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18F-FET PET Imaging in Differentiating Glioma Progression from Treatment-Related Changes: A Single-Center Experience

In glioma patients, differentiation between tumor progression (TP) and treatment-related changes (TRCs) remains challenging. Difficulties in classifying imaging alterations may result in a delay or an unnecessary discontinuation of treatment. PET using O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) has been shown to be a useful tool for detecting TP and TRCs. Methods: We retrospectively evaluated 127 consecutive patients with World Health Organization grade II–IV glioma who underwent 18F-FET PET imaging to distinguish between TP and TRCs. 18F-FET PET findings were verified by neuropathology (40 patients) or clinicoradiologic follow-up (87 patients). Maximum tumor-to-brain ratios (TBRmax) of 18F-FET uptake and the slope of the time–activity curves (20–50 min after injection) were determined. The diagnostic accuracy of 18F-FET PET parameters was evaluated by receiver-operating-characteristic analysis and 2 testing. The prognostic value of 18F-FET PET was estimated using the Kaplan–Meier method. Results: TP was diagnosed in 94 patients (74%) and TRCs in 33 (26%). For differentiating TP from TRCs, receiver-operating-characteristic analysis yielded an optimal 18F-FET TBRmax cutoff of 1.95 (sensitivity, 70%; specificity, 71%; accuracy, 70%; area under the curve, 0.75 ± 0.05). The highest accuracy was achieved by a combination of TBRmax and slope (sensitivity, 86%; specificity, 67%; accuracy, 81%). However, accuracy was poorer when tumors harbored isocitrate dehydrogenase (IDH) mutations (91% in IDH-wild-type tumors, 67% in IDH-mutant tumors, P < 0.001). 18F-FET PET results correlated with overall survival (P < 0.001). Conclusion: In our neurooncology department, the diagnostic performance of 18F-FET PET was convincing but slightly inferior to that of previous reports.




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Single-molecule level structural dynamics of DNA unwinding by human mitochondrial Twinkle helicase [Molecular Biophysics]

Knowledge of the molecular events in mitochondrial DNA (mtDNA) replication is crucial to understanding the origins of human disorders arising from mitochondrial dysfunction. Twinkle helicase is an essential component of mtDNA replication. Here, we employed atomic force microscopy imaging in air and liquids to visualize ring assembly, DNA binding, and unwinding activity of individual Twinkle hexamers at the single-molecule level. We observed that the Twinkle subunits self-assemble into hexamers and higher-order complexes that can switch between open and closed-ring configurations in the absence of DNA. Our analyses helped visualize Twinkle loading onto and unloading from DNA in an open-ringed configuration. They also revealed that closed-ring conformers bind and unwind several hundred base pairs of duplex DNA at an average rate of ∼240 bp/min. We found that the addition of mitochondrial single-stranded (ss) DNA–binding protein both influences the ways Twinkle loads onto defined DNA substrates and stabilizes the unwound ssDNA product, resulting in a ∼5-fold stimulation of the apparent DNA-unwinding rate. Mitochondrial ssDNA-binding protein also increased the estimated translocation processivity from 1750 to >9000 bp before helicase disassociation, suggesting that more than half of the mitochondrial genome could be unwound by Twinkle during a single DNA-binding event. The strategies used in this work provide a new platform to examine Twinkle disease variants and the core mtDNA replication machinery. They also offer an enhanced framework to investigate molecular mechanisms underlying deletion and depletion of the mitochondrial genome as observed in mitochondrial diseases.




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Navajo Nation Reels Under Weight of Coronavirus and History of Neglect

Source:

The Navajo Nation now has the highest per-capita coronavirus infection rate after New York and New Jersey, but it has a fraction of the resources to treat and prevent the pandemic. "This has got to end," said president Jonathan Nez after federal relief funds arrived six weeks after they were promised and a week after the U.S. government missed a congressional deadline for distribution.






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Regional Enforcement: A Profile of Migrants Deported from the United States and Mexico to the Northern Triangle

Marking the release of an MPI report, speakers on this webinar present an overview of regional immigration enforcement trends, including U.S. and Mexican apprehensions and deportations of both children and adults, along with a demographic, socioeconomic, and criminal profile of child and adult deportees.




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Migrants Deported from the United States and Mexico to the Northern Triangle: A Statistical and Socioeconomic Profile

This report examines the rising numbers of apprehensions and deportations of Central American children and adults by the United States and Mexico, and provides a demographic, socioeconomic, and criminal profile of deportees to El Salvador, Guatemala, and Honduras. The report traces how rising Mexican enforcement is reshaping regional dynamics and perhaps ushering in changes to long-lasting trends in apprehensions.




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Regional Enforcement: A Profile of Migrants Deported from the United States and Mexico to the Northern Triangle

This webinar includes an overview of regional immigration enforcement trends, including U.S. and Mexican apprehensions and deportations of Central American migrants, along with a demographic, socioeconomic, and criminal profile of child and adult deportees.




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Japan offers weekend's only top-level event as horse racing struggles to resume

Coronavirus brings worldwide horse racing almost to a halt, with only one Grade 1 event on the weekend schedule, but rays of hope exist.




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Google-related company pulls plug on Toronto 'smart city' project

A Google-related company has pulled the plug on its ambitious high-tech waterfront city project in Toronto, citing financial strains from the coronavirus, but the project had also run into local opposition.




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Ally or Exploiter? The Smuggler-Migrant Relationship Is a Complex One

As highly industrialized countries ramp up their border controls, human smugglers are playing a central role in moving migrants through key migration corridors around the world. Despite the illicit nature of their work and being cast as villains in the public eye, smugglers have complex, multifaceted relationships with their clients. At times, the relationship can be mutually beneficial or even lifesaving; at others, it can be predatory and dangerous, as this article explores.




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Google brings back 'Pac-Man' game in latest Doodle

Google's homepage features arcade classic "Pac-Man" in the latest Doodle.




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Look: Minzy to release 'Lovely' single May 24

K-pop star Minzy shared a comeback schedule for her new solo single, "Lovely."




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[ Singles & Dating ] Open Question : Muslim man looking for relief?

I know it's Ramadan, but I've been feeling urges for a few years now and it's just getting more and more now. I always imagine about sex and loving my to-be wife. Right now, I'm studying medicine, so my parents told me it's too early to get married (24 years old). I just don't know really what to do. I prone masturbate to get some relief. What should I do?




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[ Singles & Dating ] Open Question : I miss my ex girlfriend's daughter what can I do ?

Hello I am a man 36 years old and, My ex girlfriend and I and I were together from January to August 2012, my ex girlfriend's daughter was very affectionate with me, I miss her what I can do I was very fond of her, what can I do ?




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[ Singles & Dating ] Open Question : WHAT TO DO, TO MAKE FRIENDS? I NEED ADVICE?




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[ Singles & Dating ] Open Question : The man that’s showed clear/obvious interest in me had no contact with me yesterday, is this normal?

I’ve been talking to a man, we have mutual interest in each other. We talked on the phone for over an hour the night before last and it was an amazing conversation. The next day he had no contact with me, which in my mind it didn’t bother me and still kind of isn’t I think he just is doing his own thing and likes his personal space. I’m not too bothered or worried but still questioning why? Is it normal for a man to kinda disappear and have no contact for a day?




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[ Singles & Dating ] Open Question : What is this?  What is it for?




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Robustness and Locke's Wingless Gentleman

Our ancestors have made decisions under uncertainty ever since they had to stand and fight or run away, eat this root or that berry, sleep in this cave or under that bush. Our species is distinguished by the extent of deliberate thought preceding decision. Nonetheless, the ability to decide in the face of the unknown was born from primal necessity. Betting is one of the oldest ways of deciding under uncertainty. But you bet you that 'bet' is a subtler concept than one might think.

We all know what it means to make a bet, but just to make sure let's quote the Oxford English Dictionary: "To stake or wager (a sum of money, etc.) in support of an affirmation or on the issue of a forecast." The word has been around for quite a while. Shakespeare used the verb in 1600: "Iohn a Gaunt loued him well, and betted much money on his head." (Henry IV, Pt. 2 iii. ii. 44). Drayton used the noun in 1627 (and he wasn't the first): "For a long while it was an euen bet ... Whether proud Warwick, or the Queene should win."

An even bet is a 50-50 chance, an equal probability of each outcome. But betting is not always a matter of chance. Sometimes the meaning is just the opposite. According to the OED 'You bet' or 'You bet you' are slang expressions meaning 'be assured, certainly'. For instance: "'Can you handle this outfit?' 'You bet,' said the scout." (D.L.Sayers, Lord Peter Views Body, iv. 68). Mark Twain wrote "'I'll get you there on time' - and you bet you he did, too." (Roughing It, xx. 152).

So 'bet' is one of those words whose meaning stretches from one idea all the way to its opposite. Drayton's "even bet" between Warwick and the Queen means that he has no idea who will win. In contrast, Twain's "you bet you" is a statement of certainty. In Twain's or Sayers' usage, it's as though uncertainty combines with moral conviction to produce a definite resolution. This is a dialectic in which doubt and determination form decisiveness.

John Locke may have had something like this in mind when he wrote:

"If we will disbelieve everything, because we cannot certainly know all things; we shall do muchwhat as wisely as he, who would not use his legs, but sit still and perish, because he had no wings to fly." (An Essay Concerning Human Understanding, 1706, I.i.5)

The absurdity of Locke's wingless gentleman starving in his chair leads us to believe, and to act, despite our doubts. The moral imperative of survival sweeps aside the paralysis of uncertainty. The consequence of unabated doubt - paralysis - induces doubt's opposite: decisiveness.

But rational creatures must have some method for reasoning around their uncertainties. Locke does not intend for us to simply ignore our ignorance. But if we have no way to place bets - if the odds simply are unknown - then what are we to do? We cannot "sit still and perish".

This is where the strategy of robustness comes in.

'Robust' means 'Strong and hardy; sturdy; healthy'. By implication, something that is robust is 'not easily damaged or broken, resilient'. A statistical test is robust if it yields 'approximately correct results despite the falsity of certain of the assumptions underlying it' or despite errors in the data. (OED)

A decision is robust if its outcome is satisfactory despite error in the information and understanding which justified or motivated the decision. A robust decision is resilient to surprise, immune to ignorance.

It is no coincidence that the colloquial use of the word 'bet' includes concepts of both chance and certainty. A good bet can tolerate large deviation from certainty, large error of information. A good bet is robust to surprise. 'You bet you' does not mean that the world is certain. It means that the outcome is certain to be acceptable, regardless of how the world turns out. The scout will handle the outfit even if there is a rogue in the ranks; Twain will get there on time despite snags and surprises. A good bet is robust to the unknown. You bet you!


An extended and more formal discussion of these issues can be found elsewhere.




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Review Article – Within a single lifetime: Recent writings on autism

AHP readers will be interested in a review article now available online from History of the Human Sciences “Within a single lifetime: Recent writings on autism.” Written by Gregory Hollin the piece reviews five recent books on autism.




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Intimacy vs Isolation: Why Do Some People Struggle to Form Intimate Relationships?

Loneliness is a surprisingly common phenomenon in the 21st century. In 2018, a survey conducted by The Economist and the Kaiser Family Foundation revealed that 22% of adults in the United States and 23% of adults in the United Kingdom often or always feel lonely or left out. Interestingly, many people who describe themselves as […]




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Schools Struggle to Meet Students' Mounting Mental-Health Needs

Keeping up with students’ growing mental-health needs was a concern for districts long before the pandemic began. It’s even harder now, educators and psychologists say.




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Schools Struggle to Meet Students' Mounting Mental-Health Needs

Keeping up with students’ growing mental-health needs was a concern for districts long before the pandemic began. It’s even harder now, educators and psychologists say.




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Schools Struggle to Meet Students' Mounting Mental-Health Needs

Keeping up with students’ growing mental-health needs was a concern for districts long before the pandemic began. It’s even harder now, educators and psychologists say.




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Schools Struggle to Meet Students' Mounting Mental-Health Needs

Keeping up with students’ growing mental-health needs was a concern for districts long before the pandemic began. It’s even harder now, educators and psychologists say.




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A Big Charter School Struggle Has Been Galvanized by a Democratic Governor

Pennsylvania Gov. Tom Wolf, a Democrat, has become increasingly critical of charter schools this year, and his new proposals for charters would change how they operate and how they are funded.




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Schools Struggle to Meet Students' Mounting Mental-Health Needs

Keeping up with students’ growing mental-health needs was a concern for districts long before the pandemic began. It’s even harder now, educators and psychologists say.




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The Jungle Deep.




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Telling our story : the Kammermann family in Australia 1876 - 1925 / by Glen Kammermann.




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Teacher : one woman's struggle to keep the heart in teaching / Gabbie Stroud.

Stroud, G. J. (Gabrielle J.), 1977-




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The forgotten creed : Christianity's original struggle against bigotry, slavery, and sexism / Stephen J. Patterson.

Bible. Galatians, III, 28 -- Criticism, interpretation, etc




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Single and free : female migration to Australia, 1833 - 1837 / Elizabeth Rushen.

Women immigrants -- Australia -- History.




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Die Blasenbandwürmer und ihre Entwicklung : zugleich ein Beitrag zur Kentniss der Cysticercusleber / von Rud Leuckart.

Giessen : J. Ricker, 1856.




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Die Entzundung und die entzundliche Gewebebildung / [Ernst Ziegler].

Jena : H. Pohle, [1889]




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Die Furchen und Wulste am Grosshirn des Menschen : zugleich als Erlauterung zu dem Hirnmodell / von Ad. Pansch.

Berlin : R. Oppenheim, 1879.




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Die Hand und der Fuss. Ein Beitrag zur vergleichenden Osteologie der Menschen, Affen und Beutelthiere / von Joh. Christian Gustav Lucae.

Frankfurt a. M. : C. Winter, 1865.




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Die Hodgkinsche Krankheit / von Kurt Ziegler.

Jena : G. Fischer, 1911.




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Die Knochen und Muskeln der Extremitaten bei den schlangenähnlichen Sauriern : vergleichend-anatomische Abhandlung / von Max Fürbringer.

Leipzig : W. Engelmann, 1870.




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Die methodische Intestinalpalpation mittels der topographischen Gleit- und Tiefenpalpation und ihre Ergebnisse / von Dr. Theodor Hausmann.

Berlin : Karger, 1910.




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Einleitung in die vergleichende gehirnphysiologie und Vergleichende psychologie : mit besonderer berücksichtigung der wirbellosen thiere / von Jacques Loeb.

Leipzig : J.A. Barth, 1899.




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Mississippi Textbooks Gloss Over Civil Rights Struggle

Mississippi’s outdated textbooks teach an abbreviated version of civil rights, undermining the state’s new ‘innovative’ standards.




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The head of a Turk, surmounted by an eagle holding thunderbolts, and surmounting a strapwork panel announcing the manners and fashions of the Turks. Process print, 1873, after a woodcut, 1553.




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Three smugglers resting on shore. Mezzotint by G.H. Phillips, 1832, after J. Tennant.

London (6 Pall Mall) : Messrs Moon, Boys & Graves ; Manchester : J.C. Grundy, July 2 1832.




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A Scottish gamekeeper armed with a gun, standing on a mountain-top in the falling snow: he holds a shot eagle in his right hand, and a hound stands at his side. Engraving by J. Outrim, 1856, after E.H. Landseer.

[1856]




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A Scottish gamekeeper armed with a gun, standing on a mountain-top in the falling snow: he holds a shot eagle in his right hand, and a hound stands at his side. Engraving by J. Outrim, 1856, after E.H. Landseer.

London (6, Pall Mall) : Published ... by Henry Graves, & Comp.y, May 10th, 1856.




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Winter weather, associated with the struggle of high art against competition from lowlife artists. Etching by P. Testa, 1641.

Si stampano in Roma (alla Pace ; all'insegna di Parigi) : per Giovan Jacomo Rossi, [1641?]




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The storming of the Bastille, 1789. Ink drawing by R.B. Bate after H. Singleton.




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Missouri Governor Struggles to Oust State Education Chief

Margie Vandeven, the state education chief, is appointed by an appointed board, which is still split on whether to fire Vandeven.




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Marketplace, power, prestige : the healthcare professions' struggle for recognition (19th-20th century) / edited by Pierre Pfütsch.

Stuttgart : Franz Steiner Verlag, 2019.




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Deep transfer learning for improving single-EEG arousal detection. (arXiv:2004.05111v2 [cs.CV] UPDATED)

Datasets in sleep science present challenges for machine learning algorithms due to differences in recording setups across clinics. We investigate two deep transfer learning strategies for overcoming the channel mismatch problem for cases where two datasets do not contain exactly the same setup leading to degraded performance in single-EEG models. Specifically, we train a baseline model on multivariate polysomnography data and subsequently replace the first two layers to prepare the architecture for single-channel electroencephalography data. Using a fine-tuning strategy, our model yields similar performance to the baseline model (F1=0.682 and F1=0.694, respectively), and was significantly better than a comparable single-channel model. Our results are promising for researchers working with small databases who wish to use deep learning models pre-trained on larger databases.




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A hierarchical Bayesian model for single-cell clustering using RNA-sequencing data

Yiyi Liu, Joshua L. Warren, Hongyu Zhao.

Source: The Annals of Applied Statistics, Volume 13, Number 3, 1733--1752.

Abstract:
Understanding the heterogeneity of cells is an important biological question. The development of single-cell RNA-sequencing (scRNA-seq) technology provides high resolution data for such inquiry. A key challenge in scRNA-seq analysis is the high variability of measured RNA expression levels and frequent dropouts (missing values) due to limited input RNA compared to bulk RNA-seq measurement. Existing clustering methods do not perform well for these noisy and zero-inflated scRNA-seq data. In this manuscript we propose a Bayesian hierarchical model, called BasClu, to appropriately characterize important features of scRNA-seq data in order to more accurately cluster cells. We demonstrate the effectiveness of our method with extensive simulation studies and applications to three real scRNA-seq datasets.




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Weighted Lépingle inequality

Pavel Zorin-Kranich.

Source: Bernoulli, Volume 26, Number 3, 2311--2318.

Abstract:
We prove an estimate for weighted $p$th moments of the pathwise $r$-variation of a martingale in terms of the $A_{p}$ characteristic of the weight. The novelty of the proof is that we avoid real interpolation techniques.