/perfusion mismatch and predicting pathological response and recurrence-free survival (RFS) in women treated for breast cancer. METHODS: Patients undergoing neoadjuvant chemotherapy (NAC) for locally-advanced breast cancer were imaged at three timepoints (pre, mid, and post-NAC), prior to surgery. Imaging included diffusion-weighted and dynamic contrast-enhanced (DCE-) MRI and quantitative 18F-FDG PET. Tumor imaging measures included apparent diffusion coefficient, peak percent enhancement (PE), peak signal enhancement ratio (SER), functional tumor volume, and washout volume on MRI and standardized uptake value (SUVmax), glucose delivery (K1) and FDG metabolic rate (MRFDG) on PET, with percentage changes from baseline calculated at mid- and post-NAC. Associations of imaging measures with pathological response (residual cancer burden [RCB] 0/I vs. II/III) and RFS were evaluated. RESULTS: Thirty-five patients with stage II/III invasive breast cancer were enrolled in the prospective study (median age: 43, range: 31-66 years, RCB 0/I: N = 11/35, 31%). Baseline imaging metrics were not significantly associated with pathologic response or RFS (p > 0.05). Greater mid-treatment decreases in peak PE, along with greater post-treatment decreases in several DCE-MRI and 18F-FDG PET measures were associated with RCB 0/I after NAC (p < 0.05). Additionally, greater mid- and post-treatment decreases in DCE-MRI (peak SER, washout volume) and 18F-FDG PET (K1) were predictive of prolonged RFS. Mid-treatment decreases in metabolism/perfusion ratios (MRFDG/peak PE, MRFDG/peak SER) were associated with improved RFS. CONCLUSION: Mid-treatment changes in both PET and MRI measures were predictive of RCB status and RFS following NAC. Specifically, our results indicate a complementary relationship between DCE-MRI and 18F-FDG PET metrics and potential value of metabolism/perfusion mismatch as a marker of patient outcome.
- MeSH
- dospělí MeSH
- fluorodeoxyglukosa F18 terapeutické užití MeSH
- lidé MeSH
- magnetická rezonanční tomografie metody MeSH
- nádory prsu * diagnostické zobrazování farmakoterapie MeSH
- neoadjuvantní terapie metody MeSH
- pozitronová emisní tomografie metody MeSH
- prospektivní studie MeSH
- radiofarmaka terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Research Support, N.I.H., Extramural MeSH
Recent findings have shown an inverse association between circulating C15:0/C17:0 fatty acids with disease risk, therefore, their origin needs to be determined to understanding their role in these pathologies. Through combinations of both animal and human intervention studies, we comprehensively investigated all possible contributions of these fatty acids from the gut-microbiota, the diet, and novel endogenous biosynthesis. Investigations included an intestinal germ-free study and a C15:0/C17:0 diet dose response study. Endogenous production was assessed through: a stearic acid infusion, phytol supplementation, and a Hacl1-/- mouse model. Two human dietary intervention studies were used to translate the results. Finally, a study comparing baseline C15:0/C17:0 with the prognosis of glucose intolerance. We found that circulating C15:0/C17:0 levels were not influenced by the gut-microbiota. The dose response study showed C15:0 had a linear response, however C17:0 was not directly correlated. The phytol supplementation only decreased C17:0. Stearic acid infusion only increased C17:0. Hacl1-/- only decreased C17:0. The glucose intolerance study showed only C17:0 correlated with prognosis. To summarise, circulating C15:0 and C17:0 are independently derived; C15:0 correlates directly with dietary intake, while C17:0 is substantially biosynthesized, therefore, they are not homologous in the aetiology of metabolic disease. Our findings emphasize the importance of the biosynthesis of C17:0 and recognizing its link with metabolic disease.
- MeSH
- biosyntetické dráhy MeSH
- dieta MeSH
- dietní cukry aplikace a dávkování metabolismus MeSH
- dietní tuky aplikace a dávkování metabolismus MeSH
- glukózový toleranční test MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- mastné kyseliny metabolismus MeSH
- myši MeSH
- porucha glukózové tolerance * MeSH
- potravní doplňky MeSH
- střevní mikroflóra * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
V rutinních systémech sledování nemocnosti na jednotlivé diagnózy je jedním z důležitých problé-mů analýza časového vývoje například týdenních počtů hlášení. Tento článek se zabývá metodikouuvedené problematiky. V praxi se ukazuje, že počty výskytů mnohých onemocnění jsou závislé naroční době. Samozřejmě je nutno vzít v úvahu i dlouhodobý vývoj počtu onemocnění. V článku sediskutuje o dvou často používaných přístupech. Jde jednak o Boxovu-Jenkinsovu analýzu časovýchřad, která modeluje „náhodnou chybu“, a jednak o metodu dekompozice trendu, která se pokoušírozložit pozorovaný počet případů na systematické složky (dlouhodobý trend a sezonní složku)a náhodné kolísání. V článku je popsána možnost vyhlazení odhadu časové řady pomocí modifi-kovaného jádrového odhadu. Pro ilustraci obou metod jsou použity týdenní údaje o celorepubliko-vých počtech nemocných s hepatitidou A, zarděnkami a salmonelózou.
In routine systems investigating the morbidity according to diagnosis it is very useful to analysethe development in time (for example the development of weekly reports). This paper is concernedwith the methodology of such analyses. In practice it appears that the number of cases depends onseason. It stands to reason, that it is necessary to consider also long-therm trends. In this paper twodifferent approaches are discussed – the Box-Jenkins analysis, which describes the random errorand the Method of Trend Decomposition which spread the number of cases into the systematiccomponent (long term trend and seasonal effect) and random variability. The authors describe themethod of smoothing the estimate of the time series by kernel estimate. In both approaches theyuse weekly reports from the whole Czech Republic of diagnoses viral hepatitis A, rubella andsalmonellosis.
